United States - English - NLM (National Library of Medicine)

bryant ranch prepack - mesalamine (unii: 4q81i59gxc) (mesalamine - unii:4q81i59gxc) - mesalamine delayed-release tablets are indicated for the: - induction and maintenance of remission in adult patients with mildly to moderately active ulcerative colitis. pediatric use information is approved for takeda pharmaceuticals u.s.a., inc.’s lialda (mesalamine) delayed-release tablets. however, due to takeda pharmaceuticals u.s.a., inc.’s marketing exclusivity rights, this drug product is not labeled with that information. mesalamine delayed-release tablets are contraindicated in patients with known or suspected hypersensitivity to salicylates, aminosalicylates, or to any of the ingredients of mesalamine delayed-release tablets [see warnings and precautions (5.3), adverse reactions (6.2), description (11)] . risk summary published data from meta-analyses, cohort studies, and case series on the use of mesalamine during pregnancy have not reliably informed an association with mesalamine and major birth defects, miscarriage, or adverse maternal or fetal outcomes (see data ). there are adverse effects on maternal and fetal outcomes associated with ulcerative colitis in pregnancy (see clinical considerations) . in animal reproduction studies, there were no adverse developmental outcomes with administration of oral mesalamine during organogenesis to pregnant rats and rabbits at doses 1.8 and 2.9 times, respectively, the maximum recommended human dose (see data) . the estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations disease-associated maternal and embryo/fetal risk published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with ulcerative colitis. adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2,500 g) infants, and small for gestational age at birth. data human data published data from meta-analyses, cohort studies, and case series on the use of mesalamine during early pregnancy (first trimester) and throughout pregnancy have not reliably informed an association of mesalamine and major birth defects, miscarriage, or adverse maternal or fetal outcomes. there is no clear evidence that mesalamine exposure in early pregnancy is associated with an increased risk of major congenital malformations, including cardiac malformations. published epidemiologic studies have important methodological limitations which hinder interpretation of the data, including inability to control for confounders, such as underlying maternal disease, maternal use of concomitant medications, and missing information on the dose and duration of use for mesalamine products. animal data reproduction studies with mesalamine during organogenesis have been performed in rats at doses up to 1,000 mg/kg/day (1.8 times the maximum recommended human dose based on a body surface area comparison) and rabbits at doses up to 800 mg/kg/day (2.9 times the maximum recommended human dose based on a body surface area comparison) and have revealed no evidence of harm to the fetus due to mesalamine. risk summary data from published literature report the presence of mesalamine and its metabolite, n-acetyl-5-aminosalicylic acid in human milk in small amounts with relative infant doses (rid) of 0.1% or less for mesalamine (see data) . there are case reports of diarrhea in breastfed infants exposed to mesalamine (see clinical considerations) . there is no information on the effects of the drug on milk production. the lack of clinical data during lactation precludes a clear determination of the risk of mesalamine delayed-release tablets to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for mesalamine delayed-release tablets and any potential adverse effects on the breastfed child from mesalamine delayed-release tablets or from the underlying maternal condition. clinical considerations advise the caregiver to monitor the breastfed infant for diarrhea. data in published lactation studies, maternal mesalamine doses from various oral and rectal formulations and products ranged from 500 mg to 4.8 g daily. the average concentration of mesalamine in milk ranged from non-detectable to 0.5 mg/l. the average concentration of n-acetyl-5-aminosalicylic acid in milk ranged from 0.2 to 9.3 mg/l. based on these concentrations, estimated infant daily dosages for an exclusively breastfed infant are 0 to 0.075 mg/kg/day (rid 0% to 0.1%) of mesalamine and 0.03 to 1.4 mg/kg/day of n-acetyl-5-aminosalicylic acid. the safety and effectiveness of mesalamine delayed-release tablets have not been established in patients weighing less than 24 kg. pediatric use information is approved for takeda pharmaceuticals u.s.a., inc.’s lialda (mesalamine) delayed-release tablets. however, due to takeda pharmaceuticals u.s.a., inc.’s marketing exclusivity rights, this drug product is not labeled with that information. clinical trials of mesalamine delayed-release tablets did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. reports from uncontrolled clinical studies and postmarketing reporting systems suggested a higher incidence of blood dyscrasias (i.e., agranulocytosis, neutropenia, and pancytopenia) in patients who were 65 years or older who were taking mesalamine-containing products such as mesalamine delayed-release tablets compared to younger patients. monitor complete blood cell counts and platelet counts in elderly patients during treatment with mesalamine delayed-release tablets. systemic exposures are increased in elderly subjects [see clinical pharmacology (12.3)]. in general, consider the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in elderly patients when prescribing mesalamine delayed-release tablets. consider starting at the low end of the dosing range for induction in elderly patients [see dosage and administration (2), use in specific populations (8.6)] . mesalamine is known to be substantially excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function. evaluate renal function in all patients prior to initiation and periodically while on mesalamine delayed-release tablets therapy. monitor patients with known renal impairment or history of renal disease or taking nephrotoxic drugs for decreased renal function and mesalamine-related adverse reactions. discontinue mesalamine delayed-release tablets if renal function deteriorates while on therapy [see warnings and precautions (5.1), adverse reactions (6.2), drug interactions (7.1)] .

United States - English - NLM (National Library of Medicine)

bryant ranch prepack - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - morphine sulfate oral solution 2 mg/ml is indicated for the management of: - adults with acute and chronic pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. morphine sulfate oral solution 20 mg/ml is indicated for the relief of acute and chronic pain in opioid-tolerant adult patients . limitations of use because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see warnings and precautions ( 5.2 ) ], reserve morphine sulfate oral solution for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: - have not been tolerated, or are not expected to be tolerated, have not been tolerated, or are not expected to be tolerated, - have not provided adequate analgesia, or are not expected to provide adequate analgesia. have not provided adequate analgesia, or are not expected to provide adequate analgesia. pediatric use information is approved for hikma pharmaceuticals usa inc.'s morphine sulfate oral solution. however, due to hikma pharmaceuticals usa inc.'s marketing exclusivity rights, this drug product is not labeled with that informatio n. morphine sulfate oral solution is contraindicated in patients with: - significant respiratory depression [see warnings and precautions ( 5.4 ) ]. significant respiratory depression [see warnings and precautions ( 5.4 ) ]. - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions ( 5.7 ) ]. acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions ( 5.7 ) ]. - concurrent use of monoamine oxidase inhibitors (maois) or use of maois within the last 14 days [see warnings and precautions ( 5.8 ) and drug interactions ( 7 ) ]. concurrent use of monoamine oxidase inhibitors (maois) or use of maois within the last 14 days [see warnings and precautions ( 5.8 ) and drug interactions ( 7 ) ]. - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions ( 5.12 ) ] known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions ( 5.12 ) ] - hypersensitivity to morphine (e.g., anaphylaxis) [see adverse reactions ( 6 ) ]. hypersensitivity to morphine (e.g., anaphylaxis) [see adverse reactions ( 6 ) ]. prolonged use of opioid analgesics during pregnancy can cause neonatal opioid withdrawal syndrome [see warnings and precautions ( 5.5 ) ]. there are no available data with morphine sulfate oral solution in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. published studies with morphine use during pregnancy have not reported a clear association with morphine and major birth defects (see human data) . in published animal reproduction studies, morphine administered subcutaneously during the early gestational period produced neural tube defects (i.e., exencephaly and cranioschisis) at 5 and 16 times the human daily dose of 60 mg based on body surface area (hdd) in hamsters and mice, respectively, lower fetal body weight and increased incidence of abortion at 0.4 times the hdd in the rabbit, growth retardation at 6 times the hdd in the rat, and axial skeletal fusion and cryptorchidism at 16 times the hdd in the mouse. administration of morphine sulfate to pregnant rats during organogenesis and through lactation resulted in cyanosis, hypothermia, decreased brain weights, pup mortality, decreased pup body weights, and adverse effects on reproductive tissues at 3 to 4 times the hdd; and long-term neurochemical changes in the brain of offspring which correlate with altered behavioral responses that persist through adulthood at exposures comparable to and less than the hdd (see animal data) . based on animal data, advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. fetal/neonatal adverse reactions prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions ( 5.5 ) ]. labor or delivery opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. morphine sulfate oral solution is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including morphine sulfate oral solution, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. human data the results from a population-based prospective cohort, including 70 women exposed to morphine during the first trimester of pregnancy and 448 women exposed to morphine at any time during pregnancy, indicate no increased risk for congenital malformations. however, these studies cannot definitely establish the absence of any risk because of methodological limitations, including small sample size and non-randomized study design. animal data formal reproductive and developmental toxicology studies for morphine have not been conducted. exposure margins for the following published study reports are based on human daily dose of 60 mg morphine using a body surface area comparison (hdd). neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of morphine sulfate (35 to 322 mg/kg) on gestation day 8 to pregnant hamsters (4.7 to 43.5 times the hdd). a no adverse effect level was not defined in this study and the findings cannot be clearly attributed to maternal toxicity. neural tube defects (exencephaly), axial skeletal fusions, and cryptorchidism were reported following a single subcutaneous (sc) injection of morphine sulfate to pregnant mice (100 to 500 mg/kg) on gestation day 8 or 9 at 200 mg/kg or greater (16 times the hdd) and fetal resorption at 400 mg/kg or higher (32 times the hdd). no adverse effects were noted following 100 mg/kg morphine in this model (8 times the hdd). in one study, following continuous subcutaneous infusion of doses greater than or equal to 2.72 mg/kg to mice (0.2 times the hdd), exencephaly, hydronephrosis, intestinal hemorrhage, split supraoccipital, malformed sternebrae, and malformed xiphoid were noted. the effects were reduced with increasing daily dose; possibly due to rapid induction of tolerance under these infusion conditions. the clinical significance of this report is not clear. decreased fetal weights were observed in pregnant rats treated with 20 mg/kg/day morphine sulfate (3.2 times the hdd) from gestation day 7 to 9. there was no evidence of malformations despite maternal toxicity (10% mortality). in a second rat study, decreased fetal weight and increased incidences of growth retardation were noted at 35 mg/kg/day (5.7 times the hdd) and there was a reduced number of fetuses at 70 mg/kg/day (11.4 times the hdd) when pregnant rats were treated with 10, 35, or 70 mg/kg/day morphine sulfate via continuous infusion from gestation day 5 to 20. there was no evidence of fetal malformations or maternal toxicity. an increased incidence of abortion was noted in a study in which pregnant rabbits were treated with 2.5 (0.8 times the hdd) to 10 mg/kg morphine sulfate via subcutaneous injection from gestation day 6 to 10. in a second study, decreased fetal body weights were reported following treatment of pregnant rabbits with increasing doses of morphine (10 to 50 mg/kg/day) during the pre-mating period and 50 mg/kg/day (16 times the hdd) throughout the gestation period. no overt malformations were reported in either publication; although only limited endpoints were evaluated. in published studies in rats, exposure to morphine during gestation and/or lactation periods is associated with: decreased pup viability at 12.5 mg/kg/day or greater (2 times the hdd); decreased pup body weights at 15 mg/kg/day or greater (2.4 times the hdd); decreased litter size, decreased absolute brain and cerebellar weights, cyanosis, and hypothermia at 20 mg/kg/day (3.2 times the hdd); alteration of behavioral responses (play, social-interaction) at 1 mg/kg/day or greater (0.2 times the hdd); alteration of maternal behaviors (e.g., decreased nursing and pup retrievals) in mice at 1 mg/kg or higher (0.08 times the hdd) and rats at 1.5 mg/kg/day or higher (0.2 times the hdd); and a host of behavioral abnormalities in the offspring of rats, including altered responsiveness to opioids at 4 mg/kg/day (0.7 times the hdd) or greater. fetal and/or postnatal exposure to morphine in mice and rats has been shown to result in morphological changes in fetal and neonatal brain and neuronal cell loss, alteration of a number of neurotransmitter and neuromodulator systems, including opioid and non-opioid systems, and impairment in various learning and memory tests that appear to persist into adulthood. these studies were conducted with morphine treatment usually in the range of 4 to 20 mg/kg/day (0.7 to 3.2 times the hdd). additionally, delayed sexual maturation and decreased sexual behaviors in female offspring at 20 mg/kg/day (3.2 times the hdd), and decreased plasma and testicular levels of luteinizing hormone and testosterone, decreased testes weights, seminiferous tubule shrinkage, germinal cell aplasia, and decreased spermatogenesis in male offspring were also observed at 20 mg/kg/day (3.2 times the hdd). decreased litter size and viability were observed in the offspring of male rats that were intraperitoneally administered morphine sulfate for 1 day prior to mating at 25 mg/kg/day (4.1 times the hdd) and mated to untreated females. decreased viability and body weight and/or movement deficits in both first and second generation offspring were reported when male mice were treated for 5 days with escalating doses of 120 to 240 mg/kg/day morphine sulfate (9.7 to 19.5 times the hdd) or when female mice treated with escalating doses of 60 to 240 mg/kg/day (4.9 to 19.5 times the hdd) followed by a 5-day treatment-free recovery period prior to mating. similar multigenerational findings were also seen in female rats pre-gestationally treated with escalating doses of 10 to 22 mg/kg/day morphine (1.6 to 3.6 times the hdd). morphine is present in breast milk. published lactation studies report variable concentrations of morphine in breast milk with administration of immediate-release morphine to nursing mothers in the early postpartum period with a milk-to-plasma morphine auc ratio of 2.5:1 measured in one lactation study. however, there is insufficient information to determine the effects of morphine on the breastfed infant and the effects of morphine on milk production. lactation studies have not been conducted with morphine sulfate oral solution and no information is available on the effects of the drug on the breastfed infant or the effects of the drug on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for morphine sulfate oral solution and any potential adverse effects on the breastfed infant from morphine sulfate oral solution or from the underlying maternal condition. monitor infants exposed to morphine sulfate oral solution through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of morphine is stopped, or when breastfeeding is stopped. infertility chronic use of opioids may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions ( 6 ) and clinical pharmacology ( 12.2 ) ]. in published animal studies, morphine administration adversely effected fertility and reproductive endpoints in male rats and prolonged estrus cycle in female rats [see nonclinical toxicology ( 13 ) ]. the safety and effectiveness of morphine sulfate oral solution (2 mg/ml) have not been established for the management of pediatric patients 2 to 17 years of age with chronic pain severe enough to require an opioid analgesic when alternative treatments are inadequate. the safety and effectiveness of morphine sulfate oral solution (2 mg/ml) have not been established in pediatric patients less than 2 years of age. the safety and effectiveness of morphine sulfate oral solution 20 mg/ml have not been established in pediatric patients. pediatric use information is approved for hikma pharmaceuticals usa inc.'s morphine sulfate oral solution. however, due to hikma pharmaceuticals usa inc.'s marketing exclusivity rights, this drug product is not labeled with that informatio n. elderly patients (aged 65 years or older) may have increased sensitivity to morphine. in general, use caution when selecting a dose for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of morphine sulfate oral solution slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see warnings and precautions ( 5.7 ) ]. morphine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. morphine pharmacokinetics have been reported to be significantly altered in patients with cirrhosis. start these patients with a lower than usual dosage of morphine sulfate oral solution and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension [see clinical pharmacology ( 12.3 ) ]. morphine pharmacokinetics are altered in patients with renal failure. start these patients with a lower than usual dosage of morphine sulfate oral solution and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension [see clinical pharmacology ( 12.3 ) ]. morphine sulfate oral solution contains morphine, a schedule ii controlled substance. morphine sulfate oral solution contains morphine, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and tapentadol. morphine sulfate oral solution can be abused and is subject to misuse, addiction, and criminal diversion [see warnings and precautions ( 5.2 ) ]. all patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. “drug-seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control. abuse and addiction are separate and distinct from physical dependence and tolerance. healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. in addition, abuse of opioids can occur in the absence of true addiction. morphine sulfate oral solution, like other opioids, can be diverted for non-medical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of morphine sulfate oral solution: morphine sulfate oral solution is for oral use only. abuse of morphine sulfate oral solution poses a risk of overdose and death. the risk is increased with concurrent abuse of morphine sulfate oral solution with alcohol and other central nervous system depressants. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during chronic opioid therapy. tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects. physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage. do not abruptly discontinue morphine sulfate oral solution in a patient physically dependent on opioids. rapid tapering of morphine sulfate oral solution in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. when discontinuing morphine sulfate oral solution, gradually taper the dosage using a patient-specific plan that considers the following: the dose of morphine sulfate oral solution the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. to improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. in patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see dosage and administration (2.6) and warnings and precautions (5.4, 5.14)] . infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see use in specific populations ( 8.1) ]. morphine sulfate oral solution, cii 20 mg/ml oral syringe important information you need to know before using morphine sulfate oral solution: - the morphine sulfate oral solution 20 mg/ml should only be used in adults who have received opioids in the past or who are currently receiving opioids. - always use the oral syringe that comes with your morphine sulfate oral solution to measure your prescribed dose. - ask your healthcare provider or pharmacist to show you how to measure your prescribed dose. each morphine sulfate oral solution carton contains: - 1 morphine sulfate oral solution bottle - 1 oral syringe step 1: remove the morphine sulfate oral solution bottle and oral syringe from the carton. place all items on a flat surface. open the bottle by pressing downward firmly on the child-resistant cap and twisting it in the direction of the arrow (counter-clockwise). see figure a. do not throw away the child-resistant cap. figure a step 2: check the dose in milliliters (ml) as prescribed by your healthcare provider. find this number on the oral syringe. see figure b. figure b step 3: push the oral syringe plunger to the bottom of the barrel of the syringe (toward its tip) to remove excess air. see figure c. figure c step 4: on the flat surface, use one hand to hold the bottle and use your other hand to insert the oral syringe into the bottle opening. see figure d. figure d step 5: with the oral syringe in the bottle, pull the plunger to withdraw the dose prescribed by your healthcare provider (the amount of oral solution in step 2). see figure e. note: measure the dose of medicine from the widest part of the plunger. do not measure from the narrow tip. if you see air bubbles in the syringe, fully push in the plunger so that the oral solution flows back into the bottle. then withdraw your prescribed dose of oral solution. figure e step 6: remove the oral syringe from the bottle. see figure f. figure f step 7: check that the correct dose was drawn up into the oral syringe. see figure g. if the dose is not correct, insert the oral syringe tip into the bottle. fully push in the plunger so that the oral solution flows back into the bottle. repeat steps 4 through 6. figure g step 8: take the dose of morphine sulfate oral solution. see figure h. • place the tip of the oral syringe in your mouth. close your lips around the barrel of the syringe. • slowly push down the oral syringe plunger until the syringe is empty. figure h step 9: put the child-resistant cap back on the bottle. see figure i. figure i step 10: rinse the oral syringe with tap water after each use. see figure j. • remove the plunger from the oral syringe barrel. • rinse the oral syringe barrel and plunger with water and let them air dry. • when the oral syringe barrel and plunger are dry, put the plunger back into the oral syringe barrel for the next use. do not throw away the oral syringe. figure j how should i store morphine sulfate oral solution? • store morphine sulfate oral solution at room temperature 68°f to 77°f (20°c to 25°c). • protect from moisture. protect from light. store in carton, away from direct sunlight. • keep morphine sulfate oral solution and all medicines out of the reach of children. manufactured by: tris pharma, inc. monmouth junction, nj 08852 www.trispharma.com for more information, please call (732) 940-0358. this instructions for use has been approved by the u.s. food and drug administration.               revised: october 2021 lb8246 (individual printed medication guide and instructions for use only) rev. 07 10/2021

United States - English - NLM (National Library of Medicine)

bryant ranch prepack - epinephrine (unii: ykh834o4bh) (epinephrine - unii:ykh834o4bh) - epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg are indicated in the emergency treatment of allergic reactions (type i) including anaphylaxis to stinging insects (e.g., order hymenoptera, which include bees, wasps, hornets, yellow jackets and fire ants) and biting insects (e.g., triatoma, mosquitoes), allergen immunotherapy, foods, drugs, diagnostic testing substances (e.g., radiocontrast media) and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg are intended for immediate administration in patients who are determined to be at increased risk for anaphylaxis, including individuals with a history of anaphylactic reactions. anaphylactic reactions may occur within minutes after exposure and consist of flushing, apprehension, syncope, tachycardia, thready or unobtainable pulse associated with a fall in blood pressure, convulsions, vomiting, diarrhea and abdominal cramps, involuntary voiding, wheezing, dyspnea due to laryngeal spasm, pruritus, rashes, urticaria or angioedema. epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg are intended for immediate administration as emergency supportive therapy only and are not a substitute for immediate medical care. none risk summary there are no adequate and well controlled studies of the acute effect of epinephrine in pregnant women. in animal reproductive studies, epinephrine administered by the subcutaneous route to rabbits, mice, and hamsters during the period of organogenesis was teratogenic at doses 7 times and higher than the maximum recommended human intramuscular and subcutaneous dose on a mg/m2 basis. epinephrine is the first-line medication of choice for the treatment of anaphylaxis during pregnancy in humans. epinephrine should be used for treatment of anaphylaxis during pregnancy in the same manner as it is used in non-pregnant patients. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations disease-associated maternal and embryo/fetal risk: during pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate. the prevalence of anaphylaxis occurring during pregnancy is reported to be approximately 3 cases per 100,000 deliveries. management of anaphylaxis during pregnancy is similar to management in the general population. epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in pregnant and non-pregnant patients. in conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care. data animal data: in an embryofetal development study with rabbits dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including gastroschisis and embryonic lethality) at doses approximately 40 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days). in an embryofetal development study with mice dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including embryonic lethality) at doses approximately 8 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m2 basis at maternal subcutaneous dose of 1 mg/kg/day for 10 days). these effects were not seen in mice at approximately 4 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days). in an embryofetal development study with hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine was shown to be teratogenic at doses approximately 7 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day). risk summary there is no information on the presence of epinephrine in human milk, the effects on breastfed infants, or the effects on milk production. epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in breastfeeding and non-breastfeeding patients. epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg may be administered to pediatric patients at a dosage appropriate to body weight [see dosage and administration ( 2.1) ]. clinical experience with the use of epinephrine suggests that the adverse reactions seen in children are similar in nature and extent to those both expected and reported in adults. since the doses of epinephrine delivered from epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg are fixed, consider using other forms of injectable epinephrine if doses lower than 0.15 mg are deemed necessary. clinical studies for the treatment of anaphylaxis have not been performed in subjects aged 65 and over to determine whether they respond differently from younger subjects. however, other reported clinical experience with use of epinephrine for the treatment of anaphylaxis has identified that geriatric patients may be particularly sensitive to the effects of epinephrine. therefore, epinephrine injection, 0.3 mg should be administered with caution in elderly individuals, who may be at greater risk for developing adverse reactions after epinephrine administration [see warnings and precautions (5.5), overdosage (10) ]. epinephrine injection usp, 0.3 mg (auto-injector) epinephrine injection usp, 0.3 mg = one dose of 0.3 mg epinephrine usp, 0.3 mg/0.3 ml epinephrine injection usp, 0.15 mg (auto-injector) epinephrine injection usp, 0.15 mg = one dose of 0.15 mg epinephrine usp, 0.15 mg/0.3 ml for allergic emergencies (anaphylaxis) patient information read this patient information leaflet carefully before using the epinephrine injection, 0.3 mg (auto-injector) or epinephrine injection, 0.15 mg (auto-injector) and each time you get a refill. there may be new information. you, your parent, caregiver, or others who may be in a position to administer epinephrine injection, 0.3 mg (auto-injector) or epinephrine injection, 0.15 mg (auto-injector), should know how to use it before you have an allergic emergency. this information does not take the place of talking with your healthcare provider about your medical condition or your treatment. what is the most important information i should know about epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg? 1. epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg are single-dose automatic injection devices (auto-injectors) that contain epinephrine, a medicine used to treat allergic emergencies (anaphylaxis). anaphylaxis can be life threatening, can happen within minutes, and can be caused by stinging and biting insects, allergy injections, foods, medicines, exercise, or unknown causes. symptoms of anaphylaxis may include: - trouble breathing - wheezing - hoarseness (changes in the way your voice sounds) - hives (raised reddened rash that may itch) - severe itching - swelling of your face, lips, mouth, or tongue - skin rash, redness, or swelling - fast heartbeat - weak pulse - feeling very anxious - confusion - stomach pain - losing control of urine or bowel movements (incontinence) - diarrhea or stomach cramps - dizziness, fainting, or “passing out” (unconsciousness) 2. always carry your epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg with you because you may not know when anaphylaxis may happen. talk to your healthcare provider if you need additional units to keep at work, school, or other locations. tell your family members, caregivers, and others where you keep your epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg and how to use it before you need it. you may be unable to speak in an allergic emergency. 3. when you have an allergic emergency (anaphylaxis) - use epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg right away. - get emergency medical help right away.  you may need further medical attention. you may need to use a second epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg if symptoms continue or recur. only a healthcare provider should give additional doses of epinephrine if you need more than 2 injections for a single anaphylaxis episode. what are epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg? - epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg are disposable, pre-filled auto-injectors used to treat life-threatening, allergic emergencies including anaphylaxis in people who are at risk for or have a history of serious allergic emergencies. each device contains a single dose of epinephrine. - epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg are for immediate self (or caregiver) administration and do not take the place of emergency medical care. you should get emergency help right away after using epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg. - epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg are for people who have been prescribed this medicine by their healthcare provider. - the epinephrine injection, 0.3 mg (auto-injector) is for patients who weigh 66 pounds or more (30 kilograms or more). - the epinephrine injection, 0.15 mg (auto-injector) is for patients who weigh about 33 to 66 pounds (15 to 30 kilograms). - it is not known if epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg are safe and effective in children who weigh less than 33 pounds (15 kilograms). what should i tell my healthcare provider before using the epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg? before you use epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg, tell your healthcare provider about all your medical conditions, but especially if you: - have heart problems or high blood pressure. - have diabetes. - have thyroid problems. - have asthma. - have a history of depression. - have parkinson’s disease. - are pregnant or plan to become pregnant. it is not known if epinephrine will harm your unborn baby. - are breastfeeding or plan to breastfeed. it is not known if epinephrine passes into your breast milk. tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. tell your healthcare provider about all of your known allergies. especially tell your healthcare provider if you take certain asthma medicines. epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg and other medicines may affect each other, causing side effects. epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg may affect the way other medicines work, and other medicines may affect how epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg work. know the medicines you take. keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. use your epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg for treatment of anaphylaxis as prescribed by your healthcare provider, regardless of your medical conditions or the medicines you take. how should i use epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg? - each epinephrine injection, 0.3 mg (auto-injector) or epinephrine injection, 0.15 mg (auto-injector) contains only 1 dose of medicine (single-dose). - epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg auto-injectors deliver a fixed dose of epinephrine. the auto-injectors cannot be reused. do not try to reuse epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg after the device has been activated. it is normal for most of the medicine to remain in the auto-injector after the dose has been injected. the dose has been injected if the orange tip is extended and the window is blocked. - epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg should be injected into the middle of your outer thigh (upper leg). it can be injected through your clothing if needed. do not inject into a vein or into the buttocks, fingers, toes, hands or feet. - read the instructions for use at the end of this patient information leaflet about the right way to use epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg. - your healthcare provider will show you how to safely use the epinephrine injection, 0.3 mg (auto-injector) or epinephrine injection, 0.15 mg (auto-injector). - use your single-dose epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg exactly as your healthcare provider tells you to use it. you may need to use a second epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg if symptoms continue or recur. only a healthcare provider should give additional doses of epinephrine if you need more than 2 injections for a single anaphylaxis episode. - caution: never put your thumb, fingers, or hand over the orange tip. never press or push the orange tip with your thumb, fingers, or hand. the needle comes out of the orange tip. accidental injection into finger, hands or feet may cause a loss of blood flow to these areas. if an accidental injection happens, go immediately to the nearest emergency room. tell the healthcare provider where on your body you received the accidental injection. - your epinephrine injection, 0.3 mg (auto-injector) and epinephrine injection, 0.15 mg (auto-injector) may come packaged with an epinephrine injection trainer and separate epinephrine injection trainer instructions for use. the epinephrine injection trainer has a grey color.  the grey epinephrine injection trainer contains no medicine and no needle. keep the epinephrine injection trainer and the real epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg auto-injectors away from young children. the real epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg auto-injectors and epinephrine injection trainer are not toys. for young children, use of the epinephrine injection trainer and the real epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg auto-injectors should be supervised by an adult. periodically practice with your epinephrine injection trainer before an allergic emergency happens to make sure you are able to safely use the real epinephrine injection, 0.3 mg (auto-injector) and epinephrine injection, 0.15 mg (auto-injector) in an emergency. always carry your real epinephrine injection, 0.3 mg (auto-injector) or epinephrine injection 0.15 mg (auto-injector) with you in case of an allergic emergency. additional training resources are available at www.tevaepinephrine.com . - do not drop the auto-injector. if the auto-injector is dropped, check for damage and leakage. throw away (dispose of) the auto-injector and replace if damage or leakage is noticed or suspected. what are the possible side effects of epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg? epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg may cause serious side effects. - the epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg should only be injected into the middle of your outer thigh (upper leg). do not  inject the epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg into your: veins buttocks fingers, toes, hands, or feet if you accidentally inject epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg into any other part of your body, go to the nearest emergency room right away. tell the healthcare provider where on your body you received the accidental injection. - veins - buttocks - fingers, toes, hands, or feet if you accidentally inject epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg into any other part of your body, go to the nearest emergency room right away. tell the healthcare provider where on your body you received the accidental injection. - rarely, patients who have used epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg may develop infections at the injection site within a few days of an injection. some of these infections can be serious. call your healthcare provider right away if you have any of the following at an injection site: redness that does not go away swelling tenderness the area feels warm to the touch - redness that does not go away - swelling - tenderness - the area feels warm to the touch - cuts on the skin, bent needles, and needles that remain in the skin after the injection, have happened in young children who do not cooperate and kick or move during an injection. if you inject a young child with epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg, hold their leg firmly in place before and during the injection to prevent injuries. ask your healthcare provider to show you how to: - hold the young child firmly in place (restrain). - with 1 hand, quickly twist the yellow cap off the epinephrine injection, 0.3 mg auto-injector or the green cap off the epinephrine injection, 0.15 mg auto-injector in the direction of the “twist arrow” to remove it. - grasp the auto-injector in your fist with the orange tip (needle end) pointing downward. - with your other hand, pull off the blue safety release. - if you have certain medical conditions, or take certain medicines, your condition may get worse or you may have longer lasting side effects when you use your epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg.  talk to your healthcare provider about all your medical conditions. common side effects of epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg include: - fast, irregular or “pounding” heartbeat - sweating - headache - weakness - shakiness - paleness - feelings of over excitement, nervousness or anxiety - dizziness - nausea or vomiting - breathing problems these side effects may go away with rest. tell your healthcare provider if you have any side effect that bothers you or that does not go away. these are not all the possible side effects of the epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg. for more information, ask your healthcare provider or pharmacist. call your doctor for medical advice about side effects. you may report side effects to fda at 1-800-fda-1088. how should i store epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg? - store epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg at room temperature between 68° to 77°f (20° to 25°c). - protect from light. - do not  expose to extreme cold or heat. for example, do not  store in your vehicle’s glove box and do not  store in the refrigerator or freezer. - examine the contents in the clear window of your auto-injector periodically. the solution should be clear. if the solution is discolored (pinkish or darker than slightly yellow) or contains solid particles, replace the unit. - always protect your epinephrine injection, 0.3 mg (auto-injector) and epinephrine injection, 0.15 mg (auto-injector) from damage and water. - the blue safety release helps to prevent accidental injection. keep the blue safety release on until you need to use epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg. - your epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg has an expiration date. replace it before the expiration date. throw away (dispose of) expired, unwanted, or unused epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg in an fda-cleared sharps disposal container. do not throw away the epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg in your household trash. if you do not have an fda-cleared sharps disposal container, you may use a household container that is: made of heavy-duty plastic, can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, upright and stable during use, leak-resistant, and properly labeled to warn of hazardous waste inside the container. when your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. there may be state or local laws about how you should throw away used needles and syringes. for more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the fda’s website at: http://www.fda.gov/safesharpsdisposal visit the fda’s website (https://www.fda.gov/drugs/safe-disposal-medicines/disposal-unused-medicines-what-you-should-know) for more information about how to throw away (dispose of) unused, unwanted or expired medicines. - made of heavy-duty plastic, - can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, - upright and stable during use, - leak-resistant, and - properly labeled to warn of hazardous waste inside the container. when your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. there may be state or local laws about how you should throw away used needles and syringes. for more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the fda’s website at: http://www.fda.gov/safesharpsdisposal visit the fda’s website (https://www.fda.gov/drugs/safe-disposal-medicines/disposal-unused-medicines-what-you-should-know) for more information about how to throw away (dispose of) unused, unwanted or expired medicines. keep epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg and all medicines out of the reach of children. general information about the safe and effective use of epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. do not use the epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg for a condition for which it was not prescribed. do not give your epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg to other people. this patient information leaflet summarizes the most important information about epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg. if you would like more information, talk to your healthcare provider. you can ask your pharmacist or healthcare provider for information about epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg that is written for health professionals. for more information and video instructions on the use of epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg go to www.tevaepinephrine.com or call 1-888-838-2872. what are the ingredients in epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg? active ingredients : epinephrine inactive ingredients:  sodium chloride, sodium metabisulfite, sodium tartrate (dihydrate), hydrochloric acid, and water important information - the epinephrine injection, 0.3 mg (auto-injector) has a yellow colored label. - the epinephrine injection, 0.15 mg (auto-injector) has a green colored label. - the epinephrine injection trainer has a grey color and contains no medicine and no needle. - your auto-injector is designed to work through clothing. - the blue safety release on the epinephrine injection, 0.3 mg (auto-injector) and epinephrine injection, 0.15 mg (auto-injector) helps to prevent accidental injection of the device. do not remove the blue safety release until you are ready to use it. - choking hazard: the blue safety release is a small part that may become a choking hazard for children. throw away the blue safety release immediately after using epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg auto-injector. - only inject into the middle of the outer thigh (upper leg). never inject into any other part of the body. - never put your thumb, fingers, or your hand over the orange tip. the needle comes out of the orange tip. - if an accidental injection happens, get emergency medical help right away. instructions for use epinephrine injection usp, 0.3 mg (auto-injector) epinephrine injection usp, 0.3 mg = one dose of 0.3 mg epinephrine usp, 0.3 mg/0.3 ml epinephrine injection usp, 0.15 mg (auto-injector) epinephrine injection usp, 0.15 mg = one dose of 0.15 mg epinephrine usp, 0.15 mg/0.3 ml for allergic emergencies (anaphylaxis) read this instructions for use carefully before you use epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg. before you need to use your single-dose epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg auto-injector, make sure your healthcare provider shows you the right way to use it. parents, caregivers, and others who may be in a position to administer epinephrine injection, 0.3 mg (auto-injector) or epinephrine injection, 0.15 mg (auto-injector) should also understand how to use it as well. if you have any questions, ask your healthcare provider. your epinephrine injection, 0.3 mg (auto-injector) and epinephrine injection, 0.15 mg (auto-injector) a dose of epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg requires 3 steps: prepare, administer and get emergency medical help step 1. prepare epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg for injection quickly twist the yellow cap off the epinephrine injection, 0.3 mg auto-injector or the green cap off the epinephrine injection, 0.15 mg auto-injector in the direction of the “twist arrow” to remove it. grasp the auto-injector in your fist with the orange tip (needle end) pointing downward. with your other hand, pull off the blue safety release. important: the blue safety release is a small part that may become a choking hazard for children. throw away the blue safety release immediately after using epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg. note: - the needle comes out of the orange tip. - to avoid an accidental injection, never put your thumb, fingers or hand over the orange tip. if an accidental injection happens, get emergency medical help right away. step 2. administer epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg if you are administering epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg to a young child, hold the leg firmly in place while administering an injection. place the orange tip against the middle of the outer thigh (upper leg) at a right angle (perpendicular) to the thigh. swing and push the auto-injector firmly  until it ‘clicks’. the click signals that the injection has started. hold firmly in place for 3 seconds (count slowly 1,2,3). the injection is now complete. remove the auto-injector from the thigh.  the orange tip will extend to cover the needle. if the needle is still visible, do not attempt to reuse it. massage the injection area for 10 seconds. step 3. get emergency medical help now. you may need further medical attention. you may need to use a second epinephrine injection, 0.3 mg (auto-injector) or epinephrine injection, 0.15 mg (auto-injector) if symptoms continue or recur. - take your used auto-injector with you when you go to see a healthcare provider. - tell the healthcare provider that you have received an injection of epinephrine. show the healthcare provider where you received the injection. - give your used epinephrine injection, 0.3 mg (auto-injector) or epinephrine injection, 0.15 mg (auto-injector) to the healthcare provider for inspection and proper disposal. - ask for a refill, if needed. note: - keep the epinephrine injection trainer and the real epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg auto-injectors away from young children. the real epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg auto-injectors and epinephrine injection trainer are not toys. for young children, use of the epinephrine injection trainer and the real epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg auto-injectors should be supervised by an adult. - a carrying tube is not provided as seen with other products. - epinephrine injection, 0.3 mg and epinephrine injection, 0.15 mg are single-dose injectable devices that deliver a fixed dose of epinephrine. the auto-injector cannot be reused. do not attempt to reuse epinephrine injection after the device has been activated. it is normal for most of the medicine to remain in the auto-injector after the dose is injected. the correct dose has been administered if the orange needle tip is extended and the window is blocked. - your epinephrine injection, 0.3 mg (auto-injector) and epinephrine injection, 0.15 mg (auto-injector) may come packaged with an epinephrine injection trainer and separate epinephrine injection trainer instructions for use. the epinephrine injection trainer has a grey color. the grey epinephrine injection trainer contains no medicine and no needle. practice with your epinephrine injection trainer, but always carry your real epinephrine injection, 0.3 mg auto-injector or epinephrine injection, 0.15 mg auto-injector in case of an allergic emergency. - if you are administering epinephrine injection, 0.3 mg or epinephrine injection, 0.15 mg to a young child, ask your healthcare provider to show you how to (1) hold the young child firmly in place (restrain), (2) with 1 hand, quickly twist the yellow cap off the epinephrine injection, 0.3 mg (auto-injector) or the green cap off the epinephrine injection, 0.15 mg (auto-injector) in the direction of the “twist arrow” to remove it, (3) grasp the auto-injector in your fist with the orange tip (needle end) pointing downward and (4) with your other hand, pull off the blue safety release, and how to properly hold the leg in place while administering a dose. - do not try to take the epinephrine injection, 0.3 mg (auto-injector) or epinephrine injection, 0.15 mg (auto-injector) apart. this patient information and instructions for use have been approved by the u.s. food and drug administration. keep this and all medications out of the reach of children. manufactured for: teva pharmaceuticals usa, inc. north wales, pa 19454 rev. c 1/2021 epinephrine injection usp, 0.3 mg (auto-injector) epinephrine injection usp, 0.3 mg = one dose of 0.3 mg epinephrine usp, 0.3 mg/0.3 ml epinephrine injection usp, 0.15 mg (auto-injector) epinephrine injection usp, 0.15 mg = one dose of 0.15 mg epinephrine usp, 0.15 mg/0.3 ml tevaepinephrine.com register your epinephrine injection 0.3 mg (auto-injector) or epinephrine injection 0.15 mg (auto-injector) at www.tevaepinephrine.com  and find out more about: - free epinephrine injection auto-injector refill reminder program . it is important to keep your auto-injector up-to-date. register up to 6 epinephrine injection 0.3 mg (auto-injectors) or epinephrine injection 0.15 mg (auto-injectors) and receive automatic refill reminder alerts. - receive periodic information related to allergies and allergens. - instructional video for more information about epinephrine injection 0.3 mg (auto-injector) or epinephrine injection 0.15 mg (auto-injector) and proper use of the products, call teva at 1-888-838-2872 or visit www.tevaepinephrine.com . epinephrine injection trainer instructions for use in an emergency: do not use the grey trainer. use your real yellow epinephrine injection 0.3 mg auto-injector or real green epinephrine injection 0.15 mg auto-injector. important information - the trainer label has a grey color. - the trainer contains no medicine and no needle. keep the grey trainer away from young children. the trainer is not a toy. young children should only practice with the trainer under adult supervision. - periodically practice with the grey trainer before an allergic emergency (anaphylaxis) happens to make sure you are able to safely use the real yellow epinephrine injection 0.3 mg auto-injector or real green epinephrine injection 0.15 mg auto-injector in case of an emergency. - always carry your real yellow epinephrine injection 0.3 mg auto-injector or real green epinephrine injection 0.15 mg auto-injector in case of an allergic emergency. - small parts like the blue safety release may become a choking hazard for children. put the blue safety release back on the trainer and reset it immediately after practicing. the epinephrine injection trainer familiarize yourself with this grey trainer. practice until you are comfortable using it. your grey trainer: •  never put your thumb, other fingers, or hand over the orange tip (below grey safety cap). • the orange tip is where the needle comes out of your epinephrine injection 0.3 mg auto-injector or epinephrine injection 0.15 mg auto-injector. practice instructions 1 prepare  the trainer for simulated injection - grasp the grey trainer in your fist with the orange tip pointing downward  and twist off grey cap in the direction of “twist arrow”. - with your other hand, pull off blue safety release . - removing the blue safety release unlocks the trainer. 2 administer  the trainer simulation - if practicing with a young child, hold the leg firmly in place while using the epinephrine injection trainer. ask your healthcare provider to show you how to: 1. hold the young child firmly in place (restrain). 2. with 1 hand, quickly twist the grey cap off the epinephrine injection trainer in the direction of the “twist arrow” to remove it. 3. grasp the auto-injector in your fist with the orange tip (needle end) pointing downward. 4. with your other hand, pull off the blue safety release, and how to properly hold the leg to practice so that you will be prepared before an allergic emergency happens. 1. hold the young child firmly in place (restrain). 2. with 1 hand, quickly twist the grey cap off the epinephrine injection trainer in the direction of the “twist arrow” to remove it. 3. grasp the auto-injector in your fist with the orange tip (needle end) pointing downward. 4. with your other hand, pull off the blue safety release, and how to properly hold the leg to practice so that you will be prepared before an allergic emergency happens. - place the orange tip against the middle of the outer thigh (upper leg) at a right angle (perpendicular) to the thigh. - swing and push the trainer firmly  until it ‘clicks’. the click signals that the injection has started. - hold firmly in place for 3 seconds (count slowly 1,2,3). - remove the trainer from the thigh  and massage the injection area for 10 seconds. the orange tip automatically extends out after use. note: - in an actual emergency, you would need to seek emergency medical help right away. - the actual auto-injector is made to work through clothing. - do not inject into any other part of the body. 3 to reset  the trainer - put the blue safety release back on the trainer. - replace grey cap. note: with the real yellow epinephrine injection 0.3 mg auto-injector or real green epinephrine injection 0.15 mg auto-injector, the orange tip covers the needle after self-injection to help protect you from accidentally sticking yourself or others. practice session information in case of an allergic emergency, use the real yellow epinephrine injection 0.3 mg auto-injector or real green epinephrine injection 0.15 mg auto-injector and not the grey trainer. follow instructions above. repeat as often as needed until you are able to self-inject quickly and correctly. reread: - the trainer instructions for use - the “patient information” that comes with your epinephrine injection 0.3 mg auto-injector or epinephrine injection 0.15 mg auto-injector train others who could help you in an emergency: • your parents, caregivers, and others who may be in a position to administer epinephrine injection 0.3 mg or epinephrine injection 0.15 mg should know how    to help you during an allergic emergency (anaphylaxis). before an emergency occurs, have them: - practice activating the trainer - read these trainer instructions and the “patient information” for more information about the epinephrine injection 0.3 mg auto-injector and epinephrine injection 0.15 mg auto-injector and the proper use of the products, go to www.tevaepinephrine.com . caution: important differences between the trainer and your real yellow epinephrine injection 0.3 mg (auto-injector) or real green epinephrine injection 0.15 mg (auto-injector) trainer (grey) epinephrine injection 0.3 mg (yellow) epinephrine injection 0.15 mg (green) contains medicine? no yes yes has needle? no yes yes comes in carrier tube? no no no color of label grey yellow green has expiration date? no yes yes can be reused? yes no (use only one time) no (use only one time) okay to remove and replace cap and/or safety release? yes no (remove just one time before use) no (remove just one time before use) pressure needed to hold against thigh? moderate strong strong this trainer instructions for use has been approved by the u.s. food and drug administration. keep this and all medications out of the reach of children. manufactured for: teva pharmaceuticals usa, inc. north wales, pa 19454 rev. d 1/2021

United States - English - NLM (National Library of Medicine)

bryant ranch prepack - ipratropium bromide (unii: j697uz2a9j) (ipratropium - unii:gr88g0i6ul) - ipratropium bromide nasal solution 0.06% is indicated for the symptomatic relief of rhinorrhea associated with the common cold or seasonal allergic rhinitis for adults and children age 5 years and older. ipratropium bromide 0.06% does not relieve nasal congestion or sneezing associated with the common cold or seasonal allergic rhinitis. the safety and effectiveness of the use of ipratropium bromide 0.06% beyond four days in patients with the common cold or beyond three weeks in patients with seasonal allergic rhinitis has not been established. ipratropium bromide nasal solution 0.06% is contraindicated in patients with a history of hypersensitivity to atropine or its derivatives, or to any of the other ingredients. ipratropium bromide nasal solution 0.06% nasal spray, 42 mcg/spray rx only read complete instructions carefully before using. in order to ensure proper dosing, do not attempt to change the size of the spray opening. ipratropium bromide nasal solution 0.06% is indicated for the symptomatic relief of rhinorrhea (runny nose) associated with the common cold or seasonal allergic rhinitis for adults and children age 5 years and older. ipratropium bromide nasal solution 0.06% does not relieve nasal congestion or sneezing, associated with the common cold or seasonal allergic rhinitis. do not use ipratropium bromide nasal solution 0.06 % for longer than four days for a common cold or three weeks for seasonal allergic rhinitis unless instructed by your physician. read complete instructions carefully and use only as directed. to use: figure 1 figure 1 figure 2 figure 2 figure 3 figure 3 to clean: if the nasal tip becomes clogged, remove the clear plastic dust cap and safety clip. hold the nasal tip under running, warm tap water (figure 4) for about a minute. dry the nasal tip, reprime the nasal spray pump (step 2 above), and replace the plastic dust cap and safety clip. figure 4 figure 4 caution: ipratropium bromide nasal solution 0.06% is intended to relieve your rhinorrhea (runny nose) with regular use. it is therefore important that you use ipratropium bromide nasal solution 0.06% as prescribed by your physician. for most patients, some improvement in runny nose is usually apparent following the first dose of treatment with ipratropium bromide nasal solution 0.06%. do not use ipratropium bromide nasal solution 0.06% for longer than four days for your cold or three weeks for seasonal allergic rhinitis unless instructed by your physician. do not spray ipratropium bromide nasal solution 0.06% in your eyes. should this occur, immediately flush your eye with cool tap water for several minutes. if you accidentally spray ipratropium bromide nasal solution 0.06% in your eyes, you may experience a temporary blurring of vision, visual halos or colored images in association with red eyes from conjunctival and corneal congestion, development or worsening of narrow-angle glaucoma, pupil dilation, or acute eye pain/discomfort, and increased sensitivity to light, which may last a few hours. should eye pain or blurred vision occur, contact your doctor. should you experience excessive nasal dryness or episodes of nasal bleeding, contact your doctor. if you have glaucoma or difficulty urinating due to an enlargement of the prostate, be sure to tell your physician prior to using ipratropium bromide nasal solution 0.06%. if you are pregnant or breast feeding your baby, be sure to tell your physician prior to using ipratropium bromide nasal solution 0.06%. storage store at 20° to 25°c (68° to 77°f). [see usp controlled room temperature.] avoid freezing. keep out of reach of children. address medical inquiries to hikma pharmaceuticals usa inc. at 1-800-962-8364. distributed by: hikma pharmaceuticals usa inc. berkeley heights, nj 07922 c50000618/01 revised july 2022

United States - English - NLM (National Library of Medicine)

bryant ranch prepack - ipratropium bromide (unii: j697uz2a9j) (ipratropium - unii:gr88g0i6ul) - ipratropium bromide nasal solution 0.03% is indicated for the symptomatic relief of rhinorrhea associated with allergic and nonallergic perennial rhinitis in adults and children age 6 years and older. ipratropium bromide 0.03% does not relieve nasal congestion, sneezing, or postnasal drip associated with allergic or nonallergic perennial rhinitis. ipratropium bromide nasal solution 0.03% is contraindicated in patients with a history of hypersensitivity to atropine or its derivatives, or to any of the other ingredients. ipratropium bromide nasal solution, 0.03% nasal spray, 21mcg/spray read complete instructions carefully before using. in order to ensure proper dosing, do not attempt to change the size of the spray opening. ipratropium bromide nasal solution, 0.03% is indicated for the symptomatic relief of rhinorrhea (runny nose) associated with allergic and nonallergic perennial rhinitis in adults and children age 6 years and older. ipratropium bromide nasal solution, 0.03% does not relieve nasal congestion, sneezing, or postnasal drip associated with allergic or nonallergic perennial rhinitis. read complete instructions carefully and use only as directed. to use: figure 1 figure 1 figure 2 figure 2 figure 3 figure 3 to clean: if the nasal tip becomes clogged, remove the clear plastic dust cap and safety clip. hold the nasal tip under running, warm tap water (figure 4) for about a minute. dry the nasal tip, reprime the nasal spray pump (step 2 above), and replace the plastic dust cap and safety clip. figure 4 figure 4 caution: ipratropium bromide nasal solution, 0.03% is intended to relieve your rhinorrhea (runny nose) with regular use. it is therefore important that you use ipratropium bromide nasal solution, 0.03% as prescribed by your physician. for most patients, some improvement in runny nose is usually apparent during the first full day of treatment with ipratropium bromide nasal solution, 0.03% some patients may require up to two weeks of treatment to obtain maximum benefit. do not spray ipratropium bromide nasal solution, 0.03% in your eyes. should this occur, immediately flush your eye with cool tap water for several minutes. if you accidentally spray ipratropium bromide nasal solution, 0.03% in your eyes, you may experience a temporary blurring of vision, visual halos or colored images in association with red eyes from conjunctival and corneal congestion, development or worsening of narrow-angle glaucoma, pupil dilation, or acute eye pain/discomfort, and increased sensitivity to light, which may last a few hours. should acute eye pain or blurred vision occur, contact your doctor. should you experience excessive nasal dryness or episodes of nasal bleeding contact your doctor. if you have glaucoma or difficulty urinating due to an enlargement of the prostate, be sure to tell your physician prior to using ipratropium bromide nasal solution, 0.03% if you are pregnant or you are breast feeding your baby, be sure to tell your physician prior to using ipratropium bromide nasal solution, 0.03% storage store at 20° to 25°c (68° to 77°f). [see usp controlled room temperature.] avoid freezing. keep out of reach of children. address medical inquiries to hikma pharmaceuticals usa inc. at 1-800-962-8364. distributed by: hikma pharmaceuticals usa inc. berkeley heights, nj 07922 c50000619/01 revised july 2022

United States - English - NLM (National Library of Medicine)

bryant ranch prepack - dexlansoprazole (unii: uye4t5i70x) (dexlansoprazole - unii:uye4t5i70x) - dexlansoprazole delayed-release capsules are indicated in patients 12 years of age and older for healing of all grades of erosive esophagitis (ee) for up to eight weeks. dexlansoprazole delayed-release capsules are indicated in patients 12 years of age and older to maintain healing of ee and relief of heartburn for up to six months in adults and 16 weeks in patients 12 to 17 years of age. dexlansoprazole delayed-release capsules are indicated in patients 12 years of age and older for the treatment of heartburn associated with symptomatic non-erosive gastroesophageal reflux disease (gerd) for four weeks. - dexlansoprazole delayed-release capsules are contraindicated in patients with known hypersensitivity to any component of the formulation [see description (11)] . hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis and urticaria [see warnings and precautions (5.2), adverse reactions (6)] . - ppis, including dexlansoprazole delayed-release capsules, are contraindicated with rilpivirine-containing products [see drug interactions (7)] . risk summary there are no studies with dexlansoprazole use in pregnant women to inform a drug-associated risk. dexlansoprazole is the r-enantiomer of lansoprazole, and published observational studies of lansoprazole use during pregnancy did not demonstrate an association of adverse pregnancy-related outcomes with lansoprazole (see data) . in animal reproduction studies, oral administration of lansoprazole to rats during organogenesis through lactation at 1.8 times the maximum recommended human dexlansoprazole dose produced reductions in the offspring in femur weight, femur length, crown-rump length and growth plate thickness (males only) on postnatal day 21 (see data) . these effects were associated with reduction in body weight gain. advise pregnant women of the potential risk to the fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the us general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data human data dexlansoprazole is the r-enantiomer of lansoprazole. available data from published observational studies failed to demonstrate an association of adverse pregnancy-related outcomes and lansoprazole use. methodological limitations of these observational studies cannot definitely establish or exclude any drug- associated risk during pregnancy. in a prospective study by the european network of teratology information services, outcomes from a group of 62 pregnant women administered median daily doses of 30 mg of lansoprazole were compared to a control group of 868 pregnant women who did not take any ppis. there was no difference in the rate of major malformations between women exposed to ppis and the control group, corresponding to a relative risk (rr)=1.04, [95% confidence interval (ci) 0.25-4.21]. in a population-based retrospective cohort study covering all live births in denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of first trimester exposure to lansoprazole in 794 live births. a meta-analysis that compared 1,530 pregnant women exposed to ppis in at least the first trimester with 133,410 unexposed pregnant women showed no significant increases in risk for congenital malformations or spontaneous abortion with exposure to ppis (for major malformations odds ratio (or)=1.12, [95% ci 0.86- 1.45] and for spontaneous abortions or=1.29, [95% ci 0.84-1.97]). animal data an embryo-fetal development study conducted in rabbits at oral dexlansoprazole doses up to 30 mg/kg/day (approximately nine times the maximum recommended human dexlansoprazole dose [60 mg/day] based on body surface area) during organogenesis showed no effects on fetuses due to dexlansoprazole. in addition, embryo-fetal development studies performed in rats with oral lansoprazole at doses up to 150 mg/kg/day (40 times the recommended human lansoprazole dose based on body surface area) during organogenesis and in rabbits with oral lansoprazole at doses up to 30 mg/kg/day (16 times the recommended human lansoprazole dose based on body surface area) during organogenesis revealed no effects on fetuses due to lansoprazole. a pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with lansoprazole at oral doses of 10 to 100 mg/kg/day (0.2 to 1.8 times the maximum recommended human dexlansoprazole dose of 60 mg based on dexlansoprazole auc [area under the plasma concentration-time curve]) administered during organogenesis through lactation. maternal effects observed at 100 mg/kg/day (1.8 times the maximum recommended human dexlansoprazole dose of 60 mg based on dexlansoprazole auc) included increased gestation period, decreased body weight gain during gestation, and decreased food consumption. the number of stillbirths was increased at this dose, which may have been secondary to maternal toxicity. body weight of pups was reduced at 100 mg/kg/day starting on postnatal day 11. femur weight, femur length, and crown-rump length were reduced at 100 mg/kg/day on postnatal day 21. femur weight was still decreased in the 100 mg/kg/day group at age 17 to 18 weeks. growth plate thickness was decreased in the 100 mg/kg/day males on postnatal day 21, and was increased in the 30 and 100 mg/kg/day males at age 17 to 18 weeks. the effects on bone parameters were associated with reduction in body weight gain. risk summary there is no information regarding the presence of dexlansoprazole in human milk, the effects on the breastfed infant, or the effects on milk production. however, lansoprazole and its metabolites are present in rat milk. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for dexlansoprazole delayed-release capsules and any potential adverse effects on the breastfed child from dexlansoprazole delayed-release capsules or from the underlying maternal condition. the safety and effectiveness of dexlansoprazole delayed-release capsules have been established in pediatric patients 12 years to 17 years of age for the healing of all grades of ee, the maintenance of healed ee and relief of heartburn, and treatment of heartburn associated with symptomatic non-erosive gerd. use of dexlansoprazole delayed-release capsules in this age group is supported by evidence from adequate and well-controlled studies of dexlansoprazole delayed-release capsules in adults with additional safety, efficacy and pharmacokinetic data in pediatric patients 12 to 17 years of age. the adverse reaction profile in patients 12 to 17 years of age was similar to adults [see dosage and administration (2.1), adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14)] . the safety and effectiveness of dexlansoprazole delayed-release capsules has not been established in pediatric patients less than 12 years of age. dexlansoprazole delayed-release capsules are not recommended in pediatric patients less than two years of age [see warnings and precautions (5.12)] . nonclinical studies in juvenile rats treated with lansoprazole (the racemic mixture) have demonstrated adverse effects of heart valve thickening and bone changes at dexlansoprazole exposures which are expected to be similar to or higher than the dexlansoprazole exposure in pediatric patients one year to two years of age, as described below in juvenile animal toxicity data . the use of dexlansoprazole delayed-release capsules is not recommended for the treatment of symptomatic gerd in pediatric patients one month to less than one year of age because lansoprazole was not shown to be effective in a multicenter, double-blind controlled trial. juvenile animal toxicity data heart valve thickening in two oral toxicity studies, thickening of the mitral heart valve occurred in juvenile rats treated with lansoprazole. heart valve thickening was observed primarily with oral dosing initiated on postnatal day 7 (age equivalent to neonatal humans) and postnatal day 14 (human age equivalent of approximately one year) at doses of 250 mg/kg/day and higher (at postnatal day 7 and postnatal day 14 respectively, 2.5 and 1.8 times the expected dexlansoprazole exposure based on auc in pediatric patients one year to two years of age). the treatment durations associated with heart valve thickening ranged from 5 days to 8 weeks. the findings reversed or trended towards reversibility after a 4-week drug-free recovery period. the incidence of heart valve thickening after initiation of dosing on postnatal day 21 (human age equivalent of approximately two years) was limited to a single rat (1/24) in groups given 500 mg/kg/day for 4 or 8 weeks (2.1 times the expected dexlansoprazole exposure based on auc in pediatric patients one year to two years of age). based on the low incidence of heart valve thickening in 21-day old rats and the equivalent human age, the risk of heart valve injury does not appear to be relevant to patients two years of age and older. bone changes in an eight-week oral toxicity study of lansoprazole in juvenile rats with dosing initiated on postnatal day 7, doses equal to or greater than 100 mg/kg/day (dexlansoprazole exposure based on auc approximately equal to that in pediatric patients one year to two years of age) produced delayed growth, with impairment of weight gain observed as early as postnatal day 10 (age equivalent to neonatal humans). at the end of treatment, the signs of impaired growth at 100 mg/kg/day and higher included reductions in body weight (14 to 44% compared to controls), absolute weight of multiple organs, femur weight, femur length and crown-rump length. femoral growth plate thickness was reduced only in males and only at the 500 mg/kg/day dose. the effects related to delayed growth persisted through the end of the four-week recovery period. longer term data were not collected. of the total number of patients (n=4548) in clinical studies of dexlansoprazole delayed-release capsules, 11% of patients were aged 65 years and over, while 2% were 75 years and over. no overall differences in safety or effectiveness were observed between these patients and younger patients and other reported clinical experience has not identified significant differences in responses between geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see clinical pharmacology (12.3)] . no dosage adjustment for dexlansoprazole delayed-release capsules is necessary for patients with mild hepatic impairment (child-pugh class a). in a study of adult patients with moderate hepatic impairment (child-pugh class b) who received a single dose of 60 mg dexlansoprazole delayed-release capsules, there was a significant increase in systemic exposure of dexlansoprazole compared to healthy subjects with normal hepatic function [see clinical pharmacology (12.3)] . therefore, for patients with moderate hepatic impairment (child-pugh class b), dosage reduction is recommended for the healing of ee [see dosage and administration (2.2)]. no studies have been conducted in patients with severe hepatic impairment (child-pugh class c); the use of dexlansoprazole delayed-release capsules is not recommended for these patients [see dosage and administration (2.2)] . taking dexlansoprazole delayed-release capsules with applesauce: - place 1 tablespoon of applesauce into a clean container. - carefully open the capsule and sprinkle the granules onto the applesauce. - swallow the applesauce and granules right away. do not chew the granules. do not save the applesauce and granules for later use. giving dexlansoprazole delayed-release capsules with water using an oral syringe: - place 20 ml of water into a clean container. - carefully open the capsule and empty the granules into the container of water. - use an oral syringe to draw up the water and granule mixture. - gently swirl the oral syringe to keep the granules from settling. - place the tip of the oral syringe in your mouth. give the medicine right away. do not save the water and granule mixture for later use. - refill the syringe with 10 ml of water and swirl gently. place the tip of the oral syringe in your mouth and give the medicine that is left in the syringe. - repeat step 6. giving dexlansoprazole delayed-release capsules with water through a nasogastric tube (ng tube): for people who have an ng tube that is size 16 french or larger , dexlansoprazole delayed-release capsules may be given as follows: - place 20 ml of water into a clean container. - carefully open the capsule and empty the granules into the container of water. - use a 60 ml catheter-tip syringe to draw up the water and granule mixture. - gently swirl the catheter-tip syringe to keep the granules from settling. - connect the catheter-tip syringe to the ng tube. - give the mixture right away through the ng tube that goes into the stomach. do not save the water and granule mixture for later use. - refill the catheter-tip syringe with 10 ml of water and swirl gently. flush the ng tube with the water. - repeat step 7. how should i store dexlansoprazole delayed-release capsules? - store dexlansoprazole delayed-release capsules at room temperature between 68°f to 77°f (20°c to 25°c). keep dexlansoprazole delayed-release capsules and all medicines out of the reach of children. manufactured for: twi pharmaceuticals usa, inc. paramus, nj 07652 this instructions for use have been approved by the u.s. food and drug administration. manufactured by: twi pharmaceuticals, inc. taoyuan city, 320023, taiwan revised: 07/2023 all trademark names are the property of their respective owners.

Ireland - English - HPRA (Health Products Regulatory Authority)

pharmargus limited - fluorescein sodium - solution for injection - 100 milligram(s)/millilitre - fluorescein

United States - English - NLM (National Library of Medicine)

bryant ranch prepack - buprenorphine hydrochloride (unii: 56w8mw3en1) (buprenorphine - unii:40d3scr4gz) - buprenorphine sublingual tablets are indicated for the treatment of opioid dependence and are preferred for induction. buprenorphine sublingual tablets should be used as part of a complete treatment plan to include counseling and psychosocial support. buprenorphine sublingual tablets are contraindicated in patients with a history of hypersensitivity to buprenorphine, as serious adverse reactions, including anaphylactic shock, have been reported [see warnings and precautions (5.9)]. risk summary the data on use of buprenorphine, the active ingredient in buprenorphine sublingual tablets, in pregnancy, are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure. there are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations [see data] . observational studies have reported on congenital malformations among buprenorphine-exposed pregnancies, but were also not designed appropriately to assess the risk of congenital malformations specifically due to buprenorphine exposure [see data]. reproductive and developmental studies in rats and rabbits identified adverse events at clinically relevant and higher doses. embryofetal death was observed in both rats and rabbits administered buprenorphine during the period of organogenesis at doses approximately 6 and 0.3 times, respectively, the human sublingual dose of 16 mg/day of buprenorphine. pre- and post-natal development studies in rats demonstrated increased neonatal deaths at 0.3 times and above and dystocia at approximately 3 times the human sublingual dose of 16 mg/day of buprenorphine. no clear teratogenic effects were seen when buprenorphine was administered during organogenesis with a range of doses equivalent to or greater than the human sublingual dose of 16 mg/day of buprenorphine. however, increases in skeletal abnormalities were noted in rats and rabbits administered buprenorphine daily during organogenesis at doses approximately 0.6 times and approximately equal to the human sublingual dose of 16 mg/day of buprenorphine, respectively. in a few studies, some events such as acephalus and omphalocele were also observed but these findings were not clearly treatment-related [see data] . based on animal data, advise pregnant women of the potential risk to a fetus. the estimated background risks of major birth defects and miscarriage for the indicated population are unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and embryo-fetal risk untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. in addition, untreated opioid addiction often results in continued or relapsing illicit opioid use. dose adjustment during pregnancy and the postpartum period dosage adjustments of buprenorphine may be required during pregnancy, even if the patient was maintained on a stable dose prior to pregnancy. withdrawal signs and symptoms should be monitored closely and the dose adjusted as necessary. fetal/neonatal adverse reactions neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment with buprenorphine sublingual tablets. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight. signs of neonatal withdrawal usually occur in the first days after birth. the duration and severity of neonatal opioid withdrawal syndrome may vary. observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.5)] . labor or delivery opioid-dependent women on buprenorphine maintenance therapy may require additional analgesia during labor. data human data studies have been conducted to evaluate neonatal outcomes in women exposed to buprenorphine during pregnancy. limited data from trials, observational studies, case series, and case reports on buprenorphine use in pregnancy do not indicate an increased risk of major malformations specifically due to buprenorphine. several factors may complicate the interpretation of investigations of the children of women who take buprenorphine during pregnancy, including maternal use of illicit drugs, late presentation for prenatal care, infection, poor compliance, poor nutrition, and psychosocial circumstances. interpretation of data is complicated further by the lack of information on untreated opioid-dependent pregnant women, who would be the most appropriate group for comparison. rather, women on another form of opioid medication-assisted treatment, or women in the general population are generally used as the comparison group. however, women in these comparison groups may be different from women prescribed buprenorphine-containing products with respect to maternal factors that may lead to poor pregnancy outcomes. in a multicenter, double-blind, randomized, controlled trial [maternal opioid treatment: human experimental research (mother)] designed primarily to assess neonatal opioid withdrawal effects, opioid-dependent pregnant women were randomized to buprenorphine (n=86) or methadone (n=89) treatment, with enrollment at an average gestational age of 18.7 weeks in both groups. a total of 28 of the 86 women in the buprenorphine group (33%) and 16 of the 89 women in the methadone group (18%) discontinued treatment before the end of pregnancy. among women who remained in treatment until delivery, there was no difference between buprenorphine-treated and methadone-treated groups in the number of neonates requiring nows treatment or in the peak severity of nows. buprenorphine-exposed neonates required less morphine (mean total dose, 1.1 mg vs. 10.4 mg), had shorter hospital stays (10.0 days vs. 17.5 days), and shorter duration of treatment for nows (4.1 days vs. 9.9 days) compared to the methadone-exposed group. there were no differences between groups in other primary outcomes (neonatal head circumference) or secondary outcomes (weight and length at birth, preterm birth, gestational age at delivery, and 1-minute and 5-minute apgar scores), or in the rates of maternal or neonatal adverse events. the outcomes among mothers who discontinued treatment before delivery and may have relapsed to illicit opioid use are not known. because of the imbalance in discontinuation rates between the buprenorphine and methadone groups, the study findings are difficult to interpret. animal data the exposure margins listed below are based on body surface area comparisons (mg/m2 ) to the human sublingual dose of 16 mg buprenorphine via buprenorphine sublingual tablets. no definitive drug-related teratogenic effects were observed in rats and rabbits at im doses up to 30 mg/kg/day (estimated exposure approximately 20 times and 35 times, respectively, the human sublingual dose of 16 mg). maternal toxicity resulting in mortality was noted in these studies in both rats and rabbits. acephalus was observed in one rabbit fetus from the low-dose group and omphalocele was observed in two rabbit fetuses from the same litter in the mid-dose group; no findings were observed in fetuses from the high-dose group. maternal toxicity was seen in the high-dose group but not at the lower doses where the findings were observed. following oral administration of buprenorphine to rats, dose-related post-implantation losses, evidenced by increases in the numbers of early resorptions with consequent reductions in the numbers of fetuses, were observed at doses of 10 mg/kg/day or greater (estimated exposure approximately 6 times the human sublingual dose of 16 mg). in the rabbit, increased post-implantation losses occurred at an oral dose of 40 mg/kg/day. following im administration in the rat and the rabbit, post-implantation losses, as evidenced by decreases in live fetuses and increases in resorptions, occurred at 30 mg/kg/day. buprenorphine was not teratogenic in rats or rabbits after im or subcutaneous (sc) doses up to 5 mg/kg/day (estimated exposure was approximately 3 and 6 times, respectively, the human sublingual dose of 16 mg), after iv doses up to 0.8 mg/kg/day (estimated exposure was approximately 0.5 times and equal to, respectively, the human sublingual dose of 16 mg), or after oral doses up to 160 mg/kg/day in rats (estimated exposure was approximately 95 times the human sublingual dose of 16 mg) and 25 mg/kg/day in rabbits (estimated exposure was approximately 30 times the human sublingual dose of 16 mg). significant increases in skeletal abnormalities (e.g., extra thoracic vertebra or thoraco-lumbar ribs) were noted in rats after sc administration of 1 mg/kg/day and up (estimated exposure was approximately 0.6 times the human sublingual dose of 16 mg), but were not observed at oral doses up to 160 mg/kg/day. increases in skeletal abnormalities in rabbits after im administration of 5 mg/kg/day (estimated exposure was approximately 6 times the human sublingual dose of 16 mg) in the absence of maternal toxicity or oral administration of 1 mg/kg/day or greater (estimated exposure was approximately equal to the human sublingual dose of 16 mg) were not statistically significant. in rabbits, buprenorphine produced statistically significant pre-implantation losses at oral doses of 1 mg/kg/day or greater and post-implantation losses that were statistically significant at iv doses of 0.2 mg/kg/day or greater (estimated exposure approximately 0.3 times the human sublingual dose of 16 mg). no maternal toxicity was noted at doses causing post-implantation loss in this study. dystocia was noted in pregnant rats treated intramuscularly with buprenorphine from gestation day 14 through lactation day 21 at 5 mg/kg/day (approximately 3 times the human sublingual dose of 16 mg). fertility, and pre- and post-natal development studies with buprenorphine in rats indicated increases in neonatal mortality after oral doses of 0.8 mg/kg/day and up (approximately 0.5 times the human sublingual dose of 16 mg), after im doses of 0.5 mg/kg/day and up (approximately 0.3 times the human sublingual dose of 16 mg), and after sc doses of 0.1 mg/kg/day and up (approximately 0.06 times the human sublingual dose of 16 mg). an apparent lack of milk production during these studies likely contributed to the decreased pup viability and lactation indices. delays in the occurrence of righting reflex and startle response were noted in rat pups at an oral dose of 80 mg/kg/day (approximately 50 times the human sublingual dose of 16 mg). risk summary based on two studies in 13 lactating women maintained on buprenorphine treatment, buprenorphine and its metabolite norbuprenorphine were present in low levels in human milk and available data have not shown adverse reactions in breastfed infants. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for buprenorphine sublingual tablets and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. clinical considerations advise breastfeeding women taking buprenorphine products to monitor the infant for increased drowsiness and breathing difficulties. data data were consistent from two studies (n=13) of breastfeeding infants whose mothers were maintained on sublingual doses of buprenorphine ranging from 2.4 to 24 mg/day, showing that the infants were exposed to less than 1% of the maternal daily dose. in a study of six lactating women who were taking a median sublingual buprenorphine dose of 0.29 mg/kg/day 5 to 8 days after delivery, breast milk provided a median infant dose of 0.42 mcg/kg/day of buprenorphine and 0.33 mcg/kg/day of norbuprenorphine, equal to 0.2% and 0.12%, respectively, of the maternal weight-adjusted dose (relative dose/kg (%) of norbuprenorphine was calculated from the assumption that buprenorphine and norbuprenorphine are equipotent). data from a study of seven lactating women who were taking a median sublingual buprenorphine dose of 7 mg/day an average of 1.12 months after delivery indicated that the mean milk concentrations (cavg ) of buprenorphine and norbuprenorphine were 3.65 mcg/l and 1.94 mcg/l, respectively. based on the study data, and assuming milk consumption of 150 ml/kg/day, an exclusively breastfed infant would receive an estimated mean absolute infant dose (aid) of 0.55 mcg/kg/day of buprenorphine and 0.29 mcg/kg/day of norbuprenorphine, or a mean relative infant dose (rid) of 0.38% and 0.18%, respectively, of the maternal weight-adjusted dose. infertility chronic use of opioids may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2), nonclinical toxicology (13.1)]. the safety and effectiveness of buprenorphine sublingual tablets have not been established in pediatric patients. clinical studies of buprenorphine sublingual tablets, buprenorphine and naloxone sublingual film, or buprenorphine and naloxone sublingual tablet did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently than younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. due to possible decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in geriatric patients, the decision to prescribe buprenorphine sublingual tablets should be made cautiously in individuals 65 years of age or older and these patients should be monitored for signs and symptoms of toxicity or overdose. the effects of hepatic impairment on the pharmacokinetics of buprenorphine were evaluated in a pharmacokinetic study. buprenorphine is extensively metabolized in the liver and buprenorphine plasma levels were found to be higher and the half-life was found to be longer in subjects with moderate and severe hepatic impairment, but not in subjects with mild hepatic impairment. for patients with severe hepatic impairment, a dose adjustment is recommended, and patients with moderate or severe hepatic impairment should be monitored for signs and symptoms of toxicity or overdose caused by increased levels of buprenorphine [see dosage and administration (2.8), warnings and precautions (5.12), clinical pharmacology (12.3)] . no differences in buprenorphine pharmacokinetics were observed between 9 dialysis-dependent and 6 normal patients following iv administration of 0.3 mg buprenorphine. buprenorphine sublingual tablets contain buprenorphine, a schedule iii controlled substance under the controlled substances act. under the drug addiction treatment act (data) codified at 21 u.s.c. 823(g), prescription use of this product in the treatment of opioid dependence is limited to healthcare providers who meet certain qualifying requirements, and who have notified the secretary of health and human services (hhs) of their intent to prescribe this product for the treatment of opioid dependence and have been assigned a unique identification number that must be included on every prescription. buprenorphine, like morphine and other opioids, has the potential for being abused and is subject to criminal diversion. this should be considered when prescribing or dispensing buprenorphine in situations when the clinician is concerned about an increased risk of misuse, abuse, or diversion. healthcare professionals should contact their state professional licensing board or state-controlled substances authority for information on how to prevent and detect abuse or diversion of this product. patients who continue to misuse, abuse, or divert, buprenorphine products or other opioids should be provided or referred for more intensive and structured treatment. abuse of buprenorphine poses a risk of overdose and death. this risk is increased with the abuse of buprenorphine and alcohol and other substances, especially benzodiazepines. the healthcare provider may be able to more easily detect misuse or diversion by maintaining records of medication prescribed including date, dose, quantity, frequency of refills, and renewal requests of medication prescribed. proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper handling and storage of the medication are appropriate measures that help to limit abuse of opioid drugs. buprenorphine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid type, characterized by moderate withdrawal signs and symptoms upon abrupt discontinuation or rapid taper. the withdrawal syndrome is typically milder than seen with full agonists and may be delayed in onset [see warnings and precautions (5.7) ]. neonatal opioid withdrawal syndrome (nows) is an expected and treatable outcome of prolonged use of opioids during pregnancy [see warnings and precautions (5.5)] . this "instructions for use" contains information on how to correctly take buprenorphine sublingual tablets. important information you need to know before taking buprenorphine sublingual tablets: - your healthcare provider should show you how to take buprenorphine sublingual tablets the right way. preparing to take buprenorphine sublingual tablets: - put the tablets under your tongue. let them dissolve completely. - while buprenorphine sublingual tablets are dissolving, do not chew or swallow the tablet because the medicine will not work as well. - talking while the tablet is dissolving can affect how well the medicine in buprenorphine sublingual tablets is absorbed. - after buprenorphine sublingual tablet is completely dissolved, rinse your mouth with water and swallow. wait for at least one hour before brushing teeth. - if you miss a dose of buprenorphine sublingual tablets, take your medicine when you remember. if it is almost time for your next dose, skip the missed dose and take the next dose at your regular time. do not take 2 doses at the same time unless your healthcare provider tells you to. if you are not sure about your dosing, call your healthcare provider. - do not stop taking buprenorphine sublingual tablets suddenly. you could become sick and have withdrawal symptoms because your body has become used to the medicine. physical dependence is not the same as drug addiction. your healthcare provider can tell you more about the differences between physical dependence and drug addiction. to have fewer withdrawal symptoms, ask your healthcare provider how to stop using buprenorphine sublingual tablets the right way. if you take too much buprenorphine sublingual tablets or overdose, call poison control or get emergency medical help right away. storing buprenorphine sublingual tablets: - store buprenorphine sublingual tablets at room temperature between 68°f to 77°f (20°c to 25°c). - keep buprenorphine sublingual tablets in a safe place, out of the sight and reach of children. disposing of buprenorphine sublingual tablets: - dispose of unused buprenorphine sublingual tablets as soon as you no longer need them. - dispose of expired, unwanted or unused buprenorphine sublingual tablets by promptly flushing down the toilet (if a drug take-back option is not readily available). visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines. if you need help with disposal of buprenorphine sublingual tablets, call rhodes pharmaceuticals l.p. at 1-888-827-0616. this "instructions for use" has been approved by the u.s. food and drug administration . revised 06/2022

United States - English - NLM (National Library of Medicine)

bryant ranch prepack - buprenorphine hydrochloride (unii: 56w8mw3en1) (buprenorphine - unii:40d3scr4gz), naloxone hydrochloride dihydrate (unii: 5q187997ee) (naloxone - unii:36b82amq7n) - buprenorphine and naloxone sublingual tablets are indicated for maintenance treatment of opioid dependence. buprenorphine and naloxone sublingual tablets should be used as part of a complete treatment plan that includes counseling and psychosocial support. buprenorphine and naloxone sublingual tablet is contraindicated in patients with a history of hypersensitivity to buprenorphine or naloxone as serious adverse reactions, including anaphylactic shock, have been reported [see warnings and precautions (5.9)] . risk summary the data on use of buprenorphine, one of the active ingredients in buprenorphine and naloxone sublingual tablets, in pregnancy, are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure. there are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations [see data] . observational studies have reported on congenital malformations among buprenorphine-exposed pregnancies, but were also not designed appropriately to assess the risk of congenital malformations specifically due to buprenorphine exposure [see data] . the extremely limited data on sublingual naloxone exposure in pregnancy are not sufficient to evaluate a drug-associated risk. reproductive and developmental studies in rats and rabbits identified adverse events at clinically relevant and higher doses. embryo-fetal death was observed in both rats and rabbits administered buprenorphine during the period of organogenesis at doses approximately 6 and 0.3 times, respectively, the human sublingual dose of 16 mg/day of buprenorphine. pre- and post-natal development studies in rats demonstrated increased neonatal deaths at 0.3 times and above and dystocia at approximately 3 times the human sublingual dose of 16 mg/day of buprenorphine. no clear teratogenic effects were seen when buprenorphine was administered during organogenesis with a range of doses equivalent to or greater than the human sublingual dose of 16 mg/day of buprenorphine. however, increases in skeletal abnormalities were noted in rats and rabbits administered buprenorphine daily during organogenesis at doses approximately 0.6 times and approximately equal to the human sublingual dose of 16 mg/day of buprenorphine, respectively. in a few studies, some events such as acephalus and omphalocele were also observed but these findings were not clearly treatment-related [see data] . based on animal data, advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population are unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and embryo-fetal risk untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. in addition, untreated opioid addiction often results in continued or relapsing illicit opioid use. dose adjustment during pregnancy and the postpartum period dosage adjustments of buprenorphine may be required during pregnancy, even if the patient was maintained on a stable dose prior to pregnancy. withdrawal signs and symptoms should be monitored closely and the dose adjusted as necessary. fetal/neonatal adverse reactions neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment with buprenorphine and naloxone sublingual tablets. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight. signs of neonatal withdrawal usually occur in the first days after birth. the duration and severity of neonatal opioid withdrawal syndrome may vary. observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.5)] . labor or delivery opioid-dependent women on buprenorphine maintenance therapy may require additional analgesia during labor. data human data studies have been conducted to evaluate neonatal outcomes in women exposed to buprenorphine during pregnancy. limited data from trials, observational studies, case series, and case reports on buprenorphine use in pregnancy do not indicate an increased risk of major malformations specifically due to buprenorphine. several factors may complicate the interpretation of investigations of the children of women who take buprenorphine during pregnancy, including maternal use of illicit drugs, late presentation for prenatal care, infection, poor compliance, poor nutrition, and psychosocial circumstances. interpretation of data is complicated further by the lack of information on untreated opioid-dependent pregnant women, who would be the most appropriate group for comparison. rather, women on another form of opioid medication-assisted treatment, or women in the general population are generally used as the comparison group. however, women in these comparison groups may be different from women prescribed buprenorphine-containing products with respect to maternal factors that may lead to poor pregnancy outcomes. in a multicenter, double-blind, randomized, controlled trial [maternal opioid treatment: human experimental research (mother)] designed primarily to assess neonatal opioid withdrawal effects, opioid-dependent pregnant women were randomized to buprenorphine (n=86) or methadone (n=89) treatment, with enrollment at an average gestational age of 18.7 weeks in both groups. a total of 28 of the 86 women in the buprenorphine group (33%) and 16 of the 89 women in the methadone group (18%) discontinued treatment before the end of pregnancy. among women who remained in treatment until delivery, there was no difference between buprenorphine-treated and methadone-treated groups in the number of neonates requiring nows treatment or in the peak severity of nows. buprenorphine-exposed neonates required less morphine (mean total dose, 1.1 mg vs. 10.4 mg), had shorter hospital stays (10.0 days vs. 17.5 days), and shorter duration of treatment for nows (4.1 days vs. 9.9 days) compared to the methadone-exposed group. there were no differences between groups in other primary outcomes (neonatal head circumference) or secondary outcomes (weight and length at birth, preterm birth, gestational age at delivery, and 1-minute and 5-minute apgar scores), or in the rates of maternal or neonatal adverse events. the outcomes among mothers who discontinued treatment before delivery and may have relapsed to illicit opioid use are not known. because of the imbalance in discontinuation rates between the buprenorphine and methadone groups, the study findings are difficult to interpret. animal data the exposure margins listed below are based on body surface area comparisons (mg/m2 ) to the human sublingual dose of 16 mg buprenorphine via buprenorphine and naloxone sublingual tablets. effects on embryo-fetal development were studied in sprague-dawley rats and russian white rabbits following oral (1:1) and intramuscular (im) (3:2) administration of mixtures of buprenorphine and naloxone during the period of organogenesis. following oral administration to rats, no teratogenic effects were observed at buprenorphine doses up to 250 mg/kg/day (estimated exposure approximately 150 times the human sublingual dose of 16 mg) in the presence of maternal toxicity (mortality). following oral administration to rabbits, no teratogenic effects were observed at buprenorphine doses up to 40 mg/kg/day (estimated exposure approximately 50 times the human sublingual dose of 16 mg) in the absence of clear maternal toxicity. no definitive drug-related teratogenic effects were observed in rats and rabbits at im doses up to 30 mg/kg/day (estimated exposure approximately 20 times and 35 times, respectively, the human sublingual dose of 16 mg). maternal toxicity resulting in mortality was noted in these studies in both rats and rabbits. acephalus was observed in one rabbit fetus from the low-dose group and omphalocele was observed in two rabbit fetuses from the same litter in the mid-dose group; no findings were observed in fetuses from the high-dose group. maternal toxicity was seen in the high-dose group but not at the lower doses where the findings were observed. following oral administration of buprenorphine to rats, dose-related post-implantation losses, evidenced by increases in the numbers of early resorptions with consequent reductions in the numbers of fetuses, were observed at doses of 10 mg/kg/day or greater (estimated exposure approximately 6 times the human sublingual dose of 16 mg). in the rabbit, increased post-implantation losses occurred at an oral dose of 40 mg/kg/day. following im administration in the rat and the rabbit, post-implantation losses, as evidenced by decreases in live fetuses and increases in resorptions, occurred at 30 mg/kg/day. buprenorphine was not teratogenic in rats or rabbits after im or subcutaneous (sc) doses up to 5 mg/kg/day (estimated exposure was approximately 3 and 6 times, respectively, the human sublingual dose of 16 mg), after iv doses up to 0.8 mg/kg/day (estimated exposure was approximately 0.5 times and equal to, respectively, the human sublingual dose of 16 mg), or after oral doses up to 160 mg/kg/day in rats (estimated exposure was approximately 95 times the human sublingual dose of 16 mg) and 25 mg/kg/day in rabbits (estimated exposure was approximately 30 times the human sublingual dose of 16 mg). significant increases in skeletal abnormalities (e.g., extra thoracic vertebra or thoraco-lumbar ribs) were noted in rats after sc administration of 1 mg/kg/day and up (estimated exposure was approximately 0.6 times the human sublingual dose of 16 mg), but were not observed at oral doses up to 160 mg/kg/day. increases in skeletal abnormalities in rabbits after im administration of 5 mg/kg/day (estimated exposure was approximately 6 times the human sublingual dose of 16 mg) in the absence of maternal toxicity or oral administration of 1 mg/kg/day or greater (estimated exposure was approximately equal to the human sublingual dose of 16 mg) were not statistically significant. in rabbits, buprenorphine produced statistically significant pre-implantation losses at oral doses of 1 mg/kg/day or greater and post-implantation losses that were statistically significant at iv doses of 0.2 mg/kg/day or greater (estimated exposure approximately 0.3 times the human sublingual dose of 16 mg). no maternal toxicity was noted at doses causing post-implantation loss in this study. dystocia was noted in pregnant rats treated intramuscularly with buprenorphine from gestation day 14 through lactation day 21 at 5 mg/kg/day (approximately 3 times the human sublingual dose of 16 mg). fertility, and pre- and postnatal development studies with buprenorphine in rats indicated increases in neonatal mortality after oral doses of 0.8 mg/kg/day and up (approximately 0.5 times the human sublingual dose of 16 mg), after im doses of 0.5 mg/kg/day and up (approximately 0.3 times the human sublingual dose of 16 mg), and after sc doses of 0.1 mg/kg/day and up (approximately 0.06 times the human sublingual dose of 16 mg). an apparent lack of milk production during these studies likely contributed to the decreased pup viability and lactation indices. delays in the occurrence of righting reflex and startle response were noted in rat pups at an oral dose of 80 mg/kg/day (approximately 50 times the human sublingual dose of 16 mg). risk summary based on two studies in 13 lactating women maintained on buprenorphine treatment, buprenorphine and its metabolite norbuprenorphine were present in low levels in human milk and available data have not shown adverse reactions in breastfed infants. there are no data on the combination product buprenorphine/naloxone in breastfeeding, however oral absorption of naloxone is limited. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for buprenorphine and naloxone sublingual tablets and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. clinical considerations advise breastfeeding women taking buprenorphine products to monitor the infant for increased drowsiness and breathing difficulties. data data were consistent from two studies (n=13) of breastfeeding infants whose mothers were maintained on sublingual doses of buprenorphine ranging from 2.4 to 24 mg/day, showing that the infants were exposed to less than 1% of the maternal daily dose. in a study of six lactating women who were taking a median sublingual buprenorphine dose of 0.29 mg/kg/day 5 to 8 days after delivery, breast milk provided a median infant dose of 0.42 mcg/kg/day of buprenorphine and 0.33 mcg/kg/day of norbuprenorphine, equal to 0.2% and 0.12%, respectively, of the maternal weight-adjusted dose (relative dose/kg (%) of norbuprenorphine was calculated from the assumption that buprenorphine and norbuprenorphine are equipotent). data from a study of seven lactating women who were taking a median sublingual buprenorphine dose of 7 mg/day an average of 1.12 months after delivery indicated that the mean milk concentrations (cavg ) of buprenorphine and norbuprenorphine were 3.65 mcg/l and 1.94 mcg/l, respectively. based on the study data, and assuming milk consumption of 150 ml/kg/day, an exclusively breastfed infant would receive an estimated mean absolute infant dose (aid) of 0.55 mcg/kg/day of buprenorphine and 0.29 mcg/kg/day of norbuprenorphine, or a mean relative infant dose (rid) of 0.38% and 0.18%, respectively, of the maternal weight-adjusted dose. infertility chronic use of opioids may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2), nonclinical toxicology (13.1)]. the safety and effectiveness of buprenorphine and naloxone sublingual tablets have not been established in pediatric patients. this product is not appropriate for the treatment of neonatal abstinence syndrome in neonates because it contains naloxone, an opioid antagonist. clinical studies of buprenorphine and naloxone sublingual tablets, buprenorphine and naloxone sublingual film, or buprenorphine sublingual tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently than younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. due to possible decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in geriatric patients, the decision to prescribe buprenorphine and naloxone sublingual tablets should be made cautiously in individuals 65 years of age or older and these patients should be monitored for signs and symptoms of toxicity or overdose. the effect of hepatic impairment on the pharmacokinetics of buprenorphine and naloxone has been evaluated in a pharmacokinetic study. both drugs are extensively metabolized in the liver. while no clinically significant changes have been observed in subjects with mild hepatic impairment; the plasma levels have been shown to be higher and half-life values have been shown to be longer for both buprenorphine and naloxone in subjects with moderate and severe hepatic impairment. the magnitude of the effects on naloxone are greater than that on buprenorphine in both moderately and severely impaired subjects. the difference in magnitude of the effects on naloxone and buprenorphine are greater in subjects with severe hepatic impairment than in subjects with moderate hepatic impairment, and therefore the clinical impact of these effects is likely to be greater in patients with severe hepatic impairment than in patients with moderate hepatic impairment. buprenorphine/naloxone products should be avoided in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment [see warnings and precautions (5.12), clinical pharmacology (12.3)] . no differences in buprenorphine pharmacokinetics were observed between 9 dialysis-dependent and 6 normal patients following iv administration of 0.3 mg buprenorphine. the effects of renal failure on naloxone pharmacokinetics are unknown. buprenorphine and naloxone sublingual tablets contain buprenorphine, a schedule iii controlled substance under the controlled substances act. under the drug addiction treatment act (data) codified at 21 u.s.c. 823(g), prescription use of this product in the treatment of opioid dependence is limited to healthcare providers who meet certain qualifying requirements, and who have notified the secretary of health and human services (hhs) of their intent to prescribe this product for the treatment of opioid dependence and have been assigned a unique identification number that must be included on every prescription. buprenorphine, like morphine and other opioids, has the potential for being abused and is subject to criminal diversion. this should be considered when prescribing or dispensing buprenorphine in situations when the clinician is concerned about an increased risk of misuse, abuse, or diversion. healthcare professionals should contact their state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product. patients who continue to misuse, abuse, or divert buprenorphine products or other opioids should be provided with, or referred to, more intensive and structured treatment. abuse of buprenorphine poses a risk of overdose and death. this risk is increased with the abuse of buprenorphine and alcohol and other substances, especially benzodiazepines. the healthcare provider may be able to more easily detect misuse or diversion by maintaining records of medication prescribed including date, dose, quantity, frequency of refills, and renewal requests of medication prescribed. proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper handling and storage of the medication are appropriate measures that help to limit abuse of opioid drugs. buprenorphine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid-type, characterized by moderate withdrawal signs and symptoms upon abrupt discontinuation or rapid taper. the withdrawal syndrome is typically milder than seen with full agonists and may be delayed in onset [see warnings and precautions (5.7)] . neonatal opioid withdrawal syndrome (nows) is an expected and treatable outcome of prolonged use of opioids during pregnancy [see warnings and precautions (5.5)] . buprenorphine (byoo pre nor feen) and naloxone (nah lox own) sublingual tablets, usp, ciii this "instructions for use" contains information on how to correctly take buprenorphine and naloxone sublingual tablets. important information you need to know before taking buprenorphine and naloxone sublingual tablets: - your healthcare provider should show you how to take buprenorphine and naloxone sublingual tablets the right way. preparing to take buprenorphine and naloxone sublingual tablets: - put the tablets under your tongue. let them dissolve completely. - while buprenorphine and naloxone sublingual tablets are dissolving, do not chew or swallow the tablet because the medicine will not work as well. - talking while the tablet is dissolving can affect how well the medicine in buprenorphine and naloxone sublingual tablets is absorbed. - after buprenorphine and naloxone sublingual tablet is completely dissolved, rinse your mouth with water and swallow. wait for at least one hour before brushing teeth. - if you miss a dose of buprenorphine and naloxone sublingual tablets, take your medicine when you remember. if it is almost time for your next dose, skip the missed dose and take the next dose at your regular time. do not take 2 doses at the same time unless your healthcare provider tells you to. if you are not sure about your dosing, call your healthcare provider. - do not stop taking buprenorphine and naloxone sublingual tablets suddenly. you could become sick and have withdrawal symptoms because your body has become used to the medicine. physical dependence is not the same as drug addiction. your healthcare provider can tell you more about the differences between physical dependence and drug addiction. to have fewer withdrawal symptoms, ask your healthcare provider how to stop using buprenorphine and naloxone sublingual tablets the right way. - if you take too much buprenorphine and naloxone sublingual tablets or overdose, call poison control or get emergency medical help right away . storing buprenorphine and naloxone sublingual tablets: - store buprenorphine and naloxone sublingual tablets at room temperature between 68°f to 77°f (20°c to 25°c). - keep buprenorphine and naloxone sublingual tablets in a safe place, out of the sight and reach of children . disposing of buprenorphine and naloxone sublingual tablets: - dispose of unused buprenorphine and naloxone sublingual tablets as soon as you no longer need them. - dispose of expired, unwanted, or unused buprenorphine and naloxone sublingual tablets by promptly flushing down the toilet (if a drug take-back option is not readily available). visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines. if you need help with disposal of buprenorphine and naloxone sublingual tablets, call rhodes pharmaceuticals l.p. at 1‐888-827-0616. this "instructions for use" has been approved by the u.s. food and drug administration. revised: 06/2022

United States - English - NLM (National Library of Medicine)

bryant ranch prepack - buprenorphine hydrochloride (unii: 56w8mw3en1) (buprenorphine - unii:40d3scr4gz), naloxone hydrochloride dihydrate (unii: 5q187997ee) (naloxone - unii:36b82amq7n) - buprenorphine and naloxone sublingual tablets are indicated for maintenance treatment of opioid dependence. buprenorphine and naloxone sublingual tablets should be used as part of a complete treatment plan that includes counseling and psychosocial support. buprenorphine and naloxone sublingual tablet is contraindicated in patients with a history of hypersensitivity to buprenorphine or naloxone as serious adverse reactions, including anaphylactic shock, have been reported [see warnings and precautions (5.9)] . risk summary the data on use of buprenorphine, one of the active ingredients in buprenorphine and naloxone sublingual tablets, in pregnancy, are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure. there are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations [see data] . observational studies have reported on congenital malformations among buprenorphine-exposed pregnancies, but were also not designed appropriately to assess the risk of congenital malformations specifically due to buprenorphine exposure [see data] . the extremely limited data on sublingual naloxone exposure in pregnancy are not sufficient to evaluate a drug-associated risk. reproductive and developmental studies in rats and rabbits identified adverse events at clinically relevant and higher doses. embryo-fetal death was observed in both rats and rabbits administered buprenorphine during the period of organogenesis at doses approximately 6 and 0.3 times, respectively, the human sublingual dose of 16 mg/day of buprenorphine. pre- and post-natal development studies in rats demonstrated increased neonatal deaths at 0.3 times and above and dystocia at approximately 3 times the human sublingual dose of 16 mg/day of buprenorphine. no clear teratogenic effects were seen when buprenorphine was administered during organogenesis with a range of doses equivalent to or greater than the human sublingual dose of 16 mg/day of buprenorphine. however, increases in skeletal abnormalities were noted in rats and rabbits administered buprenorphine daily during organogenesis at doses approximately 0.6 times and approximately equal to the human sublingual dose of 16 mg/day of buprenorphine, respectively. in a few studies, some events such as acephalus and omphalocele were also observed but these findings were not clearly treatment-related [see data] . based on animal data, advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population are unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and embryo-fetal risk untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. in addition, untreated opioid addiction often results in continued or relapsing illicit opioid use. dose adjustment during pregnancy and the postpartum period dosage adjustments of buprenorphine may be required during pregnancy, even if the patient was maintained on a stable dose prior to pregnancy. withdrawal signs and symptoms should be monitored closely and the dose adjusted as necessary. fetal/neonatal adverse reactions neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment with buprenorphine and naloxone sublingual tablets. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight. signs of neonatal withdrawal usually occur in the first days after birth. the duration and severity of neonatal opioid withdrawal syndrome may vary. observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.5)] . labor or delivery opioid-dependent women on buprenorphine maintenance therapy may require additional analgesia during labor. data human data studies have been conducted to evaluate neonatal outcomes in women exposed to buprenorphine during pregnancy. limited data from trials, observational studies, case series, and case reports on buprenorphine use in pregnancy do not indicate an increased risk of major malformations specifically due to buprenorphine. several factors may complicate the interpretation of investigations of the children of women who take buprenorphine during pregnancy, including maternal use of illicit drugs, late presentation for prenatal care, infection, poor compliance, poor nutrition, and psychosocial circumstances. interpretation of data is complicated further by the lack of information on untreated opioid-dependent pregnant women, who would be the most appropriate group for comparison. rather, women on another form of opioid medication-assisted treatment, or women in the general population are generally used as the comparison group. however, women in these comparison groups may be different from women prescribed buprenorphine-containing products with respect to maternal factors that may lead to poor pregnancy outcomes. in a multicenter, double-blind, randomized, controlled trial [maternal opioid treatment: human experimental research (mother)] designed primarily to assess neonatal opioid withdrawal effects, opioid-dependent pregnant women were randomized to buprenorphine (n=86) or methadone (n=89) treatment, with enrollment at an average gestational age of 18.7 weeks in both groups. a total of 28 of the 86 women in the buprenorphine group (33%) and 16 of the 89 women in the methadone group (18%) discontinued treatment before the end of pregnancy. among women who remained in treatment until delivery, there was no difference between buprenorphine-treated and methadone-treated groups in the number of neonates requiring nows treatment or in the peak severity of nows. buprenorphine-exposed neonates required less morphine (mean total dose, 1.1 mg vs. 10.4 mg), had shorter hospital stays (10.0 days vs. 17.5 days), and shorter duration of treatment for nows (4.1 days vs. 9.9 days) compared to the methadone-exposed group. there were no differences between groups in other primary outcomes (neonatal head circumference) or secondary outcomes (weight and length at birth, preterm birth, gestational age at delivery, and 1-minute and 5-minute apgar scores), or in the rates of maternal or neonatal adverse events. the outcomes among mothers who discontinued treatment before delivery and may have relapsed to illicit opioid use are not known. because of the imbalance in discontinuation rates between the buprenorphine and methadone groups, the study findings are difficult to interpret. animal data the exposure margins listed below are based on body surface area comparisons (mg/m2 ) to the human sublingual dose of 16 mg buprenorphine via buprenorphine and naloxone sublingual tablets. effects on embryo-fetal development were studied in sprague-dawley rats and russian white rabbits following oral (1:1) and intramuscular (im) (3:2) administration of mixtures of buprenorphine and naloxone during the period of organogenesis. following oral administration to rats, no teratogenic effects were observed at buprenorphine doses up to 250 mg/kg/day (estimated exposure approximately 150 times the human sublingual dose of 16 mg) in the presence of maternal toxicity (mortality). following oral administration to rabbits, no teratogenic effects were observed at buprenorphine doses up to 40 mg/kg/day (estimated exposure approximately 50 times the human sublingual dose of 16 mg) in the absence of clear maternal toxicity. no definitive drug-related teratogenic effects were observed in rats and rabbits at im doses up to 30 mg/kg/day (estimated exposure approximately 20 times and 35 times, respectively, the human sublingual dose of 16 mg). maternal toxicity resulting in mortality was noted in these studies in both rats and rabbits. acephalus was observed in one rabbit fetus from the low-dose group and omphalocele was observed in two rabbit fetuses from the same litter in the mid-dose group; no findings were observed in fetuses from the high-dose group. maternal toxicity was seen in the high-dose group but not at the lower doses where the findings were observed. following oral administration of buprenorphine to rats, dose-related post-implantation losses, evidenced by increases in the numbers of early resorptions with consequent reductions in the numbers of fetuses, were observed at doses of 10 mg/kg/day or greater (estimated exposure approximately 6 times the human sublingual dose of 16 mg). in the rabbit, increased post-implantation losses occurred at an oral dose of 40 mg/kg/day. following im administration in the rat and the rabbit, post-implantation losses, as evidenced by decreases in live fetuses and increases in resorptions, occurred at 30 mg/kg/day. buprenorphine was not teratogenic in rats or rabbits after im or subcutaneous (sc) doses up to 5 mg/kg/day (estimated exposure was approximately 3 and 6 times, respectively, the human sublingual dose of 16 mg), after iv doses up to 0.8 mg/kg/day (estimated exposure was approximately 0.5 times and equal to, respectively, the human sublingual dose of 16 mg), or after oral doses up to 160 mg/kg/day in rats (estimated exposure was approximately 95 times the human sublingual dose of 16 mg) and 25 mg/kg/day in rabbits (estimated exposure was approximately 30 times the human sublingual dose of 16 mg). significant increases in skeletal abnormalities (e.g., extra thoracic vertebra or thoraco-lumbar ribs) were noted in rats after sc administration of 1 mg/kg/day and up (estimated exposure was approximately 0.6 times the human sublingual dose of 16 mg), but were not observed at oral doses up to 160 mg/kg/day. increases in skeletal abnormalities in rabbits after im administration of 5 mg/kg/day (estimated exposure was approximately 6 times the human sublingual dose of 16 mg) in the absence of maternal toxicity or oral administration of 1 mg/kg/day or greater (estimated exposure was approximately equal to the human sublingual dose of 16 mg) were not statistically significant. in rabbits, buprenorphine produced statistically significant pre-implantation losses at oral doses of 1 mg/kg/day or greater and post-implantation losses that were statistically significant at iv doses of 0.2 mg/kg/day or greater (estimated exposure approximately 0.3 times the human sublingual dose of 16 mg). no maternal toxicity was noted at doses causing post-implantation loss in this study. dystocia was noted in pregnant rats treated intramuscularly with buprenorphine from gestation day 14 through lactation day 21 at 5 mg/kg/day (approximately 3 times the human sublingual dose of 16 mg). fertility, and pre- and postnatal development studies with buprenorphine in rats indicated increases in neonatal mortality after oral doses of 0.8 mg/kg/day and up (approximately 0.5 times the human sublingual dose of 16 mg), after im doses of 0.5 mg/kg/day and up (approximately 0.3 times the human sublingual dose of 16 mg), and after sc doses of 0.1 mg/kg/day and up (approximately 0.06 times the human sublingual dose of 16 mg). an apparent lack of milk production during these studies likely contributed to the decreased pup viability and lactation indices. delays in the occurrence of righting reflex and startle response were noted in rat pups at an oral dose of 80 mg/kg/day (approximately 50 times the human sublingual dose of 16 mg). risk summary based on two studies in 13 lactating women maintained on buprenorphine treatment, buprenorphine and its metabolite norbuprenorphine were present in low levels in human milk and available data have not shown adverse reactions in breastfed infants. there are no data on the combination product buprenorphine/naloxone in breastfeeding, however oral absorption of naloxone is limited. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for buprenorphine and naloxone sublingual tablets and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. clinical considerations advise breastfeeding women taking buprenorphine products to monitor the infant for increased drowsiness and breathing difficulties. data data were consistent from two studies (n=13) of breastfeeding infants whose mothers were maintained on sublingual doses of buprenorphine ranging from 2.4 to 24 mg/day, showing that the infants were exposed to less than 1% of the maternal daily dose. in a study of six lactating women who were taking a median sublingual buprenorphine dose of 0.29 mg/kg/day 5 to 8 days after delivery, breast milk provided a median infant dose of 0.42 mcg/kg/day of buprenorphine and 0.33 mcg/kg/day of norbuprenorphine, equal to 0.2% and 0.12%, respectively, of the maternal weight-adjusted dose (relative dose/kg (%) of norbuprenorphine was calculated from the assumption that buprenorphine and norbuprenorphine are equipotent). data from a study of seven lactating women who were taking a median sublingual buprenorphine dose of 7 mg/day an average of 1.12 months after delivery indicated that the mean milk concentrations (cavg ) of buprenorphine and norbuprenorphine were 3.65 mcg/l and 1.94 mcg/l, respectively. based on the study data, and assuming milk consumption of 150 ml/kg/day, an exclusively breastfed infant would receive an estimated mean absolute infant dose (aid) of 0.55 mcg/kg/day of buprenorphine and 0.29 mcg/kg/day of norbuprenorphine, or a mean relative infant dose (rid) of 0.38% and 0.18%, respectively, of the maternal weight-adjusted dose. infertility chronic use of opioids may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2), nonclinical toxicology (13.1)]. the safety and effectiveness of buprenorphine and naloxone sublingual tablets have not been established in pediatric patients. this product is not appropriate for the treatment of neonatal abstinence syndrome in neonates because it contains naloxone, an opioid antagonist. clinical studies of buprenorphine and naloxone sublingual tablets, buprenorphine and naloxone sublingual film, or buprenorphine sublingual tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently than younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. due to possible decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in geriatric patients, the decision to prescribe buprenorphine and naloxone sublingual tablets should be made cautiously in individuals 65 years of age or older and these patients should be monitored for signs and symptoms of toxicity or overdose. the effect of hepatic impairment on the pharmacokinetics of buprenorphine and naloxone has been evaluated in a pharmacokinetic study. both drugs are extensively metabolized in the liver. while no clinically significant changes have been observed in subjects with mild hepatic impairment; the plasma levels have been shown to be higher and half-life values have been shown to be longer for both buprenorphine and naloxone in subjects with moderate and severe hepatic impairment. the magnitude of the effects on naloxone are greater than that on buprenorphine in both moderately and severely impaired subjects. the difference in magnitude of the effects on naloxone and buprenorphine are greater in subjects with severe hepatic impairment than in subjects with moderate hepatic impairment, and therefore the clinical impact of these effects is likely to be greater in patients with severe hepatic impairment than in patients with moderate hepatic impairment. buprenorphine/naloxone products should be avoided in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment [see warnings and precautions (5.12), clinical pharmacology (12.3)] . no differences in buprenorphine pharmacokinetics were observed between 9 dialysis-dependent and 6 normal patients following iv administration of 0.3 mg buprenorphine. the effects of renal failure on naloxone pharmacokinetics are unknown. buprenorphine and naloxone sublingual tablets contain buprenorphine, a schedule iii controlled substance under the controlled substances act. under the drug addiction treatment act (data) codified at 21 u.s.c. 823(g), prescription use of this product in the treatment of opioid dependence is limited to healthcare providers who meet certain qualifying requirements, and who have notified the secretary of health and human services (hhs) of their intent to prescribe this product for the treatment of opioid dependence and have been assigned a unique identification number that must be included on every prescription. buprenorphine, like morphine and other opioids, has the potential for being abused and is subject to criminal diversion. this should be considered when prescribing or dispensing buprenorphine in situations when the clinician is concerned about an increased risk of misuse, abuse, or diversion. healthcare professionals should contact their state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product. patients who continue to misuse, abuse, or divert buprenorphine products or other opioids should be provided with, or referred to, more intensive and structured treatment. abuse of buprenorphine poses a risk of overdose and death. this risk is increased with the abuse of buprenorphine and alcohol and other substances, especially benzodiazepines. the healthcare provider may be able to more easily detect misuse or diversion by maintaining records of medication prescribed including date, dose, quantity, frequency of refills, and renewal requests of medication prescribed. proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper handling and storage of the medication are appropriate measures that help to limit abuse of opioid drugs. buprenorphine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid-type, characterized by moderate withdrawal signs and symptoms upon abrupt discontinuation or rapid taper. the withdrawal syndrome is typically milder than seen with full agonists and may be delayed in onset [see warnings and precautions (5.7)] . neonatal opioid withdrawal syndrome (nows) is an expected and treatable outcome of prolonged use of opioids during pregnancy [see warnings and precautions (5.5)] . buprenorphine (byoo pre nor feen) and naloxone (nah lox own) sublingual tablets, usp, ciii this "instructions for use" contains information on how to correctly take buprenorphine and naloxone sublingual tablets. important information you need to know before taking buprenorphine and naloxone sublingual tablets: - your healthcare provider should show you how to take buprenorphine and naloxone sublingual tablets the right way. preparing to take buprenorphine and naloxone sublingual tablets: - put the tablets under your tongue. let them dissolve completely. - while buprenorphine and naloxone sublingual tablets are dissolving, do not chew or swallow the tablet because the medicine will not work as well. - talking while the tablet is dissolving can affect how well the medicine in buprenorphine and naloxone sublingual tablets is absorbed. - after buprenorphine and naloxone sublingual tablet is completely dissolved, rinse your mouth with water and swallow. wait for at least one hour before brushing teeth. - if you miss a dose of buprenorphine and naloxone sublingual tablets, take your medicine when you remember. if it is almost time for your next dose, skip the missed dose and take the next dose at your regular time. do not take 2 doses at the same time unless your healthcare provider tells you to. if you are not sure about your dosing, call your healthcare provider. - do not stop taking buprenorphine and naloxone sublingual tablets suddenly. you could become sick and have withdrawal symptoms because your body has become used to the medicine. physical dependence is not the same as drug addiction. your healthcare provider can tell you more about the differences between physical dependence and drug addiction. to have fewer withdrawal symptoms, ask your healthcare provider how to stop using buprenorphine and naloxone sublingual tablets the right way. - if you take too much buprenorphine and naloxone sublingual tablets or overdose, call poison control or get emergency medical help right away . storing buprenorphine and naloxone sublingual tablets: - store buprenorphine and naloxone sublingual tablets at room temperature between 68°f to 77°f (20°c to 25°c). - keep buprenorphine and naloxone sublingual tablets in a safe place, out of the sight and reach of children . disposing of buprenorphine and naloxone sublingual tablets: - dispose of unused buprenorphine and naloxone sublingual tablets as soon as you no longer need them. - dispose of expired, unwanted, or unused buprenorphine and naloxone sublingual tablets by promptly flushing down the toilet (if a drug take-back option is not readily available). visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines. if you need help with disposal of buprenorphine and naloxone sublingual tablets, call rhodes pharmaceuticals l.p. at 1‐888-827-0616. this "instructions for use" has been approved by the u.s. food and drug administration. revised: 06/2022