Malesia - englanti - NPRA (National Pharmaceutical Regulatory Agency, Bahagian Regulatori Farmasi Negara)

dksh malaysia sdn bhd - isoconazole nitrate -

Yhdysvallat - englanti - NLM (National Library of Medicine)

alvogen - fentanyl (unii: uf599785jz) (fentanyl - unii:uf599785jz) - fentanyl 12.5 ug - fentanyl transdermal system is indicated for the management of severe and persistent pain in opioid-tolerant patients, that requires an extended treatment period with a daily opioid analgesic in opioid-tolerant patients, and for which alternative treatment options are inadequate. patients considered opioid-tolerant are those who are taking, for one week or longer, at least 60 mg morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid. limitations of use - because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration , and because of the greater risks of overdose and death with extended-release/long-acting opioid formulations [see warnings and precautions ( 5.1) ], reserve fentanyl transdermal system for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - fentanyl transdermal system is not indicated as an as-needed (prn) analgesic. fentanyl transdermal system is contraindicated in: - patients who are not opioid-tolerant. - the management of acute or intermittent pain, or in patients who require opioid analgesia for a short period of time. - the management of post-operative pain, including use after outpatient or day surgeries, (e.g., tonsillectomies). - the management of mild pain. - patients with significant respiratory depression [see warnings and precautions ( 5.12) ]. - patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions ( 5.12) ]. - patients with known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions ( 5.19) ]. - patients with hypersensitivity to fentanyl (e.g., anaphylaxis) or any components of the transdermal system [see adverse reactions ( 6.2) ]. risk summary use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions ( 5.5) ]. available data with fentanyl transdermal system in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, fentanyl administration to pregnant rats during organogenesis was embryocidal at doses within the range of the human recommended dosing. when administered during gestation through lactation fentanyl administration to pregnant rats resulted in reduced pup survival and developmental delays at doses within the range of the human recommended dosing. no evidence of malformations were noted in animal studies completed to date [see data ]. 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 2-4% and 15-20%, respectively. clinical considerations fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time 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. fentanyl transdermal system is not recommended for use in pregnant women during or immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. opioid analgesics, including fentanyl transdermal system, can prolong labor through actions that 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 dilatation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data human data there are no adequate and well-controlled studies in pregnant women. fentanyl transdermal system should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. chronic maternal treatment with fentanyl during pregnancy has been associated with transient respiratory depression, behavioral changes, or seizures characteristic of neonatal abstinence syndrome in newborn infants. symptoms of neonatal respiratory or neurological depression were no more frequent than expected in most studies of infants born to women treated acutely during labor with intravenous or epidural fentanyl. transient neonatal muscular rigidity has been observed in infants whose mothers were treated with intravenous fentanyl. animal data no evidence of malformations or adverse effects on the fetus was reported in a published study in which pregnant rats were administered fentanyl continuously via subcutaneously implanted osmotic minipumps at doses of 10, 100, or 500 mcg/kg/day starting 2-weeks prior to breeding and throughout pregnancy. the high dose was approximately 2 times the daily human dose administered by a 100 mcg/h patch on a mg/m 2 basis). in contrast, the intravenous administration of fentanyl (0, 0.01, or 0.03 mg/kg) to pregnant rats from gestation day 6 to 18 suggested evidence of embryo-toxicity and a slight increase in mean delivery time in the 0.03 mg/kg/day group (0.1 times the human dose administered by a 100 mcg/h patch on a mg/m 2 basis). there was no clear evidence of teratogenicity noted. pregnant female new zealand white rabbits were treated with fentanyl (0, 0.025, 0.1, 0.4 mg/kg) via intravenous infusion from day 6 to day 18 of pregnancy. fentanyl produced a slight decrease in the body weight of the live fetuses at the high dose, which may be attributed to maternal toxicity. under the conditions of the assay, there was no evidence for fentanyl induced adverse effects on embryo-fetal development at doses up to 0.4 mg/kg (approximately 3 times the daily human dose administered by a 100 mcg/hour patch on a mg/m 2 basis). the potential effects of fentanyl on prenatal and postnatal development were examined in the rat model. female wistar rats were treated with 0, 0.025, 0.1, or 0.4 mg/kg/day fentanyl via intravenous infusion from day 6 of pregnancy through 3 weeks of lactation. fentanyl treatment (0.4 mg/kg/day) significantly decreased body weight in male and female pups and also decreased survival in pups at day 4. both the mid-dose and high-dose of fentanyl animals demonstrated alterations in some physical landmarks of development (delayed incisor eruption and eye opening) and transient behavioral development (decreased locomotor activity at day 28 which recovered by day 50). the mid-dose and the high-dose are 0.4 and 1.6 times the daily human dose administered by a 100 mcg/hour patch on a mg/m 2 basis. risk summary fentanyl is excreted in human milk; therefore, fentanyl transdermal system is not recommended for use in nursing women because of the possibility of effects in their infants. because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with fentanyl transdermal system. clinical considerations monitor infants exposed to fentanyl transdermal system through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breastfeeding is stopped. infertility use of opioids for an extended period of time 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 of fentanyl transdermal system was evaluated in three open-label trials in 289 pediatric patients with chronic pain, 2 years of age through 18 years of age. starting doses of 25 mcg/h and higher were used by 181 patients who had been on prior daily opioid doses of at least 45 mg/day of oral morphine or an equianalgesic dose of another opioid. initiation of fentanyl transdermal system therapy in pediatric patients taking less than 60 mg/day of oral morphine or an equianalgesic dose of another opioid has not been evaluated in controlled clinical trials. the safety and effectiveness of fentanyl transdermal system in children under 2 years of age have not been established. to guard against excessive exposure to fentanyl transdermal system by young children, advise caregivers to strictly adhere to recommended fentanyl transdermal system application and disposal instructions [see dosage and administration ( 2.7), ( 2.8) and warnings and precautions ( 5.3) ]. clinical studies of fentanyl transdermal system did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, use caution when selecting a dosage 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. data from intravenous studies with fentanyl suggest that the elderly patients may have reduced clearance and a prolonged half-life. moreover, elderly patients may be more sensitive to the active substance than younger patients. a study conducted with the fentanyl transdermal system patch in elderly patients demonstrated that fentanyl pharmacokinetics did not differ significantly from young adult subjects, although peak serum concentrations tended to be lower and mean half-life values were prolonged to approximately 34 hours [see clinical pharmacology ( 12.3) ]. 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 fentanyl transdermal system slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions ( 5.12) ]. fentanyl 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. the effect of hepatic impairment on the pharmacokinetics of fentanyl transdermal system has not been fully evaluated. a clinical pharmacology study with fentanyl transdermal system in patients with cirrhosis has shown that systemic fentanyl exposure increased in these patients. because there is in-vitro and in-vivo evidence of extensive hepatic contribution to the elimination of fentanyl transdermal system, hepatic impairment would be expected to have significant effects on the pharmacokinetics of fentanyl transdermal system. avoid use of fentanyl transdermal system in patients with severe hepatic impairment [see dosage and administration ( 2.5), warnings and precautions ( 5.17) and clinical pharmacology 12.3) ]. the effect of renal impairment on the pharmacokinetics of fentanyl transdermal system has not been fully evaluated. a clinical pharmacology study with intravenous fentanyl in patients undergoing kidney transplantation has shown that patients with high blood urea nitrogen level had low fentanyl clearance. because there is in-vivo evidence of renal contribution to the elimination of fentanyl transdermal system, renal impairment would be expected to have significant effects on the pharmacokinetics of fentanyl transdermal system. avoid the use of fentanyl transdermal system in patients with severe renal impairment [see dosage and administration ( 2.6), warnings and precautions ( 5.18) and clinical pharmacology ( 12.3) ]. fentanyl transdermal system contains fentanyl, a schedule ii controlled substance. fentanyl transdermal system contains fentanyl, a substance with a high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings and precautions ( 5.1) ]. misuse is the intentional use, for the therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance, or physical dependence. misuse and abuse of fentanyl transdermal system increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. the risk is increased with concurrent use of fentanyl transdermal system with alcohol and/or other cns depressants. abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. in addition, abuse of opioids can occur in the absence of addiction. all patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. patients at high risk of fentanyl transdermal system abuse include those with a history of prolonged use of any opioid, including products containing fentanyl, those with a history of drug or alcohol abuse, or those who use fentanyl transdermal system in combination with other abused drugs. “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 people who abuse drugs and people with substance use disorder. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. fentanyl transdermal system, like other opioids, can be diverted for nonmedical 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 reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to the abuse of fentanyl transdermal system fentanyl transdermal system is intended for transdermal use only. abuse of fentanyl transdermal system poses a risk of overdose and death. this risk is increased with concurrent use of fentanyl transdermal system with alcohol and/or other cns depressants [see warnings and precautions ( 5.4), and drug interactions ( 7) ]. intentional compromise of the transdermal delivery system may result in the uncontrolled delivery of fentanyl and pose a significant risk to the abuser that could result in overdose and death [see warnings and precautions ( 5.1) ]. abuse may occur by applying the transdermal system in the absence of legitimate purpose, or by swallowing, snorting or injecting fentanyl extracted from the transdermal system. both tolerance and physical dependence can develop during use of opioid therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), 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 use. do not abruptly discontinue fentanyl transdermal system in a patient physically dependent on opioids. rapid tapering of fentanyl transdermal system 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 fentanyl transdermal system, gradually taper the dosage using a patient-specific plan that considers the following: the dose of fentanyl transdermal system 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 an extended period of time 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 ( 2.9), and warnings and precautions ( 5.21) ]. 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) ]. instructions for use fentanyl (fen' ta nil) transdermal system cii be sure that you read, understand, and follow these instructions for use before you apply fentanyl transdermal system (patch). talk to your healthcare provider or pharmacist if you have any questions. important information about the fentanyl transdermal system (patch) appearance: - fentanyl transdermal system is a rectangular, see-through patch with rounded corners. - fentanyl transdermal system comes in 5 different dosage strengths and sizes: 12 mcg/hour 25 mcg/hour 50 mcg/hour 75 mcg/hour 100 mcg/hour - 12 mcg/hour - 25 mcg/hour - 50 mcg/hour - 75 mcg/hour - 100 mcg/hour - the product name, “fentanyl”, and dosage strength are printed in green on each patch. parts of the fentanyl transdermal system patch: before applying fentanyl transdermal system - each fentanyl transdermal system patch is sealed in its own protective pouch. do not remove a fentanyl transdermal system patch from the pouch until you are ready to use it. - do not use a fentanyl transdermal system patch if the pouch seal is broken or the patch is cut, damaged or changed in any way. - fentanyl transdermal system patches are available in 5 different dosage strengths and patch sizes. make sure you have the right dose patch or patches that have been prescribed for you. - skin areas where the fentanyl transdermal system patch may be applied: for adults: put the patch on the chest, back, flank (sides of the waist), or upper arm in a place where there is no hair (see figures a-d). for children (and adults with mental impairment): put the patch on the upper back (see figure b). this will lower the chances that the child will remove the patch and put it in their mouth. for adults and children do not put a fentanyl transdermal system patch on skin that is very oily, burned, broken out, cut, irritated, or damaged in any way. avoid sensitive areas or those that move around a lot. if there is hair, do not shave (shaving irritates the skin). instead, clip hair as close to the skin as possible (see figure e). talk to your healthcare provider if you have questions about skin application sites. - put the patch on the chest, back, flank (sides of the waist), or upper arm in a place where there is no hair (see figures a-d). for children (and adults with mental impairment): - put the patch on the upper back (see figure b). this will lower the chances that the child will remove the patch and put it in their mouth. for adults and children - do not put a fentanyl transdermal system patch on skin that is very oily, burned, broken out, cut, irritated, or damaged in any way. - avoid sensitive areas or those that move around a lot. if there is hair, do not shave (shaving irritates the skin). instead, clip hair as close to the skin as possible (see figure e). - talk to your healthcare provider if you have questions about skin application sites. figure a figure b figure c figure d figure e - prepare to apply a fentanyl transdermal system patch: choose the time of day that is best for you to apply fentanyl transdermal system. change it at about the same time of day (3 days or 72 hours after you apply the patch) or as directed by your healthcare provider. do not wear more than one fentanyl transdermal system patch at a time unless your healthcare provider tells you to do so. before applying a new fentanyl transdermal system patch, remove the patch you have been wearing. clean the skin area with clear water only. pat skin completely dry . do not use anything on the skin such as soaps, lotions, oils, or alcohol before the patch is applied. - choose the time of day that is best for you to apply fentanyl transdermal system. change it at about the same time of day (3 days or 72 hours after you apply the patch) or as directed by your healthcare provider. - do not wear more than one fentanyl transdermal system patch at a time unless your healthcare provider tells you to do so. before applying a new fentanyl transdermal system patch, remove the patch you have been wearing. - clean the skin area with clear water only. pat skin completely dry . do not use anything on the skin such as soaps, lotions, oils, or alcohol before the patch is applied. - open the pouch: fold and tear at slit, or cut at slit taking care not to cut the patch. remove the fentanyl transdermal system patch. each fentanyl transdermal system patch is sealed in its own protective pouch. do not remove the fentanyl transdermal system patch from the pouch until you are ready to use it (see figure f). - peel: peel off both parts of the release liner from the patch. each fentanyl transdermal system patch has a clear plastic release liner that can be peeled off in two pieces. this covers the sticky side of the patch. carefully peel this release liner off and throw the pieces away. touch the sticky side of the fentanyl transdermal system patch as little as possible (see figure g). figure f figure g - press: press the patch onto the chosen skin site with the palm of your hand and hold there for at least 30 seconds (see figure h). make sure it sticks well, especially at the edges. fentanyl transdermal system may not stick to all people. you need to check the patch often to make sure that they are sticking well to the skin. if the patch falls off right away after applying, throw it away and put a new one on at a different skin site. see the section below called “ disposing of a fentanyl transdermal system patch.” if you have a problem with the patch not sticking apply first-aid tape only to the edges of the patch. if you continue to have problems with the patch not sticking, you may cover the patch with a transparent adhesive film dressing such as bioclusive™ or tegaderm™. these are special see-through adhesive dressings. never cover a fentanyl transdermal system patch with any other bandage or tape. remove the backing from the bioclusive™ or tegaderm™ dressing and place it carefully over the fentanyl transdermal system patch, smoothing it over the patch and your skin. if your patch falls off before 3 days (72 hours) of use, dispose of (throw away) properly. see the section below “ disposing of a fentanyl transdermal system patch.” apply a new fentanyl transdermal system patch on at a different skin site. be sure to let your healthcare provider know that this has happened, and do not replace the new patch until 3 days (72 hours) after you put it on (or as directed by your healthcare provider). - fentanyl transdermal system may not stick to all people. you need to check the patch often to make sure that they are sticking well to the skin. - if the patch falls off right away after applying, throw it away and put a new one on at a different skin site. see the section below called “ disposing of a fentanyl transdermal system patch.” - if you have a problem with the patch not sticking apply first-aid tape only to the edges of the patch. if you continue to have problems with the patch not sticking, you may cover the patch with a transparent adhesive film dressing such as bioclusive™ or tegaderm™. these are special see-through adhesive dressings. never cover a fentanyl transdermal system patch with any other bandage or tape. remove the backing from the bioclusive™ or tegaderm™ dressing and place it carefully over the fentanyl transdermal system patch, smoothing it over the patch and your skin. - apply first-aid tape only to the edges of the patch. - if you continue to have problems with the patch not sticking, you may cover the patch with a transparent adhesive film dressing such as bioclusive™ or tegaderm™. these are special see-through adhesive dressings. never cover a fentanyl transdermal system patch with any other bandage or tape. remove the backing from the bioclusive™ or tegaderm™ dressing and place it carefully over the fentanyl transdermal system patch, smoothing it over the patch and your skin. - if your patch falls off before 3 days (72 hours) of use, dispose of (throw away) properly. see the section below “ disposing of a fentanyl transdermal system patch.” apply a new fentanyl transdermal system patch on at a different skin site. be sure to let your healthcare provider know that this has happened, and do not replace the new patch until 3 days (72 hours) after you put it on (or as directed by your healthcare provider). - wash your hands when you have finished applying a fentanyl transdermal system patch. - remove a fentanyl transdermal system patch after wearing it for 3 days (72 hours). dispose of the used patch right away. see the section below “ disposing of a fentanyl transdermal system patch.” choose a different skin site to apply a new fentanyl transdermal system patch. repeat steps 2 through 6 above when applying a new fentanyl transdermal system patch. do not apply the new patch to the same place as the last one. - you can bathe, swim or shower while you are wearing a fentanyl transdermal system patch. if the patch falls off before 3 days (72 hours) after application, dispose of properly. see the section below “ disposing of a fentanyl transdermal system patch.” apply a new fentanyl transdermal system patch on a different skin site. be sure to let your healthcare provider know that this has happened, and do not replace the new patch until 3 days (72 hours) after you put it on (or as directed by your healthcare provider). disposing of a fentanyl transdermal system patch - fold the used fentanyl transdermal system patch in half so that the sticky side sticks to itself (see figure i). flush the used fentanyl transdermal system patch down the toilet right away (see figure j). a used fentanyl transdermal system patch can be very dangerous for or lead to death in babies, children, pets, and adults who have not been prescribed fentanyl transdermal system. - throw away any fentanyl transdermal system patches that are left over from your prescription as soon as they are no longer needed. remove the leftover patches from their protective pouch and remove the release liner. fold the patches in half with the sticky sides together, and flush the patches down the toilet. do not flush the pouch or the release liner down the toilet. these items can be thrown away in a trash can. figure h figure i figure j this instructions for use has been approved by the u.s. food and drug administration. manufactured by: kindeva drug delivery l.p. northridge, ca 91324 usa distributed by: alvogen, inc. pine brook, nj 07058 usa revised: 05/2023 bioclusive™ is a trademark of ethicon, inc. tegaderm™ is a trademark of 3m

Yhdysvallat - englanti - NLM (National Library of Medicine)

alvogen inc. - methylphenidate hydrochloride (unii: 4b3sc438hi) (methylphenidate - unii:207zz9qz49) - methylphenidate hydrochloride extended-release tablets are indicated for the treatment of attention deficit hyperactivity disorder (adhd) in children 6 years of age and older, adolescents, and adults up to the age of 65  [see clinical studies (14)] . a diagnosis of attention deficit hyperactivity disorder (adhd; dsm-iv) implies the presence of hyperactive-impulsive or inattentive symptoms that caused impairment and were present before age 7 years. the symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in two or more settings, e.g., school (or work) and at home. the symptoms must not be better accounted for by another mental disorder. for the inattentive type, at least six of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention; poor listener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental effort; lose

Yhdysvallat - englanti - NLM (National Library of Medicine)

alvogen inc. - buprenorphine hydrochloride (unii: 56w8mw3en1) (buprenorphine - unii:40d3scr4gz), naloxone hydrochloride dihydrate (unii: 5q187997ee) (naloxone - unii:36b82amq7n) - buprenorphine and naloxone sublingual film is indicated for treatment of opioid dependence. buprenorphine and naloxone sublingual film should be used as part of a complete treatment plan that includes counseling and psychosocial support. buprenorphine and naloxone sublingual film 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) ] . the data on use of buprenorphine, one of the active ingredients in buprenorphine and naloxone sublingual film, 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. embryofetal death was observed in both rats and rabbits administered buprenorphine during the period of organogenesis at doses approximately 6‐times and 0.3‐times, respectively, the human sublingual dose of 16 mg per day of buprenorphine. pre‐and postnatal 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 per 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 per 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 per 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. 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. 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. neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment with buprenorphine and naloxone sublingual film. 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)] . opioid-dependent women on buprenorphine maintenance therapy may require additional analgesia during labor. studies have been conducted to evaluate neonatal outcomes in women exposed to buprenorphine during pregnancy. limited data on malformations 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 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. 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 per 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 per 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 intramuscular doses up to 30 mg/kg per 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 per 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 per day. following intramuscular 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 per day. buprenorphine was not teratogenic in rats or rabbits after intramuscular or subcutaneous doses up to 5 mg/kg per day (estimated exposure was approximately 3 times and 6 times, respectively, the human sublingual dose of 16 mg), after intravenous doses up to 0.8 mg/kg per 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 per day in rats (estimated exposure was approximately 95 times the human sublingual dose of 16 mg) and 25 mg/kg per day in rabbits (estimated exposure was approximately 30 times the human daily sublingual dose of 16 mg). significant increases in skeletal abnormalities (e.g., extra thoracic vertebra or thoraco‐lumbar ribs) were noted in rats after subcutaneous administration of 1 mg/kg per 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 per day. increases in skeletal abnormalities in rabbits after intramuscular administration of 5 mg/kg per day (estimated exposure was approximately 6 times the human daily sublingual dose of 16 mg) in the absence of maternal toxicity or oral administration of 1 mg/kg per 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 per day or greater and post‐implantation losses that were statistically significant at intravenous doses of 0.2 mg/kg per day or greater (estimated exposure approximately 0.3 times the human daily 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 per day (approximately 3 times the human sublingual dose of 16 mg). fertility, pre‐, and post‐natal development studies with buprenorphine in rats indicated increases in neonatal mortality after oral doses of 0.8 mg/kg per day and up (approximately 0.5 times the human daily sublingual dose of 16 mg), after intramuscular doses of 0.5 mg/kg per day and up (approximately 0.3 times the human sublingual dose of 16 mg), and after subcutaneous doses of 0.1 mg/kg per 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 per day (approximately 50 times the human sublingual dose of 16 mg). 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 infant urine. available data have not shown adverse reactions in breastfed infants. there are no data on the combination product buprenorphine and 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 film and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. advise breastfeeding women taking buprenorphine products to monitor the infant for increased drowsiness and breathing difficulties. data were consistent from two studies (n=13) of breastfeeding infants whose mothers were maintained on sublingual doses of buprenorphine ranging from 2.4 mg per day to 24 mg per 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 per day 5 days to 8 days after delivery, breast milk provided a median infant dose of 0.42 mcg/kg per day of buprenorphine and 0.33 mcg/kg per 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 per 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 per day, an exclusively breastfed infant would receive an estimated mean absolute infant dose (aid) of 0.55 mcg/kg per day of buprenorphine and 0.29 mcg/kg per day of norbuprenorphine, or a mean relative infant dose (rid) of 0.38% and 0.18%, respectively, of the maternal weight‐adjusted dose. 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 film 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 film, buprenorphine and naloxone sublingual tablets, 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 film 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 and 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 intravenous administration of 0.3 mg buprenorphine. the effects of renal failure on naloxone pharmacokinetics are unknown. buprenorphine and naloxone sublingual film contains buprenorphine, a schedule iii controlled substance under the controlled substances act. 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 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)] .

Yhdysvallat - englanti - NLM (National Library of Medicine)

alvogen inc. - ketorolac tromethamine (unii: 4eve5946bq) (ketorolac - unii:yzi5105v0l) - ketorolac tromethamine 15 mg in 1 ml - carefully consider the potential benefits and risks of ketorolac tromethamine and other treatment options before deciding to use ketorolac. use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see warnings ). ketorolac tromethamine is indicated for the short-term (≤5 days) management of moderately severe acute pain that requires analgesia at the opioid level, usually in a postoperative setting. therapy should always be initiated with iv or im dosing of ketorolac tromethamine, and oral ketorolac tromethamine is to be used only as continuation treatment, if necessary. the total combined duration of use of ketorolac tromethamine injection, and oral ketorolac tromethamine is not to exceed 5 days of use because of the potential of increasing the frequency and severity of adverse reactions associated with the recommended doses (see warnings, precautions, dosage and administration , and adverse reactions ). patients should be switched to alternative analgesics a

Yhdysvallat - englanti - NLM (National Library of Medicine)

alvogen inc. - buprenorphine (unii: 40d3scr4gz) (buprenorphine - unii:40d3scr4gz) - buprenorphine transdermal system is indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate. limitations of use - because of the risks of addiction, abuse and misuse with opioids, which can occur at any dosage or duration, and because of the greater risk of overdose and death with extended-release/long-acting opioid formulations [see warnings and precautions (5.1)] , reserve buprenorphine transdermal system for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - buprenorphine transdermal system is not indicated as an as-needed (prn) analgesic buprenorphine transdermal system is contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.2)] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.10)] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.15)] - hypersensitivity (e.g., anaphylaxis) to buprenorphine [see warnings and precautions (5.18), adverse reactions (6)] risk summary use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.4)] . available data with buprenorphine transdermal system in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, buprenorphine caused an increase in the number of stillborn offspring, reduced litter size, and reduced offspring growth in rats at maternal exposure levels that were approximately 10 times that of human subjects who received one buprenorphine transdermal system 20 mcg/hour, the maximum recommended human dose (mrhd) [see data] . based on animal data, advise pregnant women of the potential risk to a fetus. the 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. clinical considerations fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time 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 (5.4)]. labor and delivery opioids cross the placenta and may produce respiratory depression in neonates. an opioid antagonist such as naloxone must be available for reversal of opioid-induced respiratory depression in the neonate. buprenorphine transdermal system is not recommended for use in women immediately prior to labor, when shorter acting analgesics or other analgesic techniques are more appropriate. opioid analgesics, including buprenorphine transdermal system, can prolong labor through actions that 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 dilatation, which tends to shorten labor. data animal data studies in rats and rabbits demonstrated no evidence of teratogenicity following buprenorphine transdermal system or subcutaneous (sc) administration of buprenorphine during the period of organogenesis. rats were administered up to one buprenorphine transdermal system 20 mcg/hour every 3 days (gestation days 6, 9, 12, & 15) or received daily sc buprenorphine up to 5 mg/kg (gestation days 6 to 17). rabbits were administered four buprenorphine transdermal system 20 mcg/hour every 3 days (gestation days 6, 9, 12, 15, 18, and 19) or received daily sc buprenorphine up to 5 mg/kg (gestation days 6 to 19). no teratogenicity was observed at any dose. auc values for buprenorphine with buprenorphine transdermal system application and sc injection were approximately 110 and 140 times, respectively, that of human subjects who received the mrhd of one buprenorphine transdermal system 20 mcg/hour. in a pre- and post-natal study conducted in pregnant and lactating rats, administration of buprenorphine either as buprenorphine transdermal system or sc buprenorphine was associated with toxicity to offspring. buprenorphine was present in maternal milk. pregnant rats were administered ¼ of one buprenorphine transdermal system 5 mcg/hour every 3 days or received daily sc buprenorphine at doses of 0.05 mg/kg, 0.5 mg/kg, or 5 mg/kg from gestation day 6 to lactation day 21 (weaning). administration of buprenorphine transdermal system or sc buprenorphine at 0.5 mg/kg or 5 mg/kg caused maternal toxicity and an increase in the number of stillborns, reduced litter size, and reduced offspring growth at maternal exposure levels that were approximately 10 times that of human subjects who received the mrhd of one buprenorphine transdermal system 20 mcg/hour. maternal toxicity was also observed at the no observed adverse effect level (noael) for offspring. risk summary because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with buprenorphine transdermal system. clinical considerations monitor infants exposed to buprenorphine through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of buprenorphine is stopped or when breast-feeding is stopped. infertility use of opioids for an extended period of time 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), preclinical pharmacology (12.2), nonclinical toxicology (13.1)] . the safety and efficacy of buprenorphine transdermal system in patients under 18 years of age has not been established. buprenorphine transdermal system has been evaluated in an open-label clinical trial in pediatric patients. however, definitive conclusions are not possible because of the small sample size. of the total number of subjects in the clinical trials (5,415), buprenorphine transdermal system was administered to 1,377 patients aged 65 years and older. of those, 457 patients were 75 years of age and older. in the clinical program, the incidences of selected buprenorphine transdermal system-related aes were higher in older subjects. the incidences of application site aes were slightly higher among subjects < 65 years of age than those ≥ 65 years of age for both buprenorphine transdermal system and placebo treatment groups. in a single-dose study of healthy elderly and healthy young subjects treated with buprenorphine transdermal system 10 mcg/hour, the pharmacokinetics were similar. in a separate dose-escalation safety study, the pharmacokinetics in the healthy elderly and hypertensive elderly subjects taking thiazide diuretics were similar to those in the healthy young adults. in the elderly groups evaluated, adverse event rates were similar to or lower than rates in healthy young adult subjects, except for constipation and urinary retention, which were more common in the elderly. although specific dose adjustments on the basis of advanced age are not required for pharmacokinetic reasons, use caution in the elderly population to ensure safe use [see clinical pharmacology (12.3)] . 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 buprenorphine transdermal system slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.10)] . in a study utilizing intravenous buprenorphine, peak plasma levels (cmax ) and exposure (auc) of buprenorphine in patients with mild and moderate hepatic impairment did not increase as compared to those observed in subjects with normal hepatic function. buprenorphine transdermal system has not been evaluated in patients with severe hepatic impairment. as buprenorphine transdermal system is intended for 7-day dosing, consider the use of alternate analgesic therapy in patients with severe hepatic impairment [see dosage and administration (2.6), clinical pharmacology (12.3)] . buprenorphine transdermal system contains buprenorphine, a schedule iii controlled substance. buprenorphine transdermal system contains buprenorphine, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings and precautions (5.1)] . misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. misuse and abuse of buprenorphine transdermal system increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. the risk is increased with concurrent abuse of buprenorphine transdermal system with alcohol and/or other cns depressants. abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. in addition, abuse of opioids can occur in the absence of addiction. all patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. patients at high risk of buprenorphine transdermal system abuse include those with a history of prolonged use of any opioid, including products containing buprenorphine, those with a history of drug or alcohol abuse, or those who use buprenorphine transdermal system in combination with other abused drugs. “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 people who abuse drugs and people with substance use disorder. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. buprenorphine transdermal system, like other opioids, can be diverted for nonmedical 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 reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of buprenorphine transdermal system abuse of buprenorphine transdermal system poses a risk of overdose and death. this risk is increased with the concurrent use of buprenorphine transdermal system with alcohol and/or other substances including other opioids and benzodiazepines [see warnings and precautions (5.1, 5.3), drug interactions (7)] . buprenorphine transdermal system is approved for transdermal use only. intentional compromise of the transdermal delivery system will result in the uncontrolled delivery of buprenorphine and pose a significant risk to the abuser that could result in overdose and death [see warnings and precautions (5.1)] . abuse may occur by applying the transdermal system in the absence of legitimate purpose, or by chewing, swallowing, snorting, or injecting buprenorphine extracted from the transdermal system. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during use of opioid therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), 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 use. do not abruptly discontinue buprenorphine transdermal system in a patient physically dependent on opioids. rapid tapering of buprenorphine transdermal system 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 buprenorphine transdermal system, gradually taper the dosage using a patient-specific plan that considers the following: the dose of buprenorphine transdermal system 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 an extended period of time 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 (2.1), warnings and precautions (5.19)] . 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)]. instructions for use buprenorphine (bue” pre nor’ feen) transdermal system ciii be sure that you read, understand, and follow these instructions for use before you use buprenorphine transdermal system. talk to your healthcare provider or pharmacist if you have any questions. before applying buprenorphine transdermal system: - do not use soap, alcohol, lotions, oils, or other products to remove any leftover adhesive from a patch because this may cause more buprenorphine transdermal system to pass through the skin. - each patch is sealed in its own protective pouch. do not remove a patch from the pouch until you are ready to use it. - do not use a patch if the seal on the protective pouch is broken or if the patch is cut, damaged or changed in any way. - buprenorphine transdermal system patches are available in different strengths and patch sizes. make sure you have the right strength patch that has been prescribed for you. where to apply buprenorphine transdermal system: - buprenorphine transdermal system should be applied to the upper outer arm, upper chest, upper back, or the side of the chest (see figure a) . these 4 sites (located on both sides of the body) provide 8 possible buprenorphine transdermal system application sites. - do not apply more than 1 patch at the same time unless your doctor tells you to. however, if your healthcare provider tells you to do so, you may use 2 patches as prescribed, applied at the same site (see figure a for application sites) right next to each other (see figure b for an example of patch position when applying 2 patches). always apply and remove the two patches together at the same time. - you should change the skin site where you apply buprenorphine transdermal system each week, making sure that at least 3 weeks (21 days) pass before you re-use the same skin site. - apply buprenorphine transdermal system to a hairless or nearly hairless skin site . if needed, you can clip the hair at the skin site (see figure c ). do not shave the area. the skin site should not be irritated. use only water to clean the application site. you should not use soaps, alcohol, oils, lotions, or abrasive devices. allow the skin to dry before you apply the patch. - the skin site should be free of cuts and irritation (rashes, swelling, redness, or other skin problems). when to apply a new patch: - when you apply a new patch, write down the date and time that the patch is applied. use this to remember when the patch should be removed. - change the patch at the same time of day, one week (exactly 7 days) after you apply it. - after removing and disposing of the patch, write down the time it was removed and how it was disposed. how to apply buprenorphine transdermal system: - if you are wearing a patch, remember to remove it before applying a new one. - each patch is sealed in its own protective pouch. - if you are using two patches, remember to apply them at the same site right next to each other. always apply and remove the two patches together at the same time. - use scissors to cut open the pouch along the dotted line (see figure d ) and remove the patch. do not remove the patch from the pouch until you are ready to use it. do not use patches that have been cut or damaged in any way. - hold the patch with the protective liner facing you. - gently bend the patch (see figures e and f ) along the faint line and slowly peel the larger portion of the liner, which covers the sticky surface of the patch. - do not touch the sticky side of the patch with your fingers. - using the smaller portion of the protective liner as a handle (see figure g ), apply the sticky side of the patch to one of the 8 body locations described above (see “where to apply buprenorphine transdermal system” ). - while still holding the sticky side down, gently fold back the smaller portion of the patch. grasp an edge of the remaining protective liner and slowly peel it off (see figure h ). - press the entire patch firmly into place with the palm (see figure i ) of your hand over the patch, for about 15 seconds. do not rub the patch. - make sure that the patch firmly sticks to the skin. - go over the edges with your fingers to assure good contact around the patch. - if you are using two patches, follow the steps in this section to apply them right next to each other. - always wash your hands after applying or handling a patch. - after the patch is applied, write down the date and time that the patch is applied. use this to remember when the patch should be removed. if the patch falls off right away after applying, throw it away and put a new one on at a different skin site (see “disposing of buprenorphine transdermal system patch”) . if a patch falls off, do not touch the sticky side of the patch with your fingers. a new patch should be applied to a different site. patches that fall off should not be re-applied . they must be thrown away correctly. short-term exposure of the buprenorphine transdermal system patch to water, such as when bathing or showering, is permitted. if the edges of the buprenorphine transdermal system patch start to loosen: - apply first aid tape only to the edges of the patch. - if problems with the patch not sticking continue, cover the patch with special see-through adhesive dressings (for example bioclusive or tegaderm). remove the backing from the transparent adhesive dressing and place it carefully and completely over the buprenorphine transdermal system patch, smoothing it over the patch and your skin. - remove the backing from the transparent adhesive dressing and place it carefully and completely over the buprenorphine transdermal system patch, smoothing it over the patch and your skin. - never cover a buprenorphine transdermal system patch with any other bandage or tape. it should only be covered with a special see-through adhesive dressing. talk to your healthcare provider or pharmacist about the kinds of dressing that should be used. if your patch falls off later, but before 1 week (7 days) of use, throw it away properly (see “disposing of a buprenorphine transdermal system patch”) and apply a new patch at a different skin site. be sure to let your healthcare provider know that this has happened. do not replace the new patch until 1 week (7 days) after you put it on (or as directed by your healthcare provider). disposing of buprenorphine transdermal system patch: buprenorphine transdermal system patches should be disposed of by using the patch-disposal unit. alternatively, the patches can be flushed down the toilet if a drug take-back option is not readily available. to dispose of buprenorphine transdermal system patches in household trash using the patch-disposal unit: remove your patch and follow the directions printed on the patch-disposal unit (see figure j ) or see complete instructions below. use one patch-disposal unit for each patch. figure j 1. peel back the disposal unit liner to show the sticky surface (see figure k ). figure k 2. place the sticky side of the used or unused patch to the indicated area on the disposal unit (see figure l ). figure l 3. close the disposal unit by folding the sticky sides together (see figure m ). press firmly and smoothly over the entire disposal unit so that the patch is sealed within. figure m 4. the closed disposal unit, with the patch sealed inside may be thrown away in the trash (see figure n ). figure n do not put expired, unwanted or unused patches in household trash without first sealing them in the patch-disposal unit. always remove the leftover patches from their protective pouch and remove the protective liner. the pouch and liner can be disposed of separately in the trash and should not be sealed in the patch-disposal unit. to flush your buprenorphine transdermal system patches down the toilet: remove your buprenorphine transdermal system patch, fold the sticky sides of a used patch together and flush it down the toilet right away (see figure o ). figure o when disposing of unused buprenorphine transdermal system patches you no longer need, remove the leftover patches from their protective pouch and remove the protective liner. fold the patches in half with the sticky sides together, and flush the patches down the toilet. do not flush the pouch or the protective liner down the toilet. these items can be thrown away in the trash. if you prefer not to flush the used patch down the toilet , and if there is not a drug take-back option readily available, you must use the patch-disposal unit provided to you to discard the patch. never put used buprenorphine transdermal system patches in the trash without first sealing them in the patch-disposal unit. this “instructions for use” has been approved by the u.s. food and drug administration. made in usa distributed by: alvogen, inc. pine brook, nj 07058 usa revised: 04/2021 ifu406-00 bioclusive is a trademark of systagenix wound management (us), inc. tegaderm is a trademark of 3m.

Kenia - englanti - Pharmacy and Poisons Board

bayer pharma ag bayer pharma ag 13342 berlin germany - isoconazole nitrate - cream - 1 g travogen cream contains 10 mg (1%)… - imidazoleandtriazolederivatives antifungals for

Yhdysvallat - englanti - NLM (National Library of Medicine)

alvogen inc. - amphetamine aspartate monohydrate (unii: o1zpv620o4) (amphetamine - unii:ck833kgx7e), amphetamine sulfate (unii: 6dpv8nk46s) (amphetamine - unii:ck833kgx7e), dextroamphetamine saccharate (unii: g83415v073) (dextroamphetamine - unii:tz47u051fi), dextroamphetamine sulfate (unii: jj768o327n) (dextroamphetamine - unii:tz47u051fi) - amphetamine aspartate monohydrate 1.25 mg - dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets are indicated for the treatment of attention deficit hyperactivity disorder (adhd) and narcolepsy. attention deficit hyperactivity disorder (adhd) a diagnosis of attention deficit hyperactivity disorder (adhd; dsm-iv® ) implies the presence of hyperactive-impulsive or inattentive symptoms that caused impairment and were present before age 7 years. the symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in two or more settings, e.g., school (or work) and at home. the symptoms must not be better accounted for by another mental disorder. for the inattentive type, at least six of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention; poor listener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental eff

Yhdysvallat - englanti - NLM (National Library of Medicine)

alvogen, inc. - moxifloxacin hydrochloride (unii: c53598599t) (moxifloxacin - unii:u188xyd42p) - moxifloxacin 400 mg - moxifloxacin hydrochloride is indicated in adult patients for the treatment of community acquired pneumonia caused by susceptible isolates of streptococcus pneumoniae (including multi-drug resistant streptococcus pneumoniae [mdrsp]),  haemophilus influenzae, moraxella catarrhalis, methicillin-susceptible staphylococcus aureus, klebsiella pneumoniae, mycoplasma pneumoniae, or chlamydophila pneumoniae [see clinical studies (14.3 )] . mdrsp isolates are isolates resistant to two or more of the following antibacterial drugs: penicillin (minimum inhibitory concentrations [mic] ≥ 2 mcg/ml), 2nd generation cephalosporins (for example, cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole. moxifloxacin hydrochloride is indicated in adult patients for the treatment of uncomplicated skin and skin structure infections caused by susceptible isolates of methicillin-susceptible staphylococcus aureus or streptococcus pyogenes [see clinical studies (14.4 )]. moxifloxacin hydrochloride is indicated in

Yhdysvallat - englanti - NLM (National Library of Medicine)

alvogen inc. - felbamate (unii: x72rbb02n8) (felbamate - unii:x72rbb02n8) - felbamate 400 mg - felbamate tablets, usp are not indicated as a first line antiepileptic treatment (see warnings). felbamate tablets are recommended for use only in those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia and/or liver failure is deemed acceptable in light of the benefits conferred by its use. if these criteria are met and the patient has been fully advised of the risk, and has provided written acknowledgment, felbamate tablets can be considered for either monotherapy or adjunctive therapy in the treatment of partial seizures, with and without generalization, in adults with epilepsy and as adjunctive therapy in the treatment of partial and generalized seizures associated with lennox-gastaut syndrome in children. felbamate tablets are contraindicated in patients with known hypersensitivity to felbamate, its ingredients, or known sensitivity to other carbamates. it should not be used in patients with a history of any blood dyscras