USA - engelsk - NLM (National Library of Medicine)

padagis us llc - diclofenac sodium (unii: qtg126297q) (diclofenac - unii:144o8ql0l1) - diclofenac sodium topical solution is indicated for the treatment of the pain of osteoarthritis of the knee(s). diclofenac sodium topical solution is contraindicated in the following patients: risk summary use of nsaids, including diclofenac sodium topical solution, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. because of these risks, limit dose and duration of diclofenac sodium topical solution use between about 20 and 30 weeks of gestation, and avoid diclofenac sodium topical solution use at about 30 weeks of gestation and later in pregnancy (see clinical considerations, data) . premature closure of fetal ductus arteriosus use of nsaids, including diclofenac sodium topical solution, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment use of nsaids at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. data from observational studies regarding other potential embryofetal risks of nsaid use in women in the first or second trimesters of pregnancy are inconclusive. in animal reproduction studies, no evidence of malformations were observed in mice, rats, or rabbits given diclofenac during the period of organogenesis at doses up to approximately 0.6, 0.6, and 1.3 times, respectively, the maximum recommended human dose (mrhd) of 162 mg diclofenac sodium via diclofenac sodium topical solution, despite the presence of maternal and fetal toxicity at these doses [see data] . based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. in animal studies, administration of prostaglandin synthesis inhibitors such as diclofenac, resulted in increased pre- and post-implantation loss. prostaglandins also have been shown to have an important role in fetal kidney development. in published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. the estimated background risk of major birth defects and miscarriage for the indicated population(s) 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 premature closure of the fetal ductus arteriosus: avoid use of nsaids in women at about 30 weeks gestation and later in pregnancy, because nsaids, including diclofenac sodium topical solution, can cause premature closure of the fetal ductus arteriosus (see data) . oligohydramnios/neonatal renal impairment: if an nsaid is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. if diclofenac sodium topical solution treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. if oligohydramnios occurs, discontinue diclofenac sodium topical solution and follow up according to clinical practice (see data) . labor or delivery there are no studies on the effects of diclofenac sodium topical solution during labor or delivery. in animal studies, nsaids, including diclofenac inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. data human data premature closure of fetal ductus arteriosus: published literature reports that the use of nsaids at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment: published studies and postmarketing reports describe maternal nsaid use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. these adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after nsaid initiation. in many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. there have been a limited number of case reports of maternal nsaid use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. these limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal nsaid use. because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to nsaids through maternal use is uncertain. animal data reproductive and developmental studies in animals demonstrated that diclofenac sodium administration during organogenesis did not produce malformations despite the induction of maternal toxicity and fetal toxicity in mice at oral doses up to 20 mg/kg/day (approximately 0.6 times the maximum recommended human dose [mrhd] of diclofenac sodium topical solution, 162 mg diclofenac sodium/day, based on body surface area (bsa) comparison), and in rats and rabbits at oral doses up to 10 mg/kg/day (approximately 0.6 and 1.3-times, respectively, the mrhd based on bsa comparison). published reproductive and developmental studies of dimethyl sulfoxide (dmso, the solvent used in diclofenac sodium topical solution) are equivocal as to potential teratogenicity. in a study in which pregnant rats were orally administered 2 or 4 mg/kg diclofenac (0.12 and 0.24 times the mrhd, respectively, based on bsa comparison) from gestation day 15 through lactation day 21, significant maternal toxicity (peritonitis, mortality) was noted. these maternally toxic doses were associated with dystocia, prolonged gestation, reduced fetal weights and growth, and reduced fetal survival. diclofenac has been shown to cross the placental barrier in mice and rats. in published studies, diclofenac administration to pregnant rats prolonged gestation and produced liver toxicity and neuronal loss in offspring (1 mg/kg, ip; 0.06 times the mrhd based on bsa comparison), impaired nephrogenesis in the kidney (3.6 mg/kg, ip; 0.2 times the mrhd based on bsa comparison), and caused adverse effects on the developing testes (6.1 mg/kg, oral; 0.4 times the mrhd based on bsa comparison). risk summary based on available data, diclofenac may be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for diclofenac sodium topical solution and any potential adverse effects on the breastfed infant from the diclofenac sodium topical solution or from the underlying maternal condition. data one woman treated orally with a diclofenac salt, 150 mg/day, had a milk diclofenac level of 100 mcg/l, equivalent to an infant dose of about 0.03 mg/kg/day. diclofenac was not detectable in breast milk in 12 women using diclofenac (after either 100 mg/day orally for 7 days or a single 50 mg intramuscular dose administered in the immediate postpartum period). infertility females based on the mechanism of action, the use of prostaglandin-mediated nsaids, including diclofenac sodium topical solution, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. small studies in women treated with nsaids have also shown a reversible delay in ovulation. consider withdrawal of nsaids, including diclofenac sodium topical solution, in women who have difficulties conceiving or who are undergoing investigation of infertility. males published studies in adult male rodents report that diclofenac, at clinically relevant doses, can produce adverse effects on male reproductive tissues. the impact of these findings on male fertility is not clear [see nonclinical toxicology (13.1) ]. safety and effectiveness in pediatric patients have not been established. elderly patients, compared to younger patients, are at greater risk for nsaid-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. if the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [see warnings and precautions (5.1, 5.2, 5.3, 5.6, 5.14) ]. of the 911 patients treated with diclofenac sodium topical solution 1.5% in seven controlled, phase 3 clinical trials, 444 subjects were 65 years of age and over. there was no age-related difference in the incidence of adverse events. of the 793 patients treated with diclofenac sodium topical solution 1.5% in one open-labeled safety trial, 334 subjects were 65 years of age and over including 107 subjects 75 and over. there was no difference in the incidence of adverse events with long-term exposure to diclofenac sodium topical solution 1.5% for this elderly population. diclofenac sodium (dye kloe’ fen ak’sō-dē-əm) topical solution read the medication guide that comes with diclofenac sodium topical solution first. be sure that you read, understand and follow these instructions for use before you use diclofenac sodium topical solution for the first time. important: for use on the skin only (topical). do not get diclofenac sodium topical solution in your eyes, nose or mouth. before you use diclofenac sodium topical solution: diclofenac sodium topical solution comes in a pump bottle or in a sample packet from your healthcare provider. if you are using a diclofenac sodium topical solution pump bottle follow the steps below: before you use diclofenac sodium topical solution pump bottle for the first time, you will need to prime the pump. to prime the pump, remove the cap (see figure a ) and fully press the top of the pump all the way down 4 times while holding the bottle in an upright position (see figure b ). dispense this portion of the medicine into a tissue or paper towel and throw it away in a trash can. the pump is now ready to use. you should not need to prime the pump again. figure a. figure b. steps for using diclofenac sodium topical solution pump bottle: step 1: wash your hands with soap and water before applying diclofenac sodium topical solution. step 2: remove the bottle cap and press the pump head down firmly and fully to dispense diclofenac sodium topical solution into the palm of your hand. release the pump head and then press the pump head down firmly and fully a second time. when you use your diclofenac sodium topical solution pump bottle, you can hold the bottle at an angle. put 2 pumps of diclofenac sodium topical solution on your hand (see figure c ). figure c. step 3: apply diclofenac sodium topical solution evenly around the front, back, and sides of your knee. diclofenac sodium topical solution should be applied without massaging the knee (see figures d and e ). figure d. figure e. step 4: repeat steps 2 and 3 for your other knee if your healthcare provider has prescribed diclofenac sodium topical solution for both knees. step 5: wash your hands with soap and water right away after applying diclofenac sodium topical solution. step 6: replace the cap on the bottle and store in an upright position. if you are using a diclofenac sodium topical solution sample packet follow the steps below: steps for using a diclofenac sodium topical solution sample packet: step 1: wash your hands with soap and water before applying diclofenac sodium topical solution. step 2: cut open the sample packet using scissors or completely tear the packet at the notch on the dotted line (see figure a ). do not use your teeth to open the sample packet (see figure a ). figure a. step 3: squeeze from the bottom of the sample packet to the top to remove contents. squeeze all of the diclofenac sodium topical solution out of the sample packet into the palm of your hand (see figure b ). figure b. step 4: apply diclofenac sodium topical solution evenly around the front, back, and sides of your knee. diclofenac sodium topical solution should be applied without massaging the knee (see figures c and d ). figure c. figure d. step 5: repeat steps 2 through 4 for your other knee if your healthcare provider has prescribed diclofenac sodium topical solution for both knees. step 6: wash your hands with soap and water right away after applying diclofenac sodium topical solution. step 7: throw away the empty sample packet into a trash can. after you use diclofenac sodium topical solution: do not: how should i store diclofenac sodium topical solution? • store diclofenac sodium topical solution at room temperature between 68°f to 77°f (20°c to 25°c). keep diclofenac sodium topical solution and all medicines out of the reach of children. this instructions for use has been approved by the u.s. food and drug administration. distributed by padagis, allegan, mi 49010 7y100 rc j1     rev 07-22

USA - engelsk - NLM (National Library of Medicine)

padagis us llc - benazepril hydrochloride (unii: n1sn99t69t) (benazeprilat - unii:jrm708l703), hydrochlorothiazide (unii: 0j48lph2th) (hydrochlorothiazide - unii:0j48lph2th) - benazepril hcl and hydrochlorothiazide is indicated for the treatment of hypertension. this fixed combination drug is not indicated for the initial therapy of hypertension (see dosage and administration) . benazepril hcl and hydrochlorothiazide is contraindicated in patients who are anuric. benazepril hcl and hydrochlorothiazide is also contraindicated in patients who are hypersensitive to benazepril, to any other ace inhibitor, to hydrochlorothiazide, or to other sulfonamide-derived drugs. hypersensitivity reactions are more likely to occur in patients with a history of allergy or bronchial asthma. benazepril hcl and hydrochlorothiazide is also contraindicated in patients with a history of angioedema with or without previous ace inhibitor treatment. benazepril hcl and hydrochlorothiazide is contraindicated in combination with a neprilysin (e.g., sacubitril). do not administer benazepril hcl and hydrochlorothiazide within 36 hours of switching to or from sacubitril/valsartan a neprilysin inhibitor (see warn

USA - engelsk - NLM (National Library of Medicine)

padagis us llc - testosterone cypionate (unii: m0xw1ubi14) (testosterone - unii:3xmk78s47o) - testosterone cypionate 200 mg in 1 ml - testosterone cypionate injection is indicated for replacement therapy in the male in conditions associated with symptoms of deficiency or absence of endogenous testosterone. safety and efficacy of testosterone cypionate in men with "age-related hypogonadism" (also referred to as "late-onset hypogonadism") have not been established. 1. known hypersensitivity to the drug 2. males with carcinoma of the breast 3. males with known or suspected carcinoma of the prostate gland 4. women who are pregnant (see precautions, pregnancy) 5. patients with serious cardiac, hepatic or renal disease (see warnings) testosterone cypionate injection contains testosterone, a schedule iii controlled substance in the controlled substances act. drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. abuse and misuse of testosterone are seen in male and female adults and adolescents. testosterone, often in combination with other anabolic androgenic steroids (aas), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. there have been reports of misuse by men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice. abuse-related adverse reactions serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression. the following adverse reactions have also been reported in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility. the following additional adverse reactions have been reported in women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities. the following adverse reactions have been reported in male and female adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty. because these reactions are reported voluntarily from a population of uncertain size and may include abuse of other agents, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. behaviors associated with addiction continued abuse of testosterone and other anabolic steroids, leading to addiction is characterized by the following behaviors: • taking greater dosages than prescribed • continued drug use despite medical and social problems due to drug use • spending significant time to obtain the drug when supplies of the drug are interrupted • giving a higher priority to drug use than other obligations • having difficulty in discontinuing the drug despite desires and attempts to do so • experiencing withdrawal symptoms upon abrupt discontinuation of use physical dependence is characterized by withdrawal symptoms after abrupt drug discontinuation or a significant dose reduction of a drug. individuals taking supratherapeutic doses of testosterone may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism. drug dependence in individuals using approved doses of testosterone for approved indications has not been documented.

USA - engelsk - NLM (National Library of Medicine)

padagis us llc - nystatin (unii: bdf1o1c72e) (nystatin - unii:bdf1o1c72e) - nystatin 100000 [usp'u] in 1 g - nystatin topical powder is indicated in the treatment of cutaneous or mucocutaneous mycotic infections caused by candida albicans and other susceptible candida species. this preparation is not indicated for systemic, oral, intravaginal or ophthalmic use. nystatin topical powder is contraindicated in patients with a history of hypersensitivity to any of its components.

USA - engelsk - NLM (National Library of Medicine)

padagis us llc - flavoxate hydrochloride (unii: 9c05j6089w) (flavoxate - unii:3e74y80mey) - flavoxate hydrochloride 100 mg - flavoxate hcl tablets are indicated for symptomatic relief of dysuria, urgency, nocturia, suprapubic pain, frequency and incontinence as may occur in cystitis, prostatitis, urethritis, urethrocystitis/urethrotrigonitis. flavoxate hcl tablets are not indicated for definitive treatment, but are compatible with drugs used for the treatment of urinary tract infections. flavoxate hcl tablets are contraindicated in patients who have any of the following obstructive conditions: pyloric or duodenal obstruction, obstructive intestinal lesions or ileus, achalasia, gastrointestinal hemorrhage and obstructive uropathies of the lower urinary tract.

USA - engelsk - NLM (National Library of Medicine)

padagis us llc - estradiol (unii: 4ti98z838e) (estradiol - unii:4ti98z838e) - estradiol 1.53 mg -     evamist is contraindicated in women with any of the following conditions: risk summary evamist is not indicated for use in pregnancy. there are no data with the use of evamist in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy. 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. risk summary estrogens are present in human milk and can reduce milk production in breast-feeding females. this reduction can occur at any time but is less likely to occur once breast-feeding is well-established. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for evamist and any potential adverse effects on the breastfed child from evamist or from the underlying maternal condition. evamist is not indicated for use in pediatric patients. clinical studies have not been conducted in the pediatric population. there have not been sufficient numbers of geriatric women involved in clinical studies utilizing evamist to determine whether those over 65 years of age differ from younger subjects in their response to evamist. the women’s health initiative studies in the whi estrogen-alone substudy (daily ce [0.625 mg]-alone versus placebo), there was a higher relative risk of stroke in women greater than 65 years of age [see clinical studies (14.2)] . in the whi estrogen plus progestin substudy (daily ce [0.625 mg] plus mpa [2.5 mg] versus placebo), there was a higher relative risk of nonfatal stroke and invasive breast cancer in women greater than 65 years of age [see clinical studies (14.2)] . the women’s health initiative memory study in the whims ancillary studies of postmenopausal women 65 to 79 years of age, there was an increased risk of developing probable dementia in women receiving estrogen-alone or estrogen plus progestin when compared to placebo [see warnings and precautions (5.3), and clinical studies (14.3)] . since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women8 [see warnings and precautions (5.3), and clinical studies (14.3)]. evamist (ee-vuh-mist) (estradiol transdermal spray) read this instructions for use before you start using evamist and each time you get a refill. there may be new information. this information does not take the place of talking to your healthcare provider about your menopausal symptoms or your treatment. the parts of your evamist applicator evamist comes in a spray applicator that delivers a measured amount of estradiol to your skin with each spray (see figure a). step 1. priming your evamist step 2. using your evamist if your healthcare provider tells you to increase your dose to 2 or 3 sprays, move the cone before applying the second or third spray to an area of your skin next to but not touching the area of the previous spray (see figure d). step 3. after you use evamist step 4. throwing away used evamist applicators this patient information and instructions for use have been approved by the u.s. food and drug administration. distributed by padagis allegan, mi 49010 rev 12/2023

USA - engelsk - NLM (National Library of Medicine)

padagis us llc - cyclosporine (unii: 83hn0gtj6d) (cyclosporine - unii:83hn0gtj6d) - cyclosporine 50 mg in 1 ml - cyclosporine is indicated for the prophylaxis of organ rejection in kidney, liver, and heart allogeneic transplants. it is always to be used with adrenal corticosteroids. the drug may also be used in the treatment of chronic rejection in patients previously treated with other immunosuppressive agents. because of the risk of anaphylaxis, cyclosporine injection should be reserved for patients who are unable to take the soft gelatin capsules or oral solution. cyclosporine injection is contraindicated in patients with a hypersensitivity to cyclosporine and/or cremophor® el (polyoxyethylated castor oil).

USA - engelsk - NLM (National Library of Medicine)

padagis us llc - lidocaine (unii: 98pi200987) (lidocaine - unii:98pi200987), prilocaine (unii: 046o35d44r) (prilocaine - unii:046o35d44r) - lidocaine and prilocaine cream (a eutectic mixture of lidocaine 2.5% and prilocaine 2.5%) is indicated as a topical anesthetic for use on: • normal intact skin for local analgesia. • genital mucous membranes for superficial minor surgery and as pretreatment for infiltration anesthesia. lidocaine and prilocaine cream is not recommended in any clinical situation when penetration or migration beyond the tympanic membrane into the middle ear is possible because of the ototoxic effects observed in animal studies (see warnings). lidocaine and prilocaine cream is contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type or to any other component of the product.

USA - engelsk - NLM (National Library of Medicine)

padagis us llc - hydromorphone hydrochloride (unii: l960up2krw) (hydromorphone - unii:q812464r06) - hydromorphone hydrochloride 8 mg - hydromorphone hydrochloride extended-release tablets are 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. patients considered opioid tolerant are those who are receiving, for one week or longer, at least 60 mg oral 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 hydromorphone hydrochloride extended-release tablets are contraindicated in: 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)]. there are no adequate and well-controlled studies in pregnant women. based on animal data, advise pregnant women of the potential risk to a fetus. in animal reproduction studies, reduced postnatal survival of pups, developmental delays, and altered behavioral responses were noted following oral treatment of pregnant rats with hydromorphone during gestation and through lactation at doses 2.1 times the human daily dose of 32 mg/day (hdd), respectively. in published studies, neural tube defects were noted following subcutaneous injection of hydromorphone to pregnant hamsters at doses 4.8 times the hdd and soft tissue and skeletal abnormalities were noted following subcutaneous continuous infusion of 2.3 times the hdd to pregnant mice. no malformations were noted at 2.1 or 17 times the hdd in pregnant rats or rabbits, respectively [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 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 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. hydromorphone hydrochloride extended-release tablets are 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 hydromorphone hydrochloride extended-release tablets 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. data animal data pregnant rats were treated with hydromorphone hydrochloride from gestation day 6 to 17 via oral gavage doses of 1.75, 3.5, or 7 mg/kg/day (0.5, 1.1, or 2.1 times the hdd of 32 mg/day based on body surface area, respectively). maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in the two highest dose groups). there was no evidence of malformations or embryotoxicity reported. pregnant rabbits were treated with hydromorphone hydrochloride from gestation day 6 to 20 via oral gavage doses of 10, 25, or 50 mg/kg/day (4.3, 8.5, or 17 times the hdd of 32 mg/day based on body surface area, respectively). maternal toxicity was noted in the highest dose group (reduced food consumption and body weights). there was no evidence of malformations or embryotoxicity reported. in a published study, neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of hydromorphone hydrochloride (19 to 258 mg/kg) on gestation day 8 to pregnant hamsters (4.8 to 65.4 times the hdd of 32 mg/day based on body surface area). the findings cannot be clearly attributed to maternal toxicity. no neural tube defects were noted at 14 mg/kg (3.5 times the human daily dose of 32 mg/day). in a published study, cf-1 mice were treated subcutaneously with continuous infusion of 7.5, 15, or 30 mg/kg/day hydromorphone hydrochloride (1.1, 2.3, or 4.6 times the human daily dose of 32 mg based on body surface area) via implanted osmotic pumps during organogenesis (gestation days 7 to 10). soft tissue malformations (cryptorchidism, cleft palate, malformed ventricles and retina), and skeletal variations (split supraoccipital, checkerboard and split sternebrae, delayed ossification of the paws and ectopic ossification sites) were observed at doses 2.3 times the human dose of 32 mg/day based on body surface area. the findings cannot be clearly attributed to maternal toxicity. pregnant rats were treated with hydromorphone hydrochloride from gestation day 6 to lactation day 21 via oral gavage doses of 1.75, 3.5, or 7 mg/kg/day (0.5, 1.1, or 2.1 times the hdd of 32 mg/day based on body surface area, respectively). reduced pup weights were noted at 1.1 and 2.1 times the human daily dose of 32 mg/day and increased pup deaths, delayed ear opening, reduced auditory startle reflex, and reduced open-field activity were also noted at 2.1 times the hdd. maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in all groups) and decreased maternal care in the high dose group. 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 hydromorphone hydrochloride extended-release tablets. low concentrations of hydromorphone have been detected in human milk in clinical trials. withdrawal symptoms can occur in breastfeeding infants when maternal administration of an opioid analgesic is stopped. nursing should not be undertaken while a patient is receiving hydromorphone hydrochloride extended-release tablets since hydromorphone is excreted in the milk. clinical considerations monitor infants exposed to hydromorphone hydrochloride extended-release tablets 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 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), nonclinical toxicology (13.1)] . the safety and effectiveness of hydromorphone hydrochloride extended-release tablets in patients 17 years of age and younger have not been established. elderly patients (aged 65 years or older) may have increased sensitivity to hydromorphone. 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. 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 hydromorphone hydrochloride extended-release tablets slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions ( 5.2 )] . hydromorphone 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 regularly evaluate renal function. in a study that used a single 4 mg oral dose of immediate-release hydromorphone tablets, four-fold increases in plasma levels of hydromorphone (cmax and auc0-∞ ) were observed in patients with moderate hepatic impairment (child-pugh group b). start patients with moderate hepatic impairment on 25% of the hydromorphone hydrochloride extended-release tablets dose that would be used in patients with normal hepatic function. regularly evaluate patients with moderate hepatic impairment for respiratory and central nervous system depression during initiation of therapy with hydromorphone hydrochloride extended-release tablets and during dose titration. the pharmacokinetics of hydromorphone in severe hepatic impairment patients have not been studied. as further increases in cmax and auc0-∞ of hydromorphone in this group are expected, use of alternate analgesics is recommended [see dosage and administration ( 2.6 )] . administration of a single 4 mg dose of immediate-release hydromorphone tablets resulted in two-fold and four-fold increases in plasma levels of hydromorphone (cmax and auc0-48h ) in moderate (clcr = 40 to 60 ml/min) and severe (clcr < 30 ml/min) impairment, respectively. in addition, in patients with severe renal impairment hydromorphone appeared to be more slowly eliminated with longer terminal elimination half-life. start patients with moderate renal impairment on 50% and patients with severe renal impairment on 25% of the hydromorphone hydrochloride extended-release tablets dose that would be prescribed for patients with normal renal function. regularly evaluate patients with renal impairment for respiratory and central nervous system depression during initiation of therapy with hydromorphone hydrochloride extended-release tablets and during dose titration. as hydromorphone hydrochloride extended-release tablets are only intended for once daily administration, consider use of an alternate analgesic that may permit more flexibility with the dosing interval in patients with severe renal impairment [see dosage and administration ( 2.7 )] . hydromorphone hydrochloride extended-release tablets contain hydromorphone, a schedule ii controlled substance. hydromorphone hydrochloride extended-release tablets contain hydromorphone, 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 hydromorphone hydrochloride extended-release tablets 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 hydromorphone hydrochloride extended-release tablets with alcohol and 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 hydromorphone hydrochloride extended-release tablets abuse include those with a history of prolonged use of any opioid, including products containing hydromorphone, those with a history of drug or alcohol abuse, or those who use hydromorphone hydrochloride extended-release tablets 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. hydromorphone hydrochloride extended-release tablets, 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 hydromorphone hydrochloride extended-release tablets abuse of hydromorphone hydrochloride extended-release tablets poses a risk of overdose and death. this risk is increased with concurrent use of hydromorphone hydrochloride extended-release tablets with alcohol and/or other cns depressants. taking cut, broken, chewed, crushed, or dissolved hydromorphone hydrochloride extended-release tablets enhances drug release and increases the risk of overdose and death. hydromorphone hydrochloride extended-release tablets is approved for oral use only. inappropriate intravenous, intramuscular, or subcutaneous use of hydromorphone hydrochloride extended-release tablets can result in death, local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis, and valvular heart injury, and embolism. parenteral drug abuse is commonly associated with transmission of infectious disease 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 hydromorphone hydrochloride extended-release tablets in a patient physically dependent on opioids. rapid tapering of hydromorphone hydrochloride extended-release tablets 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 hydromorphone hydrochloride extended-release tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of hydromorphone hydrochloride extended-release tablets 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 ( 2.5 ), warnings and precautions ( 5.13 )] . 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)] .

USA - engelsk - NLM (National Library of Medicine)

padagis us llc - paroxetine mesylate (unii: m711n184je) (paroxetine - unii:41vrh5220h) - paroxetine 7.5 mg - paroxetine capsules are indicated for the treatment of moderate to severe vasomotor symptoms (vms) associated with menopause. limitation of use: paroxetine capsules are not indicated for the treatment of any psychiatric condition. paroxetine capsules contain a lower dose of paroxetine than that used to treat depression, obsessive compulsive disorder, panic disorder, generalized anxiety disorder, social anxiety disorder, and post-traumatic stress disorder. the safety and efficacy of this lower dose of paroxetine in paroxetine capsules have not been established for any psychiatric condition. patients who require paroxetine for treatment of a psychiatric condition should discontinue paroxetine capsules and initiate a paroxetine-containing medication that is indicated for such use. concomitant use of an maoi with paroxetine capsules or within 14 days of stopping treatment with paroxetine capsules is contraindicated because of an increased risk of serotonin syndrome. the use of paroxetine capsules within 14 days o