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

amneal pharmaceuticals ny llc - 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. 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 systems 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 1/4 of one buprenorphine transdermal system 5 mcg/hour every 3 days or received daily sc buprenorphine at doses of 0.05, 0.5, or 5 mg/kg from gestation day 6 to lactation day 21 (weaning). administration of buprenorphine transdermal system or sc buprenorphine at 0.5 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 transdermal system 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)   and 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 providers(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)]. 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. figure a - do not apply more than 1 patch at the same time unless your healthcare provider 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. figure b   - 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. figure c - the skin site should be free of cuts and irritation (rashes, swelling, redness, or other skin problems). when to apply a new patch: 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. figure d   - 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. figure e   figure f - 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” ). figure g   - 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 ). 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. figure i   - 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. - 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 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. fold used patch in half with sticky sides together (see figure k ). figure k   2. on flat surface, lay back cover of disposal unit and center folded patch on inside cover (see figure l ). figure l   3. remove the white instruction sheet to expose the sticky side of the disposal unit (see figure m ). figure m   4. close disposal unit containing used patch by firmly pressing together to seal (see figure n ). figure n 5. discard in trash receptacle (see figure o ). figure o     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 p ). figure p 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. manufactured by: amneal pharmaceuticals llc piscataway, nj 08854 distributed by: amneal pharmaceuticals llc glasgow, ky 42141 rev. 03-2020-02

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

amneal pharmaceuticals ny llc - mycophenolate mofetil (unii: 9242ecw6r0) (mycophenolic acid - unii:hu9dx48n0t) - mycophenolate mofetil for oral suspension is indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney [see clinical studies (14.1)] , heart [see clinical studies (14.2)]  or liver transplants [see clinical studies (14.3)] , in combination with other immunosuppressants.  allergic reactions to mycophenolate mofetil have been observed; therefore, mycophenolate mofetil for oral suspension is contraindicated in patients with a hypersensitivity to mycophenolate mofetil (mmf), mycophenolic acid (mpa) or any component of the drug product.  pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to mycophenolate during pregnancy and those becoming pregnant within 6 weeks of discontinuing mycophenolate mofetil treatment. to report a pregnancy or obtain information about the registry, visit www.mycophenolaterems.com or call 1-800-­617-8191.  risk summary  use of mycophenolate mofetil (mmf) during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of multiple congenital malformations in multiple organ systems [see human data] . oral administration of mycophenolate to rats and rabbits during the period of organogenesis produced congenital malformations and pregnancy loss at doses less than the recommended clinical dose (0.01 to 0.05 times the recommended clinical doses in kidney and heart transplant patients) [see animal data] .  consider alternative immunosuppressants with less potential for embryofetal toxicity. risks and benefits of mycophenolate mofetil should be discussed with the pregnant woman.  the estimated background risk of pregnancy loss and congenital malformations in organ transplant populations is not clear. 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.  data  a spectrum of congenital malformations (including multiple malformations in individual newborns) has been reported in 23% to 27% of live births in mmf exposed pregnancies, based on published data from pregnancy registries. malformations that have been documented include external ear, eye, and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system.  based on published data from pregnancy registries, the risk of first trimester pregnancy loss has been reported at 45% to 49% following mmf exposure.  in animal reproductive toxicology studies, there were increased rates of fetal resorptions and malformations in the absence of maternal toxicity. oral administration of mmf to pregnant rats from gestational day 7 to day 16 produced increased embryofetal lethality and fetal malformations including anophthalmia, agnathia, and hydrocephaly at doses equivalent to 0.015 and 0.01 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for bsa. oral administration of mmf to pregnant rabbits from gestational day 7 to day 19 produced increased embryofetal lethality and fetal malformations included ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical hernia at dose equivalents as low as 0.05 and 0.03 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for bsa.  risk summary  there are no data on the presence of mycophenolate in human milk, or the effects on milk production. there are limited data in the national transplantation pregnancy registry on the effects of mycophenolate on a breastfed child [see data] . studies in rats treated with mmf have shown mycophenolic acid (mpa) to be present in milk. because available data are limited, it is not possible to exclude potential risks to a breastfeeding infant. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for mycophenolate mofetil and any potential adverse effects on the breastfed infant from mycophenolate mofetil or from the underlying maternal condition.  limited information is available from the national transplantation pregnancy registry. of seven infants reported by the national transplantation pregnancy registry to have been breastfed while the mother was taking mycophenolate, all were born at 34 to 40 weeks gestation, and breastfed for up to 14 months. no adverse events were reported.  females of reproductive potential must be made aware of the increased risk of first trimester pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention and planning.  pregnancy planning  for patients who are considering pregnancy, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible. risks and benefits of mycophenolate mofetil should be discussed with the patient.  pregnancy testing  to prevent unplanned exposure during pregnancy, all females of reproductive potential should have a serum or urine pregnancy test with a sensitivity of at least 25 miu/ml immediately before starting mycophenolate mofetil. another pregnancy test with the same sensitivity should be done 8 to 10 days later. repeat pregnancy tests should be performed during routine follow-up visits. results of all pregnancy tests should be discussed with the patient. in the event of a positive pregnancy test, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible.  contraception  female patients  females of reproductive potential taking mycophenolate mofetil must receive contraceptive counseling and use acceptable contraception (see table 9  for acceptable contraception methods). patients must use acceptable birth control during the entire mycophenolate mofetil therapy, and for 6 weeks after stopping mycophenolate mofetil, unless the patient chooses abstinence.  patients should be aware that mycophenolate mofetil reduces blood levels of the hormones from the oral contraceptive pill and could theoretically reduce its effectiveness [see drug interactions (7.2)] .  table 9 acceptable contraception methods for females of reproductive potential pick from the following birth control options: option 1 methods to use alone - intrauterine devices (iuds) - tubal sterilization - patient’s partner vasectomy or option 2 hormone methods choose 1 barrier methods choose 1 choose one hormone method  and  one barrier method estrogen and progesterone - oral contraceptive pill - transdermal patch - vaginal ring progesterone-only - injection - implant and - diaphragm with spermicide - cervical cap with spermicide - contraceptive sponge - male condom - female condom or option 3 barrier methods choose 1 barrier methods choose 1 choose one barrier method from each column  (must choose two methods) - diaphragm with spermicide - cervical cap with spermicide - contraceptive sponge and - male condom - female condom male patients  genotoxic effects have been observed in animal studies at exposures exceeding the human therapeutic exposures by approximately 1.25 times. thus, the risk of genotoxic effects on sperm cells cannot be excluded. based on this potential risk, sexually active male patients and/or their female partners are recommended to use effective contraception during treatment of the male patient and for at least 90 days after cessation of treatment. also, based on the potential risk of genotoxic effects, male patients should not donate sperm during treatment with mycophenolate mofetil and for at least 90 days after cessation of treatment [see use in special populations (8.1), nonclinical toxicology (13.1), patient counseling information (17.9)] .  safety and effectiveness have been established in pediatric patients 3 months and older for the prophylaxis of organ rejection of allogeneic kidney, heart or liver transplants. kidney transplant use of mycophenolate mofetil in this population is supported by evidence from adequate and well-controlled studies of mycophenolate mofetil in adults with additional data from one open-label, pharmacokinetic and safety study of mycophenolate mofetil in pediatric patients after receiving allogeneic kidney transplant (100 patients, 3 months to 18 years of age) [see dosage and administration (2.2), adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.1)] .  heart transplant and liver transplant use of mycophenolate mofetil in pediatric heart transplant and liver transplant patients is supported by adequate and well- controlled studies and pharmacokinetic data in adult heart transplant and liver transplant patients. additional supportive data include pharmacokinetic data in pediatric kidney transplant and pediatric liver transplant patients (8 liver transplant patients, 9 months to 5 years of age, in an open-label, pharmacokinetic and safety study) and published evidence of clinical efficacy and safety in pediatric heart transplant and pediatric liver transplant patients [ see dosage and administration (2.3, 2.4), adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.1)] . clinical studies of mycophenolate mofetil 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 geriatric and younger patients. in general, dose selection for a geriatric patient should take into consideration the presence of decreased hepatic, renal or cardiac function and of concomitant drug therapies [see adverse reactions (6.1), drug interactions (7)] . patients with kidney transplant  no dosage adjustments are needed in kidney transplant patients experiencing delayed graft function postoperatively but patients should be carefully monitored [see clinical pharmacology (12.3)] . in kidney transplant patients with severe chronic impairment of the graft  (gfr <25 ml/min/1.73 m2 ), no dose adjustments are necessary; however, doses greater than 1 g administered twice a day should be avoided.  patients with heart and liver transplant  no data are available for heart or liver transplant patients with severe chronic renal impairment. mycophenolate mofetil may be used for heart or liver transplant patients with severe chronic renal impairment if the potential benefits outweigh the potential risks.  patients with kidney transplant  no dosage adjustments are recommended for kidney transplant patients with severe hepatic parenchymal disease. however, it is not known whether dosage adjustments are needed for hepatic disease with other etiologies [see clinical pharmacology (12.3)] .  patients with heart transplant  no data are available for heart transplant patients with severe hepatic parenchymal disease.  mycophenolate mofetil (mye " koe fen ' oh late moe ' fe til) for oral suspension, usp read this instructions for use before you take or give mycophenolate mofetil for oral suspension for the first time 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 medical condition or treatment. important: - always use the oral dispenser provided with mycophenolate mofetil for oral suspension to make sure you measure the right amount of medicine. if your mycophenolate mofetil for oral suspension does not come with the oral dispenser, contact your pharmacist. - call your pharmacist if your oral dispenser is lost or damaged. - your pharmacist will write the expiration date on your mycophenolate mofetil for oral suspension bottle label. do not use after the expiration date. - ask your doctor or pharmacist if you have any questions or are unsure about how to take or give the right amount of medicine. - the mycophenolate mofetil for oral suspension should not be mixed with any type of liquids before taking or giving the dose. - do not let the mycophenolate mofetil for oral suspension come in contact with the skin. if this happens, wash the skin well with soap and water. if the mycophenolate mofetil for oral suspension gets in the eyes, rinse the eyes with plain water. - if you spill any mycophenolate mofetil for oral suspension, wipe it up using paper towels wet with water. put the child-resistant bottle cap back on the bottle and wipe the outside of the bottle with wet paper towels. supplies needed to take or give a dose of mycophenolate mofetil for oral suspension : to take or give a dose of mycophenolate mofetil for oral suspension, you will need the bottle of medicine and the oral dispenser provided with the medicine (see figure 1 ). your pharmacist will insert the bottle adapter in the mycophenolate mofetil for oral suspension bottle. do not remove the bottle adapter from the bottle. taking or giving a dose of mycophenolate mofetil for oral suspension: step 1:   with the child-resistant cap on the bottle, shake the bottle well for about 5 seconds before each use. step 2:   open the bottle by firmly pressing down on the child-resistant bottle cap and turning it to the left (counter-clockwise). do not throw away the child-resistant bottle cap. step 3:   place the bottle on a flat surface. before inserting the tip of the oral dispenser into the bottle adapter, push the plunger completely down toward the tip of the oral dispenser. use 1 hand to hold the bottle upright. insert the oral dispenser tip firmly into the opening of the bottle adapter. step 4:   carefully turn the bottle upside down with the oral dispenser tip in place. slowly pull the plunger down to withdraw your prescribed dose. do not pull the plunger out of the oral dispenser (see figure 2 ). step 5:   leave the oral dispenser tip in the bottle and turn the bottle to an upright position. slowly remove the oral dispenser tip from the bottle.                if there are air bubbles in the oral dispenser or if you have withdrawn the wrong dose, insert the oral dispenser tip back into the bottle adapter while the bottle is in an upright position. push the plunger gently all the way up so the mycophenolate mofetil for oral suspension flows back into the bottle. repeat step 4 . step 6:   place the tip of the oral dispenser in the mouth directed towards the cheek and slowly push the plunger down until the oral dispenser is empty. step 7:   put the child-resistant bottle cap back on the bottle and turn the cap to the right (clockwise) to close the bottle. keep the bottle tightly closed after each use. step 8:   rinse the oral dispenser under running tap water after each use: - remove the plunger from the oral dispenser. - rinse the oral dispenser and plunger with water only and let them air dry on a paper towel. - when the oral dispenser and plunger are dry, put the plunger back in the oral dispenser for the next use. do not throw away the oral dispenser. store the oral dispenser in a clean, dry place. - do not boil the oral dispenser. do not use solvent-containing wipes to clean the oral dispenser. do not use cloths or wipes to dry the oral dispenser. how should i store mycophenolate mofetil for oral suspension? - store the mycophenolate mofetil for oral suspension at room temperature between 59°f to 86°f (15°c to 30°c), for up to 60 days. you can also store mycophenolate mofetil for oral suspension in the refrigerator between 36°f to 46°f (2°c to 8°c). - do not freeze. keep mycophenolate mofetil for oral suspension 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:  amneal pharmaceuticals llc bridgewater, nj  08807 rev. 12-2022-04

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amneal pharmaceuticals ny llc - vigabatrin (unii: gr120krt6k) (vigabatrin - unii:gr120krt6k) - vigabatrin 500 mg - vigabatrin for oral solution is indicated as adjunctive therapy for adults and pediatric patients 2 years of age and older with refractory complex partial seizures who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss [see warnings and precautions (5.1)] . vigabatrin for oral solution is not indicated as a first line agent for complex partial seizures. vigabatrin for oral solution is indicated as monotherapy for pediatric patients with infantile spasms 1 month to 2 years of age for whom the potential benefits outweigh the potential risk of vision loss [see warnings and precautions (5.1)] . none. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, including vigabatrin, during pregnancy. encourage women who are taking vigabatrin during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry. this can be done by calling the toll-free number 1-888-233-2334 or visiting the website, http://www.aedpregnancyregistry.org/. this must be done by the patient herself. risk summary there are no adequate data on the developmental risk associated with the use of vigabatrin in pregnant women. limited available data from case reports and cohort studies pertaining to vigabatrin use in pregnant women have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. however, based on animal data, vigabatrin use in pregnant women may result in fetal harm. when administered to pregnant animals, vigabatrin produced developmental toxicity, including an increase in fetal malformations and offspring neurobehavioral and neurohistopathological effects, at clinically relevant doses. in addition, developmental neurotoxicity was observed in rats treated with vigabatrin during a period of postnatal development corresponding to the third trimester of human pregnancy (see data) . 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. the background risk of major birth defects and miscarriage for the indicated population is unknown. data animal data administration of vigabatrin (oral doses of 50 to 200 mg/kg/day) to pregnant rabbits throughout the period of organogenesis was associated with an increased incidence of malformations (cleft palate) and embryofetal death; these findings were observed in two separate studies. the no-effect dose for adverse effects on embryofetal development in rabbits (100 mg/kg/day) is approximately 1/2 the maximum recommended human dose (mrhd) of 3 g/day on a body surface area (mg/m2 ) basis. in rats, oral administration of vigabatrin (50, 100, or 150 mg/kg/day) throughout organogenesis resulted in decreased fetal body weights and increased incidences of fetal anatomic variations. the no-effect dose for adverse effects on embryo-fetal development in rats (50 mg/kg/day) is approximately 1/5 the mrhd on a mg/m2 basis. oral administration of vigabatrin (50, 100, 150 mg/kg/day) to rats from the latter part of pregnancy through weaning produced long-term neurohistopathological (hippocampal vacuolation) and neurobehavioral (convulsions) abnormalities in the offspring. a no-effect dose for developmental neurotoxicity in rats was not established; the low-effect dose (50 mg/kg/day) is approximately 1/5 the mrhd on a mg/m2 basis. in a published study, vigabatrin (300 or 450 mg/kg) was administered by intraperitoneal injection to a mutant mouse strain on a single day during organogenesis (day 7, 8, 9, 10, 11, or 12). an increase in fetal malformations (including cleft palate) was observed at both doses. oral administration of vigabatrin (5, 15, or 50 mg/kg/day) to young rats during the neonatal and juvenile periods of development (postnatal days 4 to 65) produced neurobehavioral (convulsions, neuromotor impairment, learning deficits) and neurohistopathological (brain vacuolation, decreased myelination, and retinal dysplasia) abnormalities in treated animals. the early postnatal period in rats is generally thought to correspond to late pregnancy in humans in terms of brain development. the no-effect dose for developmental neurotoxicity in juvenile rats (5 mg/kg/day) was associated with plasma vigabatrin exposures (auc) less than 1/30 of those measured in pediatric patients receiving an oral dose of 50 mg/kg. risk summary vigabatrin is excreted in human milk. the effects of vigabatrin on the breastfed infant and on milk production are unknown. because of the potential for serious adverse reactions from vigabatrin in nursing infants, breastfeeding is not recommended. if exposing a breastfed infant to vigabatrin, observe for any potential adverse effects [see warnings and precautions (5.1, 5.3, 5.4, 5.8)] . the safety and effectiveness of vigabatrin as adjunctive treatment of refractory complex partial seizures in pediatric patients 2 to 16 years of age have been established and is supported by three double-blind, placebo-controlled studies in patients 3 to 16 years of age, adequate and well-controlled studies in adult patients, pharmacokinetic data from patients 2 years of age and older, and additional safety information in patients 2 years of age [see clinical pharmacology (12.3) and clinical studies (14.1)] . the dosing recommendation in this population varies according to age group and is weight-based [see dosage and administration (2.2)] . adverse reactions in this pediatric population are similar to those observed in the adult population [see adverse reactions (6.1)] . the safety and effectiveness of vigabatrin as monotherapy for pediatric patients with infantile spasms (1 month to 2 years of age) have been established [see dosage and administration (2.3) and clinical studies (14.2)] . safety and effectiveness as adjunctive treatment of refractory complex partial seizures in pediatric patients below the age of 2 and as monotherapy for the treatment of infantile spasms in pediatric patients below the age of 1 month have not been established. duration of therapy for infantile spasms was evaluated in a post hoc analysis of a canadian pediatric epilepsy network (cpen) study of developmental outcomes in infantile spasms patients. this analysis suggests that a total duration of 6 months of vigabatrin therapy is adequate for the treatment of infantile spasms. however, prescribers must use their clinical judgment as to the most appropriate duration of use [see clinical studies (14.2)] . abnormal mri signal changes and intramyelinic edema (ime) in infants and young children being treated with vigabatrin have been observed [see warnings and precautions (5.3, 5.4)] . juvenile animal toxicity data oral administration of vigabatrin (5, 15, or 50 mg/kg/day) to young rats during the neonatal and juvenile periods of development (postnatal days 4 to 65) produced neurobehavioral (convulsions, neuromotor impairment, learning deficits) and neurohistopathological (brain gray matter vacuolation, decreased myelination, and retinal dysplasia) abnormalities. the no-effect dose for developmental neurotoxicity in juvenile rats (the lowest dose tested) was associated with plasma vigabatrin exposures (auc) substantially less than those measured in pediatric patients at recommended doses. in dogs, oral administration of vigabatrin (30 or 100 mg/kg/day) during selected periods of juvenile development (postnatal days 22 to 112) produced neurohistopathological abnormalities (brain gray matter vacuolation). neurobehavioral effects of vigabatrin were not assessed in the juvenile dog. a no-effect dose for neurohistopathology was not established in juvenile dogs; the lowest effect dose (30 mg/kg/day) was associated with plasma vigabatrin exposures lower than those measured in pediatric patients at recommended doses [see warnings and precautions (5.4)] . clinical studies of vigabatrin did not include sufficient numbers of patients aged 65 and over to determine whether they responded differently from younger patients. vigabatrin is known to be substantially excreted by the kidney, and the risk of toxic 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. oral administration of a single dose of 1.5 g of vigabatrin to elderly (≥ 65 years) patients with reduced creatinine clearance (< 50 ml/min) was associated with moderate to severe sedation and confusion in 4 of 5 patients, lasting up to 5 days. the renal clearance of vigabatrin was 36% lower in healthy elderly subjects (≥ 65 years) than in young healthy males. adjustment of dose or frequency of administration should be considered. such patients may respond to a lower maintenance dose [see dosage and administration (2.4)  and clinical pharmacology (12.3)] . other reported clinical experience has not identified differences in responses between the elderly and younger patients. dose adjustment, including initiating treatment with a lower dose, is necessary in pediatric patients 2 years of age and older and adults with mild (creatinine clearance > 50 to 80 ml/min), moderate (creatinine clearance > 30 to 50 ml/min) and severe (creatinine clearance > 10 to 30 ml/min) renal impairment [see dosage and administration (2.4)  and clinical pharmacology (12.3)] . vigabatrin is not a controlled substance. vigabatrin did not produce adverse events or overt behaviors associated with abuse when administered to humans or animals. it is not possible to predict the extent to which a cns active drug will be misused, diverted, and/or abused once marketed. consequently, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of vigabatrin (e.g., incrementation of dose, drug-seeking behavior). following chronic administration of vigabatrin to animals, there were no apparent withdrawal signs upon drug discontinuation. however, as with all aeds, vigabatrin should be withdrawn gradually to minimize increased seizure frequency [see warnings and precautions (5.6)] . vigabatrin (vye ga’ ba trin) for oral solution read this instructions for use before your child starts taking vigabatrin for oral solution and each time you get a refill. there may be new information. this information does not take the place of talking with your healthcare provider about your child’s medical condition or treatment. talk to your healthcare provider if you have any questions about the right dose of medicine to give your child or how to mix it. important note:    - vigabatrin for oral solution comes in a packet - each packet contains 500 mg of vigabatrin for oral solution powder - v igabatrin for oral solution powder must be mixed with water only. the water may be cold or at room temperature. - your healthcare provider will tell you: - how many packets of vigabatrin for oral solution you will need for each dose - how many milliliters (ml) of water to use to mix one dose of vigabatrin for oral solution - how many milliliters (ml) of the powder and water mixture you will need for each dose of medicine - vigabatrin for oral solution should be given right away after it is mixed - use the oral syringes, provided by the pharmacy, to measure and give the correct dose. do not use a household teaspoon or tablespoon. supplies you will need to mix 1 dose of v igabatrin for oral solution: - the number of packets of vigabatrin for oral solution needed for each dose - 2 clean cups: 1 for mixing and 1 for water. the cup used for mixing vigabatrin for oral solution should be clear so you can see if the powder is dissolved - water to mix with the vigabatrin for oral solution powder - one small 3 ml oral syringe and one large 10 ml oral syringe which are provided by the pharmacy - small spoon or other clean utensil to stir the mixture - scissors oral syringe detail step 1: start with 1 of the empty cups and the total number of packets you will need for 1 dose. step 2: before you open the packet, tap it to settle all the powder to the bottom of the packet. step 3: use a pair of scissors to cut open the vigabatrin for oral solution packet along the dotted line. step 4: empty the entire contents of the vigabatrin for oral solution packet into 1 of the clean empty cups (see figure a). figure a - repeat steps 2 to 4 above to open all of the packets needed for 1 dose of vigabatrin for oral solution. step 5: take the second cup and fill it half way with water (see figure b). do not mix vigabatrin for oral solution with anything other than water. figure b - you will use the larger oral syringe (10 ml) to draw up the water needed to mix with the powder from the packets. you will need 10 ml of water for each packet of v igabatrin for oral solution. for example: - if you are using 1 packet of vigabatrin for oral solution, you will need to use 10 ml of water (fill the 10 ml oral syringe 1 time) - if you are using 2 packets of vigabatrin for oral solution, you will need to use 20 ml of water (fill the 10 ml oral syringe 2 times) - if you are using 3 packets of vigabatrin for oral solution, you will need to use 30 ml of water (fill the 10 ml oral syringe 3 times) step 6: use the 10 ml oral syringe to draw up 10 ml of water. to do this, put the tip of the oral syringe all the way into the water in your cup. then pull the plunger up towards you until the edge of the white plunger is at the 10 ml line on the barrel of the oral syringe (see figure c). figure c - if you see bubbles of air in the oral syringe after drawing up the water, turn the oral syringe so the tip is pointing up (see figure d). the air will move to the top of the oral syringe. pull the plunger back towards you and then push it back gently into the oral syringe to get rid of the bubbles. tiny bubbles are normal. figure d step 7: check the oral syringe to make sure it is filled with water up to the 10 ml line (see figure e). figure e step 8: get the second cup that contains the vigabatrin for oral solution needed for your dose. step 9: hold the 10 ml oral syringe that is filled with water with the tip pointing down over the vigabatrin for oral solution. step 10: slowly push the oral syringe plunger all the way down to empty the water from the oral syringe straight into the cup containing the vigabatrin for oral solution (see figure f). figure f repeat steps 6 through 10 until all of the water that is needed to mix 1 dose of v igabatrin for oral solution has been added to the cup containing the powder. step 11: stir the mixture with the small spoon or other clean utensil until the solution is clear (see figure g). this means that all of the powder is dissolved and ready for use. figure g - to give a dose of vigabatrin for oral solution to your child, you should use the oral syringe to draw up the total number of mls of the mixture that your healthcare provider tells you to. - if you are giving 3 ml or less of the mixture, use the smaller 3 ml oral syringe. - if you are giving more than 3 ml of the mixture, use the larger 10 ml oral syringe (this is the oral syringe that you just used to add the water). step 12: put the tip of the oral syringe all the way into the mixture. pull the plunger up towards you to draw up the mixture. stop when the edge of the white plunger lines up with markings on the barrel of the oral syringe that matches the number of mls of mixture your healthcare provider told you to give (see figure h). figure h - if you see bubbles of air in the oral syringe after drawing up the mixture, turn the oral syringe so the tip is pointing up (see figure i). the air will move to the top of the oral syringe. pull the plunger back towards you and then gently push it back in the oral syringe in order to get rid of the bubbles. tiny bubbles are normal. figure i step 13: place the tip of the oral syringe into your child’s mouth and point the oral syringe towards either cheek (see figure j). push on the plunger slowly, a small amount at a time, until all of the mixture in the oral syringe is given. figure j - if the dose you are giving your child is more than 10 mls, repeat steps 12 and 13 until you give the total dose of mixture prescribed by your healthcare provider. step 14: throw away any mixture that is left over. do not save or reuse any leftover mixture. step 15: wash the oral syringes and mixing cups in warm water. to clean the oral syringes, remove the plunger by gently pulling it straight out of the barrel. the barrel and plunger can be hand washed with soap and water, rinsed, and allowed to dry. this instructions for use has been approved by the u.s. food and drug administration. distributed by: amneal pharmaceuticals llc bridgewater, nj 08807 rev. 01-2020-03

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amneal pharmaceuticals ny llc - doxepin hydrochloride (unii: 3u9a0fe9n5) (doxepin - unii:5asj6huz7d) - doxepin 10 mg - doxepin hcl capsules are recommended for the treatment of: - psychoneurotic patients with depression and/or anxiety. - depression and/or anxiety associated with alcoholism (not to be taken concomitantly with alcohol). - depression and/or anxiety associated with organic disease (the possibility of drug interaction should be considered if the patient is receiving other drugs concomitantly). - psychotic depressive disorders with associated anxiety including involutional depression and manic-depressive disorders. the target symptoms of psychoneurosis that respond particularly well to doxepin hcl capsules include anxiety, tension, depression, somatic symptoms and concerns, sleep disturbances, guilt, lack of energy, fear, apprehension and worry. clinical experience has shown that doxepin hcl capsules is safe and well tolerated even in the elderly patient. owing to lack of clinical experience in the pediatric population, doxepin is not recommended for use in children under 12 years of age. doxepin is contraindicated in individuals who have shown hypersensitivity to the drug. possibility of cross sensitivity with other dibenzoxepines should be kept in mind. doxepin is contraindicated in patients with glaucoma or a tendency to urinary retention. these disorders should be ruled out, particularly in older patients.

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amneal pharmaceuticals ny llc - amphetamine sulfate (unii: 6dpv8nk46s) (amphetamine - unii:ck833kgx7e) - amphetamine sulfate tablets, usp 5 mg and 10 mg are indicated for: 1. narcolepsy 2. attention deficit disorder with hyperactivity as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate to severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. the diagnosis of the syndrome should not be made with finality when these symptoms are only of comparatively recent origin. nonlocalizing (soft) neurological signs, learning disability, and abnormal eeg may or may not be present, and a diagnosis of central nervous system dysfunction may or not be warranted. 3. exogenous obesity as a short term (a few weeks) adjunct in a regimen of weight reduction based on caloric restriction for patients refractory to alternative therapy, e.g., repeated diets, group

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amneal pharmaceuticals ny llc - chlordiazepoxide hydrochloride (unii: mfm6k1xwdk) (chlordiazepoxide - unii:6rz6xez3cr), clidinium bromide (unii: 91zqw5jf1z) (clidinium - unii:bo76jf850n) - chlordiazepoxide hydrochloride and clidinium bromide capsules are indicated to control emotional and somatic factors in gastrointestinal disorders. chlordiazepoxide hydrochloride and clidinium bromide capsules may also be used as adjunctive therapy in the treatment of peptic ulcer and in the treatment of the irritable bowel syndrome (irritable colon, spastic colon, mucous colitis) and acute enterocolitis. chlordiazepoxide hydrochloride and clidinium bromide capsules are contraindicated in the presence of glaucoma (since the anticholinergic component may produce some degree of mydriasis) and in patients with prostatic hypertrophy and benign bladder neck obstruction. it is contraindicated in patients with known hypersensitivity to chlordiazepoxide hydrochloride and/or clidinium bromide. chlordiazepoxide hydrochloride and clidinium bromide capsules contain chlordiazepoxide hydrochloride, a schedule iv controlled substance and clidinium bromide, which is not a controlled substance. chlordiazepoxide hydrochloride and clidinium bromide capsules are exempted from schedule iv and is not controlled under the controlled substances act. chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules, is a cns depressant with a potential for abuse and addiction. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. 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. even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. abuse and misuse of benzodiazepines may lead to addiction. abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death. benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders (see warnings ). the following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo. the following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. death is more often associated with polysubstance use (especially benzodiazepines with other cns depressants such as opioids and alcohol). physical dependence chlordiazepoxide hydrochloride and clidinium bromide capsules may produce physical dependence from continued therapy. physical dependence is a state that develops as a result of 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. abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use (see warnings ). to reduce the risk of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide hydrochloride and clidinium bromide capsules or reduce the dosage (see warnings and dosage and administration ). acute withdrawal signs and symptoms acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. more severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures and suicidality. protracted withdrawal syndrome protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. protracted withdrawal symptoms may last weeks to more than 12 months. as a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used. tolerance to chlordiazepoxide hydrochloride and clidinium bromide capsules may develop from continued 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). tolerance to the therapeutic effects of chlordiazepoxide hydrochloride and clidinium bromide capsules may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.

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amneal pharmaceuticals ny llc - desipramine hydrochloride (unii: 1y58do4my1) (desipramine - unii:tg537d343b) - desipramine hydrochloride 10 mg - desipramine hydrochloride tablets are indicated for the treatment of depression. the use of maois intended to treat psychiatric disorders with desipramine hydrochloride or within 14 days of stopping treatment with desipramine hydrochloride is contraindicated because of an increased risk of serotonin syndrome. the use of desipramine hydrochloride within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated (see warnings  and dosage and administration ). starting desipramine hydrochloride in a patient who is being treated with maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome (see warnings  and dosage and administration ). desipramine hydrochloride is contraindicated in the acute recovery period following myocardial infarction. it should not be used in those who have shown prior hypersensitivity to the drug. cross-sensitivity between this and other dibenzazepines is a possibility.

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amneal pharmaceuticals ny llc - etodolac (unii: 2m36281008) (etodolac - unii:2m36281008) - carefully consider the potential benefits and risks of etodolac tablets and other treatment options before deciding to use etodolac tablets. use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see warnings ). etodolac tablets are indicated: - for acute and long-term use in the management of signs and symptoms of the following: osteoarthritis rheumatoid arthritis - osteoarthritis - rheumatoid arthritis - for the management of acute pain etodolac tablets are contraindicated in patients with known hypersensitivity to etodolac or other ingredients in etodolac tablets. etodolac tablets should not be given to patients who have experienced asthma, urticaria, or other allergic-type reactions after taking aspirin or other nsaids. severe, rarely fatal, anaphylactic-like reactions to nsaids have been reported in such patients (see warnings, anaphylactoid reactions and precautions, pre-existing asthma ). - in the setting of coronary artery bypass graft (cabg) surgery (see warnings ).

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amneal pharmaceuticals ny llc - deferasirox (unii: v8g4mof2v9) (deferasirox - unii:v8g4mof2v9) - deferasirox tablets are indicated for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older. deferasirox tablets are indicated for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion-dependent thalassemia (ntdt) syndromes and with a liver iron concentration (lic) of at least 5 milligrams of iron per gram of liver dry weight (mg fe/g dw) and a serum ferritin greater than 300 mcg/l. the safety and efficacy of deferasirox tablets when administered with other iron chelation therapy have not been established. deferasirox is contraindicated in patients with: - estimated gfr less than 40 ml/min/1.73 m2 [see dosage and administration (2.5), warnings and precautions (5.1)]; - poor performance status [see warnings and precautions (5.1, 5.3)] ; - high-risk myelodysplastic syndromes (this patient population was not studied and is not expected to benefit from chelation therapy) ; - advanced malignancies [see warnings and precautions (5.1, 5.3)] ; - platelet counts less than 50 x 109 /l [see warnings and precautions (5.3, 5.4)] ; - known hypersensitivity to deferasirox or any component of deferasirox tablets [see warnings and precautions (5.7), adverse reactions (6.2)] . risk summary there are no studies with the use of deferasirox in pregnant women to inform drug-associated risks. administration of deferasirox to rats during pregnancy resulted in decreased offspring viability and an increase in renal anomalies in male offspring at doses that were about or less than the recommended human dose on a mg/m2 basis. no fetal effects were noted in pregnant rabbits at doses equivalent to the human recommended dose on an mg/m2 basis. deferasirox should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies had a background risk of birth defect, loss, or other adverse outcomes. however, the background risk in the u.s. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. data animal data in embryo-fetal developmental studies, pregnant rats and rabbits received oral deferasirox during the period of organogenesis at doses up to 100 mg/kg/day in rats and 50 mg/kg/day in rabbits (1.2 times the maximum recommended human dose (mrhd) on an mg/m2 basis). these doses resulted in maternal toxicity but no fetal harm was observed. in a prenatal and postnatal developmental study, pregnant rats received oral deferasirox daily from organogenesis through lactation day 20 at doses of 10 mg/kg/day, 30 mg/kg/day, and 90 mg/kg/day (0.1, 0.3, and 1.0 times the mrhd on a mg/m2 basis). maternal toxicity, loss of litters, and decreased offspring viability occurred at 90 mg/kg/day (1.0 times the mrhd on a mg/m2 basis), and increases in renal anomalies in male offspring occurred at 30 mg/kg/day (0.3 times the mrhd on a mg/m2 basis). risk summary no data are available regarding the presence of deferasirox or its metabolites in human milk, the effects of the drug on the breastfed child, or the effects of the drug on milk production. deferasirox and its metabolites were excreted in rat milk. because many drugs are excreted in human milk and because of the potential for serious adverse reactions in a breastfeeding child from deferasirox and its metabolites, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother. contraception counsel patients to use non-hormonal method(s) of contraception since deferasirox can render hormonal contraceptives ineffective [see drug interactions (7.2)] . transfusional iron overload the safety and effectiveness of deferasirox have been established in pediatric patients 2 years of age and older for the treatment of transfusional iron overload [see  dosage and administration (2.1)]. safety and effectiveness have not been established in pediatric patients less than 2 years of age for the treatment of transfusional iron overload. pediatric approval for treatment of transfusional iron overload was based on clinical studies of 292 pediatric patients 2 years to less than 16 years of age with various congenital and acquired anemias. seventy percent of these patients had beta-thalassemia [see indications and usage (1), dosage and administration (2.1), clinical studies (14)] . in those clinical studies, 173 children (ages 2 to < 12 years) and 119 adolescents (ages 12 to < 17 years) were exposed to deferasirox. iron overload in non-transfusion-dependent thalassemia syndromes the safety and effectiveness of deferasirox have been established in patients 10 years of age and older for the treatment of chronic iron overload with non-transfusion-dependent thalassemia (ntdt) syndromes [see dosage and administration (2.2)] . safety and effectiveness have not been established in patients less than 10 years of age with chronic iron overload in ntdt syndromes. pediatric approval for treatment of ntdt syndromes with liver iron (fe) concentration (lic) of at least 5 mg fe per gram of dry weight and a serum ferritin greater than 300 mcg/l was based on 16 pediatric patients treated with deferasirox therapy (10 years to less than 16 years of age) with chronic iron overload and ntdt. use of deferasirox in these age groups is supported by evidence from adequate and well-controlled studies of deferasirox in adult and pediatric patients [see indications and usage (1.2), dosage and administration (2.2), clinical studies (14)] . in general, risk factors for deferasirox-associated kidney injury include preexisting renal disease, volume depletion, overchelation, and concomitant use of other nephrotoxic drugs. acute kidney injury, and acute liver injury and failure has occurred in pediatric patients. in a pooled safety analysis, pediatric patients with higher deferasirox exposures had a greater probability of renal toxicity and decreased renal function, resulting in increased deferasirox exposure and progressive renal toxicity/kidney injury. higher rates of renal aes have been identified among pediatric patients receiving deferasirox (tablets for oral suspension) doses greater than 25 mg/kg/day equivalent to 17.5 mg/kg/day deferasirox when their serum ferritin values were less than 1,000 mcg/l [see dosage and administration (2.5), warnings and precautions (5.1, 5.6), adverse reactions (6.1, 6.2)] . monitoring recommendations for all pediatric patients with transfusional iron overload and ntdt it is recommended that serum ferritin be monitored every month to assess the patient’s response to therapy and to minimize the risk of overchelation [see warnings and precautions (5.6)]. monitor renal function by estimating gfr using an egfr prediction equation appropriate for pediatric patients and evaluate renal tubular function. monitor renal function more frequently in pediatric patients in the presence of renal toxicity risk factors, including episodes of dehydration, fever and acute illness that may result in volume depletion or decreased renal perfusion. use the minimum effective dose [see warnings and precautions (5.1)] . interrupt deferasirox in pediatric patients with transfusional iron overload, and consider dose interruption in pediatric patients with non-transfusion-dependent iron overload, for acute illnesses, which can cause volume depletion, such as vomiting, diarrhea, or prolonged decreased oral intake, and monitor more frequently. resume therapy as appropriate, based on assessments of renal function, when oral intake and volume status are normal. evaluate the risk benefit profile of continued deferasirox use in the setting of decreased renal function. avoid use of other nephrotoxic drugs [see dosage and administration (2.5), warnings and precautions (5.1)]. juvenile animal toxicity data renal toxicity was observed in adult mice, rats, and marmoset monkeys administered deferasirox at therapeutic doses. in a neonatal and juvenile toxicity study in rats, deferasirox was administered orally from postpartum day 7 through 70, which equates to a human age range of term neonate through adolescence. increased renal toxicity was identified in juvenile rats compared to adult rats at a dose based on mg/m2 approximately 0.4 times the recommended dose of 20 mg/kg/day. a higher frequency of renal abnormalities was noted when deferasirox was administered to non-iron overloaded animals compared to iron overloaded animals. additional pediatric use information is approved for novartis pharmaceuticals corporation’s jadenu® (deferasirox) tablets. however, due to novartis pharmaceuticals corporation’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. four hundred thirty-one (431) patients greater than or equal to 65 years of age were studied in clinical trials of deferasirox in the transfusional iron overload setting. two hundred twenty-five (225) of these patients were between 65 and 75 years of age while 206 were greater than or equal to 75 years of age. the majority of these patients had myelodysplastic syndrome (mds) (n = 393). in these trials, elderly patients experienced a higher frequency of adverse reactions than younger patients. monitor elderly patients for early signs or symptoms of adverse reactions that may require a dose adjustment. elderly patients are at increased risk for toxicity due to the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range. in elderly patients, including those with mds, individualize the decision to remove accumulated iron based on clinical circumstances and the anticipated clinical benefit and risks of deferasirox tablets for oral suspension therapy. deferasirox is contraindicated in patients with egfr less than 40 ml/min/1.73 m2 [see contraindications (4)] . for patients with renal impairment (egfr 40 to 60 ml/min/1.73 m2 ), reduce the starting dose by 50% [see dosage and administration (2.4), clinical pharmacology (12.3)] . exercise caution in pediatric patients with an egfr between 40 and 60 ml/minute/1.73 m2 [see dosage and administration (2.4)] . if treatment is needed, use the minimum effective dose with enhanced monitoring of glomerular and renal tubular function. individualize dose titration based on improvement in renal injury [see dosage and administration (2.4, 2.5)] . deferasirox can cause glomerular dysfunction, renal tubular toxicity, or both, and can result in acute renal failure. monitor all patients closely for changes in egfr and renal tubular dysfunction during deferasirox treatment. if either develops, consider dose reduction, interruption or discontinuation of deferasirox until glomerular or renal tubular function returns to baseline [see dosage and administration (2.4, 2.5), warnings and precautions (5.1)] . avoid use in patients with severe (child-pugh c) hepatic impairment. for patients with moderate (child-pugh b) hepatic impairment, reduce the starting dose by 50%. closely monitor patients with mild (child-pugh a) or moderate (child-pugh b) hepatic impairment for efficacy and adverse reactions that may require dose titration [see dosage and administration (2.4), warnings and precautions (5.2), clinical pharmacology (12.3)].

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

amneal pharmaceuticals ny llc - deferasirox (unii: v8g4mof2v9) (deferasirox - unii:v8g4mof2v9) - deferasirox oral granules are indicated for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older. deferasirox oral granules are indicated for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion-dependent thalassemia (ntdt) syndromes and with a liver iron concentration (lic) of at least 5 milligrams of iron per gram of liver dry weight (mg fe/g dw) and a serum ferritin greater than 300 mcg/l. the safety and efficacy of deferasirox oral granules when administered with other iron chelation therapy have not been established. deferasirox is contraindicated in patients with: - estimated gfr less than 40 ml/min/1.73 m2 [see dosage and administration (2.5), warnings and precautions (5.1)] ; - poor performance status [see warnings and precautions (5.1, 5.3)] ; - high-risk myelodysplastic syndromes (this patient population was not studied and is not expected to benefit from chelation therapy) ; - advanced malignancies [see warnings and precautions (5.1, 5.3)] ; - platelet counts less than 50 x 109 /l [see warnings and precautions (5.3, 5.4)] ; - known hypersensitivity to deferasirox or any component of deferasirox oral granules [see warnings and precautions (5.7), adverse reactions (6.2)] . risk summary there are no studies with the use of deferasirox in pregnant women to inform drug-associated risks. administration of deferasirox to rats during pregnancy resulted in decreased offspring viability and an increase in renal anomalies in male offspring at doses that were about or less than the recommended human dose on a mg/m2 basis. no fetal effects were noted in pregnant rabbits at doses equivalent to the human recommended dose on an mg/m2 basis. deferasirox should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies had a background risk of birth defect, loss, or other adverse outcomes. however, the background risk in the u.s. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. data animal data in embryo-fetal developmental studies, pregnant rats and rabbits received oral deferasirox during the period of organogenesis at doses up to 100 mg/kg/day in rats and 50 mg/kg/day in rabbits (1.2 times the maximum recommended human dose (mrhd) on an mg/m2 basis). these doses resulted in maternal toxicity but no fetal harm was observed. in a prenatal and postnatal developmental study, pregnant rats received oral deferasirox daily from organogenesis through lactation day 20 at doses of 10, 30, and 90 mg/kg/day (0.1, 0.3, and 1.0 times the mrhd on a mg/m2 basis). maternal toxicity, loss of litters, and decreased offspring viability occurred at 90 mg/kg/day (1.0 times the mrhd on a mg/m2 basis), and increases in renal anomalies in male offspring occurred at 30 mg/kg/day (0.3 times the mrhd on a mg/m2 basis). risk summary no data are available regarding the presence of deferasirox or its metabolites in human milk, the effects of the drug on the breastfed child, or the effects of the drug on milk production. deferasirox and its metabolites were excreted in rat milk. because many drugs are excreted in human milk and because of the potential for serious adverse reactions in a breastfeeding child from deferasirox and its metabolites, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother. contraception counsel patients to use non-hormonal method(s) of contraception since deferasirox can render hormonal contraceptives ineffective [see drug interactions (7.2)] . transfusional iron overload the safety and effectiveness of deferasirox have been established in pediatric patients 2 years of age and older for the treatment of transfusional iron overload [see dosage and administration (2.1)] . safety and effectiveness have not been established in pediatric patients less than 2 years of age for the treatment of transfusional iron overload. pediatric approval for treatment of transfusional iron overload was based on clinical studies of 292 pediatric patients 2 years to less than 16 years of age with various congenital and acquired anemias. seventy percent of these patients had beta-thalassemia [see indications and usage (1), dosage and administration (2.1), clinical studies (14)] . in those clinical studies, 173 children (ages 2 to < 12 years) and 119 adolescents (ages 12 to < 17 years) were exposed to deferasirox. iron overload in non-transfusion-dependent thalassemia syndromes the safety and effectiveness of deferasirox have been established in patients 10 years of age and older for the treatment of chronic iron overload with non-transfusion-dependent thalassemia (ntdt) syndromes [see dosage and administration (2.2)]. safety and effectiveness have not been established in patients less than 10 years of age with chronic iron overload in ntdt syndromes. pediatric approval for treatment of ntdt syndromes with liver iron (fe) concentration (lic) of at least 5 mg fe per gram of dry weight and a serum ferritin greater than 300 mcg/l was based on 16 pediatric patients treated with deferasirox therapy (10 years to less than 16 years of age) with chronic iron overload and ntdt. use of deferasirox in these age groups is supported by evidence from adequate and well-controlled studies of deferasirox in adult and pediatric patients [see indications and usage (1.2), dosage and administration (2.2), clinical studies (14)]. in general, risk factors for deferasirox-associated kidney injury include preexisting renal disease, volume depletion, overchelation, and concomitant use of other nephrotoxic drugs. acute kidney injury, and acute liver injury and failure has occurred in pediatric patients. in a pooled safety analysis, pediatric patients with higher deferasirox exposures had a greater probability of renal toxicity and decreased renal function, resulting in increased deferasirox exposure and progressive renal toxicity/kidney injury. higher rates of renal aes have been identified among pediatric patients receiving deferasirox (tablets for oral suspension) doses greater than 25 mg/kg/day equivalent to 17.5 mg/kg/day deferasirox when their serum ferritin values were less than 1,000 mcg/l [see dosage and administration (2.5), warnings and precautions (5.1, 5.6), adverse reactions (6.1, 6.2)] . monitoring recommendations for all pediatric patients with transfusional iron overload and ntdt it is recommended that serum ferritin be monitored every month to assess the patient’s response to therapy and to minimize the risk of overchelation [see warnings and precautions (5.6)]. monitor renal function by estimating gfr using an egfr prediction equation appropriate for pediatric patients and evaluate renal tubular function. monitor renal function more frequently in pediatric patients in the presence of renal toxicity risk factors, including episodes of dehydration, fever and acute illness that may result in volume depletion or decreased renal perfusion. use the minimum effective dose [see warnings and precautions (5.1)]. interrupt deferasirox in pediatric patients with transfusional iron overload, and consider dose interruption in pediatric patients with non-transfusion-dependent iron overload, for acute illnesses, which can cause volume depletion, such as vomiting, diarrhea, or prolonged decreased oral intake, and monitor more frequently. resume therapy as appropriate, based on assessments of renal function, when oral intake and volume status are normal. evaluate the risk benefit profile of continued deferasirox use in the setting of decreased renal function. avoid use of other nephrotoxic drugs [see dosage and administration (2.5), warnings and precautions (5.1)]. juvenile animal toxicity data renal toxicity was observed in adult mice, rats, and marmoset monkeys administered deferasirox at therapeutic doses. in a neonatal and juvenile toxicity study in rats, deferasirox was administered orally from postpartum day 7 through 70, which equates to a human age range of term neonate through adolescence. increased renal toxicity was identified in juvenile rats compared to adult rats at a dose based on mg/m2 approximately 0.4 times the recommended dose of 20 mg/kg/day. a higher frequency of renal abnormalities was noted when deferasirox was administered to non-iron overloaded animals compared to iron overloaded animals. additional pediatric use information is approved for novartis pharmaceuticals corporation’s jadenu® (deferasirox) granules. however, due to novartis pharmaceuticals corporation’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. four hundred thirty-one (431) patients greater than or equal to 65 years of age were studied in clinical trials of deferasirox in the transfusional iron overload setting. two hundred twenty-five (225) of these patients were between 65 and 75 years of age while 206 were greater than or equal to 75 years of age. the majority of these patients had myelodysplastic syndrome (mds) (n = 393). in these trials, elderly patients experienced a higher frequency of adverse reactions than younger patients. monitor elderly patients for early signs or symptoms of adverse reactions that may require a dose adjustment. elderly patients are at increased risk for toxicity due to the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range. in elderly patients, including those with mds, individualize the decision to remove accumulated iron based on clinical circumstances and the anticipated clinical benefit and risks of deferasirox tablets for oral suspension therapy. deferasirox is contraindicated in patients with egfr less than 40 ml/min/1.73 m2 [see contraindications (4)] . for patients with renal impairment (egfr 40 to 60 ml/min/1.73 m2 ), reduce the starting dose by 50% [see dosage and administration (2.4), clinical pharmacology (12.3)] . exercise caution in pediatric patients with an egfr between 40 and 60 ml/min/1.73 m2 [see dosage and administration (2.4)] . if treatment is needed, use the minimum effective dose with enhanced monitoring of glomerular and renal tubular function. individualize dose titration based on improvement in renal injury [see dosage and administration (2.4, 2.5)] . deferasirox can cause glomerular dysfunction, renal tubular toxicity, or both, and can result in acute renal failure. monitor all patients closely for changes in egfr and renal tubular dysfunction during deferasirox treatment. if either develops, consider dose reduction, interruption or discontinuation of deferasirox until glomerular or renal tubular function returns to baseline [see dosage and administration (2.4, 2.5), warnings and precautions (5.1)] . avoid use in patients with severe (child-pugh c) hepatic impairment. for patients with moderate (child-pugh b) hepatic impairment, reduce the starting dose by 50%. closely monitor patients with mild (child-pugh a) or moderate (child-pugh b) hepatic impairment for efficacy and adverse reactions that may require dose titration [see dosage and administration (2.4), warnings and precautions (5.2), clinical pharmacology (12.3)].