אוסטרליה - אנגלית - Department of Health (Therapeutic Goods Administration)

arrow pharma pty ltd - tacrolimus monohydrate, quantity: 5.112 mg (equivalent: tacrolimus, qty 5 mg) - capsule, hard - excipient ingredients: hypromellose; lactose monohydrate; croscarmellose sodium; magnesium stearate; gelatin; purified water; sodium lauryl sulfate; brilliant blue fcf; phloxine b; titanium dioxide; quinoline yellow; propylene glycol; butan-1-ol; isopropyl alcohol; ethanol; shellac; strong ammonia solution; potassium hydroxide; iron oxide black; ethanol absolute - adjunct to liver, kidney, lung or heart allograft transplantation in adults and children.

אוסטרליה - אנגלית - Department of Health (Therapeutic Goods Administration)

arrow pharma pty ltd - tacrolimus monohydrate, quantity: 1.022 mg (equivalent: tacrolimus, qty 1 mg) - capsule, hard - excipient ingredients: hypromellose; lactose monohydrate; croscarmellose sodium; magnesium stearate; gelatin; purified water; sodium lauryl sulfate; brilliant blue fcf; iron oxide yellow; titanium dioxide; propylene glycol; butan-1-ol; isopropyl alcohol; ethanol; shellac; strong ammonia solution; potassium hydroxide; iron oxide black; ethanol absolute - adjunct to liver, kidney, lung or heart allograft transplantation in adults and children.

אוסטרליה - אנגלית - Department of Health (Therapeutic Goods Administration)

arrow pharma pty ltd - tacrolimus monohydrate, quantity: 0.511 mg (equivalent: tacrolimus, qty 0.5 mg) - capsule, hard - excipient ingredients: hypromellose; lactose monohydrate; croscarmellose sodium; magnesium stearate; gelatin; purified water; sodium lauryl sulfate; brilliant blue fcf; allura red ac; propylene glycol; butan-1-ol; isopropyl alcohol; ethanol; shellac; strong ammonia solution; potassium hydroxide; iron oxide black; ethanol absolute - adjunct to liver, kidney, lung or heart allograft transplantation in adults and children.

ארצות הברית - אנגלית - NLM (National Library of Medicine)

hikma pharmaceuticals usa inc. - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - morphine sulfate 10 mg in 1 ml - infumorph is for use in continuous microinfusion devices and indicated only for intrathecal or epidural infusion in the management of intractable chronic pain severe enough to require an opioid analgesic and for which less invasive means of controlling pain are inadequate. limitations of use not for single-dose intravenous, intramuscular, or subcutaneous administration due to the risk of overdose. not for single-dose neuraxial injection because infumorph is too concentrated for accurate delivery of the smaller doses used in this setting. infumorph should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate. infumorph 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 (5.9)] - concurrent use of monoamine oxidase inhibitors (maois) or use of maois within the last 14 days [see warnings and precautions (5.10), drug interactions (7)] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.14)] - hypersensitivity to morphine (e.g., anaphylaxis) [see adverse reactions (6)] neuraxial administration of infumorph is contraindicated in patients with: - infection at the injection microinfusion site [see warnings and precautions (5.1)] - concomitant anticoagulant therapy [see warnings and precautions (5.1)] - uncontrolled bleeding diathesis [see warnings and precautions (5.1)] - the presence of any other concomitant therapy or medical condition which would render epidural or intrathecal administration of medication especially hazardous. risk summary use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.5)] . available data with infumorph in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. there are adverse outcomes reported with fetal exposure to opioid analgesics (see clinical considerations) . published studies with morphine use during pregnancy have not reported a clear association with morphine and major birth defects [see human data] . in published animal reproduction studies, morphine administered subcutaneously during the early gestational period produced neural tube defects (i.e., exencephaly and cranioschisis) at 5 and 16 times the human daily dose of 60 mg based on body surface area (hdd) in hamsters and mice, respectively, lower fetal body weight and increased incidence of abortion at 0.4 times the hdd in the rabbit, growth retardation at 6 times the hdd in the rat, and axial skeletal fusion and cryptorchidism at 16 times the hdd in the mouse. administration of morphine sulfate to pregnant rats during organogenesis and through lactation resulted in cyanosis, hypothermia, decreased brain weights, pup mortality, decreased pup body weights, and adverse effects on reproductive tissues at 3-4 times the hdd; and long-term neurochemical changes in the brain of offspring which correlate with altered behavioral responses that persist through adulthood at exposures comparable to and less than the hdd [see animal data] . based on animal data, advise pregnant women of the potential risk to a fetus. the 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 (5.5)] . labor or delivery infumorph 200 and 500 (10 and 25 mg/ml, respectively) are too highly concentrated for routine use in obstetric neuraxial analgesia. opioids, including intravenously, epidurally, and intrathecally administered morphine, readily cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, and resuscitative equipment must be available for reversal of opioid-induced respiratory depression in the neonate.  infumorph is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including infumorph, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data human data the results from a population-based prospective cohort, including 70 women exposed to morphine during the first trimester of pregnancy and 448 women exposed to morphine at any time during pregnancy, indicate no increased risk for congenital malformations. however, these studies cannot definitely establish the absence of any risk because of methodological limitations, including small sample size and nonrandomized study design. animal data formal reproductive and developmental toxicology studies for morphine have not been conducted. exposure margins for the following published study reports are based on human daily dose of 60 mg morphine using a body surface area comparison (hdd). neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of morphine sulfate (35-322 mg/kg) on gestation day 8 to pregnant hamsters (4.7 to 43.5 times the hdd). a no adverse effect level was not defined in this study and the findings cannot be clearly attributed to maternal toxicity. neural tube defects (exencephaly), axial skeletal fusions, and cryptorchidism were reported following a single subcutaneous (sc) injection of morphine sulfate to pregnant mice (100-500 mg/kg) on gestation day 8 or 9 at 200 mg/kg or greater (16 times the hdd) and fetal resorption at 400 mg/kg or higher (32 times the hdd). no adverse effects were noted following 100 mg/kg morphine in this model (8 times the hdd). in one study, following continuous subcutaneous infusion of doses greater than or equal to 2.72 mg/kg to mice (0.2 times the hdd), exencephaly, hydronephrosis, intestinal hemorrhage, split supraoccipital, malformed sternebrae, and malformed xiphoid were noted. the effects were reduced with increasing daily dose; possibly due to rapid induction of tolerance under these infusion conditions. the clinical significance of this report is not clear. decreased fetal weights were observed in pregnant rats treated with 20 mg/kg/day morphine sulfate (3.2 times the hdd) from gestation day 7 to 9. there was no evidence of malformations despite maternal toxicity (10% mortality). in a second rat study, decreased fetal weight and increased incidences of growth retardation were noted at 35 mg/kg/day (5.7 times the hdd) and there was a reduced number of fetuses at 70 mg/kg/day (11.4 times the hdd) when pregnant rats were treated with 10, 35, or 70 mg/kg/day morphine sulfate via continuous infusion from gestation day 5 to 20. there was no evidence of fetal malformations or maternal toxicity. an increased incidence of abortion was noted in a study in which pregnant rabbits were treated with 2.5 (0.8 times the hdd) to 10 mg/kg morphine sulfate via subcutaneous injection from gestation day 6 to 10. in a second study, decreased fetal body weights were reported following treatment of pregnant rabbits with increasing doses of morphine (10-50 mg/kg/day) during the pre-mating period and 50 mg/kg/day (16 times the hdd) throughout the gestation period. no overt malformations were reported in either publication; although only limited endpoints were evaluated. in published studies in rats, exposure to morphine during gestation and/or lactation periods is associated with: decreased pup viability at 12.5 mg/kg/day or greater (2 times the hdd); decreased pup body weights at 15 mg/kg/day or greater (2.4 times the hdd); decreased litter size, decreased absolute brain and cerebellar weights, cyanosis, and hypothermia at 20 mg/kg/day (3.2 times the hdd); alteration of behavioral responses (play, social-interaction) at 1 mg/kg/day or greater (0.2 times the hdd); alteration of maternal behaviors (e.g., decreased nursing and pup retrievals) in mice at 1 mg/kg or higher (0.08 times the hdd) and rats at 1.5 mg/kg/day or higher (0.2 times the hdd); and a host of behavioral abnormalities in the offspring of rats, including altered responsiveness to opioids at 4 mg/kg/day (0.7 times the hdd) or greater. fetal and/or postnatal exposure to morphine in mice and rats has been shown to result in morphological changes in fetal and neonatal brain and neuronal cell loss, alteration of a number of neurotransmitter and neuromodulator systems, including opioid and nonopioid systems, and impairment in various learning and memory tests that appear to persist into adulthood. these studies were conducted with morphine treatment usually in the range of 4 to 20 mg/kg/day (0.7 to 3.2 times the hdd). additionally, delayed sexual maturation and decreased sexual behaviors in female offspring at 20 mg/kg/day (3.2 times the hdd), and decreased plasma and testicular levels of luteinizing hormone and testosterone, decreased testes weights, seminiferous tubule shrinkage, germinal cell aplasia, and decreased spermatogenesis in male offspring were also observed at 20 mg/kg/day (3.2 times the hdd). decreased litter size and viability were observed in the offspring of male rats that were intraperitoneally administered morphine sulfate for 1 day prior to mating at 25 mg/kg/day (4.1 times the hdd) and mated to untreated females. decreased viability and body weight and/or movement deficits in both first and second generation offspring were reported when male mice were treated for 5 days with escalating doses of 120 to 240 mg/kg/day morphine sulfate (9.7 to 19.5 times the hdd) or when female mice treated with escalating doses of 60 to 240 mg/kg/day (4.9 to 19.5 times the hdd) followed by a 5-day treatment-free recovery period prior to mating. similar multigenerational findings were also seen in female rats pre-gestationally treated with escalating doses of 10 to 22 mg/kg/day morphine (1.6 to 3.6 times the hdd). risk summary morphine is present in breast milk. published lactation studies report variable concentrations of morphine in breast milk with administration of immediate-release morphine to nursing mothers in the early postpartum period with a milk-to-plasma morphine auc ratio of 2.5:1 measured in one lactation study. however, there is insufficient information to determine the effects of morphine on the breastfed infant and the effects of morphine on milk production. lactation studies have not been conducted with infumorph, and no information is available on the effects of the drug on the breastfed infant or the effects of the drug on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for infumorph and any potential adverse effects on the breastfed infant from infumorph or from the underlying maternal condition. clinical considerations monitor infants exposed to infumorph through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of morphine is stopped, or when breastfeeding is stopped. infertility   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), clinical pharmacology (12.2)] . in published animal studies, morphine administration adversely effected fertility and reproductive endpoints in male rats and prolonged estrus cycle in female rats [see nonclinical toxicology (13) ]. adequate studies to establish the safety and effectiveness of spinal morphine in pediatric patients have not been performed, and usage in this population is not recommended. elderly patients (aged 65 years or older) may have increased sensitivity to infumorph. in general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of infumorph slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see warnings and precautions (5.8)] . the pharmacodynamic effects of neuraxial morphine in the elderly are more variable than in the younger population. patients will vary widely in the effective initial dose, rate of development of tolerance and the frequency and magnitude of associated adverse effects as the dose is increased.  initial doses should be based on careful clinical observation following “test doses”, after making due allowances for the effects of the patient’s age and infirmity on his/her ability to clear the drug, particularly in patients receiving epidural morphine. morphine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. the elimination half-life of morphine may be prolonged in patients with reduced metabolic rates and with hepatic and/or renal dysfunction. hence, care should be exercised in administering infumorph epidurally to patients with these conditions. high blood morphine levels, due to reduced clearance, may take several days to develop. infumorph contains morphine, a schedule ii controlled drug substance. infumorph contains morphine, 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 (5.2)] . 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 infumorph 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 infumorph 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 infumorph abuse include those with a history of prolonged use of any opioid, including products containing morphine, those with a history of drug or alcohol abuse, or those who use infumorph in combination with other abused drugs. “drug-seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. infumorph, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. careful recordkeeping 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 infumorph abuse of infumorph poses a risk of overdose and death. the risk is increased with concurrent use of infumorph with alcohol and/or other cns depressants. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during 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. infumorph should not be abruptly discontinued in a physically-dependent patient [see dosage and administration (2.6)]. if infumorph is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur, typically characterized by restlessness, lacrimation, rhinorrhea, perspiration, chills, myalgia, and mydriasis. other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. 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) ].

אוסטרליה - אנגלית - Department of Health (Therapeutic Goods Administration)

astellas pharma australia pty ltd - tacrolimus, quantity: 5 mg - capsule, modified release - excipient ingredients: lactose monohydrate; titanium dioxide; hypromellose; sodium lauryl sulfate; iron oxide red; magnesium stearate; iron oxide yellow; ethylcellulose; gelatin; butan-1-ol; hyprolose; purified water; industrial methylated spirit; simethicone; lecithin; ethanol; shellac; strong ammonia solution; sulfuric acid - prograf-xl is indicated for use as an adjunct to liver, kidney, lung or heart allograft transplantation in adults and children.

אוסטרליה - אנגלית - Department of Health (Therapeutic Goods Administration)

astellas pharma australia pty ltd - tacrolimus, quantity: 1 mg - capsule, modified release - excipient ingredients: hypromellose; iron oxide yellow; gelatin; sodium lauryl sulfate; titanium dioxide; ethylcellulose; iron oxide red; magnesium stearate; lactose monohydrate; butan-1-ol; hyprolose; purified water; industrial methylated spirit; simethicone; lecithin; ethanol; shellac; strong ammonia solution; sulfuric acid - prograf-xl is indicated for use as an adjunct to liver, kidney, lung or heart allograft transplantation in adults and children.

אוסטרליה - אנגלית - Department of Health (Therapeutic Goods Administration)

astellas pharma australia pty ltd - tacrolimus, quantity: 0.5 mg - capsule, modified release - excipient ingredients: iron oxide yellow; hypromellose; iron oxide red; titanium dioxide; lactose monohydrate; ethylcellulose; magnesium stearate; sodium lauryl sulfate; gelatin; butan-1-ol; hyprolose; purified water; industrial methylated spirit; simethicone; lecithin; ethanol; shellac; strong ammonia solution; sulfuric acid - prograf-xl is indicated for use as an adjunct to liver, kidney, lung or heart allograft transplantation in adults and children.

ארצות הברית - אנגלית - NLM (National Library of Medicine)

breckenridge pharmaceutical, inc. - everolimus (unii: 9hw64q8g6g) (everolimus - unii:9hw64q8g6g) - everolimus is indicated for the prophylaxis of organ rejection in adult patients at low-moderate immunologic risk receiving a kidney transplant [see clinical studies (14.1)] . everolimus is to be administered in combination with basiliximab induction and concurrently with reduced doses of cyclosporine and with corticosteroids. therapeutic drug monitoring (tdm) of everolimus and cyclosporine is recommended for all patients receiving these products [see dosage and administration (2.2, 2.3)]. everolimus is indicated for the prophylaxis of allograft rejection in adult patients receiving a liver transplant. everolimus is to be administered no earlier than 30 days post transplant concurrently in combination with reduced doses of tacrolimus and with corticosteroids [see warnings and precautions (5.5), clinical studies (14.2)] . tdm of everolimus and tacrolimus is recommended for all patients receiving these products [see dosage and administration (2.3, 2.5)] . the safety and efficacy of everolimus has not been established in the following populations: - kidney transplant patients at high immunologic risk - recipients of transplanted organs other than kidney and liver [see warnings and precautions (5.7)] - pediatric patients (less than 18 years). everolimus is contraindicated in patients with known hypersensitivity to everolimus, sirolimus, or to components of the drug product. risk summary based on animal studies and the mechanism of action [see clinical pharmacology (12.1)], everolimus can cause fetal harm when administered to a pregnant woman. there are limited case reports of everolimus use in pregnant women; however, these reports are insufficient to inform a drug associated risk of adverse developmental outcomes. reproductive studies in animals have demonstrated that everolimus was maternally toxic in rabbits and caused embryo-fetal toxicities in rats and rabbits, at exposures near or below those achieved in human transplant patients. 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; however, in the u.s. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. data animal data everolimus crossed the placenta and was toxic to the conceptus. everolimus administered daily to pregnant rats by oral gavage at 0.1 mg/kg (approximately one tenth the exposure in humans administered the lowest starting dose of 0.75 mg twice daily), from before mating through organogenesis, resulted in increased preimplantation loss and embryonic resorptions. these effects occurred in the absence of maternal toxicities. everolimus administered daily by oral gavage to pregnant rabbits during organogenesis resulted in abortions, maternal toxicity and lethality, and increased fetal resorptions. at these doses, exposure to everolimus (auc) was approximately one-tenth, one-half, and one and one-half fold the exposures in humans administered the starting clinical dose, respectively. in a pre- and post-natal development study in rats, animals were dosed from implantation through lactation. at a dose of 0.1 mg/kg (0.6 mg/m2 ), there were no adverse effects on delivery and lactation or signs of maternal toxicity; however, there were reductions in body weight (up to 9% reduction) and in survival of offspring (~5%). there were no drug-related effects on the developmental parameters (morphological development, motor activity, learning, or fertility assessment) in the offspring. risk summary there is no data regarding the presence of everolimus in human milk, the effects on breastfed infants, or the effects on milk production. everolimus and/or its metabolites are readily transferred into milk of lactating rats at a concentration 3.5 times higher than in maternal rat serum. in pre-post-natal and juvenile studies in rats, exposure to everolimus during the postnatal period caused developmental toxicity [see use in specific populations (8.1), nonclinical toxicology (13.2)]. advise lactating women not to breastfeed because of the potential for serious adverse reactions in infants exposed to everolimus. contraception females should not be pregnant or become pregnant while receiving everolimus. advise females of reproductive potential that animal studies have been performed showing everolimus to be harmful to the mother and developing fetus [ see use in specific populations (8.1)] . females of reproductive potential are recommended to use highly effective contraception methods while receiving everolimus and up to 8 weeks after treatment has been stopped. infertility females amenorrhea occurred in female patients taking everolimus [ see adverse reactions (6.2)]. everolimus may cause pre-implantation loss in females based on animal data [see nonclinical toxicology (13.1)]. female fertility may be compromised by treatment with everolimus. males everolimus treatment may impair fertility in males based on human [see warnings and precautions (5.18), adverse reactions (6.2, 6.3)] and animal findings [see nonclinical toxicology (13.1)]. the safe and effective use of everolimus in kidney or liver transplant patients younger than 18 years of age has not been established. there is limited clinical experience on the use of everolimus in patients of age 65 years or older. there is no evidence to suggest that elderly patients will require a different dosage recommendation from younger adult patients [see clinical pharmacology (12.5)] . everolimus whole blood trough concentrations should be closely monitored in patients with impaired hepatic function. for patients with mild hepatic impairment (child-pugh class a), the dose should be reduced by approximately one-third of the normally recommended daily dose. for patients with moderate or severe hepatic impairment (child-pugh b or c), the initial daily dose should be reduced to approximately half of the normally recommended daily dose. further dose adjustment and/or dose titration should be made if a patient's whole blood trough concentration of everolimus, as measured by an lc/ms/ms assay, is not within the target trough concentration range of 3 to 8 ng/ml [see clinical pharmacology (12.6)]. no dose adjustment is needed in patients with renal impairment [see clinical pharmacology (12.6)].

ארצות הברית - אנגלית - NLM (National Library of Medicine)

advagen pharma limited - mycophenolate sodium (unii: wx877sqi1g) (mycophenolic acid - unii:hu9dx48n0t) - mycophenolic acid delayed-release tablets are indicated for the prophylaxis of organ rejection in adult patients receiving a kidney transplant. mycophenolic acid delayed-release tablets are indicated for the prophylaxis of organ rejection in pediatric patients 5 years of age and older who are at least 6 months post kidney transplant. mycophenolic acid delayed-release tablets are to be used in combination with cyclosporine and corticosteroids. mycophenolic acid delayed-release tablets and mycophenolate mofetil (mmf) tablets and capsules should not be used interchangeably without physician supervision because the rate of absorption following the administration of these two products is not equivalent. mycophenolic acid delayed-release tablets are contraindicated in patients with a hypersensitivity to mycophenolate sodium, mycophenolic acid (mpa), mycophenolate mofetil, or to any of its excipients. reactions like rash, pruritus, hypotension, and chest pain have been observed in clinical trials and post marketing reports [see adverse reactions (6) ]. 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 mycophenolic acid delayed-release tablets treatment. to report a pregnancy or obtain information about the registry, visit www.mycophenolaterems.com or call 1-800-617-8191. risk summary following oral or intravenous (iv) administration, mmf is metabolized to mycophenolic acid (mpa), the active ingredient in mycophenolic acid delayed-release tablets and the active form of the drug. use of 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 (0.05 and 1.1 times exposure at the recommended clinical doses in kidney transplant patients for rats and rabbits, respectively) (see animal data) . risks and benefits of mycophenolic acid delayed-release tablets should be discussed with the patient. when appropriate, consider alternative immunosuppressants with less potential for embryo-fetal toxicity. 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 human 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. animal data in animal reproductive toxicology studies, congenital malformations and pregnancy loss occurred when pregnant rats and rabbits received mycophenolate at dose multiples equivalent to and less than the recommended human dose. oral administration of mycophenolate sodium to pregnant rats from gestational day 7 to day 16 at a dose as low as 1 mg per kg resulted in malformations including anophthalmia, exencephaly, and umbilical hernia. the systemic exposure at this dose represents 0.05 times the clinical exposure at the human dose of 1,440 mg per day of mycophenolic acid delayed-release tablets. oral administration of mycophenolate to pregnant rabbits from gestational day 7 to day 19 resulted in embryofetal lethality and malformations, including ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical hernia at doses equal to or greater than 80 mg per kg per day, in the absence of maternal toxicity. this corresponds to about 1.1 times the recommended clinical dose based on 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 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 mycophenolic acid delayed-release tablets and any potential adverse effects on the breastfed infant from mycophenolic acid delayed-release tablets or from the underlying maternal condition. because available data are limited, it is not possible to exclude potential risks to a breastfeeding infant. data 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 female patients taking mycophenolic acid delayed-release tablets who are considering pregnancy, consider alternative immunosuppressants with less potential for embryo-fetal toxicity. risks and benefits of mycophenolic acid delayed-release tablets should be discussed with the patient. pregnancy testing to prevent unplanned exposure during pregnancy, females of reproductive potential should have a serum or urine pregnancy test with a sensitivity of at least 25 miu/ml immediately before starting mycophenolic acid delayed-release tablets. 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 embryo-fetal toxicity whenever possible.   contraception female patients females of reproductive potential taking mycophenolic acid delayed-release tablets must receive contraceptive counseling and use acceptable contraception (see table 5 for acceptable contraception methods). patients must use acceptable birth control during entire mycophenolic acid delayed-release tablets therapy, and for 6 weeks after stopping mycophenolic acid delayed-release tablets, unless the patient chooses abstinence (she chooses to avoid heterosexual intercourse completely). patients should be aware that mycophenolic acid delayed-release tablets reduces blood levels of the hormones in the oral contraceptive pill and could theoretically reduce its effectiveness [see patient counseling information (17), drug interactions (7.8) ]. male patients genotoxic effects have been observed in animal studies at exposures exceeding the human therapeutic exposures by approximately 2.5 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 mycophenolic acid delayed-release tablets and for at least 90 days after cessation of treatment [see use in specific populations (8.1), nonclinical toxicology (13.1), patient counseling information (17)] . the safety and effectiveness of mycophenolic acid delayed-release tablets have been established in pediatric kidney transplant patients 5 to 16 years of age who were initiated on mycophenolic acid delayed-release tablets at least 6 months post-transplant. use of mycophenolic acid delayed-release tablets in this age group is supported by evidence from adequate and well-controlled studies of mycophenolic acid delayed-release tablets in a similar population of adult kidney transplant patients with additional pharmacokinetic data in pediatric kidney transplant patients [see dosage and administration (2.2, 2.3), clinical pharmacology (12.3) ]. pediatric doses for patients with bsa <1.19 m2 cannot be accurately administered using currently available formulations of mycophenolic acid delayed-release tablets. the safety and effectiveness of mycophenolic acid delayed-release tablets in de novo pediatric kidney transplant patients and in pediatric kidney transplant patients below the age of 5 years have not been established. clinical studies of mycophenolic acid delayed-release tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. of the 372 patients treated with mycophenolic acid delayed-release tablets in the clinical trials, 6% (n=21) were 65 years of age and older and 0.3% (n=1) were 75 years of age and older. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

אוסטרליה - אנגלית - Department of Health (Therapeutic Goods Administration)

astellas pharma australia pty ltd - tacrolimus, quantity: 5 mg - capsule, modified release - excipient ingredients: lactose monohydrate; titanium dioxide; hypromellose; sodium lauryl sulfate; iron oxide red; magnesium stearate; iron oxide yellow; ethylcellulose; gelatin; hyprolose; butan-1-ol; purified water; industrial methylated spirit; simethicone; lecithin; ethanol; shellac; strong ammonia solution; sulfuric acid - advagraf xl is indicated for use as an adjunct to liver, kidney, lung or heart allograft transplantation in adults and children.