Singapore - English - HSA (Health Sciences Authority)

novartis (singapore) pte ltd - carbamazepine - tablet, film coated - 200 mg - carbamazepine 200 mg

Singapore - English - HSA (Health Sciences Authority)

novartis (singapore) pte ltd - carbamazepine - tablet, film coated - 400 mg - carbamazepine 400 mg

Singapore - English - HSA (Health Sciences Authority)

novartis (singapore) pte ltd - carbamazepine - suspension - 2 g/100 ml - carbamazepine 2 g/100 ml

New Zealand - English - Ministry for Primary Industries

schering-plough animal health limited - clostridium septicum toxoid; clostridium tetani toxoid; clostridium perfringens type d toxoid; clostridium novyi type b toxoid/cells; clostridium chauvoei toxoid/cells - clostridium septicum toxoid 0 vaccine; clostridium tetani toxoid 0 vaccine; clostridium perfringens type d toxoid 0 vaccine; clostridium novyi type b toxoid/cells 0 vaccine; clostridium chauvoei toxoid/cells 0 vaccine - vaccine

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

legacy pharmaceutical packaging, llc - finasteride (unii: 57gno57u7g) (finasteride - unii:57gno57u7g) - finasteride 5 mg - finasteride tablets usp, are indicated for the treatment of symptomatic benign prostatic hyperplasia (bph) in men with an enlarged prostate to:  -improve symptoms -reduce the risk of the need for surgery including transurethral resection of the prostate (turp) and prostatectomy. finasteride tablets usp administered in combination with the alpha-blocker doxazosin is indicated to reduce the risk of symptomatic progression of bph (a confirmed ≥4 point increase in american urological association (aua) symptom score). finasteride tablets usp are not approved for the prevention of prostate cancer. finasteride tablets usp are contraindicated in the following: • hypersensitivity to any component of this medication. •  pregnancy . finasteride use is contraindicated in women when they are or may potentially be pregnant. because of the ability of type ii 5α-reductase inhibitors to inhibit the conversion of testosterone to 5α-dihydrotestosterone (dht), finasteride may cause abnormalities of the external genitalia of a male fetus of a pregnant woman who receives finasteride. if this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the pregnant woman should be apprised of the potential hazard to the male fetus. [see also warnings and precautions (5.3) , use in specific populations (8.1) , how supplied/storage and handling (16) and patient counseling information (17.2) .] in female rats, low doses of finasteride administered during pregnancy have produced abnormalities of the external genitalia in male offspring. teratogenic effects: pregnancy category x. [see contraindications (4).] finasteride tablets usp are contraindicated for use in women who are or may become pregnant. finasteride tablets usp is a type ii 5α-reductase inhibitor that prevents conversion of testosterone to 5α-dihydrotestosterone (dht), a hormone necessary for normal development of male genitalia. in animal studies, finasteride caused abnormal development of external genitalia in male fetuses. if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the male fetus. abnormal male genital development is an expected consequence when conversion of testosterone to 5α-dihydrotestosterone (dht) is inhibited by 5α-reductase inhibitors. these outcomes are similar to those reported in male infants with genetic 5α-reductase deficiency. women could be exposed to finasteride through contact with crushed or broken finasteride tablets usp or semen from a male partner taking finasteride tablets usp. with regard to finasteride exposure through the skin, finasteride tablets usp are coated and will prevent skin contact with finasteride during normal handling if the tablets have not been crushed or broken. women who are pregnant or may become pregnant should not handle crushed or broken finasteride tablets usp because of possible exposure of a male fetus. if a pregnant woman comes in contact with crushed or broken finasteride tablets usp, the contact area should be washed immediately with soap and water. with regard to potential finasteride exposure through semen, two studies have been conducted in men receiving finasteride tablets usp, 5 mg/day that measured finasteride concentrations in semen [see clinical pharmacology (12.3)]. in an embryo-fetal development study, pregnant rats received finasteride during the period of major organogenesis (gestation days 6 to 17). at maternal doses of oral finasteride approximately 0.1 to 86 times the maximum recommended human dose (mrhd) of 5 mg/day (based on auc at animal doses of 0.1 to 100 mg/kg/day) there was a dose-dependent increase in hypospadias that occurred in 3.6 to 100% of male offspring. exposure multiples were estimated using data from nonpregnant rats. days 16 to 17 days of gestation is a critical period in male fetal rats for differentiation of the external genitalia. at oral maternal doses approximately 0.03 times the mrhd (based on auc at animal dose of 0.03 mg/kg/day), male offspring had decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development. decreased anogenital distance occurred in male offspring of pregnant rats that received approximately 0.003 times the mrhd (based on auc at animal dose of 0.003 mg/kg/day). no abnormalities were observed in female offspring at any maternal dose of finasteride. no developmental abnormalities were observed in the offspring of untreated females mated with finasteride treated male rats that received approximately 61 times the mrhd (based on auc at animal dose of 80 mg/kg/day). slightly decreased fertility was observed in male offspring after administration of about 3 times the mrhd (based on auc at animal dose of 3 mg/kg/day) to female rats during late gestation and lactation. no effects on fertility were seen in female offspring under these conditions. no evidence of male external genital malformations or other abnormalities were observed in rabbit fetuses exposed to finasteride during the period of major organogenesis (gestation days 6 to 18) at maternal oral doses up to 100 mg/kg /day, (finasteride exposure levels were not measured in rabbits). however, this study may not have included the critical period for finasteride effects on development of male external genitalia in the rabbit. the fetal effects of maternal finasteride exposure during the period of embryonic and fetal development were evaluated in the rhesus monkey (gestation days 20 to 100), in a species and development period more predictive of specific effects in humans than the studies in rats and rabbits. intravenous administration of finasteride to pregnant monkeys at doses as high as 800 ng/day (estimated maximal blood concentration of 1.86 ng/ml or about 143 times the highest estimated exposure of pregnant women to finasteride from semen of men taking 5 mg/day) resulted in no abnormalities in male fetuses. in confirmation of the relevance of the rhesus model for human fetal development, oral administration of a dose of finasteride (2 mg/kg/day or approximately 18,000 times the highest estimated blood levels of finasteride from semen of men taking 5 mg/day) to pregnant monkeys resulted in external genital abnormalities in male fetuses. no other abnormalities were observed in male fetuses and no finasteride-related abnormalities were observed in female fetuses at any dose. finasteride tablets usp is not indicated for use in women. it is not known whether finasteride is excreted in human milk. finasteride tablets usp is not indicated for use in pediatric patients. safety and effectiveness in pediatric patients have not been established. of the total number of subjects included in a long-term efficacy and safety study, 1480 and 105 subjects were 65 and over and 75 and over, respectively. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. no dosage adjustment is necessary in the elderly [see clinical pharmacology (12.3) and clinical studies (14)]. caution should be exercised in the administration of finasteride tablets usp in those patients with liver function abnormalities, as finasteride is metabolized extensively in the liver [see clinical pharmacology (12.3)]. no dosage adjustment is necessary in patients with renal impairment [see clinical pharmacology (12.3)].

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

mylan pharmaceuticals inc. - rizatriptan benzoate (unii: wr978s7qhh) (rizatriptan - unii:51086hbw8g) - rizatriptan 5 mg - rizatriptan benzoate orally disintegrating tablets are indicated for the acute treatment of migraine with or without aura in adults and in pediatric patients 6 to 17 years old. limitations of use: rizatriptan benzoate orally disintegrating tablets are contraindicated in patients with: there are no adequate and well-controlled studies in pregnant women. rizatriptan benzoate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. in a general reproductive study in rats, birth weights and pre- and post-weaning weight gain were reduced in the offspring of females treated prior to and during mating and throughout gestation and lactation with doses of 10 and 100 mg/kg/day. in a pre- and post-natal developmental toxicity study in rats, an increase in mortality of the offspring at birth and for the first 3 days after birth, a decrease in pre- and post-weaning weight gain, and decreased performance in a passive avoidance test (which indicates a decrease in learning capa

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

lupin pharmaceuticals, inc. - divalproex sodium (unii: 644vl95ao6) (valproic acid - unii:614oi1z5wi) - valproic acid 125 mg - divalproex sodium delayed-release tablet is a valproate and is indicated for the treatment of the manic episodes associated with bipolar disorder. a manic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood. typical symptoms of mania include pressure of speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity, poor judgment, aggressiveness, and possible hostility. the efficacy of divalproex sodium delayed-release tablets was established in 3-week trials with patients meeting dsm-iii-r criteria for bipolar disorder who were hospitalized for acute mania [see clinical studies (14.1)] the safety and effectiveness of divalproex sodium delayed-release tablets for long-term use in mania, i.e., more than 3 weeks, has not been demonstrated in controlled clinical trials. therefore, healthcare providers who elect to use divalproex sodium delayed-release tablets for extended periods should continually reevaluate the long-term usefulness of the drug for the individual patient. divalproex sodium delayed-release tablets are indicated as monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizures. divalproex sodium delayed-release tablets are also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures. simple absence is defined as very brief clouding of the sensorium or loss of consciousness accompanied by certain generalized epileptic discharges without other detectable clinical signs. complex absence is the term used when other signs are also present. divalproex sodium delayed-release tablets are indicated for prophylaxis of migraine headaches. there is no evidence that divalproex sodium delayed-release tablet is useful in the acute treatment of migraine headaches. because of the risk to the fetus of decreased iq, neurodevelopmental disorders, neural tube defects, and other major congenital malformations, which may occur very early in pregnancy, valproate should not be used to treat women with epilepsy or bipolar disorder who are pregnant or who plan to become pregnant unless other medications have failed to provide adequate symptom control or are otherwise unacceptable. valproate should not be administered to a woman of childbearing potential unless other medications have failed to provide adequate symptom control or are otherwise unacceptable [see warnings and precautions (5.2, 5.3, 5.4), use in specific populations (8.1), and patient counseling information (17)]. for prophylaxis of migraine headaches, divalproex sodium delayed-release tablets are contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see contraindications (4)]. -   divalproex sodium delayed-release tablets should not be administered to patients with hepatic disease or significant hepatic dysfunction [see warnings and precautions (5.1)] . -   divalproex sodium delayed-release tablets are contraindicated in patients known to have mitochondrial disorders caused by mutations in mitochondrial dna polymerase γ (polg; e.g., alpers-huttenlocher syndrome) and children under two years of age who are suspected of having a polg-related disorder [see warnings and precautions (5.1)] . -   divalproex sodium delayed-release tablets are contraindicated in patients with known hypersensitivity to the drug [see warnings and precautions (5.12)]. -   divalproex sodium delayed-release tablets are contraindicated in patients with known urea cycle disorders [see warnings and precautions (5.6)]. -   for use in prophylaxis of migraine headaches: divalproex sodium delayed-release tablets are contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see warnings and precautions (5.2, 5.3, 5.4) and use in specific populations (8.1)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (aeds), including divalproex sodium delayed-release tablets, during pregnancy. encourage women who are taking divalproex sodium delayed-release tablets during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling toll-free 1-888-233-2334 or visiting the website, http://www.aedpregnancyregistry.org/. this must be done by the patient herself. risk summary for use in prophylaxis of migraine headaches, valproate is contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see contraindications (4)] . for use in epilepsy or bipolar disorder, valproate should not be used to treat women who are pregnant or who plan to become pregnant unless other medications have failed to provide adequate symptom control or are otherwise unacceptable [see boxed warning warnings and precautions (5.2, 5.3)] . women with epilepsy who become pregnant while taking valproate should not discontinue valproate abruptly, as this can precipitate status epilepticus with resulting maternal and fetal hypoxia and threat to life. maternal valproate use during pregnancy for any indication increases the risk of congenital malformations, particularly neural tube defects including spina bifida, but also malformations involving other body systems (e.g., craniofacial defects including oral clefts, cardiovascular malformations, hypospadias, limb malformations). this risk is dose-dependent; however, a threshold dose below which no risk exists cannot be established. in utero exposure to valproate may also result in hearing impairment or hearing loss. valproate polytherapy with other aeds has been associated with an increased frequency of congenital malformations compared with aed monotherapy. the risk of major structural abnormalities is greatest during the first trimester; however, other serious developmental effects can occur with valproate use throughout pregnancy. the rate of congenital malformations among babies born to epileptic mothers who used valproate during pregnancy has been shown to be about four times higher than the rate among babies born to epileptic mothers who used other anti-seizure monotherapies [see warnings and precautions (5.2) and data (human)] . epidemiological studies have indicated that children exposed to valproate in utero have lower iq scores and a higher risk of neurodevelopmental disorders compared to children exposed to either another aed in utero or to no aeds in utero [see warnings and precautions (5.3) and data (human)] . an observational study has suggested that exposure to valproate products during pregnancy increases the risk of autism spectrum disorders [see data (human)]. in animal studies, valproate administration during pregnancy resulted in fetal structural malformations similar to those seen in humans and neurobehavioral deficits in the offspring at clinically relevant doses [see data (animal)] . there have been reports of hypoglycemia in neonates and fatal cases of hepatic failure in infants following maternal use of valproate during pregnancy. pregnant women taking valproate may develop hepatic failure or clotting abnormalities including thrombocytopenia, hypofibrinogenemia, and/or decrease in other coagulation factors, which may result in hemorrhagic complications in the neonate including death [see warnings and precautions (5.1, 5.8)] . available prenatal diagnostic testing to detect neural tube and other defects should be offered to pregnant women using valproate. evidence suggests that folic acid supplementation prior to conception and during the first trimester of pregnancy decreases the risk for congenital neural tube defects in the general population. it is not known whether the risk of neural tube defects or decreased iq in the offspring of women receiving valproate is reduced by folic acid supplementation. dietary folic acid supplementation both prior to conception and during pregnancy should be routinely recommended for patients using valproate [see warnings and precautions (5.2, 5.4)] . all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk: to prevent major seizures, women with epilepsy should not discontinue valproate abruptly, as this can precipitate status epilepticus with resulting maternal and fetal hypoxia and threat to life. even minor seizures may pose some hazard to the developing embryo or fetus [see warnings and precautions (5.4)] . however, discontinuation of the drug may be considered prior to and during pregnancy in individual cases if the seizure disorder severity and frequency do not pose a serious threat to the patient. maternal adverse reactions: pregnant women taking valproate may develop clotting abnormalities including thrombocytopenia, hypofibrinogenemia, and/or decrease in other coagulation factors, which may result in hemorrhagic complications in the neonate including death [see warnings and precautions (5.8)] . if valproate is used in pregnancy, the clotting parameters should be monitored carefully in the mother. if abnormal in the mother, then these parameters should also be monitored in the neonate. patients taking valproate may develop hepatic failure [see boxed warning and warnings and precautions  (5.1)] . fatal cases of hepatic failure in infants exposed to valproate in utero have also been reported following maternal use of valproate during pregnancy. hypoglycemia has been reported in neonates whose mothers have taken valproate during pregnancy. data human: neural tube defects and other structural abnormalities there is an extensive body of evidence demonstrating that exposure to valproate in utero increases the risk of neural tube defects and other structural abnormalities. based on published data from the cdc's national birth defects prevention network, the risk of spina bifida in the general population is about 0.06 to 0.07% (6 to 7 in 10,000 births) compared to the risk following in utero valproate exposure estimated to be approximately 1 to 2% (100 to 200 in 10,000 births). the naaed pregnancy registry has reported a major malformation rate of 9 to 11% in the offspring of women exposed to an average of 1,000 mg/day of valproate monotherapy during pregnancy. these data show an up to a five-fold increased risk for any major malformation following valproate exposure in utero compared to the risk following exposure in utero to other aeds taken as monotherapy. the major congenital malformations included cases of neural tube defects, cardiovascular malformations, craniofacial defects (e.g., oral clefts, craniosynostosis), hypospadias, limb malformations (e.g., clubfoot, polydactyly), and other malformations of varying severity involving other body systems [see warnings and precautions (5.2)]. effect on iq and neurodevelopmental effects published epidemiological studies have indicated that children exposed to valproate in utero have lower iq scores than children exposed to either another aed in utero or to no aeds in utero . the largest of these studies1 is a prospective cohort study conducted in the united states and united kingdom that found that children with prenatal exposure to valproate (n=62) had lower iq scores at age 6 (97 [95% c.i. 94 to 101]) than children with prenatal exposure to the other anti-epileptic drug monotherapy treatments evaluated: lamotrigine (108 [95% c.i. 105 to 110]), carbamazepine (105 [95% c.i. 102 to 108]) and phenytoin (108 [95% c.i. 104 to 112]). it is not known when during pregnancy cognitive effects in valproate-exposed children occur. because the women in this study were exposed to aeds throughout pregnancy, whether the risk for decreased iq was related to a particular time period during pregnancy could not be assessed [see warnings and precautions (5.3)]. although the available studies have methodological limitations, the weight of the evidence supports a causal association between valproate exposure in utero and subsequent adverse effects on neurodevelopment, including increases in autism spectrum disorders and attention deficit/hyperactivity disorder (adhd). an observational study has suggested that exposure to valproate products during pregnancy increases the risk of autism spectrum disorders. in this study, children born to mothers who had used valproate products during pregnancy had 2.9 times the risk (95% confidence interval [ci]: 1.7 to 4.9) of developing autism spectrum disorders compared to children born to mothers not exposed to valproate products during pregnancy. the absolute risks for autism spectrum disorders were 4.4% (95% ci: 2.6% to 7.5%) in valproate-exposed children and 1.5% (95% ci: 1.5% to 1.6%) in children not exposed to valproate products. another observational study found that children who were exposed to valproate in utero had an increased risk of adhd (adjusted hr 1.48; 95% ci, 1.09 to 2.00) compared with the unexposed children. because these studies were observational in nature, conclusions regarding a causal association between in utero valproate exposure and an increased risk of autism spectrum disorder and adhd cannot be considered definitive. other there are published case reports of fatal hepatic failure in offspring of women who used valproate during pregnancy. animal: in developmental toxicity studies conducted in mice, rats, rabbits, and monkeys, increased rates of fetal structural abnormalities, intrauterine growth retardation, and embryo-fetal death occurred following administration of valproate to pregnant animals during organogenesis at clinically relevant doses (calculated on a body surface area [mg/m2 ] basis). valproate induced malformations of multiple organ systems, including skeletal, cardiac, and urogenital defects. in mice, in addition to other malformations, fetal neural tube defects have been reported following valproate administration during critical periods of organogenesis, and the teratogenic response correlated with peak maternal drug levels. behavioral abnormalities (including cognitive, locomotor, and social interaction deficits) and brain histopathological changes have also been reported in mice and rat offspring exposed prenatally to clinically relevant doses of valproate. risk summary valproate is excreted in human milk. data in the published literature describe the presence of valproate in human milk (range: 0.4 mcg/ml to 3.9 mcg/ml), corresponding to 1% to 10% of maternal serum levels. valproate serum concentrations collected from breastfed infants aged 3 days postnatal to 12 weeks following delivery ranged from 0.7 mcg/ml to 4 mcg/ml, which were 1% to 6% of maternal serum valproate levels. a published study in children up to six years of age did not report adverse developmental or cognitive effects following exposure to valproate via breast milk [see data (human)] . there are no data to assess the effects of divalproex sodium on milk production or excretion. clinical considerations the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for divalproex sodium delayed-release tablets and any potential adverse effects on the breastfed infant from divalproex sodium delayed-release tablets or from the underlying maternal condition. monitor the breastfed infant for signs of liver damage including jaundice and unusual bruising or bleeding. there have been reports of hepatic failure and clotting abnormalities in offspring of women who used valproate during pregnancy [see use in specific populations (8.1)]. data human: in a published study, breast milk and maternal blood samples were obtained from 11 epilepsy patients taking valproate at doses ranging from 300 mg/day to 2,400 mg/day on postnatal days 3 to 6. in 4 patients who were taking valproate only, breast milk contained an average valproate concentration of 1.8 mcg/ml (range: 1.1 mcg/ml to 2.2 mcg/ml), which corresponded to 4.8% of the maternal plasma concentration (range: 2.7% to 7.4%). across all patients (7 of whom were taking other aeds concomitantly), similar results were obtained for breast milk concentration (1.8 mcg/ml, range: 0.4 mcg/ml to 3.9 mcg/ml) and maternal plasma ratio (5.1%, range: 1.3% to 9.6%). a published study of 6 breastfeeding mother-infant pairs measured serum valproate levels during maternal treatment for bipolar disorder (750 mg/day or 1,000 mg/day). none of the mothers received valproate during pregnancy, and infants were aged from 4 weeks to 19 weeks at the time of evaluation. infant serum levels ranged from 0.7 mcg/ml to 1.5 mcg/ml. with maternal serum valproate levels near or within the therapeutic range, infant exposure was 0.9% to 2.3% of maternal levels. similarly, in 2 published case reports with maternal doses of 500 mg/day or 750 mg/day during breastfeeding of infants aged 3 months and 1 month, infant exposure was 1.5% and 6% that of the mother, respectively. a prospective observational multicenter study evaluated the long-term neurodevelopmental effects of aed use on children. pregnant women receiving monotherapy for epilepsy were enrolled with assessments of their children at ages 3 years and 6 years. mothers continued aed therapy during the breastfeeding period. adjusted iqs measured at 3 years for breastfed and non-breastfed children were 93 (n=11) and 90 (n=24), respectively. at 6 years, the scores for breastfed and non-breastfed children were 106 (n=11) and 94 (n=25), respectively (p=0.04). for other cognitive domains evaluated at 6 years, no adverse cognitive effects of continued exposure to an aed (including valproate) via breast milk were observed. contraception women of childbearing potential should use effective contraception while taking valproate [see boxed warning, warnings and precautions (5.4), drug interactions (7), and use in specific populations (8.1)] . this is especially important when valproate use is considered for a condition not usually associated with permanent injury or death such as prophylaxis of migraine headaches [see contraindications (4)]. infertility there have been reports of male infertility coincident with valproate therapy [see adverse reactions (6.4)] . in animal studies, oral administration of valproate at clinically relevant doses resulted in adverse reproductive effects in males [see nonclinical toxicology (13.1)]. experience has indicated that pediatric patients under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those with the aforementioned conditions [see boxed warning and warning and precautions (5.1)]. when divalproex sodium delayed-release tablets are used in this patient group, it should be used with extreme caution and as a sole agent. the benefits of therapy should be weighed against the risks. above the age of 2 years, experience in epilepsy has indicated that the incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups. younger children, especially those receiving enzyme-inducing drugs, will require larger maintenance doses to attain targeted total and unbound valproate concentrations. pediatric patients (i.e., between 3 months and 10 years) have 50% higher clearances expressed on weight (i.e., ml/min/kg) than do adults. over the age of 10 years, children have pharmacokinetic parameters that approximate those of adults. the variability in free fraction limits the clinical usefulness of monitoring total serum valproic acid concentrations. interpretation of valproic acid concentrations in children should include consideration of factors that affect hepatic metabolism and protein binding. pediatric clinical trials divalproex sodium was studied in seven pediatric clinical trials. two of the pediatric studies were double-blinded placebo-controlled trials to evaluate the efficacy of depakote er tablets* for the indications of mania (150 patients aged 10 to 17 years, 76 of whom were on depakote er tablets*) and migraine (304 patients aged 12 to 17 years, 231 of whom were on depakote er tablets*). efficacy was not established for either the treatment of migraine or the treatment of mania. the most common drug-related adverse reactions (reported >5% and twice the rate of placebo) reported in the controlled pediatric mania study were nausea, upper abdominal pain, somnolence, increased ammonia, gastritis and rash. the remaining five trials were long term safety studies. two six-month pediatric studies were conducted to evaluate the long-term safety of depakote er tablets* for the indication of mania (292 patients aged 10 to 17 years). two twelve-month pediatric studies were conducted to evaluate the long-term safety of depakote er tablets* for the indication of migraine (353 patients aged 12 to 17 years). one twelve-month study was conducted to evaluate the safety of depakote sprinkle capsules* in the indication of partial seizures (169 patients aged 3 to 10 years). in these seven clinical trials, the safety and tolerability of divalproex sodium in pediatric patients were shown to be comparable to those in adults [see adverse reactions (6)]. juvenile animal toxicology in studies of valproate in immature animals, toxic effects not observed in adult animals included retinal dysplasia in rats treated during the neonatal period (from postnatal day 4) and nephrotoxicity in rats treated during the neonatal and juvenile (from postnatal day 14) periods. the no-effect dose for these findings was less than the maximum recommended human dose on a mg/m2 basis. no patients above the age of 65 years were enrolled in double-blind prospective clinical trials of mania associated with bipolar illness. in a case review study of 583 patients, 72 patients (12%) were greater than 65 years of age. a higher percentage of patients above 65 years of age reported accidental injury, infection, pain, somnolence, and tremor. discontinuation of valproate was occasionally associated with the latter two events. it is not clear whether these events indicate additional risk or whether they result from preexisting medical illness and concomitant medication use among these patients. a study of elderly patients with dementia revealed drug related somnolence and discontinuation for somnolence [see warnings and precautions (5.14)]. the starting dose should be reduced in these patients, and dosage reductions or discontinuation should be considered in patients with excessive somnolence [see dosage and administration (2.4)]. there is insufficient information available to discern the safety and effectiveness of valproate for the prophylaxis of migraines in patients over 65.

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

remedyrepack inc. - pregabalin (unii: 55jg375s6m) (pregabalin - unii:55jg375s6m) - pregabalin 75 mg - lyrica is indicated for:lyrica is indicated for: - management of neuropathic pain associated with diabetic peripheral neuropathy - management of postherpetic neuralgia - adjunctive therapy for the treatment of partial onset seizures in patients 4 years of age and older - management of fibromyalgia - management of neuropathic pain associated with spinal cord injury lyrica is contraindicated in patients with known hypersensitivity to pregabalin or any of its components. angioedema and hypersensitivity reactions have occurred in patients receiving pregabalin therapy [see warnings and precautions (5.2)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to lyrica during pregnancy. to provide information regarding the effects of in utero exposure to lyrica, physicians are advised to recommend that pregnant patients taking lyrica enroll in the north american antiepileptic drug (naaed) pregnancy registry. this can be done by calling the toll fr

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

apotex corp. - tizanidine hydrochloride (unii: b53e3nmy5c) (tizanidine - unii:6ai06c00gw) - tizanidine 2 mg - tizanidine is indicated for the management of spasticity. because of the short duration of therapeutic effect, treatment with tizanidine should be reserved for those daily activities and times when relief of spasticity is most important [see dosage and administration (2.1)] . tizanidine is contraindicated in patients taking potent inhibitors of cyp1a2, such as fluvoxamine or ciprofloxacin [see drug interactions (7.1, 7.2)] . risk summary there are no adequate data on the developmental risk associated with use of tizanidine in pregnant women. in animal studies, administration of tizanidine during pregnancy resulted in developmental toxicity (embryofetal and postnatal offspring mortality and growth deficits) at doses less than those used clinically, which were not associated with maternal toxicity (see animal 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 oral administration of tizanidine (0.3 to 100 mg/kg/day) to pregnant rats during the period of organogenesis resulted in embryofetal and postnatal offspring mortality and reductions in body weight at doses of 30 mg/kg/day and above. maternal toxicity was observed at the highest dose tested. the no-effect dose for embryofetal developmental toxicity in rats (3 mg/kg/day) is similar to the maximum recommended human dose (mrhd) of 36 mg/day on a body surface area (mg/m2 ) basis. oral administration of tizanidine (1 to 100 mg/kg/day) to pregnant rabbits during the period of organogenesis resulted in embryofetal and postnatal offspring mortality at all doses. maternal toxicity was observed at the highest dose tested. oral administration of tizanidine (10 and 30 mg/kg/day) during the perinatal period of pregnancy (2 to 6 days prior to delivery) resulted in increased postnatal offspring mortality at both doses. a no-effect dose for embryofetal developmental toxicity in rabbit was not identified. the lowest dose tested (1 mg/kg/day) is less than the mrhd on a mg/m2 basis. in a pre- and postnatal development study in rats, oral administration of tizanidine (3 to 30 mg/kg/day) resulted in increased postnatal offspring mortality. a no-effect dose for pre- and postnatal developmental toxicity was not identified. the lowest dose tested (3 mg/kg/day) is similar to the mrhd on a mg/m2 basis, respectively. risk summary there are no data on the presence of tizanidine in human milk, the effects on the breastfed infant, or the effects on human milk production. animal studies have reported the presence of tizanidine in the milk of lactating animals. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tizanidine and any potential adverse effects on the breastfed infant from tizanidine or from the underlying maternal condition. there are no adequate and well-controlled studies in humans on the effect of tizanidine on female or male reproductive potential. oral administration of tizanidine to male and female rats resulted in adverse effects on fertility [see nonclinical toxicology (13.1)] . safety and effectiveness in pediatric patients have not been established. tizanidine 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. clinical studies of tizanidine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. cross-study comparison of pharmacokinetic data following single dose administration of 6 mg tizanidine showed that younger subjects cleared the drug four times faster than the elderly subjects. in elderly patients with renal insufficiency (creatinine clearance < 25 ml/min), tizanidine clearance is reduced by more than 50% compared to healthy elderly subjects; this would be expected to lead to a longer duration of clinical effect. during titration, the individual doses should be reduced. if higher doses are required, individual doses rather than dosing frequency should be increased. monitor elderly patients because they may have an increased risk for adverse reactions associated with tizanidine. tizanidine 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. in patients with renal insufficiency (creatinine clearance < 25 ml/min), clearance was reduced by more than 50%. in these patients, individual doses should be reduced during titration. if higher doses are required, individual doses rather than dosing frequency should be increased. these patients should be monitored closely for the onset or increase in severity of tizanidine common adverse events (dry mouth, somnolence, asthenia and dizziness) as indicators of potential overdosage [see dosage and administration (2.2), warnings and precautions (5.7) and clinical pharmacology (12.3)] . the influence of hepatic impairment on the pharmacokinetics of tizanidine has not been evaluated. because tizanidine is extensively metabolized in the liver, hepatic impairment would be expected to have significant effects on pharmacokinetics of tizanidine [see dosing and administration (2.3), warnings and precautions (5.2), and clinical pharmacology (12.3)] . abuse potential was not evaluated in human studies. rats were able to distinguish tizanidine from saline in a standard discrimination paradigm, after training, but failed to generalize the effects of morphine, cocaine, diazepam, or phenobarbital to tizanidine. tizanidine is closely related to clonidine, which is often abused in combination with narcotics and is known to cause symptoms of rebound upon abrupt withdrawal. three cases of rebound symptoms on sudden withdrawal of tizanidine have been reported. the case reports suggest that these patients were also misusing narcotics. withdrawal symptoms included hypertension, tachycardia, hypertonia, tremor, and anxiety. withdrawal symptoms are more likely to occur in cases where high doses are used, especially for prolonged periods, or with concomitant use of narcotics. if therapy needs to be discontinued, the dose should be decreased slowly to minimize the risk of withdrawal symptoms [see dosage and administration (2.2)] .  monkeys were shown to self-administer tizanidine in a dose-dependent manner, and abrupt cessation of tizanidine produced transient signs of withdrawal at doses > 35 times the maximum recommended human dose on a mg/m2 basis. these transient withdrawal signs (increased locomotion, body twitching, and aversive behavior toward the observer) were not reversed by naloxone administration.

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

lundbeck pharmaceuticals llc - droxidopa (unii: j7a92w69l7) (droxidopa - unii:j7a92w69l7) - droxidopa 100 mg - northera is indicated for the treatment of orthostatic dizziness, lightheadedness, or the “feeling that you are about to black out” in adult patients with symptomatic neurogenic orthostatic hypotension (noh) caused by primary autonomic failure (parkinson's disease [pd], multiple system atrophy, and pure autonomic failure), dopamine beta-hydroxylase deficiency, and non-diabetic autonomic neuropathy. effectiveness beyond 2 weeks of treatment has not been established. the continued effectiveness of northera should be assessed periodically. northera is contraindicated in patients who have a history of hypersensitivity to the drug or its ingredients [see warnings and precautions (5.4)]. risk summary there are no available data on use of northera in pregnant women and risk of major birth defects or miscarriage. northera did not produce significant reproductive toxicity in pregnant female rats or rabbits or in their fetuses. however, when pregnant female rats were dosed during days 7-17 of gestation (the period of fetal organogenesis) with doses of northera corresponding to 0.3, 1 and 3 times the maximum recommended daily dose of 1,800 mg in a 60 kg patient, based on body surface area, and when their male and female offspring (who were exposed only during fetal life) were subsequently bred, the female offspring exhibited a dose-dependent reduction in the number of live fetuses across all three doses and an increased number of embryonic/fetal deaths at the two higher doses (see data ). the estimated background risk of major birth defects and miscarriage in the indicated population is unknown. 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 animal data during a multigenerational reproductive toxicity study in rats, pregnant females were dosed during days 7-17 of gestation (the period of fetal organogenesis) with doses of northera corresponding to 0.3, 1 and 3 times the maximum recommended daily dose of 1,800 mg in a 60 kg patient. reduced weight gain, renal lesions, and a small number of deaths were observed in females treated with the two higher doses. when their male and female offspring (who were exposed to northera only during fetal life) were subsequently bred, the female offspring exhibited a dose-dependent reduction in the number of live fetuses across all three doses and an increased number of embryonic/fetal deaths at the two higher doses. risk summary there is no information regarding the presence of northera or its active metabolite(s) in human milk, the effects of northera on the breastfed child, nor the effects of northera on milk production/excretion. droxidopa is present in rat milk with peak concentrations seen 4 hours after oral drug administration and drug excretion into milk still occurring 48 hours after administration (see data ). however, due to species-specific differences in lactation physiology, animal lactation data typically do not reliably predict levels in humans. because of the potential for serious adverse reactions, including reduced weight gain in breastfed infants, advise a woman not to breastfeed during treatment with northera. data animal data in rats, oral administration of droxidopa resulted in excretion into breast milk with peak concentrations seen 4 hours after administration, and excretion still occurring 48 hours after administration. when the drug was administered to nursing dams during the period of lactation at a dose corresponding to 3 times the maximum recommended daily dose of 1,800 mg in a 60 kg patient when based on body surface area, reduced weight gain and reduced survival were observed in the offspring. despite the observed decreased weight gain, physical development was normal (with respect to timing and organ morphology).   the safety and effectiveness of northera in pediatric patients have not been established. a total of 197 patients with symptomatic noh aged 75 years or above were included in the northera clinical program. no overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. northera and its metabolites are primarily cleared renally. patients with mild or moderate renal impairment (gfr greater than 30 ml/min) were included in clinical trials and did not have a higher frequency of adverse reactions. clinical experience with northera in patients with severe renal function impairment (gfr less than 30 ml/min) is limited.