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

vivus llc - pancrelipase lipase (unii: 8myc33932o) (pancrelipase lipase - unii:8myc33932o), pancrelipase amylase (unii: yoj58o116e) (pancrelipase amylase - unii:yoj58o116e), pancrelipase protease (unii: 3560d81v50) (pancrelipase protease - unii:3560d81v50) - pancreaze is indicated for the treatment of exocrine pancreatic insufficiency in adult and pediatric patients. none. risk summary published data from case reports with pancrelipase use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. pancrelipase is minimally absorbed systematically; therefore, maternal use is not expected to result in fetal exposure to the drug. animal reproduction studies have not been conducted with pancrelipase. 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. risk summary there are no data on the presence of pancrelipase in either human or animal milk, the effects on the breastfed infant or the effects on milk production. pancrelipase is minimally absorbed systemically following oral administration, therefore maternal use is not expected to result in clinically relevant exposure of breastfed infants to the drug. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for pancreaze and any potential adverse effects on the breastfed infant from pancreaze or from the underlying maternal condition. the safety and effectiveness of pancreaze for the treatment of exocrine pancreatic insufficiency have been established in pediatric patients. use of pancreaze for this indication is supported by an adequate and well-controlled trial in adult and pediatric patients 8 to 17 years of age (study 1) along with supportive data from a randomized, investigator-blinded, dose-ranging study in 17 pediatric patients aged 6 to 30 months (study 2). both study populations consisted of patients with exocrine pancreatic insufficiency due to cystic fibrosis. the safety in pediatric patients in these studies was similar to that observed in adult patients [see adverse reactions (6.1) and clinical studies (14)] . dosages exceeding 6,000 lipase units/kg/meal have been reported postmarketing to be associated with fibrosing colonopathy and colonic strictures in pediatric patients less than 12 years of age. if there is a history of fibrosing colonopathy, monitor patients during treatment with pancreaze because some patients may be at risk of progressing to stricture formation. do not exceed the recommended dosage of either 2,500 lipase units/kg/meal, 10,000 lipase units/kg/day, or 4,000 lipase units/g fat ingested/day in pediatric patients greater than 12 months of age without further investigation . [see dosage and administration (2.2)and warnings and precautions (5.1)] . crushing or chewing pancreaze capsules or mixing the capsule contents in foods having a ph greater than 4.5 can disrupt the protective enteric coating on the capsule contents and result in early release of enzymes, irritation of the oral mucosa, and/or loss of enzyme activity. instruct the patient or caregiver of the following: consume sufficient liquids (juice, water, breast milk, or formula) to ensure complete swallowing, and visually inspect the mouth of pediatric patients less than 12 months of age to ensure no drug is retained in the mouth and irritation of the oral mucosa has not occurred [see dosage and administration (2.3)and warnings and precautions (5.2)]. clinical studies of pancreaze did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. other reported clinical experience has not identified differences in responses between patients aged 65 years and over and younger adult patients.

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

vivus llc - phentermine hydrochloride (unii: 0k2i505otv) (phentermine - unii:c045tql4wp), topiramate (unii: 0h73wjj391) (topiramate - unii:0h73wjj391) - phentermine 3.75 mg - qsymia is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in: - adults with an initial body mass index (bmi) of: 30 kg/m 2 or greater (obese), or 27 kg/m 2 or greater (overweight) in the presence of at least one weight-related comorbidity such as hypertension, type 2 diabetes mellitus, or dyslipidemia - 30 kg/m 2 or greater (obese), or - 27 kg/m 2 or greater (overweight) in the presence of at least one weight-related comorbidity such as hypertension, type 2 diabetes mellitus, or dyslipidemia - pediatric patients aged 12 years and older with an initial bmi in the 95 th percentile or greater standardized for age and sex. limitations of use - the effect of qsymia on cardiovascular morbidity and mortality has not been established. - the safety and effectiveness of qsymia in combination with other products intended for weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations, have not been established. qsymia is contraindicated in patients: - who are pregnant [see warnings and precautions (5.1)and use in specific populations (8.1)] - with glaucoma [see warnings and precautions (5.4)] - with hyperthyroidism - taking or within 14 days of stopping a monoamine oxidase inhibitors [see drug interactions (7)] - with known hypersensitivity to phentermine, topiramate or excipient in qsymia, or idiosyncrasy to the sympathomimetic amines [see adverse reactions (6.2)]. risk summary qsymia is contraindicated in pregnant patients. the use of qsymia can cause fetal harm, and weight loss offers no clear clinical benefit to a pregnant patient (see clinical considerations) . available data from pregnancy registries and epidemiologic studies indicate an increased risk of major congenital malformations, including but not limited to cleft lip and/or cleft palate (oral clefts), and of being sga in infants exposed in utero to topiramate (see data) . when phentermine and topiramate were co-administered to rats at doses of 3.75 and 25 mg/kg, respectively [approximately 2 times the maximum recommended human dose (mrhd) based on area under the curve (auc)], or at the same dose to rabbits (approximately 0.1 times and 1 time, respectively, the clinical exposures at the mrhd based on auc), there were no drug-related malformations. however, structural malformations, including craniofacial defects and reduced fetal weights occurred in offspring of multiple species of pregnant animals administered topiramate at clinically relevant doses (see data) . advise pregnant women of the potential risk to a fetus. clinical considerations disease associated maternal and/or embryo/fetal risk weight loss during pregnancy may result in fetal harm. appropriate weight gain based on pre-pregnancy weight is currently recommended for all pregnant patients, including those who are already overweight or obese, due to the obligatory weight gain that occurs in maternal tissues during pregnancy. maternal obesity increases the risk for congenital malformations, including neural tube defects, cardiac malformations, oral clefts, and limb reduction defects. fetal/neonatal adverse reactions qsymia can cause metabolic acidosis [see warnings and precautions (5.8)] . the effect of topiramate-induced metabolic acidosis has not been studied in pregnancy; however, metabolic acidosis in pregnancy (due to other causes) can cause decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the fetus' ability to tolerate labor. data human data data evaluating the risk of major congenital malformations, oral clefts, and being sga with topiramate exposure during pregnancy is available from the north american antiepileptic drug (naaed) pregnancy registry and from several larger retrospective epidemiologic studies. major congenital malformations the naaed pregnancy registry indicates an increased risk of major congenital malformations, including but not limited to oral clefts in infants exposed to topiramate during the first trimester of pregnancy. other than oral clefts, no specific pattern of major congenital malformations or grouping of major congenital malformation types were observed. in the naaed pregnancy registry, when topiramate-exposed infants with only oral clefts were excluded, the prevalence of major congenital malformations (4.1%) was higher than that in infants exposed to a reference antiepileptic drug (aed) (1.8%) or in infants with mothers without epilepsy and without exposure to aeds (1.1%). oral clefts in the naaed pregnancy registry, the prevalence of oral clefts among topiramate-exposed infants (1.4%) was higher than the prevalence in infants exposed to a reference aed (0.3%) or the prevalence in infants with mothers without epilepsy and without exposure to aeds (0.11%). it was also higher than the background prevalence in united states (0.17%) as estimated by the centers for disease control and prevention (cdc). the relative risk of oral clefts in topiramate-exposed pregnancies in the naaed pregnancy registry was 12.5 (95% confidence interval [ci] 5.9-26.37) as compared to the risk in a background population of untreated women. the uk epilepsy and pregnancy register reported a prevalence of oral clefts among infants exposed to topiramate monotherapy (3.2%) that was 16 times higher than the background rate in the uk (0.2%). larger retrospective epidemiology studies showed that topiramate monotherapy exposure in pregnancy is associated with an approximately two to five-fold increased risk of oral clefts. the fortress study found an excess risk of 1.5 (95% ci = -1.1 to 4.1) oral cleft cases per 1,000 infants exposed to topiramate during the first trimester. small for gestational age data from the naaed pregnancy registry and population-based birth registry cohort indicate that exposure to topiramate in utero is associated with an increased risk of sga newborns (birth weight <10 th percentile). in the naaed pregnancy registry, 19.7% of topiramate-exposed newborns were sga compared to 7.9% of newborns exposed to a reference aed and 5.4% of newborns of mothers without epilepsy and without aed exposure. in the medical birth registry of norway, a population-based pregnancy registry, 25% of newborns in the topiramate monotherapy exposure group were sga compared to 9% in the comparison group unexposed to aeds. the long-term consequences of the sga findings are not known. animal data phentermine/topiramate embryo-fetal development studies have been conducted in rats and rabbits with combination phentermine and topiramate treatment. phentermine and topiramate co-administered to rats during the period of organogenesis (gestation day (gd) 6 through 17) caused reduced fetal body weights but did not cause fetal malformations at the maximum dose of 3.75 mg/kg phentermine and 25 mg/kg topiramate [approximately 2 times the maximum recommended human dose (mrhd) based on area under the curve (auc) estimates for each active ingredient]. in a similar study in rabbits in which the same doses were administered from gd 6 through 18, no effects on embryo-fetal development were observed at approximately 0.1 times (phentermine) and 1 time (topiramate) clinical exposures at the mrhd based on auc. significantly lower maternal body weight gain was recorded at these doses in rats and rabbits. a pre- and post-natal development study was conducted in rats with combination phentermine and topiramate treatment. there were no adverse maternal or offspring effects in rats treated throughout organogenesis and lactation with 1.5 mg/kg/day phentermine and 10 mg/kg/day topiramate (approximately 2- and 3-times clinical exposures at the mrhd, respectively, based on auc). treatment with higher doses of 11.25 mg/kg/day phentermine and 75 mg/kg/day topiramate (approximately 5 and 6 times maximum clinical doses based on auc, respectively) caused reduced maternal body weight gain and offspring toxicity. offspring effects included lower pup survival after birth, increased limb and tail malformations, reduced pup body weight and delayed growth, development, and sexual maturation without affecting learning, memory, or fertility and reproduction. the limb and tail malformations were consistent with results of animal studies conducted with topiramate alone. phentermine animal reproduction studies have not been conducted with phentermine. limited data from studies conducted with the phentermine/topiramate combination indicate that phentermine alone was not teratogenic but resulted in lower body weight and reduced survival of offspring in rats at 5-fold the mrhd of qsymia, based on auc. topiramate topiramate causes developmental toxicity, including teratogenicity, at clinically relevant doses in multiple animal species. developmental toxicity, including teratogenicity, occurred at clinically relevant doses in multiple animal species in which topiramate was administered during the period of organogenesis (gd 6 – 15 in rodents, gd 6 – 18 in rabbits. in these studies, fetal malformations (primarily craniofacial defects such as cleft palate), limb malformations (ectrodactyly, micromelia, and amelia), rib/vertebral column anomalies, and/or reduced fetal weights were observed at dosages ≥ 20 mg/kg in mice (approximately 2 times the mrhd of topiramate in qsymia 15 mg/92 mg on a mg/m 2 basis), 20 mg/kg in rats (2 times the mrhd of qsymia based on estimated auc), and 35 mg/kg in rabbits (2 times the mrhd based on estimated auc). when rats were administered topiramate from gd 15 through lactation day 20, reductions in pre- and/or post-weaning weights occurred at dosages ≥ 2 mg/kg (2 times the mrhd of qsymia based on estimated auc). risk summary topiramate and phentermine are present in human milk. there are no data on the effects of topiramate and phentermine on milk production. diarrhea and somnolence have been reported in breastfed infants with maternal use of topiramate. there are no data on the effects of phentermine in breastfed infants. because of the potential for serious adverse reactions, including changes in sleep, irritability, hypertension, vomiting, tremor, and weight loss in breastfed infants with maternal use of phentermine, advise patients that breastfeeding is not recommended during qsymia therapy. pregnancy testing pregnancy testing is recommended in patients who can become pregnant before initiating qsymia and monthly during qsymia therapy [see warnings and precautions (5.1), use in specific populations (8.1)] . contraception females qsymia can cause fetal harm when administered to a pregnant patient [see use in specific populations (8.1) ]. advise patients who can become pregnant to use effective contraception during therapy with qsymia. for patients taking combined oral contraceptives (cocs), use of qsymia may cause irregular bleeding [see drug interactions (7)] . advise patients not to discontinue taking their coc and to contact their healthcare provider. the safety and effectiveness of qsymia as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in pediatric patients aged 12 years and older with a bmi in the 95th percentile or greater standardized for age and sex have been established. use of qsymia for this indication is supported by a 56-week, double-blind, placebo-controlled study in 223 pediatric patients aged 12 years and above, a pharmacokinetic study in pediatric patients, and studies in adults with obesity [see clinical pharmacology (12.3)and clinical studies (14)] . in a pediatric clinical trial, there was one episode of serious suicidal ideation in a qsymia-treated patient requiring hospitalization and pharmacologic treatment [see warnings and precautions (5.3)] ; more patients treated with qsymia versus placebo reported adverse reactions related to mood (e.g., depression, anxiety) and sleep disorders (e.g., insomnia) [see warnings and precautions (5.5)] . increases in bone mineral density and linear growth were attenuated in qsymia- versus placebo-treated patients [see warnings and precautions (5.7)] . serious adverse reactions seen in pediatric patients using topiramate include acute angle glaucoma, oligohidrosis and hyperthermia, metabolic acidosis, cognitive and neuropsychiatric reactions, hyperammonemia and encephalopathy, and kidney stones. the safety and effectiveness of qsymia in pediatric patients below the age of 12 years have not been established. in the qsymia clinical trials, a total of 254 (7%) of the patients were 65 to 69 years of age; no patients 70 years of age or older were enrolled. clinical studies of qsymia did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. in general, dose selection for an elderly patient should be cautious, 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. compared to healthy volunteers with normal renal function, patients with moderate and severe renal impairment as estimated by the cockcroft-gault equation had higher exposures to phentermine and topiramate. the recommended dosage of qsymia in patients with mild renal impairment (crcl greater or equal to 50 and less than 80 ml/min) is the same as the recommended dosage for patients with normal renal function. in patients with moderate (crcl greater than or equal to 30 to less than 50 ml/min) and severe (crcl less than 30 ml/min) renal impairment, the maximum recommended dosage is qsymia 7.5 mg/46 mg once daily. qsymia has not been studied in patients with end-stage renal disease on dialysis. avoid qsymia in this patient population [see dosage and administration (2.5)and clinical pharmacology (12.3)] . in patients with mild (child-pugh 5 - 6) and moderate (child-pugh 7 - 9) hepatic impairment, exposure to phentermine was higher compared to healthy volunteers with normal hepatic function. exposure to topiramate was similar among patients with mild and moderate hepatic impairment and healthy volunteers. the recommended dosage of qsymia in patients with mild hepatic impairment (child-pugh 5 - 6) is the same as the recommended dosage in patients with normal hepatic function. in patients with moderate hepatic impairment, the maximum recommended dosage is qsymia 7.5 mg/46 mg once daily. qsymia has not been studied in patients with severe hepatic impairment (child-pugh score 10 - 15). avoid qsymia in this patient population [see dosage and administration (2.6)and clinical pharmacology (12.3)] . qsymia contains phentermine, a schedule iv controlled substance, and topiramate, which is not a controlled substance. phentermine has a known potential for abuse. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. phentermine is related chemically and pharmacologically to amphetamines. amphetamines and other stimulant drugs have been extensively abused. abuse of amphetamines and related drugs (e.g., phentermine) may be associated with impaired control over drug use and severe social dysfunction. there are reports of patients who have increased the dosage of these drugs to many times higher than recommended. assess the risk of abuse prior to prescribing qsymia as part of a chronic weight management program. physical dependence may occur in patients treated with qsymia. 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. the following adverse reactions have been associated with the abrupt discontinuation of the individual components of qsymia: - for topiramate, abrupt discontinuation has been associated with seizures in patients without a history of seizures or epilepsy [see warnings and precautions (5.12)] . - for phentermine, abrupt discontinuation following prolonged high dosage administration results in extreme fatigue and mental depression; changes are also noted on a sleep electroencephalogram. thus, in situations where rapid withdrawal of qsymia is required, appropriate medical monitoring is recommended. patients discontinuing qsymia 15 mg/92 mg should be gradually tapered to reduce the possibility of precipitating a seizure [see dosage and administration (2.4)] .

Australia - English - APVMA (Australian Pesticides and Veterinary Medicines Authority)

agbitech pty ltd - nuclear polyhedrosis virus of helicoverpa armigera - liquid concentrate - nuclear polyhedrosis virus of helicoverpa armigera biological-virus active 0.0 p - insecticide - adzuki bean | apple | blackberry | blueberry | boysenberry | brassica leafy vegetables - see label | brassica vegetables | broad - helicoverpa armigera | helicoverpa punctigera | bollworm | corn earworm | cotton bollworm | native budworm | tobacco budworm | tomato grub

Australia - English - APVMA (Australian Pesticides and Veterinary Medicines Authority)

agbitech pty ltd - nuclear polyhedrosis virus of helicoverpa armigera - soluble concentrate - nuclear polyhedrosis virus of helicoverpa armigera biological-virus active 0.0 ml - insecticide

Canada - English - Health Canada

vivus llc. - lipase; amylase; protease - capsule (delayed release) - 16800unit; 70000unit; 40000unit - lipase 16800unit; amylase 70000unit; protease 40000unit - digestants

Canada - English - Health Canada

vivus llc. - amylase; protease; lipase - capsule (delayed release) - 43750unit; 25000unit; 10500unit - amylase 43750unit; protease 25000unit; lipase 10500unit - digestants

Canada - English - Health Canada

vivus llc. - lipase; amylase; protease - capsule (delayed release) - 4200unit; 17500unit; 10000unit - lipase 4200unit; amylase 17500unit; protease 10000unit - digestants

Canada - English - Health Canada

vivus llc. - lipase; amylase; protease - capsule (delayed release) - 2600unit; 10850unit; 6200unit - lipase 2600unit; amylase 10850unit; protease 6200unit - digestants

Canada - English - Health Canada

vivus llc. - lipase; amylase; protease - capsule (delayed release) - 21000unit; 61000unit; 37000unit - lipase 21000unit; amylase 61000unit; protease 37000unit - digestants

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

vivus llc - avanafil (unii: dr5s136ivo) (avanafil - unii:dr5s136ivo) - stendra is a phosphodiesterase 5 (pde5) inhibitor indicated for the treatment of erectile dysfunction. administration of stendra with any form of organic nitrates, either regularly and/or intermittently, is contraindicated. consistent with its known effects on the nitric oxide/cyclic guanosine monophosphate (cgmp) pathway, stendra has been shown to potentiate the hypotensive effects of nitrates. in a patient who has taken stendra, where nitrate administration is deemed medically necessary in a life-threatening situation, at least 12 hours should elapse after the last dose of stendra before nitrate administration is considered. in such circumstances, nitrates should only be administered under close medical supervision with appropriate hemodynamic monitoring [see contraindications (4.1), dosage and administration (2.3), and clinical pharmacology (12.2)] . stendra is contraindicated in patients with a known hypersensitivity to an