ore prolonged durations than is recommended for the treatment of soil-transmitted helminth infections. monitor blood counts if emverm ® is used at higher doses or for prolonged duration. 5.3 metronidazole drug interaction and serious skin reactions stevens-johnson syndrome/toxic epidermal necrolysis (sjs/ten) have been reported with the concomitant use of mebendazole and metronidazole. avoid concomitant use of mebendazole, including emverm ® and metronidazole.

secutive days 1 tablet morning and evening for 3 consecutive days 1 tablet morning and evening for 3 consecutive days

mebendazole-treated subjects from 39 clinical trials * adverse reaction(s) gastrointestinal disorders anorexia abdominal pain diarrhea flatulence nausea vomiting skin and subcutaneous tissue disorders rash *includes mebendazole formulations, dosages and treatment duration other than emverm ® 100 mg tablet 6.2 postmarketing experience the following adverse reactions have been identified in adult and pediatric patients postmarketing with mebendazole formulations and dosages other than the emverm ® 100 mg chewable tablet. because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. table 3: adverse reactions identified during postmarketing experience with mebendazole * adverse reaction(s) blood and lymphatic system disorders agranulocytosis, neutropenia immune system disorders hypersensitivity including anaphylactic reactions nervous system disorders convulsions, dizziness hepatobiliary disorders hepatitis, abnormal liver tests renal and urinary disorders glomerulonephritis skin and subcutaneous tissue disorders toxic epidermal necrolysis, stevens-johnson syndrome, exanthema, angioedema, urticaria, alopecia *includes mebendazole formulations, dosages and treatment duration other than emverm ® 100 mg chewable tablets

rth 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 2-4% and 15-20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risks untreated soil transmitted helminth infections in pregnancy are associated with adverse outcomes including maternal iron deficiency anemia, low birth weight, neonatal and maternal death. data human data several published studies, including prospective pregnancy registries, case-control, retrospective cohort, and randomized controlled studies, have reported no association between mebendazole use and a potential risk of major birth defects or miscarriage. overall, these studies did not identify a specific pattern or frequency of major birth defects with mebendazole use. however, these studies cannot definitely establish the absence of any mebendazole-associated risk because of methodological limitations, including recall bias, confounding factors and, in some cases, small sample size or exclusion of first trimester mebendazole exposures. animal data embryo-fetal developmental toxicity studies in rats revealed no adverse effects on dams or their progeny at doses up to 2.5 mg/kg/day on gestation days 6–15 (the period of organogenesis). dosing at ≥10 mg/kg/day resulted in a lowered body weight gain and a decreased pregnancy rate. maternal toxicity, including body weight loss in one animal and maternal death in 11 of 20 animals, was seen at 40 mg/kg/day. at 10 mg/kg/day, increased embryo-fetal resorption (100% were resorbed at 40 mg/kg/day), decreased pup weight and increased incidence of malformations (primarily skeletal) were observed. mebendazole was also embryotoxic and teratogenic in pregnant rats at single oral doses during organogenesis as low as 10 mg/kg (approximately 0.5-fold the total daily mrhd, based on mg/m 2 ). in embryo-fetal developmental toxicity studies in mice dosed on gestation days 6–15, doses of 10 mg/kg/day and higher resulted in decreased body weight gain at 10 and 40 mg/kg/day and a higher mortality rate at 40 mg/kg/day. at doses of 10 mg/kg/day (approximately 0.2-fold the total daily mrhd, based on mg/m 2 ) and higher, embryo-fetal resorption increased (100% at 40 mg/kg) and fetal malformations, including skeletal, cranial, and soft tissue anomalies, were present. dosing of hamsters and rabbits did not result in embryotoxicity or teratogenicity at doses up to 40 mg/kg/day (1.6 to 3.9-fold the total daily mrhd, based on mg/m 2 ). in a peri- and post-natal toxicity study in rats, mebendazole did not adversely affect dams or their progeny at 20 mg/kg/day. at 40 mg/kg (1.9-fold the total daily mrhd, based on mg/m 2 ), a reduction of the number of live pups was observed and there was no survival at weaning. no abnormalities were found on gross and radiographic examination of pups at birth. 8.2 lactation risk summary limited data from case reports demonstrate that a small amount of mebendazole is present in human milk following oral administration. there are no reports of effects on the breastfed infant, and the limited reports on the effects on milk production are inconsistent. the limited clinical data during lactation precludes a clear determination of the risk of emverm ® to a breastfed infant; therefore, developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for emverm ® and any potential adverse effects on the breastfed infant from emverm ® or from the underlying maternal condition. 8.4 pediatric use the safety and effectiveness of emverm ® 100 mg chewable tablets has not been established in pediatric patients less than two years of age. convulsions have been reported with mebendazole use in children less than one year of age [see warnings and precautions (5.1) and adverse reactions (6.2)]. 8.5 geriatric use clinical studies of mebendazole did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects.

erse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risks untreated soil transmitted helminth infections in pregnancy are associated with adverse outcomes including maternal iron deficiency anemia, low birth weight, neonatal and maternal death. data human data several published studies, including prospective pregnancy registries, case-control, retrospective cohort, and randomized controlled studies, have reported no association between mebendazole use and a potential risk of major birth defects or miscarriage. overall, these studies did not identify a specific pattern or frequency of major birth defects with mebendazole use. however, these studies cannot definitely establish the absence of any mebendazole-associated risk because of methodological limitations, including recall bias, confounding factors and, in some cases, small sample size or exclusion of first trimester mebendazole exposures. animal data embryo-fetal developmental toxicity studies in rats revealed no adverse effects on dams or their progeny at doses up to 2.5 mg/kg/day on gestation days 6–15 (the period of organogenesis). dosing at ≥10 mg/kg/day resulted in a lowered body weight gain and a decreased pregnancy rate. maternal toxicity, including body weight loss in one animal and maternal death in 11 of 20 animals, was seen at 40 mg/kg/day. at 10 mg/kg/day, increased embryo-fetal resorption (100% were resorbed at 40 mg/kg/day), decreased pup weight and increased incidence of malformations (primarily skeletal) were observed. mebendazole was also embryotoxic and teratogenic in pregnant rats at single oral doses during organogenesis as low as 10 mg/kg (approximately 0.5-fold the total daily mrhd, based on mg/m 2 ). in embryo-fetal developmental toxicity studies in mice dosed on gestation days 6–15, doses of 10 mg/kg/day and higher resulted in decreased body weight gain at 10 and 40 mg/kg/day and a higher mortality rate at 40 mg/kg/day. at doses of 10 mg/kg/day (approximately 0.2-fold the total daily mrhd, based on mg/m 2 ) and higher, embryo-fetal resorption increased (100% at 40 mg/kg) and fetal malformations, including skeletal, cranial, and soft tissue anomalies, were present. dosing of hamsters and rabbits did not result in embryotoxicity or teratogenicity at doses up to 40 mg/kg/day (1.6 to 3.9-fold the total daily mrhd, based on mg/m 2 ). in a peri- and post-natal toxicity study in rats, mebendazole did not adversely affect dams or their progeny at 20 mg/kg/day. at 40 mg/kg (1.9-fold the total daily mrhd, based on mg/m 2 ), a reduction of the number of live pups was observed and there was no survival at weaning. no abnormalities were found on gross and radiographic examination of pups at birth.

mebendazole is extensively metabolized primarily by the liver. plasma concentrations of its major metabolites (hydrolyzed and reduced forms of mebendazole) are higher than those of mebendazole. all metabolites are devoid of anthelmintic activity. impaired hepatic function, impaired metabolism, or impaired biliary elimination may lead to higher plasma concentrations of mebendazole. excretion mebendazole, the conjugated forms of mebendazole, and its metabolites likely undergo some degree of enterohepatic recirculation. the apparent elimination half-life after an oral dose ranges from 3 to 6 hours in most patients. less than 2% of orally administered mebendazole is excreted in urine and the remainder in the feces as unchanged drug or its metabolites. 12.4 microbiology mechanism of action mebendazole interferes with cellular tubulin formation in the helminth and causes ultrastructural degenerative changes in its intestine. as a result, its glucose uptake and the digestive and reproductive functions are disrupted, leading to immobilization, inhibition of egg production and death of the helminth. antimicrobial activity mebendazole is active against: ancylostoma duodenale ascaris lumbricoides enterobius vermicularis necator americanus trichuris trichiura resistance there is a potential for development of resistance to mebendazole. the mechanism of resistance to mebendazole is likely due to changes of beta-tubulin protein, which reduces binding of mebendazole to beta-tubulin; however, the clinical significance of this is not known.

d forms of mebendazole) are higher than those of mebendazole. all metabolites are devoid of anthelmintic activity. impaired hepatic function, impaired metabolism, or impaired biliary elimination may lead to higher plasma concentrations of mebendazole. excretion mebendazole, the conjugated forms of mebendazole, and its metabolites likely undergo some degree of enterohepatic recirculation. the apparent elimination half-life after an oral dose ranges from 3 to 6 hours in most patients. less than 2% of orally administered mebendazole is excreted in urine and the remainder in the feces as unchanged drug or its metabolites.

over-the­-counter medicines, vitamins, and herbal supplements. using emverm with certain other medicines can change the way these medicines act, causing serious side effects. know the medicines you take. keep a list of them to show to your healthcare provider or pharmacist when you get a new medicine. how should i take emverm? take emverm exactly as your healthcare provider tells you to take it. take emverm by mouth with or without food. emverm tablets may be chewed, swallowed, or crushed and mixed with food. if you take too much emverm, you might have symptoms that include stomach cramps, nausea, vomiting or diarrhea. what should i avoid while taking emverm? do not take emverm with metronidazole (a medicine used to treat bacterial and protozoan infections) as serious skin reactions called stevens-johnson syndrome (sjs) and toxic epidermal necrolysis (ten) can happen. what are the possible side effects of emverm? emverm may cause serious side effects, including: low white blood cell count (neutropenia). neutropenia can cause you to get other infections. your healthcare provider will check your blood count regularly during your treatment with emverm. tell your healthcare provider right away if you have a fever or any signs of an infection while taking emverm severe skin reactions (stevens-johnson syndrome and toxic epidermal necrolysis). emverm may cause rare, but serious skin reactions when taken with metronidazole and other medicines that contain mebendazole. these severe allergic reactions may be life-threatening and need to be treated in a hospital. call your healthcare provider right away or get emergency medical help if you have any allergic reactions or the following symptoms: severe skin blisters sores around the mouth, nose, eyes, vagina or penis (genitals) peeling skin swollen face, lips, mouth, tongue or throat itchy rash (hives) the most common side effects of emverm include: loss of appetite (anorexia) stomach pain diarrhea passing gas nausea vomiting rash tell your healthcare provider if you have any side effect that bothers you or does not go away. these are not all the possible side effects of emverm. call your doctor for medical advice about side effects. you may report side effects to fda at 1-800-fda-1088. how should i store emverm? store at room temperature between 68°f to 77°f (20°c to 25°c). safely throw away medicine that is out of date or no longer needed. keep emverm and all medicines out of the reach of children. general information about the safe and effective use of emverm. medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. do not use emverm for a condition for which it was not prescribed. do not give emverm to other people, even if they have the same symptoms that you have. it may harm them. you can ask your pharmacist or healthcare provider for information about emverm that is written for health professionals. what are the ingredients in emverm? active ingredient: mebendazole, usp. inactive ingredients: microcrystalline cellulose, corn starch, anhydrous lactose nf, sodium starch glycolate, magnesium stearate, stearic acid, sodium lauryl sulfate, sodium saccharin, and fd&c yellow #6. manufactured by: alcami wilmington, nc 28405 distributed by: amneal specialty, a division of amneal pharmaceuticals llc bridgewater, nj 08807 for more information, call amneal pharmaceuticals at 1-877-835-5472. this patient information has been approved by the u.s. food and drug administration. rev. 08-2021-01