These Highlights Do Not Include All The Information Needed To Use Vermox™ Chewable Safely And Effectively. See Full Prescribing Information For Vermox™ Chewable.

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 0.2-fold the MRHD, based on mg/m²).

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 0.1-fold the MRHD, based on mg/m²) 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 (0.6 to 1.6-fold the MRHD, based on mg/m²).

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 (0.8-fold the MRHD, based on mg/m²), 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.

Clinical Studies with Mebendazole Chewable 500 mg Tablet

The safety profile of mebendazole chewable 500 mg tablets administered as a single dose was evaluated in 677 pediatric subjects aged 1 to 16 years and in 34 adults. The safety profile was consistent with the known safety profile of mebendazole.

Store below 30°C. Keep container tightly closed. Unused tablets should be discarded 1 month after the bottle is first opened. When the bottle is first opened this Discard After date should be written on the bottle label in the place provided.

In patients treated at dosages substantially higher than recommended or for prolonged periods of time, the following adverse reactions have been reported: alopecia, reversible transaminase elevations, hepatitis, agranulocytosis, neutropenia, and glomerulonephritis.

The safety and effectiveness of VERMOX™ CHEWABLE 500 mg tablets have been established in adults for the treatment of gastrointestinal infections by T. trichiura and A. lumbricoides. Use of VERMOX™ CHEWABLE 500 mg tablets in adults for these indications is supported by evidence from an adequate and well-controlled trial in pediatric patients ages 1 to 16 years [see Clinical Studies (14.1)], safety data in adults [see Adverse Reactions (6.1)], pharmacokinetic data in adults [see Clinical Pharmacology (12.3)], and the evidence from published literature.

VERMOX™ CHEWABLE (mebendazole chewable tablets) is an orally administered anthelmintic. Chemically, it is methyl 5-benzoylbenzimidazole-2-carbamate. Its molecular formula is C₁₆H₁₃N₃O_3. Its molecular weight is 295.30. It has the following chemical structure:

Mebendazole exhibits polymorphism. The polymorph used in VERMOX™ CHEWABLE is polymorph form C. Mebendazole is a white to almost white powder. It is practically insoluble in water, in ethanol (96%) and in methylene chloride.

Each round, flat radius-edged white to yellowish chewable tablet contains 500 mg of mebendazole and is debossed with "M/500" on one side and "J" on the other side.

Inactive ingredients consist of: crospovidone, magnesium stearate, microcrystalline cellulose, povidone, purified water, strawberry flavor and sucralose.

The safety and effectiveness of VERMOX™ CHEWABLE 500 mg tablets have been established in pediatric patients 1 to 16 years of age. Use of VERMOX™ CHEWABLE 500 mg tablets in children is supported by evidence from adequate and well-controlled studies of VERMOX™ CHEWABLE 500 mg tablets [see Clinical Studies (14)].

The safety and effectiveness of mebendazole, including VERMOX™ CHEWABLE have not been established in pediatric patients less than one year of age. Convulsions have been reported with mebendazole use in this age group [see Warnings and Precautions (5.1) and Adverse Reactions (6.2)].

Clinical studies of mebendazole did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects.

The efficacy of VERMOX™ CHEWABLE 500 mg tablets was evaluated in a double-blind, randomized, placebo controlled trial conducted in Africa in 295 pediatric patients between the ages of 1 year to 16 years of age with A. lumbricoides and/or T. trichiura infections. Patients were stratified by worm type and randomized to receive either VERMOX™ CHEWABLE 500 mg tablet (N=149) or placebo (N=146) at the baseline visit (double-blind period). After the 19 day double-blind period, all subjects received a single VERMOX™ CHEWABLE 500 mg tablet (open-label period).

Clinical cure was defined as zero egg count (A. lumbricoides and/or T. trichiura) at the end of the double-blind period (Day 19) in patients with positive egg count for the respective worm(s) at baseline. Patients with missing stool sample at Day 19 were considered not cured (Table 4).

In patients treated with VERMOX™ CHEWABLE 500 mg, egg count reduction rate at the end of the double-blind period (Day 19) in patients with A. lumbricoides and/or T. trichiura was statistically significant (p<0.001) compared to placebo, 100% compared to 30.0% for A. lumbricoides, respectively, and 81.2% compared to 27.4% for T. trichiura, respectively.

VERMOX™ CHEWABLE is contraindicated in persons with a known hypersensitivity to the drug or its excipients.

Adverse reactions reported in clinical trials were anorexia, abdominal pain, diarrhea, flatulence, nausea, vomiting and rash. (6.1).

To report SUSPECTED ADVERSE REACTIONS, contact Janssen Pharmaceuticals, Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Concomitant use of mebendazole and metronidazole should be avoided [see Warnings and Precautions (5.3)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of mebendazole was evaluated in 6276 adult and pediatric subjects one year of age and older who participated in 39 clinical trials for treatment of single or mixed parasitic infections of the gastrointestinal tract. In these trials, the formulations, dosages and duration of mebendazole treatment varied. Adverse reactions reported in mebendazole-treated subjects from the 39 clinical trials are shown in Table 1 below.

VERMOX™ CHEWABLE is indicated for the treatment of patients one year of age and older with gastrointestinal infections caused by Ascaris lumbricoides (roundworm) and Trichuris trichiura (whipworm).

Convulsions have been reported in infants below the age of 1 year during post-marketing experience with mebendazole [see Adverse Reactions (6.2)].

Agranulocytosis and neutropenia have been reported with mebendazole use at higher doses and for more prolonged durations than is recommended for the treatment of soil-transmitted helminth infections. Monitor blood counts if VERMOX™ CHEWABLE is used at higher doses or for prolonged duration.

Mebendazole, a benzimidazole, is an anthelmintic [see Microbiology (12.4)].

• Risk of Convulsions: Convulsions in infants below the age of 1 year have been reported (5.1)
• Hematologic Effects: Neutropenia and agranulocytosis have been reported in patients receiving mebendazole at higher doses and for prolonged duration. Monitor blood counts in these patients (5.2)
• Metronidazole 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 and metronidazole (5.3)

The recommended dosage in patients one year of age and older is one VERMOX™ CHEWABLE 500 mg tablet taken as a single dose.

Chew VERMOX™ CHEWABLE 500 mg tablet completely before swallowing. Do not swallow the tablet whole.

For patients who have difficulty chewing the tablet, approximately 2 mL to 3 mL of drinking water can be added to a suitably sized spoon and the VERMOX™ CHEWABLE 500 mg tablet placed into the water. Within 2 minutes, the tablet absorbs the water and turns into a soft mass with semi-solid consistency, which can then be swallowed.

VERMOX™ CHEWABLE 500 mg tablet can be taken without regard to food intake [see Clinical Pharmacology (12.3)].

Chewable Tablet: 500 mg round, flat radius-edged white to yellowish chewable tablet that is debossed with "M/500" on one side and "J" on the other side.

The following adverse reactions have been identified in adult and pediatric patients postmarketing with mebendazole formulations and dosages other than the VERMOX™ CHEWABLE 500 mg 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.

Advise patients that:

• VERMOX™ CHEWABLE tablet must be chewed completely before swallowing. For patients who have difficulty chewing the tablet, VERMOX™ CHEWABLE tablet can be turned into a soft mass with semi-solid consistency by adding 2 mL to 3 mL of drinking water to a spoon then placing the tablet into the water, which can then be swallowed. [see Dosage and Administration (2)]
• VERMOX™ CHEWABLE tablet must not be swallowed whole. [see Dosage and Administration (2)]
• VERMOX™ CHEWABLE tablet can be taken with or without food. [see Dosage and Administration (2)]
• Taking VERMOX™ CHEWABLE tablet and metronidazole together may cause serious skin reactions and should be avoided. [see Warnings and Precautions (5.3)]

VERMOX™ CHEWABLE tablets are supplied as 500 mg, round, flat radius-edged white to yellowish chewable tablets that are debossed with "M/500" on one side and "J" on the other side. They are supplied as follows:

NDC 50458-675-20

Vermox™ Chewable

(mebendazole chewable tablets)

500 mg

Each chewable tablet contains 500 mg

of mebendazole.

200 tablets

Rx only

USUAL DOSAGE: See package insert for

full Prescribing Information.

Chew tablets completely before swallowing.

Do not swallow tablets whole.

Store below 30°C.

Discard after _/_/_.

Discard unused portion

1 month after first

opening.

USA-AW_112506

© Janssen Pharmaceuticals, Inc. 2016

In carcinogenicity tests of mebendazole in mice and rats, no carcinogenic effects were seen at doses as high as 40 mg/kg (0.4 to 0.8-fold the MRHD, based on mg/m²) given daily over two years. No mutagenic activity was observed with mebendazole in a bacterial reverse gene mutation test. Mebendazole was mutagenic in the absence of S-9 when tested using a continuous (24 hour) treatment incubation period in the mouse lymphoma thymidine kinase assay. Mebendazole was aneugenic in vitro in mammalian somatic cells. In the in vivo mouse micronucleus assay, orally administered mebendazole induced an increased frequency of micronucleated polychromatic erythrocytes with evidence suggestive of aneugenicity. Doses up to 40 mg/kg in rats (0.8-fold the MRHD, based on mg/m²), given to males for 60 days and to females for 14 days prior to gestation, had no effect upon fetuses and offspring.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have been reported with the concomitant use of mebendazole and metronidazole. Avoid concomitant use of mebendazole and metronidazole.

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 0.2-fold the MRHD, based on mg/m²).

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 0.1-fold the MRHD, based on mg/m²) 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 (0.6 to 1.6-fold the MRHD, based on mg/m²).

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 (0.8-fold the MRHD, based on mg/m²), 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.

Clinical Studies with Mebendazole Chewable 500 mg Tablet

The safety profile of mebendazole chewable 500 mg tablets administered as a single dose was evaluated in 677 pediatric subjects aged 1 to 16 years and in 34 adults. The safety profile was consistent with the known safety profile of mebendazole.

Store below 30°C. Keep container tightly closed. Unused tablets should be discarded 1 month after the bottle is first opened. When the bottle is first opened this Discard After date should be written on the bottle label in the place provided.

In patients treated at dosages substantially higher than recommended or for prolonged periods of time, the following adverse reactions have been reported: alopecia, reversible transaminase elevations, hepatitis, agranulocytosis, neutropenia, and glomerulonephritis.

The safety and effectiveness of VERMOX™ CHEWABLE 500 mg tablets have been established in adults for the treatment of gastrointestinal infections by T. trichiura and A. lumbricoides. Use of VERMOX™ CHEWABLE 500 mg tablets in adults for these indications is supported by evidence from an adequate and well-controlled trial in pediatric patients ages 1 to 16 years [see Clinical Studies (14.1)], safety data in adults [see Adverse Reactions (6.1)], pharmacokinetic data in adults [see Clinical Pharmacology (12.3)], and the evidence from published literature.

VERMOX™ CHEWABLE (mebendazole chewable tablets) is an orally administered anthelmintic. Chemically, it is methyl 5-benzoylbenzimidazole-2-carbamate. Its molecular formula is C₁₆H₁₃N₃O_3. Its molecular weight is 295.30. It has the following chemical structure:

Mebendazole exhibits polymorphism. The polymorph used in VERMOX™ CHEWABLE is polymorph form C. Mebendazole is a white to almost white powder. It is practically insoluble in water, in ethanol (96%) and in methylene chloride.

Each round, flat radius-edged white to yellowish chewable tablet contains 500 mg of mebendazole and is debossed with "M/500" on one side and "J" on the other side.

Inactive ingredients consist of: crospovidone, magnesium stearate, microcrystalline cellulose, povidone, purified water, strawberry flavor and sucralose.

The safety and effectiveness of VERMOX™ CHEWABLE 500 mg tablets have been established in pediatric patients 1 to 16 years of age. Use of VERMOX™ CHEWABLE 500 mg tablets in children is supported by evidence from adequate and well-controlled studies of VERMOX™ CHEWABLE 500 mg tablets [see Clinical Studies (14)].

The safety and effectiveness of mebendazole, including VERMOX™ CHEWABLE have not been established in pediatric patients less than one year of age. Convulsions have been reported with mebendazole use in this age group [see Warnings and Precautions (5.1) and Adverse Reactions (6.2)].

Clinical studies of mebendazole did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects.

The efficacy of VERMOX™ CHEWABLE 500 mg tablets was evaluated in a double-blind, randomized, placebo controlled trial conducted in Africa in 295 pediatric patients between the ages of 1 year to 16 years of age with A. lumbricoides and/or T. trichiura infections. Patients were stratified by worm type and randomized to receive either VERMOX™ CHEWABLE 500 mg tablet (N=149) or placebo (N=146) at the baseline visit (double-blind period). After the 19 day double-blind period, all subjects received a single VERMOX™ CHEWABLE 500 mg tablet (open-label period).

Clinical cure was defined as zero egg count (A. lumbricoides and/or T. trichiura) at the end of the double-blind period (Day 19) in patients with positive egg count for the respective worm(s) at baseline. Patients with missing stool sample at Day 19 were considered not cured (Table 4).

In patients treated with VERMOX™ CHEWABLE 500 mg, egg count reduction rate at the end of the double-blind period (Day 19) in patients with A. lumbricoides and/or T. trichiura was statistically significant (p<0.001) compared to placebo, 100% compared to 30.0% for A. lumbricoides, respectively, and 81.2% compared to 27.4% for T. trichiura, respectively.

VERMOX™ CHEWABLE is contraindicated in persons with a known hypersensitivity to the drug or its excipients.

Adverse reactions reported in clinical trials were anorexia, abdominal pain, diarrhea, flatulence, nausea, vomiting and rash. (6.1).

To report SUSPECTED ADVERSE REACTIONS, contact Janssen Pharmaceuticals, Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Concomitant use of mebendazole and metronidazole should be avoided [see Warnings and Precautions (5.3)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of mebendazole was evaluated in 6276 adult and pediatric subjects one year of age and older who participated in 39 clinical trials for treatment of single or mixed parasitic infections of the gastrointestinal tract. In these trials, the formulations, dosages and duration of mebendazole treatment varied. Adverse reactions reported in mebendazole-treated subjects from the 39 clinical trials are shown in Table 1 below.

VERMOX™ CHEWABLE is indicated for the treatment of patients one year of age and older with gastrointestinal infections caused by Ascaris lumbricoides (roundworm) and Trichuris trichiura (whipworm).

Convulsions have been reported in infants below the age of 1 year during post-marketing experience with mebendazole [see Adverse Reactions (6.2)].

Agranulocytosis and neutropenia have been reported with mebendazole use at higher doses and for more prolonged durations than is recommended for the treatment of soil-transmitted helminth infections. Monitor blood counts if VERMOX™ CHEWABLE is used at higher doses or for prolonged duration.

Mebendazole, a benzimidazole, is an anthelmintic [see Microbiology (12.4)].

• Risk of Convulsions: Convulsions in infants below the age of 1 year have been reported (5.1)
• Hematologic Effects: Neutropenia and agranulocytosis have been reported in patients receiving mebendazole at higher doses and for prolonged duration. Monitor blood counts in these patients (5.2)
• Metronidazole 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 and metronidazole (5.3)

The recommended dosage in patients one year of age and older is one VERMOX™ CHEWABLE 500 mg tablet taken as a single dose.

Chew VERMOX™ CHEWABLE 500 mg tablet completely before swallowing. Do not swallow the tablet whole.

For patients who have difficulty chewing the tablet, approximately 2 mL to 3 mL of drinking water can be added to a suitably sized spoon and the VERMOX™ CHEWABLE 500 mg tablet placed into the water. Within 2 minutes, the tablet absorbs the water and turns into a soft mass with semi-solid consistency, which can then be swallowed.

VERMOX™ CHEWABLE 500 mg tablet can be taken without regard to food intake [see Clinical Pharmacology (12.3)].

Chewable Tablet: 500 mg round, flat radius-edged white to yellowish chewable tablet that is debossed with "M/500" on one side and "J" on the other side.

The following adverse reactions have been identified in adult and pediatric patients postmarketing with mebendazole formulations and dosages other than the VERMOX™ CHEWABLE 500 mg 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.

Advise patients that:

• VERMOX™ CHEWABLE tablet must be chewed completely before swallowing. For patients who have difficulty chewing the tablet, VERMOX™ CHEWABLE tablet can be turned into a soft mass with semi-solid consistency by adding 2 mL to 3 mL of drinking water to a spoon then placing the tablet into the water, which can then be swallowed. [see Dosage and Administration (2)]
• VERMOX™ CHEWABLE tablet must not be swallowed whole. [see Dosage and Administration (2)]
• VERMOX™ CHEWABLE tablet can be taken with or without food. [see Dosage and Administration (2)]
• Taking VERMOX™ CHEWABLE tablet and metronidazole together may cause serious skin reactions and should be avoided. [see Warnings and Precautions (5.3)]

VERMOX™ CHEWABLE tablets are supplied as 500 mg, round, flat radius-edged white to yellowish chewable tablets that are debossed with "M/500" on one side and "J" on the other side. They are supplied as follows:

NDC 50458-675-20

Vermox™ Chewable

(mebendazole chewable tablets)

500 mg

Each chewable tablet contains 500 mg

of mebendazole.

200 tablets

Rx only

USUAL DOSAGE: See package insert for

full Prescribing Information.

Chew tablets completely before swallowing.

Do not swallow tablets whole.

Store below 30°C.

Discard after _/_/_.

Discard unused portion

1 month after first

opening.

USA-AW_112506

© Janssen Pharmaceuticals, Inc. 2016

In carcinogenicity tests of mebendazole in mice and rats, no carcinogenic effects were seen at doses as high as 40 mg/kg (0.4 to 0.8-fold the MRHD, based on mg/m²) given daily over two years. No mutagenic activity was observed with mebendazole in a bacterial reverse gene mutation test. Mebendazole was mutagenic in the absence of S-9 when tested using a continuous (24 hour) treatment incubation period in the mouse lymphoma thymidine kinase assay. Mebendazole was aneugenic in vitro in mammalian somatic cells. In the in vivo mouse micronucleus assay, orally administered mebendazole induced an increased frequency of micronucleated polychromatic erythrocytes with evidence suggestive of aneugenicity. Doses up to 40 mg/kg in rats (0.8-fold the MRHD, based on mg/m²), given to males for 60 days and to females for 14 days prior to gestation, had no effect upon fetuses and offspring.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have been reported with the concomitant use of mebendazole and metronidazole. Avoid concomitant use of mebendazole and metronidazole.