BONJESTA

BONJESTA extended-release tablets consist of an enteric-coated core containing 10 mg doxylamine succinate and 10 mg pyridoxine hydrochloride, and an immediate release coating of 10 mg doxylamine succinate and 10 mg pyridoxine hydrochloride. BONJESTA tablets are round, pink, film-coated, multilayer, extended-release tablets containing a total of 20 mg doxylamine succinate and 20 mg pyridoxine hydrochloride. Tablets are imprinted on one side with the pink image of a pregnant woman and a “D” on the other side. Inactive ingredients are as follows: ammonium hydroxide, n-butanol, carnauba wax powder, colloidal silicon dioxide, croscarmellose sodium, D&C Red#27 aluminum lake, denatured alcohol, ferrosoferric oxide, FD&C Blue #2 aluminum lake, hypromellose, iron oxide red, isopropyl alcohol, magnesium stearate, magnesium trisilicate, methacrylic acid copolymer, microcrystalline cellulose 102, PEG 3350, propylene glycol, shellac glaze, simethicone, sodium bicarbonate, sodium lauryl sulfate, talc, titanium dioxide, triethyl citrate. BONJESTA is certified Kosher, Kosher for Passover and Halal . Doxylamine Succinate Doxylamine succinate is classified as an antihistamine. The chemical name for doxylamine succinate is ethanamine, N,N-dimethyl-2-[1-phenyl-1-(2-pyridinyl)ethoxy]-, butanedioate (1:1). The empirical formula is C 17 H 22 N 2 O • C 4 H 6 O 4 and the molecular mass is 388.46. The structural formula is: Doxylamine succinate is a white to creamy white powder that is very soluble in water and alcohol, freely soluble in chloroform and very slightly soluble in ether and benzene. Pyridoxine Hydrochloride Pyridoxine hydrochloride is a vitamin B 6 analog. The chemical name for pyridoxine hydrochloride is 3,4-pyridinedimethanol, 5-hydroxy-6-methyl-, hydrochloride. The empirical formula is C 8 H 11 NO 3 • HCl and the molecular mass is 205.64. The structural formula is: Pyridoxine hydrochloride is a white or practically white crystalline powder that is freely soluble in water, slightly soluble in alcohol and insoluble in ether. structure-1 structure-2 Kosher Symbol Halal Symbol

BONJESTA is indicated for the treatment of nausea and vomiting of pregnancy in women who do not respond to conservative management. Limitations of Use BONJESTA has not been studied in women with hyperemesis gravidarum. BONJESTA is a fixed dose combination drug product of 20 mg doxylamine succinate, an antihistamine, and 20 mg pyridoxine hydrochloride, a Vitamin B 6 analog, indicated for the treatment of nausea and vomiting of pregnancy in women who do not respond to conservative management. ( 1 )

On Day 1, take one tablet at bedtime. On Day 2, if symptoms are not adequately controlled, the dose can be increased to one tablet in the morning and one tablet at bedtime. The maximum recommended dose is two tablets daily, one in the morning and one at bedtime, as described in the full prescribing information. ( 2 ) 2.1 Dosage Information Initially, take one BONJESTA extended-release tablet orally at bedtime (Day 1). If this dose adequately controls symptoms the next day, continue taking one tablet daily at bedtime only. However, if symptoms persist on Day 2, increase the daily dose to one tablet in the morning and one tablet at bedtime. The maximum recommended dose is two tablets per day, one in the morning and one at bedtime. Take on an empty stomach with a glass of water [ see Clinical Pharmacology (12.3) ]. Swallow tablets whole. Do not crush, chew, or split BONJESTA tablets. Take daily and not on an as needed basis. Reassess the woman for continued need for BONJESTA as her pregnancy progresses.

BONJESTA is contraindicated in women with any of the following conditions: Known hypersensitivity to doxylamine succinate, other ethanolamine derivative antihistamines, pyridoxine hydrochloride or any inactive ingredient in the formulation Monoamine oxidase (MAO) inhibitors intensify and prolong the adverse central nervous system effects of BONJESTA [ see Drug Interactions (7.1) ] . Known hypersensitivity to doxylamine succinate, other ethanolamine derivative antihistamines, pyridoxine hydrochloride or any inactive ingredient in the formulation ( 4 ) Monoamine oxidase (MAO) inhibitors ( 4 , 7 )

The following adverse reactions are discussed elsewhere in the labeling: • Somnolence [ see Warnings and Precautions (5.1) ] • Falls or other accidents resulting from the effect of the combined use of BONJESTA with CNS depressants including alcohol [ see Warnings and Precautions (5.1) ] The most common adverse reaction (≥5 percent and exceeding the rate in placebo) with combination 10 mg doxylamine succinate and 10 mg pyridoxine hydrochloride tablets is somnolence. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Duchesnay Inc. at 1-855-722-7734 or [email protected] or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience 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 clinical practice. The safety and efficacy of combination 10 mg doxylamine succinate and 10 mg pyridoxine hydrochloride tablets compared to placebo was studied in a double-blind, randomized, multi-center trial in 261 women with nausea and vomiting of pregnancy. The mean gestational age at enrollment was 9.3 weeks, range 7 to 14 weeks gestation [ see Clinical Studies (14) ] . Adverse reactions that occurred at an incidence ≥5 percent and exceeded the incidence for placebo are summarized in Table 1. Table 1: Number (Percent) of Women with ≥ 5 Percent Adverse Reactions in a 15-Day Placebo-Controlled Trial of Combination 10 mg Doxylamine Succinate and 10 mg Pyridoxine Hydrochloride Tablets (Only Those Adverse Reactions Occurring at an Incidence ≥ 5 Percent and at a Higher Incidence than Placebo are Shown) Adverse Reaction Combination 10 mg Doxylamine Succinate and 10 mg Pyridoxine Hydrochloride Tablets (N = 133) Placebo (n = 128) Somnolence 19 (14.3%) 15 (11.7%) 6.2 Postmarketing Experience The following adverse events, listed alphabetically, have been identified during post-approval use of the combination of 10 mg doxylamine succinate and 10 mg pyridoxine hydrochloride. 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 . Cardiac disorders : dyspnea, palpitation, tachycardia Ear and labyrinth disorders : vertigo Eye disorders : vision blurred, visual disturbances Gastrointestinal disorders : abdominal distension, abdominal pain, constipation, diarrhea General disorders and administration site conditions : chest discomfort, fatigue, irritability, malaise Immune system disorders : hypersensitivity Nervous system disorders : dizziness, headache, migraines, paresthesia, psychomotor hyperactivity Psychiatric disorders : anxiety, disorientation, insomnia, nightmares Renal and urinary disorders : dysuria, urinary retention Skin and subcutaneous tissue disorders : hyperhidrosis, pruritus, rash, rash maculopapular

Severe drowsiness can occur when used in combination with alcohol or other sedating medications. ( 7 ) 7.1 Drug Interactions Use of BONJESTA is contraindicated in women who are taking monoamine oxidase inhibitors (MAOIs), which prolong and intensify the adverse central nervous system effects (the anticholinergic effects) of antihistamines. Concurrent use of alcohol and other CNS depressants (such as hypnotic sedatives and tranquilizers) with BONJESTA is not recommended. 7.2 Drug-Food Interactions A food-effect trial demonstrated that the delay in the onset of action of BONJESTA may be further delayed, and a reduction in absorption may occur when tablets are taken with food [see Dosage and Administration (2) , Clinical Pharmacology (12.3) ] . Therefore, BONJESTA should be taken on an empty stomach with a glass of water [ see Dosage and Administration (2 )]. 7.3 False Positive Urine Tests for Methadone, Opiates and PCP False positive drug screens for methadone, opiates, and PCP can occur with doxylamine succinate/pyridoxine hydrochloride use. Confirmatory tests, such as Gas Chromatography Mass Spectrometry (GC-MS), should be used to confirm the identity of the substance in the event of a positive immunoassay result. 7.1 Drug Interactions Use of BONJESTA is contraindicated in women who are taking monoamine oxidase inhibitors (MAOIs), which prolong and intensify the adverse central nervous system effects (the anticholinergic effects) of antihistamines. Concurrent use of alcohol and other CNS depressants (such as hypnotic sedatives and tranquilizers) with BONJESTA is not recommended.