Doxylamine Succinate and Pyridoxine Hydrochloride

DOXYLAMINE SUCCINATE AND PYRIDOXINE HYDROCHLORIDE- doxylamine succinate and pyridoxine hydrochloride tablet, delayed release
Mylan Pharmaceuticals Inc.

1 INDICATIONS AND USAGE

Doxylamine succinate and pyridoxine hydrochloride delayed-release tablets are indicated for the treatment of nausea and vomiting of pregnancy in women who do not respond to conservative management.

Limitations of Use: Doxylamine succinate and pyridoxine hydrochloride delayed-release tablets have not been studied in women with hyperemesis gravidarum.

2 DOSAGE AND ADMINISTRATION

2.1 Dosage Information

Initially, take two doxylamine succinate and pyridoxine hydrochloride delayed-release tablets orally at bedtime (Day 1). If this dose adequately controls symptoms the next day, continue taking two tablets daily at bedtime. However, if symptoms persist into the afternoon of Day 2, take the usual dose of two tablets at bedtime that night then take three tablets starting on Day 3 (one tablet in the morning and two tablets at bedtime). If these three tablets adequately control symptoms on Day 4, continue taking three tablets daily. Otherwise take four tablets starting on Day 4 (one tablet in the morning, one tablet mid-afternoon and two tablets at bedtime).

The maximum recommended dose is four tablets (one in the morning, one in the mid-afternoon and two at bedtime) daily.

Take on an empty stomach with a glass of water [see Clinical Pharmacology (12.3)]. Swallow tablets whole. Do not crush, chew, or split doxylamine succinate and pyridoxine hydrochloride delayed-release tablets.

Take as a daily prescription and not on an as needed basis. Reassess the woman for continued need for doxylamine succinate and pyridoxine hydrochloride delayed-release tablets as her pregnancy progresses.

3 DOSAGE FORMS AND STRENGTHS

Doxylamine Succinate and Pyridoxine Hydrochloride Delayed-Release Tablets are available containing 10 mg of doxylamine succinate, USP and 10 mg of pyridoxine hydrochloride, USP.

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The 10 mg/10 mg tablets are white to off-white, film-coated, round, unscored tablets imprinted with M over DP in black ink on one side of the tablet and blank on the other side.

4 CONTRAINDICATIONS

Doxylamine succinate and pyridoxine hydrochloride delayed-release tablets are contraindicated in women with any of the following conditions:

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Known hypersensitivity to doxylamine succinate, other ethanolamine derivative antihistamines, pyridoxine hydrochloride or any inactive ingredient in the formulation

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Monoamine oxidase (MAO) inhibitors intensify and prolong the adverse central nervous system effects of doxylamine succinate and pyridoxine hydrochloride delayed-release tablets [see Drug Interactions (7.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Activities Requiring Mental Alertness

Doxylamine succinate and pyridoxine hydrochloride delayed-release tablets may cause somnolence due to the anticholinergic properties of doxylamine succinate, an antihistamine. Women should avoid engaging in activities requiring complete mental alertness, such as driving or operating heavy machinery, while using doxylamine succinate and pyridoxine hydrochloride delayed-release tablets until cleared to do so by their healthcare provider.

Doxylamine succinate and pyridoxine hydrochloride delayed-release tablets use is not recommended if a woman is concurrently using central nervous system (CNS) depressants including alcohol. The combination may result in severe drowsiness leading to falls or accidents [see Drug Interactions (7.1)].

5.2 Concomitant Medical Conditions

​ Doxylamine succinate and pyridoxine hydrochloride delayed-release tablets have anticholinergic properties and, therefore, should be used with caution in women with: increased intraocular pressure, narrow angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction and urinary bladder-neck obstruction.

5.3 Interference with Urine Screen for Methadone, Opiates and Phencyclidine Phosphate (PCP)

There have been reports of false positive urine screening tests for methadone, opiates, and PCP with doxylamine succinate/pyridoxine hydrochloride use [see Drug Interactions (7.3)].

6 ADVERSE REACTIONS

The following adverse reactions are discussed elsewhere in the labeling:

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Somnolence [see Warnings and Precautions (5.1)]

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Falls or other accidents resulting from the effect of the combined use of doxylamine succinate and pyridoxine hydrochloride delayed-release tablets with CNS depressants including alcohol [see Warnings and Precautions (5.1)]

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 doxylamine succinate and pyridoxine hydrochloride delayed-release tablets were compared to placebo 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 for doxylamine succinate and pyridoxine hydrochloride delayed-release tablets that occurred at an incidence ≥ 5 percent and exceeded the incidence for placebo are summarized in Table 1.

Table 1: Number (Percent) of Subjects with ≥ 5 Percent Adverse Reactions in a 15-Day Placebo-Controlled Study of Doxylamine Succinate and Pyridoxine Hydrochloride Delayed-Release Tablets (Only Those Adverse Reactions Occurring at an Incidence ≥ 5 Percent and at a Higher Incidence with Doxylamine Succinate and Pyridoxine Hydrochloride Delayed-Release Tablets than Placebo are Shown)

	Doxylamine Succinate and Pyridoxine Hydrochloride Delayed-Release 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 maculo-papular