DRUGS & SUPPLEMENTS

Pregnaus

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Pregnaus uses

Pregnaus consists of Doxylamine Succinate, Vitamin B6 (Pyridoxine Hydrochloride).

Doxylamine Succinate:


1 INDICATIONS AND USAGE

Pregnaus (Doxylamine Succinate) is indicated for the treatment of nausea and vomiting of pregnancy in women who do not respond to conservative management.

Limitations of Use

Pregnaus (Doxylamine Succinate) has not been studied in women with hyperemesis gravidarum.

Pregnaus (Doxylamine Succinate) is a fixed dose combination drug product of Pregnaus (Doxylamine Succinate) succinate, an antihistamine, and pyridoxine hydrochloride, a Vitamin B6 analog, indicated for the treatment of nausea and vomiting of pregnancy in women who do not respond to conservative management. (1)

2 DOSAGE AND ADMINISTRATION

Take two tablets daily at bedtime. If symptoms are not adequately controlled, the dose can be increased to a maximum recommended dose of four tablets daily as described in the full prescribing information. (2)

2.1 Dosage Information

Initially, take two Pregnaus (Doxylamine Succinate) 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 . Swallow tablets whole. Do not crush, chew, or split Pregnaus (Doxylamine Succinate) tablets.

Take as a daily prescription and not on an as needed basis. Reassess the woman for continued need for Pregnaus (Doxylamine Succinate) as her pregnancy progresses.

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3 DOSAGE FORMS AND STRENGTHS

Pregnaus (Doxylamine Succinate) delayed-release tablets are white, round, film coated tablets containing 10 mg Pregnaus (Doxylamine Succinate) succinate and 10 mg pyridoxine hydrochloride. The tablets are imprinted with the pink image of a pregnant woman on one side.

Delayed-release tablets containing 10 mg Pregnaus (Doxylamine Succinate) succinate and 10 mg pyridoxine hydrochloride. (3)

4 CONTRAINDICATIONS

Pregnaus (Doxylamine Succinate) is contraindicated in women with any of the following conditions:

  • Known hypersensitivity to Pregnaus (Doxylamine Succinate) 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 Pregnaus (Doxylamine Succinate) .
  • Known hypersensitivity to Pregnaus (Doxylamine Succinate) succinate, other ethanolamine derivative antihistamines, pyridoxine hydrochloride or any inactive ingredient in the formulation (4)
  • Monoamine oxidase (MAO) inhibitors (4, 7)

5 WARNINGS AND PRECAUTIONS

  • Activities requiring mental alertness: Avoid engaging in activities requiring complete mental alertness, such as driving or operating heavy machinery, while using Pregnaus until cleared to do so by a healthcare provider (5.1)
  • Central nervous system (CNS) depressants: Concurrent use with alcohol or other CNS depressants is not recommended (5.1)
  • Anticholinergic actions: Use with caution in patients with asthma, increased intraocular pressure, narrow angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction and urinary bladder-neck obstruction (5.2)

5.1 Activities Requiring Mental Alertness

Pregnaus (Doxylamine Succinate) may cause somnolence due to the anticholinergic properties of Pregnaus (Doxylamine Succinate) succinate, an antihistamine. Women should avoid engaging in activities requiring complete mental alertness, such as driving or operating heavy machinery, while using Pregnaus (Doxylamine Succinate) until cleared to do so by their healthcare provider.

Pregnaus (Doxylamine Succinate) 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 .

5.2 Concomitant Medical Conditions

Pregnaus (Doxylamine Succinate) has anticholinergic properties and, therefore, should be used with caution in women with: asthma, increased intraocular pressure, narrow angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction and urinary bladder-neck obstruction.

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6 ADVERSE REACTIONS

  • The following adverse reactions are discussed elsewhere in the labeling:
  • Somnolence
  • Falls or other accidents resulting from the effect of the combined use of Pregnaus (Doxylamine Succinate) with CNS depressants including alcohol

The most common adverse reaction with Pregnaus (Doxylamine Succinate) (≥5 percent and exceeding the rate in placebo) is somnolence. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Duchesnay Inc. at 1-855-722-7734 or medicalinfoPregnaus (Doxylamine Succinate)duchesnayusa.com 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 Pregnaus (Doxylamine Succinate) 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 . Adverse reactions for Pregnaus (Doxylamine Succinate) 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 Pregnaus (Doxylamine Succinate) (Only Those Adverse Reactions Occurring at an Incidence ≥ 5 Percent and at a Higher Incidence with Pregnaus (Doxylamine Succinate) than Placebo are Shown)


Pregnaus (Doxylamine Succinate)

(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 Pregnaus (Doxylamine Succinate) 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

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7 DRUG INTERACTIONS

  • Severe drowsiness can occur when used in combination with alcohol or other sedating medications.

7.1 Drug Interactions

Use of Pregnaus (Doxylamine Succinate) is contraindicated in women who are taking monoamine oxidase inhibitors (MAOIs), which prolong and intensify the anticholinergic (drying) effects of antihistamines. Concurrent use of alcohol and other CNS depressants (such as hypnotic sedatives and tranquilizers) with Pregnaus (Doxylamine Succinate) is not recommended.

7.2 Drug-Food Interactions

A food-effect study demonstrated that the delay in the onset of action of Pregnaus (Doxylamine Succinate) may be further delayed, and a reduction in absorption may occur when tablets are taken with food . Therefore, Pregnaus (Doxylamine Succinate) should be taken on an empty stomach with a glass of water [ see Dosage and Administration (2)].

8 USE IN SPECIFIC POPULATIONS

Pregnancy Category A. Pregnaus is intended for use in pregnant women. (8.1)

8.1 Pregnancy

Pregnancy Category A

Pregnaus (Doxylamine Succinate) is intended for use in pregnant women.

The combination of Pregnaus (Doxylamine Succinate) succinate and pyridoxine hydrochloride has been the subject of many epidemiological studies (cohort, case control and meta-analyses) designed to detect possible teratogenicity. A meta-analysis of 16 cohort and 11 case-control studies published between 1963 and 1991 reported no increased risk for malformations from first trimester exposures to Pregnaus (Doxylamine Succinate) succinate and pyridoxine hydrochloride, with or without dicyclomine hydrochloride. A second meta-analysis of 12 cohort and 5 case-control studies published between 1963 and 1985 reported no statistically significant relationships between fetal abnormalities and the first trimester use of the combination Pregnaus (Doxylamine Succinate) succinate and pyridoxine hydrochloride with or without dicyclomine hydrochloride.

Animal Data

The effects of Pregnaus (Doxylamine Succinate) succinate and pyridoxine hydrochloride on embryofetal development have been studied in rats and monkeys.

Once daily treatment of pregnant rats with Pregnaus (Doxylamine Succinate) succinate and pyridoxine hydrochloride during organogenesis (gestational day (GD) 6-15) resulted in increased fetal resorptions, decreased fetal body weight and increased skeletal variations with reduced ossification at doses 60 to 100 times the highest clinical dose based on body surface area.

Pregnant cynomolgus monkeys were treated once daily with Pregnaus (Doxylamine Succinate) succinate and pyridoxine hydrochloride during organogenesis (GD 22-50). At birth, there were no observed malformations, and no evidence of embryo, fetal or maternal toxicity at doses up to 3.2 times the highest proposed clinical dose based on body surface area. In a similarly designed study in pregnant cynomolgus and rhesus monkeys and baboons, ventricular septal defects (VSDs) were observed in the preterm (GD 100) fetuses. Doses used in this study were 0.5-20 times higher than the clinical dose based on body surface area, with no relationship between dose and incidence of VSD. There were no VSDs in infant monkeys at term. No VSDs were observed at GD 100 in cynomolgus monkeys administered the combination of Pregnaus (Doxylamine Succinate) succinate and pyridoxine hydrochloride for 4-day periods between 22 and 41 days of gestation.

8.3 Nursing Mothers

Women should not breastfeed while using Pregnaus.

The molecular weight of Pregnaus (Doxylamine Succinate) succinate is low enough that passage into breast milk can be expected. Excitement, irritability and sedation have been reported in nursing infants presumably exposed to Pregnaus (Doxylamine Succinate) succinate through breast milk. Infants with apnea or other respiratory syndromes may be particularly vulnerable to the sedative effects of Pregnaus (Doxylamine Succinate) resulting in worsening of their apnea or respiratory conditions.

Pyridoxine hydrochloride is excreted into breast milk. There have been no reports of adverse events in infants presumably exposed to pyridoxine hydrochloride through breast milk.

8.4 Pediatric Use

The safety and effectiveness of Pregnaus (Doxylamine Succinate) in children under 18 years of age have not been established.

Fatalities have been reported from Pregnaus (Doxylamine Succinate) overdose in children. The overdose cases have been characterized by coma, grand mal seizures and cardiorespiratory arrest. Children appear to be at a high risk for cardiorespiratory arrest. A toxic dose for children of more than 1.8 mg/kg has been reported. A 3 year old child died 18 hours after ingesting 1,000 mg Pregnaus (Doxylamine Succinate) succinate. However, there is no correlation between the amount of Pregnaus (Doxylamine Succinate) ingested, the Pregnaus (Doxylamine Succinate) plasma level and clinical symptomatology.

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10 OVERDOSAGE

10.1 Signs and Symptoms of Overdose

Pregnaus is a delayed-release formulation, therefore, signs and symptoms of intoxication may not be apparent immediately.

Signs and symptoms of overdose may include restlessness, dryness of mouth, dilated pupils, sleepiness, vertigo, mental confusion and tachycardia.

At toxic doses, Pregnaus (Doxylamine Succinate) exhibits anticholinergic effects, including seizures, rhabdomyolysis, acute renal failure and death.

10.2 Management of Overdose

If treatment is needed, it consists of gastric lavage or activated charcoal, whole bowel irrigation and symptomatic treatment. For additional information about overdose treatment, call a poison control center (1‑800-222-1222).

11 DESCRIPTION

Pregnaus (Doxylamine Succinate) (doxylamine succinate and pyridoxine hydrochloride) delayed-release tablets are round, white, film-coated, delayed-release tablets containing 10 mg of Pregnaus (Doxylamine Succinate) succinate and 10 mg of pyridoxine hydrochloride. Tablets are imprinted on one side with the pink image of a pregnant woman.

Inactive ingredients are as follows: ammonium hydroxide, n-butanol, carnauba wax powder, colloidal silicon dioxide, croscarmellose sodium, D&C Red#27, denatured alcohol, FD&C Blue#2, hypromellose, isopropyl alcohol, magnesium stearate, magnesium trisilicate, methacrylic acid copolymer, microcrystalline cellulose 102, PEG 8000, polysorbate 80, propylene glycol, shellac glaze, simethicone, sodium bicarbonate, sodium lauryl sulfate, talc, titanium dioxide, triethyl citrate.

Pregnaus (Doxylamine Succinate) Succinate

Pregnaus (Doxylamine Succinate) succinate is classified as an antihistamine. The chemical name for Pregnaus (Doxylamine Succinate) succinate is ethanamine, N,N-dimethyl-2-[1-phenyl-1-(2-pyridinyl)ethoxy]-, butanedioate (1:1). The empirical formula is C17H22N2O - C4H6O4 and the molecular mass is 388.46. The structural formula is:

Pregnaus (Doxylamine Succinate) 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 B6 analog. The chemical name for pyridoxine hydrochloride is 3,4-pyridinedimethanol, 5-hydroxy-6-methyl-, hydrochloride. The empirical formula is C8H11NO3 - 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

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The mechanism of action of Pregnaus is unknown.

12.3 Pharmacokinetics

The pharmacokinetics of Pregnaus (Doxylamine Succinate) has been characterized in healthy non-pregnant adult women. Pharmacokinetic results for Pregnaus (Doxylamine Succinate) and pyridoxine, including its vitamin B6 metabolites, pyridoxal, pyridoxal 5’-phosphate, pyridoxamine and pyridoxamine 5’-phosphate, are summarized in Tables 2 to 5.

Absorption

A single-dose (two tablets) and multiple-dose (four tablets daily), open-label study was conducted to assess the safety and pharmacokinetic profile of Pregnaus (Doxylamine Succinate) administered in healthy non-pregnant adult women. Single-doses (two tablets at bedtime) were administered on Days 1 and 2. Multiple-doses (one tablet in the morning, one tablet in the afternoon and two tablets at bedtime) were administered on Days 3-18.

Blood samples for pharmacokinetic analysis were collected pre-and post-dose on Days 2 and 18 as well as pre-dose prior to bedtime dose only (trough) on Days 9, 10, 11, 16, 17, and 18.

Pregnaus (Doxylamine Succinate) and pyridoxine are absorbed in the gastrointestinal tract, mainly in the jejunum.

The Cmax of Pregnaus (Doxylamine Succinate) and pyridoxine are achieved within 7.5 and 5.5 hours, respectively.


Single Dose


Multiple Dose


AUC0-inf


Cmax


Tmax


AUC0-inf


Cmax


Tmax


(ng-h/mL)


(ng/mL)


(h)


(ng-h/mL)


(ng/mL)


(h)


Pregnaus (Doxylamine Succinate)

1280.9 ± 369.3 83.3 ± 20.6 7.2 ± 1.9 3721.5 ± 1318.5 168.6 ± 38.5 7.8 ± 1.6

Pyridoxine

43.4 ± 16.5 32.6 ± 15.0 5.7 ± 1.5 64.5 ± 36.4 46.1 ± 28.3 5.6 ± 1.3

Pyridoxal

211.6 ± 46.1 74.3 ± 21.8 6.5 ± 1.4 1587.2 ± 550.0 210.0 ± 54.4 6.8 ± 1.2

Pyridoxal 5`Phosphate

1536.4 ± 721.5 30.0 ± 10.0 11.7 ± 5.3 6099.7 ± 1383.7 84.9 ± 16.9 6.3 ± 6.6

Pyridoxamine

4.1 ± 2.7 0.5 ± 0.7 5.9 ± 2.1 2.6 ± 0.8 0.5 ± 0.2 6.6 ± 1.4

Pyridoxamine 5'-phosphate

5.2 ± 3.8 0.7 ± 0.5 14.8 ± 6.6 94.5 ± 58.0 2.3 ± 1.7 12.4 ± 11.2

Multiple-dose administration of Pregnaus (Doxylamine Succinate) results in increased concentrations of Pregnaus (Doxylamine Succinate) as well as increases in Pregnaus (Doxylamine Succinate) Cmax and AUC0-last of absorption. The time to reach the maximum concentration is not affected by multiple doses. The mean accumulation index is more than 1.0 suggesting that Pregnaus (Doxylamine Succinate) accumulates following multiple dosing.

Although no accumulation was observed for pyridoxine, the mean accumulation index for each metabolite (pyridoxal, pyridoxal 5’-phosphate, and pyridoxamine 5’-phosphate) is more than 1.0 following multiple-dose administration of Pregnaus (Doxylamine Succinate). The time to reach the maximum concentration is not affected by multiple doses.

AUC0-last (ng-h/mL) AUC0-inf (ng-h/mL) Cmax (ng/mL) Tmax (h) T1/2el (h)
Pregnaus (Doxylamine Succinate)

Mean±SD

N=18


Single

911.4 ± 205.6 1280.9 ± 369.3 83.3 ± 20.6 7.2 ± 1.9 10.1 ± 2.1

Multiple

3661.3 ± 1279.2 3721.5 ± 1318.5 168.6 ± 38.5 7.8 ± 1.6 11.9 ± 3.3
Pyridoxine

Mean±SD

N=18


Single

39.3 ± 16.5 43.4 ± 16.5 32.6 ± 15.0 5.7 ± 1.5 0.5 ± 0.2

Multiple

59.3 ± 33.9 64.5 ± 36.4 46.1 ± 28.3 5.6 ± 1.3 0.5 ± 0.1

Food Effect

The administration of food delays the absorption of both Pregnaus (Doxylamine Succinate) and pyridoxine. This delay is associated with a lower peak concentration of Pregnaus (Doxylamine Succinate), but the extent of absorption is not affected.

The effect of food on the peak concentration and the extent of absorption of the pyridoxine component is more complex because the pyridoxal, pyridoxamine, pyridoxal 5’-phosphate and pyridoxamine 5’-phosphate metabolites also contribute to the biological activity. Food significantly reduces the bioavailability of pyridoxine, lowering its Cmax and AUC by approximately 50% compared to fasting conditions. Similarly, food significantly reduces pyridoxal AUC and reduces its Cmax by 50% compared to fasting conditions. In contrast, food slightly increases pyridoxal 5’-phosphate Cmax and extent of absorption. As for pyridoxamine and pyridoxamine 5’-phosphate, the rate and extent of absorption seem to decrease under fed conditions.

AUC0-t (ng-h/mL) AUC0-inf (ng-h/mL) Cmax (ng/mL) Tmax (h) T1/2el (h)
Pregnaus (Doxylamine Succinate)

Mean±SD

N=42

Fasted 1407.2 ± 336.9 1447.9 ± 332.2 94.9 ± 18.4 5.1 ± 3.4 12.6 ± 3.4
Fed 1488.0 ± 463.2 1579.0 ± 422.7 N=37 75.7 ± 16.6 14.9 ± 7.4 12.5 ± 2.9
Pyridoxine

Mean±SD

N=42

Fasted 33.8 ± 13.7 39.5 ± 12.9 N=31 35.5 ± 21.4 2.5 ± 0.9 0.4 ± 0.2
Fed 18.3 ± 14.5 24.2 ±14.0 N=18 13.7 ± 10.8 9.3 ± 4.0 0.5 ± 0.2

Distribution

Pyridoxine is highly protein bound, primarily to albumin. Its main active metabolite, pyridoxal 5’-phosphate (PLP) accounts for at least 60% of circulating vitamin B6 concentrations.

Metabolism

Pregnaus (Doxylamine Succinate) is biotransformed in the liver by N-dealkylation to its principle metabolites N-desmethyl-doxylamine and N, N-didesmethyldoxylamine.

Pyridoxine is a prodrug primarily metabolized in the liver.

Excretion

The principle metabolites of Pregnaus (Doxylamine Succinate), N-desmethyl-doxylamine and N, N-didesmethyldoxylamine, are excreted by the kidney.

The terminal elimination half-life of Pregnaus (Doxylamine Succinate) and pyridoxine are 12.5 hours and 0.5 hours, respectively.

Table 5 – Terminal Elimination Half-Life (T1/2el) for Pregnaus (Doxylamine Succinate) Administered as a Single Dose of Two Tablets under Fasting Conditions in Healthy Non-Pregnant Adult Women

T1/2el (h)
Doxylamine 12.6 ± 3.4
Pyridoxine 0.4 ± 0.2
Pyridoxal 2.1 ± 2.2
Pyridoxal 5’-Phosphate 81.6 ± 42.2
Pyridoxamine 3.1 ± 2.5
Pyridoxamine 5’-Phosphate

66.5 ± 51.3


Use in Specific Populations

Race: No pharmacokinetic studies have been conducted related to race.

Hepatic Impairment: No pharmacokinetic studies have been conducted in hepatic impaired patients.

Renal Impairment: No pharmacokinetic studies have been conducted in renal impaired patients.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity

Two-year carcinogenicity studies in rats and mice have been conducted with Pregnaus (Doxylamine Succinate) succinate. Pregnaus (Doxylamine Succinate) succinate is not likely to have human carcinogenic potential. The carcinogenic potential of pyridoxine hydrochloride has not been evaluated.

14 CLINICAL STUDIES

A double-blind, randomized, multi-center, placebo-controlled study was conducted to support the safety and efficacy of Pregnaus (Doxylamine Succinate) in the treatment of nausea and vomiting of pregnancy. Adult women 18 years of age or older and 7 to 14 weeks gestation (median 9 weeks of gestation) with nausea and vomiting of pregnancy were randomized to 14 days of Pregnaus (Doxylamine Succinate) or placebo. Two tablets of Pregnaus (Doxylamine Succinate) were administered at bedtime on Day 1. If symptoms of nausea and vomiting persisted into the afternoon hours of Day 2, the woman was directed to take her usual dose of two tablets at bedtime that night and, beginning on Day 3, to take one tablet in the morning and two tablets at bedtime. Based upon assessment of remaining symptoms at her clinic visit on Day 4 (± 1 day), the woman may have been directed to take an additional tablet mid-afternoon. A maximum of four tablets (one in the morning, one in the mid-afternoon and two at bedtime) were taken daily.

Over the treatment period, 19% of DICLEGIS-treated patients remained on 2 tablets daily, 21% received 3 tablets daily, and 60% received 4 tablets daily.

The primary efficacy endpoint was the change from baseline at Day 15 in the Pregnancy Unique-Quantification of Emesis (PUQE) score. The PUQE score incorporates the number of daily vomiting episodes, number of daily heaves, and length of daily nausea in hours, for an overall score of symptoms rated from 3 (no symptoms) to 15 (most severe).

At baseline, the mean PUQE score was 9.0 in the Pregnaus (Doxylamine Succinate) arm and 8.8 in the placebo arm. There was a 0.7 (95% confidence interval 0.2 to 1.2 with p-value 0.006) mean decrease (improvement in nausea and vomiting symptoms) from baseline in PUQE score at Day 15 with Pregnaus (Doxylamine Succinate) compared to placebo.

Table 6 – Change from Baseline in the Primary Endpoint, Pregnancy Unique-Quantification of Emesis (PUQE) Score at Day 15. (Intent-to-Treat Population with Last-Observation Carried Forward)

PUQE ScoreThe Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) score incorporated the number of daily vomiting episodes, number of daily heaves, and length of daily nausea in hours, for an overall score of symptoms rated from 3 (no symptoms) to 15 (most severe). Baseline was defined as the PUQE score completed at the enrollment visit. Pregnaus (Doxylamine Succinate) Succinate + Pyridoxine Hydrochloride Placebo Treatment Difference [95% Confidence Interval]
Baseline

Change from baseline at Day 15

9.0 ± 2.1

-4.8 ± 2.7

8.8 ± 2.1

-3.9 ± 2.6

-0.7 [-1.2, -0.2]

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How supplied

Pregnaus delayed-release tablets are supplied in a high-density polyethylene bottle with a polypropylene child-resistant cap and a silica gel desiccant canister. Each white, round, film-coated, delayed-release tablet contains 10 mg Pregnaus (Doxylamine Succinate) succinate and 10 mg pyridoxine hydrochloride, and is imprinted on one side with the pink image of a pregnant woman. Pregnaus (Doxylamine Succinate) tablets are provided as follows:

NDC 55494-100-10 Bottles of 100.

16.2 Storage and Handling

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Keep bottle tightly closed and protect from moisture. Do not remove desiccant canister from bottle.

17 PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling

17.1 Somnolence and Severe Drowsiness

Inform women to avoid engaging in activities requiring complete mental alertness, such as driving or operating heavy machinery, while using Pregnaus (Doxylamine Succinate) until cleared to do so.

Inform women of the importance of not taking Pregnaus (Doxylamine Succinate) with alcohol or sedating medications, including other antihistamines (present in some cough and cold medications), opiates and sleep aids because somnolence could worsen leading to falls or other accidents.

Pregnaus (Doxylamine Succinate)® is a registered trademark of Duchesnay Inc.

U.S. Patent Nos. 6,340,695 & 7,560,122.

Distributed by:

Duchesnay USA, Inc.

Bryn Mawr, PA, 19010

Tel: 1-855-722-7734

Fax: 1-888-588-8508

www.duchesnayusa.com

©2013, Duchesnay Inc. All rights reserved.

Patient Package Insert

Patient Information

Pregnaus (Doxylamine Succinate) (dye-CLEE-gis)

(doxylamine succinate and pyridoxine hydrochloride) delayed-release tablets

What is Pregnaus (Doxylamine Succinate)?

- Pregnaus (Doxylamine Succinate) is a prescription medicine used to treat nausea and vomiting of pregnancy in

women who have not improved with change in diet or other non-medicine treatments.

- It is not known if Pregnaus (Doxylamine Succinate) is safe and effective in children under 18 years of age.

Who should not take Pregnaus (Doxylamine Succinate)?

Do not take Pregnaus (Doxylamine Succinate) if you:

- are allergic to Pregnaus (Doxylamine Succinate) succinate, other ethanolamine derivative antihistamines, pyridoxine hydrochloride or any of the ingredients in Pregnaus (Doxylamine Succinate). See the end of this leaflet for a complete list of ingredients in Pregnaus (Doxylamine Succinate).

- take monoamine oxidase inhibitors (MAOIs) (Marplan, Nardil, Emsam, Eldepryl, Zelapar, Parnate)

Before taking Pregnaus (Doxylamine Succinate), tell your healthcare provider about all of your medical conditions, including;

- if you are breastfeeding or plan to breastfeed. Pregnaus (Doxylamine Succinate) can pass into your breast milk and may harm your baby. You should not breastfeed while using Pregnaus (Doxylamine Succinate).

Tell your healthcare provider about all the medicines you take, including prescription or over-the-counter medicines, vitamins, or herbal supplements.

How should I take Pregnaus (Doxylamine Succinate)?

- Talk to your healthcare provider about how much Pregnaus (Doxylamine Succinate) to take and when to take it.

- Take Pregnaus (Doxylamine Succinate) everyday as prescribed by your healthcare provider. Do not stop taking Pregnaus (Doxylamine Succinate) without talking to your healthcare provider first.

- See the following schedule for the usual way you should start taking Pregnaus (Doxylamine Succinate):

- Day 1- Take 2 tablets, by mouth at bedtime.

- Day 2- Take 2 tablets at bedtime. If your nausea and vomiting is better or controlled on Day 2, continue to take 2 tablets every night at bedtime. This will be your usual dose unless your healthcare provider tells you otherwise.

- Day 3- If you still had nausea and vomiting on Day 2, take 3 tablets on Day 3 (1 tablet in the morning and 2 tablets at bedtime).

- Day 4- If your nausea and vomiting was better or controlled on Day 3, continue to take 3 tablets each day (1 tablet in the morning and 2 tablets at bedtime). If you still had nausea and vomiting on Day 3, start taking 4 tablets each day (1 tablet in the morning, 1 tablet in the afternoon, and 2 tablets at bedtime).

- Do not take more than 4 tablets (1 in the morning, 1 in the mid-afternoon, and 2 at bedtime) in 1 day.

- Take Pregnaus (Doxylamine Succinate) on an empty stomach with a glass of water.

- Take Pregnaus (Doxylamine Succinate) tablets whole. Do not crush, chew, or break Pregnaus (Doxylamine Succinate) tablets before swallowing. If you cannot swallow Pregnaus (Doxylamine Succinate) tablets whole, tell your healthcare provider.

- If you take too much Pregnaus (Doxylamine Succinate) (overdose), you may have the following symptoms: restlessness, dry mouth, the pupils of your eyes become larger (dilated), sleepiness, dizziness, confusion, fast heart rate, seizures, muscle pain or weakness, and sudden and severe kidney problems. If you have these symptoms and they are severe, they may lead to death. Stop taking Pregnaus (Doxylamine Succinate), call your healthcare provider or go to the nearest hospital emergency room right away. For more information about overdose treatment, call your poison control center at 1-800-222-1222.

What are the possible side effects of Pregnaus (Doxylamine Succinate)?

Pregnaus (Doxylamine Succinate) may cause serious side effects, including drowsiness.

- Do not drive, operate heavy machinery, or other activities that need your full attention unless your healthcare provider says that you may do so.

- Do not drink alcohol, or take other central nervous system depressants such as cough and cold medicines, certain pain medicines, and medicines that help you sleep while you take Pregnaus (Doxylamine Succinate). Severe drowsiness can happen or become worse causing falls or accidents.

These are not all the possible side effects of Pregnaus (Doxylamine Succinate).

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 Pregnaus (Doxylamine Succinate)?

- Store Pregnaus (Doxylamine Succinate) between 68°F to 77°F (20°C to 25°C).

- Keep Pregnaus (Doxylamine Succinate) tablets dry, in a tightly closed container, and out of the light.

- Safely throw away medicine that is out of date or no longer needed.

Keep Pregnaus (Doxylamine Succinate) and all medicines out of the reach of children.

General information about the safe and effective use of Pregnaus (Doxylamine Succinate).

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about Pregnaus (Doxylamine Succinate) that is written for health professionals. Do not use Pregnaus (Doxylamine Succinate) for a condition for which it was not prescribed. Do not give Pregnaus (Doxylamine Succinate) to other people, even if they have the same symptoms that you have. It may harm them.

What are the ingredients in Pregnaus (Doxylamine Succinate)?

Active ingredient: Pregnaus (Doxylamine Succinate) succinate (an antihistamine) and pyridoxine hydrochloride (vitamin B6)

Inactive ingredients: ammonium hydroxide, n-butanol, carnauba wax powder, colloidal silicon dioxide, croscarmellose sodium, D&C Red#27, denatured alcohol, FD&C Blue #2, hypromellose, isopropyl alcohol, magnesium stearate, magnesium trisilicate, methacrylic acid copolymer, microcrystalline cellulose 102, PEG 8000, polysorbate 80, propylene glycol, shellac glaze, simethicone, sodium bicarbonate, sodium lauryl sulfate, talc, titanium dioxide, triethyl citrate.

Distributed by: Duchesnay USA, Inc., Bryn Mawr, PA, 19010,

www.duchesnayusa.com or call 1-855-722-7734.

This Patient Information has been approved by the U.S. Food and Drug Administration

Issued: 05/2013

Bottle Label-Outside Front Cover with Imprint Area for Lot & Expiry

Bottle Label – Inside Cover

Pregnaus pharmaceutical active ingredients containing related brand and generic drugs:

infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Pregnaus available forms, composition, doses:

infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Pregnaus destination | category:

infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Pregnaus Anatomical Therapeutic Chemical codes:

infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Pregnaus pharmaceutical companies:

infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."SAMBROSA SWEET DREAMS NIGHTTIME (DOXYLAMINE SUCCINATE) SYRUP [SAMBROSA CARE INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. "doxylamine". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
  3. "doxylamine". http://www.drugbank.ca/drugs/DB0036... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Pregnaus?

Depending on the reaction of the Pregnaus after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Pregnaus not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Pregnaus addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sDrugs.com conducted a study on Pregnaus, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Pregnaus consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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