Brand names: Bonjesta (combination), Diclegis (combination), Good Sense Sleep Aid, Unisom
Drug class: First Generation Antihistamines

Medically reviewed by Drugs.com on Sep 16, 2024. Written by ASHP.

Introduction

First generation antihistamine; an ethanolamine derivative.

Uses for Doxylamine

Insomnia

Self-medication for short-term management of insomnia, particularly in individuals who have difficulty falling asleep.

Safety and efficacy not fully established; however, FDA states that, pending further accumulation of data, doxylamine-containing nighttime sleep aids approved for this use may continue to be marketed in the US.

Nausea and Vomiting of Pregnancy

Used in fixed combination with pyridoxine for treatment of nausea and vomiting of pregnancy in women not responding to conservative management.

Not studied in patients with hyperemesis gravidarum.

Allergic Rhinitis

Temporary relief of rhinorrhea, sneezing, lacrimation, itching eyes, or oronasopharyngeal itching associated with allergic rhinitis (e.g., hay fever) or other upper respiratory allergies.

Doxylamine Dosage and Administration

Administration

Oral Administration

Administer orally as tablets.

Delayed-release and extended-release tablets: Administer on an empty stomach with a glass of water. Swallow whole; do not chew, crush, or split.

Dosage

Available as doxylamine succinate; dosage expressed in terms of the salt.

Also available as fixed-combination tablets containing doxylamine succinate and pyridoxine hydrochloride.

Individualize dosage according to patient’s response and tolerance.

Pediatric Patients

Insomnia

Oral

Self-medication in children ≥12 years of age: 25 mg 30 minutes before retiring or as directed by a clinician.

Allergic Rhinitis

Children 2 to <6 years of age: 1.9–3.125 mg every 4–6 hours, not to exceed 18.75 mg in 24 hours.

Children 6 to <12 years of age: For self-medication, 3.75–6.25 mg every 4–6 hours, not to exceed 37.5 mg in 24 hours. Alternatively, under the direction of a clinician, up to 12.5 mg every 4–6 hours, or 2 mg/kg or 60 mg/m² daily in divided doses, not to exceed 75 mg daily.

Children ≥12 years of age: For self-medication, 7.5–12.5 mg every 4–6 hours, not to exceed 75 mg in 24 hours. Alternatively, under the direction of a clinician, up to 25 mg every 4–6 hours, or 2 mg/kg or 60 mg/m² daily in divided doses, not to exceed 150 mg daily.

Adults

Insomnia

Oral

Self-medication: 25 mg 30 minutes before retiring or as directed by a clinician.

Nausea and Vomiting of Pregnancy

Oral

Doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg delayed-release tablets (Diclegis): Initially, 2 tablets at bedtime. If symptoms the next day are adequately controlled, continue this dosage daily at bedtime. If symptoms persist into the afternoon of day 2, add 1 tablet in the morning on day 3. If symptoms are adequately controlled, continue this daily dosage regimen (1 tablet in the morning and 2 tablets at bedtime). If symptoms persist, add 1 tablet midafternoon on day 4.

Doxylamine succinate 20 mg/pyridoxine hydrochloride 20 mg extended-release tablets (Bonjesta): Initially, 1 tablet at bedtime. If symptoms the next day are adequately controlled, continue this dosage daily at bedtime. If symptoms persist, add 1 tablet in the morning to the regimen.

Delayed- or extended-release tablets: Take on schedule, not on an as-needed basis. Reassess need for continued therapy as pregnancy progresses.

Allergic Rhinitis

Oral

Self-medication: 7.5–12.5 mg every 4–6 hours, not to exceed 75 mg in 24 hours. Alternatively, under the direction of a clinician, up to 25 mg every 4–6 hours, or 2 mg/kg or 60 mg/m² daily in divided doses, not to exceed 150 mg daily.

Prescribing Limits

Pediatric Patients

Insomnia

Oral

Self-medication in children ≥12 years of age: Maximum 2 weeks.

Allergic Rhinitis

Oral

Children 2 to <6 years of age: Maximum 18.75 mg in 24 hours.

Children 6 to <12 years of age: For self-medication, maximum 37.5 mg in 24 hours. Under the direction of a clinician, maximum 75 mg daily.

Children ≥12 years of age: For self-medication, maximum 75 mg in 24 hours. Under the direction of a clinician, maximum 150 mg daily.

Adults

Insomnia

Oral

Self-medication: Maximum 2 weeks.

Allergic Rhinitis

Oral

For self-medication, maximum 75 mg in 24 hours. Under the direction of a clinician, maximum 150 mg daily.

Nausea and Vomiting of Pregnancy

Oral

Doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg delayed-release tablets (Diclegis): Maximum 4 tablets daily (i.e., 1 tablet in the morning, 1 tablet midafternoon, 2 tablets at bedtime).

Doxylamine succinate 20 mg/pyridoxine hydrochloride 20 mg extended-release tablets (Bonjesta): Maximum 2 tablets daily (i.e., 1 tablet in the morning, 1 tablet at bedtime).

Cautions for Doxylamine

Contraindications

Known hypersensitivity to doxylamine, other ethanolamine derivative antihistamines, or any ingredient in the formulation.

Doxylamine/pyridoxine fixed-combination therapy: Concomitant use of MAO inhibitors. (See Specific Drugs and Laboratory Tests under Interactions.)

Warnings/Precautions

Warnings

Use of Fixed Combinations

When used in fixed combination with pyridoxine, consider usual cautions, precautions, and contraindications associated with pyridoxine in addition to those associated with doxylamine.

Concomitant Diseases

Because of possible anticholinergic effects (e.g., dryness of mouth, nose, and throat; dysuria; urinary retention), patients with glaucoma, respiratory conditions (e.g., emphysema, chronic bronchitis), or difficulty urinating due to prostatic hypertrophy should consult a clinician before initiating therapy with doxylamine.

Use with caution, if at all, in patients with asthma, increased IOP, angle-closure glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, or bladder neck obstruction.

Use not recommended, unless under the direction of a clinician, in patients who have a breathing problem (e.g., emphysema, chronic bronchitis). Use generally not recommended in asthmatics who previously experienced a serious antihistamine-induced adverse bronchopulmonary effect.

CNS Effects

Risk of marked drowsiness. Caution when driving a motor vehicle or operating machinery. (See CNS Depressants under Interactions and also see Advice to Patients.)

Possible excitability (especially in children). (See Pediatric Use under Cautions.)

General Precautions

Duration of Therapy

When used for insomnia, discontinue therapy and consult a clinician if insomnia persists for >2 weeks.

Specific Populations

Pregnancy

Category A.

Doxylamine/pyridoxine in fixed combination intended for use in the management of nausea and vomiting of pregnancy. No increased risk of congenital malformations associated with the drugs reported in epidemiologic studies of pregnant women.

Women considering self-medication with doxylamine during pregnancy should consult a health professional for advice regarding the relative risks and benefits of such therapy.

Lactation

Expected to be distributed into milk. Discontinue nursing or the drug. Do not use doxylamine/pyridoxine fixed-combination therapy in nursing women.

Excitement, irritability, and sedation reported in infants presumably exposed to doxylamine through human milk; infants with respiratory syndromes (e.g., apnea) may be particularly at risk.

Pediatric Use

Use not recommended in premature or full-term neonates.

Possible paradoxical excitement (e.g., restlessness, insomnia, tremors, euphoria, nervousness, delirium, palpitation, seizures).

Safety and efficacy of doxylamine as a nighttime sleep aid in children <12 years of age not established. Consider risk of possible CNS stimulation when used as nighttime sleep aids.

Use as an antihistamine only under the direction of a clinician in children 2 to <6 years of age; use in children <2 years of age not recommended.

Safety and efficacy of doxylamine/pyridoxine in fixed combination in children <18 years of age not established.

Risk of overdosage of doxylamine in children; manifestations include coma, generalized tonic-clonic (grand mal) seizures, cardiorespiratory arrest (children at high risk), death.

Risk of overdosage and toxicity (including death) in children <2 years of age receiving OTC preparations containing antihistamines, cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection. Limited evidence of efficacy for these preparations in this age group; appropriate dosages not established. Therefore, FDA recommended not to use such preparations in children <2 years of age; safety and efficacy in older children under evaluation. Because children 2–3 years of age also are at increased risk of overdosage and toxicity, some manufacturers of oral nonprescription cough and cold preparations agreed to voluntarily revise the product labeling to state that such preparations should not be used in children <4 years of age. FDA recommends that parents and caregivers adhere to dosage instructions and warnings on the product labeling that accompanies the preparation and consult a clinician about any concerns. Clinicians should ask caregivers about use of OTC cough/cold preparations to avoid overdosage.

Geriatric Use

Possible increased risk of dizziness, sedation, and hypotension.

Common Adverse Effects

Drowsiness.

Drug Interactions

Specific Drugs and Laboratory Tests

Doxylamine Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations occur within 2–3 hours after oral administration.

Absorbed from the GI tract, mainly in the jejunum.

Doxylamine/pyridoxine delayed-release tablets in fixed combination: Peak plasma concentrations of doxylamine occur about 7.2 hours after oral administration.

Doxylamine/pyridoxine extended-release tablets in fixed combination: Peak plasma concentrations of doxylamine occur about 4.5 hours after oral administration.

One doxylamine succinate 20 mg/pyridoxine hydrochloride 20 mg extended-release tablet was bioequivalent to 2 doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg delayed-release tablets.

One doxylamine succinate 20 mg/pyridoxine hydrochloride 20 mg extended-release tablet given twice daily for 11 days was bioequivalent to 4 doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg delayed-release tablets daily given as 1 tablet in the morning, 1 tablet in the afternoon, and 2 tablets at bedtime.

Doxylamine/pyridoxine delayed-release tablets in fixed combination: Accumulation of doxylamine observed following multiple-dose administration; time to reach peak concentration not affected by multiple doses.

Onset

Sedative effects occur approximately 30 minutes after oral administration.

Effect of Food

Delayed- or extended-release tablets (doxylamine/pyridoxine in fixed combination): Administration of food may delay absorption and onset of action; extent of doxylamine absorption not affected. (See Administration under Dosage and Administration.)

Distribution

Distribution likely into human milk because of drug's low molecular weight.

Elimination

Metabolism

Metabolized in the liver by N-dealkylation to N-desmethyldoxylamine and N,N-didesmethyldoxylamine.

Half-life

Approximately 10 hours.

Delayed-release tablets (doxylamine/pyridoxine in fixed combination): Approximately 12.5 hours.

Extended-release tablets (doxylamine/pyridoxine in fixed combination): Approximately 11.9 hours.

Excretion

Principal metabolites, N-desmethyldoxylamine and N,N-didesmethyldoxylamine, excreted mainly by the kidneys.

Stability

Storage

Oral

Tablets

Doxylamine tablets: 20–25°C.

Doxylamine/pyridoxine delayed-release and extended-release tablets: 20–25°C (may be exposed to 20–25°C); protect from moisture. Keep bottle tightly closed; do not remove desiccant canister from bottle.

Actions

• Blocks H₁-receptor sites and prevents the action of histamine on the cell.

• Suppresses flare and pruritus that accompany the endogenous release of histamine.

• Exhibits some activities common to anticholinergics, ganglionic and adrenergic blocking agents, local anesthetics, and antispasmodics.

• Antihistamines do not block the stimulating effect of histamine on gastric acid secretion, which is mediated by the H₂-receptors of the parietal cells.

Advice to Patients

• Risk of marked drowsiness; avoid alcohol and use caution when driving or operating machinery. Importance of advising women receiving doxylamine/pyridoxine in fixed combination to not engage in such activities until clinician consulted.

• When used for insomnia, consult a clinician if sleeplessness persists continuously for >2 weeks.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses. Importance of patients already receiving another CNS depressant (e.g., sedatives, tranquilizers) not undertaking self-medication without first consulting a clinician. Importance of advising women receiving doxylamine/pyridoxine in fixed combination to avoid taking the drug concomitantly with alcohol or other CNS depressants.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; advise women considering self-medication with doxylamine during pregnancy to consult a clinician regarding the relative risks and benefits of such therapy.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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