Unisom - Drug Monograph

Introduction

Unisom is an over-the-counter sleep aid containing doxylamine succinate as its active ingredient. It belongs to the ethanolamine class of antihistamines and is primarily marketed for the short-term treatment of occasional insomnia. First approved by the FDA in the 1970s, doxylamine has both sedative and anticholinergic properties that make it effective for sleep induction.

Mechanism of Action

Doxylamine succinate is a first-generation ethanolamine antihistamine that competitively inhibits histamine H1 receptors in the central nervous system. Its sedative effects result from its ability to cross the blood-brain barrier and block central H1 receptors, particularly in the hypothalamus and brainstem. Additionally, doxylamine possesses significant anticholinergic activity through muscarinic receptor blockade, which contributes to its sedating properties and side effect profile.

Indications

• Short-term treatment of occasional insomnia
• Sleep onset and maintenance difficulties (typically for 2 weeks or less)
• Off-label uses include: management of nausea and vomiting in pregnancy (though other agents are preferred)

Dosage and Administration

• Geriatric patients: Consider lower starting dose due to increased sensitivity
• Hepatic impairment: Use with caution; consider dose reduction
• Renal impairment: Use with caution
• Pediatrics: Not recommended for children under 12 years

Pharmacokinetics

Contraindications

• Hypersensitivity to doxylamine succinate or any component of the formulation
• Concomitant use with monoamine oxidase inhibitors (MAOIs)
• Narrow-angle glaucoma
• Severe urinary retention
• Severe hepatic impairment
• Asthma or chronic obstructive pulmonary disease (relative contraindication)

Warnings and Precautions

• CNS Depression: May impair mental and physical abilities; caution when operating machinery
• Next-day Impairment: Residual drowsiness may occur the following day
• Anticholinergic Effects: Use with caution in patients with prostate hypertrophy, cardiovascular disease, or hyperthyroidism
• Tolerance: May develop with prolonged use (beyond 2 weeks)
• Rebound Insomnia: May occur after discontinuation of prolonged therapy
• Pregnancy: Category B - use only if clearly needed; consult healthcare provider
• Breastfeeding: Excreted in breast milk; not recommended during nursing

Drug Interactions

• Alcohol: Additive CNS depression
• Other CNS depressants (benzodiazepines, opioids, barbiturates): Enhanced sedation
• MAOIs: Risk of hypertensive crisis
• Anticholinergic agents (tricyclic antidepressants, antipsychotics): Enhanced anticholinergic effects

• CYP2D6 inhibitors: May increase doxylamine levels
• Warfarin: Possible increased anticoagulant effect (case reports)

Adverse Effects

• Somnolence
• Dry mouth
• Dizziness
• Headache
• Gastrointestinal disturbances

• Severe hypersensitivity reactions
• Paradoxical excitation (especially in children)
• Urinary retention
• Visual disturbances
• Tachycardia
• Respiratory depression (in overdose)

Monitoring Parameters

• Sleep patterns and effectiveness
• Daytime drowsiness or impairment
• Anticholinergic side effects
• Mental status changes
• Signs of tolerance or dependence with prolonged use
• Renal and hepatic function in long-term use (if applicable)

Patient Education

• Use only as directed for short-term sleep difficulties
• Allow 7-8 hours for sleep after taking medication
• Avoid alcohol and other sedating medications
• Be cautious about driving or operating machinery the next day
• Do not use for more than 2 weeks without medical supervision
• Report any unusual side effects or lack of improvement
• Store safely away from children
• Consider non-pharmacological sleep hygiene measures first

References

1. FDA OTC Monograph for Nighttime Sleep-Aid Drug Products (21 CFR Part 338) 2. Neubauer DN. Current and Emerging Treatment of Insomnia. Psychiatr Clin North Am. 2021;44(2):303-318 3. TGA Approved Product Information: Doxylamine Succinate 4. American Academy of Sleep Medicine. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults. J Clin Sleep Med. 2017;13(2):307-349 5. Micromedex® Drug Information: Doxylamine Succinate 6. NIH MedlinePlus: Doxylamine - https://medlineplus.gov/druginfo/meds/a682537.html 7. Product labeling: Unisom SleepTabs® (doxylamine succinate)