Generic Name

H1‑histamine receptor antagonist

Mechanism

Meclizine blocks peripheral and central H1 receptors.
• Peripheral blockade reduces histamine‑induced vasodilation and smooth‑muscle contraction in the gut, thereby decreasing nausea.
• Central action on the vestibular nuclei and the vomiting center in the medulla suppresses the vestibular‑induced emetic reflex.

Its anticholinergic properties (weak muscarinic blockade) further contribute to vestibular inhibition and dry‑mouth effect.

Pharmacokinetics

• Absorption: ~75‑80 % bioavailability; peak plasma concentration 1–2 h post‑oral dose.
• Distribution: High lipophilicity; extensive penetration of the blood‑brain barrier; volume of distribution ≈ 0.6 L/kg.
• Metabolism: Hepatic CYP2D6‑dependent N‑demethylation → active metabolite (2‑(2‑hydroxy‑4‑pyridyl)‑1‑pyrrolidinyl‑ethyl).
• Elimination: Primarily renal (≈ 70 % unchanged); terminal half‑life 4–6 h.
• Drug interactions: Potentiated by CNS depressants (benzodiazepines, opioids); CYP2D6 inhibitors (fluoxetine) may increase exposure.

Indications

• Acute and chronic motion sickness (in‑flight, sea, road).
• Vertigo secondary to vestibular disorders (BPPV, Ménière’s disease).
• Nausea and vomiting associated with migraine, chemotherapy, or surgical procedures.
• Adjunct to anti‑emetic regimens for postoperative nausea and vomiting.

Contraindications

• Hypersensitivity to meclizine or related phenothiazines.
• Acute angle‑closure glaucoma, uncontrolled urinary retention.
• Severe hepatic or renal impairment (dose adjustment or avoidance).
• Pediatric <1 year old; pregnancy category C (limited safety data).
• Drug‑drug interactions: CNS depressants, alcohol, anticholinergics.

Dosing

• Motion sickness: 25 mg 30 min before travel.
• Vertigo: 25–50 mg BID; titrate to ≤ 100 mg/d.
• PONV: 25–50 mg 30 min pre‑op, repeat 6–8 h post‑op.
• Migraine: 25–50 mg 30 min before onset; repeat 6 h if needed (max 200 mg/day).
• Taper: Gradual dose reduction to prevent rebound nausea.

Adverse Effects

Common
• Drowsiness, fatigue
• Dry mouth, blurred vision
• Urinary hesitancy
• Somnolent “cheese‑cake” sleep

Serious
• Severe anticholinergic syndrome (dehydration, hyperthermia)
• Exacerbation of glaucoma or urinary retention
• Rare allergic reactions (rash, angioedema)
• CNS depression in overdose (severe somnolence, seizures).

Monitoring

• Baseline: Visual acuity, intra‑ocular pressure (in glaucoma patients), renal and liver function.
• Therapeutic: Patient‑reported dizziness or excessive sleepiness.
• Post‑treatment: Evaluate for rebound vertigo or nausea after dose taper.
• Drug‑interaction screen: Concomitant CNS depressants, serotonergic agents.

Clinical Pearls

1. “Cheese‑cake” sleep – Because of strong central H1 blockade, patients often complain of a “cheese‑cake” dream‑like sleep; counsel them on safe driving practices for 24 h after dosing.

2. CYP2D6 polymorphism – Poor metabolizers may experience heightened anticholinergic effects; consider the 25 mg maintenance dose for those on fluoxetine or paroxetine.

3. Combination therapy – Pairing meclizine with a 5‑HT3 antagonist (ondansetron) provides superior PONV control compared to either alone.

4. Bipolar disorder – Meclizine’s antipsychotic‑like properties can destabilize mood; monitor closely if used in patients with bipolar disorder.

5. Pediatric caution – While effective for children over 1 yr, the risk of excessive sedation is higher; start at the lowest dose and titrate slowly.

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• Key references

1. Brunton LL, et al. *Goodman & Gilman's: The Pharmacological Basis of Therapeutics* (13th ed., 2023).

2. American Academy of Otolaryngology‑Head & Neck Surgery. Clinical practice guideline: Vertigo and dizziness (2024 update).

3. Mayo Clinic Proceedings. “Mechanisms and management of motion sickness.” 2022.

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