Cyclizine Hydrochloride

Approved Indications:

• Nausea and Vomiting:
• Prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness
• Management of postoperative nausea and vomiting (PONV)
• Vestibular Disorders:
• Symptomatic relief in Ménière’s disease, labyrinthitis, and other vestibular disturbances causing vertigo
• Radiotherapy-Induced Nausea and Vomiting: As adjunct therapy in patients undergoing radiation therapy
• Drug-induced or disease-related emesis: Including nausea and vomiting due to opioid analgesics, general anesthesia, or gastrointestinal irritation

Clinically Accepted Off-label Uses:

• Hyperemesis Gravidarum: Used as an alternative antiemetic in pregnancy when first-line agents fail
• Migraine-associated nausea
• Palliative care: Control of nausea and vomiting in advanced illness when standard agents are not suitable

Routes of Administration:
• Oral (tablets or syrup)
• Intramuscular (IM)
• Intravenous (IV) – slow injection
• Subcutaneous (SC)

Adults:

• Motion Sickness:
• Oral: 50 mg up to three times daily
• IM/IV/SC: 50 mg as needed, usually not exceeding 200 mg/day
• Postoperative or other nausea:
• IM/IV/SC: 50 mg every 4–6 hours as required
• Maximum daily dose: 200 mg in divided doses

Pediatrics (≥6 years):

• Oral: 25 mg up to three times daily
• Parenteral use in children is generally not recommended without specialist guidance

Elderly:

• Start at lower end of dosing range due to increased sensitivity to anticholinergic effects

Renal/Hepatic Impairment:

• Use with caution; dose adjustment may be necessary depending on clinical response and tolerability

Cyclizine is a first-generation H1 histamine receptor antagonist with strong anticholinergic (muscarinic-blocking) and central sedative properties. It acts primarily on the chemoreceptor trigger zone (CTZ) and the vestibular apparatus, where it inhibits histaminergic and cholinergic transmission responsible for nausea, vomiting, and motion-induced vertigo. By depressing labyrinthine function and vestibular stimulation, it stabilizes the threshold for motion sensitivity. Its central antimuscarinic effects also contribute to antiemetic efficacy and mild sedation.

• Absorption: Rapidly absorbed from the gastrointestinal tract after oral administration
• Bioavailability: High (exact value not well-defined)
• Onset of Action: Within 30 minutes orally; faster with parenteral routes
• Peak Plasma Concentration: ~2–3 hours post-oral dose
• Distribution: Widely distributed; crosses blood-brain barrier
• Metabolism: Extensively hepatic via CYP450 enzymes (primarily CYP2D6)
• Active Metabolites: None known to contribute significantly to pharmacologic activity
• Elimination: Primarily via the urine as metabolites
• Half-life: Approximately 20 hours

• Pregnancy:
  Categorized historically as Pregnancy Category B (no evidence of harm in animals; human data limited). Considered safe for occasional use in early pregnancy (e.g., hyperemesis gravidarum), but only under physician supervision.
• Lactation:
  Excreted into breast milk in small amounts. May cause infant drowsiness or irritability. Use with caution during breastfeeding; monitor infant for sedation.
• Recommendation:
  Avoid chronic use during pregnancy or lactation unless clearly indicated.

• Primary Class: Antihistamine
• Subclass: First-generation H1 receptor antagonist; Antiemetic / Antivertigo agent

• Known hypersensitivity to cyclizine or other piperazine derivatives
• Severe hepatic impairment
• Use in neonates or infants under 6 years (oral) or under 1 year (injectable)
• Patients with porphyria (may precipitate acute attacks)
• Acute urinary retention or bladder obstruction
• Narrow-angle glaucoma (due to anticholinergic effects)
• Concurrent use of other CNS depressants unless medically justified

• CNS Effects: May cause drowsiness, dizziness, and impaired alertness—avoid operating machinery or driving
• Anticholinergic burden: Use cautiously in elderly and patients with:
• Prostatic hypertrophy
• Urinary retention
• Cardiac arrhythmias
• Cognitive impairment
• Alcohol potentiation: CNS depressant effects may be enhanced by alcohol
• Parenteral administration: Rapid IV injection may cause transient hypotension or tachycardia
• Seizure threshold: May lower seizure threshold in predisposed individuals
• Monitor for paradoxical excitation in pediatric patients

Common (Dose-related or transient):

• CNS: Drowsiness, dizziness, incoordination, headache
• GI: Dry mouth, nausea, constipation
• Eyes: Blurred vision, dry eyes

Less Common:

• Palpitations, urinary retention, photosensitivity
• Tachycardia, hypotension (especially with IV use)

Rare but Serious:

• Hypersensitivity reactions (rash, urticaria, anaphylaxis)
• Confusion or hallucinations (especially in elderly)
• Seizures (in patients with predisposing factors)
• Extrapyramidal symptoms (rare)

Onset: Typically within 30–60 minutes after oral administration

• CNS depressants (e.g., alcohol, opioids, benzodiazepines):
• Additive sedation and cognitive impairment
• Anticholinergic drugs (e.g., tricyclic antidepressants, antipsychotics):
• Increased risk of dry mouth, urinary retention, blurred vision, and confusion
• Monoamine oxidase inhibitors (MAOIs):
• Prolong and intensify anticholinergic effects—concurrent use not advised
• CYP2D6 inhibitors (e.g., fluoxetine, paroxetine):
• May alter cyclizine metabolism, potentially increasing toxicity

• Updated clinical reviews reaffirm cyclizine’s place in therapy for motion sickness, vestibular nausea, and palliative nausea where dopamine antagonists or 5-HT3 antagonists are unsuitable.
• Still widely used in pregnancy-associated nausea, though pyridoxine-doxylamine combination is preferred first-line.
• Included in WHO palliative care guidelines as a symptomatic antiemetic agent.

• Temperature: Store at 15°C to 25°C (59°F to 77°F)
• Humidity & Light: Protect from moisture and direct light
• Handling:
• Do not freeze injectable forms
• Oral tablets should be stored in a dry, tightly closed container
• Shelf life: As per manufacturer labeling; typically 24–36 months unopened