Cinarin

Approved Indications:

• Motion Sickness (Prevention and Treatment):
  Prevention and control of symptoms such as nausea, vomiting, and vertigo due to motion sickness (travel-related).
• Vertigo and Vestibular Disorders:
  Treatment of vertigo, dizziness, tinnitus, and nystagmus associated with:
• Ménière’s disease
• Labyrinthitis
• Vestibular neuritis
• Other vestibular disorders
• Peripheral Circulatory Disorders (Supportive Therapy):
  As adjunct therapy in conditions like:
• Raynaud’s syndrome
• Cerebral circulatory insufficiency
• Vascular origin vertigo or hearing loss
• Acrocyanosis

Off-label/Clinically Accepted Uses:

• Migraine prophylaxis (especially vestibular migraine)
• Adjunctive treatment in cerebrovascular insufficiency
• As part of combined therapy in some antihistamine-resistant nausea/vomiting conditions

Adults:

• Motion Sickness:
  30 mg taken 2 hours before travel, then 15 mg every 8 hours during the journey, if needed.
• Vertigo and Vestibular Disorders:
  25 mg taken 3 times daily (total 75 mg/day). Dose may be reduced based on tolerance.
• Peripheral Circulatory Disorders:
  25–75 mg daily in divided doses.

Pediatrics (≥5 years):

• Motion Sickness:
  15 mg taken 2 hours before travel, then 7.5–15 mg every 8–12 hours if necessary.
  Use cautiously in children; dosing should be guided by physician.

Elderly:

• Initiate at the lowest effective dose due to potential increased sensitivity to anticholinergic and CNS effects.

Hepatic/Renal Impairment:

• Use with caution; no specific dose adjustment, but close monitoring is recommended.

Administration Route:
Oral—preferably taken after meals to reduce gastrointestinal discomfort. Swallow tablets with water; do not chew.

Cinnarizine is a selective calcium channel blocker with additional antihistaminic (H1-receptor antagonist) and anticholinergic properties. It inhibits calcium influx into vascular smooth muscle, leading to vasodilation, especially in cerebral, vestibular, and peripheral vessels. In the vestibular system, cinnarizine stabilizes nerve excitability, thereby suppressing vertigo and nausea. By antagonizing histamine H1-receptors in the vomiting center and vestibular apparatus, it also reduces motion-induced nausea and vomiting. Its sedative effects contribute to symptom control in vertigo and motion sickness.

• Absorption:
  Well absorbed orally; peak plasma concentration reached within 2–4 hours after ingestion.
• Bioavailability:
  Moderate oral bioavailability due to first-pass metabolism.
• Distribution:
  Widely distributed; crosses the blood-brain barrier. High affinity for lipid-rich tissues.
• Metabolism:
  Extensively metabolized in the liver by CYP450 enzymes, especially CYP2D6.
• Half-life:
  Approximately 3–6 hours.
• Excretion:
  Mainly excreted via feces; <10% eliminated in urine. Biliary excretion is the primary route.

• Pregnancy:
  Not assigned a specific FDA category. Use only if clearly needed. Animal data suggest no major teratogenicity, but human data are limited.
• Lactation:
  It is unknown whether cinnarizine is excreted into human breast milk. Caution is advised. Avoid use unless the benefit outweighs the risk to the infant.

• Therapeutic Class: Antivertigo agent
• Pharmacologic Class: Selective calcium channel blocker with antihistaminic and vasodilatory effects
• Subclass: H1 receptor antagonist with vestibular suppressant action

• Known hypersensitivity to cinnarizine or any component of the formulation
• Parkinson’s disease or other extrapyramidal disorders (may worsen symptoms)
• Severe hepatic impairment
• Porphyria
• Infants and children <5 years (due to CNS side effects)

• Extrapyramidal Symptoms: Use with caution in elderly and patients with movement disorders; may cause or worsen Parkinsonism.
• CNS Depression: May cause sedation; avoid operating machinery or driving.
• Anticholinergic Effects: Use with caution in patients with glaucoma, urinary retention, or prostatic hypertrophy.
• Hepatic Impairment: Use cautiously due to hepatic metabolism.
• Long-Term Use: Not recommended due to risk of extrapyramidal adverse effects.
• Alcohol: May potentiate sedative effects—avoid concurrent use.

Common:

• Drowsiness, sedation
• Dry mouth
• Gastrointestinal upset (nausea, epigastric pain)
• Weight gain (with long-term use)

Less Common:

• Headache
• Sweating
• Fatigue

Serious / Rare:

• Extrapyramidal symptoms (tremor, rigidity, bradykinesia)
• Depression
• Allergic skin reactions (rash, urticaria)
• Agranulocytosis (very rare)
• Hepatotoxicity (rare)

Onset: Sedation may occur within 1–2 hours of dosing; extrapyramidal symptoms may arise after prolonged use.

• Alcohol and CNS Depressants (e.g., benzodiazepines, opioids): Increased sedation and CNS depression.
• Anticholinergic Agents: Additive anticholinergic side effects.
• Levodopa: Antagonizes the therapeutic effect of levodopa in Parkinson’s disease.
• Antihypertensives: Possible additive hypotensive effect.
• CYP2D6 Inhibitors (e.g., fluoxetine, paroxetine): May alter metabolism and plasma levels of cinnarizine.

• Some national formularies have advised limited long-term use in elderly patients due to Parkinsonism risk.
• Recent guidelines emphasize cinnarizine as a first-line treatment in peripheral vestibular disorders and motion sickness.
• Not recommended for long-term prophylaxis in chronic cerebrovascular insufficiency.

• Temperature: Store below 25°C (77°F)
• Humidity: Keep in a dry place; protect from moisture
• Light Protection: Store in original container, protected from direct light
• Handling: Keep out of reach of children; do not use beyond expiry date
• Reconstitution: Not applicable (solid oral dosage form)