CIZIGO

What it is

CIZIGO is a fixed-dose combination tablet containing 20 mg of cinnarizine and 40 mg of dimenhydrinate. The tablets are white to almost white, round, biconvex uncoated tablets 8 mm in diameter. Diphenhydramine is a potent inhibitor of histamine H1 receptors and muscarinic acetylcholine receptors, whilst cinnarizine is a potent inhibitor of histamine H1 and H4 receptors and dopamine D2 receptors and a less potent inhibitor of pressure-sensitive potassium channels and serotonin 2 receptors. The combination provides a product with a dual mechanism of action, with cinnarizine primarily acting peripherally on the labyrinth, and dimenhydrinate acting predominately centrally on the vestibular nuclei and related vegetative centres in the brainstem.

Approved indications

— Short-term, symptomatic treatment of vertigo of various causes, in adults who have not responded to alternative treatments.

Dosing overview

The recommended dose for adults is one tablet three times daily. The lowest dose for the shortest duration to achieve symptom control should be used, and the recommended dose should not be exceeded. CIZIGO tablets should be swallowed without chewing with some liquid after meals to minimise any gastric irritation. In general, the duration of treatment should not exceed four weeks, and patients should undergo a reassessment of the risk/benefit if treatment beyond 4 weeks is contemplated.

Key safety warnings

Extrapyramidal effects including tremor, dyskinesia, parkinsonism, tardive dyskinesia and akathisia have been reported rarely with cinnarizine, and these effects are more likely to occur in older patients (over 60 years), women, those on high doses (over 150 mg daily) and those with prolonged exposure to cinnarizine. Patients should be advised to cease treatment with CIZIGO immediately and seek medical advice if any abnormal movements such as shaking, twitching or twisting movements, muscle stiffness, restless legs, stiff posture, slowed shuffling walk or a need to be in constant motion arise. Cinnarizine/dimenhydrinate tablets should be used with caution in patients with conditions that might be aggravated by anticholinergic therapy, for example raised intra-ocular pressure, pyloro-duodenal obstruction, prostatic hypertrophy, hypertension, hyperthyroidism or severe coronary heart disease. In common with other antihistamines, cinnarizine/dimenhydrinate tablets may potentiate the sedative effects of central nervous system depressants including alcohol, barbiturates, narcotic analgesics and tranquillisers, and patients should be advised to avoid alcoholic drinks. Cinnarizine/dimenhydrinate tablets may cause drowsiness, especially at the start of treatment, and patients affected in this way should not drive or operate machinery.

Contraindications

CIZIGO is contraindicated in patients with hypersensitivity to cinnarizine, dimenhydrinate, diphenhydramine, other antihistamines of a similar structure, or to any of the excipients. It is contraindicated in patients with a creatinine clearance of ≤25 mL/min (severe renal impairment). CIZIGO is contraindicated in patients with severe hepatic impairment. It is contraindicated in patients with angle-closure glaucoma, convulsions, suspicion of raised intracranial pressure, alcohol abuse or urine retention due to urethroprostatic disorders. CIZIGO is contraindicated for use in children under 6 years of age because of the potential for fatal respiratory depression, psychiatric and central nervous system events. CIZIGO should not be given to children or adolescents aged less than 18 years. CIZIGO should not be given to patients with pre-existing extrapyramidal movement disorders such as Parkinson's disease.

Regulatory history

The TGA approval decision was made on December 21, 2018. CIZIGO cinnarizine 20 mg/dimenhydrinate 40 mg uncoated tablets were first listed on the ARTG on 2019-01-08.