Cinnarizine + Dimenhydrinate

Uses

Cinnarizine + Dimenhydrinate is used for the treatment of vertigo symptoms of various origins.

Cerebral circulatory disorders: Prophylaxis and maintenance therapy for symptoms of cerebral vascular spasms and arteriosclerosis, Sequelae of cerebral and cranial trauma, Postapoplectic disorders, Migraine.

Peripheral circulatory disorders: Prophylaxis and maintenance therapy for symptoms of vascular spasms and arteriosclerosis (obliterating arteritis, thromboangitis obliterans, Raynaud's disease, diabetes, acrocyanosis pernio, etc.) such as intermittent claudication,trophic disturbances, pregangrene, trophic and varicose ulcers, paraesthesia, nocturnal cramps,cold extremities.

Disorders of balance: Prophylaxis and maintenance therapy for symptoms of labyrinthine arteriosclerosis; vestibular irritability;Meniere's syndrome such as vertigo, dizziness, giddiness, syncopal attacks, tinnitus, nystagmus, nausea and vomiting. Prophylaxis of motion sickness.

Cinnarizine + Dimenhydrinate is also used to associated treatment for these conditions: Balance Disorders, Dizziness, Motion Sickness, Nausea, Peripheral Artery Disease (PAD), Raynaud's Phenomenon, Inadequate cerebral circulation, Peripheral vasculopathyDizziness, Labyrinthine disorder, Menière's Disease, Morning Sickness, Motion Sickness, Nausea, Nausea and vomiting, Post Operative Nausea and Vomiting (PONV), Vomiting, Radiation therapy induced nausea and vomiting

How Cinnarizine + Dimenhydrinate works

Cinnarizine inhibits contractions of vascular smooth muscle cells by blocking L-type and T-type voltage gated calcium channels. Cinnarizine has also been implicated in binding to dopamine D2 receptors, histamine H1 receptors, and muscarinic acetylcholine receptors.

Dimenhydrinate is a theoclate salt that separates into diphenhydramine and 8-chlorotheophylline. While the exact mechanism of action is unknown, diphenhydramine is theorized to reduce disturbances to equilibrium through antimuscarinic effects or histamine H1 antagonism. 8-chlorotheophylline may produce excitation through blocking adenosine receptors, reducing the drowsiness produced by diphenhydramine.

Dosage

Cinnarizine + Dimenhydrinate dosage

Adults: 1 tablet three times daily, to be taken unchewed with some liquid after meals.

Children and adolescents under the age of 18 years: Cinnarizine + Dimenhydrinate is not recommended in children and adolescents under the age of 18 years because there are no data available on the use of Cinnarizine + Dimenhydrinate in this age group.

Elderly: Dosage as for adults.

In general, the duration of treatment should not exceed four weeks. The physician shall decide whether longer treatment is required.

Side Effects

The most frequently occurring side-effects are somnolence and dry mouth. These reactions are usually mild and disappear within a few days even if treatment is continued. In addition the following adverse reactions are associated with dimenhydrinate and cinnarizine:

Dimenhydrinate: paradoxical excitability (especially in children), worsening of an existing angleclosure glaucoma and reversible agranulocytosis.

Cinnarizine: constipation, weight gain, tightness of the chest, cholestatic jaundice, extrapyramidal symptoms, lupus-like skin reactions, lichen planus.

Toxicity

Infants and children experiencing an overdose may lead to hallucinations, convulsions, or death. Adults experiencing an overdose may present with drowsiness, convulsions, coma, or respiratory depression. Treat overdoses with symptomatic and supportive measures including mechanically assisted ventilation.

In mice the oral LD₅₀ is 203 mg/kg, while in rats it is 1320 mg/kg. The intraperitoneal LD₅₀ in mice is 149 mg/kg.

Precaution

Patient with hypotension (high dose), Parkinson's disease, porphyria. Renal and hepatic impairment. Childn. Pregnancy and lactation.

Interaction

The anticholinergic and sedative effects of Cinnarizine & Dimenhydrinate may be potentiated by monoamine oxidase inhibitors. In common with other antihistamines, Cinnarizine & Dimenhydrinate may potentiate the sedative effects of CNS depressants including alcohol, barbiturates, narcotic analgesics and tranquillisers. Cinnarizine & Dimenhydrinate may also enhance the effects of antihypertensives, ephedrine and anticholinergics such as atropine and tricyclic antidepressants.

Volume of Distribution

The volume of distribution of dimenhydrinate is 3-4 L/kg.

Elimination Route

A 50 mg oral film coated tablet reaches a C_max of 72.6 ng/mL with a T_max of 2.7 hours. A 100 mg suppository reaches a C_max of 112.2 ng/mL with a T_max of 5.3 hours.

Half Life

The plasma elimination half life of dimenhydrinate is 5-8 hours.

Elimination Route

Dimenhydrinate is predominantly eliminated in the urine. 1-3% of the dissociated diphenhydramine is eliminated in the urine unchanged, while 64% of diphenhydramine is eliminated in the urine as metabolites. The elimination of dimenhydrinate has not been fully studied.

Pregnancy & Breastfeeding use

Pregnancy: The safety of Cinnarizine + Dimenhydrinate in human pregnancy has not been established.

Lactation: Dimenhydrinate and cinnarizine are excreted in human breast milk. Cinnarizine + Dimenhydrinate should not be taken by women who are breast feeding.

Contraindication

Contraindications are not known. Side-effects such as somnolence and gastrointestinal disturbances are extremely rare. They are transient and may be readily prevented by achieving the optimal dosage gradually. Combination therapy with other drugs is possible whenever indicated.

Special Warning

Children and adolescents under the age of 18 years: Revert is not recommended in children and adolescents under the age of 18 years because there are no data available on the use of Revert in this age group.

Elderly: Dosage as for adults. In general, the duration of treatment should not exceed four weeks. The physician shall decide whether longer treatment is required.

Acute Overdose

Symptoms of overdosage with Cinnarizine + Dimenhydrinate include drowsiness, dizziness and ataxia with anticholinergic effects such as dry mouth, flushing of the face, dilated pupils, tachycardia, pyrexia, headache and urinary retention. General supportive measures should be used to treat respiratory insufficiency or circulatory failure. Gastric lavage with isotonic sodium chloride solution is recommended. Cramp-like symptoms may be controlled by careful application of a short-acting barbiturate. In cases of marked central-anticholinergic effects, physostigmine (after physostigmine test) should be administered slowly intravenously (or, if necessary, intramuscularly): 0.03 mg/kg body weight (adults max. 2 mg, children max. 0.5 mg). Sufficient elimination can be achieved by means of haemoperfusion using activated charcoal.

Interaction with other Medicine

The anticholinergic and sedative effects of Cinnarizine + Dimenhydrinate may be potentiated by monoamine oxidase inhibitors. In common with other antihistamines, Cinnarizine + Dimenhydrinate may potentiate the sedative effects of CNS depressants including alcohol, barbiturates, narcotic analgesics and tranquillisers. Cinnarizine + Dimenhydrinate may also enhance the effects of antihypertensives, ephedrine and anticholinergics such as atropine and tricyclic antidepressants.

Storage Condition

Store below 30° C, away from light & moisture

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