Cinarizine

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CINNARIZINE

Composition:

Active substance: cinnarizine;

1 tablet contains cinnarizine 0.025 g (25 mg);

Excipients: lactose monohydrate, potato starch, magnesium stearate, colloidal anhydrous silicon dioxide, povidone.

Pharmaceutical form. Tablets.

Main physicochemical properties: white or almost white tablets.

Pharmacotherapeutic group. Agents used in vestibular disorders. ATC code N07C A02.

Pharmacological Properties.

Pharmacodynamics.

Cinnarizine inhibits the contraction of vascular smooth muscle cells by blocking calcium channels. In addition to direct calcium antagonism, cinnarizine reduces the contractile effects of vasoactive substances such as norepinephrine and serotonin by blocking receptor-operated calcium channels. The blockade of calcium influx into cells is tissue-selective and results in reduced vasoconstriction without affecting arterial blood pressure and heart rate.

Cinnarizine may additionally improve impaired microcirculation by increasing erythrocyte membrane elasticity and reducing blood viscosity. When cinnarizine is administered, cellular resistance to hypoxia increases.

Cinnarizine suppresses stimulation of the vestibular system, resulting in suppression of nystagmus and other vegetative disturbances. Cinnarizine prevents the occurrence of or alleviates acute attacks of vertigo.

Pharmacokinetics.

Absorption. Maximum plasma concentrations of cinnarizine are reached within 1\–3 hours after oral administration.

Distribution. Plasma protein binding is 91%.

Metabolism. Cinnarizine is metabolized primarily via CYP2D6.

Elimination. The elimination half-life from plasma ranges from 4 to 24 hours. One-third of metabolites are excreted in urine and two-thirds in feces.

Clinical characteristics.

Indications.

Cerebral circulation disorders:

• symptomatic treatment of cerebrovascular disorders, including dizziness, tinnitus, vascular headache, irritability, memory loss, and inability to concentrate;
• migraine prophylaxis.

Peripheral circulation disorders:

• symptomatic treatment of peripheral vascular disorders, including Raynaud's disease, acrocyanosis, intermittent claudication, trophic disorders, trophic and varicose ulcers, paresthesia, nocturnal leg cramps, cold extremities.

Balance disorders:

• symptomatic treatment of labyrinthine disorders, including dizziness, tinnitus, nystagmus, nausea, and vomiting.

Motion sickness:

• prevention of motion sickness.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

Alcohol/CNS depressants/tricyclic antidepressants: concomitant use may enhance the sedative effect of any of these medicinal products or of Cinnarizine.

Diagnostic procedures: due to its antihistaminic effect, Cinnarizine may mask positive reactions to skin sensitivity testing agents during skin tests; therefore, its use should be discontinued 4 days prior to the test.

Special precautions for use.

Cinnarizine may cause irritation in the epigastric region; taking the medication after food may help reduce gastric mucosal irritation.

Cinnarizine is recommended for patients with Parkinson's disease only if the benefits of treatment outweigh the potential risk of worsening the course of this disease.

Since cinnarizine may cause drowsiness, especially at the beginning of treatment, concomitant use of alcohol and administration of agents that suppress CNS activity (CNS depressants) or tricyclic antidepressants should be avoided.

Cinnarizine must be avoided in patients with porphyria.

Cinnarizine should be used with caution in patients with impaired liver and/or kidney function.

The product contains lactose and therefore should not be administered to patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Pregnancy. The drug is not recommended for use during pregnancy.

Breastfeeding period. There are no data regarding the possible passage of cinnarizine into breast milk. Therefore, treatment with this drug should be avoided in women during breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Given that drowsiness may occur in sensitive patients during treatment (especially at the beginning of therapy), driving vehicles and performing other tasks requiring concentration should be avoided during treatment with this drug.

Dosage and Administration.

Cerebral circulation disorders.

Adults and children aged 12 years and older: 1 tablet three times daily.

Peripheral circulation disorders.

Adults and children aged 12 years and older: 2–3 tablets three times daily. The recommended maximum dose should not exceed 225 mg (9 tablets) per day. Since the effect in vertigo is dose-dependent, the dosage should be gradually increased.

Balance disorders.

Adults and children aged 12 years and older: 1 tablet three times daily.

Motion sickness.

Adults and children aged 12 years and older: 1 tablet half an hour before travel; the dose may be repeated every 6 hours.

Administration method.

For oral use. Cinnarizine should preferably be taken after meals.

Children.

Cinnarizine may be used in children aged 12 years and older.

Overdose.

Symptoms. In isolated cases of acute overdose (90–2250 mg), the following symptoms have been observed: altered consciousness ranging from drowsiness to stupor and coma, vomiting, extrapyramidal symptoms, and arterial hypotension. Seizures were observed in a small number of children. In most cases, the clinical outcome was not severe, but fatal cases have been reported following overdose when cinnarizine was taken concomitantly with other medicinal products.

Treatment. There is no specific antidote. Gastric lavage should be performed within one hour after ingestion. Activated charcoal may be administered if indicated.

Side effects.

Somnolence and gastrointestinal disorders may occur. These symptoms are usually temporary and disappear with gradual attainment of the optimal dose. Rarely, symptoms such as headache, dry mouth, weight gain, increased sweating, hypersensitivity (allergic reactions), and cholestatic jaundice may occur. Very rarely, Wilson's syndrome and lupus-like symptoms have been reported. Isolated cases of obstructive jaundice have been mentioned in the medical literature.

In elderly patients during long-term treatment, cases of exacerbation or emergence of extrapyramidal symptoms, sometimes associated with depressive states, have been observed. In such cases, the use of this medicinal product should be discontinued.

Frequency is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000); frequency not known (cannot be estimated from the available data).

Additional adverse reactions reported include hypersensitivity reactions, headache, and dry mouth sensation.

Shelf life.

5 years.

Storage conditions.

Store in a place inaccessible to children, in the original packaging, at a temperature not exceeding 25 °C.

Packaging.

10 tablets per blister, 3, 5, 50, or 100 blisters per carton.

Prescription status.

Prescription only.

Manufacturer.

Private Joint-Stock Company "Lekhym-Kharkiv".

Manufacturer's address and location of business activity.

36 Severina Pototskoho Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.