STUGERON 15

Cinnarizine 15 mg

For excipients, see 6.1.

Tablets

White, circular biconvex tablets marked S/15 on one side.

Stugeron 15 is effective in the control of motion sickness.

Stugeron 15 should preferably be taken after meals.

Adults, elderly and children over 12 years:

2 tablets 2 hours before you travel and 1 tablet every 8 hours during your journey.

Children 5 to 12 years:

One half the adult dose.

Method of administration: Oral

Stugeron should not be given to patients with known hypersensitivity to cinnarizine.

As with other antihistamines, Stugeron may cause epigastric discomfort; taking it after meals may diminish gastric irritation.

In patients with Parkinson's disease, Stugeron should only be given if the advantages outweigh the possible risk of aggravating this disease.

Because of its antihistamine effect, Stugeron may prevent an otherwise positive reaction to dermal reactivity indicators if used within 4 days prior to testing.

Use of cinnarizine should be avoided in porphyria.

There have been no specific studies in hepatic or renal dysfunction. Stugeron should be used with care in patients with hepatic or renal insufficiency.

Patients with rare hereditary problems of fructose or galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase insufficiency, should not take this medicine because it contains lactose and sucrose.

Concurrent use of alcohol, CNS depressants or tricyclic antidepressants may potentiate the sedative effects of either of these drugs or of Stugeron.

The safety of Stugeron in human pregnancy has not been established although studies in animals have not demonstrated teratogenic effects. As with other drugs it is not advisable to administer Stugeron in pregnancy.

There are no data on the excretion of Stugeron in human breast milk. Use of Stugeron is not recommended in nursing mothers.

Stugeron may cause drowsiness, especially at the start of treatment; patients affected in this way should not drive or operate machinery.

The safety of STUGERON was evaluated in 167 cinnarizine-treated subjects who participated in 1 placebo-controlled trial (166 placebo-treated subjects) in the prophylaxis of seasickness. In this trial, only Somnolence has been included as an ADR with an incidence of 8.4% in the cinnarizine group compared to 4.8% in the placebo group.

Including the above mentioned ADR, the following ADRs have been observed from post-marketing experiences reported with the use of STUGERON. Frequencies displayed use the following convention:

Very common ( 1/10); common ( 1/100 to < 1/10); uncommon ( 1/1,000 to < 1/100); rare ( 1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

Symptoms

The signs and symptoms are mainly due to the anticholinergic (atropine-like) activity of cinnarizine. Acute cinnarizine overdoses have been reported with doses ranging from 90 to 2,250mg. The most commonly reported signs and symptoms associated with overdose of cinnarizine include: alterations in consciousness ranging from somnolence to stupor and coma, vomiting, extrapyramidal symptoms and hypotonia.

In a small number of young children, seizures developed. Clinical consequences were not severe in most cases, but deaths have been reported after single and polydrug overdoses involving cinnarizine.

Treatment

There is no specific antidote. For any overdose, the treatment is symptomatic and supportive care. Within the first hour after ingestion, gastric lavage may be performed provided that the airway is protected. However, the benefit of gastric lavage is uncertain. Activated charcoal should only be considered in patients presenting within one hour of taking a potentially toxic overdose (i.e., more than 15mg/kg).

ATC code: Antivertigo preparations N07C A

Cinnarizine has been shown to be a non competitive antagonist of the smooth muscle contractions caused by various vasoactive agents including histamine.

Cinnarizine also acts on vascular smooth muscle by selectively inhibiting the calcium influx into depolarized cells, thereby reducing the availability of free Ca²⁺ ions for the induction and maintenance of contraction.

Vestibular eye reflexes induced by caloric stimulation of the labyrinth in guinea pigs are markedly depressed by cinnarizine.

Cinnarizine has been shown to inhibit nystagmus.

In animals, cinnarizine is extensively metabolised, N-dealkylation being the major pathway. Approximately two thirds of the metabolites are excreted with the faeces, the rest in the urine, mainly during the first five days after a single dose.

Absorption

In man, after oral administration, absorption is relatively slow, peak serum concentrations occurring after 2.5 to 4 hours.

Distribution

The plasma protein binding of cinnarizine is 91%.

Metabolism

Cinnarizine is extensively metabolised mainly via CYP2D6, but there is considerable interindividual variation in the extent of metabolism.

Elimination

The reported elimination half-life for cinnarizine ranges from 4 to 24 hours.

The elimination of metabolites occurs as follows: one third in the urine (unchanged as metabolites and glucuronide conjugates) and two-thirds in the faeces.

Nonclinical safety studies showed that effects were observed only after chronic exposures from approximately 7 to 35 times the recommended maximum daily human dose of 90 mg/day calculated on a body surface area basis. Cinnarizine blocked the cardiac hERG channel in vitro, however in isolated cardiac tissue and following intravenous application in guinea-pigs, no QTc prolongation or proarrhythmic effects were observed at substantially higher exposures than those expected clinically.

In reproductive studies in the rat, rabbit, and dog, there was no evidence of adverse effects on fertility and no teratogenicity. At high doses associated with maternal toxicity in the rat there was a decreased litter size, an increase in resorptions and a decrease in fetal birth weight.

In vitro mutagenicity studies indicated that the parent compound is not mutagenic however, after reacting with nitrite and forming the nitrosation product, a weak mutagenic activity was observed. Carcinogenicity studies have not been conducted however, no pre-neoplastic changes were evident during chronic 18-month oral administration in rats up to approximately 35 times the maximum human dose level.

Lactose monohydrate, maize starch, sucrose, talc, magnesium stearate, povidone.

Not applicable.

3years

None.

PVC/aluminium foil blisters of 15 tablets in printed cardboard cartons.

None.

McNeil Products Limited

Foundation Park

Roxborough Way

Maidenhead

Berkshire

SL6 3UG

United Kingdom

PL 15513/0349

22 January 2009

27 July 2010

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