McNeil Healthcare (Ireland) Ltd

Stugeron 15 mg Tablets

Each tablet contains cinnarizine 15 mg.

Excipients: each table contains 160mg lactose monohydrate and 15mg sucrose.

For a full list of excipients, see section 6.1.

Tablet

A biconvex, circular, white tablet engraved “S|15” on one side and “Janssen” on the other.

For the prevention and control of motion sickness.

For oral use.

Adults:

2 tablets 2 hours before travelling, then 1 tablet every 8 hours during the journey.

Children 5 - 12 years:

Half the adult dose.

Stugeron tablets are contra-indicated in patients with known hypersensitivity to the drug.

As with other antihistamines, Stugeron may cause epigastric upset, which may be diminished if taken after meals.

Cinnarizine is a vasodilator. While it has not been found to reduce blood pressure significantly, it should be used with caution in those with coronary artery disease or in patients with hypotension.

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

Stugeron may cause somnolence, especially at the start of treatment. Therefore, caution should be taken when alcohol or CNS depressants are used concomitantly.

Because of its antihistamine effect, Stugeron may prevent otherwise positive reactions to dermal reactivity indicators if used up to 4 days prior to skin 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 galactose intolerance, fructose intolerance, LAPP lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Avoid alcoholic drink.

Warning: Do not exceed the stated dose.

Stugeron may potentiate the sedative effect of CNS depressants, tricyclic antidepressants and alcohol, especially at the start of treatment. Alcoholic drink should be avoided.

Stugeron tablets should not be taken during pregnancy unless considered essential by the physician. It is not known whether cinnarizine is excreted in breast milk. Use of Stugeron is not recommended in nursing mothers.

This product may cause drowsiness. If affected, do 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

Acute cinnarizine overdoses have been reported with doses ranging from 90 to 2,250 mg. 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. Activated charcoal may be given if considered appropriate.

ATC Code N07CA02

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 depolarised 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 drug is excreted 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 K90

Not applicable.

3 years.

Do not store above 25°C.

Blister packs of aluminium foil/PVC, containing 15 tablets.

No special requirements.

McNeil Healthcare (Ireland) Ltd.

Airton Road

Tallaght

Dublin 24

Ireland

PA 823/55/1

19 April 1993 / 19 April 2008

November 2010