SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT

Mylan Travel Sickness 15 mg Tablets Boots Motion Sickness 15 mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 15 mg of cinnarizine

Excipient with known effect:

Each tablet contains 162.50 mg anhydrous lactose

For the full list of excipients, see section 6.1.

The product will be referred to Cinnarizine for the remaining portion of this SmPC.

3    PHARMACEUTICAL FORM

Tablet

White, flat bevel edged tablets marked “G” on both sides

4.    CLINICAL PARTICULARS

4.1    Therapeutic indications

Cinnarizine is effective in the control of motion sickness.

4.2    Posology and method of administration

Cinnarizine is for oral administration to both adults and children according to the following dosage regime.

Posology

Adults, elderly and children over 12 years:

Two tablets two hours before travel and one tablet every eight hours during journey if necessary.

Paediatric population (children 5 to 12 years):

One tablet two hours before travel and half a tablet every eight hours during journey if necessary.

Method of administration

Tablets may be sucked, chewed or swallowed whole with water. Cinnarizine should preferably be taken after meals.

4.3    Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4    Special warnings and precautions for use

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

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

Cinnarizine may prevent an otherwise positive reaction to dermal reactivity indicators if used within 4 days prior to skin testing as it is an antihistamine.

Use of cinnarizine should be avoided in porphyria.

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

Cinnarizine may cause somnolence, especially at the start of treatment. Therefore caution should be taken when alcohol, central nervous system (CNS) depressants or tricyclic antidepressants are used concomitantly (see section 4.5).

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Diagnostic interference

Because of its antihistamine effect, cinnarizine may prevent otherwise positive reactions to dermal reactivity indicators if used up to 4 days prior to skin testing.

4.5    Interaction with other medicinal products and other forms of interaction

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

Diagnostic interference

Because of its antihistamine effect, cinnarizine may prevent otherwise positive reactions to dermal reactivity indicators if used up to 4 days prior to skin testing (see section 4.4).

4.6    Fertility, pregnancy and lactation

Pregnancy

The safety of cinnarizine 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 cinnarizine in pregnancy.

Breast-feeding

There are no data on the secretion of cinnarizine in human breast milk. Taking cinnarizine during lactation should be avoided.

4.7    Effects on ability to drive and use machines

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

4.8    Undesirable effects

The safety of cinnarizine 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 cinnarizine.

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).

System organ class	Adverse drug reactions
	Frequency category
	Common (> 1/100 to < 1/10)		Not known
Immune system disorders			Hypersensitivity
Nervous system disorders	Somnolence		Headache; dyskinesia; extrapyramidal disorder; parkinsonism; tremor

Gastrointestinal disorders			Gastrointestinal disorder; dry mouth
Skin and subcutaneous tissue disorders			Lichen planus; subacute cutaneous lupus erythematosus; Lichenoid keratosis
Musculoskeletal and connective tissue disorders			Muscle rigidity

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

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 2250 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.

Activated charcoal may be given if considered appropriate.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antivertigo preparations, ATC code: N07CA02 Mechanism of action

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 Ca” ions for the induction and maintenance of contraction.

Pharmacodynamic effects

Cinnarizine is reported to possess smooth muscle relaxant properties and to inhibit vasoconstriction, and is thus used in the management of various vascular disorders. Sedative effects are not marked.

Clinical efficacy and safety

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.

5.2 Pharmacokinetic properties

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%. Biotransformation

Cinnarizine undergoes extensive metabolism 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 drug is excreted as follow: one third in the urine (unchanged as metabolites and glucuronide conjugates) and two thirds in the faeces.

5.3 Preclinical safety data

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 foetal 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.

6    PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Maize starch,

Lactose, anhydrous,

Mannitol,

Magnesium stearate,

Talc.

6.2. Incompatibilities

Not applicable

6.3    Shelf life

3 years

6.4    Special precautions for storage

No special precautions for storage.

6.5    Nature and contents of container

PVdC coated PVC blister strips with aluminium foil lidding containing 4, 6, 8, 10, 15, 20, 84 and 100 tablets

Polypropylene container with tamper-evident polyethylene closure containing 4, 6, 8, 10, 15, 20, 84 and 100 tablets

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements

7 MARKETING AUTHORISATION HOLDER

Generics [UK] Ltd. t/a Mylan

Station Close

Potters Bar

Herts EN6 1TL

United Kingdom

8. MARKETING AUTHORISATION NUMBER

PL 04569/0599

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

20/06/2008

10 DATE OF REVISION OF THE TEXT

19/01/2015