Summary of Product Characteristics (SmPC) - Mylan Travel Sickness 15 mg tablets
1 NAME OF THE MEDICINAL PRODUCT
Mylan Travel 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
Disorders of balance - maintenance therapy for symptoms of labyrinthine disorders, including vertigo, tinnitus, nystagmus, nausea and vomiting such as is seen in Meniere's Disease.
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.
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 Tablets contain lactose. 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 Interactions 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.
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.
Lactation
There are no data on the excretion 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 303 cinnarizine-treated subjects who participated in 6 placebo-controlled trials for the indications peripheral circulatory disorders, cerebral circulatory disorders, vertigo and control of motion sickness ; and in 937 cinnarizine-treated subjects who participated in six comparator and 13 open label clinical trials for the indications peripheral circulatory disorders, cerebral circulatory disorders and vertigo. Based on pooled safety data from these clinical trials, the most commonly reported (>1% incidence) Adverse Drug Reactions (ADRs) were: somnolence (9.9), nausea (3.0) and increased weight (1.5).
Including the above mentioned ADR, the following ADRs have been observed from clinical trials and 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) | Uncommon (≥ 1/1,000 to <1/100) | Rare (≥ 1/10,000 to <1/1,000) | Not known | |
Nervous system disorders | Somnolence | Hypersomnia | Dyskinesia; extrapyramidal disorder, parkinsonism, Tremor | |
| Gastrointesti nal disorders | Nausea, | Vomiting, | Upper abdominal pain Dyspepsia; |
| Hepatobiliary disorders |
Cholestatic jaundice
Skin and subcutaneous tissue disorders | Hyperhidrosis, lichenoid keratosis including lichen planus |
Subacute cutaneous lupus erythematosus
| Musculoskeletal and connective tissue disorders |
Muscle rigidity
| General disorders and administration site conditions | Fatigue | ||
| Investigations | Weight increased |
Cases of hypersensitivity, headache and dry mouth have been reported.
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 or search the MHRA Yellow Card in the Google Plat or Apple App Store.
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 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. It is advisable to contact a poison control centre to obtain the latest recommendation for the management of an overdose.
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.
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 that were 10 – 160 times the recommended maximum daily human dose of 100 mg/day calculated on a body surface area basis, calculated as 2mg/kg as based on a 50 kg person. . 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
07/02/2022