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 center to obtain the latest recommendations for the management of an overdose.
3 years.
None known.
Lactose monohydrate
Maize starch
Sucrose
Talc
Magnesium stearate
Polyvidone K90
The safety of Stugeron was evaluated in 372 cinnarizine-treated subjects who participated in 7 placebo-controlled trials for the indications peripheral circulatory disorders, cerebral circulatory disorders, vertigo and seasickness; and in 668 cinnarizine-treated subjects who participated in six comparator and thirteen 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 (>2% incidence) Adverse Drug Reactions (ADRs) were: somnolence (8.3) and weight increased (2.1).
Including the above mentioned ADRs, the following ADRs have been observed from clinical trials and 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).
|
System Organ Class |
Adverse Drug Reactions | ||
|
Frequency Category | |||
|
Common (> 1/100 to < 1/10) |
Uncommon (> 1/1,000 to < 1/100) |
Not Known | |
|
Nervous System Disorders |
Somnolence |
Lethargy |
Dyskinesia; Extrapyramidal disorder; Parkinsonism; Tremor |
|
Gastrointestinal Disorders |
Nausea; Dyspepsia |
Vomiting; Upper abdominal pain | |
|
Hepato-biliary disorders |
Cholestatic jaundice | ||
|
Skin and subcutaneous tissue disorders |
Hyperhydrosis; 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 for MHRA Yellow Card in the Google Play or Apple App Store.
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.
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 (unchanged as metabolites and glucuronide conjugates) and two thirds in the faeces.
30 May 2018
Janssen-Cilag Limited
50-100 Holmers Farm Way
High Wycombe
Buckinghamshire
HP12 4EG
UK
This medicinal product does not require any special storage conditions.
PVC/Aluminium foil blisters
or
Polystyrene tubs with polyethylene caps
Each pack containing 15, 25, 100, 250 or 1000 tablets.
Not all pack sizes may be marketed.
PL 00242/5009R
No special requirements.
Date of first authorisation: 14 September 1989
Date of latest renewal: 21 August 2001
