DOSAGE FORMS AND STRENGTHS
White, circular, biconvex, halfscored tablet with the inscription “JANSSEN” on one side and “S/25” on the other side. Each tablet contains 25 mg cinnarizine.
For excipients, see List of Excipients.
Cerebral circulatory disorders
• Maintenance therapy for symptoms of cerebrovascular origin, including dizziness, ear buzzing (tinnitus), vascular headache, unsociability and irritability disorders, loss of memory and lack of concentration.
• Prophylaxis of migraine.
Disorders of balance
• Maintenance therapy for symptoms of labyrinthine disorders, including vertigo, dizziness, tinnitus, nystagmus, nausea and vomiting.
Peripheral circulatory disorders
• Maintenance therapy for symptoms of peripheral circulatory disorders, including Raynaud’s phenomenon, acrocyanosis, intermittent claudication, trophic disturbances, trophic and varicose ulcers, paraesthesia, nocturnal cramps, cold extremities.
• Prophylaxis of motion sickness.
Dosage and Administration
Cerebral circulatory disorders – Adults
• 1 tablet of 25 mg three times a day.
Disorders of balance – Adults
• 1 tablet of 25 mg three times a day.
Peripheral circulatory disorders – Adults
• 2 to 3 tablets of 25 mg three times a day. The maximum recommended dosage should not exceed 225 mg daily.
• Adults and adolescents aged 13 years and above: 1 tablet of 25 mg at least half an hour before travelling; to be repeated every 6 hours.
• Children aged 6 to 12 years: half of the adult dose is recommended.
STUGERON® should preferably be taken after meals.
STUGERON® is contraindicated in patients with known hypersensitivity to the drug.
Warnings and Precautions
As with other antihistamines STUGERON® may cause epigastric distress; 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. STUGERON® 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.
Alcohol, CNS depressants and tricyclic antidepressants
The sedative effects of STUGERON® and of any of the following may be potentiated when used concomitantly: alcohol, CNS depressants, or tricyclic antidepressants.
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.
Pregnancy and Breast-feeding
Although in animal studies STUGERON® has shown no teratogenic effects, as with all drugs, STUGERON® should be used during pregnancy only if the therapeutic benefits justify the potential risks for the fetus.
There are no data on the excretion of STUGERON® in human breast milk: nursing should therefore be discouraged in women using STUGERON®.
Effects on Ability to Drive and Use Machines
Since somnolence may occur, especially at the start of treatment, caution should be taken during activities such as driving or operating machinery.
Throughout this section, adverse reactions are presented. Adverse reactions are adverse events that were considered to be reasonably associated with the use of cinnarizine based on the comprehensive assessment of the available adverse event information. A causal relationship with cinnarizine cannot be reliably established in individual cases.
Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Clinical trial data
Placebo-controlled double-blind data — adverse reactions reported at ≥1% incidence
The safety of STUGERON® (30 to 225 mg/day) was evaluated in 740 subjects (of which 372 were treated with STUGERON®, 368 were given placebo) who participated in 7 placebo-controlled, double-blind clinical trials: three in the treatment of peripheral circulatory disorders, one in the treatment of cerebral circulatory disorders, two in vertigo, and one in seasickness.
Adverse reactions reported by ≥1% of STUGERON® treated subjects noted in the double-blind clinical trials are shown in Table 1.
Table 1. Adverse Reactions Reported by ≥1 % of STUGERON®-treated Subjects in 7 Double-Blind Placebo-Controlled Clinical Trials of STUGERON®
|Nervous System Disorders
Comparator and open-label data – adverse reactions reported at ≥1% incidence
Six comparator trials and thirteen open label trials were selected to determine the incidence of adverse reactions. In these 19 studies, 668 subjects were treated with doses ranging from 50 to 225 mg/day STUGERON@, in the treatment of peripheral circulatory disorders, cerebral circulatory disorders, and vertigo.
Adverse reactions reported by ≥1% of STUGERON® treated subjects noted in the comparator and open-label clinical trials are shown in Table 2.
Table 2. Adverse Reactions Reported by ≥1% of STUGERON®-treated Subjects in 6 Comparator and 13 Open-Label Clinical Trials of STUGERON®
Placebo, comparator, and open-label data – adverse reactions reported at <1% incidence
Additional adverse reactions that occurred in <1% of STUGERON® treated subjects in the above 2 clinical datasets are listed below in Table 3.
Table 3. Adverse Reactions Reported by <1% of STUGERON®-treated Subjects in Either the Placebo- or Comparator-controlled or Open Clinical Trials.
Nervous System Disorders
Abdominal pain upper
Skin and Subcutaneous Tissue Disorders
General Disorders and Administration Site Conditions
Adverse events first identified as adverse reactions during postmarketing experience with cinnarizine are included in Table 4.
The postmarketing review was based on review of all cases where there was a use of cinnarizine. In Table 4, adverse reactions are presented by frequency category based on spontaneous reporting rates, with frequencies provided according to the following convention:
Very common ≥1/10
Common ≥1/100 to <1/10
Uncommon ≥1/1000 to <1/100
Rare ≥1/10000 to <1/1000
Very rare <1/10000 including isolated reports
Table 4. Adverse Reactions Identified During Postmarketing Experience with cinnarizine (STUGERON®) by Frequency Category Estimated From Spontaneous Reporting Rates
|Nervous System Disorders|
|Extrapyramidal disorder||Very rare|
|Skin and Subcutaneous Tissue Disorders|
|Lichenoid keratosis||Very rare|
|Lichen planus||Very rare|
|Subacute cutaneous lupus erythematosus||Very rare|
|Musculoskeletal, Connective Tissue and Bone Disorders|
|Muscle rigidity||Very rare|
Symptoms and signs
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.
There is no specific antidote. For any overdose, the treatment is symptomatic and supportive care. Activated charcoal may be given if considered appropriate.
Pharmacotherapeutic group: antivertigo preparations, ATC code: N07CA02.
Cinnarizine has an anti-histamine (H1)-effect.
Cinnarizine inhibits contractions of vascular smooth muscle cells by blocking calcium channels.
In addition to this direct calcium antagonism, cinnarizine decreases the contractile activity of vasoactive substances, such as norepinephrine and serotonin, by blocking receptor-operated calcium channels. Blockade of the cellular influx of calcium is tissue-selective, and results in antivasoconstrictor properties without effect on blood pressure and heart rate.
Cinnarizine may further improve deficient microcirculation by increasing erythrocyte deformability and decreasing blood viscosity. Cellular resistance to hypoxia is increased.
Cinnarizine inhibits stimulation of the vestibular system, which results in suppression of nystagmus and other autonomic disturbances. Acute episodes of vertigo can be prevented or reduced by cinnarizine.
The peak plasma levels of cinnarizine are obtained 1 to 3 hours after intake.
The plasma protein binding of cinnarizine is 91%.
Cinnarizine is extensively metabolized mainly via CYP2D6.
The reported elimination half-life for cinnarizine ranges from 4 to 24 hours. The elimination of metabolites is about 1/3 in the urine and 2/3 in the feces.
A comprehensive battery of nonclinical safety studies showed that effects were observed only after chronic exposures from approximately 5 to 72 times, on a mg/kg basis when compared to the maximum recommended human dose of 225 mg/day, calculated as 4.5 mg/kg as based on a 50 kg person.
List of Excipients
25mg tablets: Cotton seed oil hydrogenated, lactose monohydrate, maize starch, polyvidone. Sucrose, talc.
See expiry date on the outer pack.
See storage conditions on the outer pack.
Keep out of reach of children.
Nature and Contents of Container
Instructions for Use and Handling
No special requirements.
Instructions for Disposal
Any unused product or waste material should be disposed of in accordance with local requirements.
See outer carton.
DATE OF REVISION OF THE TEXT
18 March 2013
© Janssen-Cllag 2013