Stugeron Cinnarizine Tablets

Stugeron®

PRODUCT NAME

STUGERON® (cinnarizine)

DOSAGE FORMS AND STRENGTHS

Tablets

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.

CLINICAL INFORMATION

Indications

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.

Motion sickness

• Prophylaxis of motion sickness.

Dosage and Administration

Dosage

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.

Motion sickness

• 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.

Administration

STUGERON® should preferably be taken after meals.

Contraindications

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.

Interactions

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.

Diagnostic interference

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

Pregnancy

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.

Breast-feeding

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.

Adverse Reactions

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®

System/Organ Class
Preferred Term
STUGERON® (n=372)
%
Placebo
(n=368)
%
Nervous System Disorders

Somnolence

8.3 4.6

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®

System/Organ Class
Preferred Term
STUGERON® (n=668)
%
Gastrointestinal Disorders

Nausea

1.5
Investigations

Weight increased

2.1

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

Hypersomnia

Lethargy

Gastrointestinal Disorders

Stomach discomfort

Vomiting

Abdominal pain upper

Dyspepsia

Skin and Subcutaneous Tissue Disorders

Hyperhidrosis

General Disorders and Administration Site Conditions

Fatigue

Postmarketing data

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

System/Organ Class
Preferred Term
Frequency
Nervous System Disorders
Dyskinesia Very rare
Extrapyramidal disorder Very rare
Parkinsonism Very rare
Tremor 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

Overdose

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.

Treatment

There is no specific antidote. For any overdose, the treatment is symptomatic and supportive care. Activated charcoal may be given if considered appropriate.

PHARMACOLOGICAL PROPERTIES

Pharmacodynamic Properties

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.

Pharmacokinetic Properties

Absorption

The peak plasma levels of cinnarizine are obtained 1 to 3 hours after intake.

Distribution

The plasma protein binding of cinnarizine is 91%.

Metabolism

Cinnarizine is extensively metabolized mainly via CYP2D6.

Elimination

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.

NON-CLINICAL INFORMATION

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.

PHARMACEUTICAL INFORMATION

List of Excipients

25mg tablets: Cotton seed oil hydrogenated, lactose monohydrate, maize starch, polyvidone. Sucrose, talc.

Incompatibilities

None known.

Shelf Life

See expiry date on the outer pack.

Storage Conditions

See storage conditions on the outer pack.

Keep out of reach of children.

Nature and Contents of Container

Blister packs.

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.

MANUFACTURED BY

See outer carton.

DATE OF REVISION OF THE TEXT

18 March 2013

© Janssen-Cllag 2013

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