Cinnarizine/Dimenhydrinate Torrent 20mg/40mg Tablets – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Cinnarizine/Dimenhydrinate Torrent 20mg/40mg Tablets.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 20 mg Cinnarizine and 40 mg Dimenhydrinate. For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablet.

White to off white, round, uncoated tablets debossed with ‘V5’ on one side and plain on the other side with a diameter of approximately 8 mm.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Treatment of vertigo symptoms of various origins.

Cinnarizine/Dimenhydrinate Torrent 20mg/40mg Tablets are indicated in adults.

4.2 Posology and method of administration

Posology

Adults: 1 tablet three times daily.

Elderly: Dosage as for adults.

Renal impairment:

Cinnarizine/Dimenhydrinate tablets should be used with caution in patients with mild to moderate renal impairment. Cinnarizine/Dimenhydrinate tablets should not be used by patients with a creatinine clearance of < 25mL/min (severe renal impairment).

Hepatic impairment:

No studies in patients with hepatic impairment are available.

Cinnarizine/Dimenhydrinate tablets should not be used by patients with severe hepatic impairment.

Paediatric population:

The safety and efficacy of Cinnarizine/Dimenhydrinate tablets in children and adolescents under the age of 18 years has not been established. No data are available.

In general, the duration of treatment should not exceed four weeks. The physician shall decide whether longer treatment is required.

Method of administration

Cinnarizine/Dimenhydrinate tablets are to be taken unchewed, with some liquid after meals.

4.3 Contraindications

Hypersensitivity to the active substances, diphenhydramine or other antihistamines of similar structure or to any of the excipients listed in section 6.1. Diphenhydramine is completely excreted renally, and patients with severe renal impairment were excluded from the clinical development programme. Cinnarizine/Dimenhydrinate tablets should not be used by patients with a creatinine clearance of ≤ 25 ml/min (severe renal impairment).

Since both active components of Cinnarizine/Dimenhydrinate tablets are extensively metabolised by hepatic cytochrome P450 enzymes, the plasma concentrations of the unchanged drugs and their half-lives will increase in patients with severe hepatic impairment. This has been shown for diphenhydramine in patients with cirrhosis. Cinnarizine/Dimenhydrinate tablets should therefore not be used by patients with severe hepatic impairment.

Cinnarizine/Dimenhydrinate tablets should not be used in patients with angle-closure glaucoma, convulsions, suspicion of raised intracranial pressure, alcohol abuse or urine retention due to urethroprostatic disorders.

4.4 Special warnings and precautions for use

Cinnarizine/Dimenhydrinate tablets does not reduce blood pressure significantly, however, it should be used with caution in hypotensive patients. Cinnarizine/Dimenhydrinate tablets should be taken after meals to minimise any gastric irritation.

Cinnarizine/Dimenhydrinate tablets should be used with caution in patients with conditions that might be aggravated by anticholinergic therapy, e.g. raised intraocular pressure, pyloro-duodenal obstruction, prostatic hypertrophy, hypertension, hyperthyroidism or severe coronary heart disease.

Caution should be exercised when administering Cinnarizine/Dimenhydrinate tablets to patients with Parkinson’s disease.

Sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet that is to say essentially “sodium-free”.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

The anticholinergic and sedative effects of Cinnarizine/Dimenhydrinate tablets may be potentiated by monoamine oxidase inhibitors. Procarbazine may enhance the effect of Cinnarizine/Dimenhydrinate tablets.

In common with other antihistamines, Cinnarizine/Dimenhydrinate tablets may potentiate the sedative effects of CNS depressants including alcohol, barbiturates, narcotic analgesics and tranquillisers. Patients should be advised to avoid alcoholic drinks. Cinnarizine/Dimenhydrinate tablets may also enhance the effects of antihypertensives, ephedrine and anticholinergics such as atropine and tricyclic antidepressants.

Cinnarizine/Dimenhydrinate tablets may mask ototoxic symptoms associated with amino glycosidic antibiotics and mask the response of the skin to allergic skin tests. The concomitant administration of medicines that prolong the QT interval of the ECG (such as Class Ia and Class III anti-arrhythmics) should be avoided. The information about potential pharmacokinetic interactions with cinnarizine and diphenhydramine and other medicinal products is limited. Diphenhydramine inhibits CYP2D6 mediated metabolism and caution is advised if Cinnarizine/Dimenhydrinate tablet is combined with substrates of this enzyme, especially those with narrow therapeutic range.

4.6 Fertility, pregnancy and lactation

Pregnancy

The safety of Cinnarizine/Dimenhydrinate tablets in human pregnancy has not been established. Animal studies are insufficient with respect to effects on pregnancy, embryonal/foetal development and postnatal development (see Section 5.3). The teratogenic risk of the single actives dimenhydrinate/diphenhydramine and cinnarizine is low. No teratogenic effects were observed in animal studies. There are no data from the use of Cinnarizine/Dimenhydrinate tablets in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3).

Based on human experience dimenhydrinate is suspected to have an oxytoxic effect and may shorten labour.

Cinnarizine/Dimenhydrinate tablets is not recommended during pregnancy.

Breast-feeding

Dimenhydrinate and cinnarizine are excreted in human breast milk. Cinnarizine/Dimenhydrinate tablets should not be used during breast-feeding.

Fertility

Not known.

4.7 Effects on ability to drive and use machines

Cinnarizine/Dimenhydrinate tablets may have minor influence on the ability to drive and use machines.

Cinnarizine/Dimenhydrinate tablets 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 most frequently occurring ADRs are somnolence (including drowsiness, tiredness, fatigue, daze) occurring in about 8% of patients and dry mouth occurring in about 5% of patients in clinical trials. These reactions are usually mild and disappear within a few days even if treatment is continued. The frequency of ADRs associated with Cinnarizine/Dimenhydrinate tablets in clinical trials and following spontaneous reports are included in the next table.

Tabulated list of adverse reactions:

≥

In addition the following adverse reactions are associated with dimenhydrinate and cinnarizine (frequency cannot be estimated from the available data): Dimenhydrinate: paradoxical excitability (especially in children), worsening of an existing angle-closure glaucoma, reversible agranulocytosis.

Cinnarizine: constipation, weight gain, tightness of the chest, cholestatic jaundice, extrapyramidal symptoms, lupus-like skin reactions, lichen planus.

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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Symptoms of overdosage with Cinnarizine/Dimenhydrinate tablets include drowsiness, dizziness and ataxia with anticholinergic effects such as dry mouth, flushing of the face, dilated pupils, tachycardia, pyrexia, headache and urinary retention.

Convulsions, hallucinations, excitement, respiratory depression, hypertension, tremor and coma may occur, particularly in cases of massive overdosage.

Management of overdose: General supportive measures should be used to treat respiratory insufficiency or circulatory failure. Gastric lavage with isotonic sodium chloride solution is recommended. Body temperature should be closely monitored, since pyrexia may occur as a consequence of antihistamine intoxication, especially in children.

Cramp-like symptoms may be controlled by careful application of a shortacting barbiturate. In cases of marked central-anticholinergic effects, physostigmine (after physostigmine test) should be administered slowly intravenously (or, if necessary, intramuscularly) : 0.03 mg/kg body weight (adults max. 2 mg, children max. 0.5 mg).

Dimenhydrinate is dialyzable, however treatment of overdosage by this measure is considered as unsatisfactory. Sufficient elimination can be achieved by means of haemoperfusion using activated charcoal. No data are available concerning the dialysability of cinnarizine.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: antivertigo preparations, ATC code: N07CA52

Dimenhydrinate, the chlorotheophylline salt of diphenhydramine, acts as antihistamine with anticholinergic (antimuscarinic) properties, exerting parasympatholytic and centrally-depressant effects. The substance exhibits antiemetic and antivertiginous effects through influencing the chemoreceptor trigger zone in the region of the 4^th ventricle. Dimenhydrinate thus acts predominantly on the central vestibular system.

Due to its calcium antagonistic properties, cinnarizine acts mainly as a vestibular sedative through inhibition of the calcium influx into the vestibular sensory cells. Cinnarizine thus acts predominantly on the peripheral vestibular system.

Both cinnarizine and dimenhydrinate are known to be effective in the treatment of vertigo. The combination product is more effective than the individual compounds in the population studied.

The product has not been evaluated in motion sickness.

5.2 Pharmacokinetic properties

Absorption and Distribution

Dimenhydrinate rapidly releases its diphenhydramine moiety after oral administration. Diphenhydramine and cinnarizine are rapidly absorbed from the gastro-intestinal tract. Maximum plasma concentrations (C_max) of cinnarizine and diphenhydramine are reached in humans within 2-4 hours. The plasma elimination half-lives of both substances range from 4-5 hours, when given either alone or as the combination product.

Biotransformation

Cinnarizine and diphenhydramine are extensively metabolised in the liver. The metabolism of cinnarizine involves ring hydroxylation reactions that are in part catalysed by CYP2D6 and Ndesalkylation reactions of low CYP-enzyme specificity. The main pathway in the diphenhydramine metabolism is the sequential Ndemethylation of the tertiary amine. Studies in human liver microsomes in vitro indicate the involvement of various CYP-enzymes, including CYP2D6.

Elimination

Cinnarizine is mainly eliminated via the faeces (40-60%) and to a lower extent also in urine, mainly in the form of metabolites conjugated with glucuronic acid. The major route of elimination of diphenhydramine is in the urine, mainly in the form of metabolites, with the deaminated compound, diphenylmethoxy acetic acid, being the predominant metabolite (40-60%).

5.3 Preclinical safety data

Non-clinical data revealed no special hazard for humans based on conventional studies of repeated dose toxicity with the combination of cinnarizine and dimenhydrinate, fertility with cinnarizine or dimenhydrinate, embryo/foetal development with dimenhydrinate and teratogenicity with cinnarizine. In one study in rats, cinnarizine decreased litter size, increased the number of resorbed foetuses and decreased the birth weight of pups.

The genotoxic and carcinogenic potential of the cinnarizine/dimenhydrinate combination has not been fully evaluated.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Microcrystalline cellulose,

Maize starch,

Croscarmellose sodium,

Hypromellose 2910,

Colloidal silicon dioxide, Magnesium stearate,

Talc

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years.

6.4 Special precautions for storage

This medicinal product does not require any special temperature storage conditions. Store in the original package

6.5 Nature and contents of container

Carton containing Aluminium-Aluminium blisters or PVC/PVDC-Aluminium blisters of 100 tablets

6.6 Special precautions for disposal

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Torrent Pharma (UK) Ltd.

3rd Floor, Nexus Building

4 Gatwick Road

Crawley

West Sussex

RH10 9BG

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 36687/0460

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

13/05/2025

10 DATE OF REVISION OF THE TEXT

13/05/2025