ALIMEMAZINE TARTRATE 10 MG FILM-COATED TABLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Alimemazine tartrate 10 mg film-coated tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 10 mg of alimemazine tartrate

Excipients with known effect

Each film-coated tablet contains 38 mg lactose (as monohydrate).

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Film-coated tablets.

Blue, round, biconvex film-coated tablets, debossed with “A” on one side and “1” on other side, approximately 6.5 mm in diameter.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Aliememazine tartrate 10 mg film-coated tablets is used for second-line treatment in the symptomatic relief of urticaria and pruritus in adults.

4.2 Posology and method of administration

Adults:

10 mg two or three times daily.

Elderly:

Dose should be reduced to 10 mg once or twice daily.

Paediatric population:

Children over 3 years of age: The use of Alimemazine Syrup is recommended.

Children less than 3 years of age: Contraindicated (see sections 4.3 and 4.4) Method of administration:

The product is administered orally.

DO NOT exceed the recommended dose (see also section 4.9).

4.3 Contraindications

Alimemazine is contraindicated in patients with:

Known hypersensitivity to phenothiazines or to any of the excipients listed in section 6.1.

Hepatic or renal dysfunction

Epilepsy

Parkinson's disease

Hypothyroidism

Phaeochromocytoma

Myasthenia gravis

History of narrow angle glaucoma

History of agranulocytosis

Prostatic hypertrophy.

Alimemazine is contraindicated for use in children less than 3 years of age (see section 4.4).

4.4 Special warnings and precautions for use

Patients are strongly advised not to consume alcoholic beverages or medicines containing alcohol throughout treatment (see section 4.5).

Exposure to sunlight should be avoided during treatment (see section 4.8).

Precautions for use:

Alimemazine should be used with caution in:

Elderly or volume depleted patients who are more susceptible to orthostatic hypotension (see section 4.8).

Elderly patients presenting chronic constipation (risk of paralytic ileus).

Elderly patients with possible prostatic hypertrophy (see section 4.3).

Elderly patients in hot and cold weather (risk of hyper/hypothermia) (see section 4.8).

Patients with certain cardiovascular diseases: alimemazine may cause arrhythmias due to the tachycardia-inducing and hypotensive effects of phenothiazines (see section 4.8).

Patients with seizures

Paediatric population

Alimemazine is contraindicated for use in children less than 3 years of age due to the risk of marked sedation and respiratory depression.

Lactose

Alimemazine contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

The sedative effects of phenothiazines may be intensified (additively) by alcohol (see section 4.4), anxiolytics & hypnotics, opiates, barbiturates and other sedatives. There may be increased antimuscarinic and sedative effects of phenothiazines with tricyclic antidepressants & MAOI's (including moclobemide). Respiratory depression may occur.

The hypotensive effect of most antihypertensive drugs especially alphaadrenoreceptor blocking agents may be exaggerated by phenothiazines. The use of antimuscarinics will increase the risk of antimuscarinic side effects when in conjunction with antihistamines.

The action of some drugs may be opposed by phenothiazines; these include amphetamine, levodopa, clonidine, guanethidine and adrenaline.

The mild anticholinergic effect of phenothiazines may be enhanced by other anticholinergic drugs possibly leading to constipation, heat stroke, etc.

Anticholinergic agents may reduce the antipsychotic effect of phenothiazines.

Some drugs interfere with absorption of phenothiazines: antacids, anti-Parkinson and lithium. Increases or decreases in the plasma concentrations of a number of drugs, e.g. propranolol and phenobarbital have been observed but were not of clinical significance.

High doses of phenothiazines reduce the response to hypoglycaemic agents, the dosage of which may have to be raised. Adrenaline must not be used in patients overdosed with phenothiazines.

As with other neuroleptic phenothiazines, caution is advised with concomitant use of QT prolonging drugs or drugs that cause electrolyte imbalance.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are limited data from the use of alimemazine tartrate in pregnant women, but it has been widely used for many years without apparent ill consequence. Some phenothiazines have shown evidence of harmful effects in animals. Alimemazine, like other drugs, should be avoided in pregnancy unless the physician considers it essential. Neuroleptics may occasionally prolong labour and at such a time should be withheld until the cervix is dilated 3 – 4 cm. Possible adverse effects on the neonate include lethargy or paradoxical hyperexcitability, tremor and low Apgar score.

Breast-feeding

Phenothiazines may be excreted in human milk. Breast-feeding should be discontinued during treatment with alimemazine tartrate.

4.7 Effects on ability to drive and use machines

Patients should be warned about drowsiness during the early days of treatment, and advised not to drive or operate machinery.

4.8 Undesirable effects

Gastrointestinal disorders:

Constipation

Dry mouth

Respiratory, thoracic and mediastinal disorders:

Nasal congestion

Respiratory depression is possible in susceptible patients

Psychiatric disorders:

Insomnia

Agitation

Nervous system disorders:

Extrapyramidal effects, such as:

– Acute dystonias or dyskinesias, usually transitory are commoner in children and young adults and usually occur within the first 4 days of treatment or after dosage increases.

– Akathisia characteristically occurs after large doses.

– Parkinsonism is commoner in adults and the elderly. It usually develops after weeks or months of treatment. One or more of the following may be seen – tremor, rigidity, akinesia or other features of Parkinsonism (commonly just tremor).

– Tardive dyskinesia. If this occurs it is usually, but not necessarily, after prolonged or high dosage. It can even occur after treatment has been stopped. Dosage should therefore be kept low whenever possible.

Convulsions have been reported in some patients.

Dizziness

Headache

Drowsiness

Hepatobiliary disorders:

Jaundice, usually transient, occurs in a very small percentage of patients. A premonitory sign may be a sudden onset of fever after one to three weeks of treatment followed by the development of jaundice. Neuroleptic jaundice has the biochemical and other characteristics of obstructive jaundice and is associated with obstructions of the canaliculi by bile thrombi; the frequent presence of an accompanying eosinophilia indicates the allergic nature of this phenomenon. Treatment should be withheld on the development of jaundice.

Renal and urinary disorders:

Retention of urine

Vascular disorders:

Hypotension or pallor may occur in children

Elderly or volume depleted subjects are particularly susceptible to postural hypotension (see section 4.4).

Cardiac disorders:

Cardiac arrhythmias including atrial arrhythmia, atrioventricular (A-V) block, ventricular tachycardia and ventricular fibrillation have been reported during therapy, possibly related to dosage (see section 4.4). Pre-existing cardiac disease, old age, hypokalaemia and concurrent tricyclic antidepressants may predispose.

Investigations:

Electrocardiogram changes, usually benign, including:

QT interval prolongation

U-wave abnormality

T-wave abnormality

ST segment depression

Eye disorders:

Accommodation disorders

Blood and lymphatic system disorders:

Mild leukopenia occurs in up to 30% of patients on prolonged high dosage.

Agranulocytosis may occur rarely; it is not dose related.

The occurrence of unexplained infections or fever requires immediate haematological investigation.

Skin and subcutaneous tissue disorders:

Contact skin sensitisation is a serious but rare complication in those frequently handling preparations of phenothiazines. Care must be taken to avoid contact of the drug with the skin.

Skin rashes of various kinds may also be seen in patients treated with the drug.

Patients on high dosage may develop photosensitivity in sunny weather and should avoid exposure to direct sunlight (see section 4.4). Ocular changes and the development of a metallic greyish-mauve colouration of exposed skin have been noted in some individuals, mainly females, who have received chlorpromazine continuously for long periods (four to eight years).

Endocrine disorders:

Hyperprolactinaemia which may result in galactorrhoea, gynaecomastia, amenorrhoea, impotence.

Neuroleptic malignant syndrome (hyperthermia, rigidity, autonomic dysfunction and altered consciousness) may occur (see section 4.9).

General disorders and administration site conditions:

Paradoxical excitement has been noted.

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 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 phenothiazine overdose include drowsiness or loss of consciousness, hypotension, tachycardia, ECG changes, ventricular arrhythmias and hypothermia. Severe extra-pyramidal dyskinesias may occur.

If the patient is seen sufficiently soon (up to 6 hours) after ingestion of a toxic dose, gastric lavage may be attempted. Pharmacological induction of emesis is unlikely to be of any use. Activated charcoal should be given. There is no specific antidote. Treatment is supportive.

Generalised vasodilatation may result in circulatory collapse; Raising the patient's legs may suffice, in severe cases, volume expansion by intravenous fluids may be needed; infusion fluids should be warmed before administration in order not to aggravate hypothermia.

Positive inotropic agents such as dopamine may be tried if fluid replacement is insufficient to correct the circulatory collapse. Peripheral vasoconstrictor agents are not generally recommended; avoid the use of adrenaline.

Ventricular or supraventricular tachy-arrhythmias usually respond to restoration of normal body temperature and correction of circulatory or metabolic disturbances. If persistent or life-threatening, appropriate anti-arrhythmic therapy may be considered. Avoid lidocaine and, as far as possible, long acting anti-arrhythmic drugs.

Pronounced central nervous system depression requires airway maintenance or, in extreme circumstances, assisted respiration. Severe dystonic reactions, usually respond to procyclidine (5 – 10 mg) or orphenadrine (20 – 40 mg) administered intramuscularly or intravenously. Convulsions should be treated with intravenous diazepam.

Neuroleptic malignant syndrome (NMS) has been reported in the context of alimemazine overdose. Symptoms of NMS include a combination of hyperthermia, muscle rigidity, altered mental status and autonomic instability. Since this syndrome is potentially fatal, alimemazine must be discontinued immediately, and intensive clinical monitoring and symptomatic treatment must be initiated.

Strict adherence to the recommended dose is critical (see also section 4.2).

Neuroleptic malignant syndrome should be treated with cooling. Dantrolene sodium may be tried.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

ATC Code: R06AD01

Pharmacotherapeutic group: Phenothiazine derivatives

Alimemazine has a central sedative effect, comparable to that of chlorpromazine, but largely devoid of the latter's anti-adrenaline action. It has powerful antihistamine and anti-emetic actions.

5.2 Pharmacokinetic properties

There is little information about blood levels, distribution and excretion in humans.

The rate of metabolism and excretion of phenothiazines decreases in old age.

5.3 Preclinical safety data

Not applicable.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core contains:

Lactose monohydrate

Microcrystalline cellulose

Sodium starch glycolate (Type A)

Colloidal anhydrous silica

Magnesium stearate

Film-coating contains:

Hypromellose

Macrogol 1500

Lake indigo carmine (E132)

Talc

Titanium dioxide (E171)

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 storage conditions.

6.5 Nature and contents of container

Alimemazine film-coated tablets are available in aluminium/PVC/PVDC blisters in pack sizes of 28 and 30.

Not all pack sizes may be marketed.