Alimemazine tartrate 10mg/5ml oral solution, sugar-free

Alimemazine tartrate 10mg per 5ml

Excipient with known effect:

Each 5 ml of oral solution contain of:

- 5.0 mg (0.03 mmol) of sodium benzoate

- 5.0 mg (0.04 mmol) of sodium sulfite

- 5.0 mg (0.03 mmol) sodium metabisulfite

- 4.55 mg (0.20 mmol) of sodium

- 253.3 mg (3.33 mmol) of propylene glycol

- 1.07 mg (0.02 mmol) of ethanol

For the full list of excipients, see section 6.1.

Oral solution.

Alimemazine has powerful antihistamine and anti-emetic actions and is used for the management of urticaria and pruritus.

Alimemazine tartrate 10mg/5ml oral solution, sugar-free should be used for this indication in children.

Alimemazine may be used in pre-medication as a sedative before anaesthesia in children aged between 2 to 7 years but only Alimemazine tartrate 30mg/5ml oral solution, sugar-free should be used for this specific indication (see 4.2).

Posology

Not recommended for children less than 2 years old.

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

Urticaria and pruritus

Adults: 10 mg (5 ml) two or three times daily; up to 100 mg (50 ml) per day have been used in intractable cases.

Elderly: Dose should be reduced to 10 mg (5 ml) once or twice daily.

Children 2-5 years of age: 2.5 mg (approx. 1.25 ml) three or four times daily.

Children 5-12 years of age: 5 mg (2.5 ml) three or four times daily

Children over 12 years of age: 10 mg (5 ml) two or three times daily

As a sedative before anaesthesia

For the indication of sedation prior to anaesthesia, which requires a once only, high dose of alimemazine, the higher strength 30mg/5ml oral solution should be prescribed in order to limit propylene glycol (excipient) exposure

Method of administration

For oral administration.

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 2 years of age (see section 4.4)

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).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 a history of seizures (see section 4.8).

Paediatric population

Alimemazine is contraindicated for use in children less than 2 years of age due to the risk of marked sedation and respiratory depression.

There is a risk of post-operative restlessness especially if the child is in pain.

Excipients warnings

Sodium bisulphite, sodium metabisulfite: May rarely cause severe hypersensitivity reactions and bronchospasm.

Sodium benzoate: This medicine contains 5.0 mg sodium benzoate in 5 ml oral solution

Sodium: This medicine contains less than 1 mmol sodium (23mg) per dosage, that is to say essentially 'sodium-free'.

Propylene glycol: This medicine contains 253.3 mg propylene glycol in 5 ml oral solution

Ethanol: This medicinal product contains small amounts of ethanol (alcohol), less than 100 mg per 5 ml.

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 and MAOI's (including moclobemide). Respiratory depression may occur.

The hypotensive effect of most antihypertensive drugs especially alpha-adrenoreceptor blocking agents may be exaggerated by phenothiazines.

The use of antimuscarinics will increase the risk of antimuscarinic side effects when used in conjunction with antihistamines.

The action of some drugs may be opposed by phenothiazines. These include amfetamine, 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, 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.

Pregnancy

There is inadequate evidence of the safety of alimemazine in human pregnancy, 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 3-4cm. Possible adverse effects on the neonate include lethargy or paradoxical hyperexcitability, tremor and low Apgar score.

Breast-feeding

Phenothiazines may be excreted in milk: breast feeding should be suspended during treatment.

Fertility

There is no information on the effects of Alimemazine on human fertility

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

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

Hepatobillary 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, atrio-ventricular (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 and 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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Symptoms of phenothiazine overdosage 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 (5-10mg) or orphenadrine (20-40mg) 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.

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

There is little information about blood levels, distribution and excretion in humans. The rate of metabolism and excretion of phenothiazines decreases in old age.

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

Propylene glycol (E1520)

Sodium benzoate (E211)

Citric acid monohydrate (E330)

Sodium citrate dehydrate (E331)

Sodium metabisulfite (E223)

Sodium sulfite (E221)

Ascorbic acid (E300)

Sodium cyclamate (E952)

Peach flavor

Hydrochloric acid for pH adjustment (E507)

Water, purified

None stated.

30 months (unopened)

30 days (once opened)

This medicinal product does not require any special storage conditions.

Glass bottle 100ml

A child-resistant, tamper-evident screw cap, a syringe adaptor and a graduated 0.1mL dosing syringe of 5mL.

The adaptor is inserted in the bottle before use. The syringe is then put in the adaptor in the upright position and then turned upside down together with the bottle (Fig. 1). In this position the medicine is dosed. At the start of the measuring procedure, the transparent dosing body as well as the white plunger must be in the bottommost position. To measure

the dosing quantity, use one hand to hold the bottom, transparent dosing body and the other hand to pull on the top, white plunger until you can read the desired quantity in ml.

Afterwards the bottle is turned in the upright position again and the dosed syringe can be removed (Fig. 2). The bottle is sealed after removing the inserted adaptor by using the common closure.

Lucis Pharma Ltd

14 Aston Magna, Moreton in Marsh

Gloucestershire GL56 9QQ

United Kingdom

PL 42176/0019

17/02/2021

17/02/2021