sanofi-aventis

Vallergan 7.5mg/5ml Oral Solution.

Each 5 ml of solution contains 7.5 mg of Alimemazine (Trimeprazine) Tartrate.

For a full list of excipients, see section 6.1.

Oral Solution.

A clear, bright, straw-coloured solution with an odour of apricots.

In the management of urticaria, pruritus (including that associated with obstructive jaundice) and senile pruritus.

In short term sedation and pre-anaesthetic medication in children.

The route of administration is oral.

For use in adults and children over 2 years of age.

Use a measuring cup or measuring pipette, which should be held vertically

Recommended dosage:

Urticaria and Pruritus

Adults:

The usual total daily dosage is 30 to 40 mg in divided doses.

Children:

The usual total daily dosage is 7.5 to 20 mg in divided doses.

Dosing may be repeated as needed during the day not to exceed 4 daily doses.

Evening dosing is preferable due to the pronounced sedative effect of alimemazine.

For sedation

Children:

Aged 7 to 12 years:

60 to 90 mg daily in divided doses.

Aged 3 to 6 years:

15 to 60 mg daily in divided doses.

Use should be for as short a period as possible.

Pre-anaesthetic medication (children aged 2-7 years): The maximum dosage recommended for this indication in children is 2 mg per kg.

• Use in patients hypersensitive to the active ingredient or any of the excipients.

• Use in patients with hepatic or renal dysfunction, epilepsy, Parkinson's disease, hypothyroidism, phaeochromocytoma, myasthenia gravis, prostatic hypertrophy.

• Use in patients with a history of narrow angle glaucoma.

• Use in patients with a history of agranulocytois associated with other phenothiazines.

• Use in patients with coma particularly if associated with other central nervous system depressants.

• Use in patients on concurrent therapy with other drugs potentially haemotoxic.

• Sultopride (see Interactions).

• Pregnant women (1^st trimester) or nursing mothers (see Pregnancy and Lactation)

Phenothiazines should not be used in children under 2 years of age.

Alimemazine should be used with caution in:

• Elderly patients presenting:

- greater susceptibility to orthostatic hypotension, dizziness and sedative effects,

- chronic constipation (risk of paralytic ileus),

- possible prostatic hypertrophy

• Patients with severe hepatic and/or renal insufficiency (risk of accumulation).

Monitoring (of clinical and possible EEG parameters) should be intensified in epileptic patients because phenothiazines and terpene derivatives (menthol) may lower the seizure threshold.

• Allergic manifestations:

In the event of persistence or worsening of allergic symptoms (respiratory distress, oedema, skin lesions, etc) or signs associated with viral infection, the clinical approach should be reevaluated.

Phenothiazines should only be used with great caution in patients with a history of jaundice or with existent liver dysfunction or blood dsycrasias.

Patients receiving phenothiazines over a prolonged period require regular and careful surveillance with particular attention to potential for inducing eye changes, effects on haemopoiesis, liver dysfunction, myocardial conduction defects, particularly if other concurrently administered drugs also have potential effects on these systems.

Phenothiazines should be used with particular care in the presence of extremes of temperature because of its capacity to interfere with the body's thermoregulator.

Phenothiazines produce a photosensitizing effect, therefore exposure to sunlight should be avoided during treatment.

The sugar content should be considered in patients with diabetes or on low-sugar diets.

Patients are strongly advised not to consume alcoholic beverages or medicines containing alcohol during treatment.

Avoid concomitant use of neuroleptics. (See Interactions).

Phenothiazines should be used with great caution in patients with coronary insufficiency or cardiac disease, due to tachycardia – inducing and hypotensive effects of phenothiazines (See section 4.8). As with other neuroleptic phenothiazines, caution is advised in patients with a family history of QT prolongation.

(Galactorrhoea) Lactation and amenorrhoea are rare and tend to be dose dependant, and may be related to increased secretion or prolaction.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

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

Inadvisable combinations:

Alcohol: Alcohol enhances the sedative effect of H₁ antihistamines. Impaired alertness may be hazardous for driving and operating machines. Do not consume alcoholic beverages or take medicines containing alcohol.

Sultopride: Increased risk of ventricular rhythm disorders, particularly torsades de pointes, due to additive electrophysiological effects.

Disulfiram; cefamandole, cefoperazone, latamoxef (cephalosporin antibacterial agents); chloramphenicol (phenicol antibacterial agent); chlorpropamide, glibenclamide, glipizide, tolbutamide (hypoglycaemic sulphonamide antidiabetic agents); griseofulvin (antifungal agent); metronidazole, ornidazole, secnidazole, tinidazole (5 nitroimidazoles); ketoconazole (azole antifungal agent); procarbazine (cytostatic agent): medicines producing antabuse reactions with alcohol (heat, redness, vomiting, tachycardia). Do not consume alcoholic beverages or take medications containing alcohol.

Combinations to take into consideration:

Other central nervous system depressants: sedative antidepressants, barbiturates, benzodiazepines, clonidine, and related drugs, hypnotics, morphine derivatives (analgesics and antitussives), methadone, neuroleptics, anxiolytics: increased CNS depression.

Impaired alertness may be hazardous for driving and using machines.

Atropine and atropine-like drugs (imipramine-like antidepressants, anticholinergic antiparkinsonian agents, atropine-like antispasmodics, disopyramide, phenothiazine neuroleptics): additive atropine-like adverse effects of the type urinary retention, constipation, dry mouth.

The drug may intensify by increasing the effects of Parkinson's disease.

Simultaneous administration of prochlorperazine and desferrixoamine has been observed to induce a transient metabolic encephalopathy characterised by loss of consciousness for 48-72 hours. This may occur with trimeprazine since it shares many of the pharmacological activities of prochlorperazine.

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

Risk of malformations:

• There are no reliable data on tetratogenic effects in animals

• Currently, there are no data sufficiently relevant to assess the potential risk of malformations or foetotoxic effects when alimemazine is used during pregnancy.

Risk of foetotoxicity:

There have been rare reports of gastrointestinal disturbances related to atropine-like properties (abdominal distension, meconium ileus, delayed meconium excretion, difficulty in feeding initiation, tachycardia, neurological disorders, etc.) in neonates whose mothers had received long term treatment with high doses of anticholinergic drugs. In view of this data, this drug should not be used during the first trimester of pregnancy. It should only be used after the first trimester, and given only on an occasional basis on the third trimester.

If this drug is used at pregnancy term, a period of monitoring of the neurological and gastrointestinal function of the neonate appears warranted.

It is not known whether alimemazine is excreted into the maternal milk. In view of potential sedation or paradoxical excitation of the neonate and particularly considering the risks of sleep apnoea associated with phenothiazines, this drug should not be used by nursing mothers.

Phenothiazines may induce drowsiness especially at the start of the treatment. Persons taking these drugs should not drive or operate machinery unless the drug has been shown not to interfere with physical or mental ability.

Autonomic effects:

- sedation or drowsiness, more marked at the start of treatment;

- anticholinergic effects such as dry mouth, constipation, accommodation disorders, mydriasis, cardiac palpitations, risk of urinary retention;

- orthostatic hypotension (particularly elderly and volume depleted subjects)

- balance disorders, dizziness, impaired memory or concentration;

- lack of motor coordination, tremor (more frequent in elderly patients);

- mental confusion, hallucinations;

- more rarely, but notably in infants: excitation-type effects: agitation, nervousness, insomnia.

Sensitization reactions:

- erythema, eczema, pruritus, purpura, urticaria (including giant urticaria);

- oedema, more rarely: Quinckes (angioneurotic) oedema;

- anaphylactic shock;

- photosensitization.

Skin and Eyes: Contact skin sensitisation is a serious but rare complication in those frequently handling preparations of phenothiazines. The greatest 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.

Haematological effects:

- leucopenia, neutropenia, exceptionally: agranulocytosis;

- thrombocytopenia;

- haemolytic anaemia.

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

Liver function: jaundice, occurs in a very small percentage of patients taking neuroleptics. A premonitory sign may be a sudden onset of fever after one 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 obstruction 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.

Cardiorespiratory:

Cardiac arrhythmias, including atrial arrhythmia, A-V block, ventricular arrhythmias (ventricular tachycardia and ventricular fibrillation) have been reported during neuroleptic therapy, possible related to dosage. Pre-existing cardiac disease, old age, hypokalaemia and concurrent tricyclic anti-depressants may predispose.

ECG changes, usually benign, include QT interval prolongation, ST depression, U-waves and T-wave changes. Sudden unexplained death, cardiac arrest, Torsades de pointes have been reported with the class of neuroleptics.

Respiratory depression is possible in susceptible patients.

Extrapyramidal: acute dystonias or dyskinesias, usually transitory are commoner in children and young adults and usually occur within the first four days of treatment or after dosage increases.

Akathisia characteristically occurs after large initial 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, though not necessarily after prolonged or high dosage. It can even occur after treatment has been stopped. Dosage should therefore be kept low whenever possible.

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

Neuroleptic malignant syndrome: (hyperthermia, rigidity, autonomic dysfunction and altered consciousness) may occur with any neuroleptic.

A minor side effect is nasal stuffiness.

Symptoms of phenothiazine overdosage include drowsiness or loss of consciousness, hypotension, tachycardia, E.C.G. changes, ventricular arrhythmias and hypothermia. Severe extrapyramidal dyskinesias may occur.

If the patient is seen sufficiently soon (up to 6 hours) after ingestion of a toxic dose, gastric lavage should 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 ionotropic 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 tachyarrhythmias usually respond to restoration of normal body temperature and correction of circulatory or metabolic disturbances. If persistent or life threatening, appropriate antiarrhythmic therapy may be considered.

Avoid lignocaine and, as far as possible, long acting antiarrhythmic drugs.

Pronounced central nervous system depression requires airway maintenance or, in extreme circumstances, assisted respiration. Severe dystonic reactions usually respond to procyclidine (510 mg) or orphenadrine (2040 mg) administered intramuscularly or intravenously. Convulsions should be treated with intravenous diazepam.

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

Trimeprazine, a phenothiazine derivative, has a central sedative effect comparable to that of chlorpromazine, but is largely devoid of the latter's antiadrenaline action. It has powerful antihistamine and antiemetic actions.

A phenothiazine, well absorbed but metabolised in gut wall and in liver. Distribution is wide, elimination occurs in bile and urine with prolonged half-life.

None.

Not applicable.

3 years.

Use within one month of opening bottle.

Do not store above 25°C. Keep container in the outer carton.

Vallergan 7.5mg/5ml Oral Solution is supplied in amber glass Type III bottles with an aluminium lid with a tamper evident band. This product is available in 100ml bottles.

Vallergan 7.5mg/5ml Oral Solution may be diluted if required, using simple syrup (without preservatives).

sanofi-aventis Ireland Ltd.

Citywest Business Campus

Dublin 24.

PA 540/132/1

1^st April 1977/5^th June 2006.

February 2010.