Vallergan Tablets

1. Name Of The Medicinal Product

Vallergan tablets 10mg

2. Qualitative And Quantitative Composition

Alimemazine tartrate 10mg

3. Pharmaceutical Form

Circular, film coated biconvex tablet with bevelled edge, dark blue in colour, one face impressed V/10. The reverse side is plain

4. Clinical Particulars

4.1 Therapeutic Indications

Vallergan 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. In the management of urticaria and pruritus.

In pre-medication as a sedative before anaesthesia in children aged between 2 to 7 years.

4.2 Posology And Method Of Administration

The product is administered orally

Not recommended for infants less than 2 years old.

Urticaria and pruritus

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

Elderly: Dosage should be reduced to 10mg once or twice daily.

Children over2 years of age: The use of Vallergan Syrup is recommended.

As a sedative before anaesthesia

The dosage for children is best achieved by use of Vallergan Syrup.

4.3 Contraindications

Vallergan should be avoided in patients with hepatic or renal dysfunction, epilepsy, Parkinson's disease, hypothyroidism, phaeochromocytoma, myasthenia gravis, prostatic hypertrophy. It should be avoided in patients known to be hypersensitive to phenothiazines or to any of the excipients or with history of narrow angle glaucoma.

4.4 Special Warnings And Precautions For Use

Precautions for use:

Vallergan 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, due to the tachycardia-inducing and hypotensive effects of phenothiazines (see section 4.8)

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

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

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

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

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

Anticholinergic agents may reduce the antipsychotic effect of phenothiazines.

Some drugs interfere with absorption of phenothiazines: antacids, anti-Parkinson, lithium. Increases or decreases in the plasma concentrations of a number of drugs, eg 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.

4.6 Pregnancy And Lactation

There is inadequate evidence of the safety of Vallergan 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. Vallergan, 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. Phenothiazines may be excreted in milk: breast feeding should be suspended during treatment.

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

Minor side-effects are nasal stuffiness, dry mouth, insomnia, agitation.

Liver function: 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.

Cardiorespiratory: hypotension, or pallor may occur in children. Elderly or volume depleted subjects are particularly susceptible to postural hypotension (see section 4.4).

Cardiac arrhythmias, including atrial arrhythmia. A-V block, ventricular tachycardia and fibrillation have been reported during therapy, possibly related to dosage. Pre-existing cardiac disease, old age, hypokalaemia and concurrent tricyclic antidepressants may predispose. ECG changes, usually benign, include widened QT interval, ST depression, U-waves and T-wave changes.

Respiratory depression is possible in susceptible patients.

Blood picture: A mild leukopaenia 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.

Extrapyramidal: 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.

Skin and eyes: 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: hyperprolactinaemia which may result in galactorrhoea, gynaecomastia, amenorrhoea: impotence.

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

Paradoxical excitement has been noted.

4.9 Overdose

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 should be treated with cooling. Dantrolene sodium may be tried.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

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

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

6. Pharmaceutical Particulars

6.1 List Of Excipients

Microcrystalline cellulose

Lactose monohydrate (spray dried)

Silica, colloidal anhydrous

Magnesium stearate

Sodium starch glycollate

Hypromellose

Polyethylene glycol 300

Blue opaspray M-1-4229 (purified water EP, Indigo Carmine, Titanium Dioxide, Industrial Methylated Spirits 74 OP BP, Hydroxypropyl methylcellulose)

Purified water

6.2 Incompatibilities

None stated

6.3 Shelf Life

36 months

6.4 Special Precautions For Storage

Protect from light. Store below 30 °C

6.5 Nature And Contents Of Container

PVDC coated uPVC/Al foil blister pack containing 28 tablets

6.6 Special Precautions For Disposal And Other Handling

Not applicable

7. Marketing Authorisation Holder

sanofi-aventis

One Onslow Street

Guildford

Surrey

GU1 4YS

UK

8. Marketing Authorisation Number(S)

PL 04425/0379

9. Date Of First Authorisation/Renewal Of The Authorisation

September 2006

10. Date Of Revision Of The Text

January 2007

LEGAL CATEGORY

POM