PIZOTIFEN TABLETS BP 0.5mg

Each tablet contains 0.725mg of Pizotifen hydrogen malate equivalent to 0.500mg of Pizotifen base.

Also contains Lactose.

For a full list of excipients, see section 6.1

Film-coated tablet.

Cream film-coated, round, biconvex tablets embossed “0.5” on one side.

Prophylactic treatment of recurrent vascular headaches, including classical migraine, common migraine and cluster headache (periodic migrainous neuralgia).

Pizotifen is not effective in relieving a migraine attack once in progress.

Posology

Adults and elderly: Usually 1.5mg daily. This may be taken as a single dose at night or in three divided doses. Dosage should be adjusted to individual patients' requirements up to a maximum of 4.5mg daily. Up to 3mg may be given as a single daily dose.

Children: Pizotifen can be prescribed in children from the age of 7 years.

Use of the 1.5mg tablets is not recommended and the appropriate paediatric doses may be given using the 0.5mg Pizotifen Tablets. Daily doses up to a maximum of 1.5mg should be given usually in divided doses.

A maximum single dose of 1mg can be given at night.

Method of Administration

For oral use.

Hypersensitivity to pizotifen or other ingredients in the tablet.

Although the anticholinergic activity of pizotifen is relatively weak, caution is required in the presence of closed angle glaucoma and in patients with a predisposition to urinary retention (eg prostate hypertrophy). Dosage adjustment may be necessary in patients with kidney insufficiency.

Seizures as adverse effects have been observed more frequently in patients with epilepsy. Pizotifen should be used with caution in patients with a history of epilepsy.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

The sedating effects of antidepressants, sedatives, hypnotics, antihistamines (including certain common cold preparations) may be enhanced by Pizotifen.

Tolerance to alcohol may be reduced.

Antagonises the hypotensive effect of antihypertensive medications (adrenergic neurone blockers).

Patients receiving monoamine oxidase inhibitors should not use pizotifen.

As clinical data with pizotifen in pregnancy are very limited it should only be administered during pregnancy under compelling circumstances.

Although the concentrations of pizotifen measured in the milk of treated mothers are not likely to affect the infant, its use in nursing mothers is not recommended.

Patients should be cautioned about the possibility of drowsiness and informed of its significance in the driving of vehicles and the operation of machinery.

The most commonly occurring side-effects are drowsiness and an increased appetite which may lead to an increase in body weight.

Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention: Very common ( 1/10); common ( 1/100, < 1/10); uncommon ( 1/1000, < 1/100); rare ( 1/10,000, < 1/1000); very rare ( < 1/10,000), including isolated reports .

In children CNS stimulation may occur.

Symptoms of overdosage may include drowsiness, dizziness, hypotension, dryness of the mouth, confusion, excitatory states (in children), ataxia, nausea, vomiting, dyspnoea, cyanosis, tachycardia, convulsions (particularly in children), coma and respiratory paralysis. Treatment should be directed to the elimination of the drug by gastric lavage and diuresis. Severe hypotension must be corrected (cave: adrenaline (epinephrine) may produce paradoxical effects). Convulsions may be treated with short-acting barbiturates or benzodiazepines. General surveillance measures are indicated.

Pizotifen is a tricyclic (Benzocycloheptathiophene) compound possessing structural similarities to cyproheptadine and the tricyclic antidepressant drugs.

Pharmacodynamic studies demonstrate pizotifen to have powerful antiserotonin and antitryptaminic properties, marked antihistaminic effects and some antagonistic activity against kinins. It also possesses weak anticholinergic effects and sedative properties.

Pizotifen also possesses appetite stimulating properties.

The prophylactic effect of pizotifen in migraine is associated with its ability to modify the humoral mechanisms of headache. It inhibits the permeability increasing effect of serotonin and histamine on the affected cranial vessels, thereby checking the transudation of plasmakinin so that the pain threshold of the receptors is maintained at 'normal' levels. In the sequence of events leading to the migraine attack, depletion of plasma serotonin contributes to loss of tone in the extracranial vessels. Pizotifen inhibits serotonin re-uptake by the platelets, thus maintaining plasma serotonin and preventing the loss of tone and passive distension of the extracranial arteries.

Pizotifen is well absorbed from the gastro-intestinal tract, peak plasma concentrations occurring approximately 5 hours after oral administration. The absorption of pizotifen is fast (absorption half life 0.5 to 0.8 hours) and nearly complete (80%). Over 90% is bound to plasma proteins. Pizotifen undergoes extensive metabolism. Over half of a dose is excreted in the urine, chiefly as metabolites; a significant proportion is excreted in the faeces. The primary metabolite of pizotifen (N-glucuronide conjugate) has a long elimination half-life of about 23 hours.

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

Tablet core contains:

Povidone

Lactose monohydrate

Maize starch

Magnesium stearate

Microcrystalline cellulose (E460)

Film-coat contains:

Hypromellose

Medium Chain Triglycerides

Titanium Dioxide (E171)

Yellow Iron Oxide (E172)

Black Iron Oxide (E172)

None known

Shelf-life

Two years from date of manufacture.

Shelf-life after dilution/reconstitution

Not applicable.

Shelf-life after first opening

Not applicable.

Do not store above 25°C.

The product containers are rigid injection moulded polypropylene tablet containers with snap-on polyethylene lids.

The product may also be supplied in blister packs in cartons:

a) Carton: Printed carton manufactured from white folding box board.

b) Blister pack: (i) 250µm white rigid PVC. (ii) Surface printed 20µm hard temper aluminium foil with 5-7g/M² PVC compatible heat seal lacquer on the reverse side.

Pack sizes: 28, 30, 56, 60, 84, 90, 100, 112, 120, 168, 180.

Not applicable.

Name or style and permanent address of registered place of business of the holder of the Marketing Authorisation:

Actavis UK Limited

(Trading styles: Actavis)

Whiddon Valley

BARNSTAPLE

N Devon EX32 8NS

PL 0142/0446

December 1998

19/11/2010

IF APPLICABLE

IF APPLICABLE