SANOMIGRAN Tablets 0.5mg

The active ingredient is : 4-(1-methyl-4-piperidylidene)-9,10-dihydro-4H-benzo-[4,5]cyclohepta [1,2-b] thiophene hydrogen malate (=pizotifen hydrogen malate).

Each tablet contains 0.725mg pizotifen hydrogen malate BP.

For a full list of excipients, see section 6.1.

Coated tablets.

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

It is not effective in relieving migraine attacks once in progress.

Adults

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 patient requirements up to a maximum of 4.5mg daily. Up to 3mg may be given as a single dose.

Children (aged over 2 years)

Up to 1.5mg daily, usually as a divided dose, although up to 1mg has been given as a single dose at night.

Use in the elderly

Clinical work with SANOMIGRAN has not shown elderly patients to require different dosages from younger patients.

Method of administration

Oral.

Known hypersensitivity to pizotifen or any of the excipients (see section 6.1. List of excipients).

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

Pizotifen should be used with caution in patients with a history of epilepsy.

SANOMIGRAN coated tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose-glactose malabsorption should not take SANOMIGRAN.

The central effects of sedatives, hypnotics, antihistamines (including certain common cold preparations) and alcohol may be enhanced by SANOMIGRAN.

SANOMIGRAN antagonises the hypotensive effect of adrenergic neurone blockers

Pregnancy

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

Lactation

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

Pizotifen may cause drowsiness, somnolence and dizziness. Therefore, caution should be exercised when driving or using machines.

Patients being treated with Sanomigran and presenting with drowsiness (including somnolence and fatigue) must be instructed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk.

The most common side-effects are appetite stimulating effect, increase in body weight and drowsiness (including somnolence and fatigue).

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.

Immune system disorders:

Rare: Hypersensitivity reactions, face oedema, urticaria and rash

Metabolism and nutrition disorders:

Very common: Appetite stimulating effect and increase in body weight

Psychiatric disorders:

Rare: Depression, CNS stimulation (e.g. aggression, agitation), hallucination, insomnia, anxiety

Nervous system disorders:

Common: Drowsiness (including somnolence), dizziness

Rare: Paraesthesia

Very rare: Seizures

Gastrointestinal disorders:

Common: Nausea, dry mouth

Uncommon: Constipation

Musculoskeletal and connective tissue disorders:

Rare: Myalgia, arthralgia

General disorders and administration site conditions:

Common: Fatigue

Acute withdrawal reactions have been reported following abrupt cessation of SANOMIGRAN therefore gradual withdrawal is recommended. Withdrawal symptoms include anxiety, tremors, insomnia, nausea and loss of consciousness.

Symptoms: 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: Administration of activated charcoal is recommended; in case of very recent uptake, gastric lavage may be considered. Severe hypotension must be corrected (CAVE: adrenaline may produce paradoxical effects). If necessary, symptomatic treatment including monitoring of the cardiovascular and respiratory systems. Excitatory states or convulsions may be treated with short acting benzodiazepines.

Pharmacotherapeutic group: antimigraine drug, ATC code: N02C X01

Pharmacodynamic studies demonstrate pizotifen to have powerful anti-serotonin and anti-tryptaminic properties, marked anti-histaminic effects and some antagonistic activity against kinins. It also possesses weak anti-cholinergic effects and sedative properties.

Pizotifen also possesses appetite-stimulating properties.

The prophylactic effect of SANOMIGRAN 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 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.

Absorption

Absorption of pizotifen in man is fast (absorption half life 0.5 to 0.8 hours) and nearly complete. The absolute bioavailablility is 78%. Maximum blood levels are reached 5 hours after a single 2mg oral administration of pizotifen (parent compound and N-glucuronide-conjugate measured together).

Biotransformation

Pizotifen is extensively metabolised. Glucuronidation is the main route of biotransformation and the main metabolite is the N-glucuronide-conjugate, accounting for at least 50% of the plasma and 60-70% of urinary excreted radioactivity.

Distribution

Protein binding of pizotifen in human plasma in vitro amounts to 91%. The distribution volume in man is 833 L and 70 L for pizotifen and its N-glucuronide, respectively.

Elimination

About one-third of an orally applied dose is excreted via the biliary route into the faeces, a significant proportion, corresponding to about 18% of the applied dose, representing parent drug, likely produced in the intestine after biliary excretion of the N-glucuronide-conjugate. Less than 1% of the administered dose of pizotifen is excreted unchanged in the urine, whereas up to 55% is excreted as metabolites. Pizotifen is eliminated with a half life of approximately 23 hours (total radioactivity). Unchanged pizotifen and the N-glucuronide have, as estimated from the excretion in the urine, a comparable elimination half-life.

Special patient groups

In patients with kidney insufficiency dosage adjustment may be necessary.

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

The tablet contains lactose, maize starch, polyvinylpyrrolidone, magnesium stearate, talc (acid washed), The coating constituents are sugar (granulated no.2), talc, gum acacia, titanium dioxide, iron oxide yellow, carnauba wax, printing wax, colloidal anhydrous silica and purified water.

None.

60 months.

Protect from direct light.

The tablets are ivory, circular, biconvex printed SMG on one side and come in PVC/PVDC opaque blister packs containing 60 tablets.

None.

Novartis Pharmaceuticals UK Limited

(trading as Sandoz Pharmaceuticals)

Frimley Business Park

Frimley

Camberley

Surrey

GU16 7SR

PL 00101/0036.

15 March 1974 / 2 March 2009

13 August 2009

POM