Pizotifen 0.5mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Pizotifen 0.5mg Tablets.
2
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Pizotifen Malate equivalent to Pizotifen 0.5mg.
Excipients with known effect: Each tablet contains 66.87 mg of lactose (as lactose monohydrate)
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet.
Pale cream to yellow circular biconvex film-coated tablets with an approximate diameter of 6mm, marked “PZT 0.5” on one face
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Prophylactic treatment of recurrent vascular headaches, including classical migraine, common migraine and cluster headache (periodic migrainous neuralgia).
4.2 Posology and method of administration
Posology
Adults including the older people
Usually 1.5mg daily. This may be taken as a single dose at night or in three divided doses, using 1.5mg tablets or 0.5mg tablets as appropriate. 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.
Paediatric population
Up to 1.5mg daily, usually as a divided dose. Use of the 1.5mg tablets is not recommended but up to 1mg has been given as a single dose at night.
Method of administration:
For oral use.
4.3 Contra-indications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
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. Pizotifen should be used with caution in patients with a history of epilepsy as seizures as adverse effects have been observed more frequently in such patients.
This product contains lactose, patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
4.5 Interaction with other medicinal products and other forms of interaction
The sedating effects of anti-depressants, sedatives, hypnotics, anti-histamines (including certain common cold preparations) may be enhanced by Pizotifen.
Tolerance to alcohol may be reduced.
Pizotifen antagonizes the hypotensive effect of antihypertensive medications (adrenergic neurone blockers).
Patients receiving monoamine oxidase inhibitors should not use pizotifen.
4.6
Fertility pregnancy and lactation
Pregnancy
As clinical data with pizotifen in pregnancy are very limited, it should only be administered during pregnancy under compelling circumstances.
Breast-feeding
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.
4.7 Effects on ability to drive and use machines
Patients should be cautioned about the possibility of drowsiness, somnolence and dizziness and informed of its significance in the driving of vehicles and the operation of machinery.
4.8 Undesirable effects
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.
|
Nervous system disorders | |
|
Common Rare Very rare |
Drowsiness (including somnolence), dizziness. Paraesthesia. Seizures. |
|
Eye disorders | |
|
Very rare |
Angle closure glaucoma |
|
Gastrointestinal disorders | |
|
Common Uncommon |
Dry mouth, nausea. Constipation. |
|
Skin and subcutaneous tissue disorders | |
|
Rare |
Urticaria, rash. |
|
Musculoskeletal and connective tissue disorders | |
|
Rare |
Myalgia, arthralgia. |
|
Metabolism and nutrition disorders | |
|
Very common |
Appetite stimulating effect and increase in body weight. |
|
General disorders and administration site conditions |
|
Common |
Fatigue. |
|
Immune system disorders | |
|
Rare |
Hypersensitivity reactions, face oedema. |
|
Psychiatric disorders | |
|
Rare |
Depression, CNS stimulation (e.g. aggression, agitation ), anxiety, hallucination, insomnia, rare cases of sleep disorders. |
In children CNS stimulation may occur.
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 the internet at www.mhra.gov .uk/yellowcard.
4.9 Overdose
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 in case of very recent uptake, diuresis or administration of activated charcoal. Severe hypotension must be corrected (cave: adrenaline may produce paradoxical effects). Excitatory states or convulsions may be treated with short-acting barbiturates or benzodiazepines. General surveillance measures are indicated including monitoring of the cardiovascular and respiratory systems.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
ATC Code: N02C X01
Pizotifen is a tricyclic (benzocycloheptathiophene) compound possessing structural similarities to cyproheptadine and tricyclic antidepressant drugs.
Pizotifen has 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.
5.2 Pharmacokinetic properties
Pizotifen is well absorbed from the gastro-intestinal tract with over 80% being absorbed. Absorption is relatively fast with an absorption half-life of 0.5 to 0.8 hours. Peak plasma concentrations occur approximately 5 hours after oral administration. Over 90% of pizotifen is bound to plasma proteins. The metabolism of Pizotifen is extensive with 55% excreted as metabolites. Less than 1% is excreted unchanged. Over half a dose is excreted in the urine, chiefly as metabolites; a significant proportion is excreted in the faeces. The primary metabolite of pizotifen (N-glucuronic conjugate) has a long elimination half-life of about 23 hours.
5.3 Preclinical safety data
No preclinical data relevant to prescriber.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose Monohydrate Microcrystalline Cellulose Magnesium Stearate Hypromellose (E464)
Titanium Dioxide (El71)
Macrogol
Iron Oxide Yellow (El72)
Quinoline Yellow Aluminium Lake (B 104) Iron Oxide Black (El72)
6.2 Incompatibilities
Not applicable
Shelf life
6.3
2 years
6.4 Special precautions for storage
Store below 25°C. Keep the tablets in the original package.
6.5 Nature and contents of container
Pizotifen Tablets 0.5mg will be packed into either of the following presentations:
Blister strips constructed of 250pm PVC with a 60g/m2 PVdC coating and 20pm aluminium foil with a heat sealing lacquer. The blister strips are packed into a cardboard carton. Each carton contains 28 or 84 tablets.
Polypropylene containers fitted with a polyethylene cap and a tamper-evident tear strip. Each container holds 84 tablets.
Not all pack sizes may be marketed
6.6 Special precautions for disposal and other handling
No special requirements
Any unused medicinal product product or waste material should be disposed of in accordance with local requirements.
7. MARKETING AUTHORISATION HOLDER
Tillomed Laboratories Limited
3 Howard Road
Eaton Socon
St Neots
Cambridgeshire
PE198ET
UK
PL 11311/0379
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
07/05/2009
10 DATE OF REVISION OF THE TEXT
14/10/2016