Pizotifen Tablets Bp 0.5mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
PIZOTIFEN TABLETS BP 0.5mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
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
3 PHARMACEUTICAL FORM
Film-coated tablet.
Cream film-coated, round, biconvex tablets embossed “0.5” on one side.
4 CLINICAL PARTICULARS
4.1. Therapeutic Indications
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.
4.2. Posology and Method of Administration
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 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.
4.3. Contra-indications
Hypersensitivity to pizotifen or other ingredients in the tablet.
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.
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.
4.5. Interactions with other Medicinal products and other Forms of Interaction
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 effects of antihypertensive medications (adrenergic neurone blockers).
Patients receiving monoamine oxidase inhibitors should not use pizotifen.
4.6. Pregnancy and Lactation
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.
4.7. Effects on Ability to Drive and Use Machines
Patients should be cautioned about the possibility of drowsiness 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 ( ± / 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 |
Drowsiness (including somnolence), dizziness. |
|
Rare |
Paraesthesia. |
|
Very rare |
Seizures. |
|
Gastrointestinal disorders Common |
Dry mouth, nausea. |
|
Uncommon |
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 Yellow Card Scheme; website: 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 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.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
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.
5.2. Pharmacokinetic Properties
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 halflife of about 23 hours.
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
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)
6.2.
Incompatibilities
None known
6.3. Shelf Life
Shelf-life
Two years from date of manufacture.
Shelf-life after dilution/reconstitution Not applicable.
Shelf-life after first opening Not applicable.
6.4 Special precautions for storage
Do not store above 25 °C.
6.5. Nature and Contents of Container
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) 250pm white rigid PVC. (ii) Surface printed 20pm 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.
6.6. Instruction for Use, Handling and Disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Actavis UK Limited (Trading styles: Actavis)
Whiddon Valley BARNSTAPLE N Devon EX32 8NS
8. MARKETING AUTHORISATION NUMBER
PL 00142/0446
OF
9. DATE OF FIRST AUTHORISATION/RENEWAL AUTHORISATION
December 1998
10 DATE OF REVISION OF THE TEXT
16/03/2015