Pizotifen 0.5mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Pizotifen 0.5 mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 0.725mg of Pizotifen hydrogen malate equivalent to 0.5 mg of Pizotifen base.
Each film-coated tablet contains lactose monohydrate 32.14 mg, as excipient. For a full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Film-coated tablet
White round flat tablet marked MP84 on one side and plain on reverse.
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 migraine attacks once in progress.
4.2 Posology and method of administration
Adults including the elderly
Usually 1.5 mg daily. This may be taken as a single dose at night or in 3 divided doses. Dosage should be adjusted according to individual patient requirements, up to a maximum of 4.5 mg daily. Up to 3 mg can be given as a single dose.
Children (aged 2 years and over only)
Up to 1.5 mg daily. This must be given as two or three smaller doses. Do not give children more than 1.0 mg in a single dose.
Route of Administration: Oral
4.3 Contraindications
Hypersensitivity to the drug or to any of the other tablet ingredients.
Pizotifen should not be given to children under 2 years of age.
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. Dosage adjustment may be required in patients with renal insufficiency.
Patients should be cautioned about the possibility of drowsiness (see 4.7).
Pizotifen should be used with caution in patients with a history of epilepsy.
Pizotifen tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, sucrase-isomaltase insufficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
The central effects of sedatives, hypnotics, antihistamines (including certain common cold preparations) and alcohol may be enhanced by pizotifen.
Pizotifen antagonises the hypotensive effect of adrenergic neurone blockers
4.6 Fertility, Pregnancy and lactation
Pregnancy
As clinical data with pizotifen in pregnancy are very limited, it should only be administered under compelling circumstances.
Lactation
Use in nursing mothers is not recommended.
4.7 Effects on ability to drive and use machines
Pizotifen may cause drowsiness, somnolence and dizziness. Therefore, caution should be exercised when driving or using machines.
Patients being treated with Pizotifen and presenting with drowsiness (including somnolence and fatigue) must be instructed to refreain from driving of vehicles or engaging in activities where impaired alertness may put themselves or others at risk.
4.8 Undesirable effects
The most commonly reported side effects are drowsiness (including somnolence and fatigue) and appetite stimulating effect, 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.
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 Pizotifen therefore gradual withdrawal is recommended. Withdrawal symptoms include anxiety, tremors, insomnia, nausea and loss of consciousness.
4.9 Overdose
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 cases of very recent uptake, gastric lavage may be considered. Severe hypotension should 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.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antimigraine drug, ATC code: N02C X01
Studies in experimental animals have indicated that pizotifen has strong antiserotonin and anti-tryptaminic properties, marked antihistaminic 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 pizotifen in migraine is associated with its ability to modify the humoral mechanism 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.
5.2 Pharmacokinetic properties
Absorption: The 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 2 mg 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.
5.3
Preclinical safety data
No relevant information additional to that contained elsewhere in the SPC.
6.1 List of excipients
Lactose monohydrate
Cellulose microcrystalline Maize starch,
Povidone K30 Magnesium stearate Silicon dioxide Hypromellose Macrogol 6000 Talc
Titanium dioxide (E171)
6.2 Incompatibilities
Not applicable
6.3 Shelf life
48 months
6.4 Special precautions for storage
Do not store above 30°C. Store in the original package.
6.5 Nature and contents of container
White opaque blister, 250 pm PVC/40 gm2 PVDC sealed to 25 pm aluminium foil/PVDC.
The blistered product is available in cartons containing 28, 30, 56, 60, 84, 90, 112 and 120 tablets. (Please note that not all pack sizes may be marketed.)
6.6 Special precautions for disposal
Not applicable
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MARKETING AUTHORISATION HOLDER
Genethics Europe Limited 41 - 43 Klimentos Klimentos Tower Nicosia 1061 Cyprus
MARKETING AUTHORISATION NUMBER(S)
PL 42976/0046
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
01/12/2011
DATE OF REVISION OF THE TEXT
27/04/2016