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 0.725 mg pizotifen hydrogen malate BP, 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.
The tablets are white, marked P on one side and plain on the 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).
It is not effective in relieving migraine attacks once in progress
4.2 Posology and method of administration
Adults: Usually 1.5 mg daily, This may be taken as a single dose at night or in three 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 over 2 years): Up to 1.5 mg daily, usually as a divided dose, although up to 1 mg has been given as a single dose at night.
Elderly: As for adults.
Method 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.
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, severe lactase deficiency or glucose-glactose malabsorption should not take Pizotifen tablets.
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 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 refrain from driving 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 appetite stimulating effect, increase in body weight and drowsiness (including somnolence and fatigue).
Frequencies are defined as: 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; not known (cannot be estimated from the available data).
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Immune system disorders | |
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Rare |
Hypersensitivity reactions, face oedema, urticaria and rash |
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Metabolism and nutrition disorders | |
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Very common |
Appetite stimulating effect and increase in body weight |
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Psychiatric disorders | |
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Rare |
Depression, CNS stimulation (e.g. aggression, agitation), hallucination, insomnia, anxiety |
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Nervous system disorders | |
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Common |
Drowsiness (including somnolence) dizziness |
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Rare: |
Paraesthesia |
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Very rare: |
Seizures |
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Gastrointestina |
disorders |
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Common |
Nausea, dry mouth |
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Uncommon |
Constipation |
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Musculoskeleta |
and connective tissue disorders |
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Rare |
Myalgia, arthralgia |
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General disorders and administration site conditions | |
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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.
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 Yellow Card Scheme at www.mhra.gov.uk/yellowcard.
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 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.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Studies in experimental animals have indicated that pizotifen has a strong antiserotonin and anti-tryptaminic properties, marked antihistaminic effects and some antagonist 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 transduction 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. Pitozifen inhibits serotonin re-uptake by the platelets, thus maintaining plasma serotonin and preventing the loss of tone and passive distension of 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
There are no preclinical safety data of relevance to the prescriber which are additional to those in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
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
4 years.
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, 250pm PVC/40gm2 PVDC sealed to 25pm 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. Instruction for Use/Handling
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Edmond Pharma Srl Strada Statale dei Giovi 131 20037 Paderno Dugnano (MI)
Italy
8 MARKETING AUTHORISATION NUMBER(S)
PL 14682/0001
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
23rd August 2001
10 DATE OF REVISION OF THE TEXT
03/02/2016