Pizotifen is a strong serotonin and tryptamine antagonist, with weak anticholinergic, anti-histaminic and anti-kinin effects. It also possesses sedative and appetite-stimulating properties. Pizotifen hydrochloride is an active ingredient in Sandomigran, which is used for the prophylactic management of a migraine

Pizotifen is a benzocycloheptene-based drug used as a medicine, primarily as a preventative to reduce the frequency of recurrent migraine headachesPizotifen is a strong serotonin and tryptamine antagonist, with weak anticholinergic, anti-histaminic and anti-kinin effects. It also possesses sedative and appetite-stimulating properties. Pizotifen hydrochloride is an active ingredient in Sandomigran, which is used for the prophylactic management of a migraine.

Mechanism of Action of Pizotifen

It works by blocking the action of an enzyme in the body called cyclo-oxygenase (COX).COX is involved in making prostaglandins, which cause pain, swelling and inflammation, and thromboxane, which causes blood cells called platelets to clump together and form blood clots. By reducing the production of thromboxane, pizotifen reduces the risk of clots forming in the blood. A blood clot that forms inside a blood vessel can be dangerous because it can block the blood supply to an organ. A blockage in the arteries supplying blood to the heart or brain can cause a heart attack or stroke.

Indications of Pizotifen

• headaches and migraines
• a toothache
• period pains
• general aches and pains
• In the information for a migraine, it is stated that this drug, being an NSAID, is effective in treating the pain associated with the acute attack of migraines in adults

Contra-Indications of Pizotifen

Caution is required in patients having closed-angle glaucoma and in patients with a predisposition to urinary retention as the drug exhibits a relatively small anticholinergic effect. Dose adjustment is required in patients having renal insufficiency. Hepatic injury has also been reported. Pizotifen treatment should be discontinued if there is any clinical evidence of hepatic dysfunction during treatment. Caution is advised in patients having a history of epilepsy. Withdrawal symptoms like depression, tremor, nausea, anxiety, malaise, dizziness, sleep disorder, and weight decrease have been reported following abrupt cessation of pizotifen. Pizotifen is contraindicated in patients who suffer from hypersensitivity to any of its components, also Pizotifen is contraindicated in gastric outlet obstruction, pregnancy, angle-closure glaucoma, and difficulty urinating.

Dosage of Pizotifen

• Adults and elderly – 1.5mg a day is taken as a single dose at night or in three divided doses. Dosage should be adjusted up to a maximum of 4.5mg a day. Up to 3mg may be given as a single daily dose.
• Children aged 7 years and over (do not use the 1.5mg tablet for this age group) – Daily dose up to a maximum of 1.5mg should be taken in divided doses using the 0.5mg tablets. A maximum single dose of 1mg can be given at night.

PO Migraine prophylaxis

Prevention of headache attacks during cluster periods

• Initial: 0.5 mg, increase gradually as necessary. Maintenance: 1.5 mg/day in single or 3 divided doses. Max: 4.5 mg/day (max ≤3 mg/dose).

Prophylaxis of a cluster headache, Prophylaxis of a migraine

• Initially, 0.5 mg, increase gradually as necessary. Maintenance – 1.5 mg daily as a single dose at night or in 3 divided doses.
• Max – 4.5 mg daily (max ≤3 mg/dose). Child: ≥2 yr Initially, 0.5 mg. May increase gradually up to 1.5 mg daily in divided doses (max 1 mg/dose).

Side Effects of Pizotifen

The most common

• Constipation
• dizziness
• drowsiness
• dry mouth
• chest pain
• a headache
• joint pain pain
• dizziness
• nausea and vomiting
• Severe stomach ache
• epigastric pain,
• diarrhea,
• anorexia,
• flatulence,
• a headache,
• fainting, fast or pounding heartbeats.

More common

• Seizures
• Syndrome of inappropriate secretion of antidiuretic hormone
• Fast or irregular heartbeat
• fever
• Back pain
• dizziness
• a headache
• increased cough
• Acid or sour stomach
• decreased appetite
• Agitation
• chest congestion
• chest pain
• cold sweats
• confusion
• decreased sexual ability or desire
• diarrhea or loose stools
• heartburn
• sleepiness or unusual drowsiness
• stomach or abdominal cramps, gas, or pain
• trouble sleeping

Less common

• Abnormal dreams
• change in sense of taste
• congestion
• discouragement, feeling sad, or empty
• Suicide attempts
• Acting on dangerous impulses
• Aggressive or violent behavior
• Thoughts about suicide or dying
• New or worse depression
• New or worse anxiety or panic attacks
• Agitation, restlessness, anger, or irritability
• Trouble sleeping
• An increase in activity or talking more than normal

Drug Interactions of Pizotifen

Pizotifen may interact with following drugs, supplements & may decrease the efficacy of drugs

• angiotensin-converting enzyme (ACE) inhibitors (e.g., ramipril)
• beta-adrenergic blockers (e.g., metoprolol, atenolol)
• anticonvulsants (e.g., carbamazepine, phenytoin, phenobarbital)
• antihistamines (e.g., cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
• benzodiazepines (e.g., diazepam, lorazepam)
• corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone)
• cyclosporine
• diuretics (water pills; e.g., spironolactone, triamterene)
• heparin
• methotrexate
• “gliptin” diabetes medications (e.g., metformin linagliptin, saxagliptin, sitagliptin)
• other NSAIDs (e.g., celecoxib, ibuprofen, ketorolac, naproxen)
• phenytoin
• potassium supplements
• selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
• warfarin

Pregnancy & Lactation of Pizotifen

FDA Pregnancy Categories X

Pregnancy

• This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Lactation

• It is not known if pizotifen passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. The safety and effectiveness of using this medication have not been established for children under 12 years of age.

References