SANDOMIGRAN Tablet Ref.[27801] Active ingredients:

Renal impairment

Caution is required in patients with renal impairment. Dosage adjustment may be necessary.

Hepatic impairment

Caution is required in patients with hepatic impairment. Dosage adjustment may be necessary.

After prolonged use, hepatotoxic effects might occur and patients should be advised to report for adequate laboratory evaluation. Hepatic injury has been reported, ranging from transaminase elevations to severe hepatitis. Pizotifen treatment should be discontinued if there is any clinical evidence of hepatic dysfunction during treatment and until the cause of the liver abnormality is determined.

Withdrawal symptoms

Acute withdrawal reactions have been reported following abrupt cessation of pizotifen, therefore, gradual withdrawal is recommended. Withdrawal symptoms include depression, tremor, nausea, anxiety, malaise, dizziness, sleep disorder, loss of consciousness, anorexia and rapid weight loss (see ADVERSE REACTIONS).

Dependence / Tolerance

Some patients developed tolerance to Sandomigran with prolonged use of the drug. Increase in dosage, not exceeding the maximum recommended daily dose, may overcome this tolerance.

Effects on the ability to drive and use machines

Patients should be warned that Sandomigran may cause dizziness, somnolence, fatigue, sedation and other CNS effects. Therefore, caution should be exercised when driving or using machines. Patients being treated with Sandomigran and presenting with somnolence, dizziness and/or fatigue episodes must be instructed to refrain from engaging in activities where impaired alertness may put themselves or others at risk.

Anticholinergic effects

In view of the weak anticholinergic effect of Sandomigran, caution is required in patients with narrow-angle glaucoma or with a predisposition to urinary retention (e.g., prostatic hypertrophy). In general, patients with narrow-angle glaucoma should not be given drugs with possible anticholinergic effects, unless they are required and the patient is under special care and medical supervision for this condition.

Effects on Weight

Sandomigran treatment leads to weight gain in a significant number of patients and may be associated with excessive weight loss upon discontinuation. Caution is advised in patients who are vulnerable to excess weight gain or weight loss.

Lactose

Sandomigran coated tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, fructose intolerance, lactase deficiency, sucrose-isomaltase insufficiency or glucosegalactose malabsorption should not take Sandomigran.

Visual Impairments

A limited number of cases of lens opacities have been reported but did not appear to be drugrelated. Pizotifen use has also been associated with ocular dysfunctions including increased intraocular pressure, pupil dilation and diplopia. It is recommended that any impairment in vision be reported to the attending physician for further investigation.

Special Populations

Patients with diabetes or cardiovascular disease should be given Sandomigran with caution, and appropriate laboratory tests should be done at regular intervals.

Pregnant Women

The safety of Sandomigran for use during human pregnancy has not been established. Sandomigran should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Women

Animal studies show that pizotifen enters the milk.

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.

Pediatrics (<12 years of age)

Sandomigran is contraindicated in children under the age of 12 (see CONTRAINDICATIONS).

Adolescents (12-17 years of age)

There is limited evidence supporting the safety and efficacy of Sandomigran in children 12-17 years of age, therefore Sandomigran should be used with caution in this age group.

Epilepsy

Seizures as undesirable effects have been observed more frequently in patients with epilepsy. Sandomigran should be used with caution in patients with epilepsy.

Increased appetite, weight gain and drowsiness (including somnolence and fatigue) are the most common side effects. Physicians should be aware of the potential negative effects of Sandomigran (pizotifen as hydrogen malate) in special populations already with an excess in weight or in normal weight population where an excess in weight could be deleterious (arterial hypertension, diabetes mellitus and hypercholesterolemia). A gradual increase in the dosage of Sandomigran is recommended to minimize or reduce the incidence of drowsiness.

Table 1 is based on pizotifen post-market spontaneous adverse event reports. The percentages shown are calculated by dividing the number of adverse events reported by the estimated number of patients exposed to the drug during the same time period. The causal relationship between pizotifen and the emergence of these events has not been established.

Table 1. Pizotifen Post-Market Spontaneous Adverse Event Reports:

Sandomigran use has also been associated with ocular dysfunctions including increased IOP (intraocular pressure), pupil dilation and diplopia.

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. Anorexia and rapid weight loss have also been observed.

The following adverse reactions have also been identified during post-approval use of Sandomigran:

Hepatobiliary disorders: Fulminant hepatitis, Hepatic enzyme increased, Hepatitis, Jaundice.

Musculoskeletal and connective tissue disorders: Muscle cramps.

Nervous system disorders: Sedation.

Reproductive system and breast disorders: amenorrhoea, breast enlargement, breast pain, nonpuerperal lactation.

Pizotifen is extensively metabolized in the liver, primarily by N-glucuronidation. Increased plasma concentration of pizotifen upon concomitant administration of drugs which exclusively undergo glucuronidation cannot be excluded.

Central Nervous System (CNS) agents: Central effects of sedatives, hypnotics, antihistamines, including certain common cold preparations, alcohol, psychotherapeutic agents or other drugs with CNS depressant effects may be enhanced. Tolerance to alcohol may be reduced.

Antihypertensives: Sandomigran (pizotifen) may reduce the efficacy of antihypertensive medications (adrenergic neurone blockers) as it antagonizes their hypotensive effect. Patient blood pressure monitoring is therefore recommended.

Monoamine Oxidase Inhibitors: MAOIs can prolong and intensify the anticholinergic effects of antihistaminic substances. Concomitant use with MAOIs should therefore be avoided (see CONTRAINDICATIONS).