TOPRISAN Film-coated tablet Ref.[51160] Active ingredients: Itopride

Caution should be exercised when taking Toprisan, as itopride potentiates acetylcholine action and induce cholinergic side effects.

Itopride should be administered cautiously in elderly (see section 4.2).

Data about long-term administration of itopride is not available.

Toprisan contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

• Metabolic interactions are not expected because itopride is mainly metabolised by flavine containing monooxygenases, not by CYP450.
• There are no interactions on the concomitant use of Toprisan with warfarin, diazepam, diclofenac, ticlopidine, nifedipine and nicardipine.
• Itopride has gastrokinetic effect, which may affect the absorption of concomitantly orally administrated medicines. Particular attention should be paid to medicines with a narrow therapeutic index, medicines with prolonged-release of the active substance and enteric-coated drug formulations.
• Anti-ulcer medicines such as cimetidine, ranitidine, teprenone and cetrexate do not affect the prokinetic activity of itopride.
• Anticholinergic agents may reduce the action of itopride.

Pregnancy

The safety of itopride use in pregnancy has not been established. Therefore Toprisan should be administered to pregnant women only if the benefit outweighs the potential risk.

Breast-feeding

Itopride is excreted into the milk of lactating rats. There are no data about itopride use during breastfeeding in humans.

Because of the possibility of adverse effects to the infant, a decision should be made either to discontinue breast-feeding, or Toprisan use, taking into account the importance of the drug to the breast-feeding mother.

Although no effects on ability to drive and use machines have been found, impairment of alertness cannot be ruled out since dizziness may occur very rarely.

Adverse reactions during clinical trials

During the clinical trials, itopride was well tolerated and no serious adverse reactions were reported. In 14 clinical trials, 19 from a total of 572 patients reported adverse reactions (the incidence of the adverse reactions was 2.4%).

Most of the adverse reactions that occurred in more than one patient were diarrhea in 4 cases (0.7%), headache in 2 cases (0.3%) and abdominal pain in 2 cases (0.3%). Abnormal laboratory results reported during clinical trials were decrease in white blood cells (leucocytopenia) in 4 cases (0.7%) and elevated prolactin in 2 cases (0.3%).

Adverse reactions from clinical practice

Adverse reactions have been ranked according to MedDRA terminology under headings of frequency using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

Patients treated with itopride reported the following adverse effects:

Blood and lymphatic system disorders

Uncommon: leukopenia

Not known: thrombocytopenia

Immune system disorders

Not known: anaphylactic reactions

Endocrine disorders

Uncommon: elevated prolactin levels

Not known: gynecomastia

Nervous system disorders

Uncommon: dizziness, headache, sleep disorders

Not known: tremor

Gastrointestinal disorders

Uncommon: diarrhoea, constipation, abdominal pain, sialorrhoea

Not known: nausea

Renal and urinary disorders

Uncommon: BUN (blood urea nitrogen) and creatinine increased

Hepatobiliary disorders

Not known: jaundice

Skin and subcutaneous tissue disorders

Rare: rash, redness and pruritus

Investigations

Not known: AST, increased ALT, increased gamma – GTP, increased alkaline phosphatase and bilirubin

Musculoskeletal and connective tissue disorders

Uncommon: chest or back pain

General disorders and administration site conditions

Uncommon: fatigue

Psychiatric disorders

Uncommon: irritability

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 ADR Reporting, Website: www.medicinesauthority.gov.mt/adrportal.

Not known.