Domperidone

SECTION 2: Hazards identification

CANADIAN WHMIS SYMBOLS EMERGENCY OVERVIEW RISK Possible risk of impaired fertility. Possible risk of harm to the unborn child.

Potential Acute Health Effects

SWALLOWED ■ Accidental ingestion of the material may be damaging to the health of the individual. ■ Domperidone is readily absorbed from the gut. Domperidone may cause extrapyramidal reactions (slurred speech, confusion, difficulty in swallowing, lethargy, tremors and/or muscle restlessness) especially in young children. Some of the side effects associated with domperidone are an extension of its dopamine antagonist properties. A majority of these side effects resolve spontaneously during continued therapy or are tolerated. However, more serious or troublesome side effects (e.g., galactorrhoea, gynecomastia, or menstrual irregularities) can be dose-related and will respond to lowering the dose or discontinuing therapy. Occasional symptoms include CNS effects (dry mouth headache) conjunctivitis (itching, redness, pain, or swelling of eye) endocrinological effects (hot flushes menstrual irregularities) galactorrhoea (breast milk flowing from the nipple) gynecomastia (excessive development of the breast in the male) mastalgia (pain in the breast) pruritus (itching) rash stomatitis (swelling of the mouth) urticaria (hives). Rare symptoms include asthenia (lack or loss of strength), CNS effects (dizziness irritability nervousness thirst), change in urinary frequency, oedema (swelling of face, hands, lower legs, or feet) extrapyramidal effects (difficulty in speaking loss of balance or muscle control), gastrointestinal effects (abdominal cramps change in appetite constipation diarrhea heartburn), leg cramps, lethargy (drowsiness mental dullness sluggishness tiredness weakness), palpitations (fast, irregular, pounding, or racing heartbeat or pulse), dysuria ( burning, difficult, or painful urination ). EYE ■ Although the material is not thought to be an irritant, direct contact with the eye may cause transient discomfort characterized by tearing or conjunctival redness (as with windburn). Slight abrasive damage may also result. The material may produce foreign body irritation in certain individuals. SKIN ■ The material is not thought to be a skin irritant (as classified using animal models). Abrasive damage however, may result from prolonged exposures. Good hygiene practice requires that exposure be kept to a minimum and that suitable gloves be used in an occupational setting. ■ Skin contact with the material may damage the health of the individual; systemic effects may result following absorption. ■ Open cuts, abraded or irritated skin should not be exposed to this material. ■ Entry into the blood-stream, through, for example, cuts, abrasions or lesions, may produce systemic injury with harmful effects. Examine the skin prior to the use of the material and ensure that any external damage is suitably protected. INHALED ■ The material is not thought to produce either adverse health effects or irritation of the respiratory tract following inhalation (as classified using animal models). Nevertheless, adverse effects have been produced following exposure of animals by at least one other route and good hygiene practice requires that exposure be kept to a minimum and that suitable control measures be used in an occupational setting. ■ Persons with impaired respiratory function, airway diseases and conditions such as emphysema or chronic bronchitis, may incur further disability if excessive concentrations of particulate are inhaled.

Potential chronic health

Ample evidence from experiments exists that there is a suspicionthis material directly reduces fertility. Results in experiments suggest that this material may cause disorders in the development of the embryo or fetus, even when no signs of poisoning show in the mother. There has been some concern that this material can cause cancer or mutations but there is not enough data to make an assessment. A number of benzimidazoles have been shown to also inhibit mammalian tubulin polymerisation and to be aneugenic in vivo. Aneugens affect cell division and the mitotic spindle apparatus resulting in loss or gain of whole chromosomes, thereby inducing an "aneuploidy". Mitotic aneuploidy is a characteristic of many types of tumorigenesis (in cancer). Several benzimidazoles have been shown to be genotoxic. Genotoxicity may arise as aneugens may also be clastogens, or may produce clastogenic metabolites. Clastogens increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Studies indicate that intravenous domperidone increases lower oesophageal sphincter pressure and gastro-duodenal motility but has no effect on gastric acid secretion or gastrin release.