Gastromotil Film coated Tablets:

Each film coated tablet contains:  Domperidone (as maleate) .................................. 10 mg

Gastromotil Suspension: 

Each 100 ml contains: Domperidone .......................................................................... 100 mg

Gastromotil Suppositories: 

Each suppository contains: Domperidone ................................................................... 30 mg

Inactive ingredients: 

Gastromotil Film coated Tablets: Lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, colloidal silicone dioxide, povidone K 30, sodium lauryl sulphate, magnesium stearate.

Gastromotil Suspension:  Microcrystalline cellulose, carboxymethyl cellulose sodium, sorbitol 70 % solution, methylparaben, propylparaben, polysorbate 80, sodium hydroxide, purified water.

Gastromotil Suppositories: Hard fat, butylated hydroxyanisole, aerosil 200, polysorbate 80.

Adults and Children: The relief of the symptoms of nausea and vomiting.

It is recommended to take Gastromotil before meals. If taken after meals, absorption of the drug is somewhat delayed.

Gastromotil should not normally be used for longer than one week.

Adults and Adolescents (weighing 35 kg or more): 

The dose is 10 mg up to three times daily by mouth. These patients may also be given the medicine as suppositories of 30 mg twice daily.

Children and Adolescents (weighing less than 35 kg): 

The dose is 0.25 mg/kg body weight by mouth up to three times daily.

Tablets are unsuitable for use in Children weighing less than 35 kg.

Gastromotil is contraindicated in the following situations: 

Known hypersensitivity to domperidone or any of the excipients.

Prolactin-releasing pituitary tumour (prolactinoma).

Gastromotil should not be used when stimulation of gastric motility could be harmful: e.g. gastrointestinal haemorrhage, mechanical obstruction or perforation.

Concomitant administration with ketaconazole, erythromycin or other potent CYP3A4 inhibitors which prolong QTc interval such as fluconazole, voriconazole, clarithromycin and amiodarone.

Gastromotil must not be given to patients with moderate or severe impairment of liver function, or in those who have existing abnormalities of electrical activity in the heart or heart rhythm, or who are at increased risk of such effects.

Gastromotil should not be used with other medicines that have similar effects on the heart or reduce the breakdown of domperidone in the body (thus increasing the risk of side effects).

Precautions for use: 

Gastromotil Tablets contain lactose and may be unsuitable for patients with lactose intolerance, galactosaemia or glucose/galactose malabsorption.

Gastromotil Suspension contains sorbitol and may be unsuitable for patients with sorbitol intolerance. Also sorbitol may cause softening of stool.

Gastromotil Suppositories contain butylated hydroxyanisole and this may cause irritation of the eyes, skin and just inside body passages (such as the mouth and nose).

Use during Lactation: 

The total amount of domperidone excreted in human breast milk is expected to be less than 7 micrograms per day at the highest recommended dosing regimen. It is not known whether this is harmful to the newborn. Therefore breastfeeding is not recommended for mothers who are taking Gastromotil.

Use in Infants: 

Neurological side effects are rare (see Undesirable Effects). Since metabolic functions and the blood-brain barrier are not fully developed in the first months of life, the risk of neurological side effects is higher in young children.

Therefore, it is recommended that the dose be determined accurately and followed strictly, in neonates, infants, toddlers and small children.

Overdosing may cause extrapyramidal symptoms in children, but other causes should be taken into consideration.

Use in Liver disorders: 

Since domperidone is highly metabolised in the liver, it must not be given to patients with moderate or severe impairment of liver function.

Renal insufficiency: 

In patients with severe renal insufficiency (serum creatinine > 6 mg/100 mL, i.e., > 0.6 mmol/L) the elimination half-life of domperidone was increased from 7.4-20.8 hours, but plasma drug levels were lower than in healthy volunteers. Since very little unchanged drug is excreted via the kidneys, it is unlikely that the dose of a single administration needs to be adjusted in patients with renal insufficiency. However, on repeated administration, the dosing frequency should be reduced to once or twice daily depending on the severity of the impairment, and the dose may need to be reduced. Such patients on prolonged therapy should be reviewed regularly.

Use with CYP3A4 inhibitors: 

Co-administration with oral ketoconazole, erythromycin or other potent CYP3A4 inhibitors that prolong the QTc interval should be avoided (see Drug Interactions).

For Gastromotil Tablets and Suspension: 

The use of domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death, particularly in patients taking daily doses greater than 30 mg, and in patients older than 60 years of age.

In the first months of life and the metabolic functions of the blood brain barrier are not fully developed, the risk of neurological side effects in young children is higher.

For Gastromotil Suppositories: 

The use of domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death, particularly in patients taking daily doses greater than 30 mg, and in patients older than 60 years of age.

In the first months of life and the metabolic functions of the blood brain barrier are not fully developed, the risk of neurological side effects in young children is higher.

The main metabolic pathway of domperidone is through CYP3A4. In vitro data suggest that the concomitant use of drugs that significantly inhibit this enzyme may result in increased plasma levels of domperidone.

Separate in vivo pharmacokinetic/pharmacodynamic interaction studies with oral ketoconazole or oral erythromycin in healthy subjects confirmed a marked inhibition of domperidone's CYP3A4 mediated first pass metabolism by these drugs.

There are limited post-marketing data on the use of domperidone in pregnant women. The potential risk for humans is unknown. Therefore, Gastromotil should only be used during pregnancy when justified by the anticipated therapeutic benefit.

It is not known whether this is harmful to the newborn. Therefore breastfeeding is not recommended for mothers who are taking Gastromotil.

Gastromotil has no or negligible influence on the ability to drive or use machines.

The following frequencies are used for the description of the occurrence of adverse reactions: 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).

Immune System disorders: 

Very rare: Anaphylactic reactions including anaphylactic shock, angioedema, allergic reaction.

Endocrine disorders: 

Rare: Increased prolactin levels.

Psychiatric System disorders: 

Very rare: Agitation, nervousness.

Nervous system disorders: 

Very rare: Extrapyramidal side effects, convulsions, somnolence, headache.

Gastrointestinal disorders: 

Rare: Gastrointestinal disorders, including very rare transient intestinal cramps.

Skin and Subcutaneous tissue disorders: 

Very rare: Urticaria, pruritus, rash.

Reproductive system and Breast disorders: 

Rare: Galactorrhoea, gynaecomastia, amenorrhoea.

Cardiac disorders: 

Very rare: Ventricular arrhythmias.

Frequency not known: Prolongation of QTc.

Investigations: 

Very rare: Abnormal liver function tests.

As the hypophysis is outside the blood brain barrier, domperidone may cause an increase in prolactin levels. In rare cases this hyperprolactinaemia may lead to neuro-endocrinological side effects such as galactorrhoea, gynaecomastia and amenorrhoea.

Extrapyramidal side effects are very rare in neonates and infants, and exceptional in adults. These side effects reverse spontaneously and completely as soon as the treatment is stopped.

Other central nervous system-related effects of convulsion, agitation and somnolence, also are very rare and primarily reported in infants and children.

Symptoms: 

Overdose has been reported primarily in infants and children.

Symptoms of overdosage may include agitation, altered consciousness, convulsions, disorientation, somnolence and extrapyramidal reactions.

Treatment: 

There is no specific antidote to domperidone, but in the event of overdose, gastric lavage as well as the administration of activated charcoal, may be useful. Close medical supervision and supportive therapy is recommended.

Anticholinergic, and anti-parkinson drugs may be helpful in controlling the extrapyramidal reactions.

Pharmacodynamic properties: 

Gastromotil is a dopamine antagonist with anti-emetic properties. Domperidone does not readily cross the blood brain barrier. In domperidone users, especially in adults, extrapyramidal side effects are very rare, but domperidone promotes the release of prolactin from the pituitary. Its anti-emetic effect may be due to a combination of peripheral (gastrokinetic) effects and antagonism of dopamine receptors in the chemoreceptor trigger zone, which lies outside the blood-brain barrier in the area postrema.

Pharmacokinetic properties: 

Absorption: In fasting subjects, domperidone is rapidly absorbed after oral administration with peak plasma concentrations at 30-60 minutes. The low absolute bioavailability of oral domperidone (approximately 15%) is due to an extensive first-pass metabolism in the gut wall and liver. Although domperidone's bioavailability is enhanced in normal subjects when taken after a meal, patients with gastrointestinal complaints should take domperidone 15-30 minutes before a meal. Reduced gastric acidity impairs the absorption of domperidone. Oral bioavailability is decreased by prior concomitant administration of cimetidine and sodium bicarbonate. The time of peak absorption is slightly delayed and the AUC somewhat increased when the oral drug is taken after a meal.

Distribution: Oral domperidone does not appear to accumulate or induce its own metabolism; a peak plasma level after 90 minutes of 21 ng/ml after two weeks oral administration of 30 mg per day, was almost the same as that of 18 ng/ml after the first dose. Domperidone is 91-93% bound to plasma proteins.

Metabolism: Domperidone undergoes rapid and extensive hepatic metabolism by hydroxylation and N-dealkylation. In vitro metabolism experiments with diagnostic inhibitors revealed that CYP3A4 is a major form of cytochrome P-450 involved in the N-dealkylation of domperidone, whereas CYP3A4, CYP1A2 and CYP2E1 are involved in domperidone aromatic hydroxylation.

Excretion: Urinary and faecal excretions amount to 31 and 66% of the oral dose respectively. The proportion of the drug excreted unchanged is small (10% of faecal excretion and approximately 1% of urinary excretion). The plasma half-life after a single oral dose is 7-9 hours in healthy subjects but is prolonged in patients with severe renal insufficiency.

Gastromotil F.C. Tablets: Store at a temperature not exceeding 30^°C.

Gastromotil Suspension:  Store at a temperature not exceeding 30^°C.

Gastromotil Suppositories:  Store at a temperature 2°C - 8^°C.

Gastromotil Film coated Tablets: Box containing blisters of 10 tablets each.

Gastromotil Suspension:  Bottle of 200 ml.

Gastromotil 30 mg Suppositories: Box containing 5 suppositories.