Motilium Suppositories 30mg
- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
- Company information
- More information about this medicine
AdultsThe relief of the symptoms of nausea and vomiting, epigastric sense of fullness, upper abdominal discomfort and regurgitation of gastric contents.
ChildrenThe relief of the symptoms of nausea and vomiting.
Adults and adolescents (over 12 years and weighing 35 kg or more)The initial duration of treatment is four weeks. Patients should be re-evaluated after four weeks and the need for continued treatment re-assessed.60 mg suppositories two times per day.
Infants and childrenThe total daily dose is dependent on the child's weight:For a child weighing more than 15 kg: 30 mg suppositories two times per day.30 mg suppositories are unsuitable for use in children weighing less than 15 kg.
Precautions for use
Use during lactation:The total amount of domperidone excreted in human breast milk is expected to be less than 7μg per day at the highest recommended dosing regimen. It is not known whether this is harmful to the newborn. Therefore breast-feeding is not recommended for mothers who are taking Motilium.
Use in infants:Neurological side effects are rare (see "Undesirable effects" section). 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, Motilium should be not be used in patients with hepatic impairment.
Renal insufficiency:In patients with severe renal insufficiency (serum creatinine > 6 mg/100 ml, i.e. > 0.6 m mol/l) the elimination half-life of domperidone was increased from 7.4 to 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 Potent CYP3A4 Inhibitors:Co-administration with oral ketoconazole, erythromycin or other potent CYP3A4 inhibitors that prolong the QTc interval should be avoided (see section 4.5 Interaction with other medicinal products and other forms of interaction).
Immune System Disorder:Very rare; anaphylactic reactions including anaphylactic shock, angioedema, allergic reaction
Endocrine disorder:Rare; increased prolactin levels
Psychiatric System Disorder:Very rare; agitation, nervousness
Nervous system disorders:Very rare; extrapyramidal side effects, convulsions, somnolence, headache
Gastrointestinal disorders:Rare; gastro-intestinal 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: QTc prolongation
Investigations:Very rare; liver function test abnormalAs 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.
TreatmentThere 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, anti-parkinson drugs may be helpful in controlling the extrapyramidal reactions.
AbsorptionIn fasting subjects, domperidone is rapidly absorbed after oral administration, with peak plasma concentrations at 30 to 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 gastro-intestinal 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.After rectal administration of 60mg domperidone suppositories, a plateau is attained with domperidone plasma concentrations of about 20ng/ml lasting from 1 to 5 hours after administration. Although peak plasma levels are only about one third of that of an oral dose, the mean rectal bioavailability of 12.4% is quite similar to that after oral administration.
DistributionOral 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. Distribution studies with radiolabelled drug in animals have shown wide tissue distribution, but low brain concentration. Small amounts of drug cross the placenta in rats.
MetabolismDomperidone 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.
ExcretionUrinary 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
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