Motinorm’
Domperidone
COMPOSITION :
Tablets: Each tablet contains 10 mg domperidone
Suspension: Each 1 ml contains 1 mg domperidone (!gm/ml).
Adult suppositories: Each suppository contains 60 mg domperidone.
Children suppositories: Each suppository contains 30 mg domperidone
Infant suppositories; Each suppository contains 10 mg domperidone
INDICATIONS :
1 – The dyspeptic symptom complex that is often associated with delayed gastric emptying, gastro-oesophageal reflux and oesophagitis:
– Epigastric sense of fullness, wly satiety, feetinq of abdominal distension, upper abdominal pain;
– Bloating, eructation, ftatulence:
– Nausea and vomiting:
– Heartburn with or without regurgitations of gastric contents in the mouth.
2 – Nausea and vomitingoffunctional,organic, infectious or dietetic origin or induced by radiotherapy or drug therapy. A specific indication is nausea and vomiting induced by dopamine aqonlsts, as used in Parkinson’s disease [such as l-dopa and brcmocrtptinel.
DSAGE AND ADMINISTRATION :
1 – Chronic dyspepsia (mainly oral administration)
– Adults: 10 mg {1 tablet or 10 mll3 times daily, 15-30 minutes before meals and, if nectSS3ry, once mort before rttiring.
– Childrtn: oral suspension: 2.5 ml per 10 kg body weight, 3 times daily before meals and, if necessary, once more in the evening.
Whenresultsarenotsalisfactory,theabovedosagemaybedoubledinadults and children over 1 year of age.
2. Acute and subacute conditions (particularly nausea and vomiting)
– Adults:
Oral: 20 rng (2 tablets. 2 sachets or 20 mll 3-4 times daily before meals and before bedtime;
Rectal: 2 to 4 suppositories “adults” [ •• 6Omg) daily.
– Childrtn:
Oral: 5 rnl per 10 kg body weight. 3-4 times daily before meals and before bedtime.
Rectal:
– Up to 2 years: 1 suppository “babies” (1O mg) 2-4 times daily
– 2-4 years: I suppository “children” (30 mg} twice daily
– 4-6 years: 1 suppository “children” (30mg}3 times daily
– Older than 6 years: 1 suppository “children” (30 mg) 4 times daily.
Remarks:
Oral Motinorm is recommended to be taken bt:fore meals. If taken after meals. absorption of the drug is somewhat delayed. The tablets are not intended to be administered to children below the age of 5 sears, In patients with renal insufficiency, the dosing frequency should be reduced {see “Warnings and Precautioos”l. The suppositories should preferably be inserted into an empty rectum. They should be inserted with the blunt end first as the form of the suppository is functionally determined: the anal sphincter will exert an inward pressure on the conical point of
the suppository.
CONTRAINOICATIONS :
Motinorm is contraindicated in patients with known intolerance to the drug. Motinorm should not be used whenever stimulation of gastric motility might be dangerous. e.g. in the presence of qastro- intestinal haemorrhage, mechanical obstruction or perforation. Motinorm is also contraindicated in patients with a prolactin-releasing pituitary tumour (prolactinoma).
SPECIAL WARNINGS AND PRECAUTIONS :
Motinorrn is not recommended for chronic use for the routine prop’wlaxs of postoperative nausea and vomiting. When antacids Ot antsecretorv agents ate used concomitantly, they should be taken after meals and not before meals, Le. they should not be taken simultaneously with Motinorm.
Use in infants:
Because the metabolic and blood-brain barrier functions are not fully developed during the first months of life, any drug should only be given to infants with great caution and under close medical supervi~on. Since the typical absence of neurological side effects with Motinorm is mainly due to its poor penetration through the blood-
brain barrier, the possible occurrence of such effects cannot be totally excluded in infants under 1 veer of age.
Use in fiver disorders:
Since domperldone is highly metabolised in the liver, Motinorm should be used with caution in patients with hepatic impairment
Use in kidney disorders:
In patients with severe renal insufficiency (serum creatinine. 6 mg/1OO ml, Le. I 0.6 mmolfl) 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 acute administration needs to be adju~ted in patients with renal insufficiency.
However, on reP.tated aeeunistraticn. tbUosing fre:que:ocy should be reduced to cnce.cr twice: daily, depending On the severity of the impairment, and the dose may need to be reduced. Generally, patients on prolonged therapy should be reviewed regularly.
INTERACTION WITH OTHER MEDICAMENTS AND OTHER FORMS OF INTERACTION
As with other Dopamine antagonists. there is theoretical potential that Motinotm may antagonise the hvpercrofactlneemlc effect of drugs such as bromocriptine. In addition. the prokinetic effects of dcmperldone may alter the absorption of some drugs. Opioid analgesics and antimuscarinics may antagonise the prokinetic effects of domperidone. Antacids and antisecretory drugs should not be given simultaneously with Motinorm as they lower its oral bioavailabilitv (see also “Warnings and Precautions”]. The main metabolic pathway of domperidone is through CYPJA4. In vitro data sugge:st that the concomitant use of drugs that significantly inhibit this enzyme may result in increased plasma levels of domperidone. ExampJes ofCYP3A4 inhibitors indude rhe following:
– Azol eantifungal;
– Macrolide antibiotics:
– HIVproteaseinhibitors;
– Nefazodone
The use of with ketoconazole has been reported to produce a threefold increase in plasma concentrations of dcmperidcne. and an associated slight prolongation in aT interval. Similar increases in domperidone concentrations might theoretically be seen with other potent inhibitors of CYPJA4 such as erythromycin or ritonavir (see above), and such combinations may be best avoided. Theoretically, since Motinorm has qestro-klnetic effects it could influence the absorption of concomitantly orally administered drugs, particularly those with sustained release or enteric coated formulations. However, in patients already stabilised on digoxin or paracetamol, concomitant administration of domperidone did not influence the blood levels of these drugs. Motinorm may also be associated with:
– neuroleptics. the action of which it does not potentlate.
– dopaminergic agonists [bromocriptine, l-dopal, whose unwanted peripheral effects such as digestive disorders. nausea and vomiting it suppresses without counteracting their central properties.
PREGNANCY AND lACTATION:
Domperidone: given to animals at doses up to 160 mg/kg/day did not produce teratogenic effects. However, as most medicines. Motinorm should only be used during the first trimester of pregnancy if this is justified by the anticipated
therapeutic benefit Up to now, there has been no evidence of any increase in the: risk of malformations in humans. The drug is excreted in breast milk of lactating rats (mostly as metabolitcs: peak concentration of 40 and 800 mg/ml after oral and i.v administration of 2.5 mg/kg respectivelvl. In women, dcmperidcne concentrations in breast milk are 4 times lower than corresponding plasma concentrations, It is nct known whether this is harmful to the newborn. lherefore nulSing is not recommended for mothers who are taking Motinorm, unless the expected benefits outweigh any potential risk.
EFFECTS ON ABIUTY TO DRIVE ANa USE MACHINES :
Motinorm does not affect the mental alertness.
ADVERSE EFFECTS
Undesirable effects
Side effects are rare; exct~tionaUy some: transient intestinal cramps have: been rt20rte:d. Extrapyramidal phenomena are rare in young children and exceptional in adults; they reVerse spon13rirousrv and completely as soon as the: treatment is stepped. As the pituitary gland is located outside the blood-brain barrier, Motinorm may induce an increase in the plasma prolactin level. In rare cases this hyperprolactinaemia may give: rise to neurc-endocinoloqlcel phenomena such as qatactcrrhoea and gynae:comastia. Whe:n the: blood-brain barrier is immature (as in infants) or impaired, the possible: occurrence of neurological side: effects
cannot be tctelts excluded. Raft allergic reactions, such as rash and urticaria, have also been reported.
Overdose
Symptoms of overdosage may include drowsiness. disorientation and extrapvramide! reactions. especially in children
Treatment
In case of cverdosaqe. the administration of activated charcoal, and close observation of the: patknt are re ccmmendec. Anticholinergic, antl-parkinson drugsor antihistamines with anticholine:rgic prcpertes may be helpful in controlling the
PHARMACOKINETICS :
Pharmacodynamic properties
Indomperidone users.especlallv in adults, extrapyramidal side effects are very rare, but domperidon e promotes the release of prolactin from the pituitary. Its anti-emetic effect may be due to a combination of peripheral (gastro kinetic) effects and antagonism of dopamine receptcrs in the chemoreceptor trigger zone, which lies outside the blood-brain barrier in the area postrema. Animal studies, together with the low concentrations found in the brain, indicate a predominantly peripheral effect of domperidone on jne:rece.ltors. Studies in man have shown oral domperidone to increase the duration of’lii’im’1 and-duoirtnal cortttacfcns, to Increase the gastric emptying of liquids and semi-solids in healthy subjects and of solids in patients in whom it was delaved, and to increase lower oesophageal sphincter pressure in healthy subjects. It has no effect on gastric secretion.
Pharmacokinetic properties :
In fasting subjects. domperidone is rapidly absorbed after oral administration, with peak plasma concentrations at approximatels 1 hour. The low absolute bioavailability of oral dompendone (approximately 15Gb) is due to an extensive first- pass metabolism in the gut wall and liver. Although dompendone’s bioavailability is enhanced in normal subjects when taken after a meal. patients with gastro-intestinal complaints should take: dompe:ridone 15-30 minutes before a meal. Reduced gastric acidity impairs the absorption cf dcmperldone. Oral bioavailability is decreased by prior administration of cimettdme or sodium bicarbonate. The time of peak absorption is slightly delayed and the AUC somewhat increased when the: oral drug is taken after a meal. Oral ccmpendcne does not appear to accumulate or to induce its own metabolism; a peak plasma level after 90 minutes of 21 nglml after two weeks oral administration of 30 mg per day was almost the same as that of 18 ng/ml after the first dose. Dompe:ridone is 91-93% bound to plasma proteins. Distribution studies with radiolabe:lled drugtn animals have: shown wide: tissue distribution, but low brain concentration. Small amounts of drug cross the: placenta in rats. Domperidone concentrations in breast milk of lactating women are 4 times lower than corresponding plasma ccncentraticrs, Domperidone undergoes rapid and extensive hepatic metabolism by hydroxylation and N-dealkylation. In vitro metabolism experiments with diagnostic inhibitors reveated that CYP 3A4 is a major form of cytochrome P-450 involved in the N-de:alkytation of domperidone, whereas CYPJA4, CYP1A2 and CYP2El are involvtd in domperidone: aromatic hydroxylation.
Urinary and faecal excretions amount to 31 and 66% of the oral dose rtSptttivtly. The proportion of the drug excreted unchanged is small (lCAb of faecal excretion and approximately Iq!) of urinary excretion). The plasma half-life after a single oral dose is 7-9 hours in healthy subjects but is prolonge:d in patients with stvtrt renal
insufficiency.
Pharmaceutical precautions :
Motinorm suppositories should be stored below 25″( in a dry place.
Motinorm tablets & suspensions should be stored between 15 to 30″(.
Keep out of the reach of children.
PACKAGE :
Tablets: Strips of 10 tablets in packs of 1 or z or a strips.
Suspension: Bottles of 125 ml (1 mgl ml)
Suppositories: Packs of 5 suppositories (10 mg, 30 mg or 60 mg)
Keep all medicaments out of the reach of Children
Manufactured by:
SmithKline 8eecham.3.EJ.haram-GizlI for GlaxoSmitnKline S.A.E……1gypt
