Active ingredients: Metoclopramide Hydrochloride mg Equivalent to metoclopramide hydrochloride anhydrous mg

Transcription

1 Name Primperan 10 mg / 2 ml Metoclopramide hydrochloride anhydrous Solution for I.M. or I.V. injection (Ampoules) Composition Each 2 ml ampoule contains: Active ingredients: Metoclopramide Hydrochloride mg Equivalent to metoclopramide hydrochloride anhydrous mg Excipients: Sodium chloride mg Water for injection to. 2 ml Pharmaceutical form Solution for injection in ampoules. Pharmacodynamic Properties Stimulant of intestinal motility. Metoclopramide: neuroleptic dopamine antagonist, it prevents vomiting by blocking dopaminergic sites. Pharmacokinetics Distribution: Metoclopramide is widely distributed in the tissues. Its volume of distribution is 2.2 to 3.4 l/kg. It shows little binding to plasma proteins. It crosses the placenta and is secreted into maternal milk. Metabolism: Metoclopramide undergoes little metabolism. Excretion: It is primarily excreted in the urine as free or sulphate-conjugated metoclopramide. Its plasma elimination half-life is 5 to 6 hours. This increase in renal or hepatic impairment. Indications Symptomatic treatment of nausea and vomiting (Prokinetic action). Prevention and treatment of nausea and vomiting induced by antimitotic agents. Dosage and administration For I.M. or I.V. use: One ampoule contains 10mg of anhydrous metoclopramide. Symptomatic treatment of nausea and vomiting not induced by antimitotic agents: Adults: 1/2 to 1 ampoule per intake, 3 times daily.

2 Prevention and treatment of nausea and vomiting induced by antimitotic agents: Adults: the dosage is 2 to 10 mg/kg daily varying according to the emetic effect of the anti-cancer treatment: - Either divided into several direct intravenous injections or 15-minute infusions, - or administered as a 2 to 3-mg/kg bolus as a 15-minute infusion before chemotherapy followed by infusion of 0.5 mg/kg/hour over 6-8 hours. Children: the usual dose is 0.1 to 0.3 mg/kg/day (no dose-ranging studies have been included with the dossier). Contraindications This product must not be used in the following situations: - Hypersensitivity to metoclopramide or any of the components. - Gastrointestinal haemorrhage, mechanical obstruction or gastrointestinal perforation for which the stimulation of gastrointestinal motility constitutes a risk. - History of neuroleptic or metoclopramide-induced tardive dyskinesia. - Confirmed or suspected pheochromocytoma, because of the risk of severe hypertension episodes. - Combination with levodopa (L-dopa) because of a mutual antagonism. - Contraindication in children below 16 years. Side effects Nervous system and psychiatric disorders: The following reactions, sometimes associated, occur more frequently when high doses are used: - Extrapyramidal symptoms: acute dystonia and dyskinesia, parkinsonian syndrome, akathisia, even following administration of a single dose of the drug, particularly in children and young adults (see Warnings); - Drowsiness, decreased level of consciousness, confusion, and hallucination. Other reactions may occur: - Tardive dyskinesia, during or after prolonged treatment, particularly in elderly patients. - Seizures. - Neuroleptic malignant syndrome. - Depression. Gastro-intestinal disorders: Diarrhea. Blood and Lymphatic system disorders:

3 - Methaemoglobinaemia which could be related to NADH cytochrome b5 reductase deficiency, particularly in neonates (see Warnings). - Sulfhaemoglobinaemia, mainly with concomitant administration of high doses of sulphurreleasing drugs. Endocrine disorders: Endocrine disorders during prolonged treatment in relation with hyperprolactinaemia (amenorrhea, galactorrhoea, gynaecomastia). General disorders and administration site conditions: - Allergic reaction including anaphylaxis. - Asthenia. Cardiac and Vascular disorders: - Hypotension especially with intravenous formulation. - Bradycardia, heart block particularly with the intravenous formulation. - Cardiac arrest, occurring shortly after injectable use, and which can be subsequent to bradycardia. Drug interactions Contraindicated combination: Levodopa: Levodopa and metoclopramide have a mutual antagonism. Combination to be avoided: Alcohol: Alcohol potentiates the sedative effect of metoclopramide. Combination to be taken into account: - Anticholinergics and morphine derivatives: Anticholinergics and morphine derivatives have both a mutual antagonism with metoclopramide on the digestive tract motility. - CNS depressants (morphine derivatives, hypnotics, anxiolytics, sedative H1 antihistamines, sedative antidepressants, barbiturates, clonidine and related): Sedative effects of CNS depressants and metoclopramide are potentiated. - Neuroleptics: Metoclopramide may have an additive effect with neuroleptics on the occurrence of extrapyramidal disorders. Due to the prokinetic effect of metoclopramide, the absorption of certain drugs may be modified. Digoxin: Metoclopramide decreases digoxin bioavailability. Careful monitoring of digoxin plasma concentration is required. Cyclosporine: Metoclopramide increases cyclosporine bioavailability. Careful monitoring of cyclosporine plasma concentration is required. - Mivacurium and suxamethonium: Metoclopramide injection may prolong the duration of neuromuscular block (through inhibition of plasma cholinesterase).

4 Pregnancy Data on pregnant patients (> 1000) indicate no malformative nor foeto/ neonatal toxicity during 1rst trimester of pregnancy. A limited amount of data on pregnant patients (> 300) indicate no neonatal toxicity in other trimesters. Animal studies do not indicate reproductive toxicity. The use of metoclopramide may be considered during pregnancy, if necessary. Lactation Metoclopramide is excreted in breast milk and adverse reactions in the breast-fed baby cannot be excluded. A decision should be made whether to discontinue breast-feeding or to abstain from metoclopramide treatment. Warnings and precautions - Only the oral drops form is suitable for use in infants. - Extrapyramidal disorders may occur, particularly in children and young adults and/or when high doses are used. These adverse reactions resolve completely after treatment discontinuation. A symptomatic treatment may be necessary (benzodiazepines in children and/or anticholinergic anti-parkinsonian drugs in adults). - Treatment should not exceed 3 months because of the risk of tardive dyskinesia. - Respect the time interval (of at least 6 hours in children less than 15 years) specified in the dosage section between each metoclopramide administration, even in case of vomiting and rejection of the dose, in order to avoid overdose. - Metoclopramide is not recommended in epileptic patients as benzamides may decrease the epileptic threshold. - In patients with renal or hepatic impairment, a dose reduction is recommended. - As with neuroleptics, a Neuroleptic Malignant Syndrome (NMS) characterized by hyperthermia, extrapyramidal disorders, and autonomic nervous instability and elevated CPK, may occur. Therefore cautions have to be taken if fever, one of the symptoms of a NMS, occurs and metoclopramide has to be stopped if a NMS is suspected. - Methaemoglobinaemia which could be related to NADH cytochrome b5 reductase deficiency has been reported. In such cases, metoclopramide should be immediately and permanently discontinued and appropriate measures initiated. Storage No special precautions for storage. Store below 25 degrees C. Keep all medicines out of reach of children. Presentation Carton box containing 12 ampoules, each ampoule contains 2 ml and an inner leaflet. Company

5 Produced by: sanofi-aventis Egypt s.a.e. El Sawah El Amiriya Under license of: sanofi-aventis / France