Symptoms
Extrapyramidal disorders, drowsiness, decreased level of consciousness, confusion, hallucination, and cardio-respiratory arrest may occur.
Management
In case of extrapyramidal symptoms related or not to overdose, the treatment is only symptomatic (benzodiazepines in children and/or anticholinergic anti-parkinsonian medicinal products in adults).
A symptomatic treatment and a continuous monitoring of the cardiovascular and respiratory functions should be carried out according to clinical status.
Symptoms
Extrapyramidal disorders, drowsiness, decreased level of consciousness, confusion, hallucination, and cardio-respiratory arrest may occur.
Management
In case of extrapyramidal symptoms related or not to overdose, the treatment is only symptomatic (benzodiazepines in children and/or anticholinergic anti-parkinsonian medicinal products in adults). A symptomatic treatment and a continuous monitoring of the cardiovascular and respiratory functions should be carried out according to clinical status.
No particulars.
None known.
No abnormalities have been found in animal studies to indicate a safety risk in humans. This is based on data from pharmacological studies relating to safety, and data on toxicity following repeated administration, genotoxicity, carcinogenicity and reproductive toxicity.
Not applicable.
Metoclopramide is a substituted benzamide. It is used among other things because of its anti-emetic properties. The anti-emetic effect is the result of two mechanisms of action involving the central nervous system:
- antagonism of the dopaminergic D2 receptors in the chemoreceptor trigger zone and in the vomiting centre of the medulla which is affected in apomorphine-induced vomiting;
- antagonism of the serotoninergic 5HT3 receptors and agonist effect on the 5HT4 receptors which are affected in chemotherapy-induced vomiting.
In addition to the central action, metoclopramide has a stimulant effect on gastrointestinal motility via a peripheral mechanism of action. There is an antidopaminergic effect and potentiation of the effect of acetylcholine. This causes accelerated emptying of the stomach and there is an increase in the pressure exerted by the lower oesophageal sphincter. Metoclopramide has no effect on gastric secretions.
Primperan hydrochloride is an anti-emetic and an accelerator of gastric emptying.
Following oral administration the relative bioavailability compared with intravenous administration is 60 to 100%. Peak plasma concentrations are reached within 0.5 to 2 hours.
The distribution volume is 2-3 l/kg; 13-22% is bound to plasma proteins. Metoclopramide is excreted primarily in the urine, both in unchanged form and in sulfate or glucuronide conjugate form. The principal metabolite is an N-4 sulphur conjugate.
The plasma elimination half-life is 5 to 6 hours, irrespective of the route of administration.
Special patient populations
Renal impairment
The clearance of metoclopramide is reduced by up to 70% in patients with severe renal impairment, while the plasma elimination half-life is increased (approximately 10 hours for a creatinine clearance of 10-50 mL/minute and 15 hours for a creatinine clearance <10 mL/minute).
Hepatic impairment
In patients with cirrhosis of the liver, accumulation of metoclopramide has been observed, associated with a 50% reduction in plasma clearance.
Renal impairment
The clearance of Primperan is reduced by up to 70% in patients with severe renal impairment, while the plasma elimination half-life is increased (approximately 10 hours for a creatinine clearance of 10-50 mL/minute and 15 hours for a creatinine clearance <10 mL/minute).
Hepatic impairment
In patients with cirrhosis of the liver, accumulation of Primperan has been observed, associated with a 50% reduction in plasma clearance.
No special requirements.
Not applicable.
Administrative data
