Drug products: MCP Hexal, MCP-ratiopharm SF, Metoclopramide Accord, Metoclopramide Orifarm, Metoclopramide Orion, Metoklopramid Alternova, Primperan, Primperan 10, Primperan®
ATC code: A03FA01
Substances: metoclopramide, metoclopramide hydrochloride, metoclopramide hydrochloride monohydrate
Several studies have shown that women, particularly younger ones, have more nausea and vomiting compared to men in spite of treatment with metoclopramide.
A double blind study showed that men reacted to metoclopramide with a faster ventricular emptying while women had a larger amount of liquid passing through the ventricle and thus had a stronger effect.
A British study has shown that women had a higher incidence of dystonia and dyskinesia when treated with metoclopramide and the highest frequency was found in adolescent girls 12-19 years old.
In our opinion, the described differences do not motivate differentiated dosing or treatment in men and women.
In a bioequivalence study comparing 10 mg metoclopramide oral-disintegrating tablet and a conventional 10 mg oral metoclopramide tablet in healthy volunteers (32 men, 9 women), no sex differences were seen in AUC or Cmax for either formulation . Clinical studies have shown effect with similar doses in men and women and no sex differentiation in dosing has been suggested by the manufacturerr .
A randomized controlled study (123 men, 67 women) of metoclopramide or metoclopramide and methylprednisolone in cisplatin-treated oncology patients showed that metoclopramide was well-tolerated, but a subgroup of younger female patients still suffered nausea and vomiting . Similar results have been shown in another study (207 men, 94 women) of metoclopramide treatment in chemotherapy induced nausea .The effects of oral metoclopramide on gastric emptying have been assessed in a double-blind trial divided in two sub studies (5 men, 5 women, and 8 men, 8 women). Metoclopramide caused increased gastric emptying, men emptying their stomachs more quickly than women. Gastric residues were smaller in larger individuals (greater body surface area) after taking metoclopramide but not before. Women passed more fluid from their stomachs after metoclopramide than men, indicating that metoclopramide produced a greater response in women than in men .
Extrapyramidal adverse reactions associated with metoclopramide have been examined in UK by using reports registered in the Adverse Reactions Register of the Committee on the Safety of Medicines, combined with prescribing data collected between the years 1967-1982. Among the 455 reports of acute dystonic-dyskinetic reactions, 70% occurred in women. The overall relative risk of a reported reaction for women vs. men after correcting for prescription rates was 1.8. Highest risk for acute dystonic-dyskinetic reaction was seen in the age group 12-19 years old. Sex did not have any effect on the prescribed dose in patients with acute dystonia-dyskinesia. There was no sex difference in reporting rate of Parkinsonism [6, 7].
Incidence rates of spontaneous dyskinesia and tardive dyskinesia among patients prescribed metoclopramide or an antipsychotic drug were analyzed in a retrospective study. The incidence rates increased with age and were greater for women . Some patients appeared to be at increased risk for developing tardive dyskinesia, such as elderly and women .
In a study of patients with gastroparesis (24 men, 76 women), side effects to metoclopramide were more common in women than men (83% vs. 64%) despite similar dose and duration of treatment. Women had a lower bodyweight than men but received a similar dose of metoclopramide (mg/pound) as men. Side effects included anxiety, uncontrolled movements, fatigue, tremors, depression, confusion, dystonic reaction, seizures, Parkinsonian symptoms, tardive dyskinesia, and miscellaneous .
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
Metoclopramide stimulates prolactin secretion and can be used to enhance breast milk production in women. A placebo-controlled, crossover study in 37 women with inadequate breast milk production was treated with 5, 10 and 15 mg of metoclopramide three times a day for 2 weeks. Doses of 30 mg and 45 mg daily raised maternal serum prolactin, while 15 mg daily did not . In Sweden, the highest recommended dose of metoclopramide is 30 mg daily, regardless of indication.
The effect of metoclopramide-induced hyperprolactinemia on menstruation cycle has been investigated. In a randomized, placebo-controlled study, ten healthy women were administrated metoclopramide 10 mg three times daily orally for 7 days starting on cycle day 6 or 7 of two menstrual cycles. A control cycle without any treatment separated the two study cycles. No interference with follicular development and corpus luteum function was observed . However, a similar study found a significantly increased progesterone/estradiol ratio during hyperprolactinemia during the early follicular phase (days 5-6). This suggests that follicular development is especially sensitive to prolactin early in the cycle .
Date of litterature search: 2015-03-31
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson