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Metoklopramid

Klassificering: A

Preparat: MCP Hexal, MCP-ratiopharm SF, Metoclopramide Accord, Metoclopramide Orifarm, Metoclopramide Orion, Metoklopramid Alternova, Primperan, Primperan 10, Primperan®

ATC kod: A03FA01

Substanser: metoklopramid, metoklopramidhydroklorid, vattenfri, metoklopramidhydrokloridmonohydrat

Sammanfattning

Flera studier har visat att kvinnor, framförallt yngre, hade mer illamående och kräkningar än män trots behandling med metoklopramid.

En dubbelblind studie visade att män fick en snabbare ventrikeltömning av metoklopramid medan kvinnor hade en större mängd vätska som passerade ur magsäcken och fick således starkare effekt.

En brittisk studie har visat att incidensen av akut dystoni och dyskinesi i samband med metoklopramidbehandling var högre hos kvinnor med den högsta risken hos flickor i åldern 12-19 år.
 
Vår bedömning är att de beskrivna skillnaderna inte motiverar olika dosering eller behandling hos kvinnor och män.

Additional information

Pharmacokinetics and dosing

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 [1]. Clinical studies have shown effect with similar doses in men and women and no sex differentiation in dosing has been suggested by the manufacturerr [2].

Effects

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 [3]. Similar results have been shown in another study (207 men, 94 women) of metoclopramide treatment in chemotherapy induced nausea [4].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 [5].

Adverse effects

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 [8]. Some patients appeared to be at increased risk for developing tardive dyskinesia, such as elderly and women [9].

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 [10].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Other information

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 [11]. 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 [12]. 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 [13].

Försäljning på recept

Fler kvinnor än män hämtade ut läkemedel innehållande metoklopramid (ATC-kod A03FA01) på recept i Sverige år 2015, totalt 44 544 kvinnor och 18 685 män. Det motsvarar 9,1 respektive 3,8 personer per tusen invånare. Andelen som hämtat ut läkemedel ökade med stigande ålder hos båda könen. I genomsnitt var läkemedel innehållande metoklopramid 2,7 gånger vanligare hos kvinnor [13].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2015-03-31

Referenser

  1. Fass R, Pieniaszek HJ, Thompson JR. Pharmacokinetic comparison of orally-disintegrating metoclopramide with conventional metoclopramide tablet formulation in healthy volunteers. Aliment Pharmacol Ther. 2009;30:301-6. PubMed
  2. Primperan (metoklopramid). Summary of Product Characteristics. Medical Products Agency; 2014.
  3. Roila F, Tonato M, Basurto C, Canaletti R, Morsia D, Passalacqua R et al. Antiemetic activity of two different high doses of metoclopramide in cisplatin-treated cancer patients: a randomized double-blind trial of the Italian Oncology Group for Clinical Research. Cancer Treat Rep. 1985;69:1353-7. PubMed
  4. Tsavaris N, Mylonakis N, Bacoyiannis C, Kosmas C, Kalergis G, Iakovidis V et al. Factors that influence the antiemetic activity of metoclopramide to cisplatin based chemotherapy. Oncol Rep. 1998;5:1147-55. PubMed
  5. Kreel L, Trott M, Howells TH. The influence of oral metoclopramide on gastric emptying after a fixed water load. Clin Radiol. 1972;23:213-8. PubMed
  6. Bateman DN, Rawlins MD, Simpson JM. Extrapyramidal reactions with metoclopramide. Br Med J (Clin Res Ed). 1985;291:930-2. PubMed
  7. Pasricha PJ, Pehlivanov N, Sugumar A, Jankovic J. Drug Insight: from disturbed motility to disordered movement--a review of the clinical benefits and medicolegal risks of metoclopramide. Nat Clin Pract Gastroenterol Hepatol. 2006;3:138-48. PubMed
  8. Merrill RM, Lyon JL, Matiaco PM. Tardive and spontaneous dyskinesia incidence in the general population. BMC Psychiatry. 2013;13:152. PubMed
  9. Yassa R, Jeste DV. Gender differences in tardive dyskinesia: a critical review of the literature. Schizophr Bull. 1992;18:701-15. PubMed
  10. Parkman HP, Mishra A, Jacobs M, Pathikonda M, Sachdeva P, Gaughan J et al. Clinical response and side effects of metoclopramide: associations with clinical, demographic, and pharmacogenetic parameters. J Clin Gastroenterol. 2012;46:494-503. PubMed
  11. Kauppila A, Kivinen S, Ylikorkala O. A dose response relation between improved lactation and metoclopramide. Lancet 1981;1(8231):1175-1177. PubMed
  12. Ylikorkala O, Kauppila A. The effects on the ovulatory cycle of metoclopramide-induced increased prolactin levels during follicular development. Fertil Steril. 1981;35:588-9. PubMed
  13. Kauppila A, Leinonen P, Vihko R, Ylöstalo P. Metoclopramide-induced hyperprolactinemia impairs ovarian follicle maturation and corpus luteum function in women. J Clin Endocrinol Metab. 1982;54:955-60. PubMed
  14. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-05.] länk

Författare: Linnéa Karlsson Lind, Desirée Loikas

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson