Metoclopramide is shown to be a substrate of CYP2D6 and possibly 3A4, as well as a mechanism based inhibitor of CYP2D6 in in-vitro studies. However, it does not inhibit other CYPs in vitro, and no drug interactions that indicate inhibition or induction of CYP 2C9 or 3A4 have been reported. Metoclopramide has been used to treat nausea during attacks of acute porphyria without adverse affects. While several case reports describe attacks of acute porphyria following the use of metoclopramide, often the attack was already in progress when the drug was taken. Also, most cases describe that the patients were exposed to other factors such as known porphyrinogenic drugs, starvation and/or pregnancy that could explain the attacks.

Metoclopramide hydrochloride is a synthetic substituted benzamide. The drug is a derivative of p-aminobenzoic acid related to procainamide, but differs structurally from procainamide by the presence of 5-chloro and 2-methoxy aryl substituents.

Metoclopramide is an antiemitic used for the management of GI motility disorders, especially gastric stasis, for the management of gastroesophageal reflux, for the prevention of cancer chemotherapy-induced nausea and vomiting, and for the prevention of postoperative nausea and vomiting. It can be administered orally, rectally or by IM or direct IV injection, by IV infusion or using intranasal formulation. Raised serum prolactin levels have been observed during metoclopramide therapy: this may result in galactorrhoea, irregular periods and gynaecomastia. This side-effect may theoretically be beneficiary in some women due to the decreased levels of porphyrinogenic progesterone.

Metoclopramide is metabolised in the liver, primarily by CYP2D6, but CYP3A4 and CYP1A2 may also be involved to some extent (Desta, 2002). 20-30 % of the dose is excreted in urine as unchanged drug. In vitro, metoclopramide is an inhibitor of CYP2D6 (Ki = 0.96 µM and Kinact = 0.026 /min), possibly a mechanism based inhibitor. The effect on other isoforms was negligible (Desta, 2002). Therapeutic use: no reports describing drug interactions that indicate induction or inhibition of CYP2C9 or 3A4.

One report of uneventful use (C Andersson, Sweden).

One report of worsening of an attack of acute porphyria following the use of metoclopramide in a previously undiagnosed AIP woman, however she also was exposed for several other porphyrinogenic drugs, such as diazepam, diclophenac and phenytoin (Jose, 2008). Two reports of attacks/ worsening attacks of acute porphyria following the use of metoclopramide in pregnant, previously undiagnosed AIP-women. However, both the pregnancy itself and hyperemesis leading to starvation may have caused the attacks (Shenhav, 1997; Milo, 1989). One report of an attack following the use of metoclopramide for nausea (Doss, 1981). Kumar et al (2010) reports metoclopramide as a precipitating factor of attacks in 3 AIP patients admitted to an emergency ward, however all 3 were also using other drugs that are considered unsafe (pantoprazole, rabeprazole, diclofenac). One report of metoclopramide being used in the treatment of an acute attack (Gopinathan, 1990). Elder et al reports that they have

Uneventful use reported in 6 patients with acute porphyria.