Why does reglan cause tardive dyskinesia

These usually abate with discontinuation of metoclopramide but tardive dyskinesia may be irreversible. The FDA continues to receive reports of dyskinesia associated with metoclopramide. Metoclopramide is eliminated by several pathways. Genetic variations in CYP2D6 or P-gp may alter the risk of movement disorders in patients taking metoclopramide.

For any plasma concentration, a larger percentage of metoclopramide would be expected to collect in the brain in patients with reduced P-gp. Increasing plasma or brain concentrations of metoclopramide would be expected to increase the risk of metoclopramide side effects. Little data are available that examine the relationship of metoclopramide concentration to the incidence of side effects, except that several retrospective analyses have found that higher doses are more often associated with tardive dyskinesia.

Metoclopramide may have pharmacodynamic interactions with other drugs, including neuroleptic agents and selective serotonin reuptake inhibitors SSRIs. Antipsychotic drugs with a high risk of movement disorders include fluphenazine Prolixin , trifluoperazine Stelazine , thiothixene Navane , thioridazine Mellaril , chlorpromazine Thorazine , haloperidol Haldol , perphenazine Trilafon , risperidone Risperdal , and loxapine Loxitane. These drugs will likely potentiate the inhibition of dopamine receptors caused by metoclopramide.

Thioridazine, chlorpromazine, perphenazine, haloperidol, and risperidone have been noted to inhibit CYP2D6 and could increase the plasma concentration of metoclopramide. Theoretically, SSRIs used concomitantly with metoclopramide could increase the risk of serotonin syndrome.

Concurrent administration of metoclopramide with CYP2D6 inhibitors eg, amiodarone [Cordarone], diphenhydramine [Benadryl], propafenone [Rythmol], quinidine, ritonavir [Norvir], terbinafine [Lamisil], dronedarone [Multaq], bupropion [Wellbutrin] or P-gp inhibitors eg, clarithromycin [Biaxin], cyclosporine [Neoral], verapamil [Calan], ketoconazole [Nizoral], tacrolimus [Prograf], itraconazole [Sporanox], nelfinavir [Viracept] should probably be avoided pending further data.

There is no doubt that metoclopramide can occasionally cause severe side effects. Because it is eliminated by CYP2D6 and appears to be a substrate for P-gp, there are a large number of potential drugs that can interact with metoclopramide to increase its plasma concentration or passage into the brain. Some patients, such as those with renal failure or a genetic deficiency in CYP2D6 or P-gp activity, may be particularly susceptible to metoclopramide movement-related adverse events, including those exacerbated by drug interactions.

For an electronic version of this article, including references if any, visit www. Albibi R, et al. Metoclopramide: pharmacology and clinical application. Ann Inter Med. Tonini M et al. Review article: clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics.

Aliment Pharmacol Ther. Wright MR et al. Linearity of metoclopramide kinetics at doses of mg. Br J Clin Pharmacol. Antiparkinsonism agents have no reported effect. In some cases, the condition may be lessened or disappear after metoclopramide Reglan treatment is discontinued. Medical studies report that the development of tardive dyskinesia has a direct relation to duration and dose of metoclopramide Reglan taken.

Stated simply, the more Reglan a patient is given, and the longer he or she is given it, the greater the likelihood that the patient will develop tardive dyskinesia. Studies also report incidences of tardive dyskinesia are higher in females and the elderly, with elderly women having an elevated likelihood of developing the disorder.

Additionally, nicotine users, especially cigarette smokers, and African-Americans appear especially vulnerable, even at low doses and short durations. Contact us online or call us at to set up a FREE consultation to discuss your legal options. Please do not include any confidential or sensitive information in a contact form, text message, or voicemail.

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