CYP 3A4 Inhibitors (e.g. , Macrolide Antibiotics and Protease Inhibitors)
There have been rare reports of serious adverse events in connection with the coadministration of certain ergot alkaloid drugs (e.g., dihydroergotamine and ergotamine) and potent CYP 3A4 inhibitors, resulting in vasospasm leading to cerebral ischemia and/or ischemia of the extremities. Although there have been no reports of such interactions with methylergonovine alone, potent CYP 3A4 inhibitors should not be coadministered with methylergonovine. Examples of some of the more potent CYP 3A4 inhibitors include macrolide antibiotics (e.g., erythromycin, troleandomycin, clarithromycin), HIV protease or reverse transcriptase inhibitors (e.g., ritonavir, indinavir, nelfinavir, delavirdine) or azole antifungals (e.g., ketoconazole, itraconazole, voriconazole). Less potent CYP 3A4 inhibitors should be administered with caution. Less potent inhibitors include saquinavir, nefazodone, fluconazole, grapefruit juice, fluoxetine, fluvoxamine, zileuton, and clotrimazole. These lists are not exhaustive, and the prescriber should consider the effects on CYP 3A4 of other agents being considered for concomitant use with methylergonovine.
No pharmacokinetic interactions involving other cytochrome P450 isoenzymes are known.
Caution should be exercised when Methergine® (methylergonovine maleate) is used concurrently with other vasoconstrictors or ergot alkaloids.
Symptoms of acute overdose may include: nausea, vomiting, abdominal pain, numbness, tingling of the extremities, rise in blood pressure, in severe cases followed by hypotension, respiratory depression, hypothermia, convulsions, and coma.
Because reports of overdosage with Methergine® (methylergonovine maleate) are infrequent, the lethal dose in humans has not been established. The oral LD50 (in mg/kg) for the mouse is 187, the rat 93, and the rabbit 4.5.2 Several cases of accidental Methergine injection in newborn infants have been reported, and in such cases 0.2 mg represents an overdose of great magnitude. However, recovery occurred in all but one case following a period of respiratory depression, hypothermia, hypertonicity with jerking movements, and, in one case, a single convulsion.
Also, several children 1-3 years of age have accidentally ingested up to 10 tablets (2 mg) with no apparent ill effects. A postpartum patient took 4 tablets at one time in error and reported paresthesias and clamminess as her only symptoms.
Treatment of acute overdosage is symptomatic and includes the usual procedures of:
- removal of offending drug by inducing emesis, gastric lavage, catharsis, and supportive diuresis.
- maintenance of adequate pulmonary ventilation, especially if convulsions or coma develop.
- correction of hypotension with pressor drugs as needed.
- control of convulsions with standard anticonvulsant agents.
- control of peripheral vasospasm with warmth to the extremities if needed.3
Hypertension; toxemia; pregnancy; and hypersensitivity.
DRUG ABUSE AND DEPENDENCE
Methergine® (methylergonovine maleate) has not been associated with drug abuse or dependence of either a physical or psychological nature.
- Information on Adverse Reactions supplied by Medical Services Department, Novartis Pharmaceuticals, E. Hanover, N.J., based on computerized clinical reports.
- Berde, B. and Schild, H.O.: Ergot Alkaloids and Related Compounds, Springer-Verlag, New York, 1978, p. 810.
- Treatment of Acute Overdosage. Novartis Consumer Health, Inc. Rx Products. Novartis, Medical Services Department.
REV: OCTOBER 2006 Printed in the U.S.A. 5000981
Novartis Pharmaceuticals Corporation
East Hanover, New Jersey 07936
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