WHO Drug Information Vol. 15, No. 1, 2001
(2001; 56 pages) View the PDF document
Table of Contents
Open this folder and view contentsQuality Assurance Issues
Open this folder and view contentsPersonal Perspectives
Open this folder and view contentsCurrent Topics
Close this folderRegulatory and Safety Matters
View the documentNew formulation of DTP vaccine
View the documentBupropion safety reminder
View the documentPropofol: reactions to long-term high doses
View the documentPropofol: not for paediatric use
View the documentLeflunomide: hepatic reactions
View the documentRapacuronium bromide voluntarily withdrawn
View the documentLevacetylmethadol withdrawn
View the documentLevacetylmethadol: labelling changes
View the documentIsotretinoin and depression
View the documentNew glucose test for adult diabetics
View the documentAnti-inflammatory analgesics: hepatic reactions
View the documentGentamicin ear drops: toxicity
View the documentTetracycline and benign intracranial hypertension
View the documentErgotamine and erythromycin interaction
View the documentCelecoxib and warfarin interaction
View the documentCerivastatin: rare effect of rhabdomyolysis
View the documentSSRIs and increased ocular pressure
View the documentAmfepramone: new cases of primary pulmonary hypertension
View the documentBufexamac and contact eczema
View the documentDroperidol: prolongation of the QT interval
View the documentMofezolac: revised data sheet
View the documentMonoethanolamine oleate: revised data sheet
View the documentRivastigmine: revised product information
View the documentSarpogrelate: revised data sheet
Open this folder and view contentsATC/DDD Classification
 

Ergotamine and erythromycin interaction

Australia - Ergotism is manifested by symptoms and signs of peripheral ischaemia due to constriction of vascular smooth muscle caused by direct action of an ergot derivative. Headache, intermittent claudication, muscle pain, numbness, coldness and pallor of the extremities may occur, and gangrene has been reported. Ergotism is usually associated with excessive dosing of ergot preparations but has also been reported with normal doses of ergotamine preparations when there was concommitant use of macrolides (particularly erythromycin). The mechanism of the interaction is not established but may involve an inhibition of ergotamine metabolism or an increased gut absorption resulting in an increase in serum ergotamine concentration.

In recent years, the Australian Adverse Drug Reactions Committee (ADRAC) has received two reports describing severe ergotism in association with the combined use of ergotamine and erythromycin.

ADRAC has also received reports of ergotism arising from the combination of ergotamine with ritonavir and verapamil and has noted published reports of similar interactions with HIV protease inhibitors, particularly ritonavir (1, 2). These reports suggest that the basis of the interaction is inhibition of either cytochrome P4503A4 in the liver or gut P-glycoprotein with subsequent increase in ergotamine concentrations. As most inhibitors of CYP3A4 also inhibit P-glycoprotein, the concomitant use of erythromycin and other known inhibitors of CYP3A4 with ergotamine preparations should be avoided.

References:

1. Phan, T.G., Agaliotis, D., White, G. et al. Ischaemic peripheral neuritis secondary to ergotism associated with ritonavir therapy. Medical Journal of Australia, 171: 502– 503.(1999).

2. Blanche, P., Rigolet, A., Gombert, B. et al. Ergotism related to a single dose of ergotamine tartrate in an AIDS patient treated with ritonavir. Postgraduate Medical Journal, 75: 546–547 (1999).

3. ADRAC Bulletin, Volume 19, No 4, December 2000.

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