Ergotamine and caffeine and Erythromycin interaction
Ergotamine and caffeine and Erythromycin: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Ergotamine and caffeine (Cafergot) label · effective 2026-03-23
WARNING Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of ergotamine tartrate and caffeine tablets with potent CYP 3A4 inhibitors including protease inhibitors and macrolide antibiotics.
CONTRAINDICATIONS Coadministration of ergotamine with potent CYP 3A4 inhibitors (ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, and troleandomycin) has been associated with acute ergot toxicity (ergotism) characterized by vasospasm and ischemia of the extremities (see PRECAUTIONS : Drug Interactions ), with some cases resulting in amputation.
Because of the increased risk of ergotism and other serious vasospastic adverse events, ergotamine use is contraindicated with these drugs and other potent inhibitors of CYP 3A4 (e.g., ketoconazole, itraconazole) (see WARNINGS : CYP 3A4 Inhibitors ).
While these reactions have not been reported with less potent CYP 3A4 inhibitors, there is a potential risk for serious toxicity including vasospasm when these drugs are used with ergotamine.
The blood levels of ergotamine-containing drugs are reported to be elevated by the concomitant administration of macrolide antibiotics and vasospastic reactions have been reported with therapeutic doses of the ergotamine-containing drugs when coadministered with these antibiotics.
From the Erythromycin label · effective 2025-09-25
Erythromycin is contraindicated in patients taking terfenadine, astemizole, cisapride, pimozide, ergotamine, or dihydroergotamine (see PRECAUTIONS - Drug Interactions ).
Concomitant administration of erythromycin with ergotamine or dihydroergotamine is contraindicated (see CONTRAINDICATIONS ).
The following CYP3A based drug interactions have been observed with erythromycin products in post-marketing experience: Ergotamine/dihydroergotamine Post-marketing reports indicate that co-administration of erythromycin with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischemia of the extremities…
Drug Interactions Theophylline Erythromycin use in patients who are receiving high doses of theophylline may be associated with an increase in serum theophylline levels and potential theophylline toxicity.
In case of theophylline toxicity and/or elevated serum theophylline levels, the dose of theophylline should be reduced while the patient is receiving concomitant erythromycin therapy.
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Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.