The concomitant use of cytochrome P450 3A (CYP3A) inhibitors such as macrolide antibiotics (e.g. troleandomycin, erythromycin, clarithromycin), HIV protease or reverse transcriptase inhibitors (e.g. ritonavir, indinavir, nelfinavir, delavirdine), or azole antifungals (e.g. ketoconazole, itraconazole, voriconazole) and Cafergot must be avoided (see Contraindications), since this can result in an elevated exposure to ergotamine and ergot toxicity (vasospasm and ischemia of the extremities and other tissues).
Ergot alkaloids have also been shown to be both inhibitors and substrates of CYP3A. No pharmacokinetic interactions involving other cytochrome P450 isoenzymes are known.
A few cases of vasospastic reactions have been reported among patients treated concomitantly with ergotamine-containing preparations and propranolol.
Concurrent use of vasoconstrictor agents including preparations containing ergot alkaloids, sumatriptan and other 5HT receptor agonists, and nicotine (e.g. heavy smoking) must be avoided since this may result in enhanced vasoconstriction (see Contraindications).