Cafergot Drug Interactions

Expected interactions leading to a contraindication: Potent inhibitors of CYP3A4: 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).
Vasoconstrictors: Ergot alkaloids have also been shown to be inhibitors 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 5HT1 receptor agonists, and nicotine (e.g. heavy smoking) must be avoided since this may result in enhanced vasoconstriction (see CONTRAINDICATIONS)
Interactions observed leading to non-recommendation of concomitant use: Any potential increase in plasma caffeine concentrations due to an interaction with one or more other medicinal products may lead to a rise in ergotamine absorption. Caffeine is significantly metabolised by CYP1A2 and medicinal products that increase or reduce enzyme activity may affect the metabolic clearance of caffeine. Fluoroquinolones, mexiletine, fluvoxamine and oral contraceptives may increase plasma exposure to caffeine. Interactions between sympathomimetics and caffeine can cause a rise in blood pressure.
Observed interactions to be taken into account: Beta-blockers: A few cases of vasospastic reactions have been reported in patients treated concomitantly with medicinal products containing ergotamine and propranolol.
Expected interactions to be taken into account: Moderate/weak CYP3A4 inhibitors: Moderate to weak CYP3A4 inhibitors such as cimetidine, clotrimazole, fluconazole, grapefruit juice, quinupristin/dalfopristin and zileuton may also increase exposure to ergotamine and caution is required if they are used concomitantly.
Serotonin reuptake inhibitors: The concurrent use of ergotamine and serotonin reuptake inhibitors (e.g. amitriptyline), including selective agents (e.g. sertraline), may cause serotonin syndrome and requires caution.
CYP3A4 inducers: CYP3A4-inducing medicinal products (e.g. nevirapine, rifampicin) can cause a reduction in the pharmacological activity of ergotamine.
Absence of interaction: No pharmacokinetic interactions involving other cytochrome P450 isoenzymes are known.
Interactions related to ergotamine: Contraindicated combinations: Triptans (almotriptan, fovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan, eletriptan): risk of hypertension, coronary artery vasoconstriction. An interval of 24 hours should be left between discontinuation of the triptan and administration of the alkaloid.
Macrolides (except spiramycin): ergotism, with the possibility of necrosis in the extremities (decrease in hepatic elimination of ergot alkaloids).
Protease inhibitors (e.g. amprenavir, atazanavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir): ergotism, with the possibility of necrosis in the extremities (inhibition of hepatic metabolism of the ergot alkaloid).
Reverse transcriptase inhibitors (delavirdine, efavirenz): ergotism, with the possibility of necrosis in the extremities (inhibition of hepatic metabolism of the ergot alkaloid).
Voriconazole: ergotism, with the possibility of necrosis in the extremities (inhibition of hepatic metabolism of the ergot alkaloid).
Quinupristin-dalfopristin (in combination): ergotism, with the possibility of necrosis in the extremities (inhibition of hepatic metabolism of the ergot alkaloid).
Stiripentol: ergotism, with the possibility of necrosis in the extremities (inhibition of hepatic metabolism of the ergot alkaloid).
Diltiazem: ergotism, with the possibility of necrosis in the extremities (inhibition of hepatic metabolism of the ergot alkaloid).
Phenylpropanolamine: risk of vasoconstriction and/or episodes of hypertension.
Triclabendazole: ergotism, with the possibility of necrosis in the extremities (inhibition of hepatic metabolism of the ergot alkaloid). An interval of 24 hours should be left between the discontinuation of treatment and ergotamine, and vice versa.
Inadvisable combinations: Dopaminergic ergot alkaloids (bromocriptine, cabergolin, pergolide, lisuride): risk of vasoconstriction and/or episodes of hypertension.
Alpha sympathomimetics (oral and/or nasal route) (etilephrine, midodrine, naphazoline, oxymetazoline, phenylephrine, synephrine, tetryzoline, tuaminoheptane, tymazoline): risk of vasoconstriction and/or episodes of hypertension.
Indirect sympathomimetics (except phenylpropanolamine) (ephedrine, phenylephrine, pseudoephedrine): risk of vasoconstriction and/or episodes of hypertension.
Combinations requiring precautions for use: Beta-blockers (propanolol, oxprenolol): ergotism; some cases of arterial spasm with ischaemia in the extremities have been observed (cumulative vascular effects). Increased clinical monitoring, especially during the first weeks of combination therapy.
Interactions related to caffeine: Inadvisable combinations: Enoxacin: increase in plasma caffeine concentrations, which may lead to excitation and hallucinations due to a decrease in hepatic metabolism. Combinations to be taken into account: Ciprofloxacin, norfloxacin: increase in plasma caffeine concentrations, which may lead to excitation and hallucinations due to a decrease in hepatic metabolism.
Mexiletine: increase in plasma caffeine concentrations due to the inhibition of its hepatic metabolism by mexiletine.