Ergotamine and caffeine and Ritonavir interaction

…INTERACTIONS LEADING TO POTENTIALLY SERIOUS AND/OR LIFE THREATENING REACTIONS Co-administration of NORVIR with several classes of drugs including sedative hypnotics, antiarrhythmics, or ergot alkaloid preparations may result in potentially serious and/or life-threatening adverse events due to possible effects of NORVIR on the hepatic metabolism of certain drugs.

…THREATENING REACTIONS See full prescribing information for complete boxed warning Co-administration of NORVIR with several classes of drugs including sedative hypnotics, antiarrhythmics, or ergot alkaloid preparations may result in potentially serious and/or life-threatening adverse events due to possible effects of NORVIR on the hepatic metabolism of certain drugs.

…ranolazine ○ Antiarrhythmics: amiodarone, dronedarone, flecainide, propafenone, quinidine ○ Antifungal: voriconazole ○ Anti-gout: colchicine ○ Antipsychotics: lurasidone, pimozide ○ Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine ○ GI Motility Agent: cisapride ○ HMG-CoA Reductase Inhibitors: lovastatin, simvastatin ○ Microsomal triglyceride transfer…

Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine ↑ ergot derivatives Contraindicated due to potential for acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system [see Contraindications ( 4 ) ] .

Anesthetic: meperidine ↓ meperidine/ ↑ normeperidine (metabolite) Dosage increase and long-term use of meperidine with ritonavir are not recommended due to the increased concentrations of the metabolite normeperidine which has both analgesic activity and CNS stimulant activity (e.g., seizures).

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.

There have been rare reports of cerebral ischemia in patients on protease inhibitor therapy when ergotamine tartrate and caffeine tablets was coadministered, at least one resulting in death.

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.