Drug Interactions between hydroxychloroquine and telithromycin

GENERALLY AVOID: Coadministration with strong CYP450 3A4 or 2D6 inhibitors may significantly increase the plasma concentration and effects of hydroxychloroquine (HCQ), which is partially metabolized by the isoenzymes. Following coadministration with cimetidine, a weak to moderate CYP450 3A4 inhibitor and weak CYP450 2D6 inhibitor, a 2-fold increase in chloroquine exposure occurred. Because chloroquine and hydroxychloroquine have similar structures and metabolic elimination pathways, a similar interaction could be observed for hydroxychloroquine. The risk of QT prolongation may be further increased with concomitant use of strong CYP450 3A4 inhibitors (e.g., ceritinib, clarithromycin, mifepristone, saquinavir, telithromycin, some azole antifungals) or strong CYP450 2D6 inhibitors (e.g., fluoxetine) that are also known to prolong the QT interval. No data are available for more potent CYP450 3A4 or 2D6 inhibitors that also prolong the QT interval.

MANAGEMENT: Coadministration of hydroxychloroquine with strong CYP450 3A4 or CYP450 2D6 inhibitors that can prolong the QT interval should generally be avoided, particularly in patients with baseline QT prolongation (e.g., QTc greater than or equal to 500 msec) or congenital long QT syndrome. If concomitant use is required and benefits are anticipated to outweigh the risks, close monitoring of the QTc interval, electrolyte levels, and renal and hepatic function is recommended, and the dose adjusted as necessary whenever strong CYP450 3A4 or 2D6 inhibitor is added to or withdrawn from therapy. Electrolyte abnormalities should be corrected prior to initiating treatment with hydroxychloroquine. Patients should be advised to seek immediate medical attention if they experience symptoms of torsades de pointes (e.g., dizziness, fainting, palpitations, irregular heart rhythm, or syncope) or symptoms of other serious hydroxychloroquine-related adverse effects such as severe cutaneous adverse drug reactions (SCARs), renal or liver toxicity, hematologic toxicities, myopathy or neuropathy, retinopathy, neuropsychiatric symptoms, gastrointestinal distress, hypoglycemia, or heart failure. Because hydroxychloroquine is eliminated slowly from the body (terminal half-life: 40-50 days), potential drug interactions may persist for several weeks to months after its discontinuation.

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