Drug Interactions between fluoxetine / olanzapine and hydroxychloroquine

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function is recommended, and the dose adjusted as necessary whenever strong CYP450 3A4 or 2D6 inhibitor is added to or withdrawn from therapy.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.

MONITOR: It is uncertain whether olanzapine causes clinically significant prolongation of the QT interval. In pooled studies of adults as well as pooled studies of adolescents, there were no significant differences between olanzapine and placebo in the proportion of patients experiencing potentially important changes in ECG parameters, including QT, QTcF (Fridericia-corrected), and PR intervals. In clinical trials, clinically meaningful QTc prolongations (QTcF >=500 msec at any time post-baseline in patients with baseline QTcF <500 msec) occurred in 0.1% to 1% of patients treated with olanzapine, with no significant differences in associated cardiac events compared to placebo. Published studies have generally reported no significant effect of olanzapine on QTc interval, although both QTc prolongation and QTc shortening have also been reported. There have been a few isolated case reports of QT prolongation in patients receiving olanzapine. However, causality is difficult to establish due to confounding factors such as concomitant use of drugs that cause QT prolongation and underlying conditions that may predispose to QT prolongation (e.g., hypokalemia, congenital long QT syndrome, preexisting conduction abnormalities).

MANAGEMENT: Some authorities recommend caution when olanzapine is used with drugs that are known to cause QT prolongation. ECG monitoring may be advisable in some cases, such as in patients with a history of cardiac arrhythmias or congenital or family history of long QT syndrome. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

MONITOR: It is uncertain whether olanzapine causes clinically significant prolongation of the QT interval. In pooled studies of adults as well as pooled studies of adolescents, there were no significant differences between olanzapine and placebo in the proportion of patients experiencing potentially important changes in ECG parameters, including QT, QTcF (Fridericia-corrected), and PR intervals. In clinical trials, clinically meaningful QTc prolongations (QTcF >=500 msec at any time post-baseline in patients with baseline QTcF <500 msec) occurred in 0.1% to 1% of patients treated with olanzapine, with no significant differences in associated cardiac events compared to placebo. Published studies have generally reported no significant effect of olanzapine on QTc interval, although both QTc prolongation and QTc shortening have also been reported. There have been a few isolated case reports of QT prolongation in patients receiving olanzapine. However, causality is difficult to establish due to confounding factors such as concomitant use of drugs that cause QT prolongation and underlying conditions that may predispose to QT prolongation (e.g., hypokalemia, congenital long QT syndrome, preexisting conduction abnormalities).

MANAGEMENT: Some authorities recommend caution when olanzapine is used with drugs that are known to cause QT prolongation. ECG monitoring may be advisable in some cases, such as in patients with a history of cardiac arrhythmias or congenital or family history of long QT syndrome. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.