Drug Interactions between chloroquine and tamoxifen

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Hydroxychloroquine (HCQ) and chloroquine (CQ) can cause dose-related retinal toxicity. The risk of retinal toxicity from HCQ or CQ increases with concurrent use of drugs known to induce retinal toxicity (e.g., tamoxifen), higher doses (>/= 5 mg/kg of actual body weight for HCQ and 2.3 mg/kg of actual body weight for chloroquine), treatment duration >5 years, low body weight, advanced age, and concomitant retinal, renal, or hepatic disease. The precise mechanism of retinal toxicity is unclear, but it is thought to be associated with high concentrations of 4-aminoquinoline (4-AQ) from HCQ and CQ in the ocular tissue, which binds to melanin in the retinal pigment epithelium (RPE), ultimately leading to inner and outer retinal damage. This damage disrupts crucial steps in the visual cycle, resulting in lipofuscin accumulation and photoreceptor degradation. Retinal toxicity is more commonly associated with CQ than with HCQ and can result in the development of circular defects (bull's eye maculopathy) and diametric defects of the retina. In a retrospective case-control study evaluating 2361 patients within an integrated health organization who had used HCQ continuously for at least 5 years, visual field (VF) testing or spectral-domain optical coherence tomography (SD-OCT) were used to identify the presence of retinal toxicity. The overall prevalence of retinopathy was 7.5% and increased significantly with higher daily doses (>5.0 mg/kg) and long-term use (>10 years). Additionally, concomitant use of tamoxifen with HCQ increased the risk of retinal toxicity by approximately 5-fold.

MANAGEMENT: Coadministration of hydroxychloroquine (HCQ) or chloroquine (CQ) with other drugs that can induce retinal toxicity (e.g., tamoxifen) should generally be avoided. If coadministration is required, ophthalmological examinations including best corrected distance visual acuity (BCVA), automated threshold VF and SD-OCT tests should be started one year after therapy is initiated and repeated annually. In addition, maintaining HCQ doses of <5 mg/kg of actual body weight and CQ doses of <2.3 mg/kg of actual body weight are recommended to reduce retinal toxicity risk. Individual product labeling and local guidelines should be consulted for additional guidance.

GENERALLY AVOID: Hydroxychloroquine (HCQ) and chloroquine (CQ) can cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such advanced age, congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). In a retrospective study of electronic health records analyzing QTc prolongation risk in patients on HCQ alone or with other QT-prolonging drugs, a statistically significant QTc interval increase of 18 ms was observed in the HCQ monotherapy group. No significant QTc increase was found in patients taking HCQ with the evaluated QT-prolonging medications. However, this result may have been influenced by factors such as varying patient sensitivity to QT-prolonging drugs across treatment sites, and differences in HCQ exposure duration prior to QTc measurement in combination therapy cases.

MANAGEMENT: Coadministration of hydroxychloroquine (HCQ) or chloroquine (CQ) with other drugs that can prolong the QT interval should generally be avoided, particularly in patients with baseline QT prolongation (e.g., QTc >=500 msec) or congenital long QT syndrome. Close monitoring of QTc interval, electrolyte levels, and renal and hepatic function is recommended if concomitant use is required, and benefits are anticipated to outweigh the risks. Electrolyte abnormalities should be corrected prior to initiating treatment with hydroxychloroquine. 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. Because hydroxychloroquine and chloroquine are eliminated slowly from the body (terminal half-lives: HCQ = 40-50 days, CQ = 10-60 days), potential drug interactions may persist for several weeks to months after their discontinuation.