Drug Interactions between Opzelura and raloxifene

MONITOR CLOSELY: Coadministration of Janus kinase (JAK) inhibitors and combined hormonal contraceptives, hormone replacement therapy (HRT), or estrogen receptor modulators may potentiate the risk of venous thromboembolism (VTE). Serious and sometimes fatal VTE events including pulmonary embolism (PE) and deep vein thrombosis (DVT) have been observed in patients taking JAK inhibitors. In a randomized safety study of patients with rheumatoid arthritis with at least one cardiovascular risk factor (e.g., prior VTE, body mass index greater than or equal to 35 kg/m2, older age, history of chronic lung disease), an increased risk for VTE was observed with tofacitinib compared to tumor necrosis factor (TNF) inhibitors. Similarly, in a meta-analysis evaluating 16 randomized controlled trials for the incidence of venous thromboembolism with JAK inhibitor use (including tofacitinib, upadacitinib, filgotinib, and baricitinib), a potential increase in the risk of VTE, although not clinically significant, was observed compared to placebo or TNF inhibitors. Subgroup analyses showed higher VTE events with tofacitinib compared to TNF inhibitors and with higher doses of JAK inhibitors. Data surrounding the use of JAK inhibitors with hormonal contraceptives, HRT and or estrogen receptor modulators are not available.

MANAGEMENT: Caution and close clinical monitoring are advised when JAK inhibitors are administered in patients with an increased risk for venous thromboembolism (VTE), such as those taking combined hormonal contraceptives, hormone replacement therapy (HRT) and/or estrogen receptor modulators. While not discussed in US product labeling, international labeling for some JAK inhibitors recommends avoiding concomitant use due to their potential to increase the risk of VTE. Other international labeling suggests JAK inhibitors may be administered if necessary, but with additional monitoring. Patients and their caregivers should be advised to seek medical attention if they experience signs and symptoms of VTE. Individual product labeling should be consulted for further guidance.