Drug Interaction Report

Consumer information for this interaction is not currently available.

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.

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with the JAK inhibitor pacritinib may reduce the efficacy of oral contraceptive hormones. The exact mechanism of interaction has not been established but may involve induction of the CYP450 3A4 isoenzyme. Pacritinib is reported to decrease both the peak plasma concentration (Cmax) and systemic exposure (AUC) of midazolam, a sensitive CYP450 3A4 substrate, by 60%.. A similar effect for momelotinib, another JAK inhibitor, cannot be excluded; however, since it is not reported to be a clinically significant CYP450 3A4 inducer, it has been theorized that induction of pregnane X receptor (PXR) regulated enzymes may contribute to the interaction. Clinical data are not available. This interaction has not been reported for other JAK inhibitors.

MANAGEMENT: For women of child-bearing potential on pacritinib therapy, the manufacturer recommends use of alternative methods of contraception that are not affected by CYP450 3A4 inducers, e.g., intrauterine devices and barrier methods during and for at least 30 days after the last dose of pacritinib. Due to the uncertainties of whether momelotinib may reduce the effectiveness of hormonal contraceptives, women of child-bearing potential using oral hormonal contraceptives should use alternative or additional methods of birth control as mentioned above during and for at least one week after the last dose of momelotinib.

Grapefruit juice may increase the blood levels of pacritinib. This can increase the risk of side effects such as diarrhea, low blood platelet count, infection, and an irregular heart rhythm that may be serious or life-threatening. You should avoid consuming grapefruit and grapefruit juice during treatment with pacritinib. However, if you have been regularly consuming grapefruit or grapefruit juice with the medication, then it is advisable for you to talk with your doctor before changing the amounts of these products in your diet, as this may alter the effects of your medication. Contact your doctor if you have any questions or concerns or if you develop dizziness, lightheadedness, fainting, shortness of breath, chest pain, or heart palpitations during treatment. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Grapefruit juice may increase the blood levels of certain medications such as levonorgestrel. You may want to limit your consumption of grapefruit and grapefruit juice during treatment with levonorgestrel. However, if you have been regularly consuming grapefruit or grapefruit juice with the medication, then it is advisable for you to talk with your doctor before changing the amounts of these products in your diet, as this may alter the effects of your medication. Contact your doctor if your condition changes or you experience increased side effects. Orange juice is not expected to interact.

Information for this minor interaction is available on the professional version.