Erythrocytosis: WINREVAIR may increase hemoglobin (Hgb). Severe erythrocytosis may increase the risk of thromboembolic events or hyperviscosity syndrome. In clinical studies, moderate elevations in Hgb (>2 g/dL above upper limit of normal [ULN]) occurred in 15% of patients taking WINREVAIR while no elevations ≥4 g/dL above ULN were observed. Monitor Hgb before each dose for the first 5 doses, or longer if values are unstable, and periodically thereafter, to determine if dose adjustments are required.
Severe Thrombocytopenia: WINREVAIR may decrease platelet count. Severe thrombocytopenia may increase the risk of bleeding. In clinical studies, severe thrombocytopenia (platelet count <50,000/mm3 [<50 x 109/L]) occurred in 3% of patients taking WINREVAIR. Thrombocytopenia occurred more frequently in patients also receiving prostacyclin infusion. Do not initiate treatment if platelet count is <50,000/mm3. Monitor platelets before each dose for the first 5 doses, or longer if values are unstable, and periodically thereafter to determine whether dose adjustments are required.
Serious Bleeding: In clinical studies, serious bleeding (eg, gastrointestinal, intracranial hemorrhage) was reported in 4% of patients taking WINREVAIR and 1% of patients taking placebo. Patients with serious bleeding were more likely to be on prostacyclin background therapy and/or antithrombotic agents, or have low platelet counts. Advise patients about signs and symptoms of blood loss. Evaluate and treat bleeding accordingly. Do not administer WINREVAIR if the patient is experiencing serious bleeding.
Embryo-Fetal Toxicity: Based on findings in animal reproduction studies, WINREVAIR may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment with WINREVAIR and for at least 4 months after the final dose. Pregnancy testing is recommended for females of reproductive potential before starting WINREVAIR treatment.
Impaired Fertility: Based on findings in animals, WINREVAIR may impair female and male fertility. Advise patients on the potential effects on fertility.
Adverse Reactions: The most common adverse reactions occurring in the Phase 3 clinical trial (≥10% for WINREVAIR and at least 5% more than placebo) were headache (24.5% vs 17.5%), epistaxis (22.1% vs 1.9%), rash (20.2% vs 8.1%), telangiectasia (16.6% vs 4.4%), diarrhea (15.3% vs 10.0%), dizziness (14.7% vs 6.2%), and erythema (13.5% vs 3.1%).
Lactation: Because of the potential for serious adverse reactions in the breastfed child, advise patients that breastfeeding is not recommended during treatment with WINREVAIR, and for 4 months after the final dose.
Pediatric Use: The safety and effectiveness of WINREVAIR have not been established in patients less than 18 years of age.
Geriatric Use: A total of 81 patients ≥65 years of age participated in clinical studies for PAH, of which 52 (16%) were treated with WINREVAIR. Bleeding events occurred more commonly in the older WINREVAIR subgroup, but with no imbalance between age subgroups for any specific bleeding event.
Before prescribing WINREVAIR, please read the accompanying Prescribing Information. The Patient Information and Instructions for Use (1-vial kit, 2-vial kit) also are available.
