prolis. In a randomized, open-label, multicenter trial eva luating Kyprolis in combination with KRd versus Rd, the incidence of hypertension events was 16% in the KRd arm versus 8% in the Rd arm. In a randomized, open-label, multicenter trial of Kd versus Vd, the incidence of hypertension events was 26% in the Kd arm versus 10% in the Vd arm. Some of these events have been fatal. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold Kyprolis and eva luate. Consider whether to restart Kyprolis based on a benefit/risk assessment [see Dosage and Administration (2)].
5.8 Venous Thrombosis
Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed with Kyprolis. In a randomized, open-label, multicenter trial eva luating KRd versus Rd (with thromboprophylaxis used in both arms), the incidence of venous thromboembolic events in the first 12 cycles was 13% in the KRd arm versus 6% in the Rd arm. In a randomized, open-label, multicenter trial of Kd versus Vd, the incidence of venous thromboembolic events in months 1–6 was 9% in the Kd arm versus 2% in the Vd arm. With Kyprolis monotherapy, the incidence of venous thromboembolic events was 2%.
Thromboprophylaxis is recommended for patients being treated with the combination of Kyprolis with dexamethasone or with lenalidomide plus dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient's underlying risks.
Patients using oral contraceptives or a hormonal method of contraception associated with a risk of thrombosis should consider an alternative method of effective contraception during treatment with Kyprolis in combination with dexamethasone or lenalidomide plus dexamethasone.
5.9 Infusion Reactions
Infusion reactions, including life-threatening reactions, have occurred in patients receiving Kyprolis. Symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina. These reactions can occur immediately following or up to 24 hours after administration of Kyprolis. Administer dexamethasone prior to Kyprolis to reduce the incidence and severity of infusion reactions [see Dosage and Administration (2)]. Inform patients of the risk and of symptoms and to contact a physician immediately if symptoms of an infusion reaction occur [see Patient Counseling Information (17)].
5.10 Thrombocytopenia
Kyprolis causes thrombocytopenia with platelet nadirs observed between Day 8 and Day 15 of each 28-day cycle, with recovery to baseline platelet count usually by the start of the next cycle [see Adverse Reactions (6)]. Thrombocytopenia was reported in approximately 40% of patients in clinical trials with Kyprolis. Monitor platelet counts frequently during treatment with Kyprolis. Reduce or withhold dose as appropriate [see Dosage and Administration (2)].
5.11 Hepatic Toxicity and Hepatic Failure
Cases of hepatic failure, including fatal cases, have been reported (< 1%) during treatment with Kyprolis. Kyprolis can cause increased serum transaminases. Monitor liver enzymes regularly, regardless of baseline values. Reduce or withhold dose as appropriate [see Dosage and Administration (2) and Adverse Reactions (6)].
5.12 Thrombotic Microangiopathy
Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemol |
