Carfilzomib Disease Interactions

Cases of tumor lysis syndrome (TLS), including fatal outcomes, have been reported in patients receiving carfilzomib. Patients with multiple myeloma and a high tumor burden should be considered at a greater risk for TLS. Ensure that patients are well hydrated before administration of therapy in Cycle 1, and in subsequent cycles as recommended by the manufacturer. Consider uric acid-lowering drugs in patients at risk for TLS. It is recommended to monitor for evidence of TLS during treatment and manage promptly, including interruption of therapy until resolution of TLS.

Carfilzomib can cause new onset or worsening of preexisting cardiac failure, restrictive cardiomyopathy, myocardial ischemia, and myocardial infarction. Patients with preexisting heart problems might be at a greater risk of cardiac toxicity. It is recommended to monitor patients for clinical signs or symptoms of cardiac failure or cardiac ischemia. Evaluate promptly if cardiac toxicity is suspected. Withhold therapy for Grade 3 or 4 cardiac adverse events until recovery, and consider whether to restart at 1 dose level reduction based on a benefit/risk assessment.

Dyspnea was reported in patients treated with carfilzomib. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Withhold therapy with carfilzomib for Grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart therapy based on a benefit/risk assessment.

Fatal or serious cases of hemorrhage have been reported in patients treated with carfilzomib. Hemorrhage has been reported in patients having either low or normal platelet counts. Hemorrhage has also been reported in patients who were not on antiplatelet therapy or anticoagulation. Care should be exercised when using this agent in patients at risk of hemorrhagic events. Promptly evaluate signs and symptoms of blood loss. It is recommended to monitor platelet counts frequently during treatment and to reduce or withhold dose as appropriate.

Cases of hepatic failure, including fatal cases, have been reported in patients receiving treatment with carfilzomib. The pharmacokinetics and safety of carfilzomib were evaluated in patients with normal hepatic function, or mild, moderate, or severe hepatic impairment. The AUC of carfilzomib increased by approximately 50% in patients with mild and moderate hepatic impairment compared to patients with normal hepatic function. PK data were not collected in patients with severe hepatic impairment. It is recommended to reduce the dose of carfilzomib by 25% in patients with mild or moderate hepatic impairment. Dosing recommendation cannot be made for patients with severe hepatic function. Monitor liver enzymes regularly, regardless of baseline values, and modify dose based on toxicity. Therapy with this agent can cause increased serum transaminases. Monitor liver enzymes regularly, regardless of baseline values. It is recommended to reduce or withhold dose as appropriate.

The use of carfilzomib has been associated with hypertension, including hypertensive crisis and hypertensive emergency. It is recommended to monitor blood pressure regularly in all patients, especially in hypertensive patients. Care should be taken and if hypertension cannot be adequately controlled, withhold therapy and consider whether to restart therapy based on a benefit/risk assessment.

Cases of posterior reversible encephalopathy syndrome (PRES) have been reported with the use carfilzomib. Discontinue therapy if PRES is suspected and evaluate. Care should be exercised as the safety of reinitiating carfilzomib therapy in patients previously experiencing PRES is not known.

Pulmonary arterial hypertension was reported in patients treated with carfilzomib. It is recommended to evaluate patients with cardiac imaging and/or other tests as indicated. Care should be exercised in patients with existing pulmonary hypertension. Withhold carfilzomib therapy for pulmonary hypertension until resolved or returned to baseline, and consider whether to restart based on a benefit/risk assessment.

The use of carfilzomib has been associated with pulmonary toxicity. Patients presenting pulmonary symptoms should be carefully assessed for pulmonary toxicity. It is recommended to discontinue treatment in the event of drug-induced pulmonary toxicity.

Cases of acute renal failure have occurred in patients receiving carfilzomib. The risk was greater in patients with a baseline reduced estimated creatinine clearance. It is recommended to monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Consider reducing or withholding dose as appropriate.

Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) have been reported with the use of carfilzomib. Monitor for signs and symptoms of TTP/HUS. If the diagnosis is suspected, stop therapy and evaluate patients. If the diagnosis of TTP/HUS is excluded, therapy may be restarted. The safety of reinitiating carfilzomib therapy in patients previously experiencing TTP/HUS is not known.

Carfilzomib should be used with caution in patients with a history of venous thromboembolic events, including deep venous thrombosis and pulmonary embolism. Thromboprophylaxis is recommended for patients being treated with the combination of carfilzomib 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 carfilzomib in combination with dexamethasone or lenalidomide plus dexamethasone.