Trabectedin Disease Interactions

Cardiomyopathy including cardiac failure, congestive heart failure, ejection fraction decreased, diastolic dysfunction, or right ventricular dysfunction can occur with the use of trabectedin. Care should be taken when using this agent in patients with heart disease. Assess LVEF before initiation of therapy and at 2- to 3-month intervals thereafter. It is recommended to withhold therapy for LVEF below lower limit of normal and permanently discontinue treatment for symptomatic cardiomyopathy or persistent left ventricular dysfunction that does not recover to lower limit of normal within 3 weeks.

Hepatotoxicity, including hepatic failure, can occur with the use of trabectedin. It is recommended to assess liver function test (LFTs) prior to each administration of trabectedin and as deem appropriately based on the severity of preexisting hepatic impairment. Dose interruption, reduction, or discontinuation of treatment might be appropriate based on severity and duration of LFTs abnormality. The use of trabectedin in patients with mild hepatic impairment is not expected to cause clinically significant effects on its pharmacokinetics. Reduce dose in patients with moderate hepatic impairment as clinically appropriate and do not administer trabectedin to patients with severe hepatic impairment (bilirubin levels above 3 times to 10 times the upper limit of normal, and any AST and ALT). Close monitoring of LFTs is recommended.

The use of trabectedin has been associated with neutropenic sepsis, including fatal cases. It is recommended to monitor neutrophil count before each dose of trabectedin and periodically during treatment. Withhold treatment if the neutrophil count is less than 1,500 cells/microliter on the treatment day and permanently reduce the dose for life-threatening or prolonged, severe neutropenia in the preceding cycle. Therapy with trabectedin should be administered cautiously in patients predisposed to neutropenia. Patients should be warned to report any febrile illness.

Rhabdomyolysis and musculoskeletal toxicity can occur with the use of trabectedin. It is recommended to obtain baseline serum creatine phosphokinase (CPK) and creatinine levels prior to initiating therapy with trabectedin and periodically during treatment as clinically indicated. Withhold trabectedin for serum CPK levels more than 2.5 times the upper limit of normal. If CPK is elevated, evaluate for signs and symptoms of rhabdomyolysis or other causes. Permanently discontinue treatment for rhabdomyolysis. Care should be taken when using this agent in patients at risk for rhabdomyolysis.

The use of trabectedin in patients with mild or moderate renal impairment is not expected to cause clinically significant effects on its pharmacokinetics. No dose adjustment is recommended in patients with mild or moderate renal impairment. The effects of severe renal impairment or end-stage renal disease on trabectedin exposure are unknown. Hemodialysis is not expected to enhance the elimination of trabectedin as the product is highly bound to plasma proteins (97%) and not significantly excreted by the kidneys.