Gemcitabine

May cause bone marrow suppression (neutropenia, thrombocytopenia, and anemia); myelosuppression is generally the dose-limiting toxicity and is increased when used in combination with other chemotherapy. Monitor blood counts; dosage adjustments are frequently required.

Capillary leak syndrome (CLS) with serious consequences has been reported, both with single-agent gemcitabine and with combination chemotherapy; discontinue if CLS develops.

Hemolytic uremic syndrome (HUS) has been reported; may lead to renal failure and dialysis (including fatalities); monitor for evidence of anemia with microangiopathic hemolysis (elevation of bilirubin or LDH, reticulocytosis, severe thrombocytopenia, and/or renal failure) and monitor renal function at baseline and periodically during treatment. Permanently discontinue if HUS or severe renal impairment occurs; renal failure may not be reversible despite discontinuation.

Serious hepatotoxicity (including liver failure and death) has been reported (when used alone or in combination with other hepatotoxic medications); use in patients with hepatic impairment (history of cirrhosis, hepatitis, or alcoholism) or in patients with hepatic metastases may lead to exacerbation of hepatic impairment. Monitor hepatic function at baseline and periodically during treatment; consider dose adjustments with elevated bilirubin; discontinue if severe liver injury develops.

Posterior reversible encephalopathy syndrome (PRES) has been reported, both with single-agent therapy and with combination chemotherapy. PRES may manifest with blindness, confusion, headache, hypertension, lethargy, seizure, and other visual and neurologic disturbances. If PRES diagnosis is confirmed (by MRI), discontinue therapy.

Pulmonary toxicity, including adult respiratory distress syndrome, interstitial pneumonitis, pulmonary edema, and pulmonary fibrosis, has been observed; may lead to respiratory failure (some fatal) despite discontinuation. Onset for symptoms of pulmonary toxicity may be delayed up to 2 weeks beyond the last dose. Discontinue for unexplained dyspnea (with or without bronchospasm) or other evidence of pulmonary toxicity. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Not indicated for use with concurrent radiation therapy; radiation toxicity, including tissue injury, severe mucositis, esophagitis, or pneumonitis, has been reported with concurrent and nonconcurrent administration; has radiosensitizing activity when gemcitabine and radiation therapy are given together or ≤7 days apart; radiation recall may occur when gemcitabine and radiation therapy are given >7 days apart. Dosage form specific issues:

Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling. Other warnings/precautions:

Prolongation of the infusion duration >60 minutes or more frequent than weekly dosing have been shown to alter the half-life and increase toxicity (hypotension, flu-like symptoms, myelosuppression, weakness). A fixed-dose rate (FDR) infusion rate of 10 mg/m2/minute has been studied in adults in order to optimize the pharmacokinetics (off-label); prolonged infusion times increase the intracellular accumulation of the active metabolite, gemcitabine triphosphate (Ko 2006; Tempero 2003). Patients who receive gemcitabine FDR experience more grade 3/4 hematologic toxicity (Ko 2006; Poplin 2009).

Gemcitabine is available in multiple formulations and concentrations; verify product and concentration prior to admixture to assure appropriate dose preparation.