Gemcitabine - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Schedule-Dependent Toxicity: Increased toxicity with infusion time greater than 60 minutes or dosing more frequently than once weekly.

Myelosuppression: Monitor for myelosuppression prior to each cycle and reduce or withhold dose for severe myelosuppression.

Severe Cutaneous Adverse Reactions (SCARs) Permanently discontinue gemcitabine injection if SCARs occur.

Pulmonary Toxicity and Respiratory Failure: Discontinue gemcitabine injection for unexplained dyspnea or other evidence of severe pulmonary toxicity.

Hemolytic Uremic Syndrome (HUS): Monitor renal function prior to initiation and during treatment.

Discontinue gemcitabine for HUS or severe renal impairment.

Hepatic Toxicity: Monitor hepatic function prior to initiation and during treatment.

Discontinue gemcitabine for severe hepatic toxicity.

Embryo-Fetal Toxicity: Can cause fetal harm.

Advise females and males of reproductive potential to use effective contraception. ( 5.7 , 8.1 ) Exacerbation of Radiation Therapy Toxicity: May cause severe and life-threatening toxicity when administered during or within 7 days of radiation therapy.

Capillary Leak Syndrome: Discontinue gemcitabine.

Posterior Reversible Encephalopathy Syndrome (PRES): Discontinue gemcitabine.

5.1 Schedule-Dependent Toxicity In clinical trials evaluating the maximum tolerated dose of gemcitabine, prolongation of the infusion time beyond 60 minutes or more frequent than weekly dosing resulted in an increased incidence of clinically significant hypotension, severe flu-like symptoms, myelosuppression, and asthenia.

The half-life of gemcitabine is influenced by the length of the infusion [see Clinical Pharmacology ] .

Refer to the recommended gemcitabine dosage [see Dosage and Administration ( 2.1 , 2.2 , 2.3 , 2.4 )] .

5.2 Myelosuppression Myelosuppression manifested by neutropenia, thrombocytopenia, and anemia, occurs with gemcitabine as a single agent and the risks are increased when gemcitabine is combined with other cytotoxic drugs.

In clinical trials, Grade 3-4 neutropenia, anemia, and thrombocytopenia occurred in 25%, 8%, and 5%, respectively of the 979 patients who received single agent gemcitabine.

The frequencies of Grade 3-4 neutropenia, anemia, and thrombocytopenia varied from 48% to 71%, 8% to 28%, and 5% to 55%, respectively, in patients receiving gemcitabine in combination with another drug [see Adverse Reactions ] .

Prior to each dose of gemcitabine, obtain a complete blood count (CBC) with a differential and a platelet count.

Modify the dosage as recommended [see Dosage and Administration ( 2.1 , 2.2 , 2.3 , 2.4 )] .

5.3 Severe Cutaneous Adverse Reactions (SCARs) SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), which can be life-threatening or fatal, have been reported in association with gemcitabine treatment [see Adverse Reactions ] .

Monitor patients for signs and symptoms of severe cutaneous adverse reactions.

Permanently discontinue gemcitabine in patients who develop SCARs.

5.4 Pulmonary Toxicity and Respiratory Failure Pulmonary toxicity, including interstitial pneumonitis, pulmonary fibrosis, pulmonary edema, and adult respiratory distress syndrome (ARDS), has been reported.

In some cases, these pulmonary events can lead to fatal respiratory failure despite the discontinuation of therapy.