d bilirubin levels have been reported rarely. Serious hepatotoxicity including liver failure and death has been reported very rarely in patients receiving Gemzar alone or in combination with other potentially hepatotoxic drugs.
Pulmonary— Parenchymal toxicity, including interstitial pneumonitis, pulmonary fibrosis, pulmonary edema, and adult respiratory distress syndrome (ARDS), has been reported rarely following one or more doses of Gemzar administered to patients with various malignancies. Some patients experienced the onset of pulmonary symptoms up to 2 weeks after the last Gemzar dose. Respiratory failure and death occurred very rarely in some patients despite discontinuation of therapy.
Renal— Hemolytic–Uremic Syndrome (HUS) and/or renal failure have been reported following one or more doses of Gemzar. Renal failure leading to death or requiring dialysis, despite discontinuation of therapy, has been rarely reported. The majority of the cases of renal failure leading to death were due to HUS.
Injury, Poisoning, and Procedural Complications— Radiation recall reactions have been reported (see Radiation Therapy under PRECAUTIONS).
OVERDOSAGE
There is no known antidote for overdoses of Gemzar. Myelosuppression, paresthesias, and severe rash were the principal toxicities seen when a single dose as high as 5700 mg/m2 was administered by IV infusion over 30 minutes every 2 weeks to several patients in a Phase 1 study. In the event of suspected overdose, the patient should be monitored with appropriate blood counts and should receive supportive therapy, as necessary.
DOSAGE AND ADMINISTRATION
Gemzar is for intravenous use only.
Adults
Single–Agent Use:
Pancreatic Cancer— Gemzar should be administered by intravenous infusion at a dose of 1000 mg/m2 over 30 minutes once weekly for up to 7 weeks (or until toxicity necessitates reducing or holding a dose), followed by a week of rest from treatment. Subsequent cycles should consist of infusions once weekly for 3 consecutive weeks out of every 4 weeks.
Dose Modifications— Dosage adjustment is based upon the degree of hematologic toxicity experienced by the patient (see WARNINGS). Clearance in women and the elderly is reduced and women were somewhat less able to progress to subsequent cycles (see Human Pharmacokinetics under CLINICAL PHARMACOLOGY and PRECAUTIONS).
Patients receiving Gemzar should be monitored prior to each dose with a complete blood count (CBC), including differential and platelet count. If marrow suppression is detected, therapy should be modified or suspended according to the guidelines in Table 13.
Table 13: Dosage Reduction Guidelines Absolute granulocyte count
(x 106/L)
Platelet count
(x 106/L)
% of full dose
≥1000
and
≥100,000
100
500–999
or
50,000–99,999
75
<500
or
<50,000
Hold
Laboratory eva luation of renal and hepatic function, including transaminases and serum creatinine, should be performed prior to initiation of therapy and periodically thereafter. Gemzar should be administered with caution in patients with evidence of significant renal or hepatic impairment as there is insufficient information from clinical studies to allow clear dose recommendation for these patient populations.
Patien
