No

Antineoplastic Agent, Antimetabolite

Adenocarcinoma of the pancreas; first-line therapy for patients with locally advanced (nonresectable stage II of stage III) or metastatic (stage IV) adenocarcinoma of the pancreas (indicated for patients previously treated with 5-FU); combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (stage IIIA or IIIB) or metastatic (stage IV) non-small cell lung cancer

D

Known hypersensitivity to gemcitabine

The U.S. Food & Drug Administration (FDA) recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Prolongation of the infusion time >60 minutes and more frequent than weekly dosing have been shown to increase toxicity. Gemcitabine can suppress bone marrow function manifested by leukopenia, thrombocytopenia and anemia, and myelosuppression is usually the dose-limiting ototoxicity. The incidence of fever is 41% and gemcitabine may cause fever in the absence of clinical infection. Rash has been reported in 30% of patients - typically a macular or finely granular maculopapular pruritic eruption of mild to moderate severity involving the trunk and extremities. Gemcitabine should be used with caution in patients with pre-existing renal impairment (mild proteinuria and hematuria were commonly reported; hemolytic uremic syndrome has been reported) and hepatic impairment (associated with transient elevations of serum transaminases in 2/3 of patients - but no evidence of increasing hepatic toxicity).

>10%:

Central nervous system: Fever

Dermatologic: Rash, alopecia

Gastrointestinal: Nausea, vomiting, constipation, diarrhea, stomatitis

Hematologic: Anemia, leukopenia, neutropenia, thrombocytopenia

Hepatic: Elevated liver enzymes (ALT/AST, alkaline phosphatase) and bilirubin

Neuromuscular & skeletal: Pain

Renal: Proteinuria, hematuria, increased BUN

Respiratory: Dyspnea

Miscellaneous: Infection

Symptoms of overdose include myelosuppression, paresthesia, and severe rash - the principle toxicities seen when a single dose as high as 5,700 mg/m² was administered by I.V. infusion over 30 minutes every 2 weeks

Treatment: Monitor blood counts and administer supportive therapy as needed

Store intact vials at room temperature (20°C to 25°C/68°F to 77°F). Reconstitute gemcitabine with 0.9% sodium chloride (preservative-free). Dilute as follows:

200 mg vial - 5 mL

1 g vial - 25 mL

These dilutions yield a concentration of 40 mg/mL - maximum concentration for reconstitution is 40 mg/mL. Store at room temperature (20°C to 25°C/68°F to 77°F) for up to 24 hours. The appropriate dose should be further diluted with 0.9% sodium chloride injection to concentrations as low as 0.1 mg/mL. Store at room temperature for up to 24 hours. Do not refrigerate.

Nucleoside analogue that primarily kills cells undergoing DNA synthesis (S-phase) and blocks the progression of cells through the G1/S-phase boundary

Distribution: V_d: 50 mL/m² (short infusions); 370 L/m² (long infusions)

Metabolism: To inactive metabolite (dFdU)

Half-life: 42-94 minutes

Elimination: In urine

Adults: I.V. (refer to individual protocols): 1000 mg/m² 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

For patients who tolerate the subsequent course, at a dose of 1250 mg/m², the dose for the next cycle can be increased to 1500 mg/m², provided again that the AGC and platelet nadirs exceed 1500 x 10⁶/L and 100,000 x 10⁶/L, respectively, and again, if nonhematologic toxicity has not been greater than WHO Grade 1

Dosing adjustment in renal/hepatic impairment: Use with caution; gemcitabine has not been studied in patients with significant renal or hepatic dysfunction

I.V. over 30 minutes

Patients should be monitored prior to each dose with a complete blood count (CBC), including differential and platelet count; suspension or modification of therapy should be considered when marrow suppression is detected

None reported

Leukopenia is common; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This drug can only be administered by infusion. During therapy, do not use alcohol, aspirin-containing products, and OTC medications without consulting prescriber. It is important to maintain adequate nutrition and hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) during therapy; frequent small meals may help. You may experience mild nausea or vomiting (frequent small meals, frequent mouth care, sucking lozenges, or chewing gum may help); loss of hair (reversible); mouth sores (frequent mouth care and use of a soft toothbrush or cotton swabs may help). You will be more susceptible to infection (avoid crowds and exposure to infection as much as possible). Yogurt or buttermilk may help reduce diarrhea. This drug may cause sterility or birth defects. Report extreme fatigue; severe GI upset or diarrhea; bleeding or bruising, fever, chills, sore throat, vaginal discharge; signs of fluid retention (swelling extremities, difficulty breathing, unusual weight gain); yellowing of skin or eyes or change in color of urine or stool. This drug can only be administered by infusion. During therapy, do not use alcohol, aspirin-containing products, and OTC medications without consulting prescriber. It is important to maintain adequate nutrition and hydration during therapy; frequent small meals may help. Take 2-3 L fluid/day. You may experience mild nausea or vomiting (frequent small meals, frequent mouth care, and sucking on lozenges may help); loss of hair (reversible); mouth sores (frequent mouth care and use of a soft toothbrush or cotton swabs may help). You will be more susceptible to infection (avoid crowds and exposure to infection as much as possible). Yogurt or buttermilk may help reduce diarrhea. This drug may cause sterility or birth defects. Report extreme fatigue; severe GI upset or diarrhea; bleeding or bruising, fever, chills, sore throat, vaginal discharge; signs of fluid retention (swelling extremities, difficulty breathing, unusual weight gain); yellowing of skin or eyes or change in color of urine or stool. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures. Do not breast-feed.

Powder for injection, as hydrochloride, lyophilized: 20 mg/mL (10 mL, 50 mL)

Green MR, "Gemcitabine Safety Overview," Semin Oncol, 1996, 23(5 Suppl 10):32-5.

Guchelaar HJ, Richel DJ, and van Knapen A, "Clinical, Toxicological and Pharmacological Aspects of Gemcitabine," Cancer Treat Rev, 1996, 22(1):15-31.

Hui YF and Reitz J, "Gemcitabine: A Cytidine Analogue Active Against Solid Tumors," Am J Health Syst Pharm, 1997, 54(2):162-70.

Plunkett W, Huang P, Xu YZ, et al, "Gemcitabine: Metabolism, Mechanisms of Action, and Self-Potentiation," Semin Oncol, 1995, 22(4 Suppl 11):3-10.

Storniolo AM, Allerheiligen SR, and Pearce HL, "Preclinical, Pharmacologic, and Phase I Studies of Gemcitabine," Semin Oncol 1997, 24(2 Suppl 7):S7-2-S7-7.