Gemcitabine hydrochloride
Gemcitabine hydrochloride (Gemzar)
Gemcitabine hydrochloride
(jem- SIGHT-ah-been)
Pregnancy Category: D Gemzar (Rx)

Classification: Antineoplastic, miscellaneous

See Also: See also Antineoplastic Agents .

Action/Kinetics: A nucleoside analog that kills cells undegoing DNA synthesis (S-phase) and by blocking the progression of cells through the G1/S-phase boundary. Metabolized within cells by nucleoside kinases to the active gemcitabine diphosphate and triphosphate nucleosides. The diphosphate inhibits ribonucleotide reductase, which is responsible for catalyzing reactions that generate the deoxynucleoside triphosphate for DNA synthesis. Inhibition of the reductase enzyme causes a decrease in the levels of deoxynucleotides. The triphosphate competes with triphosphate nucleosides for incorporation into DNA, resulting in inhibition of DNA synthesis. DNA polymerase is not able to remove the gemcitabine nucleoside and repair the growing DNA strands. The metabolite of gemcitabine nucleoside is excreted through the urine.

Uses: First-line treatment for locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas. Indicated for those who have been treated previously with 5-fluorouracil. First-line therapy, with cisplatin, for treatment of inoperable, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer.

Contraindications: Lactation.

Special Concerns: Use with caution in those with preexisting renal impairment or hepatic insufficiency. Safety and efficacy have not been determined in children.

Side Effects: GI: N&V;, diarrhea, constipation, stomatitis. CNS: Somnolence, mild to severe paresthesias, insomnia. CV: Arrhythmia, hypertension, MI, CVA. Hematologic: Anemia, leukopenia, neutropenia, thrombocytopenia, platelet transfusions. Respiratory: Dyspnea, bronchospasm, cough, rhinitis, parenchymal lung toxicity (rare). Dermatologic: Alopecia, macular or finely granular maculopapular pruritic eruptions, pruritus, hair loss (minimal). Body as a whole: Pain, fever, peripheral edema, flu syndrome (including fever), asthenia, chills, myalgia, sweating, malaise. Miscellaneous: Hemorrhage, sepsis hemolytic uremic syndrome, infections, petechiae, anaphylaxis (rare).

Laboratory Test Alterations: ALT, AST, alkaline phosphatase, bilirubin, BUN, creatinine. Proteinuria, hematuria.

Overdose Management: Symptoms: Myelosuppression, paresthesias, severe rash. Treatment: Monitor with appropriate blood counts. Supportive therapy as needed.

How Supplied: Powder for injection, lyophilized: 20 mg/mL

Dosage
?IV Only Adenocarcinoma of the pancreas.
Adults: 1,000 mg/m ² given over 30 min once a week for up to 7 weeks (or until toxicity necessitates reducing or holding a dose). This is followed by a 1-week rest period. Subsequent cycles should consist of infusions once a week for 3 consecutive weeks out of 4. Those who complete the entire 7 weeks of initial therapy or a subsequent 3-week cycle at the 1,000-mg/m ² dose may have the dose for subsequent cycles increased by 25% to 1,250 mg/m ² provided that the absolute neutrophil count nadir exceeds 1,500 x 10 ⁶/L and the platlet nadir exceeds 100,000 x 10 ⁶/L and if nonhematologic toxicity has not been greater than World Health Organization Grade 1. If clients tolerate a dose of 1,250 mg/m ² once weekly, the dose for the next cycle can be increased to 1,500 mg/m ² provided the absolute neutrophil count and platelet nadirs are as defined above.
The dose should be reduced to 75% of the full dose if the absolute granulocyte count is 500-999 x 10 ⁶/L and the platelet count is 50,000-99,000 x 10 ⁶/L. The dose should be held if the absolute granulocyte count falls below 500 x 10 ⁶/L and the platelet count falls below 50,000 x 10 ⁶/L.
Non-small cell lung cancer.
Two schedules are used. (1) Four-week schedule: Gemcitabine, 1,000 mg/m ² over 30 min on days 1, 8, and 15 of each 28-day cycle. Give cisplatin, IV, 100 mg/m ² on day 1 after gemcitabine. (2) Three-week schedule: Gemcitabine, 1,250 mg/m ² over 30 min on days 1 and 8 of each 21-day cycle. Give cisplatin, IV, 100 mg/m ² after gemcitabine on day 1.