Gemtor

Approved Indications:

• Pancreatic Cancer:
• Treatment of locally advanced, unresectable, or metastatic pancreatic adenocarcinoma.
• Non-Small Cell Lung Cancer (NSCLC):
• First-line treatment for locally advanced or metastatic NSCLC, alone or in combination with cisplatin.
• Bladder Cancer:
• Treatment of locally advanced or metastatic transitional cell carcinoma of the bladder, often combined with cisplatin.
• Breast Cancer:
• Used in metastatic breast cancer, commonly combined with paclitaxel after failure of prior chemotherapy.
• Ovarian Cancer:
• Treatment of recurrent ovarian cancer in combination with carboplatin.

Off-label/Clinically Accepted Uses:

• Various other solid tumors and hematologic malignancies in clinical trials or compassionate use.

• Adults:
• Pancreatic Cancer:
• 1000 mg/m² IV infusion over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
• NSCLC:
• 1250 mg/m² IV infusion over 30 minutes on days 1 and 8 of a 21-day cycle, alone or with cisplatin.
• Bladder Cancer:
• 1000 mg/m² IV on days 1, 8, and 15 with cisplatin on day 2 of a 28-day cycle.
• Breast Cancer:
• 1250 mg/m² IV on days 1 and 8, repeated every 21 days.
• Ovarian Cancer:
• 1000 mg/m² IV on days 1 and 8 with carboplatin every 21 days.
• Pediatrics:
• Safety and efficacy not established; dosing varies in investigational settings.
• Elderly:
• No specific dose adjustment; monitor for toxicity.
• Renal Impairment:
• Use with caution; dose adjustment may be necessary depending on severity.
• Hepatic Impairment:
• No established dose adjustment; monitor liver function closely.
• Administration Route:
• Intravenous infusion only; infuse over 30 minutes.

Gemcitabine is a nucleoside analog of deoxycytidine that undergoes intracellular phosphorylation to its active diphosphate and triphosphate metabolites. The diphosphate metabolite inhibits ribonucleotide reductase, decreasing deoxynucleotide pools required for DNA synthesis. The triphosphate metabolite incorporates into DNA, causing premature chain termination and inhibiting DNA synthesis and repair. These combined effects induce apoptosis and inhibit tumor cell proliferation.

• Absorption: Administered intravenously; systemic bioavailability is 100%.
• Distribution: Widely distributed; volume of distribution approximately 43–96 L.
• Metabolism: Rapidly metabolized by cytidine deaminase to inactive metabolite 2’,2’-difluorodeoxyuridine (dFdU).
• Active Metabolites: Gemcitabine triphosphate is the active metabolite responsible for cytotoxicity inside cells.
• Elimination: Primarily renal excretion of inactive metabolites.
• Half-life: Plasma half-life is short (approximately 42–94 minutes); metabolites have longer half-life.

• Pregnancy:
• FDA Category D: Positive evidence of human fetal risk; contraindicated unless benefits outweigh risks.
• Lactation:
• Unknown if excreted in breast milk; breastfeeding not recommended during treatment due to potential toxicity.

• Primary Therapeutic Class: Antineoplastic agent
• Subclass: Antimetabolite, pyrimidine analog

• Known hypersensitivity to gemcitabine or any component of the formulation.
• Severe baseline myelosuppression.
• Significant hepatic or renal dysfunction without close monitoring.

• Myelosuppression: Dose-limiting toxicity; monitor complete blood counts closely.
• Liver Toxicity: Monitor liver enzymes; hepatotoxicity may occur.
• Pulmonary Toxicity: Rare cases of interstitial pneumonitis or pulmonary fibrosis reported.
• Renal Toxicity: Use with caution in renal impairment.
• Infusion Reactions: Monitor for fever, chills, hypotension during infusion.
• Pregnancy: Avoid use; teratogenic effects.

Common Adverse Effects:

• Hematologic: Neutropenia, thrombocytopenia, anemia
• Gastrointestinal: Nausea, vomiting, diarrhea, elevated liver enzymes
• Constitutional: Fatigue, fever, rash

Serious/Rare Side Effects:

• Pulmonary toxicity (pneumonitis, fibrosis)
• Severe myelosuppression leading to infections or bleeding
• Hepatic failure (rare)

• Increased myelosuppression risk with other myelosuppressive agents (e.g., cisplatin, carboplatin).
• Caution with nephrotoxic drugs due to renal clearance dependency.
• No significant CYP450 enzyme involvement; low potential for CYP-mediated interactions.

• Guidelines emphasize dose adjustments and close monitoring for hematologic toxicity.
• Newer protocols combine gemcitabine with immunotherapy or targeted agents in clinical trials.
• Emphasis on managing infusion reactions and supportive care to improve tolerability.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from light; keep in original container.
• Do not freeze.
• Use immediately after reconstitution or store refrigerated (2°C to 8°C) for no more than 24 hours before administration.