Gemcitabine is a chemotherapy medication used to treat various types of cancer. It is an antimetabolite drug that interferes with the synthesis of DNA, inhibiting cell division and growth. Gemcitabine is the intravenous formulation of the drug, often used for treating cancers such as non-small cell lung cancer (NSCLC), pancreatic cancer, bladder cancer, and breast cancer. The “RTU” (ready-to-use) formulation indicates that the drug is pre-diluted for intravenous administration, making it easier to use in clinical settings.

1. Mechanism of Action

Gemcitabine is a nucleoside analog, structurally similar to cytidine, which is incorporated into DNA during the S-phase of the cell cycle. Once incorporated, gemcitabine causes DNA strand termination and inhibits DNA synthesis by interfering with the activity of DNA polymerase. It also induces apoptosis (programmed cell death) in rapidly dividing cells, which is why it is effective against tumors. Gemcitabine’s activity is enhanced in the presence of deoxycytidine kinase, which helps convert gemcitabine into its active form, gemcitabine diphosphate.

2. Indications

• Pancreatic Cancer: First-line treatment for advanced pancreatic cancer, often in combination with other chemotherapeutic agents.
• Non-Small Cell Lung Cancer (NSCLC): Used in combination with other chemotherapy agents (e.g., cisplatin) for the treatment of locally advanced or metastatic NSCLC.
• Bladder Cancer: Used for advanced or metastatic bladder cancer.
• Breast Cancer: In combination with other chemotherapy agents for metastatic breast cancer.
• Ovarian Cancer: In combination with other chemotherapy agents for ovarian cancer.

3. Dosage and Administration

• Route: Intravenous (IV) infusion.
• Adult Dosage:
  • Non-Small Cell Lung Cancer (NSCLC):
    • 1,000 mg/m² IV once weekly for the first 4 weeks, followed by one week of rest, in combination with cisplatin.
  • Pancreatic Cancer:
    • 1,000 mg/m² IV on Days 1, 8, and 15 of a 28-day cycle, often in combination with other drugs like nab-paclitaxel (Abraxane).
  • Bladder Cancer:
    • 1,000 mg/m² IV on Days 1, 8, and 15 of a 28-day cycle, typically in combination with other agents.
  • Breast Cancer:
    • 1,250 mg/m² IV on Days 1 and 8 of a 21-day cycle, often with other chemotherapeutic drugs like paclitaxel.
• Preparation:
  • The RTU (Ready-to-Use) formulation requires no further dilution for use. It is pre-diluted to the correct concentration for IV administration.
  • Administered as an IV infusion over 30 minutes.
• Renal Impairment: Dosage adjustments may be necessary in patients with renal dysfunction, particularly in cases of severe renal impairment.

4. Contraindications

• Hypersensitivity: Known hypersensitivity to gemcitabine or any of its components.
• Severe Bone Marrow Suppression: Gemcitabine should not be administered to patients with severe bone marrow suppression (e.g., low white blood cell count or low platelet count).

5. Warnings and Precautions

• Hematologic Toxicity: Gemcitabine can cause severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Frequent monitoring of blood counts is required, especially during the first few cycles.
• Liver Dysfunction: Caution is advised in patients with pre-existing liver disease. Liver function tests (LFTs) should be monitored regularly.
• Renal Impairment: Renal toxicity, including acute renal failure, has been reported. Renal function should be monitored, and dose reductions may be necessary in cases of impaired renal function.
• Pulmonary Toxicity: Interstitial pneumonitis and pulmonary fibrosis have been reported, which may require discontinuation of therapy if severe symptoms occur.
• Flu-like Symptoms: Patients may experience flu-like symptoms, including fever, chills, and malaise, typically early in the course of treatment.
• Injection Site Reactions: Gemcitabine can cause reactions at the injection site, including redness, swelling, or pain. Ensure proper administration techniques to minimize these effects.

6. Side Effects

• Common:
  • Nausea and vomiting
  • Fatigue
  • Fever and chills
  • Diarrhea
  • Hair loss (alopecia)
  • Rash
  • Anemia
  • Thrombocytopenia (low platelets)
  • Neutropenia (low white blood cell count)
• Serious:
  • Severe myelosuppression (e.g., neutropenia, thrombocytopenia)
  • Hepatotoxicity (elevated liver enzymes, jaundice)
  • Pulmonary toxicity (interstitial pneumonitis, fibrosis)
  • Severe infections due to neutropenia
  • Fluid retention and peripheral edema
  • Hypersensitivity reactions (e.g., anaphylaxis, rash, difficulty breathing).

7. Drug Interactions

• Myelosuppressive Drugs: Gemcitabine may increase the risk of myelosuppression when used with other myelosuppressive agents.
• Cytotoxic Drugs: Use caution when combining gemcitabine with other cytotoxic drugs, as the risk of severe myelosuppression and other toxicities may increase.
• CYP450 Substrates: Gemcitabine is not extensively metabolized by cytochrome P450 enzymes, but concurrent use with drugs that are CYP450 substrates (e.g., paclitaxel, carboplatin) should be monitored for potential interactions.
• Live Vaccines: Gemcitabine can weaken the immune system, making the use of live vaccines (e.g., yellow fever, measles) contraindicated during treatment.

8. Pharmacokinetics

• Absorption: Gemcitabine is administered intravenously, providing 100% bioavailability.
• Distribution: It is widely distributed in tissues and has a high volume of distribution. It crosses the blood-brain barrier to a limited extent.
• Metabolism: Gemcitabine is metabolized intracellularly to its active form, gemcitabine diphosphate, by deoxycytidine kinase. It is also metabolized by the liver, albeit to a lesser degree than by its active form.
• Elimination: Gemcitabine is primarily eliminated through the kidneys, with about 90% of the drug excreted unchanged in the urine. The elimination half-life is approximately 1 to 3 hours.

9. Storage

• Unopened Vials: Store at room temperature (20°C to 25°C, 68°F to 77°F). Protect from light and moisture. Do not freeze.
• Diluted Solutions: Once the gemcitabine solution is diluted for intravenous use, it should be used within 24 hours and stored at room temperature.