Gemcitabine
Gemcitabine is a **synthetic pyrimidine nucleoside analog** used as an antineoplastic agent. - **Veterinary Use**: Currently considered investigational with limited clinical data. It shows potential as a **radiosensitizer** for non-resectable tumors or as part of combination chemotherapy protocols (e.g., with carboplatin). - **Human Use**: Efficacious in treating pancreatic, small-cell lung, bladder, and soft tissue carcinomas, as well as lymphoma. > **Clinical Pearl**: Due to its high cost and significant myelosuppressive potential, its use in veterinary medicine is typically reserved for specialized oncology practices.
Mechanism: Gemcitabine is a **cell-cycle phase-specific** antimetabolite that acts primarily during the **S phase** (DNA synthesis) and blocks progression through the G1/S-phase boundary. - It is transported intracellularly and phosphorylated to **dFdCMP**, then to active diphosphate (**dFdCDP**) and triphosphate (**dFdCTP**) metabolites. - **dFdCDP** inhibits **ribonucleotide reductase**, depleting the cellular pool of deoxynucleotides required for DNA synthesis. - **dFdCTP** competes with endogenous deoxycytidine triphosphate (**dCTP**) for incorporation into the elongating DNA strand. Once incorporated, it causes **DNA chain termination** and subsequent apoptosis.
Dosing by species
- Carcinomas (in combination with carboplatin) · 2 mg/kg IV over 20-30 minutes · IV · no more than once every 7 days · Doses have ranged widely from 45 mg/m2-800 mg/m2 depending on the study.
- Exocrine pancreatic carcinoma (Low dose) · 20-25 mg/m2 or 2 mg/kg · IV · every 7 days · Administer as a 20 minute IV infusion.
- Carcinomas (in combination with carboplatin) · 2 mg/kg IV over 20-30 minutes · IV · no more than once every 7 days · Doses have ranged widely from 45 mg/m2-800 mg/m2 depending on the study.
- Bladder urothelial carcinoma, lymphoma, and various carcinomas (High dose) · 800-900 mg/m2 · IV · every 7-14 days · for 4 doses · Administer over 20-60 minutes.
- Bladder urothelial carcinoma, lymphoma, and various carcinomas (Low dose) · 25-50 mg/m2 · IV · once or twice a week · Administer over 20-60 minutes as per protocols.
- Carcinomas (Combination therapy) · 2 mg/kg · IV · every 7 days · Administer over 20-30 minutes (in 0.9% NaCl) combined with carboplatin.
- Advanced solid tumors · Escalating doses per protocol · IV · single administration or per protocol · Phase 1 dose-escalation trial.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Hypersensitivity to gemcitabine
- Known hypersensitivity to gemcitabine
- Pre-existing bone marrow suppression
Adverse effects
- Myelosuppression (neutropenia and thrombocytopenia; nadir at 3-7 days)
- Mild to moderate gastrointestinal toxicity
- Retinal hemorrhage
- Myelosuppression (neutropenia, thrombocytopenia, anemia)
- Gastrointestinal toxicity (vomiting, diarrhea, anorexia)
- Retinal haemorrhage
- Treatment-related mortality (due to severe complications)
Drug interactions
- Other myelosuppressive agents · Additive toxic effects (myelosuppression, GI toxicity)
Monitoring
- CBC before each treatment
- Fundic exam weekly while on therapy
- Baseline renal and hepatic function prior to therapy, and periodically thereafter
- Complete Blood Count (CBC) prior to each dose (monitor for myelosuppression)
- Hepatic function panel
- Renal function panel
- Gastrointestinal signs (vomiting, diarrhea, anorexia)
- Ophthalmic exam (monitor for retinal haemorrhage)
Overdose
There is no known antidote to gemcitabine in an overdose situation. Severe myelosuppression should be expected. Treatment is supportive.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.