GEMZAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GEMZAR (GEMZAR).
Gemcitabine is a nucleoside analog that inhibits ribonucleotide reductase and DNA synthesis. It is phosphorylated intracellularly to active diphosphate and triphosphate metabolites, which are incorporated into DNA, leading to chain termination and apoptosis.
| Metabolism | Gemcitabine is primarily metabolized by cytidine deaminase in the liver, blood, and other tissues to its inactive metabolite difluorodeoxyuridine (dFdU). It is also phosphorylated intracellularly by deoxycytidine kinase to active metabolites. |
| Excretion | Primarily renal: 92-98% of the dose excreted unchanged in urine; <10% fecal. |
| Half-life | Terminal half-life: 32-94 minutes (mean 42 min) after short infusion; longer with prolonged infusion due to saturation of deamination; clinical context: short half-life necessitates frequent dosing. |
| Protein binding | <5% bound; negligible binding to plasma proteins. |
| Volume of Distribution | Vd: 0.6-0.8 L/kg (50-70 L in adults); indicates distribution into total body water with limited tissue binding. |
| Bioavailability | Intravenous only; oral bioavailability not applicable (not orally administered). |
| Onset of Action | Intravenous: Cytotoxic effect begins within hours; clinical effect (tumor response) days to weeks. |
| Duration of Action | Duration of cytotoxicity: 24-48 hours after infusion; clinical duration of effect depends on regimen and tumor type; myelosuppression nadir at 10-14 days, recovery by 21 days. |
1000 mg/m2 IV over 30 minutes on days 1, 8, and 15 of a 28-day cycle for non-small cell lung cancer; 1250 mg/m2 IV over 30 minutes on days 1 and 8 of a 21-day cycle for pancreatic cancer.
| Dosage form | INJECTABLE |
| Renal impairment | For GFR 30-80 mL/min: start at 800 mg/m2. For GFR <30 mL/min: use alternative drug. Hemodialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 25%. Child-Pugh C: not recommended. |
| Pediatric use | No established pediatric dosing; use is not recommended in children. |
| Geriatric use | No specific dose adjustment required; monitor for myelosuppression and renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GEMZAR (GEMZAR).
| Breastfeeding | No human data; due to potential toxicity, discontinue breastfeeding or discontinue drug. M/P ratio unknown. |
| Teratogenic Risk | Fetal malformations (skeletal, CNS) and embryotoxicity in animal studies at subtherapeutic doses; human data limited. Avoid in first trimester; risk during second/third trimester unknown but potentially teratogenic. |
| Fetal Monitoring | Monitor complete blood counts, liver function, renal function; fetal ultrasound for growth and anomalies if exposed. |
■ FDA Black Box Warning
Gemcitabine can cause severe and fatal myelosuppression, including neutropenia, thrombocytopenia, and anemia. It has also been associated with hemolytic uremic syndrome (HUS) and capillary leak syndrome (CLS).
| Serious Effects |
["Hypersensitivity to gemcitabine or any of its components","Severe bone marrow depression (e.g., absolute neutrophil count < 500/mm³)"]
| Precautions | ["Myelosuppression: monitor complete blood counts regularly","Hemolytic uremic syndrome: discontinue if evidence of microangiopathic hemolytic anemia","Capillary leak syndrome: discontinue if evidence of systemic capillary leak","Pulmonary toxicity: interstitial pneumonitis, pulmonary edema, ARDS","Hepatotoxicity: monitor liver function","Renal toxicity: monitor renal function","Fetal harm: can cause fetal harm when administered to a pregnant woman","Radiation sensitization and recall: increased toxicity with radiation therapy"] |
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| Fertility Effects | Impairs spermatogenesis in males; ovarian failure in females (animal data). Human fertility effects unknown but may cause amenorrhea. |