DOCETAXEL
Clinical safety rating: avoid
Contraindicated (not allowed)
Docetaxel is a taxane that promotes microtubule assembly and inhibits depolymerization, leading to cell cycle arrest in the G2/M phase and apoptosis.
| Metabolism | Hepatic metabolism primarily via CYP3A4 and CYP3A5 isoenzymes, with minor contributions from CYP2C8. |
| Excretion | Primarily biliary/fecal (≥75% as unchanged drug and metabolites). Renal excretion accounts for <10% of the dose. |
| Half-life | Terminal elimination half-life is approximately 11 to 18 hours, with an average of 13.5 hours in cancer patients. |
| Protein binding | >95% bound primarily to albumin and α1-acid glycoprotein (AAG). |
| Volume of Distribution | Large Vd of 50–100 L/m² (approximately 2–7 L/kg), indicating extensive tissue binding. |
| Bioavailability | Only available intravenously (oral bioavailability <10% due to P-glycoprotein efflux and first-pass metabolism). |
| Onset of Action | Intravenous: cytotoxicity begins within hours; clinical antimitotic effects observed within days. |
| Duration of Action | Duration of action is linked to myelosuppression, typically lasting 7–14 days. Neutrophil nadir occurs at 7–10 days. |
75 mg/m² IV over 1 hour every 3 weeks
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended for renal impairment; use caution if CrCl <30 mL/min |
| Liver impairment | Child-Pugh A: 75 mg/m²; Child-Pugh B: reduce dose to 60 mg/m²; Child-Pugh C: contraindicated |
| Pediatric use | Not established; safety and efficacy not determined; doses of 75 mg/m² IV every 3 weeks have been used in some protocols |
| Geriatric use | No specific dose adjustment; monitor for increased toxicity, especially neutropenia and neuropathy; consider starting at 60 mg/m² in frail elderly |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inhibitors may increase levels and inducers may decrease levels Can cause severe fluid retention and myelosuppression.
| Breastfeeding | Contraindicated during breastfeeding. No data on M/P ratio; docetaxel is expected to be excreted into human milk based on physicochemical properties. Potential for serious adverse reactions in nursing infants, including myelosuppression and gastrointestinal toxicity. |
| Teratogenic Risk | Pregnancy Category D. First trimester: High risk of congenital malformations, including neural tube defects, skeletal anomalies, and cardiac defects. Second and third trimesters: Increased risk of fetal growth restriction, oligohydramnios, and neonatal myelosuppression. Spontaneous abortion and fetal death reported. |
■ FDA Black Box Warning
Toxic deaths: Increased risk in patients with elevated liver function tests, low performance status, prior platinum therapy, and at higher doses. Neutropenia: Severe neutropenia can occur; monitor blood counts. Hypersensitivity reactions: Severe reactions require immediate discontinuation and appropriate therapy. Fluid retention: Severe fluid retention can occur despite premedication.
| Common Effects | other cancers |
| Serious Effects |
Severe hypersensitivity to docetaxel or polysorbate 80; baseline neutrophil count <1500 cells/mm³; severe hepatic impairment (bilirubin >ULN or AST/ALT >1.5×ULN with alkaline phosphatase >2.5×ULN).
| Precautions | Neutropenia, febrile neutropenia, infections, hypersensitivity reactions, fluid retention (edema, pleural effusion, ascites), peripheral neuropathy, stomatitis, diarrhea, hepatotoxicity, asthenia, myalgia, and nail changes. Monitor liver function and blood counts. Adjust dose in hepatic impairment. |
Loading safety data…
| Fetal Monitoring | Maternal: Complete blood count with differential before each cycle, liver function tests, renal function, and monitoring for hypersensitivity reactions. Fetal: Serial ultrasound for growth restriction and amniotic fluid index, non-stress test or biophysical profile in third trimester. Neonatal: Monitoring for myelosuppression and infections after delivery. |
| Fertility Effects | Docetaxel can cause both male and female infertility. In males: Oligospermia, azoospermia; may be irreversible. In females: Ovarian failure, premature menopause with elevated FSH, amenorrhea. Fertility preservation strategies should be discussed prior to treatment. |