VINORELBINE TARTRATE
Clinical safety rating: avoid
Contraindicated (not allowed)
Vinorelbine tartrate is a vinca alkaloid that inhibits tubulin polymerization, thereby disrupting microtubule assembly and causing mitotic arrest in the M phase of the cell cycle.
| Metabolism | Hepatic metabolism primarily via CYP3A4, with minor contributions from CYP3A5 and CYP2D6; undergoes deacetylation to form the major metabolite 4-O-deacetylvinorelbine. |
| Excretion | Vinorelbine tartrate is primarily eliminated via biliary/fecal excretion (46% of the administered dose as unchanged drug and metabolites in feces). Renal excretion accounts for approximately 18% of the dose, with <10% as unchanged drug. Hepatic metabolism is extensive, mediated by CYP3A4, and contributes to biliary elimination. |
| Half-life | Terminal elimination half-life is approximately 27–43 hours (mean ~28 hours). This prolonged half-life supports weekly dosing intervals and allows for accumulation with repeated doses. |
| Protein binding | Approximately 80–91% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution at steady state is 25–40 L/kg (mean 27 L/kg), indicating extensive tissue distribution and binding to cellular components, particularly microtubules. |
| Bioavailability | Oral bioavailability is approximately 43% (range 27–50%) due to first-pass metabolism. Intravenous administration yields 100% bioavailability. |
| Onset of Action | Intravenous administration: Onset of antimitotic activity occurs within minutes to hours post-infusion, corresponding to microtubule binding. Clinical response (e.g., tumor reduction) is typically not observed for several weeks. Oral administration: Absorption is rapid; peak plasma concentrations occur 1.5–3 hours post-dose, with similar onset of cellular effect. |
| Duration of Action | Duration of action is related to drug presence at therapeutic levels; given the half-life, suppression of microtubule dynamics persists for at least 24–48 hours post-dose. Clinical duration is not precisely defined but correlates with weekly dosing; recovery of normal tissues (e.g., bone marrow) occurs over 1–3 weeks. |
25-30 mg/m2 IV weekly as a single agent; 25 mg/m2 IV weekly in combination regimens.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for GFR >30 mL/min; insufficient data for GFR <30 mL/min; use with caution and consider dose reduction. |
| Liver impairment | Child-Pugh A: 25 mg/m2 IV weekly; Child-Pugh B: 20 mg/m2 IV weekly; Child-Pugh C: contraindicated or use with extreme caution, consider 12.5 mg/m2 IV weekly. |
| Pediatric use | Not established; limited data suggest 25 mg/m2 IV weekly, but safety and efficacy not determined. |
| Geriatric use | No specific dose adjustment; monitor for increased toxicity, especially neutropenia and neurotoxicity, and consider dose reduction based on tolerability. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inhibitors may increase levels Can cause severe myelosuppression and extravasation injury.
| Breastfeeding | It is unknown whether vinorelbine is excreted in human milk. Due to potential for serious adverse reactions in nursing infants, women should not breast-feed during therapy and for at least 1 month after the last dose. M/P ratio is not available. |
| Teratogenic Risk | Vinorelbine tartrate is embryotoxic and fetotoxic in animal studies. In humans, it is contraindicated in pregnancy (FDA Category D). First trimester exposure is associated with major congenital malformations, including skeletal, cardiac, and neural tube defects. Second and third trimester exposure may cause intrauterine growth restriction, oligohydramnios, and fetal demise. |
■ FDA Black Box Warning
Acute bronchospasm, hypotension, and severe respiratory distress have been reported in patients receiving vinorelbine, especially in those with a history of asthma or other pulmonary conditions.
| Common Effects | breast cancer |
| Serious Effects |
Absolute: Pre-existing severe granulocytopenia (ANC < 1000/mm3); severe hepatic impairment (bilirubin > 3 mg/dL); hypersensitivity to vinorelbine or other vinca alkaloids; pregnancy (category D). Relative: Active infection; prior radiation therapy with large fields (may increase myelotoxicity); renal impairment (caution).
| Precautions | Myelosuppression, particularly granulocytopenia; monitor blood counts frequently; pulmonary toxicity (acute bronchospasm, interstitial pulmonary infiltrates, respiratory failure); avoid extravasation; decrease dose in hepatic impairment; hold for severe neutropenia or infection. |
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| Fetal Monitoring | Monitor complete blood count (CBC) with differential, liver function tests, and renal function prior to each dose. Assess for neuropathy and signs of infection. In pregnant patients, monitor fetal growth and amniotic fluid volume by ultrasound. Obtain nonstress test or biophysical profile as clinically indicated. |
| Fertility Effects | Vinorelbine may impair fertility in both males and females. In males, it can cause oligospermia, azoospermia, and testicular atrophy. In females, it may lead to menstrual irregularities, premature ovarian failure, and reduced fertility. Effects may be irreversible. |