Usage
Vinorelbine is prescribed for the treatment of non-small cell lung cancer (NSCLC), both as a single agent and in combination with other chemotherapy drugs like cisplatin. It is also used in the second-line treatment of advanced breast cancer when the initial treatment, often including anthracyclines, has failed or is unsuitable. Vinorelbine is classified as an antineoplastic agent, specifically a vinca alkaloid. It acts by inhibiting microtubule polymerization, disrupting mitosis and ultimately causing cell death.
Alternate Names
Vinorelbine is also known internationally by its tartrate salt form: vinorelbine tartrate. Several brand names exist, most notably Navelbine.
How It Works
Pharmacodynamics: Vinorelbine exerts its antineoplastic effect by binding to tubulin, a protein crucial for microtubule formation. Unlike other vinca alkaloids, it preferentially binds to mitotic microtubules, leading to metaphase arrest and cell death with less neurotoxicity.
Pharmacokinetics:
- Absorption: Vinorelbine exhibits good oral bioavailability, although it is less than intravenous administration. Food intake can increase absorption.
- Distribution: It has a large volume of distribution, indicating extensive tissue penetration.
- Metabolism: Primarily metabolized in the liver by CYP3A4 enzymes. Two major metabolites are formed, but their activity is considerably less than vinorelbine itself.
- Elimination: Excreted primarily through the biliary route into the feces, with a smaller portion eliminated in the urine. It has a long terminal half-life.
Mode of Action: Vinorelbine specifically targets mitotic microtubules, preventing polymerization. It spirals around tubulin dimers, causing tubulin paracrystals to form. This disruption of microtubule dynamics inhibits mitosis at the metaphase stage, leading to cell death.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Vinorelbine’s primary action is through tubulin binding. While its metabolism involves CYP3A4, it doesn’t act as a significant inhibitor or inducer of this enzyme system.
Dosage
Standard Dosage
Adults:
- Intravenous:
- Single agent (NSCLC): 30 mg/m² once weekly.
- Combination with cisplatin (NSCLC): 25 mg/m² on days 1, 8, 15, and 22 of a 28-day cycle with cisplatin 100 mg/m² on day 1.
- Single agent (Breast cancer, after anthracycline failure): 25-30 mg/m² once weekly.
- Combination therapy (Breast Cancer): 25-30 mg/m² with reduced frequency (e.g., days 1 and 8 or days 1 and 5 every 3 weeks).
- Oral:
- Single agent (NSCLC): Initial dose of 60 mg/m² once weekly for three weeks, escalating to 80 mg/m² weekly if tolerated. Maximum dose is 160 mg/week.
- Combination with trastuzumab (HER2-positive breast cancer): Dosing varies depending on the specific protocol, with 3-weekly cycles or combinations with daily oral cyclophosphamide.
Children: Limited clinical data exist for pediatric use. Studies suggest a dose of 30 mg/m² weekly, but safety and efficacy are not fully established. Dosage needs to be cautiously adjusted based on tolerability and hematological parameters.
Special Cases:
- Elderly Patients: Often initiate treatment with a reduced dose (e.g., 25mg/m² IV for heavily pretreated patients or those with comorbidities) and monitor closely for toxicity. Metronomic dosing (lower doses more frequently) can be an option.
- Patients with Renal Impairment: No specific dose adjustments are usually necessary, but careful monitoring is recommended.
- Patients with Hepatic Dysfunction:
- Moderate: Reduce dose to 50% for moderate impairment (bilirubin 1.5-3 times the upper limit of normal).
- Severe: Contraindicated in severe hepatic impairment.
- Patients with Comorbid Conditions: Dosage should be individualized considering the patient’s overall health and potential for drug interactions.
Clinical Use Cases
Vinorelbine is not typically used in acute settings such as intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. Its administration requires close monitoring and is unsuitable for these scenarios.
Dosage Adjustments
Dose reductions are necessary for patients with myelosuppression (neutropenia, thrombocytopenia) or elevated bilirubin. Monitor complete blood counts and liver function tests regularly.
Side Effects
Common Side Effects
- Neutropenia (low white blood cell count)
- Constipation
- Nausea and vomiting
- Fatigue
- Alopecia (hair loss)
- Peripheral neuropathy (numbness or tingling in hands and feet)
Rare but Serious Side Effects
- Severe neutropenia with fever or infection
- Paralytic ileus (bowel obstruction)
- Severe hepatic toxicity
- Extravasation injury (tissue damage at injection site)
- Guillain-Barre syndrome (immune system attacking the nervous system)
Long-Term Effects
- Peripheral neuropathy can persist after treatment discontinuation.
Adverse Drug Reactions (ADR)
- Severe hypersensitivity reactions (rare)
- Severe myelosuppression
Contraindications
- Hypersensitivity to vinorelbine or other vinca alkaloids
- Severe neutropenia or thrombocytopenia
- Severe hepatic impairment
- Pregnancy and breastfeeding
- Yellow fever vaccination and other live attenuated vaccines
Drug Interactions
- CYP3A4 Inhibitors (e.g., azole antifungals like itraconazole, macrolide antibiotics): May increase vinorelbine levels.
- CYP3A4 Inducers (e.g., rifamycins, St. John’s wort, anticonvulsants): May decrease vinorelbine levels.
- Mitomycin: Increased risk of bronchospasm and shortness of breath when combined with vinorelbine.
- Several other clinically significant drug interactions: Refer to a comprehensive drug interaction database for a complete list before initiating treatment.
Pregnancy and Breastfeeding
Vinorelbine is contraindicated in pregnancy (FDA Category D) and breastfeeding. It is highly embryotoxic and teratogenic. Effective contraception is essential during and after treatment (at least 3 months for women and 6 months for men).
Drug Profile Summary
- Mechanism of Action: Inhibits microtubule polymerization, leading to metaphase arrest and cell death.
- Side Effects: Neutropenia, constipation, nausea/vomiting, fatigue, alopecia, peripheral neuropathy.
- Contraindications: Hypersensitivity, severe myelosuppression, severe hepatic impairment, pregnancy, breastfeeding.
- Drug Interactions: CYP3A4 inhibitors and inducers, mitomycin, numerous others (consult drug interaction database).
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: See detailed dosage guidelines above.
- Monitoring Parameters: Complete blood count, liver function tests, neurological assessment.
Popular Combinations
- Cisplatin (for NSCLC)
- Trastuzumab (for HER2-positive breast cancer)
- Metronomic cyclophosphamide
Precautions
- Monitor for myelosuppression, hepatic toxicity, and neurological symptoms.
- Prevent extravasation during intravenous administration.
- Manage constipation proactively.
- Provide patient education on side effects and precautions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Vinorelbine?
A: The dosage depends on the indication, administration route, and patient characteristics. See detailed dosage guidelines above.
Q2: How is Vinorelbine administered?
A: It can be given intravenously as an infusion or injection or orally as capsules.
Q3: What are the most common side effects of Vinorelbine?
A: Neutropenia, constipation, nausea/vomiting, fatigue, alopecia, and peripheral neuropathy.
Q4: What are the major contraindications for Vinorelbine?
A: Hypersensitivity, severe myelosuppression, severe hepatic impairment, pregnancy, breastfeeding, and yellow fever vaccination.
Q5: How does Vinorelbine interact with other medications?
A: It interacts with CYP3A4 inhibitors and inducers, mitomycin, and several other drugs. Consult a drug interaction database for a comprehensive list.
Q6: Can Vinorelbine be used during pregnancy or breastfeeding?
A: No, it is contraindicated due to the risk of fetal harm and potential excretion in breast milk.
Q7: What monitoring is required during Vinorelbine treatment?
A: Regular complete blood counts, liver function tests, and neurological assessment.
Q8: How does oral Vinorelbine differ from intravenous Vinorelbine?
A: Oral vinorelbine has good bioavailability but is generally less than intravenous. Food can enhance absorption. Dose adjustments are needed when switching between the two routes.
A: Stop the infusion immediately and follow established extravasation management protocols, which may involve local injection of hyaluronidase or other interventions.
Q10: Is Vinorelbine used in children?
A: Its use in children is limited due to scarce safety and efficacy data. Dosing must be carefully adjusted based on individual tolerance.
This information is current as of February 17, 2025, and may change with future research and clinical experience. Always consult the latest prescribing information and appropriate guidelines.
