Vinorelbine

BRAND NAMES

Navelbine- 50mg Injection helps to treat breast cancer.

Biovelbin-A foreign brand name listed in the NCI Drug Dictionary.

Vinelbine-50mg Injection helps to treat certain types of cancer.

MECHANISM OF ACTION

Vinorelbine, a vinca alkaloid, is a chemotherapy drug that binds to tubulin, preventing the assembly of microtubules. This destabilization breaks down the mitotic spindle, arresting cell division at the metaphase stage and triggering apoptosis (programmed cell death) in cancer cells. Vinorelbine, unlike earlier vinca alkaloids, shows greater selectivity for mitotic microtubules over neuronal axonal microtubules, leading to a lower risk of neurotoxicity.

PHARMACOKINETICS

Absorption

Oral vinorelbine is quickly absorbed; however, it has low bioavailability, with only about 40% of the drug reaching systemic circulation due to significant first-pass metabolism in the liver and gastrointestinal tract. While intravenous administration provides 100% bioavailability, the oral capsule offers patients the convenience of at-home dosing.

Distribution

Vinorelbine is extensively distributed throughout the body, with a high volume of distribution ranging from 25.4 to 40.1 L/kg.

Metabolism

Vinorelbine is mainly metabolized in the liver through the cytochrome P450 3A4 (CYP3A4) enzyme system, producing deacetylvinorelbine as its primary identified metabolite. Following metabolism, vinorelbine and its metabolites are predominantly excreted in the feces via the bile. In patients with hepatic impairment, dose adjustments may be necessary due to reduced metabolic clearance, and there is a potential for drug interactions with other CYP3A4-metabolized medications.

Excretion

Less than 20% of an intravenous dose of vinorelbine is excreted unchanged in the urine, while an additional 30% to 60% is eliminated through the feces.

PHARMACODYNAMICS

Vinorelbine is a vinca alkaloid chemotherapy drug that disrupts microtubule function by binding to tubulin, the protein that forms microtubules. By inhibiting microtubule polymerization, vinorelbine disrupts the mitotic spindle, causing cancer cells to arrest in metaphase and undergo programmed cell death (apoptosis).  Vinorelbine also affects other cellular processes, such as metabolism, and can act as a radiosensitizer when used alongside radiation therapy.

ADMINISTRATION

Vinorelbine is used as a chemotherapy treatment and can be administered either intravenously (IV) or taken orally. The specific method, dosage, and schedule depend on the type of cancer being treated, whether it is used as a single agent or in combination with other drugs, and the patient's individual health status.

DOSAGE AND STRENGTH

Vinorelbine is available in two main dosage forms: an intravenous (IV) injection and an oral soft capsule.

Available in 10mg/1mL; 50mg/5mL.

DRUG INTERACTIONS

Vinorelbine has numerous drug interactions, primarily involving drugs that alter its metabolism via the CYP3A4 enzyme system in the liver. Co-administration with strong CYP3A4 inhibitors, such as certain antifungals like itraconazole, can increase vinorelbine levels and toxicity, including a heightened risk of neurotoxicity. Conversely, CYP3A4 inducers, like some anti-epileptics (e.g., phenytoin) or herbal products like St. John's Wort, can decrease vinorelbine's effectiveness. Grapefruit and grapefruit juice can also inhibit CYP3A4 and should be avoided. 

FOOD INTERACTIONS

For patients on vinorelbine, a critical food interaction is avoiding grapefruit, grapefruit juice, and Seville oranges, as they can inhibit the enzyme that metabolizes the drug, leading to potentially increased side effects. If taking oral vinorelbine capsules, they should be swallowed whole with cold water and food to reduce nausea and vomiting, and never chewed or taken with a hot drink. To manage common side effects, staying hydrated, eating small frequent meals, increasing fiber for constipation, and avoiding spicy foods for diarrhea are helpful dietary practices.

CONTRAINDICATIONS

Vinorelbine should not be used in patients with a known allergy to the drug or other vinca alkaloids. It must not be used in patients with severe blood conditions, including severe granulocytopenia, neutropenia (neutrophil count below 1,500 cells/mm³), severe thrombocytopenia (platelet count below 100,000 cells/mm³).Additionally, it should not be used in combination with the yellow fever vaccine due to the risk of a severe, generalized vaccine-related disease. 

SIDE EFFECTS

• Fatigue and nausea.

• Bone marrow suppression.

• neutropenia, anemia, thrombocytopenia.

• Gastrointestinal issues.

• Injection site reactions.

• Hair loss.

• Mouth sores.

• Bowel blockage.

• Severe allergic reaction.

• Cardiovascular issues.

• Fertility impairment.

OVER DOSE

• Severe myelosuppression.

• Neutropenic fever.

• Unusual bleeding or bruising.

• Severe constipation.

• Partial or slight paralysis.

• Acute respiratory distress syndrome (ARDS).

• Severe peripheral neuropathy.

• Rapid heartbeat.

• Severe abdominal pain, cramps, and vomiting.

TOXICITY

Vinorelbine is a chemotherapy drug that can cause significant side effects, with the major dose-limiting toxicity being myelosuppression, primarily neutropenia. Other notable toxicities include neurotoxicity, gastrointestinal problems, and injection site reactions.