What Is Vinorelbine (Navelbine)? FDA Approval, Licensing in Turkey, and Reimbursement Status

• FDA Approval: Yes (Initial approval: 1994)
• Brand Name: Navelbine (NVB)
• Active Ingredient: Vinorelbine
• Route of Administration: Intravenous (IV) injection; oral tablet form (PO)
• Pharmacological Class: Vinca alkaloid, antimicrotubule agent
• Category: Chemotherapy agent
• Manufacturer: Pierre Fabre İlaç
• Availability in Turkey: Pierre Fabre İlaç, Gensenta İlaç, Koçak Farma İlaç
• Approved Cancers: Non-small cell lung cancer (NSCLC), breast cancer, ovarian cancer

What Is Vinorelbine (Navelbine)? FDA Approval, Licensing in Turkey, and Reimbursement Status

Navelbine, containing the active ingredient vinorelbine, is a potent chemotherapy drug derived from the rosy periwinkle plant and used particularly to treat lung and breast cancers. It stops cell division and inhibits tumor growth by inhibiting microtubule formation.

What Are Vinca Alkaloids?

Vinca alkaloids are plant-derived chemotherapy drugs that target the microtubules responsible for cell division. These agents act during the M phase of the cell cycle, preventing mitotic spindle formation. Through this mechanism, tumor cells cannot divide and die. Vinca alkaloids offer an effective treatment option for various tumors, including lung, breast, and hematological cancers.

How Does It Work?

• Vinorelbine is a semisynthetic vinca alkaloid that inhibits tubulin polymerization.
• It prevents mitotic spindle formation, arresting the cell cycle in the M phase and suppressing division.
• Inhibition of cell division leads to cell death (apoptosis) in tumor cells.
• It has high specificity for mitotic microtubules and lower binding to axonal microtubules, resulting in lower rates of neurotoxicity than other vinca alkaloids.
• It stops cancer cell growth by inhibiting DNA, RNA, and protein synthesis.

FDA (United States Food and Drug Administration) Approval History

• December 27, 1994: It received FDA approval for the treatment of non-small cell lung cancer (NSCLC).
• April 3, 1998: It was approved for use in metastatic breast cancer.
• June 15, 2004: It was approved as a single agent for patients with advanced NSCLC who were unsuitable for platinum-based treatment.
• November 22, 2011: Approval of the oral formulation was expanded in Europe, but it was not approved by the FDA.

Licensing in Turkey

The situations in which Navelbine is licensed in Turkey / its therapeutic indications are specified as follows:

Therapeutic Indications:

Indicated alone or in combination with platinum agents for locally advanced unresectable (stage IIIB) and metastatic (stage IV) non-small cell lung cancer, and for metastatic breast cancer resistant to anthracyclines and taxanes.

Is Navelbine Reimbursed?

It is on the list of drugs for which no indication restriction applies in patients diagnosed with cancer. It is reimbursed by SGK for all cancer diagnoses.

Price: As of April 2025;

• Navelbine 50 mg/5 ml vial pharmacy retail price: 1576.79₺
• Navelbine 20 mg soft capsule pharmacy retail price: 884.16₺
• Navelbine 30 mg soft capsule pharmacy retail price: 1271.79₺

Mechanisms of Resistance

• Overproduction of P170 glycoprotein (multidrug resistance – MDR)
• Cross-resistance with other drugs
• Mutations in tubulin proteins

Absorption

Formulations are available for intravenous (IV) and oral (PO) administration.

Distribution

• It distributes rapidly and extensively into most body tissues.
• It has a large apparent volume of distribution (>30 L/kg).
• It is highly bound to plasma proteins (~80%).

Metabolism

• It is metabolized in the liver by the cytochrome P450 microsomal system.
• It has an active metabolite called deacetylvinorelbine.
• Most of the drug is excreted in the feces through bile, while 15-20% is eliminated through the kidneys.
• Its half-life ranges from 27-43 hours.

Dose Range

Intravenous (IV) Administration:

Recommended dose: 30 mg/m² IV infused over 6-10 minutes, once weekly.

Oral (Capsule) Administration:

• Starting dose: 60 mg/m² once weekly

Maintenance dose: 80 mg/m² once weekly if there is no neutropenia

Drug Interactions 

• Metabolism Through Liver Enzymes: Vinorelbine is metabolized in the liver by the cytochrome P450 (CYP3A4) enzyme system. Drugs that inhibit CYP3A4, such as ketoconazole, itraconazole, and erythromycin, may therefore increase blood levels of vinorelbine and the risk of adverse effects. Drugs that induce CYP3A4, such as rifampin, phenytoin, and carbamazepine, may accelerate vinorelbine metabolism and reduce its effectiveness. Dose adjustments should be made if these drugs must be used together.
• Interaction With Phenytoin: Vinorelbine may reduce blood levels of phenytoin. This may occur through reduced intestinal absorption of phenytoin or increased elimination from the body. Seizure control may decline when they are used together, so patients should be monitored carefully.
• Interaction With Cisplatin: Combining vinorelbine with cisplatin may increase the risk of bone marrow suppression (myelosuppression). This interaction may particularly increase the risk of neutropenia (a low white blood cell count). Blood counts should be monitored closely, and doses adjusted when the drugs are used together.
• Interaction With Mitomycin-C: Combining it with mitomycin-C may increase the risk of acute allergic reactions.
• Patients should be monitored for shortness of breath (dyspnea), bronchospasm, or signs of an anaphylactic reaction. This combination should be used cautiously, with close monitoring during treatment.

Precautions

• Dose and Administration Precautions: There is a risk of extravasation (leakage outside the vein) during intravenous (IV) administration. Leakage outside the vein can cause severe tissue damage. When the oral form is used, capsules should not be chewed or broken.
• Monitoring Blood Counts: Because the risk of myelosuppression (bone marrow suppression) is high, regular blood tests should be performed before and during treatment. If neutropenia (a decreased white blood cell count) develops, dosing should be delayed or reduced.
• Use in Hepatic (Liver) Impairment: Because it is metabolized in the liver, it should be used cautiously in patients with severe liver impairment, with dose reduction if necessary.
• Renal Impairment: Because it is eliminated largely through bile, dose adjustments are generally unnecessary in patients with renal impairment. However, patients with severe renal impairment should be monitored closely.
• Pregnancy and Breastfeeding: It is in pregnancy category D (teratogenic) and may harm the fetus. Its use is not recommended during pregnancy. Breastfeeding mothers should stop breastfeeding during treatment.
• Immunosuppression and Infection Risk: It may suppress the immune system, so patients should be monitored closely for signs of infection. Fever, sore throat, or signs of infection require immediate medical attention.

Adverse Effects 

• Myelosuppression: This is dose-dependent, and neutropenia is the most common adverse effect. Neutropenia generally reaches its nadir on day 7, with recovery on day 14. Thrombocytopenia (a low platelet count) and anemia (a low red blood cell count) are less common.
• Nausea and Vomiting: Usually mild to moderate and occur within the first 24 hours after treatment.
• Gastrointestinal (GI) Toxicities: Constipation (35%), diarrhea (17%), stomatitis (mouth sores) (<20%), anorexia (loss of appetite) (<20%)
• Transient Elevation of Liver Enzymes: SGOT and bilirubin levels may rise temporarily, usually without clinical symptoms.
• Tissue Damage (Vesicant Effect): Extravasation (leakage outside the vein) can cause local tissue damage and inflammation.
• Neurotoxicity (Effects on the Nervous System): Less common than with other vinca alkaloids. It binds less strongly to axonal microtubules than vincristine or vinblastine. Patients with preexisting neuromuscular disease may have an increased risk of neurotoxicity.
• Hair Loss (Alopecia): Observed in 10-15% of patients.
• SIADH (Syndrome of Inappropriate ADH Secretion): May cause water retention.
• Allergic Reactions: Hypersensitivity and/or allergic reactions may occur, presenting as dyspnea (shortness of breath) and bronchospasm. The risk of allergic reactions increases when used with mitomycin-C.
• General Fatigue: Fatigue may occur in 35% of patients and worsen with repeated doses.