Vinorel10 mg/ml

FDA-Approved Indications

• Non-Small Cell Lung Cancer (NSCLC), first-line: Vinorel is indicated, in combination with cisplatin, for the first-line treatment of patients with unresectable, advanced non-small cell lung cancer.
• Non-Small Cell Lung Cancer (NSCLC), single agent: Vinorel is indicated as a single agent for the first-line treatment of patients with advanced non-small cell lung cancer for whom cisplatin-based therapy is not appropriate.

Other Guideline-Supported / Off-Label Use

• Metastatic Breast Cancer: Vinorel is used, as a single agent or in combination with other antineoplastic agents, for the treatment of metastatic breast cancer that has progressed after anthracycline- and/or taxane-containing therapy. This use is supported by oncology treatment guidelines and is well established in clinical practice internationally, although it is off-label in some jurisdictions where Vinorel is approved for NSCLC only.

Vinorel is a cytotoxic chemotherapy agent that must only be prescribed, dispensed, and administered under the direct supervision of a physician experienced in the use of cancer chemotherapeutic agents. It is not an outpatient self-administered medication.

Each mL of Vinorelbine Tartrate injection contains Vinorelbine Tartrate equivalent to 10 mg of vinorelbine base, supplied as a sterile solution in single-dose vials (commonly 1 mL/10 mg and 5 mL/50 mg strengths).

Vinorel is a semisynthetic vinca alkaloid antineoplastic agent (a microtubule inhibitor) derived from vinblastine. It is administered by intravenous injection or infusion for the treatment of certain advanced cancers, principally non-small cell lung cancer, and is also used for metastatic breast cancer.

Vinorel carries boxed warnings for severe, dose-limiting bone marrow suppression and for fatal outcomes if given by the intrathecal route. It is strictly for intravenous use only and must be administered exclusively by, or under the direct supervision of, trained oncology personnel in a facility equipped to manage chemotherapy-related complications.

Vinca alkaloid antineoplastic agent (microtubule inhibitor); Vinorel belongs to this class.

Mechanism of Action

Vinorelbine Tartrate binds to tubulin, predominantly at the mitotic microtubules of the spindle apparatus, inhibiting microtubule assembly. This blocks cells in metaphase of mitosis, arresting cell division and ultimately leading to cell death of rapidly dividing malignant cells. Compared with some other vinca alkaloids, Vinorelbine Tartrate shows relatively greater selectivity for mitotic over axonal microtubules, which may contribute to its comparatively lower incidence of severe peripheral neuropathy.

Pharmacokinetics

Following intravenous administration, Vinorelbine Tartrate is extensively bound to platelets and lymphocytes and has a large volume of distribution, consistent with extensive tissue binding. It is metabolized in the liver, mainly via the CYP3A4 enzyme pathway, to metabolites including deacetylvinorelbine (which retains activity). Elimination is predominantly hepatic/biliary via the feces, with a smaller fraction excreted renally. The terminal elimination half-life is approximately 27 to 43 hours.

Vinorel is administered only by intravenous injection or infusion by trained oncology healthcare professionals; it is never given by mouth, intramuscularly, subcutaneously, or - under any circumstance - by the intrathecal route, which is fatal. Each dose is preceded by blood count monitoring, and the treating team will confirm the intravenous line is patent before and during administration to reduce the risk of extravasation and tissue injury. Patients do not self-administer Vinorel.

CYP3A4 Inhibitors

Concomitant use of Vinorel with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, clarithromycin, ritonavir) may increase Vinorel plasma concentrations and increase the risk/severity of toxicity, particularly myelosuppression. Such combinations should be used with caution and close monitoring.

CYP3A4 Inducers

Strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, St. John's Wort) may reduce Vinorel exposure and potentially reduce efficacy.

Mitomycin

Concurrent or sequential use of Vinorel with mitomycin has been associated with an increased risk of acute pulmonary reactions, including bronchospasm and interstitial pneumonitis/dyspnea.

Phenytoin and Other Anticonvulsants

Cytotoxic chemotherapy including Vinorel may reduce absorption/serum levels of phenytoin, with a risk of breakthrough seizures; serum phenytoin levels should be monitored closely during and after Vinorel therapy.

Other Myelosuppressive Therapies and Radiotherapy

Concomitant use of Vinorel with other bone marrow-suppressing drugs or radiation therapy may result in additive myelosuppression; more frequent blood count monitoring is advised.

Live Vaccines

Administration of live or live-attenuated vaccines should generally be avoided during Vinorel therapy because of the risk of severe infection in an immunosuppressed patient.

Very Common / Common Side Effects

• Myelosuppression: granulocytopenia (dose-limiting), anemia, thrombocytopenia
• Nausea, vomiting, constipation, diarrhea, stomatitis
• Peripheral neuropathy (paresthesia, decreased or absent deep tendon reflexes)
• Fatigue, asthenia, malaise
• Mild, reversible alopecia
• Injection-site reactions: pain, erythema, phlebitis at the injection site
• Elevated liver transaminases
• Jaw pain

Serious Side Effects

Serious myelosuppression with risk of infection/sepsis, fatal outcomes with intrathecal administration, vesicant tissue injury from extravasation, and acute pulmonary reactions (particularly with mitomycin) are discussed in Precautions and Warnings. Rare severe complications include paralytic ileus, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and severe hepatic dysfunction.

Vinorel can cause fetal harm when administered to a pregnant woman, based on its mechanism of action (microtubule inhibition affecting rapidly dividing cells) and findings in animal reproduction studies. Vinorel should be used during pregnancy only if clearly needed and the potential benefit to the mother justifies the potential risk to the fetus; a physician must be consulted before use in pregnancy. Women and men of reproductive potential should use effective contraception during Vinorel treatment and for a period after the last dose, as advised by their oncologist.

It is not known whether Vinorel passes into human breast milk; because of the potential for serious adverse reactions in a nursing infant, breastfeeding is not recommended during Vinorel treatment and for a period after the last dose. Consult a physician before breastfeeding.

Boxed Warning: Fatal if Given Intrathecally

Vinorel is for intravenous use only. Fatal outcomes have occurred when vinca alkaloids, including Vinorel, were administered intrathecally by error. Institutions should use dispensing and administration safeguards (e.g., labeling syringes/bags "FOR INTRAVENOUS USE ONLY - FATAL IF GIVEN BY OTHER ROUTES," dispensing in a minibag rather than a syringe where feasible) to prevent this catastrophic medication error.

Boxed Warning: Bone Marrow Suppression

Vinorel causes dose-limiting granulocytopenia, which can lead to serious infection and sepsis. A complete blood count with differential must be obtained before every dose, and Vinorel must not be given to patients with a granulocyte count below 1,000 cells/mm³; see Dosage and Administration for the required dose-modification schedule.

Vesicant / Extravasation Risk

Vinorel is a vesicant. Extravasation during intravenous administration can cause severe local tissue damage, cellulitis, and necrosis. Vinorel must be given only by personnel experienced in the administration of vesicant chemotherapy, with confirmed patency of the intravenous line; if extravasation occurs, the infusion must be stopped immediately and managed per institutional protocol.

Peripheral Neuropathy

Peripheral neuropathy can occur with Vinorel and may worsen with cumulative dosing. Patients should be assessed periodically for paresthesia and loss of deep tendon reflexes; dose modification or discontinuation may be required for severe neuropathy.

Hepatic Impairment

Because Vinorel is eliminated mainly by the liver, dose reduction is required in patients with elevated serum bilirubin; see Dosage and Administration.

Pulmonary Toxicity

Acute shortness of breath, bronchospasm, and interstitial pulmonary changes have been reported with Vinorel, with a higher risk when combined with mitomycin. Onset of unexplained dyspnea requires prompt evaluation.

Constipation and Bowel Obstruction

Vinorel can cause constipation, and rarely paralytic ileus; a bowel regimen may be needed, particularly in patients with risk factors for constipation.

Specialist Administration Only

Vinorel is a cytotoxic chemotherapy agent requiring specialist oncology administration and monitoring. It is not intended for outpatient self-administration and must be handled with standard cytotoxic drug precautions.

There is no specific antidote for Vinorel overdose. Overdose would be expected to result in an exaggeration of known toxicities, principally severe bone marrow suppression with risk of life-threatening infection, and possibly severe mucositis, paralytic ileus, or neurotoxicity. If overdose of Vinorel is suspected, seek immediate medical attention or contact emergency services/a poison control center right away. Management is supportive and should include intensive monitoring of blood counts, use of hematopoietic growth factors and prophylactic anti-infectives as clinically indicated, and general supportive care under close medical supervision; there is no role for unsupervised home treatment.

Store under refrigeration at 2°C to 8°C (36°F to 46°F). Protect from light; keep the vial in its outer carton until the time of use. Do not freeze. Keep out of reach of children. Once diluted for administration, use within the timeframe specified by the treating facility's pharmacy protocol.

Pediatric Use

Safety and efficacy of Vinorel have not been established in pediatric patients; Vinorel is not recommended for use in children outside of a clinical trial setting.

Elderly

Elderly patients may have increased susceptibility to Vinorel-induced myelosuppression and neuropathy. Vinorel should be used with caution in elderly patients, with close monitoring of blood counts and neurological status; dose modification may be needed based on tolerability.

Hepatic Impairment

See Dosage and Administration for the required bilirubin-based dose reduction of Vinorel in hepatic impairment.

Renal Impairment

Data are limited; use Vinorel with caution and appropriate monitoring in patients with significant renal impairment.

Vinorel is typically given once weekly and continued for as long as clinical benefit is observed and toxicity remains manageable, i.e., until disease progression or unacceptable toxicity occurs, or for a defined number of cycles per the specific treatment protocol, as determined by the treating oncologist.

Vinca alkaloids; antineoplastic/antimitotic agents; microtubule inhibitors - Vinorelbine Tartrate belongs to these classes.

Vinorelbine Tartrate works by binding to tubulin in the mitotic spindle apparatus and inhibiting microtubule assembly. This prevents the mitotic spindle from forming correctly, arresting rapidly dividing cancer cells in metaphase and ultimately triggering cell death, thereby slowing or stopping tumor growth.

D

The safety and efficacy of Vinorel have not been established in pediatric patients. Vinorel is intended for use in adults and is not recommended for children or adolescents outside of a clinical trial setting.