Vinorelbine Tartrate

A to Z Drug Facts

Actions Vinorelbine interferes with microtubule assembly primarily by inhibiting mitosis at metaphase through its interaction with tubulin. The terminal phase half-life averages 27.7 to 43.6 hr and the mean plasma clearance ranges from 0.97 to 1.26 L/hr/kg. Steady-state volume of distribution values range from 25.4 to 40.1 L/kg. Vinorelbine demonstrated high binding to human platelets and lymphocytes. Vinorelbine undergoes substantial hepatic elimination, with large amounts recovered in feces.

 Indications Unresectable, advanced non-small cell lung cancer.

Breast cancer, cisplatin-resistant ovarian cancer, Hodgkin's lymphoma.

 Contraindications Pretreatment granulocyte counts < 1000 cells/mm³.

 Route/Dosage

Unresectable, Advanced Non-Small Cell Lung Cancer

ADULTS: IV 30 mg/m² once weekly until either disease progression or dose-limiting toxicity occur.

Dosage Adjustment for Hematologic Toxicity

Granulocyte counts should be ³ 1000 cells/mm³ prior to the administration of vinorelbine. Base dosage adjustments on granulocyte counts. See manufacturer's recommendations.

Dosage Adjustment in Hepatic Dysfunction

ADULTS: IV Reduce dose 50% if total bilirubin is 2.1 to 3 mg/dL. Reduce dose 25% if total bilirubin is > 3 mg/dL.

Interactions

Cisplatin

Incidence of granulocytopenia increases when vinorelbine is used in combination with cisplatin.

Cytochrome P450 3A enzyme inhibitors (eg ketoconazole, itraconazole, macrolides)

May increase vinorelbine serum levels and toxicity.

Mitomycin

Acute pulmonary reactions were noted when vinca alkaloids were given with mitomycin.

Paclitaxel

Monitor for signs and symptoms of neuropathy with concomitant use of vinorelbine and paclitaxel.

Radiation

Radiation recall reactions may occur.

Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Chest pain. CNS: Fatigue; mild to moderate peripheral neuropathy. DERMATOLOGIC: Mild alopecia; rash and injection site reactions; pain at injection site. GI: Transient elevations in LFTs; constipation; paralytic ileus; mild stomatitis; anorexia; diarrhea. HEMATOLOGIC: Dose-limiting granulocytopenia occurs with a nadir of 7 to 10 days. HYPERSENSITIVITY: Anaphylaxis; angioedema; pruritus. MUSCULOSKELETAL: Jaw pain; myalgia; arthralgia. RESPIRATORY: Dyspnea.

 Precautions

Pregnancy: Category D. Lactation: Undetermined. Children: Safety and efficacy in children have not been established. Interstitial pulmonary changes: Cases of interstitial pulmonary changes and ARDS, most of which were fatal, occurred in patients. GI: May cause severe constipation, paralytic ileus, intestinal obstruction, necrosis, and perforation. Granulocytopenia: Granulocytopenia is dose-limiting. Do not administer to patients with granulocyte counts < 1000 cells/mm³. Hepatic function impairment: Administer with caution to patients with hepatic insufficiency. IV use only: Intrathecal use may result in death. Extravasation: Extravasation can cause severe local necrosis.

 Administration/Storage

• Refrigerate but do not freeze. Protect from light. Unopened vials may be stored at room temperature £ 25°C (77°F) for £ 72 hr. Diluted solutions may be stored at room temperature or under refrigeration for £ 24 hr in polypropylene syringes or PVC bags. Solutions are preservative-free and should be discarded within 24 hr of preparation.
• Vinorelbine must be further diluted prior to administration.
• Administer by IV infusion
• Infuse IV over 6 to 10 min into the side port of a freely flowing IV line closest to the IV bag. Follow injection with ³ 75 to 125 mL 5% Dextrose or 0.9% Sodium Chloride.

 Assessment/Interventions

• Monitor CBC with differential and serum bilirubin concentrations at baseline and prior to each dose.
• Use with caution in patients receiving other bone marrow suppressants, with prior radiation therapy, or with a history of neuropathy or pulmonary dysfunction.
• Patients who develop bronchospasm during infusions may be treated with supplemental oxygen, bronchodilators, or corticosteroids.
• Monitor patients developing severe granulocytopenia for evidence of infection or fever.
• Monitor patients with a history of or with preexisting neuropathy, for new or worsening signs and symptoms of neuropathy.
• Promptly evaluate patients with alterations in their baseline pulmonary symptoms or with new onset of dyspnea, cough, hypoxia, or other symptoms.

 Patient/Family Education

• Advise patients to report fever or chills immediately.
• Advise women of childbearing potential to avoid pregnancy during treatment.
• Advise patients to contact the health care provider if experiencing increased shortness of breath, cough, or other new pulmonary symptoms, or if experiencing symptoms of abdominal pain or constipation.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts