drug-information.ru

|Vinorelbine Tartrate

Vinorelbine Tartrate

Trade Names:
Navelbine
- Solution for Injection 10 mg/mL

Mechanism of Action

Pharmacology

Vinorelbine interferes with microtubule assembly primarily by inhibiting mitosis at metaphase through its interaction with tubulin.

Pharmacokinetics

Distribution

Vd is 25 to 40.1 L/kg.

Metabolism

One metabolite, deacetylvinorelbine, has been shown to possess antitumor activity.

Elimination

T _½ is 28 to 44 hr. Mean plasma clearance is about 1 to 1.26 L/hr/kg. Substantial hepatic elimination in humans, with large amounts recovered in feces after IV administration.

Special Populations

Based on experience with other anticancer vinca alkaloids, dosage adjustments are recommended for patients with impaired hepatic function taking vinorelbine.

Indications and Usage

Unresectable, advanced non-small cell lung cancer.

Unlabeled Uses

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

Contraindications

Pretreatment granulocyte counts less than 1000 cells/mm ³ .

Dosage and Administration

IV 30 mg/m ² once weekly until either disease progression or dose-limiting toxicity occur.

Granulocyte counts should be at least 1,000 cells/mm ³ prior to the administration of vinorelbine. Base dosage adjustments on granulocyte counts. See manufacturer"s recommendations.

IV Reduce dose 50% if total bilirubin is 2.1 to 3 mg/dL. Reduce dose 25% if total bilirubin is more than 3 mg/dL.

General Advice

• 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 at least 75 to 125 mL 5% dextrose or 0.9% sodium chloride.

Storage/Stability

Refrigerate but do not freeze. Protect from light. Unopened vials may be stored at room temperature up to 25°C (77°F) for up to 72 hr. Diluted solutions may be stored at room temperature or under refrigeration for up to 24 hr in polypropylene syringes or PVC bags. Solutions are preservative-free and should be discarded within 24 hr of preparation.

Drug Interactions

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

May increase vinorelbine serum levels and toxicity.

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

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

Radiation recall reactions may occur.

Laboratory Test Interactions

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.

Hepatic Function

Administer with caution to patients with hepatic insufficiency.

GI

May cause severe constipation, paralytic ileus, intestinal obstruction, necrosis, and perforation.

Interstitial pulmonary changes

Cases of interstitial pulmonary changes and ARDS, most of which were fatal, occurred in patients.

Overdosage

Symptoms

Paralytic ileus, stomatitis, esophagitis, bone marrow aplasia, sepsis, paresis.

Patient Information

• 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.