Velban (Vinblastine) for Injection

By | March 11, 2016

ANTINEOPLASTIC

Highlights of Prescribing Information

  • A Vinca alkaloid antineoplastic used for a variety of tumors in dogs (& sometimes cats)
  • Contraindications: Preexisting leukopenia or granulocytopenia (unless a result of the disease being treated) or active bacterial infection; reduce dose if hepatic disease
  • Adverse Effects: Gastroenterocolitis (nausea/vomiting), myelosuppression (more so than with vincristine); may also cause constipation, alopecia, stomatitis, ileus, inappropriate ADH secretion, jaw & muscle pain, & loss of deep tendon reflexes
  • CATS can develop neurotoxicity causing constipation or paralytic ileus & aggravating anorexia; can also develop reversible axon swelling & paranodal demyelination
  • Potentially teratogenic
  • Avoid extravasation; wear gloves & protective clothing when preparing or administering
  • Drug Interactions

What Is Drug Used For?

Vinblastine may be employed in the treatment of lymphomas, carcinomas, mastocytomas, and splenic tumors in small animals. It is more effective than vincristine in the treatment of canine mast cell tumors.

Pharmacology / Actions

Vinblastine apparently binds to microtubular proteins (tubulin) in the mitotic spindle, thereby preventing cell division during metaphase. It also interferes with amino acid metabolism by inhibiting glutamic acid utilization and preventing purine synthesis, citric acid cycle, and urea formation.

Pharmacokinetics

Vinblastine is administered IV After injection, it is rapidly distributed to tissues. In humans, approximately 75% is bound to tissue proteins and the drug does not appreciably enter the CNS.

Vinblastine is extensively metabolized by the liver and is primarily excreted in the bile/feces; lesser amounts are eliminated in the urine.

Before you take Drug

Contraindications / Precautions / Warnings

Vinblastine is contraindicated in patients with preexisting leukopenia or granulocytopenia (unless a result of the disease being treated), or active bacterial infection.

Doses of vinblastine should be reduced in patients with hepatic disease. A 50% reduction in dose should be considered if serum bilirubin levels are greater than 2 mg/dl.

Because vinblastine is potentially a neurotoxic substrate of P-glycoprotein, it should be used with caution in those herding breeds (e.g., Collies) that may have the gene mutation that causes a nonfunctional protein.

As vinblastine maybe a skin irritant, gloves and protective clothing should be worn when preparing or administering the medication. If skin/mucous membrane exposure occurs, thoroughly wash area with soap and water.

Adverse Effects

Vinblastine can cause gastroenterocolitis (nausea/vomiting) which generally lasts less than 24-hours. It can be myelosuppressive at usual dosages (nadir at 4-9 days after treatment; recovery at 7-14 days). Vinblastine is considered more myelosuppressive than is vincristine.

Vinblastine may not possess the degree of peripheral neurotoxic effects seen with vincristine, but at high doses, these effects may be seen. Additionally, vinblastine may cause constipation, alopecia, stomatitis, ileus, inappropriate ADH secretion, jaw and muscle pain, and loss of deep tendon reflexes.

Cats can develop neurotoxicity that can be associated with constipation or paralytic ileus thereby aggravating anorexia. They may develop reversible axon swelling and paranodal demyelination.

Extravasation of vinblastine may cause significant tissue irritation and cellulitis. Because of the vesicant action of this drug, it is recommended to use a different needle for injecting the drug than the one used to withdraw the drug from the vial. Should clinical signs of extravasation be noted, discontinue infusion immediately at that site and apply moderate heat to the area to help disperse the drug. Injections of hyaluronidase have also been suggested to help diffuse the drug.

Reproductive / Nursing Safety

Little is known about the effects of vinblastine on developing fetuses, but it is believed that the drug possesses some teratogenic and embryotoxic properties. It may also cause aspermia in males. In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, hut the potential benefits from the use of the drug in pregnant women may he acceptable despite its potential risks.)

It is not known whether vinblastine is excreted in milk. Because of the potential for serious adverse reactions in nursing offspring, consider using milk replacer if dams are being given this drug.

Overdosage / Acute Toxicity

In dogs, the lethal dose for vinblastine has been reported as 0.2 mg/ kg. Effects of an overdosage of vinblastine are exacerbations of the adverse effects outlined above. Additionally, neurotoxic effects similar to those associated with vincristine may also be noted.

In humans, cardiovascular and hematologic monitoring are performed after an overdose. Treatment can include anticonvulsants, and prevention of ileus. Additionally, an attempt is made to prevent the effects associated with the syndrome of inappropriate antidiuretic hormone (SIADH) with fluid restriction and loop diuretics to maintain serum osmolality.

Drug Interactions

The following drug interactions have either been reported or are theoretical in humans or animals receiving vinblastine and may be of significance in veterinary patients:

■ OTOTOXIC DRUGS (e.g., cisplatin, carboplatin): May cause additive risk for ototoxicity

Caution is advised if using other drugs that can inhibit p-glycoprotein particularly in those dogs at risk for MDRl-allele mutation (Collies, Australian Shepherds, Shelties, Long-haired Whippet, etc. “white feet”), unless tested “normal”. Drugs and drug classes involved include:

■ AMIODARONE

■ AZOLE ANTIFUNGALS (e.g., ketoconazole)

■ CARVEDILOL

■ CYCLOSPORINE

■ DILTIAZEM

■ ERYTHROMYCIN; CLARITHROMYCIN

■ QUINIDINE

■ SPIRONOLACTONE

■ TAMOXIFEN

■ VERAPAMIL

Laboratory Considerations

■ Vinblastine may significantly increase both blood and urine concentrations of uric acid

How to use Drug

For more information on using vinblastine as part of chemotherapy protocols, refer to the protocols found in the appendix or other dosages/protocols found in numerous references, including: Withrow and MacEwen’s Small Animal Clinical Oncology, 4th Ed. (); Canine and Feline Geriatric Oncology (); Small Animal Internal Medicine, 3rd Edition (); Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat 6th Edition (); and The 5-Minute Veterinary Consult Canine & Feline, 3rd Ed. ().

Drug dosage for dogs:

For susceptible neoplastic diseases:

a) 2 mg/m2 IV every 7-14 days ()

b) For mast cell tumors after surgical removal: vinblastine at 2 mg/m2 IV, weekly for four weeks then every two weeks for eight weeks. Prednisolone is given concurrently starting at 2 mg/kg/day, tapering to 0.5 mg/kg day. ()

c) For lymphoma and mastocytoma: 2 mg/m2 weekly. For lymphosarcoma and various carcinomas: 2.5 mg/m2 IV weekly ()

Drug dosage for cats:

For susceptible neoplastic diseases:

a) For lymphosarcoma and mast cell neoplasms: 2 mg/m2 IV every 7-14 days ()

b) 2 mg/m2 slow IV every 7-14 days ()

Monitoring

■ Efficacy

■ Toxicity (complete blood counts with platelets; liver function tests prior to therapy and repeated as necessary; serum uric acid)

Client Information

■ Clients must be briefed on the possibilities of severe toxicity developing from this drug, including drug-related mortality

■ Contact the veterinarian if the patient exhibits any symptoms of profound depression, abnormal bleeding (including bloody diarrhea) and/or bruising

Chemistry / Synonyms

Commonly referred to as a Vinca alkaloid, vinblastine sulfate is isolated from the plant Cantharanthus roseus (Vinca rosea Linn) and occurs as a white or slightly yellow, hygroscopic, amorphous or crystalline powder that is freely soluble in water. The commercially available injection has a pH of 3-5.5.

Vinblastine may also be known as: 29060-LE, NSC-49842, sulfato de vimblastina, vinblastini sulfas, vincaleukoblastine sulphate, VBL, Alkaban, Blastovin, Cellblastin, Cytoblastin, Ifabla, Lemblastine, Periblastine, Serovin, Solblastin, Velban, Velbe, Velsar, or Xintoprost.

Storage / Stability / Compatibility

The sterile powder for injection, solution for injection and reconstituted powder for injection should all be protected from light. The powder for injection and injection should be stored in the refrigerator (2-8°C). The intact powder for injection is stable at room temperature for at least one month. After reconstituting with bacteriostatic saline, the powder for injection is stable for 30 days if refrigerated.

Vinblastine sulfate is reportedly physically compatible with the following intravenous solutions and drugs: D5W and bleomycin sulfate. In syringes or at Y-sites with: bleomycin sulfate, cisplatin, cyclophosphamide, droperidol, fluorouracil, leucovorin calcium, methotrexate sodium, metoclopramide HCL, mitomycin, and vincristine sulfate.

Vinblastine sulfate compatibility information conflicts or is dependent on diluent or concentration factors with the following drugs or solutions: doxorubicin HCL and heparin sodium (in syringes).

Vinblastine sulfate is reportedly physically incompatible with furosemide. Compatibility is dependent upon factors such as pH, concentration, temperature and diluent used; consult specialized references or a hospital pharmacist for more specific information.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

Human-Labeled Products:

Vinblastine Sulfate Injection: 1 mg/mL in 10 mL and 25 mL vials; generic; (Rx)

Vinblastine Powder for Injection: 10 mg in vials; Velban (Lilly); generic; (Rx)

 

Selections from the book: “Plumb’s Veterinary Drug Handbook. Sixth Edition”. 2008

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