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Vinblastine Sulfate

Pronouncation: (vin-BLAST-een)
Class: Vinca alkaloid

Trade Names:
Vinblastine Sulfate
- Injection 10 mg

Pharmacology

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Vinblastine interferes with metabolic pathways of amino acids leading from glutamic acid to the citric acid cycle and urea. Vinblastine has an effect on cell energy production required for mitosis and interferes with nucleic acid synthesis.

Pharmacokinetics

Absorption

Rapidly absorbed 15 to 30 min following IV triphasic serum decay pattern.

Distribution

Undergoes rapid distribution (from blood to tissue) and extensive tissue binding.

Metabolism

Metabolized by the hepatic P450 3A cytochromes. The metabolite, deacetyl vinblastine, is more active than parent drug.

Elimination

Major route of excretion is the biliary system (liver). Terminal t _½ is 24.8 h.

Special Populations

Hepatic Function Impairment

Toxicity may be enhanced. A dose reduction is recommended. In patients with a direct serum bilirubin value more than 3 mg/dL, a 50% dose reduction is recommended.

Pregnancy

Category D . Information is very limited.

Indications and Usage

Adult

Hodgkin disease, non-Hodgkin lymphoma, mycosis fungoides, advanced testicular carcinoma, Kaposi sarcoma, choriocarcinoma, breast cancer.

Children

Hodgkin disease, non-Hodgkin lymphoma, mycosis fungoides, Letterer-Siwe disease, choriocarcinoma.

Unlabeled Uses

Non-small cell lung carcinoma, bladder cancer, cervical cancer, refractory idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia.

Contraindications

Leukopenia; presence of bacterial infection (infections must be under control prior to initiating therapy); significant granulocytopenia unless it is a result of the disease being treated.

Dosage and Administration

Initial
Adults

IV Initially 3.7 mg/m ² as a single dose/wk. Then increase at weekly intervals in 1.8 mg/m ² increments until the leukocyte count decreases to about 3,000/mm ³ . The maximum weekly dose is 18.5 mg/m ² .

Pediatric

IV Initially 2.5 mg/m ² as a single dose/wk. Then increase at weekly intervals in 1.25 mg/m ² increments until the leukocyte count decreases to about 3,000/mm ³ . The maximum weekly dose is 12.5 mg/m ² .

Maintenance
Adults

IV The maintenance dose is 1.8ߙmg/m ² less than the dose required to produce a leukocyte count of 3,000/mm ³ every 7 to 14ߙdays. The optimum weekly dose is normally 5.5 to 7.4 mg/m ² . Maintenance doses should not be given until the WBC reaches 4,000/mm ³ . For an adequate trial, vinblastine must be continued for at least 4 to 6ߙwk.

Children

IV The maintenance dose is 1.25ߙmg/m ² less than the dose required to produce a leukocyte count of 3,000/mm ³ every 7 to 14 days. Maintenance doses should not be given until the WBC reaches 4,000/mm ³ . For an adequate trial, vinblastine must be continued for at least 4 to 6 wk.

Adjustment in Hepatic Insufficiency
Adults

IV Reduce the dose 50% in patients with a direct serum bilirubin exceeding 3 mg/dL.

General Advice

Reconstitute sterile powder with 10ߙmL of bacteriostatic sodium chloride 0.9% containing phenol or benzyl alcohol (final concentration 1ߙmg/mL). Powder also may be reconstituted with 10 mL of preservative-free sodium chloride 0.9%.
Give IV push injection or IV side arm into a running infusion.

Storage/Stability

Refrigerate. Protect from light. Unopened vials are stable at room temperature for 2ߙwk, but this is not recommended for storage. Solutions reconstituted with bacteriostatic sodium chloride 0.9% are stable for 30ߙdays in the refrigerator. Solutions reconstituted with preservative-free sodium chloride 0.9% should be used within 24ߙh.

Drug Interactions

CYP-450 inhibitors

Vinblastine elimination may be reduced by CYP-450 enzyme inhibitors.

Erythromycin

Erythromycin may decrease metabolism of vinblastine causing increased toxicity.

Mitomycin

Acute shortness of breath and severe bronchospasm have occurred following concomitant or previous use of mitomycin.

Phenytoin

May reduce phenytoin plasma concentration.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension.

CNS

Malaise; weakness; dizziness; numbness of digits or paresthesia; loss of deep tendon reflexes; peripheral neuritis; mental depression; headache; convulsions.

Dermatologic

Alopecia; photosensitivity.

Endocrine

Syndrome of inappropriate antidiuretic hormone secretion.

GI

Pharyngitis; vesiculation of the mouth; mucositis; ileus; diarrhea; constipation; anorexia; abdominal pain; rectal bleeding; hemorrhagic enterocolitis; bleeding from an old peptic ulcer.

Genitourinary

Amenorrhea; loss of sperm or semen.

Hematologic

Bone marrow suppression, usually selective for leukocytes, nadir at 5 to 10 days.

Musculoskeletal

Bone or jaw pain acutely.

Respiratory

Acute bronchospasm, especially in combination with mitomycin.

Precautions

Warnings

IV use only

Intrathecal use of other vinca alkaloids has been fatal. Label syringe “Warning - For IV Use Only; fatal if given intrathecally.”

Granulocytopenia

May be severe and predispose to infection. Do not administer to patients with granulocyte counts less than 1,000 cells/mm ³ .

Avoid extravasation

Proper placement of needle/catheter prior to administration. Extravasation can cause severe local necrosis. Local irritation or phlebitis may occur. Refer to your institution specific protocol.

Pregnancy

Category D .

Lactation

Undetermined.

Hepatic Function

Toxicity may be enhanced in the presence of hepatic insufficiency. A dose reduction is recommended.

Dosage adjustment guidelines (children)

Follow dosage adjustment guidelines recommended for adults.

Hematologic effects

Leukopenia is expected. If leukopenia (less than 2,000 WBC/mm ³ ) occurs following a dose of this drug, carefully watch the patient for evidence of infection until a safe WBC count has returned.

Pulmonary reactions

Acute shortness of breath and severe bronchospasm have occurred. These reactions occur most frequently when used with mitomycin.

Overdosage

Symptoms

Side effects are dose-related. Expect exaggerated effects.

Patient Information

Immediately report sore throat, fever, chills, or sore mouth to the health care provider.
The following may occur: alopecia, jaw pain, pain in the organs containing tumor tissue, nausea, and vomiting. Scalp hair will regrow to its pretreatment extent, even with continued treatment. Report any other serious medical event to the health care provider.
Avoid constipation.