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(vin-BLAST-een)

Class: Vinca alkaloid

 Actions 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. Vinblastine undergoes rapid distribution and extensive tissue binding, and localizes in platelets and leukocyte fractions of whole blood. Vinblastine is partially metabolized to deacetyl vinblastine which is more active than the parent drug. Plasma decline follows a triphasic pattern. The initial, middle and terminal half-lives are 3.7 min, 1.6 hr, and 24.8 hr, respectively. Vinblastine is metabolized by the hepatic P450 3A cytochromes, and the major route of excretion may be through the biliary system.

 Indications

Adult

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

Pediatric

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

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.

 Route/Dosage

Initial

ADULTS: IV Initially 3.7 mg/m² as a single dose/wk. Then increase at weekly intervals in 1.8 mg/m² increments until the leukocyte count decreases to » 3000/mm³. The maximum weekly dose is 18.5 mg/m².

PEDIATRIC: IV Initially 2.5 mg/m² as a single dose/wk. Then increase at weekly intervals in 1.25 mg/m² increments until the leukocyte count decreases to » 3000/mm³. The maximum weekly dose is 12.5 mg/m².

Maintenance

ADULTS: IV The maintenance dose is 1.8 mg/m² less than the dose required to produce a leukocyte count of 3000/mm³ every 7 to 14 days. The optimum weekly dose is normally 5.5 to 7.4 mg/m². Maintenance doses should not be given until the WBC reaches 4000/mm³. For an adequate trial, vinblastine must be continued for ³ 4 to 6 wk.

PEDIATRIC: IV The maintenance dose is 1.25 mg/m² less than the dose required to produce a leukocyte count of 3000/mm³ every 7 to 14 days. Maintenance doses should not be given until the WBC reaches 4000/mm³. For an adequate trial, vinblastine must be continued for ³ 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.

Interactions

CYP450 inhibitors

Vinblastine elimination may be reduced by cytochrome P450 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.

Lab Test Interferences 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. GU: 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

Pregnancy: Category D. Lactation: Undetermined. Dosage adjustment guidelines (pediatric): Follow dosage adjustment guidelines recommended for adults. IV use only: Intrathecal administration has resulted in death. Hematologic effects: Leukopenia is expected. If leukopenia (< 2000 WBC/mm³) occurs following a dose of this drug, carefully watch the patient for evidence of infection until a safe WBC count has returned. Hepatic function impairment: Toxicity may be enhanced in the presence of hepatic insufficiency. A dose reduction is recommended. Pulmonary reactions: Acute shortness of breath and severe bronchospasm have occurred. These reactions occur most frequently when used with mitomycin. Extravasation risk: Local irritation or phlebitis may occur. Refer to your institution specific protocol.

PATIENT CARE CONSIDERATIONS

 Administration/Storage

• Refrigerate. Protect from light. Unopened vials are stable at room temperature for 2 wk, but this is not recommended for storage. Solutions reconstituted with bacteriostatic 0.9% Sodium Chloride are stable for 30 days in the refrigerator. Solutions reconstituted with preservative-free 0.9% Sodium Chloride should be used within 24 hr.
• Reconstitute sterile powder with 10 mL of bacteriostatic 0.9% Sodium Chloride containing phenol or benzyl alcohol (final concentration 1 mg/mL). Powder also may be reconstituted with 10 mL of preservative-free 0.9% Sodium Chloride.
• Give IV push injection or IV side arm into a running infusion.

 Assessment/Interventions

• Monitor CBC closely.
• Carefully watch the patient for evidence of infection until a safe WBC count has returned.
• Hyperuricemia may occur because of rapid cell lysis; monitor serum uric acid. Minimize effects of hyperuricemia with hydration, urinary alkalinization, and allopurinol.

OVERDOSAGE: SIGNS & SYMPTOMS   Side effects are dose-related. Expect exaggerated effects.

 Patient/Family Education

• 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.

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