Vinblastine PCH

Uses

Vinblastine PCH is effective as a single agent, but its therapeutic effect is enhanced when used in combination with other antineoplastic drugs. Vinblastine PCH has been used in the treatment of Hodgkin’s disease (Stages III and IV) in combination therapy (with adriamycin (doxorubicin), bleomycin and dacarbazine as ABVD) and in the treatment of advanced testicular carcinoma (with cisplatin and bleomycin). Vinblastine PCH has been used in the palliative treatment of lymphocytic lymphoma, histiocytic lymphoma, advanced stages of mycosis fungoides, Kaposi's sarcoma and Histiocytosis X.

Vinblastine PCH may be used in the treatment of choriocarcinoma resistant to other chemotherapeutic agents; carcinoma of the breast, unresponsive to appropriate endocrine surgery and hormonal therapy. One of the most effective single agents for treatment of Hodgkin’s disease is vinblastine. A protocol substituting cyclophosphamide for nitrogen mustard and vinblastine for vincristine in MOPP is an alternative therapy for previously untreated patients with advanced Hodgkin’s disease. Patients suffering relapse have also responded to combination therapy that included vinblastine. Advanced testicular germ-cell cancers are sensitive to vinblastine alone but the administration of vinblastine concomitantly with other antineoplastic agents, produces better clinical results. Bleomycin effectiveness is enhanced when vinblastine is administered 6 to 8 hours prior to bleomycin administration; this schedule permits more cells to be arrested during metaphase, in which bleomycin is active.

Vinblastine PCH is also used to associated treatment for these conditions: Advanced Soft Tissue Sarcoma, Autoimmune Hemolytic Anemia, Cancer, Bladder, Immune Thrombocytopenic Purpura ( ITP ), Kaposi’s sarcoma, Letterer-Siwe disease, Lymphoma, Hodgkins, Metastatic Melanoma, Non-Small Cell Lung Carcinoma (NSCLC), Advanced Alibert-Bazin syndrome, Advanced Testicular cancer, Histiocytic lymphoma, Refractory Breast cancer

How Vinblastine PCH works

The antitumor activity of vinblastine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Vinblastine PCH binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death.

Dosage

Vinblastine PCH dosage

Adult (Intravenous): Initially, 3.7 mg/m2, increase dose wkly based on WBC counts in increments of about 1.8 mg/m2 until leukocyte count decreases to about 3000/mm3, or max wkly dose of 18.5 mg/m2 reached. Do not increase dose if leukocyte count is reduced to approximately 3000 cells/mm3; administer the max dose that does not cause leucopenia for maintenance. Do not increase subsequent doses if onolytic activity occurs before leucopenic effect. Usual dose: 5.5-7.4 mg/m2 per wk. Do not admin next dose, even though 7 days have lapsed unless the leukocyte count has returned to at least 4000/mm3.

Child (Intravenous): Initial 2.5 mg/m2 of BSA, increased dose at wkly intervals in increments of about 1.25 mg/m2 until leukocyte count decreases to about 3000/ mm3, or max wkly dose of 12.5 mg/m2 reached. Do not increase dose once leukocyte count reaches approximately 3000 cells/mm3, instead, a dose of 1 increment smaller to be admin at wkly intervals for maintenance i.e. patient receives the max dose that does not cause leucopenia. If onolytic activity is encountered before leucopenic effect, then there is no need to increase subsequent doses. Do not admin next dose, even though 7 days have lapsed unless the leukocyte count has returned to at least 4000/mm3. Duration of maintenance therapy depends on disease state and the antineoplastic agent combination.

Side Effects

Alopecia, constipation, malaise, stomatitis, dose-limiting bone marrow suppression (e.g. granulocytopenia, thrombocytopenia, anaemia), hypertension, central and peripheral neurotoxicity, 8th cranial nerve damage resulting in vestibular and auditory toxicity, ischaemic cardiac toxicity, breathlessness, bone, tumour or jaw pain. Nausea, vomiting, GI bleed, syndrome of inappropriate antidiuretic hormone. Necrosis, cellulitis if extravasation occurs.

Toxicity

Oral, mouse: LD₅₀ = 423 mg/kg; Oral, rat: LD₅₀ = 305 mg/kg.

Precaution

Hepatic impairment; neurotoxicity; ischemic heart disease; preexisting pulmonary dysfunction; extravasation may cause tissue damage and pain. Discontinue immediately if extravasation occurs, with local Inj of hyaluronidase and local heat application to decrease discomfort and risk of cellulitis; remaining Inj to be injected into another vein. Routine prophylaxis against constipation recommended especially in high doses. Nadir in leukocyte count occur 4-10 days after vinblastine admin; recovery observed 7-14 days after treatment.

Interaction

Possible increase in vinblastine levels with aprepitant. Reduced vinblastine metabolism with miconazole. Variable interactions with phenytoin, monitor serum phenytoin levels. Reduced immune response with vaccines. Additive myelotoxicity with zidovudine. Concurrent admin of vinblastine with CYP3A inhibitors may cause an earlier onset and/or an increased severity of side effects.

Food Interaction

• Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of vinblastine.
• Exercise caution with St. John's Wort. This herb induces CYP3A metabolism, which may reduce serum levels of vinblastine.

Vinblastine PCH Drug Interaction

Moderate: dexamethasone, aprepitant, mechlorethamineMinor: doxorubicin, etoposideUnknown: amoxicillin, lorazepam, amoxicillin / clavulanate, arginine, levocarnitine, cysteine, lithium, valproic acid, thiamine, cyanocobalamin, pyridoxine, cholecalciferol, phytonadione, menaquinone, ondansetron

Vinblastine PCH Disease Interaction

Major: infections, myelosuppression, pulmonary dysfunctionModerate: hepatic dysfunction

Half Life

Triphasic: 35 min, 53 min, and 19 hours

Elimination Route

The major route of excretion may be through the biliary system.

Pregnancy & Breastfeeding use

Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Contraindication

Severe bone marrow suppression; presence of bacterial infection; maglignant cell infiltration of bone marrow; Inj into extremity with poor circulation; porphyria; granulocytopenia. Elderly with cachexia or extreme skin ulcerations. Pregnancy; lactation. Intrathecal use may result in death.

Special Warning

Hepatic Impairment: Serum bilirubin >3 mg/100ml: Reduce dose by 50%.

Acute Overdose

Symptoms: Severe bone marrow suppression and extensions of its usual side effects.

Management: Treatment is supportive. Restrict fluid and use of loop diuretics to counteract the effects of syndrome of inappropriate secretion of antidiuretic hormone. Monitor the patient's CV system and daily blood counts for transfusion requirement.

Storage Condition

Store at 2-8° C.

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