Yes

Antineoplastic Agent, Natural Source (Plant) Derivative

Treatment of Hodgkin's and non-Hodgkin's lymphoma, testicular, lung, head and neck, breast, and renal carcinomas, Mycosis fungoides, Kaposi's sarcoma, histiocytosis, choriocarcinoma, and idiopathic thrombocytopenic purpura

D

For I.V. use only; I.T. use may result in death; severe bone marrow suppression or presence of bacterial infection not under control prior to initiation of therapy

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Avoid extravasation; dosage modification required in patients with impaired liver function and neurotoxicity. Using small amounts of drug daily for long periods may increase neurotoxicity and is therefore not advised. For I.V. use only. Intrathecal administration may result in death. Use with caution in patients with cachexia or ulcerated skin; monitor closely for shortness of breath or bronchospasm in patients receiving mitomycin C.

>10%:

Dermatologic: Alopecia

Gastrointestinal: Nausea and vomiting are most common and are easily controlled with standard antiemetics; constipation, diarrhea (less common), stomatitis, abdominal cramps, anorexia, metallic taste

Emetic potential: Moderate (30% to 60%)

Hematologic: May cause severe bone marrow suppression and is the dose-limiting toxicity of VLB (unlike vincristine); severe granulocytopenia and thrombocytopenia may occur following the administration of VLB and nadir 7-10 days after treatment

Myelosuppressive:

WBC: Moderate - severe

Platelets: Moderate - severe

Onset (days): 4-7

Nadir (days): 4-10

Recovery (days): 17

1% to 10%:

Cardiovascular: Hypertension, Raynaud's phenomenon

Central nervous system: Depression, malaise, headache, seizures

Dermatologic: Rash, photosensitivity, dermatitis

Endocrine & metabolic: Hyperuricemia

Extravasation: VLB is a vesicant and can cause tissue irritation and necrosis if infiltrated; if extravasation occurs, follow institutional policy, which may include hyaluronidase and hot compresses

Vesicant chemotherapy

Gastrointestinal: Paralytic ileus, stomatitis

Genitourinary: Urinary retention

Neuromuscular & skeletal: Jaw pain, myalgia, paresthesia

Respiratory: Bronchospasm

<1%: VLB rarely produces neurotoxicity at clinical doses; however, neurotoxicity may be seen, especially at high doses; if it occurs, symptoms are similar to VCR toxicity (ie, peripheral neuropathy, loss of deep tendon reflexes, headache, weakness, urinary retention, and GI symptoms, tachycardia, orthostatic hypotension, convulsions); hemorrhagic colitis

Symptoms of overdose include bone marrow suppression, mental depression, paresthesia, loss of deep reflexes, neurotoxicity

There is no information regarding the effectiveness of dialysis. There are no antidotes for vinblastine; treatment is supportive and symptomatic, including fluid restriction or hypertonic saline (3% sodium chloride) for drug-induced secretion of inappropriate antidiuretic hormone (SIADH), diazepam or phenytoin for seizures, laxatives for constipation, and antiemetics for toxic emesis

CYP3A3/4 and 3A5-7 enzyme substrate; CYP2D6 enzyme inhibitor

Phenytoin plasma levels may be reduced with concomitant combination chemotherapy with vinblastine

Alpha-interferon enhances interferon toxicity; phenytoin may decrease plasma levels

Increased toxicity:

Previous or simultaneous use with mitomycin-C has resulted in acute shortness of breath and severe bronchospasm within minutes or several hours after vinca alkaloid injection and may occur up to 2 weeks after the dose of mitomycin

Mitomycin-C in combination with administration of VLB may cause acute shortness of breath and severe bronchospasm, onset may be within minutes or several hours after VLB injection

Store intact vials under refrigeration (2°C to 8°C) and protect from light; stable for 24 hours at room temperature

Further dilution in D₅W or NS is stable for 21 days at room temperature (25°C) and refrigeration (4°C)

Standard I.V. dilution:

I.V. push: Dose/syringe (concentration = 1 mg/mL)

Maximum syringe size for IVP is a 30 mL syringe and syringe should be less than or equal to 75% full

CIV: Dose/250-1000 mL D₅W or NS

Protect from light

VLB binds to tubulin and inhibits microtubule formation, therefore, arresting the cell at metaphase by disrupting the formation of the mitotic spindle; it is specific for the M and S phases; binds to microtubular protein of the mitotic spindle causing metaphase arrest

Absorption: Not reliably absorbed from the GI tract and must be given I.V.

Distribution: V_d: 27.3 L/kg; binds extensively to tissues; does not penetrate CNS or other fatty tissues; distributes to the liver

Protein binding: 99% rapidly

Metabolism: Hepatic metabolism to an active metabolite

Half-life (biphasic): Initial 0.164 hours; Terminal: 25 hours

Elimination: Biliary excretion (95%); <1% eliminated unchanged in urine

Refer to individual protocols. Varies depending upon clinical and hematological response. Give at intervals of at least 14 days and only after leukocyte count has returned to at least 4000/mm³; maintenance therapy should be titrated according to leukocyte count. Dosage should be reduced in patients with recent exposure to radiation therapy or chemotherapy; single doses in these patients should not exceed 5.5 mg/m².

Dosing adjustment in hepatic impairment:

Serum bilirubin 1.5-3.0 mg/dL or AST 60-180 units: Administer 50% of normal dose

Serum bilirubin 3.0-5.0 mg/dL: Administer 25% of dose

Serum bilirubin >5.0 mg/dL or AST >180 units: Omit dose

CBC with differential and platelet count, serum uric acid, hepatic function tests

May cause depression

Bone marrow suppression is common; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This medication can only be administered by infusion, usually on a cyclic basis. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) and nutrition (small frequent meals will help). You will most likely loss your hair (will grow back after therapy); experience nausea or vomiting (request antiemetic); photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight); or feel weak or lethargic (use caution when driving or engaging in tasks requiring alertness until response to drug is known). Use good oral care to reduce incidence of mouth sores. You will be more susceptible to infection; avoid crowds or exposure to infection. Report numbness or tingling in fingers or toes (use care to prevent injury); signs of infection (eg, fever, chills, sore throat, burning urination, fatigue); unusual bleeding (eg, tarry stools, easy bruising, blood in stool, urine, or mouth); unresolved mouth sores; skin rash or itching; or difficulty breathing. Pregnancy/breast-feeding precautions: Do not get pregnant. Breast-feeding is not recommended.

May be administered by I.V. push or into a free flowing I.V.; monitor for life-threatening bronchospasm (most likely to occur if patient is also taking mitomycin). Maintain adequate hydration; allopurinol may be given to prevent uric acid nephropathy; may cause sloughing upon extravasation.

Mix 250 units hyaluronidase with 6 mL of NS

Inject the hyaluronidase solution subcutaneously through 6 clockwise injections into the infiltrated area using a 25-gauge needle; change the needle with each new injection

Apply heat immediately for 1 hour; repeat 4 times/day for 3-5 days

Application of cold or hydrocortisone is contraindicated

Injection, as sulfate: 1 mg/mL (10 mL)

Powder for injection, as sulfate: 10 mg

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Chong CD, Logothetis CJ, Savaraj N, et al, "The Correlation of Vinblastine Pharmacokinetics to Toxicity in Testicular Cancer Patients," J Clin Pharmacol, 1998, 28(8):714-8.

Crom WR, Glynn-Barnhart AM, Rodman JH, et al, "Pharmacokinetics of Anticancer Drugs in Children," Clin Pharmacokinet, 1987, 12(3):168-213.

Dorr RT and Alberts DS, "Vinca Alkaloid Skin Toxicity: Antidote and Drug Disposition Studies in the Mouse," J Natl Cancer Inst, 1985, 74(1):113-20.

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