Vinblastine Sulfate

Description

DESCRIPTION: Vinblastine sulfate is the salt of an alkaloid extracted from Vinca rosea Linn., a common flowering herb known as the periwinkle (more properly known as Catharanthus roseus G. Don). Previously, the generic name was vincaleukoblastine, abbreviated VLB. It is a stathmokinetic oncolytic agent. When treated in vitro with this preparation, growing cells are arrested in metaphase. Chemical and physical evidence indicate that vinblastine sulfate is a dimeric alkaloid containing both indole and dihydroindole moieties. The accompanying structural formula has been proposed. C 46 H 58 N 4 O 9

What Is Vinblastine Sulfate Used For?

INDICATIONS AND USAGE: Vinblastine Sulfate Injection is indicated in the palliative treatment of the following: I. Frequently Responsive Malignancies

Dosage and Administration

DOSAGE AND ADMINISTRATION: This preparation is for intravenous use only (see WARNINGS ). Special Dispensing Information - To reduce the potential for fatal medication errors due to incorrect route of administration, vinblastine sulfate injection should be diluted in a flexible plastic container and prominently labeled (as indicated), “FOR INTRAVENOUS USE ONLY – FATAL IF GIVEN BY OTHER ROUTES.” (see WARNINGS ). Preparation for flexible plastic container Vinblastine sulfate injection when diluted with 0.9% sodium chloride injection to concentrations of 0.1 mg/mL to 0.4 mg/mL is stable at room temperature for up to 24 hours when protected from light or 8 hours in normal light. Caution–It is extremely important that the intravenous needle or catheter be properly positioned before any vinblastine sulfate is injected. Leakage into surrounding tissue during intravenous administration of vinblastine sulfate may cause considerable irritation. If extravasation occurs, the injection should be discontinued immediately and any remaining portion of the dose should then be introduced into another vein. Local injection of hyaluronidase and the application of moderate heat to the area of leakage will help disperse the drug and may minimize discomfort and the possibility of cellulitis. There are variations in the depth of the leukopenic response that follows therapy with vinblastine sulfate. For this reason, it is recommended that the drug be given no more frequently than once every seven days . Adult Patients It is wise to initiate therapy for adults by administering a single intravenous dose of 3.7 mg/m 2 of body surface area (bsa). Thereafter, white blood cell counts should be made to determine the patient’s sensitivity to vinblastine sulfate. A simplified and conservative incremental approach to dosage at weekly intervals for adults may be outlined as follows: First dose ....................................... 3.7 mg/m 2 bsa Second dose .................................. 5.5 mg/m 2 bsa Third dose ...................................... 7.4 mg/m 2 bsa Fourth dose .................................. 9.25 mg/m 2 bsa Fifth dose ..................................... 11.1 mg/m 2 bsa The above-mentioned increases may be used until a maximum dose not exceeding 18.5 mg/m 2 bsa for adults is reached. The dose should not be increased after that dose which reduces the white cell count to approximately 3,000 cells/mm 3 . In some adults, 3.7 mg/m 2 bsa may produce this leukopenia; other adults may require more than 11.1 mg/m 2 bsa; and, very rarely, as much as 18.5 mg/m 2 bsa may be necessary. For most adult patients, however, the weekly dosage will prove to be 5.5 to 7.4 mg/m 2 bsa. When the dose of vinblastine sulfate which will produce the above degree of leukopenia has been established, a dose of one increment smaller than this should be administered at weekly intervals for maintenance. Thus, the patient is receiving the maximum dose that does not cause leukopenia. It...

Side Effects (Adverse Reactions)

ADVERSE REACTIONS: Prior to the use of the drug, patients should be advised of the possibility of untoward symptoms . In general, the incidence of adverse reactions attending the use of vinblastine sulfate appears to be related to the size of the dose employed. With the exception of epilation, leukopenia and neurologic side effects, adverse reactions generally have not persisted for longer than 24 hours. Neurologic side effects are not common; but when they do occur, they often last for more than 24 hours. Leukopenia, the most common adverse reaction, is usually the dose-limiting factor. The following are manifestations that have been reported as adverse reactions, in decreasing order of frequency. The most common adverse reactions are underlined: Hematologic - Leukopenia (granulocytopenia), anemia, thrombocytopenia (myelosuppression). Dermatologic - Alopecia is common. A single case of light sensitivity associated with this product has been reported. Gastrointestinal - Constipation , anorexia, nausea, vomiting, abdominal pain, ileus, vesiculation of the mouth, pharyngitis, diarrhea, hemorrhagic enterocolitis, bleeding from an old peptic ulcer and rectal bleeding. Neurologic - Numbness of digits (paresthesias), loss of deep tendon reflexes, peripheral neuritis, mental depression, headache, convulsions. Treatment with vinca alkaloids has resulted rarely in both vestibular and auditory damage to the eighth cranial nerve. Manifestations include partial or total deafness which may be temporary or permanent, and difficulties with balance including dizziness, nystagmus and vertigo. Particular caution is warranted when vinblastine sulfate is used in combination with other agents known to be ototoxic such as the platinum-containing oncolytics. Cardiovascular - Hypertension —Cardiac effects such as myocardial infarction, angina pectoris and transient abnormalities of ECG related to coronary ischemia have been reported very rarely. Cases of unexpected myocardial infarction and cerebrovascular accidents have occurred in patients undergoing combination chemotherapy with vinblastine, bleomycin and cisplatin. Raynaud’s phenomenon has also been reported with this combination. Pulmonary - See PRECAUTIONS . Miscellaneous - Malaise, bone pain, weakness, pain in tumor-containing tissue , dizziness, jaw pain , skin vesiculation, hypertension, Raynaud’s phenomenon when patients are being treated with vinblastine sulfate in combination with bleomycin and cis-platinum for testicular cancer. The syndrome of inappropriate secretion of antidiuretic hormone has occurred with higher than recommended doses. Nausea and vomiting usually may be controlled with ease by antiemetic agents. When epilation develops, it frequently is not total; and, in some cases, hair regrows while maintenance therapy continues. Extravasation during intravenous injection may lead to cellulitis and phlebitis. If the amount of extravasation is great, sloughing may occur.

Drug Interactions

Drug Interactions The simultaneous oral or intravenous administration of phenytoin and antineoplastic chemotherapy combinations that included vinblastine sulfate has been reported to have reduced blood levels of the anticonvulsant and to have increased seizure activity. Dosage adjustment should be based on serial blood level monitoring. The contribution of vinblastine sulfate to this interaction is not certain. The interaction may result from either reduced absorption of phenytoin or an increase in the rate of its metabolism and elimination. Caution should be exercised in patients concurrently taking drugs known to inhibit drug metabolism by hepatic cytochrome P450 isoenzymes in the CYP 3A subfamily, or in patients with hepatic dysfunction. Concurrent administration of vinblastine sulfate with an inhibitor of this metabolic pathway may cause an earlier onset and/or an increased severity of side effects. Enhanced toxicity has been reported in patients receiving concomitant erythromycin (see ADVERSE REACTIONS ).

Contraindications

CONTRAINDICATIONS: Vinblastine sulfate is contraindicated in patients who have significant granulocytopenia unless this is a result of the disease being treated. It should not be used in the presence of bacterial infections. Such infections must be brought under control prior to the initiation of therapy with vinblastine sulfate.

Pregnancy and Breastfeeding

Usage in Pregnancy Pregnancy Category D - (See WARNINGS ). Vinblastine sulfate should be given to a pregnant woman only if clearly needed. Animal studies suggest that teratogenic effects may occur.

Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions from vinblastine sulfate in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.

Overdosage

OVERDOSAGE: Signs and Symptoms Side effects following the use of vinblastine sulfate are dose related. Therefore, following administration of more than the recommended dose, patients can be expected to experience these effects in an exaggerated fashion. (See CLINICAL PHARMACOLOGY , CONTRAINDICATIONS , WARNINGS , PRECAUTIONS and ADVERSE REACTIONS .) There is no specific antidote. In addition, neurotoxicity similar to that with vincristine sulfate may be observed. Since the major route of excretion may be through the biliary system, toxicity from this drug may be increased when there is hepatic insufficiency. Treatment To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians’ Desk Reference (PDR) . In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs and unusual drug kinetics in your patient. Overdoses of vinblastine sulfate have been reported rarely. The following is provided to serve as a guide should such an overdose be encountered. Supportive care should include the following: (1) prevention of side effects that result from the syndrome of inappropriate secretion of antidiuretic hormone (this would include restriction of the volume of daily fluid intake to that of the urine output plus insensible loss and perhaps the administration of a diuretic affecting the function of the loop of Henle and the distal tubule); (2) administration of an anticonvulsant; (3) prevention of ileus: (4) monitoring the cardiovascular system; and (5) determining daily blood counts for guidance in transfusion requirements and assessing the risk of infection. The major effect of excessive doses of vinblastine sulfate will be myelosuppression, which may be life-threatening. There is no information regarding the effectiveness of dialysis nor of cholestyramine for the treatment of...

How Supplied

HOW SUPPLIED: Vinblastine Sulfate Injection is supplied as follows: Product Code NDC No. Strength 27810 63323-278-10 10 mg per 10 mL (1 mg per mL) 10 mL flip-top vial, individually packaged. Store products in refrigerator 2° to 8°C (36° to 46°F) to assure extended stability. PROTECT FROM LIGHT . Retain vial in carton until time of use.