PHARMACOLOGICAL CLASSIFICATION: A 26. Cytostatic Agents
PHARMACOLOGICAL ACTION: Although the exact mechanism of action is unknown, three hypotheses have been offered:
a) Inhibition of DNA synthesis by acting as a purine analogue.
b) Action as an alkylating agent.
c) Interaction with SH groups.
INDICATIONS: Metastatic malignant melanoma.
It is also indicated for the treatment of metastatic sarcoma in combination with other chemotherapeutic drugs.
In addition DTIC-DOME has been shown, when used in combination with other cytotoxic agents, to be of value in other malignant diseases, including carcinomas of colon, ovary, breast and lung and testicular teratoma.
CONTRA-INDICATIONS: Pregnancy, lactation and patients who are hypersensitive to dacarbazine.
WARNINGS: Extravasation of the drug subcutaneously during intravenous administration may result in tissue damage and severe pain.
DOSAGE AND DIRECTIONS FOR USE: DTIC-DOME 200 mg vials are reconstituted with 19,7 mL of Water for Injection. The resulting solution contains an equivalent of 10 mg/mL of dacarbazine. After the solution has been prepared, the calculated dose of the resulting solution is drawn into a syringe and injected intravenously. Injection may be completed in approximately one minute.
The following schedule is recommended:
2-4,5 mg/kg/day for 10 days which may be repeated at 3 week intervals. It has been found that dacarbazine may be as efficacious at the lower dosage as at the higher dosage. Combinations of cancer chemotherapeutic agents have often shown an improved response over the use of a single agent.
If desired, the reconstituted solution may be further diluted with 150-250 mL of 5% Dextrose for Injection or Normal Saline for Injection and administered by intravenous infusion over a period of 15-30 minutes.
ALL RECONSTITUTED SOLUTIONS MUST BE PROTECTED FROM LIGHT AND USED WITHIN ONE HOUR.
SIDE EFFECTS AND SPECIAL PRECAUTIONS: DTIC-DOME should be administered preferably to patients who are hospitalized and who can be observed carefully and frequently during and after therapy, with particular reference to the haemopoietic system. Studies have demonstrated this agent to have a carcinogenic and teratogenic effect when used in animals. In the treatment of each patient, the physician must weigh carefully the possibility of achieving therapeutic benefit against the risk of toxicity. Haemopoietic depression may be severe and lead to fatality, although the total clinical experience suggests that it is rarely necessary to transfuse patients with blood fractions. Symptoms of anorexia, nausea and vomiting are the most frequently noted of all toxic reactions. Over 90% of patients are affected with the initial few doses.
The vomiting lasts 1-12 hours and is incompletely and unpredictably palliated with phenobarbitone and/or proclorperazine.
Rarely DTIC-DOME has caused diarrhoea. Some helpful suggestions include restricting the patient's oral intake of fluids and food for 4-6 hours prior to treatment. The rapid toleration of these symptoms suggest that a central nervous system mechanism may be involved, and usually these symptoms subside after the first 1 or 2 days. Rarely, intractable nausea and vomiting have necessitated discontinuance of DTIC-DOME therapy.
There are a number of minor toxicities that are infrequently noted. Patients have experienced an influenza-like syndrome of fever, myalgia and malaise. This syndrome usually occurs after large, single doses approximately 7 days after treatment with DTIC-DOME, lasting 7-21 days, and it may recur with successive treatments. Toxicity is enhanced when kidney malfunction occurs.
Alopecia has been noted as has facial flushing and facial paraesthesias. Liver function impairment as indicated by increased levels of SGOT and SGPT has been observed in a small percentage of patients. However, generally this is a transient effect and levels return to normal within two weeks. There have been no reports of significant renal function test abnormalities.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT: See under Special Precautions.
IDENTIFICATION: Colourless to ivory, fine crystalline powder. When reconstituted with Water for Injection a clear pale-yellow solution results, pH 3.0-4.0.
PRESENTATION: Vials containing 200 mg of sterile dacarbazine as a lyophilised cake.
STORAGE INSTRUCTIONS: Protect from light. Store between 2°C to 8°C. Keep out of reach of children.
REGISTRATION NUMBER: H/26/312
ZIMBABWE PP 76/9.1.4/582 (200 mg)
NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Bayer (Pty) Ltd 27 Wrench Rd Isando 1600
DATE OF PUBLICATION OF THIS PACKAGE INSERT: May 1976
® = Registered TM of DOME CHEMICALS 17028500/1298
Updated on this site: February 2003 Source: Pharmaceutical Industry