DACARBAZINE

Chemistry - An antineoplastic agent, dacarbazine occurs as a colorless to ivory colored crystallinesolid. It is slightly soluble in water or alcohol. After reconstituting with sterile water, the injectionhas a pH of 3-4. Dacarbazine may also be known as DTIC, DIC, or imidazole carboxamide.

Storage, Stability, Compatibility

The powder for injection should be protected from light andkept refrigerated. If exposed to heat the powder may change color from ivory to pink, indicatingsome decomposition.
After reconstituting with sterile water for injection the resultant solution is stable for up to 72hours if kept refrigerated or up to 8 hours at room temperature. If further diluted (up to 500 ml)with either D5W or normal saline the solution is stable for at least 24 hours when refrigerated (8hours at room temperature under normal room lighting).

Pharmacology - DACARBAZINE

The mechanism for dacarbazine's antineoplastic activity has not been preciselydetermined, but it is believed the drug acts as an alkylating agent. It possesses minimal immunosuppressant activity and is probably not a cell cycle-phase specific drug.
Uses, Indications - Dacarbazine has been used to treat lymphoreticular neoplasms in dogs. It hasminimal activity against osteosarcomas and malignant melanomas.

Pharmacokinetics - DACARBAZINE

Dacarbazine (DTIC) is poorly absorbed from the GI tract and is administeredintravenously. The drug's distribution characteristics are not well known, but it is only slightlybound to plasma proteins and probably concentrates in the liver. Only limited amounts cross theblood-brain barrier and it is unknown if it crosses the placenta or enters maternal milk. Dacarbazineis extensively metabolized in the liver and is excreted in the urine via tubular secretion.

Contraindications, Precautions, Reproductive Safety

Dacarbazine (DTIC) is contraindicatedin patients who are hypersensitive to it. DTIC can cause life-threatening toxicity. It should only beused where adequate monitoring and support can be administered. It should be used with caution inpatients with preexisting bone marrow depression, hepatic or renal dysfunction, or infection.
DTIC is teratogenic in rats at higher than clinically used dosages. It should be used duringpregnancy only when the potential benefits outweigh its risks. While it is unknown if DTIC entersmaternal milk, the potential carcinogenicity of the drug warrants using extreme caution in allowingthe mother to continue nursing while receiving DTIC.

Adverse Effects, Warnings

Gastrointestinal toxicity (including vomiting, anorexia, diarrhea) canbe commonly seen after administration. Bone marrow toxicity is usually asymptomatic withleukocyte and platelet nadirs seen several weeks after therapy. Occasionally severe hematopoietictoxicity can occur with fatal consequences. Other delayed toxic effects can include, alopecia, severehepatotoxicity, renal impairment, and photosensitivity reactions. These delayed reactions are morerarely seen.
Because DTIC can cause extensive pain and tissue damage, avoid extravasation injuries. Severepain at the injection site can occur if giving the concentrated drug; dilution and administration by IVinfusion is recommended.
There is increasing evidence that chronic exposure by health care-givers to antineoplastic drugsincreases the mutagenic, teratogenic and carcinogenic risks associated with these agents. Properprecautions in the handing, preparation, administration and disposal of these drugs and suppliesassociated with their use is strongly recommended.

Overdosage, Acute Toxicity

Because of the toxic potential of this agent, iatrogenic overdosesmust be avoided. Recheck dosage calculations. See Adverse Effects above for additional information on toxicity.

Drug Interactions

Drugs that induce liver microsomal enzymes (e.g., phenobarbital) mayincrease the metabolism of DTIC. Other bone marrow depressant drugs (e.g., other neoplastics, chloramphenicol, flucytosine, amphotericin B or colchicine) may cause additive myelosuppression when used with DTIC.