Dacarbazine (Monograph)

Brand name: DTIC-Dome
Drug class: Antineoplastic Agents
VA class: AN300
CAS number: 4342-03-4

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Introduction

Antimetabolite antineoplastic agent; a purine analog.

Uses for Dacarbazine

Melanoma

A systemic treatment of choice for the palliative treatment of metastatic melanoma. Has been used alone and in combination regimens^{† [off-label]}. Optimal regimen remains to be established.

Hodgkin’s Disease

Treatment of advanced Hodgkin’s disease in combination with other antineoplastic agents. Often used with doxorubicin, bleomycin, and vinblastine (ABVD regimen).

Dacarbazine Dosage and Administration

General

• Consult specialized references for procedures for proper handling and disposal of antineoplastic drugs.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer only by IV injection or infusion. Extremely irritating to tissues; avoid extravasation. (See Local Effects under Cautions.)

Reconstitution

Reconstitute vial containing 100 or 200 mg of dacarbazine powder with 9.9 or 19.7 mL, respectively, of sterile water for injection to provide a solution containing 10 mg/mL.

Dilution

Reconstituted solution may be further diluted with 5% dextrose or 0.9% sodium chloride injection and infused IV.

Rate of Administration

IV injection: Administer over 1 minute.

IV infusion: Infuse diluted solution over 15–30 minutes.

Dosage

Optimize results and minimize adverse effects by basing dose on clinical and hematologic response, patient tolerance, and other chemotherapy or irradiation being used.

Consult published protocols for dosages in combination regimens and method and sequence of administration.

Adults

Melanoma

Metastatic Melanoma

IV

2–4.5 mg/kg daily for 10 days; may repeat at 4-week intervals.

Alternatively, 250 mg/m² daily for 5 days; may repeat at 3-week intervals.

Hodgkin’s Disease

IV

150 mg/m² daily for 5 days in combination with other antineoplastic agents; may repeat every 4 weeks.

Alternatively, 375 mg/m² on day 1, in combination with other antineoplastic agents; repeat every 15 days.

Cautions for Dacarbazine

Contraindications

• Hypersensitivity to dacarbazine or any ingredient in the formulation.

Warnings/Precautions

Warnings

Administer only under supervision of a qualified clinician experienced in therapy with antineoplastic agents. (See Boxed Warning.)

Hematologic Effects

Myelosuppression (principally severe leukopenia and thrombocytopenia) occurs commonly, generally 2–4 weeks after the last dose; fatal leukopenia and thrombocytopenia reported. Anemia can occur.

Carefully monitor hematologic status during therapy; evaluate leukocyte, erythrocyte, and platelet counts at frequent intervals.

Hematopoietic toxicity (generally leukocyte count <3000/mm³ and platelet count <100,000/mm³) may require temporary withdrawal or discontinuance of the drug.

Hepatic Effects

Hepatotoxicity complicated by hepatic vein thrombosis and hepatocellular necrosis resulting in death has been reported. More common with combination regimens but also occurs with dacarbazine alone.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity and embryolethality demonstrated in animals.

Sensitivity Reactions

Hypersensitivity Reactions

Possible hypersensitivity reactions, including anaphylaxis.

Photosensitivity

Photosensitivity reactions reported rarely.

General Precautions

Carcinogenicity

Carcinogenic effects reported in animals; importance in humans not known.

Local Effects

Extravasation may result in tissue damage and severe pain.

Undiluted solutions administered by IV injection may cause severe pain and phlebitis; some clinicians recommend dilution and infusion.

Hot packs may relieve local pain, burning sensation, and irritation at the injection site.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether dacarbazine is distributed into milk; discontinue nursing or the drug.

Common Adverse Effects

Anorexia, nausea, vomiting, leukopenia, thrombocytopenia.

Drug Interactions

Metabolized by hepatic microsomal enzymes.

Drugs Affecting Hepatic Microsomal Enzymes

Enzyme inducers: Possible increased metabolism of dacarbazine.

Specific Drugs

Dacarbazine Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from the GI tract.

Distribution

Extent

Volume of distribution exceeds total body water content, suggesting localization in a body tissue, probably the liver.

Crosses blood-brain barrier to a limited extent; CSF concentrations approximately 14% of plasma concentrations.

Not known whether dacarbazine crosses the placenta or is distributed into milk.

Plasma Protein Binding

Slightly bound.

Elimination

Metabolism

Extensively metabolized; hepatic microsomal enzymes are involved. Some metabolites may contribute to the antineoplastic effect of the drug.

Elimination Route

Excreted in urine by tubular secretion; about 46% of an administered dose is excreted in urine within 6 hours (about 50% as unchanged drug and 50% as 5-amino-1H-imidazole-4-carboxamide [AIC]). (See Actions.)

Half-life

Biphasic; initial-phase half-life averages 19 minutes; terminal half-life averages 5 hours.

Stability

Storage

Parenteral

Powder for Injection

2–8°C; protect from light.

Use reconstituted solutions containing 10 mg/mL in sterile water for injection within 8 hours if stored at room temperature or 72 hours if stored at 4°C.

Use solutions further diluted with ≤500 mL of 5% dextrose or 0.9% sodium chloride injection within 8 hours if stored at room temperature or 24 hours if stored at 4°C.

Compatibility

Parenteral

Solution Compatibility

Drug Compatibility

Actions

• Appears to exert cytotoxic effect by acting as an alkylating agent.

• Does not exhibit cell cycle-phase specificity.

• Synthetic analog of naturally occurring purine precursor 5-amino-1H-imidazole-4-carboxamide (AIC).

Advice to Patients

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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