Index
It is an anticancer chemotherapy drug used alone or with other drugs to slow or stop the growth of cancer cells.
Dacarbazine uses
Dacarbazine is used to treat types of cancer , such as skin cancer that spreads (metastatic malignant melanoma) and Hodgkin’s disease.
Dosage
Soft tissue sarcoma : intravenous.
Adult : in combination with doxorubicin: 250 mg / m 2 once daily by infusion over 15-30 minutes for 5 days, repeat at 3 week intervals.
Metastatic melanoma: intravenous.
Adult : 2-4.5 mg / kg daily for 10 days, repeat at 4-week intervals or 200-250 mg / m 2 period through inj for 1 min for 5 days, repeat at 3-week intervals or 850 mg / m 2 through infusion for 15-30 minutes once every 3 weeks.
Hodgkin’s disease: intravenous.
Adult : In combination with doxorubicin, bleomycin and vinblastine (ABVD regimen): 150 mg / m 2 daily for 5 days, repeat at 4-week intervals or 375 mg / m 2 by infusion over 15-30 minutes once every 15 days.
Reconstitution
Reconstitute 100 mg and 200 mg w / 9.9 ml and 19.7 ml sterile water for inj, respectively, at a concentration of 10 mg / ml. Further dilute for infusion by adding up to 250 ml of 5% dextrose or 0.9% NaCl.
Incompatibility
Dacarbazine is incompatible with allopurinol, cefepime, piperacillin / tazobactam, heparin, hydrocortisone , sodium succinate, L-cysteine, sodium hydrogen carbonate.
Dacarbazine contraindications
This medicine is contraindicated in the following cases:
- Hypersensitivity Severe myelosuppression (eg, Leukopenia and / or thrombocytopenia ).
- Severe liver or kidney insufficiency.
- Pregnancy and breastfeeding.
Special precautions
Liver and kidney failure.
Adverse reactions
- Anorexia.
- Vomiting
- Sickness.
- Acne.
- Alopecia.
- Facial redness and paresthesia.
- Orthostatic hypotension.
- ECG abnormalities.
- Pseudofluenza syndrome.
- Myalgia.
- General discomfort.
- Blurry vision.
- Seizures
- Headache.
- Confusion.
- Lethargy.
- Pain at the graft site.
- Tissue damage
- Cellulitis.
Rarely
- Diarrhea.
- Photosensitivity.
- Estomatitis.
Potentially fatal
- Anaphylaxis.
- Bone marrow suppression (particularly leukopenia and thrombocytopenia).
- Hepatotoxicity accompanied by hepatic vein thrombosis and hepatocellular necrosis.
Counseling the patient
It can affect the ability to drive or operate machinery.
Monitoring parameters
CBC monitoring with differential, leukocytes, erythrocytes and platelet count, LFT; infusion site for extravasation. Assess for signs of infection and hepatotoxicity.
Overdose
Symptoms:
- Severe bone marrow suppression.
- Sickness.
- Vomiting
- Diarrhea.
Management: supportive treatment.
Dacarbazine interactions
Increased metabolism when used with enzyme inducers (eg, barbiturates, rifampin, phenytoin).
May enhance the effect of mercaptopurine, azathioprine, and allopurinol. It can impair the immune response to vaccines. May enhance the effects of methoxsalen due to photosensitization.
Interaction with food
Increased hepatotoxic effect with alcohol.
Mechanism of action
Description
Dacarbazine is a non-cell cycle specific antineoplastic agent. The exact mechanism of action by which it exerts cytotoxic effects is not yet clear.
However, three possible mechanisms have been postulated, including inhibition of DNA synthesis by acting as a purine analog, action as an alkylating agent, and interaction with the sulfhydryl group in inhibiting bacterial cell growth.
Distribution
Dacarbazine is distributed rapidly; located in some tissues of the body, probably in the liver. Cross the blood-brain barrier. Volume of distribution: exceeds total body water content. Plasma protein binding: 5%.
Metabolism
It is extensively metabolized in the liver by CYP1A2 and CYP2E1 enzymes (and possibly in tissues by CYP1A1) to 5- (3-methyl-triazene-1-yl) -imidazole-4-carboxamide (MTIC) which is further metabolized to the main metabolite, 5-amino-imidazole-4-carboxamide (AIC).
Excretion
Dacarbazine is excreted in the urine, approximately 40% as unchanged drug. Elimination half-life: Biphasic: 19 min (initial); 5 hours (terminal).
Storage
Store between 2-8 ° C. Protect from light Protect from light This is a cytotoxic drug, avoid contact with skin or mucous membranes by wearing gloves and protective equipment.
Wash your hands before and after handling. Pregnant staff should not handle this product. Any unused portion should be disposed of according to standard procedures.
MIMS class
Cytotoxic chemotherapy.
ATC classification
L01AX04 – dacarbazine; it belongs to the class of other alkylating agents. Used in the treatment of cancer.
