Dacarbazine

DACARBAZINE

Complete information including dosage, side effects, interactions and pregnancy & breast feeding warnings for patient and professional use

Overview and uses

Dacarbazine is an alkylating agent belonging to triazine, used for the treatment of cancer.

Indication (uses)

  • For the treatment of metastatic malignant melanoma.
  • For the treatment of Hodgkin’s disease as a second line therapy when used in combination with other effective agents.

Pharmacological classification

Alkylating agent (triazine) used for the treatment of cancer.

Brand names

DTIC-Dome, Dacarin

Dosage form

  • Available as an injection in strengths of 100 mg, 200 mg, and 500 mg.
  • Available as vials in the strength of 200 mg/vial.

Mechanism of action

After activation in the liver, it acts by methylating DNA and interfering with its function.

Dosage

  • For malignant melanoma (adult dose)
    • 2 to 4.5 mg/kg IV once a day for 10 days, repeated every 4 weeks or 250 mg/m² IV once a day for 5 days, repeated every 3 weeks.
  • For Hodgkin’s disease (adult dose)
    • 150 mg/m² IV once a day for 5 days repeated every 4 weeks or 375 mg/m² IV once, repeated every 15 days in combination therapy.

Renal dose adjustments

  • Data not available. Dose adjustments may be required.

Hepatic dose adjustments

  • Data not available. Dose adjustments may be required.

Geriatric dose adjustments

  • Data not available. Dose adjustments may be required.

Pediatric Use

  • Data not available. Dose adjustments may be required.

Overdosage

  • No specific antidote is known.
  • Treatment of Overdosage involves
  • General supportive measures.

Side effects or adverse effects

Side effects specific to Dacarbazine

  • Redness, pain or swelling at the site of injection.
  • nausea
  • vomiting
  • loss of appetite
  • diarrhea
  • sores in the mouth and throat
  • hair loss
  • feeling of burning or tingling on the face
  • flushing
  • flu-like symptoms
  • Hemopoietic depression is the most common toxicity with dacarbazine.
  • Hepatic necrosis has been reported.
  • Studies have demonstrated this agent to have a carcinogenic and teratogenic effect when used in animals.
  • In treatment of each patient, the physician must weigh carefully the possibility of achieving therapeutic benefit against the risk of toxicity.

Other side effects

  • Bone marrow depression
    • Bone marrow depression is the most serious side effect/toxicity. It is also a limiting factor for the dose. Infections and bleeding are the common complications.
    • Bone marrow depression results in granulocytopenia, agranulocytosis, thrombocytopenia and aplastic anemia.
    • Consult your doctor as soon as possible if you observe any of the below mentioned symptoms:
      • Sore throat
      • Chills
      • Sudden fever
      • Weakness in limbs
      • Mouth ulcers
      • Bleeding gums
      • Sore mouth
      • Fast heart rate
      • Low blood pressure
      • Sore gums
      • Skin abscesses
      • Rapid breathing
      • Rapid progression of infection of any organ
      • Rapid progression of Septicemia
    • Gastrointestinal side effects
      • Nausea and vomiting are commonly observed with anti-cancer medicines.
      • Mucositis – painful inflammation and ulceration of mucus membrane lining the digestive tract.
      • Diarrhea, shredding of mucosa and haemorrhage due to decreased rate of renewal of gastrointestinal mucosa lining.
    • Skin
      • Alopecia or hair loss.
      • Dermatitis
    • Oral side effects
      • Breaches during chewing.
      • Depression of immunity due to reduction in number of WBCs largely increases the risk of oral infections.
      • Bleeding gums
      • Rapid progression of dental caries.
    • Gonadal side effects
      • Infertility due to Oligozoospermia in males.
      • Impotence in males.
      • Loss or reduces sex drive.
      • Inhibition of ovulation in females
      • Amenorrhea in females.
      • Damage to germinal cells may lead to mutagenesis.
    • Lymphoreticular tissue
      • Lymphocytopenia (reduced number of lymphocytes)
      • Inhibition of lymphocyte function.
      • Suppression of immunity due to bone marrow depression and reduced lymphocyte function highly increases the risk of opportunistic infections like:
        • Candida and other infections causing deep mycosis.
        • Cytomegalo virus
        • Herpes zoster
        • Pneumocystis jiroveci
        • Toxoplasma
      • Fetal side effects
        • Use of anti-cancer medicines in pregnant women may cause fetal damage leading to:
          • Fetal death
          • Abortion
          • Teratogenesis
        • Renal side effects
          • Renal failure, Gout and Urate stones may develop in urinary tract.
        • Hyperuricemia
          • An elevated level of uric acid is common in leukemia and bulky lymphomas.
  • Please note: The side effects mentioned above are from the reported cases. However, side effects are not limited to above mentioned conditions and symptoms. Consult your doctor as soon as possible if you feel or observe any symptoms that you relate to your treatment.

Warnings & Precautions

  • The hematologic profile should be monitored.
  • Hematopoietic toxicity may warrant suspension or cessation of therapy.
  • Patients should be advised to use sunscreens and to avoid sun exposure following administration of this drug.

Contraindications

  • Contraindicated in patients with previous hypersensitivity to Dacarbazine.

Pregnancy & breast feeding warnings

  • Pregnancy
    • Category C, which means animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
  • Nursing
    • It is not known whether Dacarbazine is excreted in human breast milk or not.
    • Since many drugs are excreted in milk and because of the potential for side effects in nursing infants, a decision should be made whether to discontinue drug or to discontinue nursing.

Interactions

Drug – drug interactions

  • Concomitant use of Dacarbazine with following drugs/medicines should be strictly avoided.
    • Leflunomide as it increases the risk of infections.
    • Adalimumab as it increases the risk of infections.
    • Teriflunomide as it increases the risk of infections.
    • Certolizumab as it increases the risk of infections.
    • Clozapine as it may lower the WBC count.
    • Tofacitinib as it increases the risk of infections.
    • Deferiprone as it may lower the WBC count.
    • Etanercept as it increases the risk of infections.
    • Fingolimod as it increases the risk of infections.
    • Anakinra as it increases the risk of infections.
    • Golimumab as it increases the risk of infections.
    • Infliximab as it increases the risk of infections.
    • Thalidomide may increase the risk of dangerous blood clots.
    • Lomitapide may cause liver problems and concomitant use with Dacarbazine may increase that risk.
    • Talimogene may increase the risk of potentially life threatening herpes infection.
    • Nalidixic acid as the combination may cause unusual bruising or bleeding, nausea, stomach pain, unusual weakness, low fever and loss of appetite.
    • Natalizumab as it increases the risk of infections.
    • Thiotepa as it may affect the bone marrow function.
    • Brentuximab may cause liver problems and concomitant use with Dacarbazine may increase that risk.
    • Doxorubicin may increase the side effects of Dacarbazine, especially on bone marrow function.
    • Aldesleukin may increase the risk of tumor lysis syndrome, which is associated with certain electrolyte and chemical imbalances in the blood and kidney failure.
    • Alefacept as it increases the risk of infections.
    • Alemtuzumab as it increases the risk of infections.
    • Efalizumab as it increases the risk of infections.
    • Filgrastim as it may affect the effect of Dacarbazine.
    • Fluorouracil as it may increase the side effect of Dacarbazine.
    • Fludarabine as it may affect the bone marrow function.
    • Azathioprine as it increases the risk of infections.
    • Bedaquiline may cause liver problems and concomitant use with Dacarbazine may increase that risk.
    • Etoposide as it may affect bone marrow function.
    • Efavirenz as it may increase the risk of liver toxicity.
    • Docetaxel as it may affect the bone marrow function.
    • Bendamustine may increase the side effects of Dacarbazine, especially on bone marrow function.
    • Vinorelbine as it may affect the bone marrow function.
    • Busulfan may increase the side effects of Dacarbazine, especially on bone marrow function.
    • Bleomycin may increase the side effects of Dacarbazine, especially on bone marrow function.
    • Canakinumab as it increases the risk of infections.
    • Cisplatin may increase the side effects of Dacarbazine, especially on bone marrow function.
    • Cladribine as it increases the risk of infections.
    • Clofarabine may increase the risk of liver toxicity.
    • Capecitabine may increase the side effects of Dacarbazine, especially on bone marrow function.
    • Carboplatin may increase the side effects of Dacarbazine, especially on bone marrow function.
    • Daunorubicin may increase the side effects of Dacarbazine, especially on bone marrow function.
    • Imatinib as it may affect the bone marrow function.
    • Ifosfamide as it may affect the bone marrow function.
    • Idarubicin as it may affect the bone marrow function.
    • Mechlorethamine as it may affect the bone marrow function.
    • Melphalan as it may affect the bone marrow function.
    • Mitomycin as it may affect the bone marrow function.
    • Mitoxantrone as it may affect the bone marrow function.
    • Mercaptopurine as it may affect the bone marrow function.
    • Nelarabine as it may affect the bone marrow function.
    • Niraparib as it may potentiate the bone marrow toxicity.
    • Omacetaxine as it increases the risk of serious infections.
    • Oxaliplatin as it may affect the bone marrow function.
    • Olaparib as it increases the risk of bone marrow impairment which may lead to myelodysplastic syndrome or acute myeloid leukemia.
    • Ganciclovir may increase the side effects of Dacarbazine, especially on bone marrow function.
    • Gemcitabine as it may affect the bone marrow function.
    • Dacarbazine may increase the side effects of Carmustine, especially on bone marrow function.
    • Decitabine may increase the side effects of Dacarbazine, especially on bone marrow function.
    • Dactinomycin may increase the side effects of Dacarbazine, especially on bone marrow function.
    • Denosumab may increase the risk of serious infections involving the skin.
    • Ocrelizumab may increase the risk of serious infections.
    • Pentostatin as it may affect the bone marrow function.
    • Ruxolitinib as it may affect the bone marrow function.
    • Rilonacept as it increases the risk of serious infections.
    • Streptozocin as it may affect the bone marrow function.
    • Ustekinumab as it increases the risk of serious infections.
    • Topotecan as it may affect the bone marrow function.
    • Trabectedin as it may increase the risk of liver toxicity.
    • Abiraterone may increase the serum concentration of Dacarbazine.
    • Acetyldigitoxin may decrease the cardiotoxic effects of Dacarbazine.

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By |2018-05-17T06:02:48+00:00August 11th, 2017|medicines|0 Comments

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