Dacarbazine drug.pptx management of cancer

Dacarbazine.pptx management of cancer

1. Dacarbazine Allan Oywaya Odera GMOP/M/3405/09/24 1

2. Class and Mechanism of Action Class: Alkylating agent (Thiazine) Mechanism of action: Non-cell cycle specific Inhibit cell division by forming covalent bonds between alkyl groups of the drug and guanine bases of DNA Cross linking causes DNA double strands breaks, interferes with transcription , stops replication of DNA 2

3. Pharmacokinetics Absorption : A dministered IV, bypasses gastrointestinal absorption. Distribution : M oderately bound to plasma proteins (around 5%) and widely distributed in tissues. It crosses the blood-brain barrier poorly Metabolism : It is metabolized in the liver, primarily by cytochrome P450 enzymes, to active metabolites MTIC (5-aminoimidazole-4-carboxamide) Excretion : Excreted primarily via the kidneys. About 40%-50% of the dose is excreted unchanged in the urine, with a half-life of approximately 5 hrs 3

4. Indications, Dose, Route Indications: Hodgkin’s lymphoma, metastatic m alignant m elanoma, soft t issue s arcomas, neuroendocrine tumors Dose: Calculated based on patient characteristics, type of tumor. Hodgkin Lymphoma (150 mg/m² IV qDay for 5 days, repeat q4Weeks) Metastatic malignant melanoma ( 250 mg/m² IV qDay for 5 days, repeat q3Weeks) Dacarbazine is administered IV (infusion, usually over a period of 15 to 60 minutes) 4

5. Dose limiting factors Bone Marrow Suppression: M ost significant dose-limiting factor Gastrointestinal Toxicity: Severe nausea and vomiting Hepatotoxicity: Liver toxicity and elevated liver enzymes. Renal Dysfunction: Primarily excreted by the kidneys 5

6. Side effects and Mitigation Most Common Side Effects: Nausea and Vomiting (use of pre-medication with antiemetics , ensuring good hydration) Myelosuppression i.e., Leukopenia, thrombocytopenia, anemia (regular blood count monitoring, provide blood/platelet transfusions) Fatigue (adequate rest, light physical activity, and balanced nutrition) 6

7. Side effects and Mitigation Minor Side Effects: Flu-like Symptoms i.e., fever, chills, muscle aches (Symptomatic treatment with acetaminophen or NSAIDs, ensure hydration and rest) Injection Site Reactions i.e., pain, redness, swelling (Ensure proper IV technique, apply warm or cold compresses) Diarrhea (Encourage hydration, and use antidiarrheal agents like loperamide ) Loss of Appetite (Recommend small, frequent meals, high-calorie snacks, and nutritional supplements) 7

8. Side effects and Mitigation Rare Side Effects: Hepatotoxicity :(Mitigation: Regular monitoring of liver function tests (LFTs). Discontinue or reduce dosage if liver dysfunction occurs) Renal Toxicity:Mitigation : Monitor renal function (creatinine, BUN) regularly, a djust the dose in patients with impaired renal function. Photosensitivity:Mitigation : Advise patients to avoid direct sunlight, use protective clothing and sunscreen. 8

9. Contraindications Hypersensitivity to Dacarbazine Severe Hepatic or Renal Impairment Pregnancy Breastfeeding Severe Bone Marrow Suppression 9

10. Interactions and consequences Myelosuppressive Agents : R isk of severe bone marrow suppression Live Vaccines : Immunosuppression - infection or reduced vaccine efficacy Hepatotoxic Drugs : Heightened risk of liver damage CYP450 Interactions : CYP1A2 inhibitors increase toxicity Photosensitizing Drugs : Enhanced risk of skin reactions; avoid sun exposure 10

11. Monitoring parameters Complete Blood Count (CBC) Liver Function Tests (LFTs) Renal Function Electrolytes Signs of Infection or Bleeding 11

12. Storage Unopened Vials: Store at 2°C to 8°C (36°F to 46°F), in the refrigerator. Protect from Light: Dacarbazine is sensitive to light Reconstituted Solution: Used immediately or stored at 2°C to 8°C and used within 8 hours. 12

13. References Brunton , L. L., Hilal-Dandan , R., & Knollmann , B. C. (2017). Goodman & Gilman's: The pharmacological basis of therapeutics (13th ed.). McGraw-Hill Education. Ritter, J. M., Flower, R. J., Henderson, G., & Loke , Y. K. (2020). Rang & Dale's pharmacology (9th ed.). Elsevier.Katzung , B. G. (2018). Basic and clinical pharmacology (14th ed.). McGraw-Hill Education. Wecker , L., & Golan, D. E. (2018). Brody’s human pharmacology: Molecular to clinical (6th ed.). Elsevier. Bennett, P. N., Brown, M. J., & Sharma, P. (2019). Clinical pharmacology (12th ed.). Elsevier. 13

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