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Hodgkin lymphoma: Treatment of Hodgkin lymphoma (in combination with other chemotherapy agents)
Metastatic malignant melanoma: Treatment of metastatic malignant melanoma
Hypersensitivity to dacarbazine or any component of the formulation
Canadian labeling: Additional contraindications (not in the US labeling): Prior severe myelosuppression
It is recommended that dacarbazine be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents.
In treatment of each patient, the physician must weigh carefully the possibility of achieving therapeutic benefit against the risk of toxicity.
Bone marrow suppression:Hemopoietic depression is the most common toxicity with dacarbazine.
Hepatic effects:Hepatic necrosis has been reported.
Carcinogenic/teratogenic:Studies have demonstrated this agent to have a carcinogenic and teratogenic effect when used in animals.
Note: Dacarbazine is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Basch 2011; Roila 2010).
Hodgkin lymphoma: ABVD regimen: IV: 375 mg/m2 on days 1 and 15 every 4 weeks (in combination with doxorubicin, bleomycin, and vinblastine)
Metastatic malignant melanoma: IV: 250 mg/m2 over 30 minutes once daily on days 1 to 5 every 3 weeks (Middleton 2000)
Metastatic melanoma (off-label dosing/combinations): IV:
CVD regimen: 800 mg/m2 over 60 minutes on day 1 every 3 weeks (in combination with cisplatin and vinblastine) (Atkins 2008; Eton 2002)
Biochemotherapy regimen: 800 mg/m2 over 60 minutes on day 1 every 3 weeks (in combination with cisplatin, vinblastine, interleukin-2 and interferon alfa-2b) (Flaherty 2014) Medullary thyroid cancer, advanced (off-label use): IV: 200 mg/m2 once daily for 5 days every 6 weeks (in combination with fluorouracil and streptozocin) or 600 mg/m2 once daily for 2 days every 3 or 4 weeks (in combination with cyclophosphamide and vincristine) or 250 mg/m2 over 15 to 30 minutes once daily for 5 days every 4 weeks (in combination with fluorouracil) (Orlandi 1994; Schlumberger 1995; Wu 1994). Additional data may be necessary to further define the role of dacarbazine in this condition.
Pancreatic neuroendocrine tumors, advanced (off-label use): IV: 850 mg/m2 over 60 to 90 minutes on day 1 every 4 weeks (Ramanathan 2001).
Pheochromocytoma, malignant (off-label use): IV: 600 mg/m2 once daily for 2 days every 3 or 4 weeks (in combination with cyclophosphamide and vincristine) (Huang 2008). Additional data may be necessary to further define the role of dacarbazine in this condition.
Soft tissue sarcoma, advanced (off-label use): MAID regimen: IV: 250 mg/m2/day as a continuous infusion for 4 days every 3 weeks (total of 1,000 mg/m2/cycle) (in combination with mesna, doxorubicin, and ifosfamide) (Antman 1993; Antman 1998)
Refer to adult dosing.
Note: Dacarbazine is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011).
Hodgkin lymphoma: Children and Adolescents: ABVD regimen: IV: 375 mg/m2 over 30 to 60 minutes on days 1 and 15 every 4 weeks (in combination with doxorubicin, bleomycin, and vinblastine) (Hutchinson 1998)
There are no dosage adjustments provided in the manufacturers labeling. The following adjustments have been recommended (Kintzel 1995):
CrCl 46 to 60 mL/minute: Reduce dose to 80% of usual dose
CrCl 31 to 45 mL/minute: Reduce dose to 75% of usual dose
CrCl ≤30 mL/minute: Reduce dose to 70% of usual dose
There are no dosage adjustments provided in the manufacturers labeling. May cause hepatotoxicity; monitor closely for signs of toxicity.
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]). The manufacturer recommends reconstituting 100 mg and 200 mg vials with 9.9 mL and 19.7 mL SWFI, respectively, to a concentration of 10 mg/mL; some institutions use different standard dilutions (eg, 20 mg/mL). Further dilute for infusion in D5W or NS.
Canadian labeling: Reconstitute the 600 mg vial with 59.1 mL SWFI; further dilute with 150 or 250 mL D5W or NS.
Dacarbazine is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Basch 2011; Dupuis 2011; Roila 2010).
Infuse over 15 to 60 minutes; rapid infusion may cause severe venous irritation. Other infusion durations have been reported; refer to literature and/or regimen for infusion details (may vary by protocol).
Dacarbazine is an irritant; local reactions may occur (Perez Fidalgo 2012). Monitor infusion site.
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
Store intact vials at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F). Protect from light. Extended stability of intact vials outside of the refrigerator has been reported; intact vials are stable for 3 months at room temperature (Cohen 2007). Reconstituted solution is stable for 24 hours at room temperature (20 ‚ °C) and 96 hours under refrigeration (4 ‚ °C) when protected from light (El Aatmani 2002), although the manufacturer recommends use within 72 hours (in the vial) if refrigerated and 8 hours at room temperature. Solutions diluted for infusion (in D5W or NS) are stable for 24 hours refrigerated and for 8 hours at room temperature if protected from light. Decomposed drug turns pink.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Generic: 100 mg (1 ea); 200 mg (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Generic: 200 mg (1 ea)
Stable in NS, SWFI; variable stability (consult detailed reference) in D5W.
Y-site administration: Incompatible with allopurinol, cefepime, piperacillin/tazobactam.
Abiraterone Acetate: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Cannabis: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
CYP1A2 Inducers (Strong): May increase the metabolism of CYP1A2 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Monitor therapy
CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Consider therapy modification
CYP2E1 Inhibitors (Moderate): May decrease the metabolism of CYP2E1 Substrates. Monitor therapy
CYP2E1 Inhibitors (Strong): May decrease the metabolism of CYP2E1 Substrates. Consider therapy modification
Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy
Cyproterone: May decrease the serum concentration of CYP2E1 Substrates. Monitor therapy
Deferasirox: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Obeticholic Acid: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy
Osimertinib: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy
Peginterferon Alfa-2b: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
SORAfenib: May decrease the serum concentration of Dacarbazine. Sorafenib may also increase the concentration of dacarbazines active metabolite. Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Teriflunomide: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination
Vemurafenib: May increase the serum concentration of CYP1A2 Substrates. Management: Consider alternatives to such combinations whenever possible, particularly if the CYP1A2 substrate has a relatively narrow therapeutic index. Consider therapy modification
CBC with differential, liver function
Frequency not always defined.
Central nervous system: Infusion-site pain
Dermatologic: Alopecia
Gastrointestinal: Nausea and vomiting (>90%), anorexia
Hematologic & oncologic: Bone marrow depression (onset: 5 to 7 days; nadir: 7 to 10 days; recovery: 21 to 28 days), leukopenia, thrombocytopenia
<1% (Limited to important or life-threatening): Anaphylaxis, anemia, diarrhea, dysgeusia, eosinophilia, erythema, facial flushing, facial paresthesia, flu-like symptoms (fever, myalgia, malaise), hepatic necrosis, increased liver enzymes (transient), paresthesia, renal function test abnormality, skin photosensitivity, skin rash, urticaria, venous obstruction (hepatic vein)
The terminal half-life is extended to 7.2 hours in patients with renal impairment.
The terminal half-life is extended to 7.2 hours in patients with hepatic impairment.
Concerns related to adverse effects:
- Anaphylaxis: May occur following dacarbazine administration.
- Bone marrow suppression: [US Boxed Warning]: Bone marrow suppression is the most common toxicity; leukopenia and thrombocytopenia may be severe; may result in treatment delays or discontinuation; anemia may also occur. Monitor CBC with differential. The onset for leukopenia is ~14 days (range: 10 to 30 days) and the duration is ~1 to 3 weeks. The onset for thrombocytopenia is ~18 days (range: 12 to 30 days) and the duration is ~1 to 3 weeks.
- Carcinogenic/teratogenic: [US Boxed Warning]: Studies have demonstrated this agent to be carcinogenic and/or teratogenic when used in animals.
- Extravasation: Dacarbazine is an irritant; local reactions may occur (Perez Fidalgo 2012). According to the manufacturer, extravasation may result in tissue damage and severe pain.
- Gastrointestinal toxicity: Dacarbazine is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Basch 2011; Dupuis 2011; Roila 2010).
- Hepatic effects: [US Boxed Warning]: Hepatic necrosis has been reported. Hepatotoxicity may be accompanied with hepatic vein thrombosis and hepatocellular necrosis; may be fatal. Hepatotoxicity usually occurs with combination chemotherapy, but may occur with dacarbazine alone.
Disease-related concerns:
- Hepatic impairment: Use with caution in patients with hepatic impairment; half-life is increased, monitor for toxicity and consider dosage reduction.
- Renal impairment: Use with caution in patients with renal impairment; half-life is increased, monitor for toxicity and consider dosage reduction.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special handling:
- Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
Other warnings/precautions:
- Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician. Carefully evaluate the potential benefits of therapy against the risk for toxicity. Adequate laboratory facilities should be available for appropriate monitoring.
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[US Boxed Warning]: Studies have demonstrated this agent to be carcinogenic and/or teratogenic when used in animals; adverse effects have been observed in animal reproduction studies. Women of reproductive potential should avoid becoming pregnant during treatment. The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). In general, if chemotherapy is indicated, it should be avoided during in the first trimester, there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (Peccatori 2013). An international consensus panel has published guidelines for hematologic malignancies during pregnancy. Dacarbazine is a component of the ABVD regimen, which is used for the treatment of Hodgkin lymphoma. If treatment cannot be deferred until after delivery in patients with early stage Hodgkin lymphoma, ABVD may be administered safely and effectively in the latter phase of pregnancy (based on limited data); for patients with advanced-stage disease, ABVD can be administered in the second and third trimesters (Lishner 2016).
Alkylating agent which is converted to the active alkylating metabolite MTIC [(methyl-triazene-1-yl)-imidazole-4-carboxamide] via the cytochrome P450 system. The cytotoxic effects of MTIC are manifested through alkylation (methylation) of DNA at the O6, N7 guanine positions which lead to DNA double strand breaks and apoptosis. Dacarbazine is non-cell cycle specific (Marchesi 2007).
Exceeds total body water; suggesting binding to some tissue (probably liver) (Perry 2012)
Extensively hepatic to the active metabolite MTIC [(methyl-triazene-1-yl)-imidazole-4-carboxamide]
Urine (~40%; as unchanged drug)
Biphasic: Initial: 19 minutes, Terminal: 5 hours
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience lack of appetite or alopecia. Have patient report immediately to prescriber signs of infection, signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any bleeding that is very bad or that will not stop), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), severe dizziness, passing out, severe nausea, vomiting, or injection site pain or irritation (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.