DTIC-Dome

Other Alkylating Agents

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Emetic Risk
High
Administer routine antiemetic prophylaxis prior to treatment.
Extravasation Risk
Irritant

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Dacarbazine is administered intravenously.
Reconstitution:
Reconstitute 100 or 200 mg vials with 9.9 or 19.7 mL, respectively, of sterile water for injection to give IV solutions containing 10 mg/mL of dacarbazine.
Intravenous bolus:
Withdraw the appropriate dose from the reconstituted IV solution and administer by slow IV push over 2 to 3 minutes.
Intravenous infusion:
Withdraw the appropriate dose from the reconstituted IV solution and dilute in 250 mL of 5% Dextrose injection or 0.9% Sodium Chloride injection. Infuse over 15 to 30 minutes.

Reconstitution:
Reconstitute dacarbazine to a concentration of 5 mg/0.5 mL. Add 0.2 mL of 8.4% sodium bicarbonate solution (1 mEq/mL) per 5 mg of dacarbazine to neutralize citric acid present in the commercial formulation (DTIC-Dome(R)).

thrombosis / Delayed / 0-1.0
hepatic necrosis / Delayed / 0-1.0
hepatotoxicity / Delayed / Incidence not known
tissue necrosis / Early / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
new primary malignancy / Delayed / Incidence not known

erythema / Early / 1.0-10.0
elevated hepatic enzymes / Delayed / 0-1.0
neutropenia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
bone marrow suppression / Delayed / Incidence not known
anemia / Delayed / Incidence not known

urticaria / Rapid / 1.0-10.0
malaise / Early / 1.0-10.0
myalgia / Early / 1.0-10.0
fever / Early / 1.0-10.0
diarrhea / Early / 0-1.0
photosensitivity / Delayed / 0-1.0
vomiting / Early / 90.0
nausea / Early / 90.0
anorexia / Delayed / 90.0
flushing / Rapid / Incidence not known
alopecia / Delayed / Incidence not known
paresthesias / Delayed / Incidence not known
injection site reaction / Rapid / Incidence not known

Dacarbazine therapy is commonly associated with bone marrow suppression, especially neutropenia and thrombocytopenia, but anemia may also occur. Patients should be allowed to recover their blood cell counts to normal prior to dacarbazine administration. Dacarbazine should be used cautiously in patients who have had previous myelosuppressive therapy such as chemotherapy or radiation therapy. Close monitoring of hematologic parameters is necessary during dacarbazine therapy. Administration of dacarbazine requires an experienced clinician knowledgeable in the use of cancer chemotherapeutic agents. Patients with an active infection should be treated prior to receiving dacarbazine. Patients with a history of varicella zoster, other herpes infection (e.g., herpes simplex), or other viral infection are at risk for reactivation of the infection when treated with chemotherapy.

Dacarbazine is metabolized via hepatic pathways, so dosage adjustments may be necessary. Preexisting hepatic disease or renal impairment can cause accumulation of the drug worsening dacarbazine's toxicity. Dosing may need to be reduced in either clinical situation. Rarely, hepatotoxicity, including hepatic vein thrombosis and hepatic necrosis resulting in death, has been reported with dacarbazine therapy. Hepatic toxicity has been observed mostly when dacarbazine has been administered concomitantly with other chemotherapy agents; however, it has also been reported in some patients treated with dacarbazine alone.

Dacarbazine has been shown to be carcinogenic in animal studies. The development of a new primary malignancy is a possibility following dacarbazine therapy.

Dacarbazine was teratogenic in rats at doses 20-times the daily human dose on day 12 of gestation; fetal skeletal anomalies were observed in rabbits who received doses 7-times the daily human dose on days 6 to 15 of gestation. Dacarbazine may cause fetal harm when used during pregnancy, based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid pregnancy during dacarbazine therapy.

DTIC-Dome

Rx

Alkylating antineoplastic agent; used in the treatment of melanoma, sarcoma, and Hodgkin's disease.

250 mg/m2 IV once daily for 5 days repeated every 3 weeks OR 2 to 4.5 mg/kg IV once daily for 10 day repeated every 4 weeks.

850 mg/m2 IV plus ipilimumab 10 mg/kg IV repeated every 3 weeks (at weeks 1, 4, 7, and 10) for 4 doses followed by dacarbazine 850 mg/m2 IV every 3 weeks through week 22 (if no progressive disease) as induction therapy resulted in favorable overall survival in a randomized, double-blind, placebo-controlled, phase III trial. At week 24, patients with stable disease or an objective response received maintenance therapy with ipilimumab 10 mg/kg IV every 12 weeks until progressive disease.

375 mg/m2 IV day 1 repeated every 15 days in combination with other effective drugs. An alternative regimen is dacarbazine 150 mg/m2 IV daily on days 1, 2, 3, 4, and 5 repeated every 4 weeks in combination with other effective drugs.

375 mg/m2 IV in combination with brentuximab vedotin 1.2 mg/kg IV (not to exceed 120 mg/dose), doxorubicin 25 mg/m2 IV, and vinblastine 6 mg/m2 IV each given on days 1 and 15 repeated every 28 days for up to 6 cycles was evaluated in a randomized, phase III trial. Patients should receive primary prophylaxis with a granulocyte colony-stimulating factor due to the high incidence of febrile neutropenia.

250 mg/m2/day as a continuous IV infusion (CIV) for 4 days plus doxorubicin 15 mg/m2/day CIV for 4 days, ifosfamide 2,000 mg/m2/day CIV for 3 days, and mesna 2,000 mg/m2/day CIV for 4 days repeated every 21 days (MAID regimen) until disease progression (or a cumulative doxorubicin dose of 450 mg/m2) was evaluated in 69 patients with unresectable or metastatic Ewing sarcoma, osteosarcoma, or rhabdomyosarcoma in a nonrandomized, phase II trial. Due to life-threatening myelosuppression in the first 15 patients treated, the ifosfamide and mesna doses were reduced from 2,500 mg/m2/day to 2,000 mg/m2/day. Of the 31 patients with osteosarcoma, the ORR was 26% (complete response, 3%), the median time to progression was 6 months, and the median overall survival time was 10 months. Additionally, 1 patient with osteosarcoma who received multimodal therapy with surgery and/or radiotherapy had long-term disease free survival.

250 mg/m2/day as a continuous IV infusion (CIV) for 4 days plus doxorubicin 15 mg/m2/day CIV for 4 days, ifosfamide 2,000 mg/m2/day CIV for 3 days, and mesna 2,000 mg/m2/day CIV for 4 days repeated every 21 days (MAID regimen) until disease progression (or a cumulative doxorubicin dose of 450 mg/m2) has been studied. The MAID regimen was evaluated in 69 patients with unresectable or metastatic Ewing sarcoma, osteosarcoma, or rhabdomyosarcoma in a nonrandomized, phase II trial. Due to life-threatening myelosuppression in the first 15 patients treated, the ifosfamide and mesna doses were reduced from 2,500 mg/m2/day to 2,000 mg/m2/day. Of the 13 patients with Ewing sarcoma, the overall response rate was 77% (complete response, 15%), the median time to progression was 14 months, and the median overall survival time was 28 months. Additionally, 3 patients with Ewing sarcoma who received multimodal therapy with surgery, radiotherapy, or both had long-term disease free survival.

250 mg/m2/day as a continuous IV infusion (CIV) for 4 days plus doxorubicin 15 mg/m2/day CIV for 4 days, ifosfamide 2,000 mg/m2/day CIV for 3 days, and mesna 2,000 mg/m2/day CIV for 4 days repeated every 21 days (MAID regimen) until disease progression (or a cumulative doxorubicin dose of 450 mg/m2) was evaluated in 69 patients with unresectable or metastatic Ewing sarcoma, osteosarcoma, or rhabdomyosarcoma (RMS) in a nonrandomized, phase II trial. Due to life-threatening myelosuppression in the first 15 patients treated, the ifosfamide and mesna doses were reduced from 2,500 mg/m2/day to 2,000 mg/m2/day. Of the 25 patients with RMS, the ORR was 64% (complete response, 28%), the median time to progression was 10 months, and the median overall survival time was 15 months. Additionally, 3 patients with RMS who received multimodal therapy with surgery and/or radiotherapy had long-term disease-free survival.

250 mg/m2 per day as a continuous IV infusion over 24 hours (CIV) for 4 days in combination with doxorubicin 15 mg/m2 per day CIV for 4 days, ifosfamide 2,000 mg/m2 per day CIV for 3 days, and mesna 2,500 mg/m2 per day CIV for 4 days repeated every 21 days (median of 3 cycles) (MAID regimen) was evaluated in patients with soft-tissue and bone sarcomas in a randomized, phase III trial. Five cycles of an intensified MAID regimen was compared with 6 cycles of a more standard MAID regimen (dacarbazine 300 mg/m2 per day IV over 1 hour on days 1, 2, and 3 plus doxorubicin 20 mg/m2 per day as an IV bolus or CIV on days 1, 2, and 3; ifosfamide 2.5 grams/m2 per day IV over 3 hours on days 1, 2 and 3; and mesna 2.5 grams/m2 per day CIV on days 1, 2, and 3) in patients with inoperable locally advanced or metastatic soft-tissue sarcoma in another randomized, phase III study.

The use of dacarbazine for the treatment of carcinomatous meningitis due to melanoma has not been established. Dacarbazine doses of 5 mg, 10 mg, or 20 mg administered by lumbar puncture or intraventricularly via an Ommaya reservoir in 2 patients with melanoma and CNS involvement in a small case series. Both patients had received radiotherapy (2,000 cGy in 4 fractions) prior to receiving dacarbazine. In a 25-year-old woman, 6 doses of intrathecal dacarbazine (5 mg, 10 mg, 10 mg, 10 mg, 20 mg, and 20 mg) were given over a period of 25 days. Cerebrospinal fluid (CSF) cytology decreased from Papanicolaou class IV to II and the patient experienced symptom improvement. However, she presented with a 1.9 cm left occipital metastasis 21 weeks after treatment and received an additional 30 mg of dacarbazine intraventricularly through an Ommaya reservoir over a period of 15 days. The CSF cytology class again decreased (from class V to II) but the patient died 4 months later. In a 52-year-old man, intrathecal dacarbazine was given twice weekly for 6 doses (5 mg, 10 mg, 10 mg, 10 mg, 20 mg, and 20 mg); the first 3 doses were administered via lumbar puncture and the last 3 doses were administered intraventricularly via an Ommaya reservoir. The patient experienced severe hypertension (blood pressure increase from 140/90 to 300/170 mmHg), hyperventilation, flushing, and fecal incontinence during the sixth intrathecal dacarbazine dose; the episode abated 45 minutes after antihypertension medicine was given. Therapy was discontinued and the patient died 4 months later.
intrathecal

Dacarbazine as a component of MADDOC and ACVD has been studied. 750 mg/m2 IV every 6 to 8 weeks plus mechlorethamine 4 mg/m2 IV, doxorubicin 40 mg/m2 IV, cisplatin 45 mg/m2 IV, vincristine 2 mg/m2 IV (Max dose: 2 mg), and cyclophosphamide 750 mg/m2 IV repeated every 3 to 4 weeks (MADDOC regimen) was given to 25 patients aged 13 to 38 months in a nonrandomized study; 7 patients received MADDOC for up to 2 years (n = 7) and 18 patients received 2 cycles of induction therapy with cisplatin 100 mg/m2 IV on day 1 and cyclophosphamide 1,000 mg/m2/day IV on days 1 through 3 repeated every 3 to 4 weeks followed by 10 cycles of MADDOC. Treatment with MADDO led to an event-free survival (EFS) rate of 72% and a failure-free local control rate of 84% at a median follow-up time of 85 months (range, 23 to 137 months). All patients had surgery and/or a biopsy, and 19 patients received radiotherapy (dose range, 14.4 to 36 Gy). Additionally, 13 of 18 surviving patients had no evidence of disease at a median follow-up of 94 months. Dacarbazine 250 mg/m2/day IV over 30 minutes on days 1 through 4 plus doxorubicin 35 mg/m2 IV push on day 1, cyclophosphamide 150 mg/m2/day IV push or PO on days 1 through 7, and vincristine 1.5 mg/m2 IV push on day 8 (ACVD regimen) every 3 to 4 weeks followed by or alternating with other chemotherapy regimens was evaluated in 299 children (median age, 33 months) with stage IV neuroblastome in 3 clinical trials (Trial NB 79, NB 82, and NB 85). Favorable initial overall remission rates (ORR) of 86% to 100% (complete remission [CR] rates, 11% to 37%) were seen. Additionally, the median EFS and overall survival (OS) times for all patients were 11.6 and 17 months, respectively, and the 5- to 8-year EFS and OS rates were 13% and 10%, respectively.

†Indicates off-label use

Dosage should be modified depending on clinical response and degree of hepatic dysfunction, but no quantitative recommendations are available.

Dosage should be modified depending on clinical response and degree of renal impairment, but no quantitative recommendations are available.

Acetaminophen; Ibuprofen: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Amlodipine; Celecoxib: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Bupivacaine; Meloxicam: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Carbidopa; Levodopa: (Moderate) Levodopa response may be decreased during chemotherapy with dacarbazine, DTIC. If dacarbazine is used in a patient stabilized on levodopa therapy, practitioners may wish to be alert for needed adjustments in the levodopa regimen to maintain patient status.
Carbidopa; Levodopa; Entacapone: (Moderate) Levodopa response may be decreased during chemotherapy with dacarbazine, DTIC. If dacarbazine is used in a patient stabilized on levodopa therapy, practitioners may wish to be alert for needed adjustments in the levodopa regimen to maintain patient status.
Celecoxib: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Celecoxib; Tramadol: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Diclofenac: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diclofenac; Misoprostol: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diflunisal: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Diphenhydramine; Ibuprofen: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diphenhydramine; Naproxen: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Etodolac: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Febuxostat: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
Fenoprofen: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Flurbiprofen: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Fosphenytoin: (Moderate) Subtherapeutic phenytoin concentrations may occur during the use of selected concurrent chemotherapy treatments; patients receiving phenytoin or fosphenytoin may require close clinical monitoring to ensure appropriate clinical outcomes are achieved during and following the completion of chemotherapy cycles.
Hydrocodone; Ibuprofen: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Famotidine: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Oxycodone: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Pseudoephedrine: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Indomethacin: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ketoprofen: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ketorolac: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Levodopa: (Moderate) Levodopa response may be decreased during chemotherapy with dacarbazine, DTIC. If dacarbazine is used in a patient stabilized on levodopa therapy, practitioners may wish to be alert for needed adjustments in the levodopa regimen to maintain patient status.
Live Vaccines: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Meclofenamate Sodium: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Mefenamic Acid: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Meloxicam: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Nabumetone: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen; Esomeprazole: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen; Pseudoephedrine: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Nonsteroidal antiinflammatory drugs: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Oxaprozin: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Pegfilgrastim: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Phenytoin: (Moderate) Subtherapeutic phenytoin concentrations may occur during the use of selected concurrent chemotherapy treatments. Because case reports of this interaction often include chemotherapy regimens of several different agents, it is not always clearly known which agent may be involved in the interaction, or the precise mechanism of interaction.
Piroxicam: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Quinine: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with quinine, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. In addition, the therapeutic effects of quinine, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Sulindac: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Sumatriptan; Naproxen: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Tolmetin: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Valdecoxib: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.

Dacarbazine/DTIC-Dome Intravenous Inj Pwd F/Sol: 100mg, 200mg

1000 mg/m2 IV as a single dose.

1000 mg/m2 IV as a single dose.

375 mg/m2 IV as a single dose; single doses of 900 mg/m2 IV have been given off-label for neuroblastoma.

375 mg/m2 IV as a single dose; single doses of 900 mg/m2 IV have been given off-label for neuroblastoma.

Dacarbazine is classified as an alkylating agent and exerts its chemotherapeutic effects by substituting an alkyl group for a hydrogen ion in various organic compounds, forming covalent linkages with sulfhydryl groups and thereby inhibiting DNA replication, RNA transcription, and nucleic acid function. It requires activation by the cytochrome P-450 system to its alkylating form. Dacarbazine exhibits minimal immunosuppressive activity, and it does not appear to be schedule-dependent.

Dacarbazine, DTIC is administered intravenously.  At therapeutic concentrations DTIC is not appreciably bound to human plasma protein. Dacarbazine, DTIC is extensively degraded. Besides unchanged DTIC, 5-aminoimidazole -4 carboxamide (AIC) is a major metabolite of DTIC that is excreted in the urine. Some of the drug's metabolites may be active and may contribute to antineoplastic activity. The drug's disappearance from the plasma is biphasic with initial half-life of 19 minutes and a terminal half-life of 5 hours. 

After intravenous (IV) administration, the volume of distribution exceeds total body water content, which suggests localization in tissues such as the liver. Roughly 40% of an IV dose is excreted by the kidneys unchanged within 6 hours, mostly by renal tubular secretion versus glomerular filtration.

Dacarbazine was teratogenic in rats at doses 20-times the daily human dose on day 12 of gestation; fetal skeletal anomalies were observed in rabbits who received doses 7-times the daily human dose on days 6 to 15 of gestation. Dacarbazine may cause fetal harm when used during pregnancy, based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid pregnancy during dacarbazine therapy.

It is not known whether dacarbazine is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for tumorigenicity from dacarbazine demonstrated in animal studies, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother.