Dacarzin200 mg/vial

Dacarzin is a cytotoxic alkylating chemotherapy medicine given only by intravenous infusion under the direct supervision of an oncology specialist. It is never a self-administered, outpatient take-home medicine.

Established, FDA-approved indications

• Metastatic malignant melanoma - used as a single agent or combined with other anticancer drugs.
• Hodgkin lymphoma (second-line treatment) - approved only for use in combination with other effective antineoplastic agents (for example, as part of the ABVD combination regimen); Dacarzin is not used alone for this indication.

Guideline-supported and commonly used off-label indications

• Soft tissue sarcoma in adults - used off-label, in combination with other agents such as doxorubicin, based on oncology treatment guidelines.
• Selected advanced neuroendocrine tumours - used off-label in specific combination protocols under specialist oncology guidance.

All uses of Dacarzin require individualized dosing and monitoring by a qualified oncologist as part of a complete cancer treatment plan.

Each single-dose vial of Dacarbazine for Injection contains sterile, lyophilized Dacarbazine powder (as dacarbazine base, citrate, or hydrochloride depending on the manufacturer), typically supplied as 100 mg and 200 mg vials for reconstitution before intravenous use. No preservatives are included; each vial is intended for single use only.

Dacarzin (also referred to by its older name, DTIC) is a synthetic cytotoxic antineoplastic agent belonging to the triazene class of alkylating-type chemotherapy drugs. It works by damaging the DNA of rapidly dividing cancer cells, which stops tumour growth. Dacarzin is supplied as a powder for reconstitution and is given exclusively by intravenous infusion in a hospital or specialist oncology setting, as part of treatment for certain cancers including malignant melanoma and Hodgkin lymphoma.

Antineoplastic (anticancer) agent - Alkylating agent, triazene derivative; cytotoxic chemotherapy.

Dacarbazine is a prodrug that requires hepatic activation to exert its cytotoxic effect (see Mode of Action for the detailed mechanism).

Pharmacokinetics

• Absorption: Given only by intravenous infusion; not used orally in clinical practice.
• Distribution: Widely distributed in body tissues; does not cross the blood-brain barrier appreciably under normal conditions.
• Metabolism: Extensively metabolised in the liver (cytochrome P450-mediated N-demethylation) to its active metabolite, MTIC.
• Elimination: Eliminated mainly by the kidneys as unchanged drug and metabolites; plasma elimination is biphasic, with an initial half-life of about 20 minutes and a terminal half-life of roughly 5 hours (prolonged in renal or hepatic impairment).

Dacarzin is given strictly by the intravenous route, as a slow injection or short infusion, through a securely placed IV line, by trained oncology healthcare staff only. It must never be given intramuscularly, subcutaneously, or orally. Because Dacarzin is a vesicant/irritant, extravasation (leakage into surrounding tissue) can cause significant local pain, tissue damage, or necrosis; the infusion site is monitored closely throughout administration and extravasation management protocols are kept ready. Antiemetic medicines are usually given before infusion because Dacarzin has a high potential to cause nausea and vomiting. The reconstituted and diluted solution should be protected from light during administration. See Reconstitution for preparation details.

Only well-established, clinically significant interactions are listed; theoretical or minor interactions are not included.

• Live or live-attenuated vaccines: Avoid during Dacarzin treatment; the immunosuppression it causes can lead to serious or disseminated vaccine-strain infection.
• Other myelosuppressive chemotherapy or radiotherapy: Concurrent use increases the risk and severity of bone marrow suppression (low blood counts); combination regimens require closer blood count monitoring.
• Phenytoin and other hepatic enzyme-inducing drugs: May theoretically alter the hepatic activation of Dacarzin to its active metabolite; clinical significance is not firmly established, but caution and monitoring are reasonable.
• Other hepatotoxic medicines: Concurrent use may add to the risk of liver injury; liver function should be monitored closely (see Precautions and Warnings).

Because Dacarzin is a cytotoxic chemotherapy agent, side effects are frequent and some are serious; treatment is always given under close specialist monitoring.

Very common

• Nausea and vomiting (occurs in more than 90% of patients; Dacarzin is highly emetogenic; typically begins within 1-3 hours and may last up to 12 hours after a dose)
• Loss of appetite (anorexia)
• Bone marrow suppression - low white blood cells, low platelets, anemia (see Precautions and Warnings)

Common

• Flu-like syndrome (fever, muscle aches, general tiredness), which may occur even in later cycles
• Temporary hair thinning (alopecia)
• Facial flushing and a pins-and-needles (paresthesia) sensation during infusion
• Skin rash (erythematous or urticarial)
• Pain, redness, or tissue irritation at the injection/infusion site

Uncommon or rare but serious

• Liver toxicity, including rare hepatic vein thrombosis and hepatic necrosis (see Precautions and Warnings)
• Photosensitivity reactions after sun exposure
• Severe allergic reaction/anaphylaxis
• Tissue damage from extravasation at the injection site

Patients should report any of these effects to their oncology care team promptly.

Pregnancy: Dacarzin has shown teratogenic and embryotoxic effects in animal studies and, as a cytotoxic chemotherapy agent, is expected to cause fetal harm. It should not be used during pregnancy unless the treating oncologist determines that the potential benefit to the mother clearly justifies the potential risk to the fetus, and only after full discussion with the patient. Women of reproductive potential should use effective contraception during, and for a period after, treatment; men receiving Dacarzin should also be counselled on contraception, as advised by their oncologist.

Lactation: It is not known whether Dacarzin passes into human breast milk. Because of the potential for serious adverse effects in a nursing infant, breastfeeding should be discontinued during treatment and for a period afterward as advised by the treating physician.

Always consult the treating oncologist before any use in pregnancy or breastfeeding.

Boxed warning: Dacarzin must be administered under the supervision of a qualified oncology specialist. Bone marrow suppression is common and can be severe; complete blood counts must be checked before treatment and regularly during each cycle, with dose modified or delayed per protocol. Hepatotoxicity, including rare but serious hepatic vein thrombosis and hepatic necrosis (sometimes fatal), has been reported and requires monitoring of liver function.

• Bone marrow suppression: The main dose-limiting toxicity; regular blood count monitoring is required throughout treatment.
• Severe nausea and vomiting: Very common; standard practice is to give antiemetic medicines beforehand, often using more intensive antiemetic regimens because Dacarzin is highly emetogenic.
• Extravasation: Leakage of Dacarzin outside the vein can cause significant local tissue damage or necrosis; it must be given through a securely placed intravenous line, with extravasation management protocols available.
• Flu-like symptoms: Fever, muscle aches, and malaise can occur after administration, sometimes even in later treatment cycles.
• Photosensitivity: Patients should avoid excessive sun exposure and use sun protection during treatment.
• Hepatotoxicity: Liver function should be monitored, particularly for signs of rare but serious hepatic vein thrombosis.
• Hepatic or renal impairment: Requires careful, individualized risk-benefit assessment and dose adjustment by the oncologist (see Contraindications).
• Specialist administration only: Dacarzin requires dosing and administration to be individualized by an oncology specialist; it is not an outpatient, self-administered medicine.

An overdose of Dacarzin can cause severe and prolonged bone marrow suppression (with an increased risk of serious infection and bleeding), along with worsening of its other known effects such as severe nausea/vomiting and liver injury. Because Dacarzin is given only by trained healthcare professionals in a hospital or clinic setting, suspected overdose should be treated as a medical emergency: seek immediate medical attention, contact the treating oncology team or emergency services right away, or contact a poison control center. Management is supportive and includes close monitoring of blood counts and organ function; there is no specific antidote. Do not attempt home treatment for a suspected overdose.

Store unopened Dacarzin vials in a refrigerator at 2°C-8°C (36°F-46°F) and protect from light. Do not freeze unless specifically directed. After reconstitution, the solution should be used promptly and protected from light; any unused reconstituted or diluted solution should be discarded per the treating facility's protocol and not reused. Keep out of reach of children. Dacarzin is handled and stored only by trained healthcare staff in a hospital/clinic setting.

Renal impairment: Dacarzin and its metabolites are partly eliminated by the kidneys; caution and dose modification may be needed in significant renal impairment (see Contraindications).

Hepatic impairment: Since Dacarzin requires liver activation to its active form, impaired liver function may affect its activity and toxicity; use with caution and close monitoring (see Contraindications).

Elderly patients: Limited specific data are available; older patients may be more susceptible to bone marrow suppression and organ toxicity, so closer monitoring is advised.

Pediatric patients: See Pediatric Uses.

Patients of reproductive potential: Effective contraception is advised during and after treatment (see Pregnancy and Lactation).

The number of treatment cycles and overall duration of Dacarzin therapy are individualized by the treating oncologist based on the specific cancer, chosen regimen, response to treatment, and tolerability. Cycles are typically repeated every 3 to 4 weeks (or every 15 days in some Hodgkin lymphoma regimens), and treatment usually continues for a defined, protocol-specified number of cycles or until disease progression or unacceptable toxicity occurs. Dacarzin is not intended for indefinite or open-ended self-directed use.

Dacarzin for Injection is a lyophilized powder that must be reconstituted before use, by trained pharmacy or nursing staff:

• 100 mg vial: reconstitute with 9.9 mL Sterile Water for Injection to yield a 10 mg/mL solution.
• 200 mg vial: reconstitute with 19.7 mL Sterile Water for Injection to yield a 10 mg/mL solution.

The reconstituted solution may be further diluted in a compatible intravenous fluid (such as 5% Dextrose Injection or 0.9% Sodium Chloride Injection) before administration. The reconstituted/diluted solution should be protected from light and used promptly; if storage is unavoidable, follow facility protocol for the maximum permitted storage time and temperature before discarding. Discard any unused portion; each vial is for single use only.

Alkylating agent (triazene/DNA-methylating derivative); cytotoxic antineoplastic chemotherapy agent.

Dacarbazine is a prodrug. It is activated in the liver, mainly through cytochrome P450-mediated N-demethylation, to form the active metabolite MTIC (5-(3-methyltriazen-1-yl)imidazole-4-carboxamide). MTIC acts as a methylating agent, transferring methyl groups onto DNA (particularly at the O6 position of guanine). This DNA methylation disrupts normal DNA replication and function, interferes with RNA and protein synthesis, and ultimately triggers cell cycle arrest and programmed cell death (apoptosis), particularly in rapidly dividing malignant cells.

C

The safety and efficacy of Dacarzin in children have not been formally established in large controlled trials, and it is not FDA-approved specifically for pediatric use. However, Dacarzin is used off-label in children and adolescents, under close specialist pediatric oncology supervision, as part of established combination regimens for conditions such as Hodgkin lymphoma and certain sarcomas, following pediatric oncology protocols. Dosing in children, when used, is individualized by the treating pediatric oncologist based on body surface area/weight and protocol, with close monitoring for bone marrow suppression, liver toxicity, and other adverse effects (see Precautions and Warnings). Dacarzin should never be given to a child except under specialist pediatric oncology care.