Doxorubicin HEXAL2 mg/ml

Established / FDA-Approved Uses

Doxorubicin HEXAL injection is a cytotoxic anthracycline antibiotic indicated, usually as part of combination chemotherapy regimens, in the treatment of:

• Acute lymphoblastic leukemia (ALL)
• Acute myeloblastic leukemia (AML)
• Hodgkin lymphoma
• Non-Hodgkin lymphoma
• Wilms' tumor
• Neuroblastoma
• Soft tissue sarcoma and osteosarcoma
• Breast carcinoma
• Ovarian carcinoma
• Transitional cell bladder carcinoma
• Thyroid carcinoma
• Gastric carcinoma
• Bronchogenic carcinoma (certain types)

Guideline-Supported / Combination Regimen Use

Doxorubicin HEXAL is a core component of many standard multi-drug protocols (for example ABVD for Hodgkin lymphoma, CHOP for non-Hodgkin lymphoma, and AC/EC regimens for early and advanced breast cancer). In these settings it is used together with other cytotoxic agents rather than as monotherapy.

Off-Label Use

Doxorubicin HEXAL is sometimes used off-label, at the discretion of the treating oncologist, in other soft-tissue and rare tumor types where anthracycline-based chemotherapy is considered beneficial. Such use should only occur under specialist oncology supervision.

Each vial of Doxorubicin Hydrochloride for injection contains Doxorubicin Hydrochloride as the active ingredient, equivalent to a stated amount of doxorubicin base.

• Injection (ready-to-use solution): commonly available as 2 mg/mL solution in vials of 10 mg/5 mL, 50 mg/25 mL, and 200 mg/100 mL.
• Powder for reconstitution (lyophilized): commonly available as 10 mg, 50 mg, and 150 mg vials.

Strength and pack size vary by manufacturer; the prescribing physician and dispensing pharmacist should confirm the exact product strength before administration.

Doxorubicin HEXAL is a cytotoxic anthracycline antibiotic derived from Streptomyces peucetius var. caesius. It is used intravenously as part of chemotherapy regimens for a wide range of hematologic and solid tumor malignancies.

Doxorubicin HEXAL works by intercalating into DNA and inhibiting topoisomerase II, which disrupts DNA synthesis and repair in rapidly dividing cancer cells. It is administered only by, or under the direct supervision of, a physician experienced in the use of cytotoxic chemotherapy, because of its narrow therapeutic index and significant toxicity profile, including cumulative dose-dependent cardiotoxicity.

Antineoplastic anthracycline antibiotic (cytotoxic chemotherapy agent); Doxorubicin HEXAL belongs to this class.

Mechanism of Action

Doxorubicin Hydrochloride exerts its cytotoxic effect through several mechanisms:

• Intercalation between DNA base pairs, distorting the DNA helix and blocking DNA and RNA synthesis.
• Inhibition of topoisomerase II, stabilizing the DNA-topoisomerase II complex and causing DNA strand breaks.
• Generation of reactive oxygen species (free radicals), which contributes to its antitumor activity but is also the principal mechanism believed to underlie its cumulative, dose-dependent cardiotoxicity.

Pharmacokinetics

Doxorubicin Hydrochloride is administered intravenously (it is not orally bioavailable). It is extensively distributed into tissues, undergoes hepatic metabolism (primarily to the active metabolite doxorubicinol), and is eliminated mainly via biliary/fecal excretion, with a small renal component. Clearance is reduced in hepatic impairment, requiring dose adjustment.

Doxorubicin HEXAL is for intravenous use only and must be administered by a healthcare professional experienced with cytotoxic agents. It is given as a slow IV push into a free-flowing IV line or as a short infusion; it must never be injected intramuscularly or subcutaneously. Because Doxorubicin HEXAL is a vesicant, the IV line must be checked for patency before and during administration, and the infusion stopped immediately if extravasation is suspected.

Clinically Significant Drug Interactions

• Other cardiotoxic agents (e.g., trastuzumab, other anthracyclines, high-dose cyclophosphamide): Concomitant or sequential use increases the risk of cardiotoxicity; cardiac function should be monitored more closely.
• Hepatotoxic drugs: Drugs that impair hepatic function can reduce clearance of Doxorubicin HEXAL, increasing systemic toxicity; dose adjustment based on liver function may be needed.
• Cyclophosphamide: Combination increases the risk of hemorrhagic cystitis and myelosuppression.
• Live or live-attenuated vaccines: Should be avoided during Doxorubicin HEXAL therapy because of immunosuppression, which can result in serious or fatal infection from the vaccine strain.
• Radiation therapy: Doxorubicin HEXAL can cause a "radiation recall" reaction at previously irradiated sites, and concurrent radiation increases both cardiac and local tissue toxicity.
• Other myelosuppressive drugs: Additive bone marrow suppression; blood counts should be monitored closely.

Very Common

• Myelosuppression (leukopenia, neutropenia, thrombocytopenia, anemia) — usually dose-limiting
• Alopecia (hair loss), often complete but reversible after treatment
• Nausea and vomiting
• Mucositis / stomatitis
• Red-orange discoloration of urine for 1–2 days after dosing (harmless)

Common

• Fatigue, anorexia, diarrhea
• Skin hyperpigmentation, nail changes

Serious (see also Precautions and Warnings)

• Cumulative, dose-dependent cardiotoxicity, including arrhythmias and delayed, potentially irreversible cardiomyopathy/heart failure
• Severe local tissue necrosis if extravasation occurs during administration
• Secondary malignancies, including secondary acute myeloid leukemia
• Severe infection due to neutropenia
• Tumor lysis syndrome in patients with large tumor burden

Doxorubicin HEXAL can cause fetal harm when administered to a pregnant woman, based on its mechanism of action and animal reproduction data. Doxorubicin HEXAL should not be used during pregnancy unless the potential benefit to the mother clearly justifies the potential risk to the fetus, and only after full discussion with the treating physician. Women of reproductive potential should use effective contraception during and for a period after treatment.

Doxorubicin HEXAL is excreted into human breast milk. Because of the potential for serious adverse reactions in a breastfeeding infant, breastfeeding should be discontinued before starting treatment and should not be resumed without consulting the physician.

Boxed Warnings

• Cardiotoxicity: Doxorubicin HEXAL can cause cumulative, dose-dependent cardiotoxicity, including acute arrhythmias and delayed cardiomyopathy/congestive heart failure that may appear months to years after treatment and can be irreversible. Baseline and periodic monitoring of left ventricular ejection fraction (LVEF) by echocardiogram or MUGA scan is required, and cumulative lifetime dose must be tracked.
• Myelosuppression: Severe bone marrow suppression can occur; complete blood counts must be monitored before and during each cycle.
• Extravasation and tissue necrosis: Doxorubicin HEXAL is a vesicant. Extravasation can cause severe local tissue damage and necrosis. It must be administered only into a securely, freely-flowing intravenous line by personnel trained in cytotoxic drug administration.
• Secondary malignancies: Secondary acute myeloid leukemia and myelodysplastic syndrome have been reported, usually years after treatment, particularly when combined with DNA-damaging antineoplastic agents or radiotherapy.
• Administration: Doxorubicin HEXAL must be administered under the supervision of a physician experienced in the use of cytotoxic chemotherapeutic agents, and only via the intravenous route.

Additional Precautions

• Use with caution and reduced dose in hepatic impairment (see Dosage and Administration).
• Monitor for hyperuricemia and tumor lysis syndrome, especially in patients with high tumor burden (e.g., leukemia, lymphoma).
• Radiation recall reactions can occur at sites of previous irradiation.
• Immunosuppression increases susceptibility to infection; avoid live vaccines during therapy.

Acute overdose of Doxorubicin HEXAL can cause severe myelosuppression (with risk of serious infection and bleeding), severe mucositis/gastrointestinal toxicity, and acute cardiac toxicity that may manifest within 24 hours. Delayed cardiomyopathy may also occur weeks after an overdose.

There is no specific antidote. Suspected overdose is a medical emergency — the patient should be taken immediately to a hospital or seek emergency medical attention, where supportive care (including hospitalization, cardiac monitoring, blood product support, and treatment of infection) can be provided. Do not attempt to manage a suspected Doxorubicin HEXAL overdose at home.

Store Doxorubicin HEXAL injection under refrigeration (2°C to 8°C), protected from light, in the original carton until time of use, unless the specific product labeling states otherwise. Do not freeze. Keep out of reach of children. Doxorubicin HEXAL should be handled and disposed of according to institutional cytotoxic drug handling procedures.

Elderly

Elderly patients may be at increased risk of Doxorubicin HEXAL-related cardiotoxicity and myelosuppression; closer cardiac and hematologic monitoring is recommended, and dose modification may be considered.

Hepatic Impairment

Dose reduction is required based on serum bilirubin, as Doxorubicin HEXAL is cleared primarily by the liver (see Dosage and Administration).

Renal Impairment

No formal dose adjustment is established for renal impairment alone; use with caution and clinical judgment.

Pediatric Use

Doxorubicin HEXAL is used in established pediatric oncology protocols (e.g., acute leukemias, Wilms' tumor, neuroblastoma, sarcomas) with weight/BSA-based dosing. Long-term cardiac follow-up is important because children treated with Doxorubicin HEXAL remain at risk of late-onset cardiotoxicity into adulthood.

Duration of Doxorubicin HEXAL therapy is determined by the treating oncologist based on the specific cancer type, chemotherapy protocol, response to treatment, and cumulative dose already administered. Treatment is typically given in cycles (commonly every 3–4 weeks) for a pre-specified number of cycles, and is stopped earlier if the lifetime cumulative dose limit is approached or if unacceptable toxicity (especially cardiac) develops.

Lyophilized powder formulations of Doxorubicin HEXAL for injection must be reconstituted before use, typically with 0.9% Sodium Chloride Injection or Sterile Water for Injection, to achieve a final concentration commonly around 2 mg/mL, according to the specific product's package insert. The reconstituted solution should be inspected visually for particulate matter and discoloration before administration and used within the time period specified by the manufacturer. Ready-to-use liquid formulations of Doxorubicin HEXAL do not require reconstitution. Reconstitution and handling must be performed by trained personnel using appropriate cytotoxic drug safety precautions.

Doxorubicin Hydrochloride belongs to the anthracycline class of antineoplastic (cytotoxic) antibiotics, a subclass of DNA-damaging chemotherapy agents.

Doxorubicin Hydrochloride acts by intercalating into DNA, inhibiting topoisomerase II (causing DNA strand breaks and preventing religation), and generating reactive oxygen species that damage cellular macromolecules. These combined effects block DNA replication and transcription in rapidly dividing tumor cells, leading to cell death, while also contributing to its characteristic cardiotoxicity.

D

Doxorubicin HEXAL is used in children as part of established combination chemotherapy protocols for malignancies such as acute lymphoblastic leukemia, acute myeloblastic leukemia, Wilms' tumor, neuroblastoma, and soft tissue sarcomas/osteosarcoma. Dosing is calculated by body surface area (or body weight in infants) according to the specific pediatric oncology protocol being followed. Safety and efficacy outside recognized pediatric oncology protocols have not been established. Because of the risk of cumulative, potentially delayed cardiotoxicity, children treated with Doxorubicin HEXAL require long-term cardiac follow-up well into adulthood.