Dobixin

FDA-Approved Indications:

• Breast Cancer: As adjuvant therapy for node-positive breast cancer following surgery; also for metastatic disease.
• Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML): As part of induction and consolidation chemotherapy regimens.
• Hodgkin’s Lymphoma and Non-Hodgkin’s Lymphoma: In combination regimens such as ABVD and CHOP.
• Neuroblastoma: Advanced and high-risk disease in pediatric patients.
• Osteosarcoma: As part of multi-agent chemotherapy.
• Wilms’ Tumor: For advanced stages in pediatric patients.
• Bladder Cancer: For locally advanced or metastatic urothelial carcinoma.
• Small Cell Lung Cancer (SCLC): As part of combination chemotherapy.
• Thyroid Cancer (Anaplastic or Refractory): For progressive or metastatic disease.
• Ovarian and Endometrial Cancer: Advanced, recurrent, or metastatic forms.
• Multiple Myeloma: As part of combination regimens in relapsed cases.
• Soft Tissue Sarcomas: Including leiomyosarcoma and liposarcoma.

Clinically Accepted Off-Label Uses:

• Kaposi’s Sarcoma (AIDS-related): Especially in liposomal formulation.
• Gastric and Esophageal Carcinoma: In advanced or metastatic settings.
• Pancreatic Cancer: As part of investigational or salvage regimens.
• Central Nervous System (CNS) Tumors: Including medulloblastoma in pediatric oncology.
• Retinoblastoma: In advanced-stage disease as part of multi-agent therapy.

Adults (Conventional Doxorubicin):

• Monotherapy: 60–75 mg/m² IV once every 21 days.
• Combination therapy: 40–60 mg/m² IV every 21–28 days depending on regimen.
• Cumulative dose limit: Do not exceed 450–550 mg/m² to avoid cardiotoxicity.

Pediatrics:

• Dose depends on protocol and diagnosis, commonly 30 mg/m² IV daily for 2–3 days every 3–4 weeks or 45–60 mg/m² every 21 days.
• Monitor for increased risk of cardiotoxicity in long-term survivors.

Elderly:

• Start at lower end of dosing range due to higher risk of cardiac dysfunction. Monitor cardiac function regularly.

Hepatic Impairment:

• Bilirubin 1.2–3.0 mg/dL: Reduce dose by 50%.
• Bilirubin >3.0 mg/dL: Reduce dose by 75% or avoid use.

Renal Impairment:

• No specific dose adjustment necessary, but caution advised in severe renal impairment.

Administration Route:

• IV only, given by slow injection (2–10 minutes) or short infusion.
• Avoid IM or SC use due to severe tissue damage risk.
• Liposomal doxorubicin must be administered via a separate dosing regimen and is not interchangeable.

Doxorubicin is a cytotoxic anthracycline antibiotic that acts through multiple mechanisms. It intercalates between DNA base pairs, inhibiting topoisomerase II and thereby blocking DNA replication and transcription. This action also generates free radicals, causing DNA strand breaks and cell death. These mechanisms lead to inhibition of rapidly dividing tumor cells, contributing to its potent antineoplastic activity.

• Absorption: Not applicable (IV administration).
• Distribution: Extensive tissue binding; volume of distribution ~25–30 L/kg.
• Protein Binding: Approximately 70–75%.
• Metabolism: Primarily hepatic to active metabolite doxorubicinol.
• Half-life: Biphasic; terminal half-life ~20–48 hours.
• Elimination: Mainly via biliary/fecal route (~40–60%); renal excretion ~5–12%.
• Onset of Action: Varies by cancer type, typically within days of administration.

• Pregnancy: Category D. Positive evidence of human fetal risk. Use only when potential benefits justify potential fetal harm. Known teratogenic and embryotoxic effects in animals and humans.
• Lactation: Excreted into breast milk. Breastfeeding is contraindicated during treatment and for 10 days after final dose due to risk of serious adverse effects in the infant.

• Primary Class: Antineoplastic Agent
• Subclass: Anthracycline Cytotoxic Antibiotic

• Hypersensitivity to doxorubicin or other anthracyclines
• Recent or ongoing myocardial infarction or cardiomyopathy
• Severe hepatic impairment or elevated bilirubin >3 mg/dL
• Persistent myelosuppression
• Cumulative lifetime dose ≥550 mg/m² (or ≥400 mg/m² with cardiac risk factors)
• Pregnancy (unless life-threatening disease requires treatment)

• Cardiotoxicity: Irreversible, dose-dependent heart failure; monitor LVEF before and during treatment.
• Myelosuppression: Severe neutropenia, anemia, thrombocytopenia common; frequent blood counts required.
• Secondary Malignancy: Risk of therapy-related AML and MDS increases with cumulative exposure.
• Extravasation Risk: Severe local necrosis; administer through a central line when possible.
• Hepatotoxicity: Requires liver function monitoring and dose adjustments.
• Radiation Recall Reaction: Dermatitis or soft tissue inflammation in previously irradiated areas.
• Tumor Lysis Syndrome: May occur in high-burden hematologic malignancies.
• Infections: High risk due to immunosuppression; monitor for fever and sepsis.

Common (≥10%):

• Hematologic: Neutropenia, leukopenia, anemia, thrombocytopenia
• GI: Nausea, vomiting, stomatitis, diarrhea, mucositis
• Dermatologic: Alopecia, hyperpigmentation
• General: Fatigue, weakness, fever

Serious/Rare:

• Cardiac: Heart failure, cardiomyopathy, arrhythmias
• Hepatic: Elevated transaminases, hepatotoxicity
• Secondary cancers: AML, MDS with long-term use
• Allergic reactions: Anaphylaxis, urticaria
• Injection site: Phlebitis, local tissue necrosis with extravasation

• Trastuzumab: Increases cardiotoxic risk; avoid concurrent use.
• Cyclophosphamide, Paclitaxel: Additive cardiotoxicity.
• CYP450 Interactions: Substrate of CYP3A4 and CYP2D6. Inhibitors (e.g., ketoconazole) increase levels; inducers (e.g., rifampin) reduce efficacy.
• Verapamil: Inhibits P-glycoprotein, may increase doxorubicin exposure.
• Live vaccines: Contraindicated due to immunosuppression.
• Phenytoin: Doxorubicin may reduce serum phenytoin levels.

• Cardiotoxicity Monitoring: ASCO and ESMO recommend more frequent LVEF monitoring, particularly in patients receiving >300 mg/m² or with cardiovascular risk.
• EMA Safety Update: Conventional and liposomal forms are not interchangeable; labels updated to emphasize formulation differences.
• FDA Guidance Update: Contraindication added for breastfeeding during and after treatment for 10 days.

• Powder for injection:
• Store at 2°C to 8°C (refrigerated).
• Do not freeze.
• Reconstituted solution:
• Use immediately or store at 2°C to 8°C for up to 24 hours.
• Protect from light.
• Handling precautions:
• Use personal protective equipment.
• Prepare in biological safety cabinet.
• Dispose of according to cytotoxic waste protocols.