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Doxorubicin Hydrochloride
Doxorubicin intercalates nucleotide bases and interacts with topoisomerase II to form DNA-cleavable complexes, inhibiting DNA/RNA replication.
Doxorubicin hydrochloride is an anthracycline topoisomerase inhibitor indicated for adjuvant breast cancer treatment and multiple metastatic malignancies. The drug intercalates DNA and forms topoisomerase II-cleavable complexes, with dose-independent pharmacokinetics and metabolism via CYP3A4, CYP2D6, and P-gp. Significant risks include cardiotoxicity (especially with trastuzumab), myelosuppression, and hepatotoxicity, requiring careful patient selection and monitoring. Clinical use requires assessment of cardiac function, hepatic status, and avoidance of contraindicated drug combinations.
At a glance
| Generic name | Doxorubicin Hydrochloride |
|---|---|
| Sponsor | Pfizer Inc. |
| Drug class | Anthracycline topoisomerase inhibitor |
| Target | DNA topoisomerase II, nucleotide bases |
| Modality | Small molecule |
| Therapeutic area | Oncology |
| Phase | FDA-approved |
Mechanism of action
Doxorubicin exerts its cytotoxic effects through multiple mechanisms. The drug intercalates into DNA by inserting itself between nucleotide base pairs, which inhibits the replication of nucleotides and blocks the action of DNA and RNA polymerases. Additionally, doxorubicin interacts with topoisomerase II to form DNA-cleavable complexes, which appears to be a critical mechanism for its cytocidal activity against malignant cells. The toxic effects of doxorubicin on various organs are thought to be related to its nucleotide base intercalation and cell membrane lipid binding activities. Enzymatic reduction at the 7 position and cleavage of the daunosamine sugar yields aglycones accompanied by free radical formation, the local production of which may contribute to the cardiotoxic activity of doxorubicin hydrochloride.
Approved indications
- Adjuvant chemotherapy for women with axillary lymph node involvement following resection of primary breast cancer
- Acute lymphoblastic leukemia
- Acute myeloblastic leukemia
- Hodgkin lymphoma
- Non-Hodgkin lymphoma
- Metastatic breast cancer
- Metastatic Wilms' tumor
- Metastatic neuroblastoma
- Metastatic soft tissue sarcoma
- Metastatic bone sarcoma
- Metastatic ovarian carcinoma
- Metastatic transitional cell bladder carcinoma
- Metastatic thyroid carcinoma
- Metastatic gastric carcinoma
- Metastatic bronchogenic carcinoma
Boxed warnings
- WARNING: CARDIOMYOPATHY, SECONDARY MALIGNANCIES, EXTRAVASATION AND TISSUE NECROSIS, and SEVERE MYELOSUPPRESSION • Cardiomyopathy: Myocardial damage, including acute left ventricular failure, can occur with doxorubicin hydrochloride. The risk of cardiomyopathy is proportional to the cumulative exposure with incidence rates from 1%–20% for cumulative doses ranging from 300 mg/m 2 to 500 mg/m 2 when doxorubicin hydrochloride is administered every 3 weeks. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Assess left ventricular ejection fraction (LVEF) before and regularly during and after treatment with doxorubicin hydrochloride [see Warnings and Precautions (5.1) ] . • Secondary Malignancies: Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at a higher incidence in patients treated with anthracyclines, including doxorubicin hydrochloride [see Warnings and Precautions (5.2) ] . • Extravasation and Tissue Necrosis: Extravasation of doxorubicin hydrochloride can result in severe local tissue injury and necrosis requiring wide excision of the affected area and skin grafting. Immediately terminate the drug and apply ice to the affected area [see Warnings and Precautions (5.3) ] . • Severe myelosuppression resulting in serious infection, septic shock, requirement for transfusions, hospitalization, and death may occur [see Warnings and Precautions (5.4) ] . WARNING: CARDIOMYOPATHY, SECONDARY MALIGNANCIES, EXTRAVASATION AND TISSUE NECROSIS, and SEVERE MYELOSUPPRESSION See full prescribing information for complete boxed warning. • Cardiomyopathy: Myocardial damage can occur with doxorubicin hydrochloride with incidences from 1%–20% for cumulative doses from 300 mg/m 2 to 500 mg/m 2 when doxorubicin hydrochloride is administered every 3 weeks. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Assess left ventricular ejection fraction (LVEF) before and regularly during and after treatment with doxorubicin hydrochloride. ( 5.1 ) • Secondary Malignancies: Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at a higher incidence in patients treated with anthracyclines, including doxorubicin hydrochloride. ( 5.2 ) • Extravasation and Tissue Necrosis: Extravasation of doxorubicin hydrochloride can result in severe local tissue injury and necrosis requiring wide excision and skin grafting. Immediately terminate the drug, and apply ice to the affected area. ( 5.3 ) • Severe myelosuppression resulting in serious infection, septic shock, requirement for transfusions, hospitalization, and death may occur. ( 5.4 )
Common side effects
- Anemia
- Nausea
- Fatigue
- Platelet count decreased
- White blood cell decreased
- Diarrhea
- Lymphocyte count decreased
- Neutrophil count decreased
- Alopecia
- Anorexia
- Insomnia
- Urinary frequency
Drug interactions
- CYP3A4 inhibitors
- CYP2D6 inhibitors
- P-glycoprotein inhibitors
- CYP3A4 inducers
- CYP2D6 inducers
- P-glycoprotein inducers
- Paclitaxel
- Trastuzumab
Key clinical trials
- Durvalumab in Combination With Chemotherapy in Treating Patients With Advanced Solid Tumors, DURVA+ Trial (PHASE2)
- Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma (PHASE3)
- Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma (PHASE3)
- Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia (PHASE2)
- Pegylated Liposomal Doxorubicin Hydrochloride With Atezolizumab and/or Bevacizumab in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (PHASE2,PHASE3)
- A Clinical Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) in People With Breast Cancer (MK-2870-032) (PHASE3)
- A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia (PHASE3)
- Virotherapy and Natural History Study of KHSV-Associated Multricentric Castleman s Disease With Correlates of Disease Activity (PHASE2)
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
Competitive intelligence
For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:
- Doxorubicin Hydrochloride CI brief — competitive landscape report
- Doxorubicin Hydrochloride updates RSS · CI watch RSS
- Pfizer Inc. portfolio CI