6 ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling.
- Cardiomyopathy and Arrhythmias [see Warnings and Precautions (5.1)]
- Secondary Malignancies [see Warnings and Precautions (5.2)]
- Extravasation and Tissue Necrosis [see Warnings and Precautions (5.3)]
- Severe Myelosuppression [see Warnings and Precautions (5.4)]
- Tumor Lysis Syndrome [see Warnings and Precautions (5.6)]
- Radiation Sensitization and Radiation Recall [see Warnings and Precautions (5.7)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Breast Cancer
The safety data below were collected from 1492 women who received doxorubicin hydrochloride at a dose of 60 mg/m2 and cyclophosphamide at a dose of 600 mg/m2 (AC) every 3 weeks for 4 cycles for the adjuvant treatment of axillary lymph node positive breast cancer. The median number of cycles received was 4. Selected adverse reactions reported in this study are provided in Table 2. No treatment-related deaths were reported in patients on either arm of the study.
| Adverse Reactions | AC* N=1492 | Conventional CMF N=739 |
|---|---|---|
| % | % | |
| AC = doxorubicin hydrochloride, cyclophosphamide; CMF = cyclophosphamide, methotrexate, fluorouracil | ||
| ||
| Alopecia | 92 | 71 |
| Vomiting | ||
| Vomiting ≤12 hours | 34 | 25 |
| Vomiting >12 hours | 37 | 12 |
| Intractable | 5 | 2 |
| Leukopenia | ||
| Grade 3 (1,000–1,999 /mm3) | 3.4 | 9.4 |
| Grade 4 (<1000 /mm3) | 0.3 | 0.3 |
| Shock, sepsis | 2 | 1 |
| Systemic infection | 2 | 1 |
| Cardiac dysfunction | ||
| Asymptomatic | 0.2 | 0.1 |
| Transient | 0.1 | 0 |
| Symptomatic | 0.1 | 0 |
| Thrombocytopenia | ||
| Grade 3 (25,000–49,999 /mm3) | 0 | 0.3 |
| Grade 4 (<25,000 /mm3) | 0.1 | 0 |
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of Doxorubicin Hydrochloride Injection/for Injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiac – Cardiogenic shock
Cutaneous – Skin and nail hyperpigmentation, oncolysis, rash, itching, photosensitivity, urticaria, acral erythema, palmar plantar erythrodysesthesia
Gastrointestinal – Nausea, mucositis, stomatitis, necrotizing colitis, typhlitis, gastric erosions, gastrointestinal tract bleeding, hematochezia, esophagitis, anorexia, abdominal pain, dehydration, diarrhea, hyperpigmentation of the oral mucosa
Hypersensitivity – Anaphylaxis
Laboratory Abnormalities – Increased ALT, increased AST
Neurological – Peripheral sensory and motor neuropathy, seizures, coma
Ocular – Conjunctivitis, keratitis, lacrimation
Vascular – Phlebosclerosis, phlebitis/thrombophlebitis, hot flashes, thromboembolism
Other – Malaise/asthenia, fever, chills, weight gain