Doxorubicin (Adriamycin) is a chemotherapeutic drug of the anthracycline class. It prevents the proliferation of tumor cells by inhibiting the enzyme topoisomerase 2.

Doxorubicin (Adriamycin) Uses:

• Breast cancer:

  • The treatment component of adjuvant therapy (multi-agent) in women with evidence of axillary lymph node involvement following resection of primary breast cancer

• Metastatic cancers or disseminated neoplastic conditions:

  • Treatment of:
    • acute lymphoblastic leukemia,
    • acute myeloid leukemia,
    • Wilms tumor,
    • neuroblastoma,
    • soft tissue and bone sarcomas,
    • breast cancer,
    • ovarian cancer,
    • transitional cell bladder carcinoma,
    • thyroid carcinoma,
    • gastric carcinoma,
    • Hodgkin lymphoma,
    • non-Hodgkin lymphoma, and
    • bronchogenic carcinoma in which the small cell histologic type is the most responsive compared with other cell types

• Off Label Use of Doxorubicin in Adults:

  • Endometrial carcinoma
  • Hepatoblastoma (pediatrics)
  • Hepatocellular carcinoma (metastatic)
  • Multiple myeloma
  • Renal carcinoma (advanced)
  • Salivary gland cancers (advanced)
  • Thymomas and thymic malignancies
  • Uterine sarcoma
  • Waldenström macroglobulinemia

Adult dose:

• Doxorubicin is associated with a moderate to high emetic potential depending upon dose or regimen; antiemetics are required to prevent nausea and vomiting.
• Monitor cumulative dose (doxorubicin and other anthracyclines) received; the risk for cardiomyopathy rises as the cumulative dose increases and is also dependent upon other/additional risk factors.

Doxorubicin (Adriamycin) Dose in the treatment of Acute lymphoblastic leukemia (off-label dosing): IV:

• Hyper-CVAD regimen:

  • 50 mg/m² on the 4th day of Courses 1, 3, 5, and 7 (in combination with vincristine, cyclophosphamide, and dexamethasone);
  • alternating cycles with high-dose methotrexate and cytarabine.

• CALGB 8811 regimen:

  • 30 mg/m² on days 1, 8, and 15 of late intensification (Course IV; 8 weeks cycle);
  • in combination with vincristine, dexamethasone, cyclophosphamide, thioguanine, and cytarabine.

Doxorubicin (adriamycin) Dose in the treatment of Transitional cell Bladder cancer (off-label dosing): IV: Dose-dense

• MVAC regimen:

  • 30 mg/m² on day 2 every 14 days (in combination with methotrexate, vinblastine, and cisplatin).

Doxorubicin (Adriamycin) Dose in the treatment of Breast cancer: IV:

• AC regimen:

  • 60 mg/m² on day 1 every 21 days for 4 cycles (adjuvant therapy; in combination with cyclophosphamide).

• CAF regimen (off-label dosing ):

  • 30 mg/m² on days 1 and 8 every 28 days for 6 cycles (in combination with cyclophosphamide and fluorouracil).

• FAC regimen:

  • 50 mg/m² on day 1 (or administered as a 72-hour continuous infusion) every 3 weeks for 6 cycles (in combination with cyclophosphamide and fluorouracil )

• TAC regimen:

  • 50 mg/m² on day 1 every 21 days for 6 cycles (in combination with docetaxel and cyclophosphamide).

Doxorubicin Dose in the treatment of advanced Endometrial carcinoma, (off-label):

• IV: 60 mg/m² on day 1 every 21 days for 8 cycles;
• The maximum cumulative dose: 420 mg/m² (in combination with cisplatin).

Doxorubicin Dose in the treatment of Ewing sarcoma (off-label dosing): IV:

• VDC/IE regimen:

  • Adults ≤30 years:
    • 75 mg/m² in age <30 years on day 1 every 3 weeks for 5 cycles (in combination with cyclophosphamide and vincristine;
    • after five cycles, dactinomycin replaced doxorubicin), alternating cycles with ifosfamide and etoposide for a total of 17 cycles

• VAIA regimen:

  • Adults <35 years:
    • 30 mg/m²/day on days 1 and 2 every 21 days (doxorubicin alternates with dactinomycin; in combination with vincristine and ifosfamide) for14 cycles.

• VIDE regimen:

  • 20 mg/m²/day over 4 hours on days 1 to 3 every 21 days for 6 cycles (in combination with vincristine, ifosfamide, and etoposide).

Doxorubicin Dose in the treatment of metastatic Hepatocellular cancer, (off-label):

• IV: 60 mg/m² on day 1 every 28 days (in combination with cisplatin) for up to 6 cycles or
• 60 mg/m² on day 1 every 21 days (in combination with cisplatin and capecitabine) for up to 6 cycles.

Doxorubicin (Adriamycin) Dose in the treatment of Hodgkin lymphoma (off-label dosing): IV:

• ABVD regimen:

  • 25 mg/m² on days 1 and 15 every 28 days (in combination with bleomycin, vinblastine, and dacarbazine) for 2 to 4 cycles.

• A-AVD regimen:

  • 25 mg/m² on days 1 and 15 every 4 weeks (in combination with brentuximab vedotin, vinblastine, and dacarbazine) for up to 6 cycles.
  • Administer primary prophylaxis with G-CSF (filgrastim) beginning with cycle 1.

• BEACOPP and escalated BEACOPP regimens:

  • 25 mg/m² (BEACOPP) or 35 mg/m² (escalated BEACOPP) on day 1 every 21 days (in combination with bleomycin, etoposide, cyclophosphamide, vincristine, procarbazine, and prednisone).

• Stanford V regimen:

  • 25 mg/m² on weeks 1, 3, 5, 7, 9, and 11 of a 12-week cycle (in combination with mechlorethamine, vinblastine, vincristine, bleomycin, etoposide, and prednisone).

Doxorubicin (Adriamycin) Dose in the treatment of Metastatic solid tumors, leukemia, or lymphoma:

• Manufacturer's labeling:

  • Dosing in the prescribing information may not reflect current clinical practice.
  • Note: Consider lower dosages in patients with inadequate marrow reserve (due to advanced age, prior treatment, or neoplastic marrow infiltration). IV:
    • Single-agent therapy:
      • 60 to 75 mg/m² every 21 days.
    • Combination therapy:
      • 40 to 75 mg/m² every 21 to 28 days.

Doxorubicin (Adriamycin) Dose in the treatment of Multiple myeloma (off-label): IV:

• PAD regimen:

  • Induction: 9 mg/m² /day on days 1 to 4 for 3 cycles (in combination with bortezomib and dexamethasone).

• VDT-PACE regimen:

  • 10 mg/m²/day administered as a continuous infusion on days 1 to 4 of each cycle (in combination with bortezomib, dexamethasone, thalidomide, cisplatin, cyclophosphamide, and etoposide).

Doxorubicin (Adriamycin) Dose in patients with Non-Hodgkin lymphoma (off-label dosing): IV:

• CHOP or RCHOP regimen:

  • 50 mg/m² on day 1 every 21 days (in combination with cyclophosphamide, vincristine, and prednisone +/- rituximab)

• Hyper-CVAD + rituximab regimen:

  • 50 mg/m² administered as a continuous infusion over 24 hours on day 4 of Courses 1, 3, 5, and 7 (21-day treatment cycles;
  • in combination with cyclophosphamide, vincristine, dexamethasone, and rituximab); alternating cycles with high-dose methotrexate and cytarabine.

• Dose-adjusted EPOCH or REPOCH regimen:

  • 10 mg/m²/day administered as a continuous infusion on days 1 to 4 every 21 days (in combination with etoposide, vincristine, cyclophosphamide, and prednisone +/- rituximab).

• Nordic regimen (Maxi-CHOP):

  • 75 mg/m² on day 1 every 21 days (in combination with cyclophosphamide, vincristine, prednisone, and rituximab), alternating cycles with high-dose cytarabine.

Doxorubicin (Adriamycin) Dose in the treatment of Osteosarcoma (off-label dosing): IV:

• Cisplatin/doxorubicin regimen:

  • Adults ≤40 years:
    • 25 mg/m² (bolus infusion) on days 1 to 3 every 21 days (in combination with cisplatin).

• High-dose methotrexate/ cisplatin/ doxorubicin/ ifosfamide regimen:

  • Adults <40 years:

    • Preoperative:
      • 75 mg/m² administered as a continuous infusion over 24 hours on day 3 of weeks 1 and 7 (in combination with methotrexate, cisplatin, and ifosfamide).
    • Postoperative:
      • 90 mg/m² administered as a continuous infusion over 24 hours on weeks 13, 22, and 31 (in combination with methotrexate, cisplatin, and ifosfamide).

• MAP regimen:

  • Adults ≤40 years:

    • Preoperative:
      • 37.5 mg/m²/day administered as a continuous infusion (over 48 hours) days 1 and 2 of weeks 1 and 6 (in combination with cisplatin, high-dose methotrexate, and leucovorin rescue)
    • Postoperative:
      • 37.5 mg/m²/day administered as a continuous infusion (over 48 hours) days 1 and 2 of weeks 12, 17, 22, and 26 (in combination with cisplatin, high-dose methotrexate, and leucovorin rescue);
      • refer to protocol for criteria, frequency, and other specific information.

Doxorubicin (Adriamycin) Dose in the treatment of Advanced Renal cell carcinoma (with sarcomatoid features) (off-label):

• IV: 50 mg/m² on day 1 every 14 days (in combination with gemcitabine and growth factor support) for 6 to 9 cycles.

Doxorubicin Dose in the treatment of advanced Salivary gland cancers, (off-label):

• IV: 50 mg/m² on day 1 every 21 days (in combination with cisplatin and cyclophosphamide);
• continue until disease progression or unacceptable toxicity or 50 mg/m² on day 1 every 21 days (in combination with cisplatin and cyclophosphamide) for 6 to 8 cycles or until disease progression or unacceptable toxicity.

Doxorubicin Dose in the treatment of Small cell lung cancer, recurrent (off-label dosing): IV:

• CAV regimen:

  • 45 mg/m² (maximum dose: 100 mg) on day 1 every 21 days (in combination with cyclophosphamide and vincristine) until disease progression or unacceptable toxicity or for at least 4 or 6 cycles past maximum response.

Doxorubicin Dose in the treatment of Soft tissue sarcoma (off-label dosing): IV:

• Nonspecific histologies:

  • AD regimen:
    • 60 mg/m² on day 1 every 21 days (either as a bolus infusion or administered continuously over 96 hours; in combination with dacarbazine).
  • AIM regimen:
    • 30 mg/m² on days 1 and 2 every 21 days (in combination with ifosfamide and mesna).
  • MAID regimen:
    • 20 mg/m²/day as a continuous infusion on days 1 to 3 every 21 days (in combination with ifosfamide, mesna, and dacarbazine).
  • Single-agent regimen:
    • 75 mg/m² on day 1 every 21 days until disease progression or unacceptable toxicity.

Doxorubicin Dose in the treatment of Rhabdomyosarcoma:

• VAC/IE regimen:

  • Adults <21 years:
    • 5 mg/m² on days 1 and 2 (administered over 18 hours each day) every 6 weeks (in combination with vincristine and cyclophosphamide), alternating cycles with ifosfamide and etoposide.

• VAI regimen (based on a limited number of patients):

  • Adults:
    • 25 mg/m²/day on days 1 to 3 every 21 days (in combination with vincristine and ifosfamide).

Doxorubicin Dose in the treatment of Thymomas and thymic malignancies (off-label): IV:

• CAP regimen:

  • 50 mg/m² on day 1 every 21 days for up to 8 cycles (in combination with cisplatin and cyclophosphamide).

• ADOC regimen:

  • 40 mg/m² on day 1 every 21 days (in combination with cisplatin, vincristine, and cyclophosphamide).

Doxorubicin Dose in the treatment of Uterine sarcoma (off-label):

• IV: 60 mg/m² on day 1 every 21 days;
• maximum cumulative dose: 480 mg/m² or 50 mg/m² (over 15 minutes) on day 1 every 21 days;
• maximum cumulative dose: 450 mg/m² (in combination with ifosfamide/mesna).

Doxorubicin (Adriamycin) Dose in the treatment of Waldenstrom macroglobulinemia (off-label): IV:

• R-CHOP regimen:

  • 50 mg/m² on day 1 every 21 days for 4 to 8 cycles (in combination with cyclophosphamide, vincristine, prednisone, and rituximab).

Dose in children:

• Note:

  • Dose, frequency, number of doses, and start date may vary by protocol and treatment phase; refer to individual protocols.
  • Lower dosages should be considered for patients with inadequate marrow reserve (due to advanced age, prior treatment, or neoplastic marrow infiltration).
  • Cumulative doses above 550 mg/m² are associated with an increased risk of cardiomyopathy.
  • Doxorubicin is associated with a moderate to high emetic potential (depending on dose or regimen);
  • antiemetics are recommended to prevent nausea and vomiting.

Doxorubicin Dose in the treatment of Malignancy (metastatic solid tumors, leukemia, or lymphoma; general dosing):

• Manufacturer's labeling: IV:

  • Infants, Children, and Adolescents:

    • Single-agent therapy:
      • 60 to 75 mg/m² every 21 days
    • Combination therapy:
      • 40 to 75 mg/m² every 21 to 28 days

Doxorubicin Dose in the treatment of Acute lymphoblastic leukemia: IV:

• Children and Adolescents:

  • DFCI Consortium Protocol 00-01 (Vrooman, 2013):

    • Induction:
      • 30 mg/m²/dose on days 0 and 1 of a 4-week cycle (in combination with vincristine, methotrexate, E.coli asparaginase, prednisone, intrathecal cytarabine, and intrathecal methotrexate/cytarabine/hydrocortisone)
    • CNS therapy:
      • High-risk patients: 30 mg/m² on day 1 of a 3-week cycle (in combination with dexrazoxane, vincristine, 6-mercaptopurine, and intrathecal methotrexate/cytarabine)
    • Intensification:
      • High-risk patients: 30 mg/m² on day 1 of every 3-week cycle (in combination with dexrazoxane, vincristine, 6-mercaptopurine, E.coli asparaginase, prednisone or dexamethasone, and intrathecal methotrexate/cytarabine/hydrocortisone);
      • cumulative doxorubicin dose: 300 mg/m²

Doxorubicin (Adriamycin) Dose in the treatment of Ewing's sarcoma: IV:

• Children and Adolescents:

  • VAC/IE regimen:
    • 75 mg/m² on day 1 every 21 days for 5 cycles (in combination with vincristine and cyclophosphamide;
    • after 5 cycles, dactinomycin replaced doxorubicin), alternating cycles with ifosfamide and etoposide for a total of 17 cycles.
  • VAIA regimen:
    • 30 mg/m²/day on days 1 and 2 every 21 days (doxorubicin alternates with dactinomycin; in combination with vincristine and ifosfamide) for 14 cycles.
  • VIDE regimen:
    • 20 mg/m²/day over 4 hours on days 1 to 3 every 21 days for 6 cycles (in combination with vincristine, ifosfamide, and etoposide).

Doxorubicin (Adriamycin) Dose in the treatment of Hodgkin lymphoma: IV:

• Children and Adolescents:

  • BEACOPP regimen:
    • 35 mg/m² administered on day 0 of a 21-day treatment cycle (in combination with bleomycin, etoposide, cyclophosphamide, vincristine, procarbazine, and prednisone) (Kelly, 2002)

Doxorubicin (Adriamycin) Dose in the treatment of Osteosarcoma: IV:

• Children and Adolescents:

  • Cisplatin/doxorubicin regimen:
    • 25 mg/m² IV (bolus infusion) on days 1 to 3 every 21 days (in combination with cisplatin)

  • High-dose methotrexate/cisplatin/doxorubicin/ifosfamide regimen (Bacci, 2003):

    • Preoperative:
      • 75 mg/m² administered as a continuous infusion over 24 hours on day 3 of weeks 1 and 7 (in combination with methotrexate, cisplatin, and ifosfamide; refer to protocol for criteria, frequency, and other specific information)
    • Postoperative:
      • 90 mg/m² administered as a continuous infusion over 24 hours on weeks 13, 22, and 31 (alternating methotrexate, cisplatin, and ifosfamide)

  • High-dose methotrexate/cisplatin/doxorubicin regimen (Bacci, 2000):

    • Preoperative:
      • 60 mg/m² over 8 hours on days 9 and 36 (in combination with methotrexate and cisplatin)
    • Postoperative:
      • 45 mg/m² /day over 4 hours for 2 consecutive days (in alternating cycles of methotrexate, ifosfamide, and cisplatin/etoposide;
      • refer to protocol for criteria, frequency, and other specific information)

Doxorubicin (Adriamycin) Dose in the treatment of Rhabdomyosarcoma:

• Children and Adolescents:

  • VAC/IE regimen:

    • 5 mg/m² IV on days 1 and 2 (administered over 18 hours each day) every 6 weeks (in combination with vincristine and cyclophosphamide), alternating cycles with ifosfamide and etoposide.

Pregnancy Risk Factor D

• Animal reproduction studies have seen adverse events.
• According to the manufacturer's labeling, doxorubicin can cause fetal harm during pregnancy based on its mechanism of action.
• Females with reproductive potential and male partners who have female reproductive potential should be encouraged to use non-hormonal contraception methods during and 6 months after treatment.
• A retrospective study of women who received doxorubicin in combination with cyclophosphamide during their second or third trimester to treat pregnancy-associated breast carcinoma has limited information.
• Pregnant women may experience some changes in the pharmacokinetic properties.
• Guidelines for treatment and follow-up for cancer in pregnancy have been published by the European Society for Medical Oncology.
• The guidelines recommend that you refer to a cancer center during pregnancy. They also encourage multidisciplinary team approaches (obstetrician/neonatalian and oncology team).
• If chemotherapy is necessary, it should not begin in the first trimester. Instead, it may be started in the second trimester.
• Between the last dose of chemotherapy and delivery, there should be 21 days. Additionally, chemotherapy should not exceed 33 weeks gestation.

Doxorubicin can be used during breastfeeding

• Breast milk contains Doxorubicin as well as its metabolites.
• The drug manufacturer recommends that a decision is made about whether to stop breastfeeding or discontinue using the drug. This will take into consideration the mother's importance.

Renl dose:

Doxorubicin (Adriamycin) Dose in Kidney disease:

• Mild, moderate or severe impairment

  • The drug manufacturer's labeling does not include any dosage adjustments. However, due to limited renal excretion adjustments, adjustments may not be necessary.

• These adjustments are also recommended:

  • CrCl 50mL/minute

    • There is no need to adjust the dosage.

  • Hemodialysis

    • It is not necessary to take a supplement.

  • Hemodialysis or renal insufficiency:

    • Patients with kidney impairment have a higher AUC for doxorubicin (active metabolite), but their half-lives are comparable to patients without.
    • In patients with renal impairment or those on hemodialysis, dosage adjustment is not necessary.
    • Dosage adjustments can be administered after dialysis or on a day that is not designated for dialysis.

  • Recommendations of the International Myeloma Working Group:

    • According to the International Myeloma Working Group's recommendations, doxorubicin can be given without any dosage adjustments in multiple myeloma patients suffering from renal impairment.
    • The IMWG recommends that you use the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI), or the Modification Of Diet In Renal Disease formula (MDRD), to assess renal function estimation in multiple myeloma patients who have stable serum creatinine.

Doxorubicin (Adriamycin) Dose in Liver disease:

• The manufacturers' labeling recommends the following adjustments:

  • Serum bilirubin 1.2 to 3 mg/dL:
    • Administer 50% of dose.
  • Serum bilirubin 3.1 to 5 mg/dL:
    • Administer 25% of the dose.
  • Severe hepatic impairment (Child-Pugh class C or bilirubin >5 mg/dL):
    • Use is contraindicated.

• The following adjustments have also been recommended (Floyd 2006):

  • Transaminases 2 to 3 times ULN:
    • Administer 75% of dose.
  • Transaminases >3 times ULN:
    • Administer 50% of dose.

Side effects of Doxorubicin (Adriamycin)

• Cardiovascular:

  • Acute Cardiotoxicity:
    • Atrioventricular Block
    • Bradycardia
    • Bundle Branch Block
    • ECG Abnormality
    • Extrasystoles (Atrial Or Ventricular)
    • Nonspecific ST Or T Wave Changes On ECG
    • Sinus Tachycardia
    • Supraventricular Tachycardia
    • Tachyarrhythmia
    • Ventricular Tachycardia
  • Delayed Cardiotoxicity:
    • Cardiac Failure Manifestations Include
      • Ascites
      • Cardiomegaly
      • Dyspnea
      • Edema
      • Gallop Rhythm
      • Hepatomegaly
      • Oliguria
      • Pleural Effusion
      • Pulmonary Edema
      • Tachycardia
    • Decreased Left Ventricular Ejection Fraction
    • Myocarditis
    • Pericarditis

• Central Nervous System:

  • Malaise

• Dermatologic:

  • Alopecia
  • Discoloration Of Sweat
  • Pruritus
  • Skin Photosensitivity
  • Skin Rash; Urticaria

• Endocrine & Metabolic:

  • Amenorrhea
  • Dehydration
  • Hyperuricemia

• Gastrointestinal:

  • Abdominal Pain
  • Anorexia
  • Diarrhea
  • Discoloration Of Saliva
  • Gastrointestinal Ulcer
  • Mucositis
  • Nausea
  • Vomiting

• Genitourinary:

  • Urine Discoloration
  • Infertility (May Be Temporary)

• Hematologic & Oncologic:

  • Leukopenia
  • Neutropenia
  • Anemia
  • Thrombocytopenia

• Local:

  • Post-Injection Flare

• Neuromuscular & Skeletal:

  • Weakness

• Ophthalmic:

  • Discoloration Of Tears

• Miscellaneous:

  • Necrosis (Colon)
  • Radiation Recall Phenome

Contraindications to Doxorubicin (Adriamycin):

• Hypersensitivity/anaphylaxis of doxorubicin or any other anthracyclines/anthracenediones, or to any component of the formulation;
• Recent MI (in the past 4 to 6 week), severe arrhythmias, severe myocardial dysfunction;
• In cases of prior therapy that included maximum cumulative doses doxorubicin or daunorubicin as well as idarubicin or any other anthracycline/anthracenediones
• Chronic drug-induced myelosuppression severe or baseline neutrophil count 1,500/mm3
• severe hepatic impairment (Child Pugh class C, bilirubin >5mg/dL).

Warnings and precautions

• Suppression of bone marrow: [US Boxed Warning]

  • Severe myelosuppression can lead to severe infection, septichock, transfusion needs, hospitalization and even death.
  • Myelosuppression can be dose-limiting. It manifests primarily as neutropenia, leukopenia, and neutropenia. Anemia and thrombocytopenia could also occur.
  • The nadir usually occurs between 10 and 14 days after administration, with cell count recovery taking place approximately every 3 weeks.
  • Monitor your blood pressure at baseline and during treatment.

• Cardiomyopathy [US Boxed Warning]

  • Doxorubicin can cause Myocardial Damage. The incidences range from 1% to 20% when administered in cumulative doses of 300 mg/m2 up to 500 mg/m2 every 21 days.
  • Concomitant use of cardiotoxic therapy can increase the risk of developing cardiomyopathy.
  • Before and during doxorubicin therapy, the left ventricular ejection fraction should be evaluated.
  • Assess LVEF using MUGA or an echocardiogram.
  • Use the same assessment method for all occasions;
  • Frequent assessments are necessary if the cumulative dose is greater than 300 mg/m2.
  • Stop using doxorubicin if patients develop symptoms or signs of cardiomyopathy.
  • Late-stage or even years later, delayed cardiotoxicity can occur. It is usually manifested as a decreased LVEF and/or signs/symptoms related to heart failure.
  • Doxorubicin should be taken into account when it is combined with anthracyclines and anthracenediones.
  • Cardiotoxicity can be caused by cumulative lifetime doses ranging from 300 mg/m to 6% or 20% for cumulative doses of 500 mg/m2 every 3 weeks.
  • Patients who have had radiotherapy to their mediastinum, or received concomitant therapy using other cardiotoxic agents like cyclophosphamide or trastuzumab, are at greater risk of developing cardiomyopathy.
  • Pericarditis or myocarditis can also be observed after or during doxorubicin therapy.
  • Arrhythmias may occur, including potentially life-threatening arrhythmias.
  • Tachyarrhythmias may include premature ventricular contractions and sinus tachycardia.
  • ECG changes may include non-specific STT wave changes, bundle-branch and atrioventricular changes.
  • ECG changes can be temporary and self-limiting. Doxorubicin dose adjustments may not be necessary.
  • ASCO has published guidelines to prevent and monitor cardiac dysfunction in adult cancer survivors (ASCO [Armenian 2017]).
  • The following guidelines indicate that there is an increased risk of developing cardiac dysfunction:
    • High-dose anthracycline treatment (eg, epirubicin >=600mg/m2, doxorubicin>=250 mg/m2, epirubicin>=600 mg/m2)
    • High-dose radiotherapy (>=30 Gy), with the heart being in the treatment area
    • Low-dose anthracycline (eg doxorubicin 250 mg/m2, epirubicin 600 mg/m2) in combination with radiotherapy (30 Gy), with the heart in treatment field
    • Low-dose anthracycline (eg doxorubicin at 250 mg/m2, epirubicin at 600 mg/m2), or trastuzumab by itself AND any of these risk factors:
      • Multiple cardiovascular risk factors (>=2 risk factor factors), such as smoking, hypertension and diabetes, or obesity (during therapy or after).
      • Treatment for cancer in older people (>=60) is not recommended.
      • Prior to or during treatment, compromised cardiac function (eg borderline low LVEF [50%-55%], history MI, moderate or greater valvular disease)
    • Tratuzumab (sequential treatment) is followed by lower-dose anthracycline.
    • Anthracycline-induced cardiotoxicity can also be caused by age 60 or older and 2 or more cardiovascular risk factor (smoking or diabetes, hypertension, hypertension or obesity) that are present during treatment.
  • ASCO guidelines recommend that patients with cancer undergo a thorough assessment prior to treatment. This includes a history, physical examination, screening for cardiovascular disease risk factors like hypertension, diabetes and dyslipidemia.
  • Before you start potentially cardiotoxic therapies, it is important to obtain an echocardiogram.
  • Before initiating potentially dangerous therapies, it is important to manage modifiable risk factors such as smoking, diabetes, hypertension, and obesity.
  • Patients who are likely to be receiving high-dose anthracycline therapy should consider cardio-protectives (eg dexrazoxane), continuous injections or liposomal formulations (if applicable).
  • For patients with signs or symptoms of cardiac dysfunction, echocardiograms are recommended. If an echocardiogram cannot be obtained or is not possible, a cardiac MRI (preferred), or MUGA scan can be used.
  • It is recommended to have serum cardiac biomarkers and, if necessary, referral to a cardiologist.

• Extravasation: [US Boxed Warning]

  • It is a vesicant. Extravasation can cause severe tissue injury or necrosis, requiring extensive excision and skin grafting.
  • Apply ice immediately to the area.
  • Only for IV administration; Do not use intramuscular (IM), or subcutaneous routes.
  • Before and during infusion, ensure proper placement of the needle or catheter.
  • Avoid excessive use.

• Infertility impairment

  • Doxorubicin can cause spermatozoa damage and tissue damage in men. This could lead to genetic fetal abnormalities.
  • This may lead to oligospermia or azoospermia and permanent loss in fertility. Some men have reported that their sperm counts return to normal several years after treatment has ended.
  • Doxorubicin can cause infertility in females with reproductive potential. It can also lead to amenorrhea.

• Gastrointestinal toxicities:

  • Doxorubicin has a moderate to high emetic potency (depending upon the dose and regimen).
  • Antiemetic medications are recommended to prevent nausea or vomiting.

• Secondary malignancy: [US-Boxed Warnings]

  • Patients treated with anthracyclines (including doxorubicin) are more likely to develop secondary acute myelogenous lymphoma (AML) or myelodysplastic (MDS).
  • MDS and AML typically develop within 1 to 3 Years of treatment.

• Tumor lysis syndrome

  • Hyperuricemia and tumor lysis syndrome may occur in patients with rapidly growing tumors.
  • Prophylaxis with anti-hyperuricemic agents and urinary alkalinization may be required.
  • Monitor electrolytes and renal function.

• Hepatic impairment

  • Patients with bilirubin levels between 1.2 and 5 mg/dL should reduce their doses. Patients with hepatic impairment may have toxicities that are greater.
  • Patients with severe impairment (Child Pugh class C or bilirubin>5 mg/dL) are not recommended to use this medication.
  • Monitor hepatic function (ALT, AST and alkaline phosphatase) at baseline as well as during treatment.

Doxorubicin (conventional): Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy).
Ajmaline	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Bosentan	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Cardiac Glycosides	May decrease the cardiotoxic effects of Anthracyclines. Anthracyclines can decrease serum levels of Cardiac Glycosides. Liposomal formulations can have different effects than those of free drugs. They may also have unique drug dispositions and toxicity profiles. Additionally, liposomes can alter digoxin absorption/distribution.
Chloramphenicol Ophthalmic	May increase the toxic/adverse effects of Myelosuppressive Agents.
CloBAZam	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Clofazimine	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
CloZAPine	CloZAPine's toxic/adverse effects may be exacerbated by myelosuppressive agents. Particularly, there may be an increase in the risk of neutropenia.
Coccidioides immitis skin test	Coccidioides immitis Skin Test may be affected by immunosuppressants.
Cyclophosphamide	May increase the cardiotoxic effects of Anthracyclines.
Moderate CYP3A4 Inducers	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Moderate CYP3A4 inhibitors	Might decrease metabolism of CYP3A4 substrates (High Risk with Inhibitors).
Deferasirox	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Denosumab	Might increase the toxic/adverse effects of Immunosuppressants. In particular, there may be an increase in the risk of serious infections.
Erdafitinib	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Erdafitinib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Erdafitinib	Increased serum concentrations of P-glycoprotein/ABCB1 Substrates may be possible.
Fosaprepitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Ivosidenib	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Larotrectinib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Lumefantrine	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Mercaptopurine	DOXOrubicin (Conventional), may increase the hepatotoxic effects of Mercaptopurine.
Ocrelizumab	May increase the immunosuppressive effects of Immunosuppressants.
Palbociclib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Panobinostat	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Peginterferon Alfa-2b	High risk with inhibitors. May lower serum concentration of CYP2D6 substrates. Peginterferon Alf-2b could increase serum concentrations of CYP2D6 Substrates.
Pidotimod	Pidotimod's therapeutic effects may be diminished by immunosuppressants.
Promazine	May increase the myelosuppressive effects of Myelosuppressive Drugs.
Sarilumab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Siltuximab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Siponimod	Siponimod's immunosuppressive effects may be enhanced by taking immunosuppressants.
Sipuleucel - T	Sipuleucel T's therapeutic effects may be diminished by immunosuppressants
SORAfenib	Increase the serum level of DOXOrubicin (Conventional)
Stavudine	DOXOrubicin (Conventional), may reduce the therapeutic effects of Stavudine.
Tertomotide	Tertomotide's therapeutic effects may be diminished by immunosuppressants.
Tocilizumab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Vinflunine	Vinflunine may be affected by DOXOrubicin (Conventional). Particularly, there may be an increase in the risk of hematologic toxicities.
Risk Factor D (Still a possibility of therapy modification)
Abiraterone Acetate	High risk of Inhibitors causing an increase in serum concentrations of CYP2D6 substrates. When possible, avoid concurrent use of abiraterone and CYP2D6 Substrates with a narrow therapeutic index. If concurrent use cannot be avoided, closely monitor patients for signs/symptoms and treatment.
Ado-Trastuzumab Emtansine	May increase the cardiotoxic effects of Anthracyclines. Treatment: Patients treated with adotrastuzumab-emtansine should not use anthracycline-based treatment for more than 7 months after discontinuing adotrastuzumab-emtansine. Patients receiving this combination should be closely monitored for any signs of cardiac dysfunction.
Asunaprevir	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Baricitinib	Baricitinib's immunosuppressive effects may be enhanced by immunosuppressants. Baricitinib should not be used in combination with immunosuppressants like azathioprine and cyclosporine. It is permissible to use methotrexate antirheumatically or nonbiologic disease-modifying antirheumatic drug (DMARDs), concurrently.
CycloSPORINE Systemic	Increased serum levels of DOXOrubicin may occur (Conventional). Treatment: If you are using cyclosporine and doxorubicin, reduce the dose as needed. This combination should be used with caution. Increase monitoring for toxic effects ofdoxorubicin.
Moderate CYP2D6 inhibitors	Increased serum levels of DOXOrubicin may occur (Conventional). Treatment: If possible, seek alternatives to moderate CYP2D6 inhibitors for patients who have been treated with doxorubicin. These combinations should be avoided according to one U.S. manufacturer, Pfizer Inc.
Strong CYP2D6 inhibitors	Increased serum levels of DOXOrubicin may occur (Conventional). Treatment: If possible, seek out strong CYP2D6 inhibitors for patients who are being treated with doxorubicin. These combinations should be avoided according to one U.S. manufacturer, Pfizer Inc.
Strong CYP3A4 Inducers	The serum concentration of DOXOrubicin may be decreased (Conventional). Management: Look for alternatives to strong CYP3A4 inducers for patients who have been treated with doxorubicin. These combinations should be avoided according to one U.S. manufacturer, Pfizer Inc.
Moderate CYP3A4 inhibitors	Increased serum levels of DOXOrubicin may occur (Conventional). Treatment: If possible, seek alternatives to moderate CYP3A4 inhibitors for patients who have been treated with doxorubicin. These combinations should be avoided according to one U.S. manufacturer, Pfizer Inc. Grapefruit Juice is an exception.
Strong CYP3A4 inhibitors	Increased serum levels of DOXOrubicin may occur (Conventional). Treatment: If possible, seek out strong CYP3A4 inhibitors for patients who are being treated with doxorubicin. These combinations should be avoided according to one U.S. manufacturer, Pfizer Inc.
Dabrafenib	High risk of Inducers causing a decrease in serum CYP3A4 substrates. Management: If possible, seek alternatives to the CYP3A4 substrate. Concomitant therapy should be avoided if possible. Monitor the clinical effects of the substrate carefully (especially therapeutic effects).
Dacomitinib	High risk of Inhibitors causing an increase in serum concentrations of CYP2D6 substrates. Management: Do not use dacomitinib concurrently with CYP2D6 Substrates that have a narrow therapeutic Index.
Dexrazoxane	DOXOrubicin (Conventional) may cause a decrease in therapeutic effects. Management: Doxorubicin should not be administered to the heart during doxorubicin's initiation. This does not apply to dexrazoxane being used for any other indications, such as extravasation, or later in treatment.
Echinacea	Might decrease the therapeutic effects of Immunosuppressants.
Enzalutamide	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Management: Avoid concurrent use of enzalutamide and CYP3A4 substrates with a narrow therapeutic index. You should exercise caution when using enzalutamide or any other CYP3A4 sub-substance.
Fingolimod	Fingolimod may be immunosuppressed by immunosuppressants. When possible, avoid the use of fingolimod with other immunosuppressants. Patients should be closely monitored for any additive immunosuppressant effects, such as infections, if they are used together.
Leflunomide	Leflunomide's toxic/adverse effects may be exacerbated by immunosuppressants. The risk of hematologic toxicities such as pancytopenia and agranulocytosis may increase. Patients on immunosuppressants should not be given a leflunomide loading dosage. Patients who are receiving leflunomide or another immunosuppressant must be checked for bone marrow suppression at minimum monthly.
Lenograstim	Antineoplastic Agents can reduce the therapeutic effects of Lenograstim. Management: Lenograstim should be avoided 24 hours prior to and 24 hours following the completion of myelosuppressive, cytotoxic chemotherapy.
Lipegfilgrastim	Antineoplastic agents may reduce the therapeutic effects of Lipegfilgrastim. Management: It is important to avoid the simultaneous use of lipegfilgrastim with myelosuppressive, cytotoxic chemotherapy. After myelosuppressive chemotherapy has been completed, lipegfilgrastim must be given at least 24 hours.
Lorlatinib	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Management: Do not use lorlatinib concurrently with any CYP3A4 Substrates. Even a slight decrease in serum concentrations could cause therapeutic failure or serious clinical consequences.
MiFEPRIStone	High risk of Inhibitors causing an increase in serum concentrations of CYP3A4 substrates. Management: Reduce CYP3A4 Substrates and monitor for elevated concentrations/toxicity during and after treatment with mifepristone. Avoid dihydroergotamine and ergotamine.
Mitotane	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Treatment: Patients receiving mitotane may require significant adjustments in the dosage of CYP3A4 Substrates.
Nivolumab	Nivolumab's therapeutic effects may be diminished by immunosuppressants.
Palifermin	Can increase the toxic/adverse effects of Antineoplastic Agents. In particular, oral mucositis can be more severe and prolonged. Management: Avoid palifermin administration within the first 24 hours of infusion or 24 hours following myelotoxic chemotherapy.
Inducers of P-glycoprotein/ABCB1	Could lower the serum level of DOXOrubicin (Conventional). Management: If possible, seek alternatives to P-glycoprotein inducers for patients who have been treated with doxorubicin. These combinations should be avoided according to one U.S. manufacturer, Pfizer Inc.
Inhibitors of P-glycoprotein/ABCB1	Increased serum levels of DOXOrubicin may occur (Conventional). Treatment: If possible, seek alternatives to P-glycoprotein inhibiters for patients who have been treated with doxorubicin. These combinations should be avoided according to one U.S. manufacturer, Pfizer Inc.
Pitolisant	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates Management: Avoid combining pitolisant and a CYP3A4 substrat with a low therapeutic index. Pitolisant should not be combined with other CYP3A4 sub-substances.
Roflumilast	May increase the immunosuppressive effects of Immunosuppressants.
St John's Wort	The serum concentration of DOXOrubicin may be decreased (Conventional). Treatment: If you are being treated with doxorubicin, consider other options to St. John's Wort. Pfizer, a US manufacturer recommends that this combination not be used.
Stiripentol	High risk of Inhibitors causing an increase in serum concentrations of CYP3A4 substrates. Management: Avoid stiripentol use with CYP3A4 Substrates that have a narrow therapeutic Index. This is to avoid adverse effects and toxicities. Monitoring of any CYP3A4 substrate that is used with stiripentol should be closely done.
Taxane Derivatives	May reduce the metabolism of DOXOrubicin. Management: Docetaxel may be used instead of paclitaxel to avoid the potential interaction. Also, monitor for toxic effects of docetaxel. If paclitaxel is being used concurrently, doxorubicin should be administered first. DOCEtaxel is an exception.
Taxane Derivatives	May increase the toxic/adverse effects of Anthracyclines. Taxane Derivatives can increase serum levels of Anthracyclines. Taxane Derivatives can also increase the formation toxic anthracycline compounds in heart tissue.
Tofacitinib	Tofacitinib's immunosuppressive effects may be enhanced by immunosuppressants. Management: It is permissible to use methotrexate (or nonbiologic disease-modifying antirheumatic drug (DMARDs), concurrently with methotrexate. This warning appears to be particularly targeted at more potent immunosuppressants.
Trastuzumab	May increase the cardiotoxic effects of Anthracyclines. Trazuzumab-treated patients should not be treated with anthracycline-based therapy until 7 months after the treatment has ended. Patients receiving anthracyclines and trastuzumab should be closely monitored for any signs of cardiac dysfunction.
Vaccines (Inactivated).	Immunosuppressants can reduce the therapeutic effects of Vaccines (Inactivated). Management: The effectiveness of vaccines may be decreased. All age-appropriate vaccines must be completed at least two weeks before you start an immunosuppressant. Re-vaccinate anyone who was vaccinated while on immunosuppressant therapy.
Zidovudine	DOXOrubicin (Conventional), may increase the toxic/adverse effects of Zidovudine. DOXOrubicin (Conventional), may decrease the therapeutic effects of Zidovudine.
Risk Factor X (Avoid Combination)
BCG (Intravesical).	The therapeutic effects of BCG (Intravesical) may be diminished by immunosuppressants
BCG (Intravesical).	Myelosuppressive agents may reduce the therapeutic effects of BCG (Intravesical).
Bevacizumab	May increase the cardiotoxic effects of Anthracyclines.
Cladribine	May increase the immunosuppressive effects of Immunosuppressants.
Cladribine	May increase the myelosuppressive effects of Myelosuppressive Drugs.
Conivaptan	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Deferiprone	Deferiprone may have a neutropenic effect that myelosuppressive agents can increase.
Dipyrone	May increase the toxic/adverse effects of Myelosuppressive Agents. In particular, there may be an increase in the risk of pancytopenia and agranulocytosis.
Fusidic Acid (Systemic).	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Idelalisib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Natalizumab	Natalizumab's toxic/adverse effects may be exacerbated by immunosuppressants. Particularly, concurrent infections may increase.
Pimecrolimus	May increase the toxic/adverse effects of Immunosuppressants
Tacrolimus - Topical	May increase the toxic/adverse effects of Immunosuppressants
Vaccines (Live).	Immunosuppressants can increase the toxic/adverse effects of Vaccines (Live). Immunosuppressants can decrease the therapeutic effects of Vaccines. Management: Live-attenuated vaccines should be avoided for at least three months following immunosuppressants.

Monitoring parameters:

• CBC with platelet count and differential;
• Tests of liver function (bilirubin and ALT/AST, alkaline phosphatase)
• Serum uric acid and serum calcium, potassium, phosphate, and creatinine
• Hydration status
• Cardiac function (baseline, periodic and follow-up)
  • ECG, left-ventricular ejection fraction (echocardiography or multigated radionuclide angiography [MUGA]);
• Monitor the infusion site.

Cardiovascular monitoring (ASCO [Armenian 2017]).:

• A comprehensive assessment is required before treatment.
• This includes a history and physical exam, as well as screening for risk factors related to cardiovascular disease such hypertension, diabetes and dyslipidemia.
• Prior to treatment, echocardiogram
• If a patient develops signs or symptoms that suggest cardiac dysfunction, an echo is necessary for diagnostic workup.
• If echo is not possible or available, then a cardiac MRI (preferred), or MUGA scan can be used to obtain serum cardiac biomarkers.

How to administer Doxorubicin (Adriamycin)?

• Doxorubicin has a moderate-to-high emetic potency depending on the dose and regimen. Antiemetic medications are needed to prevent nausea or vomiting.
• Infuse IV push for at least 3-10 minutes or continuous infusion (infusion via central vein line is recommended).
• SubQ and IM should not be administered.
• Protocols vary in the rate of administration. Refer to each protocol for more details.
• Keep away from sunlight until the infusion is complete.
• Avoid contact with alkaline solutions.
• If you notice erythematous streaking or facial flushing, it is important to monitor the area.

Vesicant

• To avoid extravasation, ensure that the needles and catheters are properly placed before and during infusion.

Extravasation management

• Extravasation should be stopped immediately and the needle/ cannula left in place.
• Extravasated solution can be gently aspirated, but the line should not be flushed.
• Remove needle/cannula
• Elevate extremity
• Initiate antidote [dexrazoxane, dimethyl sulfate]
• Apply dry cold compresses for 20 minutes four times per day for 1 to 2-days. Continue withholding cooling for 15 mins before the dexrazoxane injection.
• Topical DMSO should not be used in conjunction with dexrazoxane. It may reduce dexrazoxane's efficacy.

Dexrazoxane:

• 1000 mg/m (maximum dosage: 2000 mg) IV (administered in a large vein distant from the site of extravasation) for 1 to 2 hour days 1 and 2. Then 500 mg/m2 IV (maximum dosing is 1000 mg) IV for 1 to 2 hour time days 3; start within 6 hours.
• Day 2 and day 3 should be administered approximately at the exact same time (+- 3 hrs) as day 1.
• NotificationReduce the dose of dexrazoxane by half for patients with severe or moderate renal impairment (CrCl 40mL/minute).

DMSO:

• For 7 days, apply topically to the same area twice as often as you can every 8 hours;
• Begin within 10 minutes after extravasation. Do not cover with a dressing.

Mechanism of action of Doxorubicin (adriamycin):

• Doxorubicin inhibits DNA synthesis and RNA synthesis through intercalation of DNA base pairs via inhibition of topoisomerase II or steric obstruction.
• Doxorubicin is intercalated at points of local coiling of the double-helix.
• It is not clear what the mechanism of blockage of DNA, RNA synthesis, and fragmentation occurs.
• Doxorubicin can also be used as an iron chelator. The iron-doxorubicin compound can bind to DNA and cell membranes, and then produce free radicals which immediately cleave the DNA.

Distribution:

• It does not cross the blood-brain barrier

Protein binding in the plasma:

• About 75%

Metabolism:

• Primarily hepatic to doxorubicinol (active), then to inactive aglycones, conjugated sulfates, and glucuronides

Half-life elimination:

• ~5 minutes
• Terminal: 20 to 48 hours
• Male: 54 hours;
• Female: 35 hours

Excretion:

• Feces (~40% as unchanged drug);
• urine (5% to 12% as unchanged drug and metabolites)

International Brands of Doxorubicin:

• Adriamycin
• Adriamycin PFS
• Myocet
• D. Mycin
• D.Mycin
• AD Mycin
• Adorucin
• Adriablastina
• Adriablastina RD
• Adriacin
• Adriamycin
• Adriamycin CS
• Adriamycin PFS
• Adriamycin RDF
• Adrib
• Adriblastin
• Adriblastina
• Adriblastina CS
• Adriblastina PFS
• Adriblastina RTU
• Adriblastina Soluzione Pronta
• Adriblastine
• AdriCept
• Adricin
• Adrim
• Adrim-10
• Adrim-50
• Adrimedac
• Adrosal
• Axibin
• Biorrub
• Colhidrol
• Dicladox
• DOXO-cell
• Doxocris
• Doxolem RU
• Doxopeg
• Doxorbin
• Doxorub
• Doxoruba
• Doxorubicin
• Doxorubicin Azupharma
• Doxorubicin Bigmar
• Doxorubicin Bristol
• Doxorubicin Ebewe
• Doxorubicin Hexal
• Doxorubicin NC
• Doxorubicin R.P.
• Doxorubicin ”Paranova”
• Doxorubicina
• Doxorubicine Asta
• Doxorubicine Dakota
• Doxorubin
• Doxosol
• Doxotil
• Doxtie
• Farmiblastina
• Fauldoso
• Flavicina
• Leubex
• Nagun
• Oncodox
• Oncodox-o
• Pallagicin
• Quimotus
• Rastocin
• Ribodoxo
• Robol
• Roxorin
• Rubex
• Rubicin
• Sandobicin
• Sindroxocin
• Urokit Doxo-cell
• Xorubin

Doxorubicin Brand Names in Pakistan:

Doxorubicin Injection 10 mg
Adriblastina-Rd	Pfizer Laboratories Ltd.
Adrim	Atco Laboratories Limited
D-Rubicin	Pharmedic (Pvt) Ltd.
Doxobin	Umair Associates
Doxocin	Consolidated Chemical Laboratories (Pvt) Ltd.
Doxolem	Scharper Pharmaceuticals (Pvt) Ltd.
Doxorubicin	Atco Laboratories Limited
Doxorubicin	Turner Grahams Of Pakistan (Pvt) Ltd.
Ku Doxorubicin	Al-Habib Pharmaceuticals.
Oncodox	A. J. Mirza Pharma (Pvt) Ltd
Rubicin	Bio Pharma

Doxorubicin Injection 20 mg
D-Rubicin	Pharmedic (Pvt) Ltd.
Doxopeg	Ferozsons Laboratoies Ltd.

Doxorubicin Injection 50 mg
Adrim	Atco Laboratories Limited
D-Rubicin	Pharmedic (Pvt) Ltd.
Doxobin	Umair Associates
Doxocin	Consolidated Chemical Laboratories (Pvt) Ltd.
Doxolem	Scharper Pharmaceuticals (Pvt) Ltd.
Doxorubicin	Turner Grahams Of Pakistan (Pvt) Ltd.
Doxorubicin	Atco Laboratories Limited
Ku Doxorubicin	Al-Habib Pharmaceuticals.
Oncodox	A. J. Mirza Pharma (Pvt) Ltd
Rubicin	Bio Pharma

Doxorubicin Injection Cs 50 Mg
Adriblastina-Rd	Pfizer Laboratories Ltd.