Doxorubicin is an anthracycline antibiotic that has been used extensively as an anti-neoplastic (anti-cancer) agent. It's a chemotherapy drug that's used to treat many types of cancer, including breast cancer, ovarian cancer, bladder cancer, lung cancer, and certain types of leukemia and lymphoma, among others.

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

Doxorubicin (Adriamycin) Dose in Adults:

• Doxorubicin is a drug that can make people feel really nauseous or even cause them to vomit.
• It's important to take other medicines with it to help prevent this.
• This drug can also hurt the heart, especially if taken a lot over time.
• It's important to keep track of how much of this drug someone has taken over their lifetime.
• Taking too much can increase the risk of heart problems, especially if someone has other risks for heart issues.

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

Hyper-CVAD Regimen:

• Doxorubicin is given at a dose of 50 mg/m².
• It is administered on day 4 during Courses 1, 3, 5, and 7 of the treatment.
• It is used in combination with other drugs like cyclophosphamide, vincristine, and dexamethasone.
• The treatment alternates with cycles of high-dose methotrexate and cytarabine.

CALGB 8811 Regimen:

• Doxorubicin is given at a dose of 30 mg/m².
• It is administered on days 1, 8, and 15 during the late intensification phase, which is part of Course IV.
• It is used in combination with other drugs including vincristine, dexamethasone, cyclophosphamide, thioguanine, and cytarabine.
• The treatment follows an 8-week cycle.

These regimens are designed to treat ALL, and doxorubicin is used as part of a combination therapy to increase its effectiveness in fighting the cancer.

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

Dose-dense MVAC Regimen:

• Doxorubicin is given at a dose of 30 mg/m².
• It's administered on day 2 and repeated every 14 days.
• It's used together with other drugs: methotrexate, vinblastine, and cisplatin.

This regimen uses doxorubicin and other drugs to more effectively treat bladder cancer.

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

AC Regimen:

• Doxorubicin is given at a dose of 60 mg/m².
• It's administered on day 1 every 21 days for a total of 4 cycles.
• This is used as adjuvant therapy and is combined with cyclophosphamide.

CAF Regimen (Off-label Dosing):

• Doxorubicin is given at a dose of 30 mg/m².
• It's administered on days 1 and 8 every 28 days for a total of 6 cycles.
• It's used in combination with cyclophosphamide and fluorouracil.

FAC Regimen:

• Doxorubicin is given at a dose of 50 mg/m².
• It's administered on day 1, and in some cases, it can be given as a continuous infusion over 72 hours.
• The treatment is repeated every 21 days for a total of 6 cycles.
• Doxorubicin is used along with fluorouracil and cyclophosphamide.

TAC Regimen:

• Doxorubicin is given at a dose of 50 mg/m².
• It's administered on day 1 every 21 days for a total of 6 cycles.
• It's used in combination with docetaxel and cyclophosphamide.

These regimens utilize doxorubicin, often in combination with other drugs, for the treatment of breast cancer. The specific regimen chosen depends on the patient's individual circumstances and the stage of breast cancer being treated. Patients should always follow their oncologist's recommendations and the prescribed dosages during breast cancer treatment.

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

For Advanced Endometrial Carcinoma (Off-label use):

• Doxorubicin is given at a dose of 60 mg/m².
• It's administered on day 1 and repeated every 21 days.
• The treatment continues for 8 cycles.
• The maximum total dose someone can receive over time is 420 mg/m².
• Doxorubicin is used together with another drug called cisplatin.

This regimen is specifically for treating advanced endometrial carcinoma, which is a type of cancer that starts in the lining of the uterus.

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

VDC/IE Regimen:

• For adults who are 30 years old or younger.
• Doxorubicin is given at a dose of 75 mg/m².
• It's administered on day 1 every 21 days for 5 cycles.
• This is combined with vincristine and cyclophosphamide.
• After the initial 5 cycles, dactinomycin is used instead of doxorubicin.
• Treatment also alternates with cycles of ifosfamide and etoposide, for a total of 17 cycles in all.

VAIA Regimen:

• For adults who are younger than 35 years old.
• Doxorubicin is given at a dose of 30 mg/m² per day.
• It's administered on days 1 and 2, and repeated every 21 days.
• Doxorubicin is alternated with dactinomycin and is also combined with vincristine and ifosfamide.
• This regimen lasts for 14 cycles.

VIDE Regimen:

• Doxorubicin is given at a dose of 20 mg/m² per day.
• It's given over a 4-hour period on days 1 to 3, and repeated every 21 days.
• This regimen goes on for 6 cycles.
• Doxorubicin is used together with vincristine, ifosfamide, and etoposide.

Ewing sarcoma is a type of cancer that mainly affects children and young adults. These regimens are specific treatment options using doxorubicin for Ewing sarcoma.

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

Doxorubicin with Cisplatin (Lee 2004 Regimen):

• Doxorubicin is given at a dose of 60 mg/m².
• It's administered on day 1 and repeated every 28 days.
• It's used together with another drug called cisplatin.
• This treatment is carried out for up to 6 cycles.

Doxorubicin with Cisplatin and Capecitabine (Park 2006 Regimen):

• Doxorubicin is given at a dose of 60 mg/m².
• It's administered on day 1 and repeated every 21 days.
• It's used in combination with two other drugs: cisplatin and capecitabine.
• This treatment is carried out for up to 6 cycles.

Metastatic hepatocellular cancer means that the liver cancer has spread to other parts of the body. These regimens use doxorubicin alongside other drugs to help treat this advanced stage of liver cancer.

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

ABVD Regimen:

• Doxorubicin is given at a dose of 25 mg/m².
• It's administered on days 1 and 15 and is repeated every 28 days.
• It's combined with other drugs: bleomycin, vinblastine, and dacarbazine.
• The treatment is done for 2 to 4 cycles.

A-AVD Regimen:

• Doxorubicin is given at a dose of 25 mg/m².
• It's administered on days 1 and 15 and is repeated every 4 weeks.
• It's used in combination with brentuximab vedotin, vinblastine, and dacarbazine.
• The regimen lasts for up to 6 cycles.
• It's recommended to also give a medicine called G-CSF (filgrastim) starting from the first cycle to help the body produce more white blood cells.

BEACOPP and Escalated BEACOPP Regimens:

• In the regular BEACOPP regimen, doxorubicin is given at a dose of 25 mg/m². In the escalated version, it's given at 35 mg/m².
• It's administered on day 1 and repeated every 21 days.
• This regimen includes a combination of many drugs: bleomycin, etoposide, cyclophosphamide, vincristine, procarbazine, and prednisone.

Stanford V Regimen:

• Doxorubicin is given at a dose of 25 mg/m².
• It's administered during weeks 1, 3, 5, 7, 9, and 11 in a 12-week cycle.
• The regimen includes several drugs: mechlorethamine, vinblastine, vincristine, bleomycin, etoposide, and prednisone.

Hodgkin lymphoma is a type of lymphoma, which is a cancer that starts in cells that are part of the body's immune system. These regimens use doxorubicin along with other drugs to combat this type of cancer.

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

Manufacturer's Recommendations (Note: Actual clinical practice might differ):

For patients with weaker bone marrow (due to being older, prior treatments, or cancer affecting the marrow), doctors might consider giving lower doses.

When Doxorubicin is Used Alone (Single-agent therapy):

• The dose is between 60 to 75 mg/m².
• It's given once every 21 days.

When Doxorubicin is Used with Other Drugs (Combination therapy):

• The dose ranges from 40 to 75 mg/m².
• It's administered every 21 to 28 days.

This information provides general dosing guidelines. The actual dose a patient receives will depend on various factors, including their overall health, other medical conditions, and specific type of cancer.

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

PAD Regimen:

• Doxorubicin is given at a dose of 9 mg/m² per day.
• It's administered from day 1 to day 4.
• This treatment is repeated for 3 cycles.
• It's used together with two other drugs: bortezomib and dexamethasone.

VDT-PACE Regimen:

• Doxorubicin is given at a dose of 10 mg/m² per day.
• It's given as a continuous infusion from day 1 to day 4 for each cycle.
• Doxorubicin is part of a combination with several drugs: bortezomib, dexamethasone, thalidomide, cisplatin, cyclophosphamide, and etoposide.

Multiple myeloma is a type of cancer that starts in plasma cells, a type of white blood cell. These regimens utilize doxorubicin alongside other drugs to treat this condition.

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

CHOP or RCHOP Regimen:

• Doxorubicin is given at a dose of 50 mg/m².
• It's administered on day 1 and is repeated every 21 days.
• It's used with a combination of drugs: cyclophosphamide, vincristine, and prednisone. Rituximab might also be added (that's when it's called RCHOP).

Hyper-CVAD + Rituximab Regimen:

• Doxorubicin is given at a dose of 50 mg/m².
• It's administered as a continuous infusion over 24 hours on day 4.
• This treatment is repeated for Courses 1, 3, 5, and 7 (each course lasts 21 days).
• It's used alongside cyclophosphamide, vincristine, dexamethasone, and rituximab.
• Treatment alternates with cycles of high-dose methotrexate and cytarabine.

Dose-adjusted EPOCH or REPOCH Regimen:

• Doxorubicin is given at a dose of 10 mg/m² per day.
• It's administered as a continuous infusion from day 1 to day 4 and is repeated every 21 days.
• It's combined with etoposide, vincristine, cyclophosphamide, and prednisone. Rituximab might also be added (making it REPOCH).

Nordic Regimen (Maxi-CHOP):

• Doxorubicin is given at a dose of 75 mg/m².
• It's administered on day 1 and is repeated every 21 days.
• It's used together with cyclophosphamide, vincristine, prednisone, and rituximab.
• Treatment alternates with cycles of high-dose cytarabine.

Non-Hodgkin lymphoma is a diverse group of blood cancers that includes all types of lymphoma except Hodgkin lymphomas. These regimens utilize doxorubicin along with other drugs to combat the disease.

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

Cisplatin/Doxorubicin Regimen:

• For adults up to 40 years old.
• Doxorubicin is given at a dose of 25 mg/m².
• It's administered on days 1 to 3 and repeated every 21 days.
• Used in combination with another drug called cisplatin.

High-dose Methotrexate/Cisplatin/Doxorubicin/Ifosfamide Regimen:

• For adults younger than 40 years.

Preoperative:

• • Doxorubicin dose: 75 mg/m².
  • Given as a continuous infusion over 24 hours on day 3 of weeks 1 and 7.
  • Used with methotrexate, cisplatin, and ifosfamide.

Postoperative:

• • Doxorubicin dose: 90 mg/m².
  • Given as a continuous infusion over 24 hours on weeks 13, 22, and 31.
  • Used with methotrexate, cisplatin, and ifosfamide.

MAP Regimen:

• For adults up to 40 years old.

Preoperative:

• • Doxorubicin dose: 37.5 mg/m² per day.
  • Administered as a continuous infusion over 48 hours on days 1 and 2 of weeks 1 and 6.
  • Used in combination with cisplatin, high-dose methotrexate, and a drug to reduce methotrexate side effects called leucovorin.

Postoperative:

• • Doxorubicin dose: 37.5 mg/m² per day.
  • Administered as a continuous infusion over 48 hours on days 1 and 2 of weeks 12, 17, 22, and 26.
  • Used in combination with cisplatin, high-dose methotrexate, and leucovorin.

Osteosarcoma is a type of bone cancer that typically develops in the long bones, such as those in the leg or arm. These regimens utilize doxorubicin, often alongside other drugs, to treat this type of cancer.

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

Doxorubicin with Gemcitabine Regimen:

• Doxorubicin is given at a dose of 50 mg/m².
• It's administered on day 1 and is repeated every 14 days.
• It's used alongside another drug called gemcitabine.
• Growth factor support is provided to help the body produce more blood cells.
• The treatment is carried out for 6 to 9 cycles.

Renal carcinoma with sarcomatoid features refers to a subtype of kidney cancer that exhibits specific cellular characteristics. This regimen uses doxorubicin in combination with other treatments to tackle this specific form of cancer.

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

Doxorubicin with Cisplatin and Cyclophosphamide (Lictra 1996):

• Doxorubicin is given at a dose of 50 mg/m².
• Administered on day 1, then repeated every 21 days.
• Combined with two other drugs: cisplatin and cyclophosphamide.
• Continue this treatment either until the cancer starts growing again or if side effects become too challenging.

Doxorubicin with Cisplatin and Cyclophosphamide (Debaere 2011):

• Doxorubicin is given at a dose of 50 mg/m².
• Administered on day 1 and repeated every 21 days.
• Combined with cisplatin and cyclophosphamide.
• This treatment is done for 6 to 8 cycles or until the cancer starts growing again or side effects become too severe.

Salivary gland cancers are rare cancers that start in the salivary glands of the mouth. This regimen utilizes doxorubicin along with other drugs to treat this particular kind of cancer.

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

CAV Regimen:

• Doxorubicin is given at a dose of 45 mg/m².
• The highest dose someone can receive at once is 100 mg.
• It's administered on day 1 and repeated every 21 days.
• It's used together with two other drugs: cyclophosphamide and vincristine.
• The treatment continues either until the cancer starts growing again, the side effects become too severe, or for a minimum of 4 or 6 cycles beyond the best response seen.

This regimen focuses on recurrent small cell lung cancer, a type of lung cancer that tends to grow and spread quickly. Patients should always follow their oncologist's advice and adhere to the prescribed dosages during their cancer treatment.

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

AD Regimen:

• Doxorubicin is given at a dose of 60 mg/m².
• Administered on day 1 every 21 days.
• Can be given either all at once (bolus) or continuously over 96 hours.
• Used together with another drug called dacarbazine.

AIM Regimen:

• Doxorubicin is given at a dose of 30 mg/m².
• Administered on days 1 and 2, repeated every 21 days.
• Used in combination with ifosfamide and mesna, a drug that helps protect the bladder from side effects of ifosfamide.

MAID Regimen:

• Doxorubicin dose is 20 mg/m² per day.
• Given continuously over 3 days (days 1 to 3) and repeated every 21 days.
• It's combined with ifosfamide, mesna, and dacarbazine.

Single-agent Regimen:

• Doxorubicin is given at a dose of 75 mg/m².
• Administered on day 1 every 21 days.
• Treatment continues until the cancer grows again or side effects become too challenging.

Soft tissue sarcoma is a type of cancer that starts in the soft tissues of the body, like muscle, tendons, fat, lymph vessels, blood vessels, and nerves. These regimens use doxorubicin, often with other drugs, to combat this kind of cancer.

Doxorubicin Dose in the treatment of Rhabdomyosarcoma:

VAC/IE Regimen:

• Intended for adults younger than 21 years.
• Doxorubicin is given at a dose of 37.5 mg/m².
• Administered over 18 hours on both day 1 and day 2.
• This treatment is repeated every 6 weeks.
• It's combined with vincristine and cyclophosphamide.
• Treatment cycles alternate with cycles of ifosfamide and etoposide.

VAI Regimen (Please note this is based on limited patient data):

• For adults.
• Doxorubicin is given at a dose of 25 mg/m² per day.
• Administered on days 1 to 3 and repeated every 21 days.
• It's used together with vincristine and ifosfamide.

Rhabdomyosarcoma is a cancer that originates in muscles and is most common in children. These regimens utilize doxorubicin alongside other drugs to treat this specific kind of cancer.

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

CAP Regimen:

• Doxorubicin is given at a dose of 50 mg/m².
• Administered on day 1 and is repeated every 21 days.
• Treatment continues for up to 8 cycles.
• It's combined with two other drugs: cisplatin and cyclophosphamide.

ADOC Regimen:

• Doxorubicin is given at a dose of 40 mg/m².
• Administered on day 1 and repeated every 21 days.
• It's used in combination with cisplatin, vincristine, and cyclophosphamide.

Thymomas and thymic malignancies are types of tumors that originate from the thymus, a small organ located in the upper chest. These regimens use doxorubicin along with other drugs to treat these specific cancers.

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

Doxorubicin Alone Regimen (Omura 1983):

• Doxorubicin is given at a dose of 60 mg/m².
• Administered on day 1 and repeated every 21 days.
• The maximum total dose someone can receive over time is 480 mg/m².

Doxorubicin with Ifosfamide/Mesna Regimen (Sutton 1996):

• Doxorubicin is given at a dose of 50 mg/m².
• Administered over 15 minutes on day 1 and repeated every 21 days.
• Used in combination with ifosfamide (a chemotherapy drug) and mesna (a drug that helps protect the bladder from the side effects of ifosfamide).
• The maximum total dose someone can receive over time is 450 mg/m².

Uterine sarcoma is a rare type of cancer that starts in the muscle and supportive tissues of the uterus. These regimens utilize doxorubicin, either alone or with other drugs, to tackle this specific kind of cancer.

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

R-CHOP Regimen:

• Doxorubicin is given at a dose of 50 mg/m².
• Administered on day 1 and repeated every 21 days.
• Treatment can last for 4 to 8 cycles.
• It's combined with other drugs: cyclophosphamide, vincristine, prednisone, and rituximab.

Waldenstrom macroglobulinemia is a rare type of non-Hodgkin lymphoma. The R-CHOP regimen uses doxorubicin in conjunction with a combination of other drugs to treat this specific condition.

Doxorubicin (Adriamycin) Dose in children:

Remember: The amount, how often, and how long you take doxorubicin can change based on the treatment plan. Always check the specific instructions.

• If a patient has weak bone marrow because of age, past treatments, or cancer in the marrow, they might need a smaller dose.
• Taking more than 550 mg/m² of doxorubicin in total can increase the risk of heart problems.
• Doxorubicin can make you feel very nauseous. Depending on the dose, this feeling can range from medium to very strong. So, doctors usually give medicines to help prevent feeling sick to the stomach.

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

Doxorubicin dosing in the treatment of metastatic solid tumors, leukemia, or lymphoma based on the manufacturer's labeling:

Infants, Children, and Adolescents:

For single-agent therapy (using doxorubicin alone):

• The dose is between 60 to 75 mg/m².
• It's administered once every 21 days.

For combination therapy (using doxorubicin with other drugs):

• The dose ranges from 40 to 75 mg/m².
• It's given every 21 to 28 days.

Please note that actual dosages may vary depending on the specific treatment plan, patient's condition, and medical guidelines.

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

Children and Adolescents:

Induction Phase:

• Doxorubicin dose: 30 mg/m².
• Given on days 0 and 1 of a 4-week cycle.
• Used with other drugs: vincristine, methotrexate, E.coli asparaginase, prednisone. It also includes two drugs given directly into the spinal fluid (intrathecal): cytarabine and a combination of methotrexate, cytarabine, and hydrocortisone.

CNS (Central Nervous System) Therapy (for High-risk patients):

• Doxorubicin dose: 30 mg/m².
• Given on day 1 of a 3-week cycle.
• Combined with dexrazoxane, vincristine, 6-mercaptopurine. It also includes an intrathecal combination of methotrexate and cytarabine.

Intensification Phase (for High-risk patients):

• Doxorubicin dose: 30 mg/m².
• Given on day 1 of every 3-week cycle.
• Combined with dexrazoxane, vincristine, 6-mercaptopurine, E.coli asparaginase, prednisone or dexamethasone. Plus, an intrathecal combination of methotrexate, cytarabine, and hydrocortisone.
• The total amount of doxorubicin used during the treatment should not exceed 300 mg/m².

Remember, acute lymphoblastic leukemia (ALL) is a type of blood cancer. These treatment regimens use doxorubicin along with other drugs to fight the disease.

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

Children and Adolescents:

VAC/IE Regimen (Grier, 2003):

• Doxorubicin dose: 75 mg/m².
• Given on day 1, repeated every 21 days.
• This is done for 5 cycles and combined with vincristine and cyclophosphamide.
• After 5 cycles, dactinomycin takes doxorubicin's place.
• Treatment alternates with another set: ifosfamide and etoposide.
• The entire treatment plan has 17 cycles in total.

VAIA Regimen (Paulussen, 2008):

• Doxorubicin dose: 30 mg/m² per day.
• Given on days 1 and 2, repeated every 21 days.
• Doxorubicin is alternated with dactinomycin.
• It's combined with vincristine and ifosfamide.
• The treatment is done for 14 cycles.

VIDE Regimen (Juergens, 2006):

• Doxorubicin dose: 20 mg/m² per day.
• Given over 4 hours on days 1 to 3.
• Repeated every 21 days and is done for 6 cycles.
• It's used together with vincristine, ifosfamide, and etoposide.

Ewing's sarcoma is a rare type of cancer that occurs in bones or in the soft tissue around the bones. These treatment regimens use doxorubicin with other drugs to combat this particular cancer type.

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

Children and Adolescents:

BEACOPP Regimen (Kelly, 2002):

• Doxorubicin dose: 35 mg/m².
• Given on day 0, repeated every 21 days.
• Used alongside a combination of other drugs: bleomycin, etoposide, cyclophosphamide, vincristine, procarbazine, and prednisone.

Hodgkin lymphoma is a type of lymphoma, which is a blood cancer that starts in the lymphatic system. The BEACOPP regimen combines doxorubicin with several other drugs to fight this specific kind of cancer.

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

Children and Adolescents:

Cisplatin/Doxorubicin Regimen (Bramwell, 1992):

• Doxorubicin dose: 25 mg/m².
• Given as a quick infusion (bolus) on days 1 to 3.
• Repeated every 21 days.
• Used alongside another drug: cisplatin.

High-dose Methotrexate/Cisplatin/Doxorubicin/Ifosfamide Regimen (Bacci, 2003):

• Preoperative:
  • Doxorubicin dose: 75 mg/m².
  • Given continuously over 24 hours on day 3 of weeks 1 and 7.
  • Combined with methotrexate, cisplatin, and ifosfamide.
• Postoperative:
  • Doxorubicin dose: 90 mg/m².
  • Given continuously over 24 hours on weeks 13, 22, and 31.
  • Used in cycles that include methotrexate, cisplatin, and ifosfamide.

High-dose Methotrexate/Cisplatin/Doxorubicin Regimen (Bacci, 2000):

• Preoperative:
  • Doxorubicin dose: 60 mg/m².
  • Given over 8 hours on days 9 and 36.
  • Combined with methotrexate and cisplatin.
• Postoperative:
  • Doxorubicin dose: 45 mg/m² per day.
  • Given over 4 hours for 2 consecutive days.
  • Used in cycles that switch between methotrexate, ifosfamide, and a combination of cisplatin and etoposide.

Osteosarcoma is a type of bone cancer most commonly seen in children and adolescents. These regimens use doxorubicin alongside other drugs to tackle this cancer.

Doxorubicin (Adriamycin) Dose in the treatment of Rhabdomyosarcoma:

Children and Adolescents:

VAC/IE Regimen (Arndt, 1998):

• Doxorubicin dose: 37.5 mg/m².
• Given over 18 hours on both days 1 and 2.
• Repeated every 6 weeks.
• Used with two other drugs: vincristine and cyclophosphamide.
• Treatment alternates with another combination: ifosfamide and etoposide.

Rhabdomyosarcoma is a cancer that typically starts in muscles. The VAC/IE regimen combines doxorubicin with other drugs to treat this particular kind of cancer in children and adolescents.

Pregnancy Risk Factor D

• Doxorubicin can harm the baby if given during pregnancy, so it should be avoided if possible.
• If you're a woman capable of getting pregnant or if you're a man with a female partner who can get pregnant, use effective non-hormonal birth control during doxorubicin treatment and for six months afterward.
• There's limited information on using doxorubicin during pregnancy, but it's generally not recommended during the first trimester.
• If you're pregnant and have cancer, it's best to consult with a specialized medical team, including an obstetrician and oncology experts.
• Chemotherapy with doxorubicin can be considered in the second trimester of pregnancy but should not be given in the first trimester.
• There should be a 3-week gap between the last chemotherapy dose and the expected delivery date, and chemotherapy should not continue past week 33 of pregnancy.

Doxorubicin can be used during breastfeeding

• Doxorubicin can get into breast milk.
• This means that when a mother takes doxorubicin, her baby can get some of the drug through breastfeeding.
• This can pose risks to the baby since the drug might cause serious side effects.
• Therefore, if a mother is on doxorubicin, she needs to decide whether to stop breastfeeding or to stop the drug. This decision should be based on how important the treatment is for her.

Doxorubicin (Adriamycin) Dose in Kidney disease:

Doxorubicin & Kidney Function:

• General Information:
  • Doxorubicin doesn't majorly get removed by the kidneys, so if a person has mild, moderate, or severe kidney problems, the dosage generally doesn't need to change.
  • Even in the official guidance from the drug manufacturer, there aren’t any specific dose changes suggested for kidney problems.
• Specific Recommendations:
  • If a person’s kidneys are functioning at less than 50% of normal (CrCl <50 mL/minute): No need to adjust the dose (Aronoff 2007).
  • For patients on hemodialysis: There's no need for an extra dose of doxorubicin after dialysis (Aronoff 2007).
  • Even if a person has kidney issues or is on hemodialysis, the amount of doxorubicin and its active metabolite in the body is a bit higher, but the time it stays in the body is the same. So, no dose changes are suggested. It's also recommended to give doxorubicin after dialysis or on a day when dialysis isn't scheduled (Janus 2010).
  • For patients with multiple myeloma: The International Myeloma Working Group (IMWG) says that doxorubicin can be given without changing the dose, even if a patient has kidney problems or is on dialysis. They suggest using specific formulas (CKD-EPI or MDRD) to check kidney function in these patients (Dimopoulos 2016).

Doxorubicin (Adriamycin) Dose in Liver disease:

• Official Recommendations from the Drug Manufacturer:
  • If the serum bilirubin (a liver function marker) is between 1.2 and 3 mg/dL: Give half (50%) the usual dose.
  • If the serum bilirubin is between 3.1 and 5 mg/dL: Give one fourth (25%) the usual dose.
  • If there's severe liver damage (Child-Pugh class C) or serum bilirubin is more than 5 mg/dL: Doxorubicin should not be used (it's contraindicated).
• Additional Recommendations (Floyd 2006):
  • If liver enzymes (transaminases) are 2 to 3 times the upper limit of normal (ULN): Give three fourths (75%) the usual dose.
  • If liver enzymes (transaminases) are more than 3 times the upper limit of normal (ULN): Give half (50%) the usual 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):

Do not use Doxorubicin if:

• You're allergic to doxorubicin, any ingredient in the drug, or similar drugs like other anthracyclines (e.g., daunorubicin) or anthracenediones.
• You've recently had a heart attack (in the last 4-6 weeks).
• You have severe heart problems or irregular heart rhythms.
• You've already taken the highest allowed doses of doxorubicin or similar drugs in the past.
• You have extremely low blood counts caused by drugs, or your neutrophil count (a type of white blood cell) is less than 1,500/mm³.
• You have severe liver problems, especially if classified as Child-Pugh class C or if your bilirubin level (a liver function marker) is more than 5 mg/dL.

Warnings and precautions

Suppression of bone marrow: [US Boxed Warning]

• Doxorubicin can severely affect your bone marrow, which is where your body produces blood cells. This is so important that it comes with a special warning (a "boxed warning") in the US.
• When the bone marrow doesn't produce enough blood cells, it can lead to serious infections, shock from those infections, the need for blood transfusions, having to stay in the hospital, and even death.
• The main concern is a big drop in white blood cells, especially a type called neutrophils. But it can also reduce the number of red blood cells and platelets.
• The lowest point (nadir) of blood cell counts usually happens around 10 to 14 days after taking the drug. But by day 21, the counts usually start to improve.
• It's crucial to check blood counts before starting the drug and then keep checking regularly during treatment to ensure safety.

Cardiomyopathy [US Boxed Warning]

• Doxorubicin can harm the heart and lead to heart problems. This is a significant concern, especially when higher doses are used.
• The risk of heart problems increases when doxorubicin is combined with other treatments that can harm the heart.
• Doctors need to regularly check the heart's pumping ability (called left ventricular ejection fraction or LVEF) before, during, and after doxorubicin treatment. They usually use methods like MUGA or echocardiograms for this.
• If someone shows signs of heart problems during doxorubicin treatment, the drug should be stopped.
• Heart problems can also appear months or even years after treatment ends. Symptoms might include a drop in LVEF or signs of heart failure (like difficulty breathing or swelling).
• The risk of heart issues is higher if patients have received radiation therapy in the chest area, have used other treatments that can harm the heart (like cyclophosphamide or trastuzumab), or have certain risk factors like age, smoking, high blood pressure, diabetes, high cholesterol, obesity, or existing heart issues.
• To lower the risk, doctors should assess patients' heart health before treatment and manage any modifiable risk factors like smoking, high blood pressure, and diabetes.
• In some cases, cardioprotective treatments or special forms of doxorubicin might be considered.
• If heart issues arise during treatment, doctors should perform heart tests, use cardiac biomarkers, and refer patients to a cardiologist as needed.

Extravasation: [US Boxed Warning]

• Doxorubicin is a vesicant, which means if it leaks out of the vein during injection, it can cause serious damage to the surrounding tissue, leading to tissue death.
• If doxorubicin leaks into the tissue, it might require surgical removal of the damaged area and possibly skin grafting.
• If there's a leak during the injection, the infusion should be stopped immediately and ice should be applied to the area to reduce damage.
• Doxorubicin should ONLY be given through an IV (in the vein). It should never be given as a muscle (IM) or under-the-skin (subcutaneous) injection.
• To prevent leaks, healthcare professionals need to ensure the needle or catheter is correctly placed in the vein before and during the injection.

Infertility impairment

• For men: Doxorubicin might harm sperm and the tissue inside the testicles. This could lead to potential birth defects if a child is conceived. It can also decrease the number of sperm or completely stop sperm production, potentially causing permanent infertility. However, some men might regain normal sperm counts a few years after stopping the treatment.
• For women: Doxorubicin can cause issues with fertility. It might lead to missed periods or cause early menopause.

Gastrointestinal toxicities:

• Doxorubicin can cause stomach issues.
• Depending on the dose, it can make people feel like throwing up.
• Doctors usually give medicines to help prevent this feeling of nausea and vomiting.

Secondary malignancy: [US-Boxed Warnings]

• Using Doxorubicin can increase the chance of getting other types of blood cancers, specifically AML and MDS. These can develop 1 to 3 years after the treatment.

Tumor lysis syndrome

• Doxorubicin can cause tumor lysis syndrome, which is when cancer cells release their contents rapidly into the bloodstream after breaking down.
• This can lead to high levels of uric acid in the blood.
• It's especially a risk in patients with fast-growing tumors.
• To help manage this, it may be necessary to make the urine more alkaline and give medicines to reduce uric acid levels.
• It's important to keep an eye on electrolyte levels, kidney function, uric acid levels, and ensure the patient is well-hydrated.

Hepatic impairment

• Doxorubicin can affect the liver, especially in patients with pre-existing liver issues.
• If a patient has bilirubin levels between 1.2 and 5 mg/dL, the dose of doxorubicin may need to be reduced.
• However, it should not be used in patients with severe liver impairment (Child-Pugh class C) or bilirubin levels over 5 mg/dL.
• Regular monitoring of liver function tests, including ALT, AST, alkaline phosphatase, and bilirubin, is essential both before and during treatment with doxorubicin.

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:

Blood Tests:

• Complete Blood Count (CBC): Check white blood cells, red blood cells, and platelets.
• Liver Function: Measure bilirubin, ALT/AST, and alkaline phosphatase.
• Kidney and Electrolytes: Monitor uric acid, calcium, potassium, phosphate, and creatinine.
• Hydration: Ensure the patient is properly hydrated.

Heart Monitoring:

• Initial Checks: Do an ECG and measure the left ventricular ejection fraction using either an echocardiography (ECHO) or a multigated radionuclide angiography (MUGA) scan.
• Regular Check-ups: Especially if there are signs/symptoms of heart problems. If you can't do an echocardiogram, consider using a cardiac MRI or a MUGA scan.

Cardiovascular Risk Assessment:

• Before Treatment: Get a detailed medical history and physical exam.
• Screen for Risk Factors: Look for hypertension, diabetes, high cholesterol, obesity, and smoking habits.
• Before Starting Treatment: Get an echocardiogram.
• If Problems Arise: Use an echocardiogram, or if not possible, a cardiac MRI or MUGA scan. Also, check serum cardiac biomarkers.

Infusion Site:

• Watch for reactions or issues where the medication is given.

How to administer Doxorubicin (Adriamycin)?

Preventing Nausea and Vomiting:

• Doxorubicin can cause nausea and vomiting.
• Antiemetics (medicines to prevent nausea) are often given before doxorubicin to reduce these side effects.

How to Administer:

• IV Only: Given through a vein in your arm, typically as a slow push over a few minutes or through a continuous infusion using a central venous line.
• Protect from Light: Keep the medication away from light until the infusion is complete.
• Avoid Alkaline Solutions: Don't mix it with alkaline solutions.
• Rate of Administration: The speed of infusion varies, so follow your specific treatment plan.

Preventing Extravasation:

• Doxorubicin can be harmful if it leaks into the surrounding tissue.
• Make sure the needle or catheter is correctly placed before and during the infusion.
• If leakage occurs, stop the infusion, remove the needle, and elevate the affected area.
• Use antidotes like dexrazoxane or dimethyl sulfate (DMSO).

Managing Extravasation:

• If there's leakage, stop the infusion, but don't remove the needle.
• Gently aspirate (draw out) the leaked solution without flushing the line.
• Apply dry cold compresses for 20 minutes, four times a day for 1 to 2 days.
• Antidotes like dexrazoxane or DMSO can be used, but follow specific dosing instructions.

Dexrazoxane (Antidote):

• Given through an IV in a large vein not near the site of leakage.
• Typically administered over several hours on multiple days.

DMSO (Antidote):

• Applied topically (on the skin) to a larger area than the affected site.
• Applied every 8 hours for about a week.
• Shouldn't be covered with a dressing.

Mechanism of action of Doxorubicin (adriamycin):

Doxorubicin is a potent chemotherapy drug that works against cancer by interfering with the DNA and RNA in cancer cells.

• DNA and RNA Interference:
  • Doxorubicin slips between the base pairs of the DNA, a process called "intercalation".
  • This insertion disrupts the DNA from functioning properly, which hinders the cancer cell's ability to replicate and divide.
• Topoisomerase II Inhibition:
  • Topoisomerase II is an enzyme that helps in DNA replication, condensation, and segregation.
  • Doxorubicin inhibits this enzyme, further blocking the synthesis of DNA and leading to DNA fragmentation.
• Iron Binding and Free Radical Production:
  • Doxorubicin can bind with iron to form the iron-doxorubicin complex.
  • This complex can produce free radicals – unstable molecules that can damage the DNA and cell membranes.

In essence, Doxorubicin hampers the cancer cells' ability to replicate by messing with its DNA structure, function, and the enzymes that assist in DNA processes. These combined actions lead to the death of cancer cells.

Distribution:

• Volume of Distribution (Vd): Ranges from 809 to 1,214 L/m. This suggests the drug is widely distributed in the body.
• Blood-Brain Barrier: Doxorubicin doesn't effectively pass through, meaning it doesn't significantly enter the brain.

Protein Binding:

• In the plasma, about 75% of doxorubicin binds to proteins.

Metabolism:

• The liver is primarily responsible for metabolizing doxorubicin.
• It first gets converted to doxorubicinol, which is still active.
• Further metabolism turns it into inactive substances, including conjugated sulfates and glucuronides.

Half-Life Elimination:

• Distribution Phase: Roughly 5 minutes. This phase represents the initial decline after distribution.
• Terminal Phase: Between 20 and 48 hours, with an average of 54 hours in males and 35 hours in females.

Excretion:

• Feces: About 40% of the drug is excreted unchanged.
• Urine: Between 5% to 12% is excreted in the urine, including both the unchanged drug and its metabolites.

Clearance Rate (The speed at which a drug is removed from the body):

• Infants and Children (<2 years): 813 mL/minute/m.
• Children and Adolescents (>2 years): 1,540 mL/minute/m.
• Adults: Ranges from 324 to 809 mL/minutes/m. The rate seems to be higher in men than in women.

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.