Doxorubicin (Conventional)

• If you have an allergy to doxorubicin or any other part of doxorubicin.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Anemia, heart problems, liver disease, a low platelet count, or a low white blood cell count.
• If you have had a recent heart attack.
• If you have had daunorubicin, doxorubicin, epirubicin, idarubicin, or mitoxantrone before, talk with your doctor.
• If you are taking any of these drugs: Phenobarbital, phenytoin, St. John's wort, or verapamil.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take doxorubicin with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
• Mouth irritation or mouth sores.
• A burning, numbness, or tingling feeling that is not normal.
• Seizures.
• Chest pain.
• Change in eyesight, eye pain, or very bad eye irritation.
• Patients with cancer who take this medicine may be at a greater risk of getting a bad health problem called tumor lysis syndrome (TLS). Sometimes, this has been deadly. Call your doctor right away if you have a fast heartbeat or a heartbeat that does not feel normal; any passing out; trouble passing urine; muscle weakness or cramps; upset stomach, throwing up, loose stools, or not able to eat; or feel sluggish.

• If you need to store doxorubicin at home, talk with your doctor, nurse, or pharmacist about how to store it.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take doxorubicin or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to doxorubicin. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous, as hydrochloride:

Adriamycin: 2 mg/mL (5 mL, 10 mL, 25 mL, 100 mL)

Generic: 2 mg/mL (5 mL, 10 mL, 25 mL, 100 mL)

Solution, Intravenous, as hydrochloride [preservative free]:

Generic: 2 mg/mL (5 mL, 10 mL, 25 mL, 75 mL, 100 mL)

Solution Reconstituted, Intravenous, as hydrochloride:

Adriamycin: 10 mg (1 ea); 20 mg (1 ea); 50 mg (1 ea)

Generic: 50 mg (1 ea)

Solution Reconstituted, Intravenous, as hydrochloride [preservative free]:

Generic: 10 mg (1 ea); 50 mg (1 ea [DSC])

Hypersensitivity (including anaphylaxis) to doxorubicin, any component of the formulation, or to other anthracyclines or anthracenediones; recent MI (within past 4 to 6 weeks), severe myocardial insufficiency, severe arrhythmia; previous therapy with high cumulative doses of doxorubicin, daunorubicin, idarubicin, or other anthracycline and anthracenediones; severe persistent drug-induced myelosuppression or baseline neutrophil count <1500/mm3; severe hepatic impairment (Child-Pugh class C or bilirubin >5 mg/dL)

Doxorubicin is associated with a moderate to high emetic potential (depending on dose or regimen); antiemetics are recommended to prevent nausea and vomiting (Basch 2011; Roila 2016).

Manufacturer's labeling: Note: 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.

Breast cancer: IV: 60 mg/m2 on day 1 of a 21-day cycle (in combination with cyclophosphamide) for 4 cycles

Metastatic solid tumors, leukemia, or lymphoma: IV:

Single-agent therapy: 60 to 75 mg/m2 every 21 days

Combination therapy: 40 to 75 mg/m2 every 21 to 28 days

Indication-specific dosing (off-label dosing):

Acute lymphoblastic leukemia: IV:

Hyper-CVAD regimen: 50 mg/m2 on day 4 of Courses 1, 3, 5, and 7 (in combination with cyclophosphamide, vincristine, and dexamethasone); alternating cycles with high-dose methotrexate and cytarabine (Kantarjian 2004)

CALGB 8811 regimen: 30 mg/m2 on days 1, 8 and 15 of late intensification (Course IV; 8-week cycle); in combination with vincristine, dexamethasone, cyclophosphamide, thioguanine, and cytarabine (Larson1995)

Bladder cancer, transitional cell: IV: Dose-dense MVAC regimen: 30 mg/m2 on day 2 every 14 days (in combination with methotrexate, vinblastine, and cisplatin) (Sternberg 2001)

Breast cancer: IV:

CAF regimen: 30 mg/m2 on days 1 and 8 every 28 days for 6 cycles (in combination with cyclophosphamide and fluorouracil) (Bull 1978)

FAC regimen: 50 mg/m2 on day 1 (or administered as a 72-hour continuous infusion) every 21 days for 6 cycles (in combination with fluorouracil and cyclophosphamide) (Assikis 2003)

TAC regimen: 50 mg/m2 on day 1 every 21 days for 6 cycles (in combination with docetaxel and cyclophosphamide) (Martin 2005)

Ewing sarcoma: IV:

VAC/IE regimen: Adults ≤30 years: 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 (Grier 2003)

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 (Paulussen 2008)

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) (Juergens 2006)

Hodgkin lymphoma: 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 (Bonadonna 2004; Engert 2010)

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) (Engert 2009)

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) (Horning 2002)

Non-Hodgkin lymphoma: IV:

CHOP or RCHOP regimen: 50 mg/m2 on day 1 every 21 days (in combination with cyclophosphamide, vincristine, and prednisone +/- rituximab) (Coiffier 2010; McKelvey 1976)

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 (Thomas 2006)

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) (Garcia-Suarez 2007; Wilson 2002)

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 (Geisler 2008)

Osteosarcoma: IV:

Cisplatin/doxorubicin regimen: Adults ≤40 years: 25 mg/m2 (bolus infusion) on days 1 to 3 every 21 days (in combination with cisplatin) (Bramwell 1992)

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) (Bacci 2003)

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) (Bacci 2003)

High-dose methotrexate/cisplatin/doxorubicin regimen: Adults <40 years:

Preoperative: 60 mg/m2 over 8 hours on days 9 and 36 (in combination with methotrexate and cisplatin) (Bacci 2000)

Postoperative: 45 mg/m2/day over 4 hours for 2 consecutive days (in combination with methotrexate, cisplatin +/- ifosfamide, +/- etoposide; refer to protocol for criteria, frequency, and other specific information) (Bacci 2000)

Small cell lung cancer, recurrent: 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 (von Pawel 1999)

Soft tissue sarcoma: 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) (Zalupski 1991)

AIM regimen: 30 mg/m2 on days 1 and 2 every 21 days (in combination with ifosfamide and mesna) (Edmonson, 1993)

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) (Elias 1989)

Single-agent regimen: 75 mg/m2 on day 1 every 21 days until disease progression or unacceptable toxicity (Santoro 1995)

Rhabdomyosarcoma:

VAC/IE regimen: Adults <21 years: 37.5 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 (Arndt 1998)

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) (Ogilvie 2010)

Off-label uses:

Endometrial carcinoma, advanced: IV: 60 mg/m2 on day 1 every 21 days for 8 cycles; maximum cumulative dose: 420 mg/m2 (in combination with cisplatin) (Randall 2006)

Multiple myeloma: IV:

PAD regimen: Induction: 9 mg/m2/day on days 1 to 4 for 3 cycles (in combination with bortezomib and dexamethasone) (Sonneveld 2012)

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) (Lee 2003; Pineda-Roman 2008)

Thymomas and thymic malignancies: IV:

CAP regimen: 50 mg/m2 on day 1 every 21 days for up to 8 cycles (in combination with cisplatin and cyclophosphamide) (Loehrer 1994)

ADOC regimen: 40 mg/m2 on day 1 every 21 days (in combination with cisplatin, vincristine, and cyclophosphamide) (Fornasiero 1991)

Uterine sarcoma: IV: 60 mg/m2 on day 1 every 21 days; maximum cumulative dose: 480 mg/m2 (Omura, 1983) or 50 mg/m2 (over 15 minutes) on day 1 every 21 days; maximum cumulative dose: 450 mg/m2 (in combination with ifosfamide/mesna) (Sutton 1996)

Waldenstrom macroglobulinemia: 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) (Buske 2009)

Cardiotoxicity: Discontinue in patients who develop signs/symptoms of cardiomyopathy.

Reconstitute lyophilized powder with NS (using 5 mL for the 10 mg vial; 10 mL for the 20 mg vial; or 25 mL for the 50 mg vial) to a final concentration of 2 mg/mL; gently shake until contents are dissolved. May further dilute doxorubicin solution or reconstituted doxorubicin solution in 50 to 1000 mL D5W or NS for infusion. Unstable in solutions with a pH <3 or >7.