Version May 2024
Myocardial damage, including acute left ventricular failure, can occur with doxorubicin. The risk of cardiomyopathy is proportional to the cumulative exposure with incidences from 1% to 20% for cumulative doses from 300 mg/m2 to 500 mg/m2 when doxorubicin is administered every 3 weeks. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Assess left ventricular ejection fraction before and regularly during and after treatment with doxorubicin.
Extravasation of doxorubicin can result in severe local tissue injury and necrosis requiring wide excision of the affected area and skin grafting. Immediately terminate the drug and apply ice to the affected area.
Secondary acute myelogenous leukemia and myelodysplastic syndrome occur at a higher incidence in patients treated with anthracyclines, including doxorubicin.
Severe myelosuppression resulting in serious infection, septic shock, requirement for transfusions, hospitalization, and death may occur.
Note: Monitor cumulative dose (doxorubicin and other anthracyclines) received; the risk for cardiomyopathy increases as the cumulative dose increases and is also dependent on other/additional risk factors. Actively manage modifiable cardiac risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) before initiating treatment (ASCO [Armenian 2017]). Doxorubicin is associated with a moderate to high emetic potential (depending on dose or regimen); antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]). Do NOT substitute conventional doxorubicin for or with doxorubicin (liposomal); products are different and are NOT interchangeable. Use caution when selecting product for preparation and dispensing (both products are the same concentration).
Acute lymphoblastic leukemia (off-label dosing):
Hyper-CVAD regimen: IV: 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: IV: 30 mg/m2 on days 1, 8 and 15 of late intensification (Course 4; 8-week cycle); in combination with vincristine, dexamethasone, cyclophosphamide, thioguanine, and cytarabine (Larson 1995).
DFCI Consortium regimen: Patients ≤50 years of age: IV: Induction phase: 30 mg/m2 on days 1 and 2 (4-week treatment cycle); CNS therapy phase: 30 mg/m2 for one dose (3-week treatment cycle); Intensification phase: 30 mg/m2 on day 1 (3-week cycle; continue to a cumulative doxorubicin dose of 300 mg/m2); Continuation phase: 30 mg/m2 on day 1 (3-week cycle; continue to a cumulative doxorubicin dose of 300 mg/m2 [if not already reached]); phases are part of combination chemotherapy; refer to protocol for details (DeAngelo 2015).
Adrenocortical carcinoma, advanced (off-label use): IV: 40 mg/m2 on day 1 every 4 weeks (in combination with cisplatin, etoposide, and mitotane) (Fassnacht 2012) or 20 mg/m2 on days 1 and 8 every 4 weeks (in combination with cisplatin, etoposide, and mitotane) until disease progression or unacceptable toxicity up to a maximum of 6 cycles (Berruti 2005).
Adult T-cell leukemia/lymphoma (off-label use): IV: 40 mg/m2 on day 1 and 30 mg/m2 on day 8 every 28 days (as part of the VCAP-AMP-VECP multiagent chemotherapy regimen) for 6 cycles (Tsukasaki 2007).
Bladder cancer, advanced (off-label dosing):
Locally advanced or metastatic disease:
Dose-dense MVAC regimen: IV: 30 mg/m2 on day 2 every 14 days (in combination with methotrexate, vinblastine, cisplatin, and growth factor support) until disease progression or unacceptable toxicity (Sternberg 2001; Sternberg 2006).
MVAC regimen: IV: 30 mg/m2 on day 2 every 28 days (in combination with methotrexate, vinblastine, and cisplatin) for up to 6 cycles (von der Maase 2000) or 30 mg/m2 on day 2 every 28 days (in combination with methotrexate, vinblastine, and cisplatin) until disease progression or unacceptable toxicity (Sternberg 2001; Sternberg 2006) or 30 mg/m2 on day 1 every 28 days (in combination with methotrexate, vinblastine, cisplatin, and filgrastim) for up to 6 cycles or until loss of clinical benefit (Bamias 2004).
Neoadjuvant treatment:
Note: Patients with non-organ confined disease at cystectomy who did not receive cisplatin-based neoadjuvant chemotherapy should be offered an adjuvant cisplatin-based chemotherapy regimen (AUA/ASCO/ASTRO/SUO [Chang 2017]).
Dose-dense MVAC regimen: IV: 30 mg/m2 on day 1 or on day 2 every 14 days (in combination with methotrexate, vinblastine, cisplatin, and pegfilgrastim) for 3 or 4 cycles (Choueiri 2014; Plimack 2014).
MVAC regimen: IV: 30 mg/m2 on day 2 every 28 days (in combination with methotrexate, vinblastine, and cisplatin) for 3 cycles (Grossman 2003).
Small cell carcinoma of the bladder:
Neoadjuvant treatment: IV: 25 mg/m2 on days 1 to 3 every 21 days (in combination with ifosfamide, mesna, and growth factor support; IA cycle); IA cycle alternates with etoposide and cisplatin (EP cycle) for a total of 4 cycles (2 cycles of IA and 2 cycles of EP) (Siefker-Radtke 2009).
Metastatic disease: IV: 25 mg/m2 on days 1 to 3 every 21 days (IA cycle); IA cycle alternates with EP cycle for 2 cycles beyond maximal response (Siefker-Radtke 2009).
Breast cancer:
AC regimen: IV: 60 mg/m2 on day 1 every 21 days for 4 cycles (in combination with cyclophosphamide) (Fisher 1990).
Dose dense AC (ddAC) followed by T regimen: IV: 60 mg/m2 on day 1 every 14 days for 4 cycles (in combination with cyclophosphamide [and filgrastim], then followed by paclitaxel) (Citron 2003).
AC-TH (HER-2 positive): IV: 60 mg/m2 once every 3 weeks (in combination with cyclophosphamide) for 4 cycles, followed by paclitaxel and trastuzumab (Romond 2005) or 60 mg/m2 every 2 weeks (in combination with cyclophosphamide) for 4 cycles (with growth factor support; followed by paclitaxel and trastuzumab) (Dang 2008).
AC-THP (neoadjuvant therapy; HER-2 positive): IV: 60 mg/m2 once every 2 weeks for 4 cycles (in combination with cyclophosphamide; followed by paclitaxel, pertuzumab, and trastuzumab) (Swain 2017).
TAC regimen: IV: 50 mg/m2 on day 1 every 21 days for 6 cycles (in combination with docetaxel and cyclophosphamide) (Martin 2005).
Keynote- 522 regimen (early triple-negative breast cancer; neoadjuvant therapy): IV: 60 mg/m2 once every 3 weeks (in combination with cyclophosphamide [AC] and pembrolizumab) for 4 cycles (second neoadjuvant treatment); first neoadjuvant treatment was 4 cycles of pembrolizumab/paclitaxel/carboplatin, followed by second neoadjuvant treatment of 4 cycles of AC plus pembrolizumab. After definitive surgery, patients received adjuvant therapy with pembrolizumab and radiation for up to 9 cycles. Refer to protocol for further information (Schmid 2020).
Endometrial carcinoma, advanced (off-label use): 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) or 45 mg/m2 on day 1 every 3 weeks (in combination with cisplatin and optional growth factor support) for up to 6 cycles (Homesley 2009) or 60 mg/m2 (as a single agent) once every 3 weeks until disease progression or unacceptable toxicity (Cohen 1986; McMeekin 2015).
Ewing sarcoma (off-label dosing):
VDC/IE regimen: Adults ≤30 years: IV: 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: IV: 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: IV: 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).
Hepatocellular cancer, intermediate stage, chemoembolization (off-label use): Note: Refer to protocol and institutional policies for additional dosing/administration details.
Conventional transcatheter arterial chemoembolization (cTACE): Intra-arterial: 50 to 75 mg/m2 (maximum: 150 mg) as a single dose via intra-arterial injection every 2 months for a maximum of 3 doses; dose may require adjustment based on bilirubin level (Lammer 2010).
Drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE): Intra-arterial: 150 mg administered via loaded drug-eluting bead every 2 months for a maximum of 3 doses (Lammer 2010); drug-eluting beads loaded with doses ranging from 25 to 150 mg have been shown to be safe and effective.
Hepatocellular cancer, metastatic (off-label use): IV: 60 mg/m2 on day 1 every 28 days (in combination with cisplatin) for up to 6 cycles (Lee 2004) or 60 mg/m2 on day 1 every 21 days (in combination with cisplatin and capecitabine) for up to 6 cycles (Park 2006).
Hodgkin lymphoma (off-label dosing):
ABVD regimen: IV: 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). The number of cycles required and follow-up treatment may be determined by PET scan after 2 cycles (Johnson 2016).
A-AVD regimen: IV: 25 mg/m2 on days 1 and 15 every 4 weeks (in combination with brentuximab vedotin, vinblastine, and dacarbazine) for up to 6 cycles (Connors 2018). Administer primary prophylaxis with G-CSF (filgrastim) beginning with cycle 1.
BEACOPP and escalated BEACOPP regimens: IV: 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) for 8 cycles (Diehl 2003; Engert 2009).
Stanford V regimen: IV: 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).
Multiple myeloma (off-label use):
PAD regimen: Induction: IV: 9 mg/m2/day on days 1 to 4 for 3 cycles (in combination with bortezomib and dexamethasone) (Sonneveld 2012).
VDT-PACE regimen: IV: 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).
Neuroendocrine tumors, pancreatic (off-label use): IV: 40 mg/m2 on day 1 of a 28-day cycle (in combination with streptozocin and fluorouracil) until disease progression or unacceptable toxicity (Kouvaraki 2004) or 50 mg/m2 on days 1 and 22 of a 6-week cycle (in combination with streptozocin) until disease progression or unacceptable toxicity (Moertel 1992).
Non-Hodgkin lymphomas (off-label dosing):
Burkitt lymphoma:
CALGB 10002 regimen (cycles 3, 5, and 7): IV: 25 mg/m2/day on days 4 and 5 every 3 weeks (in combination with cyclophosphamide, vincristine, prednisone, ifosfamide, dexamethasone, methotrexate, leucovorin, cytarabine, etoposide, rituximab, intrathecal therapy, and filgrastim); refer to protocol for further information (Rizzieri 2014).
Hyper-CVAD + rituximab regimen: IV: 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).
R-CODOX-M/IVAC: Cycles 1 and 3 (CODOX-M): IV: 50 mg/m2 on day 1 (Barnes 2011; Lacasce 2004) or 40 mg/m2 on day 1 (Mead 2002), in combination with cyclophosphamide, vincristine, methotrexate, and CNS prophylaxis; CODOX-M alternates with IVAC (ifosfamide, mesna, etoposide, cytarabine, and CNS prophylaxis) ± rituximab for a total of 4 cycles.
Diffuse large B-cell lymphoma (DLBCL):
CHOP or RCHOP regimen: IV: 50 mg/m2 on day 1 every 21 days (in combination with cyclophosphamide, vincristine, and prednisone ± rituximab) (Coiffier 2010; McKelvey 1976).
Dose-adjusted EPOCH or REPOCH regimen: IV: 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).
Pola-R-CHP regimen (previously untreated DLBCL): IV: 50 mg/m2 on day 1 every 21 days (in combination with polatuzumab vedotin, rituximab, cyclophosphamide, and prednisone) for 6 cycles; following the completion of 6 cycles of Pola-R-CHP, rituximab monotherapy was continued for 2 cycles (Tilly 2022).
Follicular lymphoma: R-CHOP regimen: IV: 50 mg/m2 on day 1 of a 21-day treatment cycle for 6 to 8 cycles (in combination with rituximab, cyclophosphamide, vincristine, and prednisone) (Hiddemann 2005).
Mantle cell lymphoma:
Nordic regimen (Maxi-CHOP): IV: 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).
RCHOP/RDHAP: IV: 50 mg/m2 on day 1 of a 21-day treatment cycle (in combination with rituximab, cyclophosphamide, vincristine, and prednisone), alternating or sequentially with RDHAP (rituximab, dexamethasone, cytarabine, and cisplatin) for a total of 6 cycles (3 cycles of each) followed by autologous stem cell transplant (Delarue 2013; Hermine 2016).
Peripheral T-cell lymphoma:
BV-CHP (or A-CHP) regimen: IV: 50 mg/m2 on day 1 of a 21-day treatment cycle (in combination with brentuximab vedotin, cyclophosphamide, and prednisone) for 6 to 8 cycles (Horwitz 2019).
CHOEP regimen: IV: 50 mg/m2 on day 1 of a 21-day treatment cycle (in combination with cyclophosphamide, vincristine, etoposide, and prednisone) for 6 to 8 cycles (Pfreundschuh 2004; Schmitz 2010).
CHOP regimen: IV: 50 mg/m2 on day 1 of a 21-day treatment cycle (in combination with cyclophosphamide, vincristine, and prednisone) for 6 to 8 cycles (Pfreundschuh 2004; Schmitz 2010).
Primary mediastinal B-cell lymphoma: DA-EPOCH-R regimen: IV: 10 mg/m2/day administered as a continuous infusion on days 1 to 4 every 21 days, dose-adjusted for subsequent cycles based on neutrophil and platelet counts during nadir (in combination with etoposide, prednisone, vincristine, cyclophosphamide, rituximab, and filgrastim); repeat cycle every 3 weeks for a total of 6 to 8 cycles (Dunleavy 2013). Refer to protocol for dosage adjustments.
Osteosarcoma (off-label dosing):
Cisplatin/doxorubicin regimen: Adults ≤40 years: IV: 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: IV: 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: IV: 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).
MAP regimen: Adults ≤40 years:
Preoperative: IV: 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) (Bielack 2015; Marina 2016; Whelan 2015).
Postoperative: IV: 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 (Bielack 2015; Marina 2016; Whelan 2015).
Renal carcinoma, advanced; with sarcomatoid features (off-label use): IV: 50 mg/m2 on day 1 every 14 days (in combination with gemcitabine and growth factor support) for 6 to 9 cycles (Haas 2012).
Salivary gland cancers, advanced (off-label use): IV: 50 mg/m2 on day 1 every 21 days (in combination with cisplatin and cyclophosphamide); continue until disease progression or unacceptable toxicity (Lictra 1996) 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 (Debaere 2011).
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 (von Pawel 1999).
Soft tissue sarcoma:
Nonspecific histologies:
AD regimen: IV: 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 (off-label dosing): IV: 30 mg/m2 on days 1 and 2 every 21 days (in combination with ifosfamide and mesna) (Edmonson 1993).
MAID regimen (off-label dosing): IV: 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: IV: 75 mg/m2 on day 1 every 21 days until disease progression or unacceptable toxicity (Santoro 1995).
Rhabdomyosarcoma (off-label dosing):
VAC/IE regimen: Adults <21 years: IV: 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: IV: 25 mg/m2/day on days 1 to 3 every 21 days (in combination with vincristine and ifosfamide) (Ogilvie 2010).
Thymomas and thymic malignancies (off-label use):
CAP regimen: IV: 50 mg/m2 on day 1 every 21 days for up to 8 cycles (in combination with cisplatin and cyclophosphamide) (Loehrer 1994).
CAP with prednisone regimen:
Induction: IV: 20 mg/m2/day administered as a continuous infusion on days 1 to 3 (total dose per cycle: 60 mg/m2) every 3 to 4 weeks (in combination with cyclophosphamide, cisplatin, and prednisone) for 3 cycles, followed by surgical resection, radiation, and consolidation chemotherapy (Kim 2004).
Consolidation: IV: 16 mg/m2/day administered as a continuous infusion on days 1 to 3 (total dose per cycle: 48 mg/m2) every 3 to 4 weeks (in combination with cyclophosphamide, cisplatin, and prednisone) for 3 cycles. Note: During consolidation, cyclophosphamide, cisplatin, and doxorubicin were dosed at 80% of the induction therapy doses; refer to protocol for further information (Kim 2004).
ADOC regimen: IV: 40 mg/m2 on day 1 every 21 days (in combination with cisplatin, vincristine, and cyclophosphamide) (Fornasiero 1991).
Uterine sarcoma (off-label use): IV: 60 mg/m2 on day 1 every 21 days (either as a single agent or in combination with dacarbazine); maximum cumulative doxorubicin 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 (off-label use): 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).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Kenar D. Jhaveri, MD; Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: IV: No dosage adjustment necessary for any degree of kidney impairment (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
IV: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Not significantly dialyzable (large Vd): IV: Initial: Consider administering 75% of the usual indication-specific dose. May increase to 100% of the usual indication-specific dose if well tolerated (Ref).
Peritoneal dialysis: Not likely to be significantly dialyzable (large Vd): IV: Initial: Consider administering 75% of the usual indication-specific dose. May increase to 100% of the usual indication-specific dose if well tolerated (Ref).
CRRT: IV: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): IV: No dosage adjustment necessary (Ref).
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 dose.
Severe hepatic impairment (Child-Pugh class C or bilirubin >5 mg/dL): Use is contraindicated.
The following adjustments have also been recommended:
Serum bilirubin 1.2 to 2.9 mg/dL: Administer 50% of dose (Krens 2019).
Serum bilirubin 3 to 5 mg/dL: Administer 25% of dose (Krens 2019).
Serum bilirubin >5 mg/dL: Use is not recommended (Krens 2019).
Transaminases 2 to 3 times ULN: Administer 75% of dose (Floyd 2006).
Transaminases >3 times ULN: Administer 50% of dose (Floyd 2006).
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (ASCO [Griggs 2021]).
Cardiotoxicity: Discontinue in patients who develop signs/symptoms of cardiomyopathy. Consider dexrazoxane (if appropriate) to reduce cardiac toxicity in patients who have received a high cumulative dose of anthracycline therapy (ESC [Lyon 2022]).
Asymptomatic cardiac dysfunction : Consider initiating heart failure medications (eg, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and/or beta blockers) in patients with asymptomatic (stage B) heart disease (ASCO [Armenian 2017]; ESC [Lyon 2022]).
Mild cardiac dysfunction: Continue treatment with close cardiovascular monitoring (ESC [Lyon 2022]).
Moderate or severe cardiac dysfunction: Interrupt treatment and utilize a multidisciplinary approach when deciding if/when to restart. Initiation of heart failure medications is recommended (ESC [Lyon 2022]).
Symptomatic cardiac dysfunction: Initiate heart failure medications (ESC [Lyon 2022]).
Mild cardiac dysfunction: Consider a multidisciplinary approach for decisions regarding treatment interruption versus continuation (ESC [Lyon 2022]).
Moderate cardiac dysfunction: Interrupt treatment; consider a multidisciplinary approach for decisions regarding treatment reinitiation (ESC [Lyon 2022]).
Severe cardiac dysfunction: Discontinue anthracycline therapy (ESC [Lyon 2022]).
Hematologic toxicity: May require treatment delay or dose reduction (depending on the severity).
Also refer to protocol and/or study reference for specific dosage adjustment details.
Refer to adult dosing.
(For additional information see "Doxorubicin (conventional): Pediatric drug information")
Note: Dose, frequency, number of doses, and start date may vary by protocol and treatment phase; refer to individual protocols. In pediatric patients, dosing may be based on either BSA (mg/m2) or weight (mg/kg); use extra precaution to verify dosing parameters during calculations.
Monitor cumulative anthracycline dose (combined); the risk for cardiomyopathy increases as the cumulative dose increases (>250 mg/m2 in pediatric patients <18 years and 550 mg/m2 in patients >18 years); also dependent on other/additional risk factors; interpatient variability exists (eg, some patients may experience left ventricular dysfunction at lower doses) (ESC [Zamorano 2016]; Long-Term Follow-Up Guidelines [COG 2018]).
Doxorubicin is associated with a moderate or high emetic potential (depending on dose or regimen); antiemetics are recommended to prevent nausea and vomiting (POGO [Paw Cho Sing 2019]). Do NOT substitute conventional doxorubicin for or with doxorubicin (liposomal); products are different and are NOT interchangeable. Use caution when selecting product for preparation and dispensing (both products are the same concentration).
Acute lymphoblastic leukemia (ALL): Limited data available: Children and Adolescents: IV:
DFCI Consortium Protocol 00-01 (Vrooman 2013):
Induction: 30 mg/m2/day on days 0 and 1 of a 4-week cycle (in combination with dexrazoxane [high-risk patients], vincristine, methotrexate, Escherichia coli asparaginase, prednisone, intrathecal cytarabine, and intrathecal methotrexate/cytarabine/hydrocortisone).
CNS therapy: High-risk patients: 30 mg/m2/day on day 1 of a 3-week cycle (in combination with dexrazoxane, vincristine, mercaptopurine, intrathecal methotrexate/cytarabine, and cranial radiation).
Intensification: High-risk patients: 30 mg/m2/day on day 1 of every 3-week cycle (in combination with dexrazoxane, vincristine, mercaptopurine, E. coli asparaginase, prednisone or dexamethasone, and intrathecal methotrexate/cytarabine/hydrocortisone); cumulative doxorubicin dose: 300 mg/m2.
AALL0232 (High risk, newly diagnosed) (Larsen 2016): Delayed Intensification I: 25 mg/m2/day on days 1, 8, and 15 of an 8-week cycle (in combination with vincristine, pegaspargase, dexamethasone, cytarabine, cyclophosphamide, thioguanine, and intrathecal methotrexate).
Desmoplastic small round cell tumor (DSRCT): Limited data available: Children and Adolescents: IV: HD -CAV regimen: 25 mg/m2/day administered as a continuous infusion on days 1, 2, and 3 (total course dose: 75 mg/m2) (in combination with vincristine and cyclophosphamide for courses 1, 2, 4, and 6) alternating cycles with ifosfamide and etoposide for courses 4, 5, and 7 (Kushner 1996).
Ewing sarcoma: Limited data available: Children and Adolescents: IV:
VAC/IE regimen: 75 mg/m2/day 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: 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 (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).
Hepatoblastoma: Limited data available:
INT-0098 protocol (Ortega 2000): Children and Adolescents: IV:
Regimen B (Stage I-Unfavorable Histology, II, III, IV): 20 mg/m2/day administered as a continuous infusion for 4 days (total dose per course: 80 mg/m2) (in combination with cisplatin).
Regimen C (Stage I-Favorable Histology): 20 mg/m2/day on days 1, 2, and 3 every 3 weeks for 4 cycles.
PLADO regimen: Children and Adolescents: IV: 30 mg/m2/day administered as a continuous infusion on days 2 and 3 (total dose per course: 60 mg/m2) every 21 days for up to 6 courses (in combination with cisplatin) administered preoperatively (Czauderna 2002).
Siopel-3HR regimen: High risk: Infants, Children, and Adolescents <16 years: IV: 30 mg/m2/day administered as a continuous infusion over 48 hours (total dose per course: 60 mg/m2 in combination with carboplatin and alternating with cisplatin) beginning on day 15 every 28 days (days 15, 43, and 71) for up to 3 preoperative cycles of doxorubicin/carboplatin. If the tumor is not resectable after 3 preoperative cycles another 2 cycles of doxorubicin/carboplatin may be given. Regardless of when surgery takes place a maximum of 5 cycles of each doxorubicin/carboplatin and cisplatin were administered (Zsíros 2010).
Hodgkin lymphoma: Limited data available: Children and Adolescents: IV:
Low risk, lymphocyte-predominant Hodgkin lymphoma: AV-PC regimen: 50 mg/m2/day on day 1 of a 21-day cycle (in combination with vincristine, prednisone, cyclophosphamide) (Appel 2016).
Low risk, classical Hodgkin lymphoma: AVPC regimen : 25 mg/m2/day on days 1 and 2 of a 21-day cycle (in combination with vincristine, prednisone, cyclophosphamide) (Keller 2018).
Intermediate or high risk: ABVE-PC regimen: 30 mg/m2/day on days 0 and 1 of a 21-day cycle (in combination with bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide) (Schwartz 2009).
Advanced stage or high risk:
AVBD regimen: 25 mg/m2/day on days 0 and 14 of a 28-day cycle (in combination with bleomycin, vinblastine, and dacarbazine) (Kelly 2011).
BEACOPP regimen: 35 mg/m2/day administered on day 0 of a 21-day treatment cycle (in combination with bleomycin, etoposide, cyclophosphamide, vincristine, procarbazine, and prednisone) (Kelly 2011).
Neuroblastoma: Limited data available:
High risk (Stage IV disease):
CAV-P/VP regimen: Infants and Children: IV:
≤12 kg: 0.83 mg/kg/day as a continuous infusion on days 1, 2, and 3 (total dose: 2.49 mg/kg) of courses 1, 2, 4, and 6 (in combination with cyclophosphamide, and vincristine [CAV] with etoposide and cisplatin [P/VP] during courses 3, 5, and 7) (Park 2016).
>12 kg: 25 mg/m2/day as a continuous infusion on days 1, 2, and 3 (total dose: 75 mg/m2) of courses 1, 2, 4, and 6 (in combination with cyclophosphamide, and vincristine [CAV] with etoposide and cisplatin [P/VP] during courses 3, 5, and 7) (Kreissman 2013; Kushner 1994; Park 2016).
Cisplatin-Doxorubicin-Etoposide-Cyclophosphamide regimen: Infants, Children, and Adolescents: IV:
<10 kg: 1 mg/kg/day on day 2 of a 28-day cycle (in combination with cisplatin, etoposide, and cyclophosphamide) for a total of 5 cycles (Parikh 2015).
≥10 kg: 30 mg/m2/day on day 2 of a 28-day cycle (in combination with cisplatin, etoposide, and cyclophosphamide) for a total of 5 cycles (Matthay 1999; Parikh 2015).
Unresectable disease: CE-CAdO regimen:
Infants: IV: 2 mg/kg/day on day 5 of cycles 3 and 4 (CAdO; 21-day cycles) (in combination with cyclophosphamide, vincristine [CAdO], and carboplatin and etoposide [CE]) (Rubie 2001).
Children: IV: 60 mg/m2/day on day 5 of cycles 3 and 4 (CAdO; 21-day cycles) (in combination with cyclophosphamide, vincristine [CAdO], and carboplatin and etoposide [CE]) (Rubie 1998).
Non-Hodgkin lymphoma: Limited data available: Children and Adolescents: IV:
Anaplastic large cell lymphoma (ALCL):
NHL-BFM 90 Regimen, Course B and BB: 25 mg/m2/day infused over 1 hour on days 4 and 5 of a 21- to 28-day cycle (depending on neutrophil recovery) (in combination with dexamethasone, cyclophosphamide, methotrexate, and intrathecal prophylaxis therapy) (Seidemann 2001).
ALCL-99 Regimen, Course BM and BV: 25 mg/m2/day on days 4 and 5 of a 21-day cycle (in combination with cyclophosphamide, methotrexate, vinblastine, and intrathecal prophylaxis therapy) (Wrobel 2011).
Mature B-cell Lymphomas (Burkitt lymphoma, Burkitt-like lymphoma, etc):
High risk (Group C):
COPADM 1 and 2 regimen: Induction: 60 mg/m2/day on day 2 of a 16- to 21-day cycle (depending on neutrophil recovery) (in combination with cyclophosphamide, vincristine, prednisone, methotrexate, and intrathecal chemotherapy [refer to protocol and institution guidelines]) (Cairo 2007; Goldman 2014).
COPA regimen: Maintenance 1 (M1) and 3 (M3): 60 mg/m2/day over 30 to 60 minutes on Day 2 (M1) or Day 1 (M3) (in combination with cyclophosphamide, vincristine, prednisone, with/without methotrexate) (Cairo 2007; Goldman 2014).
Intermediate risk (Group B): COPADM 1 and 2: Induction: 60 mg/m2/day over ≤1 hour on day 1 (in combination with cyclophosphamide, vincristine, prednisone, methotrexate with/without rituximab) (Goldman 2013).
Primary mediastinal large B-cell lymphoma (PMBCL): Very limited data available: Children ≥9 years and Adolescents: DA-EPOCH-R regimen: IV: 10 mg/m2/day as a continuous infusion on days 1 to 4 (96 hours) (total dose: 40 mg/m2 per course); dose-adjusted for subsequent cycles based on neutrophil and platelet counts during nadir (in combination with etoposide, vincristine, cyclophosphamide, prednisone, and rituximab) (Dunleavy 2013; Giulino-Roth 2017; Wilson 2013).
Osteosarcoma: Limited data available: Children and Adolescents: IV: High-dose methotrexate/cisplatin/doxorubicin (MAP) regimen:
Preoperative: 37.5 mg/m2/day on days 1 and 2 of week 1 and 6 (in combination with cisplatin and alternating with cycles of methotrexate) (Marina 2016).
Postoperative: 37.5 mg/m2/day on days 1 and 2 of weeks 12, 17, 22, and 26 (weeks 12 and 17 are in combination with cisplatin and alternating with methotrexate); refer to protocol for criteria, frequency, and other specific information (Marina 2016).
Rhabdomyosarcoma: Limited data available: Children and Adolescents: IV: VAC/IE regimen: 37.5 mg/m2/day 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).
Wilms tumor:
DD-4A regimen: Note: Begin regimen when ANC ≥750 mm3 and platelet count ≥75,000 mm3.
Infants: IV: 1.5 mg/kg/day on day 1 of weeks 4 and 10 and then 1 mg/kg/day on day 1 of week 16 and 22 (in combination with dactinomycin and vincristine). Reduce dose by 50% (ie, 0.75 mg/kg/day) for the first dose given within 6 weeks following whole lung or whole abdominal radiation (but not after flank radiation) unless administered concurrently with the start of radiation therapy (Ehrlich 2017).
Children and Adolescents: IV: 45 mg/m2/day on day 1 of weeks 4 and 10 and then 30 mg/m2/day on day 1 of weeks 16 and 22 (in combination with dactinomycin and vincristine). Reduce dose by 50% (ie, 22.5 mg/m2/day) for the first dose given within 6 weeks following whole lung or whole abdominal radiation (but not after flank radiation) unless administered concurrently with the start of radiation therapy (Ehrlich 2017).
NWTS-5 Regimen I (unresectable tumors or stage II to IV tumors with blastemal predominance at time of definitive surgical procedure at either week 6 or 12 or relapsed disease):
Infants: IV: 1.5 mg/kg/day administered as an IV push on day 1 of weeks 7, 13, 19, and 25 (in combination with vincristine, cyclophosphamide, mesna, etoposide, and filgrastim); reduce dose by 50% (ie, 0.75 mg/kg) at week 6 if patient undergoes radiation; omit week 25 if patient received 6 or 12 weeks of preoperative therapy with Regimen VAD (Ehrlich 2017).
Children and Adolescents: IV: 45 mg/m2/day administered as IV push on day 1 of weeks 7, 13, 19, and 25 (in combination with vincristine, cyclophosphamide, mesna, etoposide, and filgrastim); reduce dose by 50% (ie, 22.5 mg/m2) at week 6 if patient undergoes radiation; omit week 25 if patient received 6 or 12 weeks of preoperative therapy with Regimen VAD (Ehrlich 2017).
Revised UH-1 Regimen:
Infants: IV: 1.5 mg/kg/day administered as an IV push on day 1 of weeks 1, 10, 13, 22, and 28 (in combination with vincristine, cyclophosphamide, mesna, carboplatin, and filgrastim); reduce dose by 50% (0.75 mg/kg) if administered during or within 6 weeks of completing radiation; omit week 28 if patient received 6 weeks of Regimen VAD; omit weeks 13, 22, and 28 if patient received 12 weeks of Regimen VAD (Ehrlich 2017).
Children and Adolescents: IV: 45 mg/m2/day administered as IV push on day 1 of weeks 1, 10, 13, 22, and 28 (in combination with vincristine, cyclophosphamide, mesna, carboplatin, and filgrastim); reduce dose by 50% (22.5 mg/m2) if administered during or within 6 weeks of completing radiation; omit week 28 if patient received 6 weeks of Regimen VAD; omit weeks 13, 22, and 28 if patient received 12 weeks of Regimen VAD (Ehrlich 2017).
VAD regimen:
Infants: IV: 1.2 mg/kg/day on day 1 of weeks 1, 4, 7, and 10 (in combination with vincristine and dactinomycin) (Ehrlich 2017).
Children and Adolescents: IV: 35 mg/m2/day on day 1 of weeks 1, 4, 7, 10 (in combination with vincristine and dactinomycin) (Ehrlich 2017).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
All patients: Mild, moderate, or severe impairment: There are no dosage adjustments provided in the manufacturers' labeling (has not been studied); however, adjustments are likely not necessary given limited renal excretion. The following adjustments have also been recommended (Aronoff 2007):
CrCl <50 mL/minute: No dosage adjustment necessary.
Hemodialysis: Supplemental dose is not necessary.
Infants, Children, and Adolescents:
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 dose.
Severe hepatic impairment (eg, bilirubin >5 mg/dL): Use is contraindicated.
The following adjustments have also been recommended based on experience in adults (Floyd 2006):
Transaminases 2 to 3 times ULN: Administer 75% of dose.
Transaminases >3 times ULN: Administer 50% of dose.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Percentages may be reported as part of combination chemotherapy regimens in adults.
>10%:
Cardiovascular: Cardiomyopathy (1% to 20%; including cardiac insufficiency [<1%], decreased left ventricular ejection fraction, heart failure, myocarditis, and pericarditis) (Felker 1999, Kumar 2012, Suto 2023)
Dermatologic: Alopecia (92%)
Gastrointestinal: Vomiting (34% to 37%; intractable vomiting: 5%)
1% to 10%:
Hematologic & oncologic: Bone marrow depression (can be severe; leukopenia [grades 3/4: ≤3%], neutropenia, and thrombocytopenia [grades 3/4: <1%]), myelodysplastic syndrome (≤2%), secondary acute myelocytic leukemia (≤2%)
Infection: Sepsis (2%; septic shock [2%])
Postmarketing:
Cardiovascular: Arterial thrombosis (Jang 2019), atrial fibrillation (Hassan 2023), cardiogenic shock (Chong 2021), cardiotoxicity (including cardiomegaly, systolic heart murmur, and potential endomyocardial fibrosis) (Fitter 1981), phlebitis, phlebosclerosis, thromboembolism, thrombophlebitis
Dermatologic: Nail hyperpigmentation (Bird 2006, Prajapati 2017), onycholysis (Jones 1989), palmar-plantar erythrodysesthesia (Jones 1989), pruritus, skin hyperpigmentation, skin photosensitivity, skin rash, urticaria
Endocrine & metabolic: Dehydration, hot flash, weight gain
Gastrointestinal: Abdominal pain, anorexia, diarrhea, dysgeusia (Rehwaldt 2009), esophagitis, gastrointestinal erosion, gastrointestinal hemorrhage, hematochezia, nausea, necrotizing enterocolitis, neutropenic typhlitis, oral mucosal hyperpigmentation, stomatitis
Hepatic: Exacerbation of hepatitis B (including acute hepatic failure, increased serum alkaline phosphatase, increased serum bilirubin, and jaundice) (Hakami 2022), increased serum transaminases (including increased serum alanine aminotransferase, increased serum aspartate aminotransferase) (Hakami 2022)
Hypersensitivity: Anaphylaxis
Nervous system: Asthenia, chills, coma, malaise, peripheral motor neuropathy, peripheral sensory neuropathy, seizure
Ophthalmic: Conjunctivitis, keratitis, lacrimation
Miscellaneous: Fever, radiation recall phenomenon (Burris 2010)
Severe hypersensitivity (including anaphylaxis) to doxorubicin or any component of the formulation; recent myocardial infarction (within past 4 to 6 weeks), severe myocardial insufficiency; severe persistent drug-induced myelosuppression; severe hepatic impairment (Child-Pugh class C or bilirubin >5 mg/dL).
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to other anthracyclines or anthracenediones; severe arrhythmias; history of severe cardiac disease; previous treatment with maximum cumulative doses of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other anthracyclines and anthracenediones.
Concerns related to adverse effects:
• Bone marrow suppression: Severe myelosuppression resulting in serious infection, septic shock, transfusion requirements, hospitalization, and death may occur. Dose-dependent and reversible neutropenia commonly occurs. Grade 3 and 4 leukopenia and thrombocytopenia have occurred; anemia may also occur. When administered on an every-3-week schedule, the nadir typically occurs 10 to 14 days after administration with cell count recovery by day 21.
• Cardiomyopathy: Myocardial damage (including acute left ventricular failure) can occur with doxorubicin with incidences from 1% to 20% for cumulative doses from 300 mg/m2 to 500 mg/m2 when doxorubicin is administered every 3 weeks. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Delayed cardiotoxicity may occur late in treatment or within months to years after completion of therapy, and is typically manifested by decreased left ventricular ejection fraction (LVEF) and/or signs/symptoms of heart failure. The total cumulative doxorubicin dose should take into account prior treatment with other anthracyclines or anthracenediones. The risk for developing cardiotoxicity is estimated to range from 1% to 2% at cumulative lifetime doses of 300 mg/m2 to 6% to 20% at cumulative lifetime doses of 500 mg/m2. The risk of cardiomyopathy is increased in patients who have received radiotherapy to the mediastinum or concomitant therapy with other known cardiotoxic agents such as cyclophosphamide and trastuzumab. Pericarditis and myocarditis have also been reported during or following doxorubicin treatment. Doxorubicin can result in arrhythmias, including life-threatening arrhythmias, during or within a few hours after administration and at any time point during treatment. Tachyarrhythmias (including sinus tachycardia, premature ventricular contractions, and ventricular tachycardia), and bradycardia may occur; ECG changes including non-specific ST-T wave changes, atrioventricular and bundle-branch block may also occur; ECG changes may be transient and self-limiting and may not require doxorubicin dose modifications.
According to ASCO guidelines (ASCO [Armenian 2017]), the risk of cardiac dysfunction is increased with high-dose anthracycline therapy (eg, doxorubicin ≥250 mg/m2); high-dose radiotherapy (≥30 Gy) with the heart in the treatment field; lower-dose anthracyclines (eg, doxorubicin <250 mg/m2) in combination with lower-dose radiotherapy (<30 Gy) with the heart in the treatment field; lower-dose anthracyclines AND any of the following risk factors: ≥2 cardiovascular risk factors (including smoking, hypertension, diabetes, dyslipidemia, and obesity) during or after completion of therapy or age ≥60 years at cancer treatment, or compromised cardiac function (eg, borderline low LVEF [50% to 55%], history of MI, moderate or higher valvular heart disease) before or during treatment; treatment with lower-dose anthracycline followed by trastuzumab (sequential therapy); other risk factors for anthracycline-induced cardiotoxicity include age ≥60 years at time of treatment and 2 or more cardiovascular risk factors (smoking, hypertension, diabetes, dyslipidemia, or obesity) during or after treatment.
• Extravasation: Vesicant; extravasation may result in severe local tissue injury and necrosis requiring wide excision of the affected area and skin grafting. If extravasation is suspected, immediately terminate infusion and apply ice to the affected area. For IV administration only; do not administer by IM or SUBQ routes. Ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.
• Secondary malignancy: Secondary acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) occur at a higher incidence in patients treated with anthracyclines, including doxorubicin. AML and MDS typically occur within 1 to 3 years of treatment.
• Tumor lysis syndrome: May cause tumor lysis syndrome and hyperuricemia (in patients with rapidly growing tumors). Urinary alkalinization and prophylaxis with an antihyperuricemic agent may be necessary.
Disease-related concerns:
• Hepatic impairment: Doxorubicin clearance is decreased in patients with elevated serum bilirubin and toxicities may be increased.
Special populations:
• Pediatric: Children are at increased risk for developing delayed cardiotoxicity; long-term periodic cardiac function monitoring is recommended. A panel from the American Society of Pediatric Hematology/Oncology (ASPHO) and International Society of Pediatric Oncology (SIOP) recommends in favor of an anthracycline infusion duration of at least 1 hour in pediatric patients to reduce the potential for cardiotoxicity (ASPHO/SIOP [Loeffen 2017]). However, extravasation risks should also be minimized and the protocol infusion duration specified in a protocol should be followed, particularly if the patient is receiving dexrazoxane as a cardioprotectant. Doxorubicin may contribute to prepubertal growth failure in children; may also contribute to gonadal impairment (usually temporary). Radiation recall pneumonitis has been reported in children receiving concomitant dactinomycin and doxorubicin.
• Radiation recipients: Use with caution in patients who have received radiation therapy; radiation recall may occur. May increase radiation-induced toxicity to the myocardium, mucosa, skin, and liver.
Dosage form specific issues:
• Formulations (conventional vs liposomal): Use caution when selecting product for preparation and dispensing; indications, dosages and adverse event profiles differ between conventional doxorubicin hydrochloride solution and doxorubicin liposomal. Both formulations are the same concentration. As a result, serious errors have occurred.
Pediatric patients are at increased risk for developing delayed cardiac toxicity and CHF during early adulthood due to an increasing census of long-term survivors; risk factors include: Young treatment age (<5 years), cumulative exposure, and concomitant cardiotoxic therapy. Up to 40% of pediatric patients may have subclinical cardiac dysfunction and 5% to 10% may develop heart failure. Long-term monitoring is recommended for all pediatric patients (Long-Term Follow-Up Guidelines [COG 2018]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous, as hydrochloride:
Generic: 2 mg/mL (5 mL, 10 mL, 25 mL, 100 mL)
Solution, Intravenous, as hydrochloride [preservative free]:
Adriamycin: 2 mg/mL (5 mL [DSC], 10 mL [DSC], 25 mL [DSC], 100 mL [DSC])
Generic: 2 mg/mL (5 mL, 10 mL, 25 mL, 75 mL [DSC], 100 mL)
Solution Reconstituted, Intravenous, as hydrochloride:
Generic: 10 mg (1 ea); 50 mg (1 ea)
Solution Reconstituted, Intravenous, as hydrochloride [preservative free]:
Adriamycin: 10 mg (1 ea [DSC]); 50 mg (1 ea) [contains lactose monohydrate]
Yes
Solution (DOXOrubicin HCl Intravenous)
2 mg/mL (per mL): $0.36 - $1.71
Solution (reconstituted) (Adriamycin Intravenous)
50 mg (per each): $315.64
Solution (reconstituted) (DOXOrubicin HCl Intravenous)
10 mg (per each): $63.13
50 mg (per each): $315.64
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as hydrochloride:
Generic: 2 mg/mL (5 mL, 10 mL, 25 mL, 100 mL)
Solution Reconstituted, Intravenous:
Generic: 150 mg (1 ea)
Solution Reconstituted, Intravenous, as hydrochloride:
Generic: 10 mg (1 ea); 50 mg (1 ea)
Doxorubicin is associated with a moderate to high emetic potential (depending on dose or regimen); antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).
IV: Administer IV push over at least 3 to 10 minutes or by continuous infusion (infusion via central venous line recommended). Do not administer IM or SubQ. Rate of administration varies by protocol, refer to individual protocol for details. Protect from light until completion of infusion. Avoid contact with alkaline solutions. Monitor for local erythematous streaking along vein and/or facial flushing (may indicate rapid infusion rate); decrease the rate if occurs.
Ensure appropriate product is being administered (conventional doxorubicin and doxorubicin [liposomal] are different products and are NOT interchangeable).
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Initiate antidote (dexrazoxane or dimethyl sulfate [DMSO]). Apply dry cold compresses for 20 minutes 4 times daily for 1 to 2 days (ESMO/EONS [Perez Fidalgo 2012]); withhold cooling beginning 15 minutes before dexrazoxane infusion; continue withholding cooling until 15 minutes after infusion is completed. Topical DMSO should not be administered in combination with dexrazoxane; may lessen dexrazoxane efficacy.
Dexrazoxane: 1000 mg/m2 (maximum dose: 2000 mg) IV (administer in a large vein remote from site of extravasation) over 1 to 2 hours days 1 and 2, then 500 mg/m2 (maximum dose: 1000 mg) IV over 1 to 2 hours day 3; begin within 6 hours of extravasation. Day 2 and day 3 doses should be administered at approximately the same time (± 3 hours) as the dose on day 1 (Mouridsen 2007; ESMO/EONS [Perez Fidalgo 2012]). Note: Reduce dexrazoxane dose by 50% in patients with moderate to severe renal impairment (CrCl <40 mL/minute).
DMSO: Apply topically to a region covering twice the affected area every 8 hours for 7 days; begin within 10 minutes of extravasation; do not cover with a dressing (ESMO/EONS [Perez Fidalgo 2012]).
Transcatheter arterial chemoembolization (TACE): For conventional TACE, doxorubicin was administered with lipiodol followed by particle embolization with an embolic agent (Lammer 2010). IV antibiotics were administered prior to the procedure and embolic material was injected through the catheter until hemostasis was achieved (Morse 2012). For drug-eluting bead TACE, patients received a 4 mL bead loaded with doxorubicin mixed with non-ionic contrast media (Lammer 2010). Refer to protocol and institutional policies for additional administration details.
Doxorubicin is associated with a moderate or high emetic potential (depending on dose or regimen); antiemetics are recommended to prevent nausea and vomiting (POGO [Paw Cho Sing 2019).
Parenteral: Administer IV push over at least 3 to 10 minutes or by continuous IV infusion (infusion via central venous line recommended). Do not administer IM or SubQ. Rate of administration varies by protocol; however, some experts recommend infusing anthracyclines over at least 1 hour to reduce the potential for cardiotoxicity (ASPHO/SIOP [Loeffen 2017]). Refer to individual protocol for details, particularly if the patient is receiving dexrazoxane as a cardioprotectant (including timing with respect to dexrazoxane administration); take precautions to minimize extravasation risks.
Protect from light until completion of infusion. Avoid contact with alkaline solutions. Monitor for local erythematous streaking along vein and/or facial flushing (may indicate rapid infusion rate); decrease rate if occurs.
Ensure appropriate product is being administered (conventional doxorubicin and doxorubicin [liposomal] are different products and are NOT interchangeable).
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Initiate antidote (dexrazoxane (adults) or dimethyl sulfate [DMSO]) (see Management of Drug Extravasations for more details). Apply dry cold compresses for 20 minutes 4 times daily for 1 to 2 days (Pérez Fidalgo 2012); withhold cooling beginning 15 minutes before dexrazoxane infusion; continue withholding cooling until 15 minutes after infusion is completed. Topical DMSO should not be administered in combination with dexrazoxane; may lessen dexrazoxane efficacy.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Breast cancer, adjuvant therapy: Treatment component of adjuvant therapy (multi-agent) in women with evidence of axillary lymph node involvement following resection of primary breast cancer
Other cancers: Treatment of acute lymphoblastic leukemia, acute myeloid leukemia, bladder cancer (transitional cell, metastatic), bone sarcoma (metastatic), breast cancer (metastatic), bronchogenic carcinoma (metastatic), Hodgkin lymphoma, non-Hodgkin lymphomas, neuroblastoma (metastatic), ovarian cancer (metastatic), soft tissue sarcoma (metastatic), thyroid carcinoma (metastatic), Wilms tumor (metastatic).
Adrenocortical carcinoma, advanced; Adult T-cell leukemia/lymphoma; Endometrial carcinoma; Hepatocellular carcinoma (intermediate stage; chemoembolization); Hepatocellular carcinoma (metastatic); Multiple myeloma; Neuroendocrine tumors, pancreatic; Renal carcinoma (advanced); Salivary gland cancers (advanced); Thymomas and thymic malignancies; Uterine sarcoma; Waldenström macroglobulinemia
Conventional formulation (Adriamycin) may be confused with the liposomal formulation (Doxil)
DOXOrubicin may be confused with DACTINomycin, DAUNOrubicin, DAUNOrubicin liposomal, doxapram, doxazosin, DOXOrubicin liposomal, epiRUBicin, IDArubicin, valrubicin
Adriamycin may be confused with achromycin, Aredia, Idamycin
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Use caution when selecting product for preparation and dispensing; indications, dosages, rate of administration, and adverse event profiles differ between conventional DOXOrubicin hydrochloride solution and DOXOrubicin liposomal. Both formulations are the same concentration. As a result, serious errors have occurred.
ADR is an error-prone abbreviation
Rubex, a discontinued brand name for DOXOrubicin in the US, is a brand name for ascorbic acid in Ireland
Substrate of CYP2D6 (major), CYP3A4 (major), P-glycoprotein/ABCB1 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Ado-Trastuzumab Emtansine: May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with ado-trastuzumab emtansine should avoid anthracycline-based therapy for up to 7 months after stopping ado-trastuzumab emtansine. Monitor closely for cardiac dysfunction in patients receiving this combination. Risk D: Consider therapy modification
Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Asciminib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Bevacizumab: May enhance the cardiotoxic effect of Anthracyclines. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CycloPHOSphamide: May enhance the cardiotoxic effect of Anthracyclines. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
CYP2D6 Inhibitors (Strong): May increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Dexrazoxane: May diminish the therapeutic effect of DOXOrubicin (Conventional). Management: Do not administer dexrazoxane for cardioprotection at the time of doxorubicin initiation. This recommendation does not apply to the use of dexrazoxane for other indications (eg, extravasation), or to the use of dexrazoxane later in treatment. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Elacestrant: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: If coadministration with these narrow therapeutic index/sensitive P-gp substrates is unavoidable, separate erdafitinib administration by at least 6 hours before or after administration of these P-gp substrates. Risk D: Consider therapy modification
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Fam-Trastuzumab Deruxtecan: May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with fam-trastuzumab deruxtecan should avoid anthracycline-based therapy for up to 7 months after stopping fam-trastuzumab deruxtecan. Monitor closely for cardiac dysfunction in patients receiving this combination. Risk D: Consider therapy modification
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Futibatinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Gilteritinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Margetuximab: Anthracyclines may enhance the adverse/toxic effect of Margetuximab. Specifically, the risk of cardiac dysfunction may be increased. Management: Avoid anthracycline-based therapy for up to 4 months after discontinuing margetuximab due to an increased risk of cardiac dysfunction. If anthracyclines must be used with margetuximab monitor cardiac function closely. Risk D: Consider therapy modification
Mercaptopurine: DOXOrubicin (Conventional) may enhance the hepatotoxic effect of Mercaptopurine. Risk C: Monitor therapy
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
PACLitaxel (Conventional): May increase the serum concentration of DOXOrubicin (Conventional). Management: Administer doxorubicin prior to paclitaxel if these agents are used in combination. Monitor cardiac function if combined. Risk D: Consider therapy modification
PACLitaxel (Protein Bound): May increase the serum concentration of DOXOrubicin (Conventional). Management: Administer doxorubicin prior to paclitaxel if these agents are used in combination. Monitor cardiac function if combined. Risk D: Consider therapy modification
Pacritinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
Phenytoin: May decrease the serum concentration of DOXOrubicin (Conventional). DOXOrubicin (Conventional) may decrease the serum concentration of Phenytoin. Risk X: Avoid combination
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Pretomanid: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sparsentan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Stavudine: DOXOrubicin (Conventional) may diminish the therapeutic effect of Stavudine. Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Taurursodiol: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Taxane Derivatives: May enhance the adverse/toxic effect of Anthracyclines. Taxane Derivatives may increase the serum concentration of Anthracyclines. Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue. Management: Consider separating doxorubicin and paclitaxel administration by as much time as possible, using liposomal doxorubicin or epirubicin instead of doxorubicin, or using docetaxel instead of paclitaxel. Monitor closely for cardiovascular and other toxicities. Risk D: Consider therapy modification
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Trastuzumab: May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with trastuzumab should avoid anthracycline-based therapy for up to 7 months after stopping trastuzumab. Monitor closely for cardiac dysfunction in patients receiving anthracyclines with trastuzumab. Risk D: Consider therapy modification
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Vinflunine: DOXOrubicin (Conventional) may enhance the adverse/toxic effect of Vinflunine. Specifically, the risk for hematologic toxicities may be increased. Risk C: Monitor therapy
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Zidovudine: DOXOrubicin (Conventional) may enhance the adverse/toxic effect of Zidovudine. DOXOrubicin (Conventional) may diminish the therapeutic effect of Zidovudine. Management: Avoid concomitant use of doxorubicin and zidovudine due to the possibility of reduced zidovudine efficacy and increased myelosuppressive effects. Risk D: Consider therapy modification
Evaluate pregnancy status prior to use in patients who could become pregnant.
Patients who could become pregnant should use highly effective contraception during treatment and for 6 months after the last doxorubicin dose.
Patients with partners who could become pregnant should use effective contraception during treatment and for 3 to 6 months (depending on manufacturer) after the last doxorubicin dose. In addition, patients with pregnant partners should use condoms during treatment and for at least 10 days after the last dose of doxorubicin.
Doxorubicin may impair fertility in males and females. In males, doxorubicin may damage spermatozoa and testicular tissue, resulting in possible genetic fetal abnormalities; may also result in oligospermia, azoospermia, and permanent loss of fertility (sperm counts have been reported to return to normal levels in some men, occurring several years after the end of therapy). In females of reproductive potential, doxorubicin may cause infertility and result in amenorrhea; premature menopause can occur.
Doxorubicin crosses the placenta (Ryu 2014). First trimester exposure should be avoided (Azim 2010a; Azim 2010b). A neonatal echocardiogram and ECG are recommended following intrauterine anthracycline exposure (Amant 2019).
Some pharmacokinetic properties of doxorubicin may be altered in pregnant patients (Ryu 2014; van Hasselt 2014). Use of doxorubicin in pregnant patients has been described for indications such as acute myeloid leukemia, breast cancer, and aggressive Hodgkin and non-Hodgkin lymphomas (Ali 2015; Azim 2011; Lishner 2016; Ring 2005).
The European Society for Medical Oncology (ESMO) has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). If chemotherapy is indicated, it should not be administered in the first trimester, but may begin in the second trimester. There should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (ESMO [Peccatori 2013]).
A pregnancy registry is available for all cancers diagnosed during pregnancy at Cooper Health (877-635-4499).
Doxorubicin and its metabolites are present in breast milk.
Information related to the presence of doxorubicin in breast milk is available from a lactating woman treated for ovarian cancer. Doxorubicin was infused over 15 minutes at 7 months postpartum. Breast milk doxorubicin concentrations peaked 24 hours after treatment and were detectable for up to 72 hours after the dose. Peak doxorubicin concentrations in breast milk were 4.4 times greater than maternal plasma concentrations (Egan 1985). A second case evaluated doxorubicin in the breast milk following maternal treatment for stage IV diffuse large B-cell lymphoma at 4 months postpartum. Doxorubicin and the doxorubicinol metabolite were detectable in breast milk for 21 days after the first dose (Codacci-Pisanelli 2019).
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer does not recommend breastfeeding during doxorubicin therapy and for 10 days after the last doxorubicin dose. Others suggest breastfeeding should be avoided for at least 6 weeks after the last dose of doxorubicin (Codacci-Pisanelli 2019).
Monitor cumulative (lifetime) anthracycline/doxorubicin dose. Monitor CBC with differential and platelet count (at baseline and regularly during treatment); LFTs (bilirubin, ALT/AST, alkaline phosphatase; at baseline and during treatment); renal function (creatinine), serum uric acid, and electrolytes (calcium, potassium, phosphate). Assess cardiac function (baseline, periodic, and follow-up): ECG, left ventricular ejection fraction (baseline and regularly during treatment; assess via echocardiography or multigated radionuclide angiography; use the same assessment method at all time points; increase the frequency of assessments as the cumulative dose exceeds 300 mg/m2). Evaluate pregnancy status prior to use in patients who could become pregnant. Monitor hydration status and for signs/symptoms of tumor lysis syndrome and secondary malignancies. Monitor infusion site.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Additional cardiovascular monitoring (ASCO [Armenian 2017], ESC [Lyon 2022]): Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking. Echocardiogram (transthoracic preferred, perform at baseline and 12 months after therapy completion for all patients; in addition, perform every 2 cycles and within 3 months after therapy completion for high- or very high-risk patients). Cardiac biomarkers (troponin and natriuretic peptide at baseline for high and very high-risk patients [may consider for low- and moderate-risk]; also prior to each cycle during anthracycline treatment and at 3 and 12 months after therapy completion for high- and very high-risk patients). In patients who develop signs/symptoms of cardiac dysfunction during therapy, echocardiogram is recommended for diagnostic workup; if echocardiogram is not available or feasible, a cardiac MRI (preferred) or MUGA scan may be utilized; obtain serum cardiac biomarkers. Refer to a cardiologist when clinically indicated.
Doxorubicin inhibits DNA and RNA synthesis by intercalation between DNA base pairs by inhibition of topoisomerase II and by steric obstruction. Doxorubicin intercalates at points of local uncoiling of the double helix. Although the exact mechanism is unclear, it appears that direct binding to DNA (intercalation) and inhibition of DNA repair (topoisomerase II inhibition) result in blockade of DNA and RNA synthesis and fragmentation of DNA. Doxorubicin is also a powerful iron chelator; the iron-doxorubicin complex can bind DNA and cell membranes and produce free radicals that immediately cleave the DNA and cell membranes.
Distribution: Vd: 809 to 1,214 L/m2; does not cross the blood-brain barrier
Protein binding, plasma: ~75%
Metabolism: Primarily hepatic to doxorubicinol (active), then to inactive aglycones, conjugated sulfates, and glucuronides
Half-life elimination:
Distribution: ~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)
Clearance:
Infants and Children <2 years: 813 mL/minute/m2
Children and Adolescents >2 years: 1,540 mL/minute/m2
Adults: 324 to 809 mL/minutes/m2 (appears to be higher in men than women)
Hepatic function impairment: Clearance is reduced.
Obesity: Systemic clearance is significantly reduced in females with ideal body weight >130%. There was a significant reduction in clearance without any change in Vd in these patients when compared with healthy patients with <115% ideal body weight.
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