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Mitoxantrone Side Effects

Not all side effects for mitoxantrone may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to mitoxantrone: intravenous solution

In addition to its needed effects, some unwanted effects may be caused by mitoxantrone. In the event that any of these side effects do occur, they may require medical attention.

If any of the following side effects occur while taking mitoxantrone, check with your doctor or nurse immediately:

More common
  • Black, tarry stools
  • bladder pain
  • bloody or cloudy urine
  • cough or shortness of breath
  • difficult, burning, or painful urination
  • dizziness
  • fainting
  • fast, slow, or irregular heartbeat
  • frequent urge to urinate
  • lower back or side pain
  • pale skin
  • stomach pain
  • swelling or inflammation of the mouth
  • troubled breathing with exertion
  • ulcers, sores, or white spots in the mouth
  • unusual bleeding or bruising
  • unusual tiredness or weakness
Less common
  • Blood in the urine or stools
  • decrease in urination
  • fever or chills
  • pinpoint red spots on the skin
  • seizures
  • sore, red eyes
  • swelling of the feet and lower legs
  • yellow eyes or skin
  • Blue skin at the place of injection
  • pain or redness at the place of injection
  • skin rash

Some of the side effects that can occur with mitoxantrone may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Absent, missed, or irregular menstrual periods
  • back pain
  • body aches or pains
  • congestion
  • constipation
  • diarrhea
  • dryness or soreness of the throat
  • hair loss
  • headache
  • longer or heavier menstrual periods
  • nausea or vomiting
  • oral bleeding
  • pain or tenderness around the eyes and cheekbones
  • runny nose
  • sneezing
  • stopping of menstrual bleeding
  • stuffy nose
  • tender, swollen glands in the neck
  • thinning of the hair

For Healthcare Professionals

Applies to mitoxantrone: intravenous solution


Myelosuppression associated with mitoxantrone may be cumulative with successive therapy. Its severity appears to be correlated with total dose, patient performance status, treatment history, and the degree of marrow disease involvement.

Early data have shown the ratio of equi-myelosuppressive doses of mitoxantrone to doxorubicin is approximately 1:5.

Autologous bone marrow rescue and recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used to ameliorate mitoxantrone-induced myelosuppression.[Ref]

Hematologic side effects including leukopenia have been reported. Dose-limiting leukopenia usually occurs within 7 to 14 days, and is the most profound and potentially fatal hematologic side effect. Six percent of patients develop leukocyte counts below 1,000/mm3 and less than 50% have nadir counts below 3,000/mm3. Most patients receiving mitoxantrone for ANLL become neutropenic. Leukocyte nadirs usually occur by day 10 to 14, with recovery by day 21 (rarely day 35). Thrombocytopenia occurs less commonly, but can be severe. Only rarely do platelet counts fall below 100,000/mm3 (1% of patients develop platelet counts less than 25,000/mm3). Erythrocytes do not appear to be significantly affected. Granulocytopenia may result in mild to severe infections, including urinary tract infections (7%), pneumonia (9%), bacteremia/sepsis (34%), and fungal infections (9% to 15%). A case of acute myelogenous leukemia following treatment with mitoxantrone has also been reported.[Ref]


Oncologic side effects including secondary myelogenous leukemia have been reported in both cancer patients and multiple sclerosis patients treated with mitoxantrone.[Ref]


Appropriate antiemetic therapy usually ameliorates mitoxantrone-induced nausea and vomiting.

Nausea and vomiting associated with mitoxantrone is usually less troublesome than with equivalent doses of doxorubicin or daunorubicin.[Ref]

Gastrointestinal side effects are experienced by most patients and have included nausea and vomiting (31% to 72%, severe in 10% to 16%), diarrhea (18% to 47%), abdominal pain (9% to 15%), and mucositis/stomatitis (7% to 29%, severe in 4%).[Ref]


Cardiovascular side effects have included significantly decreased left ventricular (LV) systolic function and congestive heart failure (CHF). Mitoxantrone-induced CHF may be more common in patients with prior treatment with anthracyclines, prior mediastinal radiotherapy, advanced age, multiple sclerosis, or preexisting cardiovascular disease. The overall cumulative probability rate of moderate or serious decreases in LV ejection fraction and CHF at total doses of 140 mg/m2 averages 13% and 2%, respectively. The risk of CHF increases significantly with total doses of greater than 160 mg/m2 (140 mg/m2 if there is a history of receiving anthracyclines). Other cardiovascular side effects include tachycardia, ECG changes (including arrhythmias, prolonged PR, QT, and QRS intervals, and T-wave inversions). Bradycardia and myocardial infarction have rarely been reported.[Ref]

Mitoxantrone is less cardiotoxic than similar drugs, the anthracyclines.

In first-line comparative trials of mitoxantrone + cytosine arabinoside versus daunorubicin + cytosine arabinoside in adults with previously untreated acute nonlymphocytic leukemia, the incidence of CHF in each arm was 6.5%. A causal relationship between drug therapy and cardiotoxicity is difficult to establish in this setting since myocardial function is frequently depressed by fever, anemia, infection, and hemorrhage, which often accompany the underlying disease.

Most experts recommend stopping mitoxantrone therapy or at least considering endomyocardial biopsy if the LV ejection fraction (per MUGA scan) is reduced by 20% or more during therapy.

Mitoxantrone is chemically related to the anthracyclines, doxorubicin and daunorubicin, which can form free radicals. Free radicals can directly interact with oxygen, causing peroxidation of the lipid membranes of the heart. Supposedly, mitoxantrone does not form free radicals.[Ref]


Checking for blue streaking in or around the vein is recommended.[Ref]

Local infusion site problems have included phlebitis and tissue necrosis following IV extravasation.[Ref]

Nervous system

Nervous system side effects have included rare cases of lethargy, fatigue, seizures, and headache. Myelodysplasia has also been reported.[Ref]

Intrathecal administration is contraindicated due to cases of paraplegia in humans and hypoactivity, muscle tremors, and paraparesis in animals associated with this route of administration.[Ref]


Hypersensitivity reactions including hypotension, urticaria, dyspnea, and/or rashes have been reported occasionally.[Ref]


Patients should be warned that this drug may cause a blue-green discoloration of their skin, but should be reminded that this strange discoloration will fade and is reversible.[Ref]

Dermatologic side effects are often associated with hypersensitivity reactions. In addition, reversible alopecia may present in 25% to 50% of patients (complete in up to 10%). Other, rare dermatologic side effects include onycholysis, photosensitivity, and hyperpigmentation.[Ref]


Renal side effects including new or worsened renal insufficiency have rarely been associated with the use of mitoxantrone.[Ref]


Mild, transient elevations of bilirubin and aspartate and alanine aminotransferase levels have been reported from 4 to 24 days after treatment, returning to baseline or normal a median of 8 days later. In rare cases the abnormalities persisted.[Ref]

Hepatic side effects including rare cases of elevated hepatic enzymes have been reported.[Ref]


Other side effects have included urinary and scleral blue-green discoloration and hypomagnesemia and/or hypocalcemia. A case of drug rash with eosinophilia and systemic signs (DRESS) syndrome has been reported.[Ref]

Drug rash with eosinophilia and systemic signs (DRESS) syndrome is defined by the triad of fever, dermatitis, and internal organ involvement, characteristically occurring with a delay of 3 to 8 weeks after the initiation of treatment with the associated drug.[Ref]


Genitourinary side effects including uroepithelial necrosis and green urine (blue mixed with yellow green) have been associated with intravesicular administration of mitoxantrone for superficial bladder tumors.[Ref]


Endocrine side effects including amenorrhea have been reported.[Ref]

The mechanism of mitoxantrone-associated amenorrhea is believed to be direct toxic effects on the ovary, as is seen with other forms of chemotherapy.[Ref]


1. Saletan S "Mitoxantrone: an active, new antitumor agent with an improved therapeutic index." Cancer Treat Rev 14 (1987): 297-303

2. Arzoomanian RZ, Tombes MB, Alberti D, Tutsch KD, Spriggs D, Schiller J "PHASE I TRIAL OF GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR AND MITOXANTRONE (MEETING ABSTRACT)." Proc Annu Meet Am Assoc Cancer Res 32 (1991): a11181991

3. Jodrell DI, Iveson TJ, Smith IE "Myelosuppression after methotrexate, mitoxantrone, and mitomycin C." Lancet 1 (1987): 1211

4. Koeller J, Eble M "Mitoxantrone: a novel anthracycline derivative." Clin Pharm 7 (1988): 574-81

5. Bajetta E, Buzzoni R, Valagussa P, Bonadonna G "Mitoxantrone: an active agent in refractory non-Hodgkin's lymphomas." Am J Clin Oncol 11 (1988): 100-3

6. Neijt JP, Lacave AJ, Splinter TA, Taal BG, Veenhof CH, Sahmoud T, Lips CJ "Mitoxantrone in metastatic apudomas: a phase II study of the EORTC Gastro-Intestinal Cancer Cooperative Group." Br J Cancer 71 (1995): 106-8

7. Dugan M, Choy D, Ngai A, Sham J, Choi P, Shiu W, Leung T, Teo P, Prasad U, Lee S, et al "Multicenter phase II trial of mitoxantrone in patients with advanced nasopharyngeal carcinoma in Southeast Asia: an Asian-Oceanian Clinical Oncology Association Group study." J Clin Oncol 11 (1993): 70-6

8. Sridhar KS, Hussein AM, Benedetto P, Waldman SM, Feun LG, Savaraj N, Richman SP, Ardalan B, Desai P "Phase II trial of mitoxantrone in head and neck carcinoma." Am J Clin Oncol 14 (1991): 298-304

9. Harris AL, Cantwell BM, Carmichael J, Wilson R, Farndon J, Dawes P, Ghani S, Evans RG "Comparison of short-term and continuous chemotherapy (mitozantrone) for advanced breast cancer." Lancet 335 (1990): 186-90

10. Stewart DJ, Cripps C, Maroun JA "Phase II study of high-dose mitoxantrone in the treatment of recurrent squamous cell carcinoma of the head and neck." Am J Clin Oncol 10 (1987): 307-9

11. ten Bokkel Huinink WW, Clavel M, Rodenhuis S, Franklin HR, Koier IJ "MITOXANTRONE (M) AND GM-CSF, A PHASE I STUDY WITH AN ESCALATED DOSE OF M IN BREAST CANCER (MEETING ABSTRACT)." Proc Annu Meet Am Soc Clin Oncol 9 (1990): a1511990

12. Henderson IC, Allegra JC, Woodcock T, Wolff S, Bryan S, Cartwright K, Dukart G, Henry D "Randomized clinical trial comparing mitoxantrone with doxorubicin in previously treated patients with metastatic breast cancer." J Clin Oncol 7 (1989): 560-71

13. Muss HB, Bundy BN, Christopherson WA "Mitoxantrone in the treatment of advanced vulvar and vaginal carcinoma. A gynecologic oncology group study." Am J Clin Oncol 12 (1989): 142-4

14. Muhonen TT, Wiklund TA, Blomqvist CP, Pyrhonen SO "Unexpected prolonged myelosuppression after mitomycin, mitoxantrone and methotrexate." Eur J Cancer 28a (1992): 1974-6


16. Lenk H, Muller U, Tanneberger S "Mitoxantrone: mechanism of action, antitumor activity, pharmacokinetics, efficacy in the treatment of solid tumors and lymphomas, and toxicity." Anticancer Res 7 (1987): 1257-64

17. O'Connor BM, Ziegler P, Spaulding MB "Excessive toxicity of mitoxantrone combined with etoposide in advanced non-small cell lung cancer." Eur J Cancer 27 (1991): 1334-5

18. Khalil A, Ciobanu N, Sparano JA, Gucalp R, Dutcher JP, Wiernik PH "Pilot study of high-dose mitoxantrone and busulfan plus autologous bone transplantation in patients with advanced malignancies." Bone Marrow Transplant 15 (1995): 93-7

19. Larson RA, Daly KM, Choi KE, Han DS, Sinkule JA "A clinical and pharmacokinetic study of mitoxantrone in acute nonlymphocytic leukemia." J Clin Oncol 5 (1987): 391-7

20. Nicoletto MO, Padrini R, Ferrazzi E, Nascimben O, Visona E, Tumolo S, Palumbo M, Costa L, Vinante O, Monfardini S, et al "Phase I-II intraperitoneal mitoxantrone in advanced pretreated ovarian cancer." Eur J Cancer 29a (1993): 1242-8

21. van Breukelen FJ, Mattson K, Giaccone G, van Zandwijk N, Planteydt HT, Kirkpatrick A, Dalesio O "Mitoxantrone in malignant pleural mesothelioma: a study by the EORTC Lung Cancer Cooperative Group." Eur J Cancer 27 (1991): 1627-9

22. "Product Information. Novantrone (mitoxantrone)." Immunex Corporation, Seattle, WA.

23. Markman M, Hakes T, Reichman B, Lewis JL Jr, Rubin S, Jones W, Almadrones L, Hoskins W "Phase II trial of weekly or biweekly intraperitoneal mitoxantrone in epithelial ovarian cancer." J Clin Oncol 9 (1991): 978-82

24. Keller JW, Omura GA, Gams RA, Bartolucci AA "Weekly mitoxantrone therapy of Hodgkin's disease, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia. A Southeastern Cancer Study Group Trial." Am J Clin Oncol 10 (1987): 194-5

25. Morton AR, Anderson H, Howell A "Myelotoxicity of methotrexate, mitozantrone, and mitomycin C." Lancet 1 (1987): 1494

26. LeMaistre CF, Herzig R "Mitoxantrone: potential for use in intensive therapy." Semin Oncol 17 (1 Suppl) (1990): 43-8

27. Faulds D, Balfour JA, Chrisp P, Langtry HD "Mitoxantrone: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer." Drugs 41 (1991): 400-49

28. Cotter FE "Therapeutic milestones. Novantrone (mitozantrone)." Br J Clin Pract 42 (1988): 207-9

29. Powles TI, Ashley S "Myelosuppression after methotrexate, mitozantrone, and mitomycin C combination chemotherapy." Lancet 2 (1987): 853

30. Crossley RJ "Clinical safety and tolerance of mitoxantrone (Novantrone)." Cancer Treat Rev 10 Suppl B (1983): 29-36

31. Bowles DW, Flaig TW "Mitoxantrone-associated acute myelogenous leukemia in a patient with high-risk adenocarcinoma of the prostate: a case report and brief review." Cancer Invest 24 (2006): 517-20

32. Pai GR, Reed NS, Ruddell WS "A case of mitozantrone-associated cardiomyopathy without prior anthracycline therapy." Br J Radiol 60 (1987): 1125-6

33. Ghalie RG, Edan G, Laurent M, et al. "Cardiac adverse effects associated with mitoxantrone (Novantrone) therapy in patients with MS." Neurology 59 (2002): 909-13

34. Pratt CB, Crom DB, Wallenberg J, Sanyal SK, Miliauskas J, Sohlberg K "Fatal congestive heart failure following mitoxantrone treatment in two children previously treated with doxorubicin and cisplatin." Cancer Treat Rep 67 (1983): 85-8

35. Villani F, Galimberti M, Crippa F "Evaluation of ventricular function by echocardiography and radionuclide angiography in patients treated with mitoxantrone." Drugs Exp Clin Res 15 (1989): 501-6

36. de Leonardis V, Bartalucci S, Cinelli P, De Scalzi M, Becucci A, Lottini G, Neri B "Ventricular late potentials in the assessment of mitoxantrone cardiotoxicity." Cardiology 79 (1991): 110-5

37. Mather FJ, Simon RM, Clark GM, Von Hoff DD "Cardiotoxicity in patients treated with mitoxantrone: Southwest Oncology Group phase II studies." Cancer Treat Rep 71 (1987): 609-13

38. Strotmann J JM, Spindler M, Weilbach FX, Gold R, Ertl G, Voelker W "Myocardial function in patients with multiple sclerosis treated with low-dose mitoxantrone." Am J Cardiol 89 (2002): 1222-5

39. Umemoto M, Kawasaki H, Azuma E, Komada Y, Ito M, Sakurai M "Bradycardia due to mitoxantrone exacerbated by previous anthracycline therapy." Am J Hematol 52 (1996): 327-8


41. Schell FC, Yap HY, Blumenschein G, Valdivieso M, Bodey G "Potential cardiotoxicity with mitoxantrone." Cancer Treat Rep 66 (1982): 1641-3

42. Benjamin RS "Rationale for the use of mitoxantrone in the older patient: cardiac toxicity." Semin Oncol 22 (1 Suppl) (1995): 11-3

43. ChanTack K "Sinus bradycardia due to mitoxantrone." South Med J 93 (2000): 440

44. Cassidy J, Merrick MV, Smyth JF, Leonard RC "Cardiotoxicity of mitozantrone assessed by stress and resting nuclear ventriculography." Eur J Cancer Clin Oncol 24 (1988): 935-8

45. Lewkow LM, Hooker JL, Movahed A "Cardiac complications of intensive dose mitoxantrone and cyclophosphamide with autologous bone marrow transplantation in metastatic breast cancer." Int J Cardiol 34 (1992): 273-6

46. Janmohammed R, Milligan DW "Mitoxantrone induced congestive heart failure in patients previously treated with anthracyclines." Br J Haematol 71 (1989): 292-3

47. Fountzilas G, Afthonidis D, Geleris P, Salem N, Kottas G, Halkidis C, Apostolidis P, Beer M, Tourkantonis A "Cardiotoxicity evaluation in patients treated with a mitoxantrone combination as adjuvant chemotherapy for breast cancer." Anticancer Res 12 (1992): 231-4

48. Benekli M, Kars A, Guler N "Mitoxamtrone-induced bradycardia." Ann Intern Med 126 (1997): 409

49. Peters FT, Beijnen JH, ten Bokkel Huinink WW "Mitoxantrone extravasation injury." Cancer Treat Rep 71 (1987): 992-3

50. Ketelbey JW "Cytotoxic-drug extravasation." Med J Aust 150 (1989): 52

51. Hall C, Dougherty WJ, Lebish IJ, Brock PG, Man A "Warning against use of intrathecal mitoxantrone." Lancet 1 (1989): 734

52. Lakhani AK, Zuiable AG, Pollard CM, Milne A, Treleaven J, Powles RL "Paraplegia after intrathecal mitozantrone." Lancet 2 (1986): 1393

53. Taylor WB, Cantwell BM, Roberts JT, Harris AL "Allergic reactions to mitoxantrone." Lancet 1 (1986): 1439

54. Mitchell PL, Harvey VJ "Mitozantrone-induced onycholysis." Eur J Cancer 28 (1992): 243-4

55. Arlin ZA, Friedland ML, Atamer MA "Selective alopecia with mitoxantrone." N Engl J Med 310 (1984): 1464

56. Speechly-Dick ME, Owen ER "Mitozantrone-induced onycholysis." Lancet 1 (1988): 113

57. Van Belle SJ, Dehou MF, De Bock V, Volckaert A "Nail toxicity due to the combination adriamycin-mitoxantrone." Cancer Chemother Pharmacol 24 (1989): 69-70

58. Scheithauer W, Ludwig H, Kotz R, Depisch D "Mitoxantrone-induced discoloration of the nails." Eur J Cancer Clin Oncol 25 (1989): 763-5

59. Paciucci PA, Sklarin NT "Mitoxantrone and hepatic toxicity." Ann Intern Med 105 (1986): 805-6

60. Griffiths KD, Parry DH "Hypomagnesaemia and hypocalcaemia after treatment with mitoxantrone." BMJ 297 (1988): 488

61. Caruso A, Vecchio R, Patti F, Neri S "Drug rash with eosinophilia and systemic signs syndrome in a patient with multiple sclerosis." Clin Ther 31 (2009): 580-4

62. Stewart DJ, Green R, Futter N, Walsh W, McKay D, Verma S, Maroun JA, Redmond D "Phase I and pharmacology study of intravesical mitoxantrone for recurrent superficial bladder tumors." J Urol 143 (1990): 714-6

63. Shenkenberg TD, Von Hoff DD "Possible mitoxantrone-induced amenorrhea." Cancer Treat Rep 70 (1986): 659-61

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