Mitoxantrone (Novantrone) is a chemotherapeutic (cytotoxic) drug that is indicated for the treatment of certain hematological malignancies and other cancers.

Mitoxantrone (Novantrone) Uses:

• Acute myeloid leukemia:

  • Initial treatment (in combination with other agents) of severe nonlymphocytic leukemia (ANLL [includes myelogenous, promyelocytic, monocytic, and erythroid leukemias]).

• Multiple sclerosis, relapsing or secondary progressive:

  • Treatment of secondary (chronic) progressive, progressive relapsing, or worsening or relapsing-remitting various sclerosis (RRMS) to reduce neurologic disability and/or the frequency of a clinical relapse.
  • Limitation of use:
    • Mitoxantrone is not referred to as the treatment of primary progressive MS.
    • Reserve use for rapidly-advancing, refractory multiple sclerosis.

• Prostate cancer:

  • It is useful in the treatment of advanced hormone-refractory prostate cancer (in combination with corticosteroids).

• Off Label Use of Mitoxantrone in Adults:

  • Relapsed/ refractory acute lymphoblastic leukemia,
  • Relapsed/ refractory Acute myeloid leukemia,
  • Newly diagnosed Acute promyelocytic leukemia,
  • Autologous Hematopoietic stem cell transplantation, (conditioning regimen)
  • Hodgkin lymphoma
  • Relapsed/refractory Non-Hodgkin lymphomas,

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Mitoxantrone Dose in Adults:

Mitoxantrone (Novantrone) Dose in the treatment of relapsed/refractory Acute lymphoblastic leukemia:

• FLAM regimen:

  • 10 mg/m² IV on days 3 and 10 (use in combination with fludarabine and cytarabine).

Mitoxantrone (Novantrone) dose in the initial treatment of acute myeloid leukemia (AML):

• AML induction:

  • 12 mg/m² IV once a day for 3 days (use in combination with cytarabine);
  • in case of incomplete response, it may be repeated (7 to 10 days later) at 12 mg/m² once a day for 2 days (in combination with cytarabine).

• AML consolidation (beginning ~6 weeks after initiation of the final induction course):

  • 12 mg/m² IV once a day for 2 days (use in combination with cytarabine), it must be repeated in 4 weeks.

Mitoxantrone (Novantrone) Dose in the treatment of relapsed/refractory acute myeloid leukemia:

• CLAG-M regimen:

  • 10 mg/m² once a day for 3 days on days 1, 2, and 3 (use it in combination with cladribine, cytarabine, and filgrastim),  it may be repeated once if needed.

• MEC regimen:

  • 6 mg/m² once on a daily basis for 6 days on days 1 to 6 (use it in combination with cytarabine and etoposide).

• Mitoxantrone/Etoposide:

  • 10 mg/m² once daily for 5 days on days 1 to 5 (must be used in combination with etoposide).

Mitoxantrone (Novantrone) Dose in the treatment of newly diagnosed Acute promyelocytic leukemia (off-label): IV:

• Consolidation:

  • 10 mg/m² once on a daily basis for 5 days on days 1 to 5 of consolidation course 2 (use in combination with tretinoin all-trans retinoic acid; ATRA).

Mitoxantrone (Novantrone) Dose in the treatment of autologous hematopoietic stem cell transplantation (off-label):

• Conditioning regimen:

  • 60 mg/m² intravenous administered 4 to 5 days beforehand to autografting (as 3 divided doses over 1 hour each at 1- to 2-hour intervals on the same day in combination with melphalan).

Mitoxantrone (Novantrone) Dose in the treatment of Hodgkin lymphoma:

• Relapsed or refractory Hodgkin lymphoma:

  • MINE-ESHAP regimen:
    • 10 mg/m² on day 1 every 28 days for up to 2 cycles (MINE is combination with mesna, ifosfamide, mitoxantrone, and etoposide;
    • MINE alternates with ESHAP for up to 2 cycles of each).

• Newly diagnosed Hodgkin lymphoma (reduced-intensity regimen):

  • Adults ≥66 years:
    • VEPEMB regimen: 6 mg/m² on day 15 every 28 days (use in combination with vinblastine, cyclophosphamide, procarbazine, etoposide, and bleomycin) for 3 to 6 cycles.

Mitoxantrone (Novantrone) Dose in the treatment of relapsed/refractory Non-Hodgkin lymphomas:

• B-cell lymphomas:

  • R-MINE regimen:
    • 8 mg/m² on day 1 (use in combination with rituximab, mesna, ifosfamide, and etoposide) for up to 3 cycles.

• Follicular lymphoma:

  • R-FCM regimen:
    • 8 mg/m² on day 1 every 28 days (must be used in combination with rituximab, fludarabine, and cyclophosphamide) for 4 cycles.

Mitoxantrone (Novantrone) Dose as an alternative agent in the treatment of relapsing or secondary progressive multiple sclerosis:

• 12 mg/m² IV every 3 months (maximum lifetime cumulative dose: 140 mg/m²; discontinue if LVEF <50% or clinically significant reduction in LVEF).
• Note: Its use must be reserved for rapidly advancing, refractory multiple sclerosis.

Mitoxantrone (Novantrone) Dose in the treatment of advanced hormone-refractory prostate cancer:

• 12 mg/m² IV once every 3 weeks (must be used in combination with prednisone or prednisolone) for up to 10 cycles or
• 12 to 14 mg/m² once every 3 weeks (in combination with prednisone) until disease progression or unacceptable toxicity, up to a maximum cumulative mitoxantrone dose of 144 mg/m².

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Mitoxantrone Dose in Children:

Note:

• Dosing regimens may vary by dose, cycles, and combination therapy, it also indicates to individual protocols.
• Mitoxantrone is made a bridge with low emetic potential;
• antiemetics are suggested to prevent nausea and vomiting.

Mitoxantrone (Novantrone) Dose in the treatment of Relapsed Acute lymphocytic leukemia (ALL), relapsed:

• Children and Adolescents:

  • Induction: 10 mg/m²/dose once on daily basis on days 1 and 2 (use in combination with dexamethasone, vincristine, pegaspargase, and intrathecal methotrexate), with follow-up therapy (allogeneic stem cell transplant or continued chemotherapy) determined by risk stratification.

Mitoxantrone (Novantrone) Dose in the treatment of Acute myeloid leukemia (AML):

• Gamis 2014:

  • Infants, Children, and Adolescents:
  • Note:
    • Some features of protocol dosing explicated in previous reports (Cooper 2012).

    • Intensification Course 2:

      • BSA <0.6 m²:
        • 0.4 mg/kg IV once a day for 4 days on Days 3 to 6 of a 28-day cycle (in combination with cytarabine)
      • BSA ≥0.6 m²:
        • IV: 12 mg/m² once a day for 4 days on Days 3 to 6 of a 28-day cycle (in combination with cytarabine)

    • Perel 2002: LAME 89/91 regimen:

      • Infants, Children, and Adolescents:

        • Remission Induction:

          • <1 year:
            • IV: 8 mg/m² a day for 5 days (must be used in combination with cytarabine);
            • if persistent disease, an additional course of 8 mg/m² for 2 days (in combination with cytarabine) was administered.
          • ≥1 year:
            • IV: 12 mg/m² once on a daily basis for 5 days (use in combination with cytarabine);
            • if persistent disease, an additional course of 12 mg/m² for 2 days (in combination with cytarabine) was administered.

    • Gibson 2011: MAE and MidAC regimens:

      • Induction Course 1 (MAE 3+10+5) or Course 2 (MAE 3+8+5):

        • Infants:
          • 9 mg/m² once on a daily basis on Days 1, 3, and 5 (use in combination with cytarabine and etoposide)
        • Children and Adolescents <17 years:
          • 12 mg/m² IV once on a daily basis on Days 1, 3, and 5 (in combination with cytarabine and etoposide)

      • Consolidation Course 4/5 (MidAC):

        • Infants:
          • 7.5 mg/m² intravenous once daily on Days 1 to 5 (must be used in combination with cytarabine)
        • Children and Adolescents <17 years:
          • 10 mg/m² intravenous once a day on Days 1 to 5 (in combination with cytarabine)

Mitoxantrone (Novantrone) Dose in the treatment of Acute promyelocytic leukemia (APL):

• Consolidation Course 2:

  • Children ≥2 years and Adolescents:
    • 10 mg/m² intravenously once a day for 5 days of a 28-day cycle (combined with tretinoin [ATRA]).

Mitoxantrone (Novantrone) Dosing adjustment for toxicity:

• The above-mentioned dosing adjustments are based on experience in adult patients; specific suggestions for pediatric patients are limited.
• It refers to a specific protocol for management in pediatric patients if available.

• Adult:

  • Oncology uses:
    • Severe or life-threatening nonhematologic toxicity:
      • put down treatment until toxicity gets resolve.

  • Multiple sclerosis:

    • Neutrophils <1,500/mm³:
      • Its use is not recommended.
    • Signs/symptoms of HF:
      • Evaluate for cardiac signs/symptoms and monitor LVEF.
    • LVEF <50% or baseline LVEF below the lower limit of normal (LLN):
      • Its use is not recommended.

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Mitoxantrone (Novantrone) Pregnancy Risk Category: D

• Mitoxantrone can cause harm to fetal health if administered during pregnancy, based on its mechanism of action.
• Limited information is available on pregnancy outcomes after maternal use of mitoxantrone during pregnancy.
• Most MS-modifying treatments are not started during pregnancy.
• For females planning to have a baby, it is worth considering other agents than mitoxantrone.
• For females with high levels of disease activity, it is a good idea to postpone pregnancy.
• Other agents may be preferred if the patient requires disease-modifying treatment.
• The European Society for Medical Oncology published guidelines for diagnosing, treating, and following-up on cancer in pregnancy.
• These guidelines recommend that you refer to a cancer center during pregnancy.
• They also encourage the use of a multidisciplinary team (obstetrician/neonatalian, oncology team).
• If chemotherapy is being considered, it should not be used in the first trimester.
• There must be a minimum of three weeks between the last dose and the delivery date. Additionally, chemotherapy should not continue beyond week 33.
• Before treatment of females with reproductive potential, it is important to determine if you are pregnant. 
• Mitoxantrone is associated with amenorrhea and ovarian failure as well as male infertility.

Use of Mitoxantrone while breastfeeding

• Breast milk contains mitoxantrone.
• After treatment for acute proyelocytic lymphoma, the breast milk concentrations of mitoxantrone were measured in a woman.
• As part of consolidation therapy, the patient received mitoxantrone 6mg/m2 for 3 consecutive days.
• The therapy was initiated during pregnancy. Breast milk was collected after the third postpartum consolidation treatment.
• The continuation of mitoxantrone administration resulted in the highest milk concentrations (120ng/mL); significant concentrations (18ng/mL were still observed 28-days after the last dose.
• Due to the possibility of serious adverse reactions in breastfed babies, the manufacturer suggests that you stop breastfeeding before beginning mitoxantrone therapy.

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Mitoxantrone (Novantrone) Dose in Kidney Disease:

So far, there are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Mitoxantrone (Novantrone) Dose in Liver disease:

• As in, there are no dosage adjustments provided in the manufacturer's labeling; although, clearance is reduced in hepatic dysfunction.
• Patients suffering from severe hepatic dysfunction (bilirubin >3.4 mg/dL) have an AUC of 3 times greater than patients with normal hepatic function; consider dose adjustments.
• MS patients having hepatic impairment should not receive mitoxantrone.

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Underpins events reported with any indication; incidence varies based on treatment, dose, and/or concomitant medications.

Side Effects of Mitoxantrone (Novantrone):

• Cardiovascular:

  • Edema
  • Cardiac Disease
  • Cardiac Arrhythmia
  • ECG Changes

• Central Nervous System:

  • Pain
  • Fatigue
  • Headache

• Dermatologic:

  • Alopecia
  • Nail Bed Changes

• Endocrine & Metabolic:

  • Menstrual Disease
  • Amenorrhea
  • Hyperglycemia
  • Weight Gain
  • Weight Loss
  • Increased Gammaglutamyl Transferase

• Gastrointestinal:

  • Nausea
  • Vomiting
  • Diarrhea
  • Mucositis
  • Stomatitis
  • Anorexia
  • Constipation
  • Gastrointestinal Hemorrhage
  • Abdominal Pain
  • Dyspepsia

• Genitourinary:

  • Urinary Tract Infection
  • Hematuria
  • Urine Abnormality

• Hematologic & Oncologic:

  • Neutropenia
  • Leukopenia
  • Lymphocytopenia
  • Anemia
  • Decreased Hemoglobin
  • Thrombocytopenia
  • Bruise
  • Febrile Neutropenia
  • Petechia

• Hepatic:

  • Increased Serum Alkaline Phosphatase
  • Increased Serum Transaminases

• Infection:

  • Infection
  • Sepsis
  • Fungal Infection

• Neuromuscular & Skeletal:

  • Weakness

• Renal:

  • Increased Blood Urea Nitrogen
  • Increased Serum Creatinine

• Respiratory:

  • Upper Respiratory Tract Infection
  • Pharyngitis
  • Dyspnea
  • Cough

• Miscellaneous:

  • Fever

Less Common Side Effects of Mitoxantrone (Novantrone):

• Cardiovascular:

  • Cardiac Failure
  • Ischemia
  • Decreased Left Ventricular Ejection Fraction
  • Hypertension

• Central Nervous System:

  • Chills
  • Anxiety
  • Depression
  • Seizure

• Dermatologic:

  • Diaphoresis
  • Skin Infection

• Endocrine & Metabolic:

  • Hypocalcemia
  • Hypokalemia
  • Hyponatremia
  • Hypermenorrhea

• Gastrointestinal:

  • Aphthous Stomatitis

• Genitourinary:

  • Impotence
  • Proteinuria
  • Sterility

• Hematologic & Oncologic:

  • Granulocytopenia
  • Hemorrhage
  • Acute Leukemia

• Hepatic:

  • Jaundice

• Infection:

  • Fungal Infection

• Neuromuscular & Skeletal:

  • Back Pain
  • Arthralgia
  • Myalgia

• Ophthalmic:

  • Conjunctivitis
  • Blurred Vision

• Renal:

  • Renal Failure

• Respiratory:

  • Rhinitis
  • Pneumonia
  • Sinusitis

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Contraindications to Mitoxantrone (Novantrone):

Hypersensitivity to mitoxantrone and any component of the formulation Canadian labeling

• Additional contraindications not listed in the US labeling
• Hypersensitivity to anthracyclines beforehand
• If there is an abnormality in cardiac function before mitoxantrone therapy, you may have had significant anthracycline intake.
• Radiation therapy and earlier chemotherapy may have caused severe myelosuppression.
• Hepatic impairment severe;
• Intrathecal administration

Warnings and precautions

• Suppression of bone marrow

  • Mitoxantrone can cause severe myelosuppression at any dose.
  • [US Boxed Warning] - Usually, it is not recommended to administer if the baseline neutrophil count is 1,500/mm (except in the treatment for AML). Monitoring blood counts is important and monitoring for neutropenia.
  • Patients with myelosuppression are generally advised not to receive mitoxantrone unless they have received earlier chemotherapy.

• Extravasation

  • Mitoxantrone, an irritant that has vesicant-like characteristics, is available.
  • [US Boxed Warning] - IV administration should only be done into a free flowing IV. Extravasation can cause severe tissue damage.
  • There have been reports of extravasation, which can cause skin discoloration (blue), burning, erythema and pain. 
  • This could lead to tissue necrosis, which will require debridement in order to graft skin.
  • Before and during infusion, ensure proper placement of the needle or catheter.
  • Avoid excessive use.

• Hypersensitivity

  • It could contain sodium metabisulfite. This can cause allergic-type reactions, including anaphylactic symptoms or potentially severe asthmatic episodes.
  • Asthma sufferers are at greater risk for hypersensitivity.

• Myocardial toxicity: [US Boxed Warning]

  • It can cause myocardial toxicities and possibly fatal heart failure (HF). The risk of this happening increases with cumulative doses.
  • The possibility of developing cardiotoxicity during therapy may occur, or it may be delayed for months or years.
  • Patients may be at higher risk for mitoxantrone-induced cardiactoxicity if they have had anthracycline, anthracenedione, or other anthracycline therapy.
  • Before initiating therapy, assess all patients for cardiac-related symptoms and signs, including history and ECG. Next, examine baseline left ventricular ejection (LVEF) using an echocardiogram, multigated radionuclide angiography, (MUGA), or MRI.
  • MS patients should not use mitoxantrone if their baseline LVEF is below the lower limit normal (LLN).
  • Assess for any cardiac signs and symptoms (by history, physical exam and ECG), and determine if there has been any changes in LVEF.
  • This is the same procedure as when baseline LVEF was used in MS patients prior to each dose.
  • Patients with MS should not receive a cumulative dose exceeding 140 mg/m2.
  • If LVEF is below LLN, or if a significant reduction in LVEF occurs during treatment, do not give mitoxantrone.
  • To monitor for delayed cardiotoxicity, patients with MS should have an annual LVEF assessment after discontinuation of treatment.
  • Patients who have had anthracycline therapy previously should be evaluated for their potential risk and benefits.
  • If you notice signs or symptoms of heart failure, it is important to check the LVEF and ECG.

• Secondary malignancy: [US-Boxed Warning]

  • Patients with MS and patients with cancer have a higher risk of developing secondary acute meeloid leukemia (SAML) after treatment with mitoxantrone.
  • A similar trend has been observed in acute promyelocytic (APL) patients.
  • Acute leukemia symptoms include bleeding and excessive bruising.
  • Patients who have been heavily pretreated with chemotherapy, at higher doses and/or combination chemotherapy, are at greater risk of secondary leukemia.

• Tumor lysis syndrome

  • Rapid lysis may lead to hyperuricemia or tumor lysis syndrome.
  • It is important to monitor the levels of uric acid and administer antihyperuricemic treatment. As well as aggressive hydration, if necessary.

• Hepatic impairment

  • Clearance is reduced in patients with hepatic impairment.
  • Be careful
  • Recommendation: Dosage adjustment
  • It is not used to treat multiple sclerosis in patients who have concurrent hepatic impairment.

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Mitoxantrone: Drug Interaction

Note: Drug Interaction Categories:

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

Risk Factor C (Monitor therapy)
Chloramphenicol (Ophthalmic)	May enhance the adverse/toxic effect of Myelosuppressive Agents.
CloZAPine	Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased.
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Mesalamine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Smallpox and Monkeypox Vaccine (Live)	Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live).
Tertomotide	Immunosuppressants may diminish the therapeutic effect of Tertomotide.
Trastuzumab	May enhance the neutropenic effect of Immunosuppressants.
Risk Factor D (Consider therapy modification)
Baricitinib:	Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted.
CycloSPORINE (Systemic)	May increase the serum concentration of MitoXANTRONE. Management: Consider mitoxantrone dose reduction, as clinically appropriate, when used with cyclosporine. Use this combination with caution and monitor closely for toxic effects of mitoxantrone.
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.
Echinacea	May diminish the therapeutic effect of Immunosuppressants.
Fingolimod	Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections).
Leflunomide	Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly.
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.
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.
Nivolumab	Immunosuppressants may diminish the therapeutic effect of Nivolumab.
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.
Roflumilast	May enhance the immunosuppressive effect of Immunosuppressants.
Sipuleucel-T	Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy.
Tofacitinib	Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants.
Vaccines (Inactivated)	Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.
Risk Factor X (Avoid combination)
BCG (Intravesical)	Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).
BCG (Intravesical	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Cladribine	May enhance the immunosuppressive effect of Immunosuppressants.
Cladribine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
Natalizumab	Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
Pimecrolimus	May enhance the adverse/toxic effect of Immunosuppressants.
Tacrolimus (Topical)	May enhance the adverse/toxic effect of Immunosuppressants.
Upadacitinib	Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib.
Vaccines (Live)	Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live).

 

Monitoring parameters:

• CBC with differential, serum uric Acid (for leukemia treatment), liver function tests
• Before you start treatment for multiple sclerosis, have a pregnancy test done on females with reproductive potential.
• Extravasation must be monitored at the injection site.
• Cardiac monitoring
  • All patients with cardiac-related symptoms/signs/symptoms must be seen sooner than the initiation. This includes history, physical exam and ECG.
  • Analyze baseline and periodic left ventricular ejection (LVEF) using an echocardiogram, multigated radionuclide angiography or MRI.
  • Patients with MS should be evaluated for cardiac signs and symptoms by history, physical exam and ECG. LVEF (using same method as baseline) should also be checked before each dose. If signs/symptoms of heart failure develop, they should be treated immediately.
  • To monitor for delayed cardiotoxicity, patients with MS should have an annual LVEF assessment.

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How to administer Mitoxantrone (Novantrone)?

• It is only intended to be intravenous administered
• It can be given intra-arterially, subcutaneously or intrathecally.
• It should be dilute before use.
• It is usually administered by IV infusions lasting between 5 and 15 minutes. Avoid rapid infusions of the drug (in less that 3 to 5 minutes).
• Some regimens used mitoxantrone for 20-30 minutes. There are also hints about the protocol for infusion.
• High doses, especially for bone marrow transplantation (off-label usage), are typically given in 3 divided doses of 1 to 2 hours each.
• It can be irritating and has vesicant-like qualities.
• Avoid extravasation by ensuring proper catheter or needle placement prior to and during infusion.

Extravasation management

• Infusion should be stopped immediately. If extravasation does occur, leave the needle/cannula in place. However, you can gently aspirate any extravasated solution.NOTFlush the line
• Lift the extremity up and take out the needle/cannula.
• Initiate antidote [dexrazoxane, dimethyl sulfate]
• For up to two days, apply dry cold compresses four times per day for 20 minutes.
• Begin cooling 15 minutes prior to dexrazoxane injection
• Keep the infusion going for at least 15 minutes.
• Topical DMSO should not be used in conjunction with dexrazoxane. It may reduce dexrazoxane's efficacy.

Dexrazoxane

• 1,000 mg/m2 (maximum dosage: 2,000 mg) IV (administered in a large vein distant from the site of extravasation) for 1 to 2 hour days 1 and 2. Then 500 mg/m2 IV for 1 to 2 hour days 2 and 3.
• Start within 6 hours after extravasation
• Day 2 and 3 should be taken at the same time (+-3 hrs) as day 1.

Notification

• Patients with severe or moderately impaired renal function (CrCl 40mL/minute) should have their dexrazoxane doses reduced by 50%.
• DMSO: Apply topically to the affected area for up to 7 days. Do this within 10 minutes.

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Mechanism of action of Mitoxantrone (Novantrone):

• Mitoxantrone, an anthracenedione, is related to anthracyclines.
• Mitoxantrone is an intercalating agent in DNA, resulting both cross-links as well as strand breaks.
• It binds with nucleic acid and inhibits DNA andRNA synthesis through template disordering and obstruction.
• The binding of DNA topoisomerase 2 to cellular replication can decrease cellular replication and may prevent the incorporation uridine into DNA and thymidine in DNA.
• Mitoxantrone is also active throughout the entire cycle (cell-cycle not specific).

Distribution:

• Mitoxantrone distributes extensively into kidney, liver, heart, lung, and bone marrow, but does not cross the blood-brain barrier.

Protein binding:

• 78%

Metabolism:

• Hepatic

Half-life elimination:

• Terminal: 23 to 215 hours (median: ~75 hours)

Excretion:

• Feces (25%);
• urine (11%; 65% as unchanged drug)

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International Brands of Mitoxantrone:

• Bluxantron
• Bresnix
• Domitrone
• Ebexantron
• Elsep
• Evomixan
• Formyxan
• Heng En
• Mi Xi Ning
• Misostol
• Mitoxgen
• Mitroxone
• Mittrone
• Neotalem
• Novantron
• Novantrone
• Oncotron
• Oncotrone
• Onkotrone
• Refador
• Santrone
• Strimax

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Mitoxantrone Brand Names in Pakistan:

Mitoxantrone (HCl) [Inj 20 mg]
Mitostate	Neo Medix
Mitoxantron	Bio Pharma
Mitoxantrona	Atco Laboratories Limited

 

Mitoxantrone Injection 30 mg
Mitostate	Neo Medix