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MitoXANTRONE is a brand name for Mitoxantrone. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: INDICATIONS AND USAGE Mitoxantrone injection, USP (concentrate) is indicated for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (i.e., patients whose neurologic status…
Verbatim from this product's FDA label. Tap a section to expand.
) Multiple Sclerosis The recommended dosage of mitoxantrone injection (concentrate) is 12 mg/m 2 given as a short (approximately 5 to 15 minutes) intravenous infusion every 3 months. Left ventricular ejection fraction (LVEF) should be evaluated by echocardiogram or MUGA prior to administration of the initial dose of mitoxantrone injection (concentrate) and all subsequent doses.
In addition, LVEF evaluations are recommended if signs or symptoms of congestive heart failure develop at any time during treatment with mitoxantrone injection (concentrate). Mitoxantrone injection (concentrate) should not be administered to multiple sclerosis patients with an LVEF < 50%, with a clinically significant reduction in LVEF, or to those who have received a cumulative lifetime dose of > 140 mg/m 2 .
Complete blood counts, including platelets, should be monitored prior to each course of mitoxantrone injection (concentrate) and in the event that signs or symptoms of infection develop. Mitoxantrone injection (concentrate) generally should not be administered to multiple sclerosis patients with neutrophil counts less than 1500 cells/mm 3 .
Liver function tests should also be monitored prior to each course. Mitoxantrone injection (concentrate) therapy in multiple sclerosis patients with abnormal liver function tests is not recommended because mitoxantrone injection (concentrate) clearance is reduced by hepatic impairment and no laboratory measurement can predict drug clearance and dose adjustments.
Women with multiple sclerosis who are biologically capable of becoming pregnant, even if they are using birth control, should have a pregnancy test, and the results should be known, before receiving each dose of mitoxantrone injection (concentrate) (see WARNINGS, Pregnancy ).
Hormone-Refractory Prostate Cancer Based on data from two Phase 3 comparative trials of mitoxantrone injection (concentrate) plus corticosteroids versus corticosteroids alone, the recommended dosage of mitoxantrone injection (concentrate) is 12 to 14 mg/m 2 given as a short intravenous infusion every 21 days.
Combination Initial Therapy for ANLL in Adults For induction, the recommended dosage is 12 mg/m 2 of mitoxantrone injection (concentrate) daily on Days 1 to 3 given as an intravenous infusion, and 100 mg/m 2 of cytarabine for 7 days given as a continuous 24 hour infusion on Days 1 to 7.
ADVERSE REACTIONS
Multiple Sclerosis Mitoxantrone injection has been administered to 149 patients with multiple sclerosis in two randomized clinical trials, including 21 patients who received mitoxantrone injection in combination with corticosteroids.
1% (n = 2) in the placebo arm (hepatitis and myocardial infarction). The following clinical adverse experiences were significantly more frequent in the mitoxantrone injection groups: nausea, alopecia, urinary tract infection, and menstrual disorders, including amenorrhea.
Table 4a summarizes clinical adverse events of all intensities occurring in ≥ 5% of patients in either dose group of mitoxantrone injection and that were numerically greater on drug than on placebo in Study 1. The majority of these events were of mild to moderate intensity, and nausea was the only adverse event that occurred with severe intensity in more than one patient (three patients [5%] in the 12 mg/m 2 group).
Of note, alopecia consisted of mild hair thinning. Two of the 127 patients treated with mitoxantrone injection in Study 1 had decreased LVEF to below 50% at some point during the 2 years of treatment. An additional patient receiving 12 mg/m 2 did not have LVEF measured, but had another echocardiographic measure of ventricular function (fractional shortening) that led to discontinuation from the study.
Table 4a:
Adverse Events of Any Intensity Occurring in ≥ 5% of Patients on Any Dose of Mitoxantrone Injection and That Were Numerically Greater Than in the Placebo Group Study 1 Percent of Patients Preferred Term Placebo (N = 64) 5 mg/m 2 Mitoxantrone Injection (N = 65) 12 mg/m 2 Mitoxantrone Injection (N = 62) Nausea 20 55 76 Alopecia 31 38 61 Menstrual disorder Percentage of female patients.
WARNINGS WHEN MITOXANTRONE INJECTION IS USED IN HIGH DOSES (> 14 mg/m 2 /d × 3 days) SUCH AS INDICATED FOR THE TREATMENT OF LEUKEMIA, SEVERE MYELOSUPPRESSION WILL OCCUR. THEREFORE, IT IS RECOMMENDED THAT MITOXANTRONE INJECTION BE ADMINISTERED ONLY BY PHYSICIANS EXPERIENCED IN THE CHEMOTHERAPY OF THIS DISEASE.
LABORATORY AND SUPPORTIVE SERVICES MUST BE AVAILABLE FOR HEMATOLOGIC AND CHEMISTRY MONITORING AND ADJUNCTIVE THERAPIES, INCLUDING ANTIBIOTICS. BLOOD AND BLOOD PRODUCTS MUST BE AVAILABLE TO SUPPORT PATIENTS DURING THE EXPECTED PERIOD OF MEDULLARY HYPOPLASIA AND SEVERE MYELOSUPPRESSION.
PARTICULAR CARE SHOULD BE GIVEN TO ASSURING FULL HEMATOLOGIC RECOVERY BEFORE UNDERTAKING CONSOLIDATION THERAPY (IF THIS TREATMENT IS USED) AND PATIENTS SHOULD BE MONITORED CLOSELY DURING THIS PHASE. MITOXANTRONE INJECTION ADMINISTERED AT ANY DOSE CAN CAUSE MYELOSUPPRESSION.
General Patients with preexisting myelosuppression as the result of prior drug therapy should not receive mitoxantrone injection unless it is felt that the possible benefit from such treatment warrants the risk of further medullary suppression.
The safety of mitoxantrone injection (concentrate) in patients with hepatic insufficiency is not established (see CLINICAL PHARMACOLOGY ). Safety for use by routes other than intravenous administration has not been established. Mitoxantrone injection is not indicated for subcutaneous, intramuscular, or intra-arterial injection.
There have been reports of local/regional neuropathy, some irreversible, following intra-arterial injection. Mitoxantrone injection must not be given by intrathecal injection. There have been reports of neuropathy and neurotoxicity, both central and peripheral, following intrathecal injection.
These reports have included seizures leading to coma and severe neurologic sequelae, and paralysis with bowel and bladder dysfunction. Topoisomerase II inhibitors, including mitoxantrone injection, have been associated with the development of secondary acute myeloid leukemia and myelosuppression.
CONTRAINDICATIONS
Mitoxantrone injection (concentrate) is contraindicated in patients who have demonstrated prior hypersensitivity to it.
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Most complete remissions will occur following the initial course of induction therapy. In the event of an incomplete antileukemic response, a second induction course may be given. Mitoxantrone injection (concentrate) should be given for 2 days and cytarabine for 5 days using the same daily dosage levels.
If severe or life-threatening nonhematologic toxicity is observed during the first induction course, the second induction course should be withheld until toxicity resolves. Consolidation therapy which was used in two large randomized multicenter trials consisted of mitoxantrone injection (concentrate), 12 mg/m 2 given by intravenous infusion daily on Days 1 and 2 and cytarabine, 100 mg/m 2 for 5 days given as a continuous 24 hour infusion on Days 1 to 5.
The first course was given approximately 6 weeks after the final induction course; the second was generally administered 4 weeks after the first. Severe myelosuppression occurred (see CLINICAL PHARMACOLOGY ). Hepatic Impairment For patients with hepatic impairment, there is at present no laboratory measurement that allows for dose adjustment recommendations (see CLINICAL PHARMACOLOGY, Special Populations, Hepatic Impairment ).
Preparation and Administration Precautions MITOXANTRONE INJECTION CONCENTRATE MUST BE DILUTED PRIOR TO USE. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
9% Sodium Chloride Injection (USP) or 5% Dextrose Injection (USP). Mitoxantrone injection (concentrate) may be further diluted into Dextrose 5% in Water, Normal Saline or Dextrose 5% with Normal Saline and used immediately. DO NOT FREEZE.
Mitoxantrone injection (concentrate) should not be mixed in the same infusion as heparin since a precipitate may form. Because specific compatibility data are not available, it is recommended that mitoxantrone injection (concentrate) not be mixed in the same infusion with other drugs.
9% Sodium Chloride Injection (USP) or 5% Dextrose Injection (USP) over a period of not less than 3 minutes. Unused infusion solutions should be discarded immediately in an appropriate fashion. In the case of multidose use, after penetration of the stopper, the remaining portion of the undiluted mitoxantrone injection concentrate should be stored not longer than 7 days between 15° to 25°C (59° to 77°F) or 14 days under refrigeration.
DO NOT FREEZE. CONTAINS NO PRESERVATIVE. Care in the administration of mitoxantrone injection (concentrate) will reduce the chance of extravasation. 9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. The tubing should be attached to a Butterfly needle or other suitable device and inserted preferably into a large vein.
If possible, avoid veins over joints or in extremities with compromised venous or lymphatic drainage. Care should be taken to avoid extravasation at the infusion site and to avoid contact of mitoxantrone injection (concentrate) with the skin, mucous membranes, or eyes.
MITOXANTRONE INJECTION (CONCENTRATE) SHOULD NOT BE ADMINISTERED SUBCUTANEOUSLY. If any signs or symptoms of extravasation have occurred, including burning, pain, pruritis, erythema, swelling, blue discoloration, or ulceration, the injection or infusion should be immediately terminated and restarted in another vein.
During intravenous administration of mitoxantrone injection (concentrate) extravasation may occur with or without an accompanying stinging or burning sensation even if blood returns well on aspiration of the infusion needle. If it is known or suspected that subcutaneous extravasation has occurred, it is recommended that intermittent ice packs be placed over the area of extravasation and that the affected extremity be elevated.
Because of the progressive nature of extravasation reactions, the area of injection should be frequently examined and surgery consultation obtained early if there is any sign of a local reaction. Skin accidentally exposed to mitoxantrone injection (concentrate) should be rinsed copiously with warm water and if the eyes are involved, standard irrigation techniques should be used immediately.
The use of goggles, gloves, and protective gowns is recommended during preparation and administration of the drug. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.
1-4 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
26 51 61 Amenorrhea 3 28 43 Upper respiratory tract infection 52 51 53 Urinary tract infection 13 29 32 Stomatitis 8 15 19 Arrhythmia 8 6 18 Diarrhea 11 25 16 Urine abnormal 6 5 11 ECG abnormal 3 5 11 Constipation 6 14 10 Back pain 5 6 8 Sinusitis 2 3 6 Headache 5 6 6 The proportion of patients experiencing any infection during Study 1 was 67% for the placebo group, 85% for the 5 mg/m 2 group, and 81% for the 12 mg/m 2 group.
However, few of these infections required hospitalization: one placebo patient (tonsillitis), three 5 mg/m 2 patients (enteritis, urinary tract infection, viral infection), and four 12 mg/m 2 patients (tonsillitis, urinary tract infection [two], endometritis).
Table 4b summarizes laboratory abnormalities that occurred in ≥ 5% of patients in either mitoxantrone injection dose group, and that were numerically more frequent than in the placebo group.
Table 4b:
Laboratory Abnormalities Occurring in ≥ 5% of Patients* on Either Dose of Mitoxantrone Injection and That Were More Frequent Than in the Placebo Group Study 1 Percent of Patients Event Placebo (N = 64) 5 mg/m 2 Mitoxantrone Injection (N = 65) 12 mg/m 2 Mitoxantrone Injection (N = 62) Leukopenia a 0 9 19 Gamma-GT increased 3 3 15 SGOT increased 8 9 8 Granulocytopenia b 2 6 6 Anemia 2 9 6 SGPT increased 3 6 5 * Assessed using World Health Organization (WHO) toxicity criteria.
a < 4000 cells/mm 3 b < 2000 cells/mm 3 There was no difference among treatment groups in the incidence or severity of hemorrhagic events. In Study 2, mitoxantrone injection was administered once a month. Clinical adverse events most frequently reported in the mitoxantrone injection group included amenorrhea (53% of female patients), alopecia (33% of patients), nausea (29% of patients), and asthenia (24% of patients).
Tables 5a and 5b respectively summarize adverse events and laboratory abnormalities occurring in > 5% of patients in the mitoxantrone injection group and numerically more frequent than in the control group.
Table 5a:
Adverse Events of Any Intensity Occurring in > 5% of Patients* in the Mitoxantrone Injection Group and Numerically More Frequent Than in the Control Group Study 2 Percent of Patients Event MP (n = 21) M + MP (n = 21) Amenorrhea a 0 53 Alopecia 0 33 Nausea 0 29 Asthenia 0 24 Pharyngitis/throat infection 5 19 Gastralgia/stomach burn/epigastric pain 5 14 Aphthosis 0 10 Cutaneous mycosis 0 10 Rhinitis 0 10 Menorrhagia a 0 7 M = Mitoxantrone Injection, MP = Methylprednisolone * Assessed using National Cancer Institute (NCI) common toxicity criteria.
a Percentage of female patients.
Table 5b:
Laboratory Abnormalities Occurring in > 5% of Patients* in the Mitoxantrone Injection Group and Numerically More Frequent Than in the Control Group Study 2 Percent of Patients Event MP (n = 21) M + MP (n = 21) WBC low a 14 100 ANC low b 10 100 Lymphocytes low 43 95 Hemoglobin low 48 43 Platelets low c 0 33 SGOT high 5 15 SGPT high 10 15 Glucose high 5 10 Potassium low 0 10 M = Mitoxantrone Injection, MP = Methylprednisolone.
* Assessed using National Cancer Institute (NCI) common toxicity criteria. a < 4000 cells/mm 3 b < 1500 cells/mm 3 c < 100,000 cells/mm 3 Leukopenia and neutropenia were reported in the M + MP group (see Table 5b ). Neutropenia occurred within 3 weeks after mitoxantrone injection administration and was always reversible.
Only mild to moderate intensity infections were reported in 9 of 21 patients in the M + MP group and in 3 of 21 patients in the MP group; none of these required hospitalization. There was no difference among treatment groups in the incidence or severity of hemorrhagic events.
There were no withdrawals from Study 2 for safety reasons. Leukemia Mitoxantrone injection has been studied in approximately 600 patients with acute nonlymphocytic leukemia (ANLL). S. comparative study of mitoxantrone + cytarabine vs.
daunorubicin + cytarabine. Experience in the large international study was similar. A much wider experience in a variety of other tumor types revealed no additional important reactions other than cardiomyopathy (see WARNINGS ). , dyspnea, cough and pneumonia.
In addition, the listed adverse reactions cannot all necessarily be attributed to chemotherapy as it is often impossible to distinguish effects of the drug and effects of the underlying disease. It is clear, however, that the combination of mitoxantrone injection + cytarabine was responsible for nausea and vomiting, alopecia, mucositis/stomatitis, and myelosuppression.
S. trial. Adverse reactions are presented as major categories and selected examples of clinically significant subcategories.
Table 6:
Adverse Events Occurring in ANLL Patients Receiving Mitoxantrone Injection or Daunorubicin Induction [% pts entering induction] Consolidation [% pts entering induction] Event MIT N = 102 DAUN N = 102 MIT N = 55 DAUN N = 49 MIT = Mitoxantrone Injection, DAUN = Daunorubicin.
Cardiovascular 26 28 11 24 CHF 5 6 0 0 Arrhythmias 3 3 4 4 Bleeding 37 41 20 6 GI 16 12 2 2 Petechiae/ecchymoses 7 9 11 2 Gastrointestinal 88 85 58 51 Nausea/vomiting 72 67 31 31 Diarrhea 47 47 18 8 Abdominal pain 15 9 9 4 Mucositis/stomatitis 29 33 18 8 Hepatic 10 11 14 2 Jaundice 3 8 7 0 Infections 66 73 60 43 UTI 7 2 7 2 Pneumonia 9 7 9 0 Sepsis 34 36 31 18 Fungal infections 15 13 9 6 Renal failure 8 6 0 2 Fever 78 71 24 18 Alopecia 37 40 22 16 Pulmonary 43 43 24 14 Cough 13 9 9 2 Dyspnea 18 20 6 0 CNS 30 30 34 35 Seizures 4 4 2 8 Headache 10 9 13 8 Eye 7 6 2 4 Conjunctivitis 5 1 0 0 Hormone-Refractory Prostate Cancer Detailed safety information is available for a total of 353 patients with hormone-refractory prostate cancer treated with mitoxantrone injection, including 274 patients who received mitoxantrone injection in combination with corticosteroids.
Table 7 summarizes adverse reactions of all grades occurring in ≥ 5% of patients in Trial CCI-NOV22.
Table 7:
Adverse Events of Any Intensity Occurring in ≥ 5% of Patients Trial CCI-NOV22 Event M + P (n = 80) % P (n = 81) % M = Mitoxantrone Injection, P = Prednisone. Nausea 61 35 Fatigue 39 14 Alopecia 29 0 Anorexia 25 6 Constipation 16 14 Dyspnea 11 5 Nail bed changes 11 0 Edema 10 4 Systemic infection 10 7 Mucositis 10 0 UTI 9 4 Emesis 9 5 Pain 8 9 Fever 6 3 Hemorrhage/bruise 6 1 Anemia 5 3 Cough 5 0 Decreased LVEF 5 0 Anxiety/depression 5 3 Dyspepsia 5 6 Skin infection 5 3 Blurred vision 3 5 No nonhematologic adverse events of Grade 3/4 were seen in > 5% of patients.
Table 8 summarizes adverse events of all grades occurring in ≥ 5% of patients in Trial CALGB 9182.
Table 8:
Adverse Events of Any Intensity Occurring in ≥ 5 % of Patients Trial CALGB 9182 M + H (n = 112) H (n = 113) Event n % n % M= Mitoxantrone Injection, H= Hydrocortisone Decreased WBC 96 87 4 4 Abnormal granulocytes/bands 88 79 3 3 Decreased hemoglobin 83 75 42 39 Abnormal lymphocytes count 78 72 27 25 Pain 45 41 44 39 Abnormal platelet count 43 39 8 7 Abnormal alkaline phosphatase 41 37 42 38 Malaise/fatigue 37 34 16 14 Hyperglycemia 33 31 32 30 Edema 31 30 15 14 Nausea 28 26 9 8 Anorexia 24 22 16 14 Abnormal BUN 24 22 22 20 Abnormal transaminase 22 20 16 14 Alopecia 20 20 1 1 Abnormal cardiac function 19 18 0 0 Infection 18 17 4 4 Weight loss 18 17 13 12 Dyspnea 16 15 9 8 Diarrhea 16 14 4 4 Fever in absence of infection 15 14 7 6 Weight gain 15 14 16 15 Abnormal creatinine 14 13 11 10 Other gastrointestinal 13 14 11 11 Vomiting 12 11 6 5 Other neurologic 11 11 5 5 Hypocalcemia 10 10 5 5 Hematuria 9 11 5 6 Hyponatremia 9 9 3 3 Sweats 9 9 2 2 Other liver 8 8 8 8 Stomatitis 8 8 1 1 Cardiac dysrhythmia 7 7 3 3 Hypokalemia 7 7 4 4 Neuro/constipation 7 7 2 2 Neuro/motor disorder 7 7 3 3 Neuro/mood disorder 6 6 2 2 Skin disorder 6 6 4 4 Cardiac ischemia 5 5 1 1 Chills 5 5 0 0 Hemorrhage 5 5 3 3 Myalgias/arthralgias 5 5 3 3 Other kidney/bladder 5 5 3 3 Other endocrine 5 6 3 4 Other pulmonary 5 5 3 3 Hypertension 4 4 5 5 Impotence/libido 4 7 2 3 Proteinuria 4 6 2 3 Sterility 3 5 2 3 General Allergic Reaction Hypotension, urticaria, dyspnea, and rashes have been reported occasionally.
Anaphylaxis/anaphylactoid reactions have been reported rarely. Cutaneous Extravasation at the infusion site has been reported, which may result in erythema, swelling, pain, burning, and/or blue discoloration of the skin. Extravasation can result in tissue necrosis with resultant need for debridement and skin grafting.
Phlebitis has also been reported at the site of the infusion. Hematologic Topoisomerase II inhibitors, including mitoxantrone injection, in combination with other antineoplastic agents or alone, have been associated with the development of acute leukemia (see WARNINGS ).
Leukemia Myelosuppression is rapid in onset and is consistent with the requirement to produce significant marrow hypoplasia in order to achieve a response in acute leukemia. S. trial are consistent with those reported for other standard induction regimens.
Hormone-Refractory Prostate Cancer In a randomized study where dose escalation was required for neutrophil counts greater than 1000/mm 3 , Grade 4 neutropenia (ANC <500/mm 3 ) was observed in 54% of patients treated with mitoxantrone injection + low-dose prednisone.
In a separate randomized trial where patients were treated with 14 mg/m 2 , Grade 4 neutropenia in 23% of patients treated with mitoxantrone injection + hydrocortisone was observed. Neutropenic fever/infection occurred in 11% and 10% of patients receiving mitoxantrone injection + corticosteroids, respectively, on the two trials.
Platelets <50,000/mm 3 were noted in 4% and 3% of patients receiving mitoxantrone injection + corticosteroids on these trials, and there was one patient death on mitoxantrone injection + hydrocortisone due to intracranial hemorrhage after a fall.
Gastrointestinal Nausea and vomiting occurred acutely in most patients and may have contributed to reports of dehydration, but were generally mild to moderate and could be controlled through the use of antiemetics. Stomatitis/mucositis occurred within 1 week of therapy.
Cardiovascular Congestive heart failure, tachycardia, EKG changes including arrhythmias, chest pain, and asymptomatic decreases in left ventricular ejection fraction have occurred (see WARNINGS ). Pulmonary Interstitial pneumonitis has been reported in cancer patients receiving combination chemotherapy that included mitoxantrone injection.
To report SUSPECTED ADVERSE REACTIONS, contact Meitheal Pharmaceuticals, Inc. gov/medwatch .
Cardiac Effects Because of the possible danger of cardiac effects in patients previously treated with daunorubicin or doxorubicin, the benefit-to-risk ratio of mitoxantrone injection therapy in such patients should be determined before starting therapy.
Functional cardiac changes including decreases in left ventricular ejection fraction (LVEF) and irreversible congestive heart failure can occur with mitoxantrone injection. Cardiac toxicity may be more common in patients with prior treatment with anthracyclines, prior mediastinal radiotherapy, or with preexisting cardiovascular disease.
Such patients should have regular cardiac monitoring of LVEF from the initiation of therapy. 6% probability of clinical congestive heart failure. In comparative oncology trials, the overall cumulative probability rate of moderate or severe decreases in LVEF at this dose was 13%.
Multiple Sclerosis Changes in cardiac function may occur in patients with multiple sclerosis treated with mitoxantrone injection. In one controlled trial (Study 1, see CLINICAL TRIALS, Multiple Sclerosis ), two patients (2%) of 127 receiving mitoxantrone injection, one receiving a 5 mg/m 2 dose and the other receiving the 12 mg/m 2 dose, had LVEF values that decreased to below 50%.
An additional patient receiving 12 mg/m 2 , who did not have LVEF measured, had a decrease in another echocardiographic measurement of ventricular function (fractional shortening) that led to discontinuation from the trial (see ADVERSE REACTIONS, Multiple Sclerosis ).
There were no reports of congestive heart failure in either controlled trial. MS patients should be assessed for cardiac signs and symptoms by history, physical examination, ECG, and quantitative LVEF evaluation using appropriate methodology (ex.
) prior to the start of mitoxantrone injection therapy. MS patients with a baseline LVEF below the lower limit of normal should not be treated with mitoxantrone injection. Subsequent LVEF and ECG evaluations are recommended if signs or symptoms of congestive heart failure develop and prior to every dose administered to MS patients.
Mitoxantrone injection should not be administered to MS patients who experience a reduction in LVEF to below the lower limit of normal, to those who experience a clinically significant reduction in LVEF, or to those who have received a cumulative lifetime dose of 140 mg/m 2 .
MS patients should have yearly quantitative LVEF evaluation after stopping mitoxantrone injection to monitor for late-occurring cardiotoxicity. Leukemia Acute congestive heart failure may occasionally occur in patients treated with mitoxantrone injection for ANLL.
In first-line comparative trials of mitoxantrone injection + cytarabine vs. 5% of patients on each arm. A causal relationship between drug therapy and cardiac effects is difficult to establish in this setting since myocardial function is frequently depressed by the anemia, fever and infection, and hemorrhage that often accompany the underlying disease.
Hormone-Refractory Prostate Cancer Functional cardiac changes such as decreases in LVEF and congestive heart failure may occur in patients with hormone-refractory prostate cancer treated with mitoxantrone injection. In a randomized comparative trial of mitoxantrone injection plus low-dose prednisone vs.
5 %) treated with mitoxantrone injection had a cardiac event defined as any decrease in LVEF below the normal range, congestive heart failure (n = 3), or myocardial ischemia. Two patients had a prior history of cardiac disease. The total mitoxantrone injection dose administered to patients with cardiac effects ranged from > 48 to 212 mg/m 2 .
Among 112 patients evaluable for safety on the mitoxantrone injection + hydrocortisone arm of the CALGB trial, 18 patients (19%) had a reduction in cardiac function, 5 patients (5%) had cardiac ischemia, and 2 patients (2%) experienced pulmonary edema.
The range of total mitoxantrone injection doses administered to these patients is not available. Pregnancy Mitoxantrone injection may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant.
Mitoxantrone is considered a potential human teratogen because of its mechanism of action and the developmental effects demonstrated by related agents. 01 times the recommended human dose on a mg/m 2 basis). 01 times the recommended human dose on a mg/m 2 basis).
05 times in rats and rabbits, respectively, on a mg/m 2 basis). There are no adequate and well-controlled studies in pregnant women. Women with multiple sclerosis who are biologically capable of becoming pregnant should have a pregnancy test prior to each dose, and the results should be known prior to administration of the drug.
If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to the fetus. Secondary Leukemia Mitoxantrone injection therapy increases the risk of developing secondary leukemia in patients with cancer and in patients with multiple sclerosis.
7 years follow-up. 6% (3/509) of patients. 8% in cohorts of patients with MS treated with mitoxantrone injection and followed for varying periods of time. This leukemia risk exceeds the risk of leukemia in the general population. The most commonly reported types were acute promyelocytic leukemia and acute myelocytic leukemia.
6% at 5 and 10 years, respectively. The second largest report involved 449 patients with breast cancer treated with mitoxantrone injection, usually in combination with radiotherapy and/or other cytotoxic agents. 2% at 4 years. Secondary acute myeloid leukemia has also been reported in cancer patients treated with anthracyclines.
Mitoxantrone injection is an anthracenedione, a related drug. The occurrence of secondary leukemia is more common when anthracyclines are given in combination with DNA-damaging antineoplastic agents, when patients have been heavily pretreated with cytotoxic drugs, or when doses of anthracyclines have been escalated.
Symptoms of acute leukemia may include excessive bruising, bleeding, and recurrent infections.