Novantrone Side Effects

Generic Name: mitoxantrone

Note: This page contains side effects data for the generic drug mitoxantrone. It is possible that some of the dosage forms included below may not apply to the brand name Novantrone.

It is possible that some side effects of Novantrone may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

For the Consumer

Applies to mitoxantrone: intravenous solution

As well as its needed effects, mitoxantrone (the active ingredient contained in Novantrone) may cause unwanted side effects that 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
Rare
  • Blue skin at the place of injection
  • pain or redness at the place of injection
  • skin rash

Some mitoxantrone side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

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

Hematologic

Myelosuppression associated with mitoxantrone (the active ingredient contained in Novantrone) 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

Oncologic side effects including secondary myelogenous leukemia have been reported in both cancer patients and multiple sclerosis patients treated with mitoxantrone (the active ingredient contained in Novantrone) [Ref]

Gastrointestinal

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

Nausea and vomiting associated with mitoxantrone (the active ingredient contained in Novantrone) 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

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]

Local

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

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

Dermatologic

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

Renal side effects including new or worsened renal insufficiency have rarely been associated with the use of mitoxantrone (the active ingredient contained in Novantrone) [Ref]

Hepatic

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

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

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

Endocrine

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]

References

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