Mitoxantrona

Mitoxantrone
Drug Name │Mechanism of Action & Pharmacokinetics │ Indications & Status │ Adverse Effects │ Dosing │ Administration Guidelines │ Special Precautions │ Interactions │ Recommended Clinical Monitoring │ References

A

DRUG NAME:

MITOXANTRONE

SYNONYM(S): DHAD, Dihydroxyanthracenedione dihydrochloride, Mitozantrone, MX, MXR COMMON TRADE NAME(S):
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Novantrone®(OSI Pharmaceuticals US)

B

MECHANISM OF ACTION AND PHARMACOKINETICS Mitoxantrone is an anthracenedione structurally similar to doxorubicin and daunorubicin. The exact mechanism of action is unknown but includes intercalation with DNA to cause inter/intrastrand cross-linking, inhibition of RNA synthesis and DNA topoisomerase II. Mitoxantrone is cell cycle phase-nonspecific. Oral AbsorptionDistribution Poor Widely distributed into tissues. Cross blood brain barrier? PPB Metabolism Minimal 78%

In liver to polar compounds, pathways not known Active metabolite(s) Inactive metabolite(s) No Yes

Excretion

Triphasic. Mainly in bile (25% in feces within 5 days), small amount in urine Urine t ½ (terminal) 11% within 5 days, 65% unchanged 23-215 hours

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CINDICATIONS AND STATUS      Acute nonlymphocytic leukemia in adults (in combination) Acute leukemia in adults (relapsed) Metastatic breast cancer Non-Hodgkin’s lymphoma Hepatocellular cancer Other uses include: Ovarian cancer Hormone refractory prostate cancer (with steroids)

* Health Canada approved indication
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CCO Formulary

Revised January 2010

Mitoxantrone

D

ADVERSEEFFECTS (mainly in combination with corticosteroid in prostate cancer) ORGAN SITE Cardiovascular SIDE EFFECT Transient arrhythmias (7%) Cardiac ischemia (5%), hypotension Edema (30%), hypertension (4%) Congestive heart failure (2.6%) Dermatologic Nail changes / oncholysis (11%) Alopecia (29%) Extravasation hazard (refer to Appendix 2) Gastrointestinal Minimal-moderate, tissue necrosis (rare)Nausea and vomiting (61%) Stomatitis (29%) Constipation (16%) Weight changes (17%) Abdominal pain, dyspepsia (5%) GI bleeding (rare) Diarrhea (14%), dehydration (rare) Anorexia (25%) Hematologic Myelosuppression, Nadir 10 days, recovery 21 days ↑ LFTS (20%) Leukemia and MDS (1-2%) Type I (anaphylactoid), (rare) Phlebitis (10%) Blue discolouration of vein (rare) I I I E I E E D D L ONSET

I I E E EE E E E

E E L

Hepatic Neoplastic Hypersensitivity Injection site

CCO Formulary

Revised January 2010

Mitoxantrone

D

ADVERSE EFFECTS (Continued, mainly in combination with corticosteroid in prostate cancer) ORGAN SITE Renal/metabolic SIDE EFFECT Blue-green urine (for 1-2 days) Electrolyte changes (up to 10%) Tumour lysis syndrome (rare, AML) Renal damage, proteinuria (6%) ↑creatinine (13%) Other Pneumonitis (rare) Cough (5%), dyspnea (15%) Amenorrhea Fatigue (39%), myalgia/arthralgia (5%) Fever, infection (10%) Conjunctivitis, blurred vision (3%) Neurologic Paresthesia (rare) Confusion (rare), drowsiness (rare) Anxiety/depression (5%) Seizures, headache (rare) Dose-limiting side effects are underlined. I = immediate (onset in hours to days); E = early (days toweeks); D = delayed (weeks to months); L = late (months to years) I E E E E E E E I I E E E E D D I E ONSET

Mitoxantrone may be associated with less nausea and vomiting, stomatitis and alopecia than doxorubicin. Cardiotoxicity may occur with mitoxantrone for months to years after treatment, whether or not cardiac risk factors are present. It is cumulative across members of this class andanthracyclines. The 2 recommended maximum cumulative dose of mitoxantrone is 140 mg/m . At this dose, 13% of patients have moderate to severe decreases in LVEF while 3% of patients may have clinical cardiac failure. The cumulative dose is lower with prior anthracycline therapy, in patients who have received radiation to the mediastinal area or concomitant therapy with other cardiotoxic agents such as...