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ONKOTRONE is a brand name for Mitoxantrone. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Onkotrone Injection is indicated for the treatment of: - Metastatic breast cancer - Non-Hodgkin's Lymphoma - Acute myeloid leukaemia (AML) in adults - In combination regimens is indicated in the remission-induction treatment of blast crisis in chronic myeloid leukaemia - In combination with corticosteroids for…
Verbatim from this product's MHRA label. Tap a section to expand.
Posology Onkotrone should be administered under the supervision of a physician experienced in the use of cytotoxic chemotherapy agents. Metastatic breast cancer, non-Hodgkin’s lymphoma Single agent therapy The recommended initial dosage of mitoxantrone used as a single agent is 14 mg/m2 of body surface area, given as a single intravenous dose, which may be repeated at 21-day intervals.
g. due to prior chemotherapy or poor general condition. Dosage modification and the timing of subsequent dosing should be determined by clinical judgment depending on the degree and duration of myelosuppression. For subsequent courses, the prior dose can usually be repeated if white blood cell and platelet counts have returned to normal levels after 21 days.
The following table is suggested as a guide to dosage adjustment, in the treatment of metastatic breast cancer and non-Hodgkin’s lymphoma according to haematological nadir (which usually occurs about 10 days after dosing). WBC and platelet nadir Time to recovery Subsequent dosing If WBC nadir > 1,500 μl and platelet nadir > 50,000 μl Recovery ≤ 21 days Repeat prior dose If WBC nadir > 1,500 μl and platelet nadir > 50,000 μl Recovery > 21 days Withhold until recovery, then repeat prior dose.
If WBC nadir < 1,500 μl or platelet nadir < 50,000 μl Any duration Decrease by 2 mg/m2 from prior dose, after recovery. If WBC nadir < 1,000 μl or platelet nadir < 25,000 μl Any duration Decrease by 4 mg/m2 from prior dose, after recovery.
Combination therapy Mitoxantrone has been given as part of combination therapy. In metastatic breast cancer, combinations of mitoxantrone with other cytotoxic agents including cyclophosphamide and 5-fluorouracil or methotrexate and mitomycin C have been shown to be effective.
Mitoxantrone has also been used in various combinations for non-Hodgkin’s lymphoma; however, data are presently limited and specific regimens cannot be recommended. In combination regimens mitoxantrone, in starting doses ranging from 7 to 8 to 10 to 12 mg/m2, dependent on the combination and frequency used, has shown effectiveness.
As a guide, when mitoxantrone is used in combination chemotherapy with another myelosuppressive agent, the initial dose of mitoxantrone should be reduced by 2 to 4 mg/m2 below the doses recommended for single agent usage; subsequent dosing, as outlined in the table above, depends on the degree and duration of myelosuppression.
Summary of the safety profile The most serious side effects with mitoxantrone are myocardial toxicity and myelosuppression. The most common side effects with mitoxantrone (seen in more than 1 patient in 10) are anaemia, leucopenia, neutropenia, infections, amenorrhoea, alopecia, nausea and vomiting.
Tabulated list of adverse reactions The table below is based on safety data derived from clinical trials and spontaneous reporting. Frequencies are defined according to the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).
Frequency Adverse Reaction Infections and Infestations Very common Infection (including fatal outcome) Uncommon Urinary tract infection Upper respiratory tract infection Sepsis Opportunistic infections Rare Pneumonia Neoplasms benign and malignant (including cysts and polyps) Uncommon Acute myeloid leukaemia, myelodysplastic syndrome, acute leukaemia Blood and lymphatic system disorders Very common Anaemia Neutropenia Leukopenia Common Thrombocytopenia Granulocytopenia Uncommon Myelosuppression Bone marrow failure White blood cell count abnormal Immune system disorders Uncommon Anaphylaxis/anaphylactoid reactions (including shock) Metabolism and nutrition disorders Common Anorexia Uncommon Weight fluctuations Tumour lysis syndrome* * Acute T and B lymphoblastic leukaemia and non-Hodgkin lymphomas (NHL) are most commonly associated with TLS Nervous system disorders Common Lethargy Uncommon Anxiety Confusion Headache Paraesthesia Eye disorders Uncommon Scleral discolouration Cardiac disorders Common Congestive heart failure Myocardial infarction (including fatal events) Uncommon Arrhythmia Sinus bradycardia Electrocardiogram abnormal Left ventricular ejection fraction decreased Rare Cardiomyopathy Vascular disorders Uncommon Contusion Haemorrhage Hypotension Respiratory, thoracic and mediastinal disorders Common Dyspnoea Gastrointestinal disorders Very common Nausea Vomiting Common Constipation Diarrhoea Stomatitis Uncommon Abdominal pain Gastrointestinal haemorrhage Mucosal inflammation Pancreatitis Hepatobiliary disorders Uncommon Hepatotoxicity Elevated aspartate aminotransferase levels Skin and subcutaneous tissue disorders Very common Alopecia Uncommon Erythema Nail disorders Rash Skin discolouration Tissue necrosis (after extravasation) Renal and urinary disorders Uncommon Elevated serum creatinine Elevated blood urea nitrogen levels Nephropathy toxic Urine discolouration Reproductive system and breast disorders Uncommon Amenorrhoea General disorders and administration site conditions Common Asthenia Fatigue Pyrexia Uncommon Oedema Extravasation* Dysgeusia * Extravasation at the infusion site has been reported, which may result in erythema, swelling, pain, burning and/or blue discolouration of the skin.
Precautions to be taken before handling or administering the medicinal product Mitoxantrone should be given slowly into a freely flowing intravenous infusion. Mitoxantrone must not be given subcutaneously, intramuscularly, or intra-arterially.
There have been reports of local/regional neuropathy, some irreversible, following intra-arterial injection. Severe local tissue damage may occur if there is extravasation during administration. To date, only isolated cases of severe local reactions (necroses) have been described due to extravasation.
Mitoxantrone must not be given by intrathecal injection. Severe injury with permanent sequelae can result from intrathecal administration. 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. Cardiac function Myocardial toxicity, manifested in its most severe form by potentially irreversible and fatal congestive heart failure (CHF), may occur either during therapy with mitoxantrone or months to years after termination of therapy.
This risk increases with cumulative dose. 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%. Active or dormant cardiovascular disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, or concomitant use of other cardiotoxic medicinal products may increase the risk of cardiac toxicity.
Evaluation of the left-ventricular ejection fraction (LVEF) by echocardiogram or multiple-gated acquisition (MUGA) is recommended prior to administration of the initial dose of mitoxantrone in cancer patients. Cardiac function for cancer patients should be carefully monitored during treatment.
1, including sulphites that may be produced during the manufacturing of mitoxantrone. 6).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Acute myeloid leukaemia Single Agent Therapy in Relapse The recommended dosage for remission induction is 12 mg/m2 of body surface area, given as a single intravenous dose daily for five consecutive days (total of 60 mg/m2). In clinical studies with a dosage of 12 mg/m2 daily for 5 days, patients who achieved a complete remission did so as a result of the first induction course.
Combination Therapy For induction, the recommended dosage is 12 mg/m2 of mitoxantrone daily on Days 1 to 3 given as an intravenous infusion, and 100 mg/m2 of cytarabine for 7 days given as a continuous 24-hour infusion on Days 1 to 7.
Most complete remissions will occur following the initial course of induction therapy. In the event of an incomplete antileukaemic response, a second induction course may be given with mitoxantrone given for 2 days and cytarabine for 5 days, using the same daily dosage levels.
If severe or life- threatening non-haematological 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 randomised multicentre trials, consists of mitoxantrone 12 mg/m2 given by intravenous infusion daily on Days 1 and 2, and cytarabine, 100 mg/m2 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. A single course of mitoxantrone 6 mg/m2 intravenous (IV) bolus, etoposide 80 mg/m2 intravenous for a period of 1 hour, and cytarabine (Ara-C) 1 g/m2 intravenous for a period of 6 hours daily for 6 days (MEC) showed antileukaemic activity as salvage therapy for refractory AML.
Treatment of blast crisis in (chronic) myeloid leukaemia Single dose therapy in relapse The recommended dosage in relapse is 10 to 12 mg/m2 body surface area given as a single intravenous dose daily over 5 consecutive days (total of 50 to 60 mg/m2).
Advanced castrate-resistant prostate cancer Based on data from two comparative trials of mitoxantrone plus corticosteroids versus corticosteroids alone, the recommended dosage of mitoxantrone is 12 to 14 mg/m2 given as a short intravenous infusion every 21 days, in combination with low oral doses of corticosteroids.
6% probability of clinical congestive heart failure. For this reason, patients should be monitored for evidence of cardiac toxicity and questioned about symptoms of heart failure prior to the initiation of and during treatment. Special populations Elderly In general, dose selection for an elderly patient should be initiated at the low end of the dosing range, reflecting the greater frequency of decreasing hepatic, renal, or cardiac function, and of concomitant disease or treatment with other medicinal products.
Renal Impairment The safety of mitoxantrone in patients with renal impairment is not established. Mitoxantrone should be used with caution. Hepatic Impairment The safety of mitoxantrone in patients with hepatic insufficiency is not established.
For patients with hepatic impairment dose adjustment may be necessary as mitoxantrone clearance is reduced by hepatic impairment. There are insufficient data that allows for dose adjustment recommendations. Laboratory measurement […]
Extravasation can result in tissue necrosis with resultant need for debridement and skin grafting. Phlebitis has also been reported at the site of infusion. Description of selected adverse reactions Myocardial toxicity, manifested in its most severe form by potentially irreversible and fatal congestive heart failure (CHF), may occur either during therapy with mitoxantrone or months to years after termination of therapy.
This risk increases with cumulative dose. 6% probability of clinical congestive heart failure. Myelosuppression is a dose-limiting undesirable effect of mitoxantrone. Myelosuppression can be more pronounced and longer-lasting in patients who have previously received chemotherapy or radiotherapy.
In a clinical trial with acute leukaemia patients, significant myelosuppression occurred in all patients who were given mitoxantrone therapy. 500/μl (WHO grade 4), respectively. Haematological toxicity is difficult to evaluate in acute leukaemia because traditional parameters of bone marrow depression such as white blood cell and platelet counts are confounded by marrow replacement with leukemic cells.
Paediatric population Treatment with mitoxantrone is not recommended in the paediatric population. Safety and efficacy have not been established. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
LVEF evaluation is recommended at regular intervals and/or if signs or symptoms of congestive heart failure develop. Cardiotoxicity can occur at any time during mitoxantrone therapy, and the risk increases with cumulative dose. Cardiac toxicity with mitoxantrone may occur at lower cumulative doses whether or not cardiac risk factors are present.
Because of the possible danger of cardiac effects in patients previously treated with daunorubicin or doxorubicin, the benefit-to-risk ratio of mitoxantrone therapy in such patients should be determined before starting therapy. Acute congestive heart failure may occasionally occur in patients treated with mitoxantrone for acute myeloid leukaemia.
Bone marrow suppression Therapy with mitoxantrone should be accompanied by close and frequent monitoring of haematological and chemical laboratory parameters, as well as frequent patient observation. A complete blood count, including platelets, should be obtained prior to administration of the initial dose of mitoxantrone, 10 days following the administration and prior to each subsequent infusion and in the event that signs and symptoms of infection develop.
Patients should be informed about risks, symptoms and signs of acute leukaemia and prompted to seek medical attendance if any such symptoms should occur even after the five year period has passed. Myelosuppression may be more severe and prolonged in patients with poor general condition, or prior chemotherapy and/or radiotherapy.
Except for the treatment of acute myeloid leukaemia, mitoxantrone therapy generally should not be given to patients with baseline neutrophil counts of less than 1,500 cells/mm3. It is recommended that frequent peripheral blood cell counts are performed on all patients receiving mitoxantrone in order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection.
When mitoxantrone is used in high doses (> 14 mg/m2/d x 3 days) such as indicated for the treatment of leukaemia, severe myelosuppression will occur. Particular care should be given to assuring full haematological recovery before undertaking consolidation therapy (if this treatment is used) and patients should be monitored closely during this phase.
Mitoxantrone administered at any dose can cause myelosuppression. Secondary acute myeloid leukaemia and myelodysplastic syndrome Topoisomerase II inhibitors, including mitoxantrone, when used as monotherapy or especially concomitantly with other antineoplastic agents and/or radiotherapy, have been associated with the development of Acute Myeloid Leukaemia or Myelodysplastic Syndrome.
Because of the risk of development of secondary malignancies, the benefit-to-risk ratio of mitoxantrone therapy should be determined before starting therapy. Non-metastatic breast cancer In the absence of sufficient efficacy data in the adjuvant treatment of breast cancer and accounting for the increased risk of leukaemia, mitoxantrone should only be used for metastatic breast cancer.
Infections Patients who receive immunosuppressive agents like mitoxantrone have a reduced immunological response to infection. Systemic infections should be treated concomitantly with or just prior to commencing therapy with mitoxantrone.
g. yellow fever vaccination) increases the risk of infection and other adverse reactions such as vaccinia gangrenosa and generalised vaccinia, in patients with reduced immunocompetence, such as during treatment with mitoxantrone. Therefore, live virus vaccines should not be administered during therapy.
5). Contraception in males and females Mitoxantrone is […]