Chemical formula: C₂₆H₂₇NO₉ Molecular mass: 497.494 g/mol PubChem compound: 42890
Idarubicin interacts in the following cases:
Concomitant use of live attenuated vaccines (e.g. yellow fever) is not recommended, due to a risk of possibly fatal systemic disease. The risk is increased in subjects who are already immunosuppressed by their underlying disease. An inactivated vaccine should be used if available.
At combination of oral anticoagulants and anticancer chemotherapy, increased frequency of the INR (International Normalised Ratio) monitoring is recommended, since the risk for an interaction cannot be excluded.
Idarubicin can induce chromosomal damage in human spermatozoa. For this reason, males undergoing treatment with idarubicin should use effective contraceptive methods up to 3 months after treatment.
The co-adminstration of cyclosporin A as a single chemosensitizer significantly increased idarubicin AUC (1.78-fold) and idarubicinol AUC (2.46-fold) in patients with acute leukaemia. The clinical significance of this interaction is unknown.
An additive myelosuppressant effect may occur when radiotherapy is given concomitantly or within 2-3 weeks prior to treatment with idarubicin.
Idarubicin may induce hyperuricaemia as a consequence of the extensive purine catabolism that accompanies rapid drug-induced lysis of neoplastic cells (‘tumour lysis syndrome’). Blood uric acid levels, potassium, calcium phosphate, and creatinine should be evaluated after initial treatment. Hydration, urine alkalinisation, and prophylaxis with allopurinol to prevent hyperuricaemia may minimize potential complications of tumour lysis syndrome.
Idarubicin is a potent bone marrow suppressant. Severe myelosuppression, will occur in all patients given a therapeutic dose of this agent.
Haematological profiles should be assessed before and during each cycle of therapy with idarubicin, including differential white blood cell (WBC) counts.
A dose-dependent, reversible luekopenia and/or granulocytopenia (neutropenia) is the predominant manifestation of idarubicin haematologic toxicity and is the most common acute dose limiting toxicity of the drug.
Leukopenia and neutropenia are usually severe, thrombocytopenia and anaemia may also occur. Neutrophil and platelet counts usually reach their nadir 10 to 14 days after drug administration; however, cell counts generally return to normal levels during the third week.
During the phase of severe myelosuppression, deaths due to infections and/or haemorrhages have been reported.
Clinical consequences of severe myelosuppression include fever, infections, sepsis/septicaemia, septic shock, haemorrhage, tissue hypoxia or death. If febrile neutropenia occurs, treatment with an i.v. antibiotic is recommended.
Cardiotoxicity is a risk of anthracycline treatment that may be manifested by early (i.e. acute) or late (i.e. delayed) events.
Early (i.e. acute) events: Early cardiotoxicity of idarubicin consists mainly of sinus tachycardia and/or electrocardiogram (ECG) abnormalities, such as non-specific ST-T wave changes. Tachyarrhythmias, including premature ventricular contractions and ventricular tachycardia, bradycardia, as well as atrioventricular and bundle-branch block have also been reported. These effects do not usually predict subsequent development of delayed cardiotoxicity, are rarely of clinical importance, and are generally not a reason for the discontinuation of idarubicin treatment.
Late (i.e. delayed) events: Delayed cardiotoxicity usually develops late in the course of therapy or within 2 to 3 months after treatment termination, but later events, several months to years after completion of treatment have also been reported. Delayed cardiomyopathy is manifested by reduced left ventricular ejection fraction (LVEF) and/or signs and symptoms of congestive heart failure (CHF) such as dyspnoea, pulmonary oedema, dependent oedema, cardiomegaly hepatomegaly, oliguira, ascitres, pleural effusion, and gallop rhythm. Subacute effects such as pericarditis/myocarditis have also been reported. Life-threatening CHF is the most severe form of anthracycline-induced cardiomyopathy and represents the cumulative dose-limiting toxicity of the drug.
Cumulative dose limits for i.v. or oral idarubicin hydrochloride have not been defined. However, idarubicin-related cardiomyopathy was reported in 5% of patients who received cumulative i.v. doses of 150 to 290mg/m². Available data on patients treated with oral idarubicin hydrochloride total cumulative doses up to 400 mg/m² suggest a low probability of cardiotoxicity.
Cardiac function should be assessed before patients undergo treatment with idarubicin and must be monitored throughout therapy to minimize the risk of incurring severe cardiac impairment. The risk may be decreased through regular monitoring of LVEF during the course of treatment with prompt discontinuation of idarubicin at the first sign of impaired function. The appropriate quantitative method for repeated assessment of cardiac function (evaluation of LVEF) includes Multiple Gated Acquisition (MUGA) scan or echocardiography (ECHO). A baseline cardiac evaluation with an ECG and either a MUGA scan or an ECHO is recommended, especially in patients with risk factors for increased cardiotoxicity. Repeated MUGA or ECHO determinations of LVEF should be performed, particularly with higher, cumulative anthracycline doses. The technique used for assessment should be consistent throughout follow-up.
Risk factors for cardiac toxicity include active or dormant cardiovascular disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, and concomitant use of drugs with the ability to suppress cardiac contractility or cardiotoxic drugs (e.g. trastuzumab). Anthracyclines including idarubicin should not be administered in combination with other cardiotoxic agents unless the patient’s cardiac function is closely monitored. Patients receiving anthracyclines after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, may also be at an increased risk of developing cardiotoxicity. The reported half-life of trastuzumab is approximately 28–38 days and may persist in the circulation for up to27 weeks. Therefore, physicians should avoid anthracycline-based therapy for up to 27 weeks after stopping trastuzumab when possible. If anthracyclines are used before this time, careful monitoring of cardiac function is recommended.
Cardiac function monitoring must be particularly strict in patients receiving high cumulative doses and in those with risk factors, however, cardiotoxicity with idarubicin may occur at lower cumulative doses whether or not cardiac risk factors are present.
In infants and children there appears to be a greater susceptibility to anthracycline induced cardiac toxicity, and a long-term periodic evaluation of cardiac function has to be performed.
It is probable that the toxicity of idarubicin and other anthracyclines or anthracenediones is additive.
As with other cytotoxic agents, thrombophlebitis and thromboembolic phenomena, including pulmonary embolism have been coincidentally reported with the use of idarubicin.
Idarubicin is emetigenic. Mucositis (mainly stomatitis, less often oesophagitis) generally appears early after drug administration and, if severe, may progress over a few days to mucosal ulcerations. Most patients recover from this adverse event by the third week of therapy.
Occasionally, episodes of serious gastrointestinal events (such as perforation or bleeding) have been observed in patients receiving oral idarubicin who had acute leukaemia or a history of other pathologies or had received medications known to lead to gastrointestinal complications. In patients with active gastrointestinal disease with increased risk of bleeding and/or perforation, the physician must balance the benefit of oral idarubicin therapy against the risk.
The embryotoxic potential of idarubicin has been demonstrated in both in vitro and in vivo studies. However, there are no adequate and well-controlled studies in pregnant women. Women of child bearing potential should be advised not to become pregnant during treatment and adopt adequate contraceptive measures during therapy as suggested by a physician.
Idarubicin should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. The patient should be informed of the potential hazard to the foetus. Patients desiring to have children after completion of therapy should be advised to obtain genetic counselling first if appropriate and available.
It is not known whether idarubicin or its metabolites are excreted in human milk. Mothers should not breast-feed during treatment with idarubicin hydrochloride.
Idarubicin can induce chromosomal damage in human spermatozoa. For this reason, males undergoing treatment with idarubicin should use effective contraceptive methods up to 3 months after treatment.
The effect of idarubicin on the ability to drive or use machinery has not been systematically evaluated.
The frequencies of undesirable effects are based on the following categories: 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 (frequency cannot be estimated from the available data).
Very common: Infections
Uncommon: Sepsis, septicaemia
Uncommon: Secondary leukaemia (acute myeloid leukaemia and myelodysplastic syndrome)
Very common: Anaemia, severe leukopenia and neutropenia, thrombocytopenia
Not known: Pancytopenia
Very rare: Anaphylaxis
Very common: Anorexia
Uncommon: Dehydration
Uncommon: Hyperuricaemia
Not known: Tumour Lysis Syndrome
Rare: Cerebral haemorrhages
Common: Bradycardia, sinus tachycardia, tachyarrhythmia, asymptomatic reduction of left ventricular ejection fraction, congestive heart failure, cardiomyopathies
Uncommon: ECG abnormalities (e.g. nonspecific ST segment changes), myocardial infarction
Very rare: Pericarditis, myocarditis, atrioventricular and bundle branch block
Common: Local phlebitis, thrombophlebitis, haemorrhages
Uncommon: Shock
Very rare: Thromboembolism, flush
Very common: Nausea, vomiting, mucositis/stomatitis, diarrhoea, abdominal pain or burning sensation
Common: Gastrointestinal tract bleeding, bellyache
Uncommon: Oesophagitis, colitis (including severe enterocolitis/neutropenic enterocolitis with perforation)
Very rare: Gastric erosions or ulcerations
Common: Elevation of the liver enzymes and bilirubin
Very common: Alopecia
Common: Rash, itch, hypersensitivity of irradiated skin (‘radiation recall reaction’)
Uncommon: Skin and nail hyperpigmentation, urticaria, cellulitis (this event can be severe), tissue necrosis
Very rare: Acral erythema
Not known: Local reaction
Very common: Red coloration of the urine for 1–2 days after the treatment.
Very common: Fever, headache, chills
Pronounced myelosuppression is the most severe adverse effect of idarubicin treatment. However, this is necessary for the eradication of leukemic cells.
Life-threatening CHF is the most severe form of anthracycline-induced cardiomyopathy and represents the cumulative dose-limiting toxicity of the drug.
Stomatitis and in severe cases ulceration of mucosa, dehydration caused by severe vomiting and diarrhoea; risk of perforation of colon etc.
Phlebitis/thrombophlebitis and prevention measures; unintended paravenous infiltrates may cause pain, severe cellulites and tissue necrosis.
Prevention of symptoms by hydration, urine alkalinisation, and prophylaxis with allopurinol may minimise potential complications of tumour lysis syndrome.
Undesirable effects are similar in adults and children except a greater susceptibility to anthracycline-induced cardiac toxicity of children.
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