Adverse Drug Reaction Classification System

Pharmaceutical Information
Drug Name Pixantrone
Drug ID BADD_D01786
Description Pixantrone is an aza-anthracenedione and DNA intercalator which inhibits topoisomerase II. It is similar in structure to anthracyclines such as mitoxantrone, but exerts fewer toxic effects on cardiac tissue. [2] The lower cardio-toxic effects of pixantrone may be explained, in part, by its redox inactivity [3]. Pixantrone does not bind iron and promotes the formation of reactive oxygen species to a lesser degree than other anthracyclines. It also inhibits doxorubicinol formation in human myocardium. [3] As a result, it is believed to be less cardiotoxic while still exerting efficacy. Pixantrone was designed to treat relapsed or refractory aggressive non-Hodgkin's lymphoma(NHL) in patients who have failed two prior lines of therapy. [2] For patients suffering from NHL, first line therapies consist of anthracycline containing multi-drug treatments which unfortunately are known to cause irreversible myocardial tissue damage. Patients refractory to treatment, or those who relapse, are discouraged from further anthracycline use due to cumulative cardiotoxicity. Pixantrone dimaleate, administered intravenously, was designed by Cell Therapeutics Incorporated as an alternative second line therapy in refractory or relapsed NHL. It is currently being tested in Phase III trials. [2] Although pixantrone has not yet received FDA approval in the United States, it has been granted conditional marketing approval by the European Union. Conditional approval was granted by the European Medicines Agency after a phase III EXTEND trial of patients with NHL showed that pixantrone was tolerable and that it resulted in significantly higher complete response rate and progression free survival in comparison to other single chemotherapy agents. However, it is notable that the EXTEND trial was stopped early, leaving the statistical significance of the results in question. Based on this uncertainty, in 2009, the FDA ultimately rejected Cell Therapeutic's initial application for accelerated approval for pixantrone use in relapsed or refractory NHL. Another phase III trial, PIX-R, is now ongoing to clarify pixantrones place in therapy. It will compare pixantrone efficacy to that of gemcitabine. [2]
Indications and Usage Currently in Phase III investigation for treatment of relapsed or refractory aggressive non-Hodgkin's lymphoma in patients who have failed two prior lines of therapy. Presently, no standard therapy exists for patients with relapsed or refractory NHL. [2] After first line therapy has been initiated, most patients have received their lifetime limit of doxorubicin and further use of anthracyclines may potentially lead to anthracycline-induced congestive heart failure (CHF). Pixantrone is an attractive alternative as a second line agent, due to its lack of cardiac toxicity. [2] The phase III trial, PIX-R, is ongoing and will compare pixantrone multidrug therapy with an equivalent regimen in patients with diffuse large B-cell lymphoma (the most common type of NHL). Previous study results have also suggested the possibility that pixantrone may be safe and effective in doxorubicin naive patients. In myocardial strips which are doxorubicin naive, pixantrone is taken up to a higher degree than in myocardial strips which are doxorubicin exposed, and once absorbed exhibits redox inactivity. [3] Pixantrone dimaleate has also been investigated as a treatment for acute myelogenous leukemia, diffuse large B-cell lymphoma, follicular lymphoma, metastatic breast cancer, low grade small lymphocytic lymphomas and general metastatic cancers.
Marketing Status approved; investigational
ATC Code L01DB11
DrugBank ID DB06193
KEGG ID D05522
MeSH ID C086548
PubChem ID 134019
TTD Drug ID D0Q4OW
NDC Product Code Not Available
UNII F5SXN2KNMR
Synonyms pixantrone | 5,8-bis(2-aminoethylamino)-2-azaanthracene-9,10-dione | 6,9-bis((2-aminoethyl)amino)benzo(g)isoquinoline-5,10-dione | 5,8-bis((2-aminoethyl)amino)-2-aza-anthracene-9,10-dione | 6,9-AEA-BIQDO | BBR 2778 | BBR2778 | BBR-2778
Chemical Information
Molecular Formula C17H19N5O2
CAS Registry Number 144510-96-3
SMILES C1=CC(=C2C(=C1NCCN)C(=O)C3=C(C2=O)C=NC=C3)NCCN
Chemical Structure
ADRs Induced by Drug
*The priority for ADR severity classification is based on FAERS assessment, followed by the most severe level in CTCAE rating. If neither is available, it will be displayed as 'Not available'.
**The 'Not Available' level is hidden by default and can be restored by clicking on the legend twice.
ADR Term ADReCS ID ADR Frequency (FAERS) ADR Severity Grade (FAERS) ADR Severity Grade (CTCAE)
Leukopenia01.02.02.001---
Local reaction08.01.03.012---
Lymphopenia01.02.02.002---
Meningitis11.01.03.001; 17.06.03.001--
Mucosal inflammation08.01.06.002---
Muscular weakness15.05.06.001; 17.05.03.005--
Nail disorder23.02.05.002--
Nasopharyngitis11.01.13.002; 22.07.03.002---
Nausea07.01.07.001--
Neck pain15.03.04.009--
Neoplasm16.16.02.001---
Nervous system disorder17.02.10.001---
Neutropenia01.02.03.004---
Neutrophil count increased13.01.06.011---
Night sweats08.01.03.031; 23.02.03.006---
Oedema08.01.07.006; 14.05.06.010---
Oesophagitis07.08.05.001--
Oliguria20.01.03.004---
Opportunistic infection11.01.08.007---
Pain in extremity15.03.04.010--
Pallor08.01.03.032; 23.03.03.031; 24.03.04.001---
Pancytopenia01.03.03.003---
Paraesthesia17.02.06.005; 23.03.03.094--
Petechiae01.01.03.002; 23.06.01.003; 24.07.06.004---
Pleural effusion22.05.02.002--
Pneumonia11.01.09.003; 22.07.01.003---
Proteinuria20.02.01.011--
Pruritus23.03.12.001--
Rash macular23.03.13.003---
Rectal haemorrhage07.12.03.001; 24.07.02.018--
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