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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.


Last Update: October 20, 2018.



Copanlisib is an intravenously administered phosphatidylinositol-3 kinase inhibitor that is used to treat relapsed and refractory follicular lymphoma. Copanlisib is associated with a high rate of minor serum enzyme elevations during therapy and has been reported to cause clinically apparent acute liver injury that can be severe and even fatal.


Copanlisib (koe" pan lis' ib) is an intravenously administered small molecule inhibitor of phosphatidylinositol 3-kinase (PI3K) alpha and delta which are essential components in B cell signaling pathways that drive survival of B cells and their migration to lymph nodes and bone marrow. Inhibition of this pathway inhibits B cell chemotaxis and adherence and reduces cell viability. This pathway is upregulated in many B cell malignancies and is known to be critical for proliferation and survival of leukemia and lymphomatous malignant B lymphocytes. Copanlisib has been shown to result in high rates of objective response in patients with refractory or relapsed follicular lymphoma and was given accelerated approval for this use in the United States in 2017. Copanlisib is available in as lyophilized powder in 60 mg single dose vials under the brand name Aliqopa. The recommended dose is 60 mg given as an intravenous infusion on days 1, 8 and 15 of 28-day cycles. Side effects are common but usually mild-to-moderate in severity, and include nausea, diarrhea, headache, stomatitis, fever, pain, rash, infections, arthralgia and fatigue. Common laboratory abnormalities can include hyperglycemia and cytopenias. Severe adverse events can include marked hypertension, severe diarrhea, neutropenia, infectious and non-infectious pneumonitis, severe cutaneous reactions and embryo-fetal toxicity.


In clinical trials of copanlisib the rates of serum enzyme elevations during therapy ranged from 23% to 25% but were above 5 times the ULN in only 1% to 2%. Instances of clinically apparent liver injury were not reported in prelicensure trials of copanlisib, but the total number of patients exposed was limited. Since its approval and more general use, there have been no published reports of liver injury with jaundice associated with copanlisib therapy. In contrast, idelalisib, another small molecule inhibitor of PI3K, has been linked to instances of clinically apparent acute liver injury some of which have been fatal.

Likelihood score: E* (unproven but suspected rare cause of clinically apparent liver injury).

Mechanism of Injury

The reason why copanlisib causes serum enzyme elevations is not known, but may relate to direct toxicity to hepatocytes caused by inhibition of PI3K activity, which plays a central role in many metabolic pathways. Copanlisib is metabolized primarily by the cytochrome P450 system and it is susceptible to drug-drug interactions with strong inducers or inhibitors of CPY 3A.

Outcome and Management

Serum enzyme elevations are not uncommon during cancer chemotherapy with copanlisib and may occasionally be dose limiting. Monitoring of liver tests is recommended in patients receiving copanlisib. Copanlisib should be temporarily discontinued if ALT or AST values rise above 5 times the ULN and treatment resumed only if and when values improve significantly and then with a careful monitoring. Elevations of aminotransferase values of more than 20 times the ULN, or appearance of jaundice or symptoms of liver injury should trigger permanent discontinuation. There is no published information on cross sensitivity to hepatic injury among the different PI3K kinase inhibitors.

Drug Class: Antineoplastic Agents, Protein Kinase Inhibitors



Copanlisib – Aliqopa®


Antineoplastic Agents


Product labeling at DailyMed, National Library of Medicine, NIH


Copanlisib 1032568-63-0 C26-H23-N7-O2
Copanlisib structure


References updated: 20 October 2018

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    (Among 84 patients with lymphoma treated with copanlisib on days 1, 8 and 15 of 28-day cycles, the objective response rate was 44% in patients with indolent lymphoma and 27% with aggressive lymphoma and common adverse events were hyperglycemia [57%], hypertension [55%] and diarrhea [41%]; ALT elevations occurred in 26% of patients and were above 5 times ULN in 4%).
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