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Isolated Bilirubin Elevation Associated with Alecensa

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

This article responds to your request for information on Alecensa® (alectinib) and the management of isolated bilirubin elevations.

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Last updated September 11, 2023


  • Bilirubin elevations associated to Alecensa is a very common adverse drug reaction and should be closely monitored as biomarker of hepatotoxicity.
    • Cases of isolated bilirubin elevations have been reported.
      • Haemolytic anemia has been reported as ADR associated to Alecensa and could lead to isolated bilirubin elevations.
        • FDA has established recommendations for management of isolated bilirubin elevations
          • Refer to the local Alecensa label for information on the management of Alecensa related adverse events. Any deviation from this information is considered off-label and any treatment decisions based on such deviations are the full responsibility of the prescribing physician.


            CTCAE = NCI Common Terminology Criteria for Adverse Events

            ALT = alanine aminotransferase

            ADR= adverse drug reaction

            AST = aspartate aminotransferase

            ULN= upper limit of normal

            Bilirubin elevations associated with Alecensa

            Incidence of bilirubin elevations

            Bilirubin elevations are considered a very common adverse drug reaction (ADR) associated with Alecensa,and cases include

            • blood bilirubin increases
              • hyperbilirubinaemia
                • bilirubin conjugated increases and
                  • blood bilirubin unconjugated increases.

                    Bilirubin elevations were reported in 21% of Alecensa patients across clinical trials [1](NP28761 [2], NP28673 [3], BO28984 [4]; n=405).

                    Monitoring bilirubin elevations

                    Label recommendations regarding bilirubin elevations associated with Alecensa are related to the management of hepatotoxicity. Table 1 shows recommendations for monitoring liver function during treatment with Alecensa, please refer to your local product label for further information.[5]


                    Table 1: Monitoring of liver function during treatment with Alecensa

                    The first 3 months... for Monitor ALT, AST, and total bilirubin at baseline and then every 2 weeks. and Thereafter...

                    Isolated bilirubin elevation associated with Alecensa

                    Incidence of isolated bilirubin elevations

                    Cases of bilirubin elevations without concurrent elevation of liver enzymes have been reported in the clinical practice [6,7].

                    Causes of isolated bilirubin elevations

                    There are multiple causative factors of isolated bilirubin elevation and a differential diagnosis should be performed.

                    Moreover, please be aware that haemolytic anemia is considered as an adverse drug reaction associated with Alecensa. Cases of haemolytic anemia have been reported in clinicals trials and post-marketing setting.[5,7] Refer to your local label for more information on haemolytic anemia associated to Alecensa.

                    Management of isolated bilirubin elevation

                    Please refer to your local Alecensa label for further information.

                    There is no guidance regarding the management of patients who experience isolated bilirubin elevations in the EMA label. The dose modification recommendations only cover total bilirubin elevations with concurrent elevations of ALT and AST. The general guidance in case of severe adverse events is to withhold Alecensa and resume at a reduced dose or permanently discontinue.[1]

                    However, the FDA label does provide recommendations for isolated total bilirubin elevations as described in Table 2.


                    Table 2. Dose modification recommendations for isolated bilirubin elevations with Alecensa treatment from the FDA label [8]

                    If... for Total bilirubin elevation of greater than 3 times ULN and then...


                    1. Alecensa Summary of Product Characteristics. Available at https://www.ema.europa.eu/en/documents/product-information/alecensa-epar-product-information_en.pdf. Accessed on July 12, 2023.
                      1. Clinicaltrials.gov : A Study of Alectinib (CH5424802/RO5424802) in Participants With Anaplastic Lymphoma Kinase (ALK)-Rearranged Non-Small Cell Lung Cancer (NSCLC). Available at https://classic.clinicaltrials.gov/ct2/show/NCT01871805. Accessed on July 12, 2023.
                        1. Clinicaltrials.gov : A Study of Alectinib (RO5424802) in Participants With Non-Small Cell Lung Cancer Who Have Anaplastic Lymphoma Kinase (ALK) Mutation and Failed Crizotinib Treatment. Available at https://classic.clinicaltrials.gov/ct2/show/NCT01801111. Accessed on July 12, 2023.
                          1. Clinicaltrials.gov : A Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Participants (ALEX). Available at https://clinicaltrials.gov/study/NCT02075840. Accessed on July 12, 2023.
                            1. Roche Internal Regulatory Report, accessed on 12-Jul-2023.
                              1. Roche Internal Safety Report, accessed on 24-Aug-2023.
                                1. Roche Internal Safety Report, accessed on 24-Aug-2023.
                                  1. FDA Alecensa Highlights of Prescribing Information. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208434s010lbl.pdf. Accessed on July 12, 2023.

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