The link you clicked on will take you to a site maintained by a third party, which is solely responsible for its content. Eli Lilly and Company does not control, influence, or endorse this site, and the opinions, claims or comments expressed on this site should not be attributed to Eli Lilly and Company. Eli Lilly and Company is not responsible for the privacy policy of any third party websites. We encourage you to read the privacy policy of every website you visit.
Tips for searching:
• You have to select a product and type at least 2 words to activate the search
• Use only words that are specific to the information you are looking for
• Avoid typing questions or sentences
Please do not use this field to report adverse events or product complaints. Adverse events and product complaints should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow card in the Google play or Apple app store. Adverse events and product complaints should also be reported to Lilly: please call Lilly UK on 01256 315 000.
This information is intended for UK registered healthcare professionals only in response to your search for information. For current information for all Lilly products, including Summaries of Product Characteristics, Patient Information Leaflets and Instructions for Use, please visit: www.medicines.org.uk
Hypertension is a very common side effect of selpercatinib. Section 4.8 of the Retsevmo Summary of Product Characteristics (SmPC) provides further details regarding the frequency.1
Patients blood pressure should be controlled before starting treatment and monitored during treatment. Section 4.2 of the summary of product characteristics (SmPC) provides full information on management.1
For complete information, please consult the Retsevmo Summary of Product Characteristics, particularly:
Below is additional data from clinical trials, including information on definition, incidence, severity, time to onset, management, and mechanism of action of hypersensitivity reactions. A full description of the clinical studies referenced is available in Section 5.1 of the SmPC.1
Selpercatinib and definition of hypertension in clinical trials
Incidence of hypertension with selpercatinib across clinical trials
Time to onset of hypertension with selpercatinib
Dose modifications due to hypertension in selpercatinib-treated patients
Antihypertensive therapy use during LIBRETTO-001
Patients with a history of hypertension
The composite term of hypertension included the preferred terms of hypertension, blood pressure increased, and blood pressure abnormal.2 Severity of hypertension was graded using National Cancer Institute-Common Terminology Criteria for Adverse Events v 4.03 (National Cancer Institute-Common Terminology Criteria for Adverse Events v 4.03 Grade Definitions for Hypertension).3
Hypertension in Selpercatinib-Treated Patients provides a summary of the incidence of hypertension in selpercatinib-treated patients in LIBRETTO-001, LIBRETTO-431 and LIBRETTO-531. Incidence of hypertension was similar across cohorts in LIBRETTO-001 and in patients receiving selpercatinib, cabozantinib, or vandetanib in LIBRETTO-531.2
Hypertension, %a |
LIBRETTO-001 |
LIBRETTO-431 |
LIBRETTO-531 |
|||
Overall incidence |
||||||
All grades |
41 |
48 |
43 |
|||
Grade ≥3 |
20 |
20 |
19 |
|||
SAE |
1 |
<1 |
1 |
|||
Related to selpercatinib |
||||||
All grades |
28 |
44 |
41 |
|||
SAE |
1 |
<1 |
<1 |
|||
Abbreviations: SAE = serious adverse event.
aThe composite term of hypertension included the preferred terms of hypertension, blood pressure increased, and blood pressure abnormal.
bData cutoff June 2021.
cData cutoff May 2023.
As of LIBRETTO-001 data cutoff June 2021, the median time to hypertension onset was 4.1 weeks (range 0.1 to 169.1 weeks).2
As of LIBRETTO-431 data cutoff May 2023, the median time to hypertension onset in selpercatinib-treated patients was 3.5 weeks (range 0.1 to 49.3 weeks).2
As of LIBRETTO-531 data cutoff May 2023, the median time to hypertension onset in selpercatinib-treated patients was 2.3 weeks (range 0.1 to 44.6 weeks.2
Overall, hypertension was managed with dosing adjustments ( Selpercatinib Dosing Adjustments Due to Hypertension).
Treatment-emergent hypertension was successfully managed through the addition or adjustment of concomitant antihypertensive medications and selpercatinib dose modifications. Most patients tolerated continued therapy while receiving concomitant antihypertensive therapy such as amlodipine.2
The decision to add antihypertensive medication(s) should be made in accordance with institutional guidelines and incorporating clinical judgment. Eli Lilly and Company does not have any recommendation regarding which antihypertensive medications should be used to treat hypertension while on selpercatinib.
In LIBRETTO-001, approximately 41% of the population had a documented history of hypertension. Although the overall incidence of treatment-emergent hypertension was similar in patients with and without a history of hypertension (44% vs 39%), patients with a preexisting history of hypertension displayed a higher frequency of treatment-emergent grade 3 hypertension than patients without a documented history of hypertension. During selpercatinib treatment, these patients also were more likely to have had
Hypertension is a result of off-target vascular endothelial growth factor inhibition by selpercatinib. The inhibition of VEGF induces vasoconstriction and hypertension.4
Grade |
Definition |
1 |
Prehypertension (SBP 120-139 mmHg or DBP 80-89 mmHg) |
2 |
Stage I hypertension (SBP 140-159 mmHg or DBP 90-99 mmHg), medical intervention indicated; recurrent or persistent (≥24 hours), symptomatic increase by >20 mmHg (diastolic) or to >140/90 mmHg if previously within normal limits, monotherapy indicated |
3 |
Stage 2 hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg); medical intervention indicated; more than one drug or more intensive therapy than previously used indicated |
4 |
Life-threatening consequences (e.g., malignant hypertension, transient or permanent neurologic deficit, hypertensive crisis); urgent intervention indicated |
5 |
Death |
Abbreviations: DBP = diastolic blood pressure; SBP = systolic blood pressure.
1Retsevmo [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.
2Data on file, Eli Lilly and Company and/or one of its subsidiaries.
3US Department of Health and Human Services; National Institutes of Health and National Cancer Institute. Common terminology criteria for adverse events (CTCAE). Version 4.03. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Published May 28, 2009. Updated June 14, 2010. Accessed November 14, 2023.
4Eskens FA, Verweij J. The clinical toxicity profile of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) targeting angiogenesis inhibitors; a review. European J Cancer. 2006;42(18):3127-39. https://doi.org/10.1016/j.ejca.2006.09.015.
5US Department of Health and Human Services; National Institutes of Health and National Cancer Institute. Common terminology criteria for adverse events (CTCAE). Version 4.03. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Published May 28, 2009. Updated June 14, 2010. Accessed January 30, 2020.
Links to references and third-party websites are provided solely for your convenience and to facilitate easy access to the sources cited.
▼ 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.
Date of Last Review: 14 November 2023