Safety profile for PEMAZYRE — 1 of 1
The safety profile of PEMAZYRE was investigated in the FIGHT–202 study
In FIGHT-202, the most common AR observed with PEMAZYRE was hyperphosphataemia1
- The safety of PEMAZYRE was investigated in the FIGHT–202 study in previously treated patients with CCA (N=147)1
and additional information
Warnings and precautions
For further safety information, please refer to the PEMAZYRE Swissmedic Professional Information.1
Healthcare professionals are required to report any suspected new or serious side effects. See the “Undesirable effects” section of the Swissmedic Professional Information for the terms and conditions for reporting side effects. Adverse events should also be reported to Incyte immediately by phoning 00800 000 274 23 or via email at email@example.com.
MOST COMMON ARs OBSERVED WITH PEMAZYRE (>15%)1
Most common ARs (any grade)
- The most common serious ARs with PEMAZYRE were:1
- Hyponatraemia (2.0%)
- Blood creatinine increase (1.4%)
- No serious AR led to PEMAZYRE dose reduction1
- One serious AR of hyponatraemia (0.7%) led to dose interruption. One serious AR of blood creatinine increase (0.7%) led to dose discontinuation1
- Eye disorder serious ARs were retinal detachment (0.7%), non-arteritic optic ischaemic neuropathy (0.7%) and retinal artery occlusion (0.7%)1
Description of specific adverse reactions and additional information
- Hyperphosphataemia was reported in 60.5% of all patients treated with PEMAZYRE and usually developed within the first 15 days. None of the reactions were ≥ Grade 3 in severity, serious or led to discontinuation of PEMAZYRE1
- Dose interruption occurred in 1.4% of patients and dose reduction in 0.7% of patients1
- These results suggest that dietary phosphate restriction and/or administration of phosphate-lowering therapy along with the 1-week dose holiday were effective strategies for managing this on-target effect of PEMAZYRE1
- Hypophosphataemia reactions were Grade ≥3 in 14.3% of patients1
Serous retinal detachment
- Serous retinal detachment occurred in 4.8% of all patients treated with PEMAZYRE1
- Reactions were generally Grade 1 or 2 (4.1%) in severity; ≥ Grade 3 and serious reactions included retinal detachment in one patient (0.7%)1
- Two ARs of retinal detachment (0.7%) and detachment of retinal pigment epithelium (0.7%) led to dose interruption. None of the reactions led to dose reduction or discontinuation1
- An increase from baseline in mean creatinine levels of approximately 16 μmol/L occurred on Days 8 and 15 of the 1st cycle. These higher lever generally returned close to baseline by Cycle 2 Day 1. Above-normal creatinine values occurred in 12.9% of patients at baseline, increased to 34% on Day 15 of Cycle 1 and were observed in approximately 20% to 30% of participants on Day 1 of subsequent cycles1
- The reactions were Grade 1 or 2 with the exception of 2 patients (1.4%) with Grade 3 changes, and resolved without sequelae1
- However, normal creatinine values were observed after a one-week treatment suspension period1
Warnings and precautions
- Hyperphosphataemia is a pharmacodynamic effect expected with PEMAZYRE administration1
- Prolonged hyperphosphataemia can cause precipitation of calcium-phosphate crystals that can lead to hypocalcaemia, soft tissue mineralisation, secondary hyperparathyroidism, muscle cramps, seizure activity, QT interval prolongation and arrhythmias. Soft tissue mineralisation, including cutaneous calcification, calcinosis and non-uraemic calciphylaxis have been observed with PEMAZYRE treatment1
- Recommendations for management of hyperphosphataemia include dietary phosphate restriction, administration of phosphate-lowering therapy and dose modification when required1
- Phosphate-lowering therapy was used by 19% of patients during treatment with PEMAZYRE1
- Discontinuing phosphate-lowering therapy and diet should be considered during PEMAZYRE treatment breaks or if serum phosphate level falls below normal range1
- Severe hypophosphataemia may present with confusion, seizures, focal neurological findings, heart failure, respiratory failure, muscle weakness, rhabdomyolysis, and hemolytic anaemia1
For patients presenting with hyperphosphataemia or hypophosphataemia, additional close monitoring and follow-up is recommended regarding dysregulation of bone mineralisation1
Serous retinal detachment
- PEMAZYRE can cause serous retinal detachment reactions, which may present with symptoms such as blurred vision, visual floaters or photopsia. This can moderately influence the ability to drive and use machines1
- Ophthalmological examination, including OCT, should be performed prior to initiation of therapy and every 2 months for the first 6 months of treatment, every 3 months afterwards, and urgently at any time for visual symptoms. For serous retinal detachment reactions, the dose modification guidelines should be followed1
- During the conduct of the clinical study, there was no routine monitoring, including OCT, to detect asymptomatic serous retinal detachment; therefore, the incidence of asymptomatic serous retinal detachment with PEMAZYRE is unknown
- Careful consideration should be taken with patients that have clinically significant medical eye disorders, such as retinal disorders, including but not limited to, central serous retinopathy, macular/retinal degeneration, diabetic retinopathy and previous retinal detachment1
- PEMAZYRE can cause dry eye. Patients should use ocular demulcents in order to prevent or treat dry eye as needed1
- Based on the mechanism of action and findings in an animal reproduction study, PEMAZYRE can cause foetal harm when administered to a pregnant woman. Pregnant women should be advised of the potential risk to the foetus1
- Women of childbearing potential should be advised not to become pregnant and men should be advised not to father a child during treatment1
- An effective method of contraception should be used during treatment with PEMAZYRE and for 1 week following completion of therapy1
- A pregnancy test should be performed before treatment initiation to exclude pregnancy1
Blood creatinine increase
- PEMAZYRE may increase serum creatinine by decreasing renal tubular secretion of creatinine; this may occur due to inhibition of renal transporters OCT2 and MATE1 and may not affect glomerular function1
- Within the first cycle, serum creatinine increased (mean increase of 0.2 mg/dL) and reached steady state by Day 8, and then decreased during the 7 days off therapy. Alternative markers of renal function should be considered if persistent elevations in serum creatinine are observed1
- Since untreated or progressing brain/CNS metastasis were not allowed in the study, efficacy in this population has not been evaluated and no dose recommendations can be made; however, the blood-brain barrier penetration of PEMAZYRE is expected to be low1
- Swiss Professional Information PEMAZYRE® (pemigatinib) on www.swissmedicinfo.ch.
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All references are available upon request
Abbreviated Prescribing Information
▼ This medicinal product is subject to additional monitoring. For further information, see product information Pemazyre on www.swissmedicinfo.ch.
Revision date: January 2023. Marketing authorisation holder: Incyte Biosciences International Sàrl, CH-1110 Morges. Refer to www.swissmedicinfo.ch for detailed information.
Resources and support
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