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)1,27
Special Warnings and
Precautions for use
For further safety information, please refer to the PEMAZYRE Summary of Product Characteristics.1
Healthcare professionals are asked to report any suspected ARs via the Yellow Card Scheme. Visit www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.1 Adverse events should also be reported to Incyte immediately by phoning 0330-100-3677 (Great Britain) or 00-800-0002-7423 (United Kingdom [Northern Ireland]).
MOST COMMON ARs OBSERVED WITH
Most common ARs (any grade)
- Serious ARs were reported in 46.3% (n=68) of patients27
- The most common serious ARs with PEMAZYRE were:1,27
- Hyponatraemia (2.0% [n=3])
- Blood creatinine increase (1.4% [n=2])
- 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% [n=1]), non-arteritic optic ischaemic neuropathy (0.7% [n=1]) and retinal artery occlusion (0.7% [n=1])1,27
- Hyperphosphataemia was reported in 60.5% (n=89) 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 PEMAZYRE1,27
- Dose interruption occurred in 1.4% (n=2) of patients and dose reduction in 0.7% (n=1) of patients1,27
- 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
Serous retinal detachment
- Serous retinal detachment occurred in 4.8% of all patients treated with PEMAZYRE1
- Reactions were generally Grade 1 or 2 (3.4%) in severity; ≥ Grade 3 and serious reactions included retinal detachment in one patient (0.7%)1
- Two ARs of retinal detachment (0.7% [n=1]) and detachment of retinal pigment epithelium (0.7% [n=1]) led to dose interruption. None of the reactions led to dose reduction or discontinuation1,27
Special warnings and precautions for use
- 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, anaemia, secondary hyperparathyroidism, muscle cramps, seizure activity, QT interval prolongation, and arrhythmias. Soft tissue mineralisation, including cutaneous calcification and calcinosis, 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 28.5% 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
- Hypophosphataemia reactions were ≥ Grade 3 in 12.3% of participants. None of the events were serious, led to discontinuation or to dose reduction. Dose interruption occurred in 1.4% (n=2) of participants1,27
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
- 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 to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose1
- Male patients with female partners of childbearing potential should be advised to use effective contraception during treatment with PEMAZYRE and for at least 1 week after the last dose1
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
- PEMAZYRE® (pemigatinib). Summary of Product Characteristics. 2021 (data cutoff: April 2020).
- Rizvi S, et al. J Gastrointest Oncol. 2016;7:789–96.
- Ghouri YA, et al. J Carcinog. 2015;14:1.
- Sharma P, et al. Ann Gastroenterol. 2018;31:231–6.
- Blechacz B. Gut Liver. 2017;11:13–26.
- Valle JW, et al. Cancer Discov. 2017;7:943–62.
- Bañales JM, et al. Nat Rev Gastroenterol Hepatol. 2020;17:557–88.
- Bañales JM, et al. Nat Rev Gastroenterol Hepatol. 2016;13:261–80.
- Bertuccio P, et al. Ann Oncol. 2013;24:1667–74.
- Blechacz B, et al. Nat Rev Gastroenterol Hepatol. 2011;8:512–22.
- Forner A, et al. Liver Int. 2019;39 (Suppl 1):98–107.
- Valle JW, et al. Ann Oncol. 2016;27 (Suppl 5):v28–37.
- Lamarca A, et al. J Natl Cancer Inst. 2020;112:200–10.
- Valle JW, et al. N Engl J Med. 2010;362:1273–81.
- Lamarca A, et al. Lancet Oncol. 2021;22:690–701.
- Lowery MA, et al. Clin Cancer Res. 2018;24:4154–61.
- Jain A, et al. JCO Precis Oncol. 2018;2:1–12.
- Ross JS, et al. Oncologist. 2014;19:235–42.
- Farshidfar F, et al. Cell Rep. 2017;18:2780–94.
- Graham RP, et al. Hum Pathol. 2014;45:1630–8.
- Churi CR, et al. PLoS One. 2014;9:e115383.
- Arai Y, et al. Hepatology. 2014;59:1427–34.
- Borad MJ, et al. Curr Opin Gastroenterol. 2015;31:264–8.
- Silverman I, et al. Cancer Discov. 2021;11:326–39.
- Barr FG, et al. Expert Rev Mol Diagn. 2016;16:921–3.
- Mosele F, et al. Ann Oncol. 2020;31:1491–505.
- Incyte Data on File.
- Liu PCC, et al. PLoS ONE. 2020;15(4): e0231877.
- Abou-Alfa GK, et al. Lancet Oncol. 2020;21:671–84 (data cutoff: March 2019).
PEMAZYRE®▼(pemigatinib) 4.5, 9, 13.5 mg tablets
contains Microcrystalline cellulose (E-460), Sodium starch glycolate (Type A), Magnesium stearate (E-572).
▼ 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. See below for how to report adverse reactions.
Indication: Pemazyre monotherapy is indicated for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy.
Dosage and administration: The recommended dose is 13.5 mg pemigatinib taken once daily for 14 days followed by 7 days off therapy. Therapy should be initiated by a physician experienced in biliary tract cancer. Confirm FGFR2 positive status prior to starting treatment. Treatment should be continued as long as the patient does not show evidence of disease progression or unacceptable toxicity.
Contraindications: Hypersensitivity to pemigatinib or excipients. Concomitant use of pemigatinib with St John’s wort.
Warnings and precautions: Consult the Summary of Product Characteristics (SmPC) for full details of potential toxicities and drug interactions, as well as information on monitoring and management, including recommended dose modifications.
Hyperphosphataemia: Hyperphosphataemia is a pharmacodynamic effect expected with pemigatinib. Effective management strategies for hyperphosphataemia include dietary phosphate restriction, phosphate-lowering therapy and dose modification. Consult the SmPC for full details.
Hypophosphataemia: Consider discontinuing phosphate-lowering therapy and increasing dietary phosphate if hypophosphataemia occurs. Consult the SmPC for full details.
Serous retinal detachment: Pemigatinib can cause serous retinal detachment reactions. Symptoms can include blurred vision, visual floaters, or photopsia. Ophthalmological examination, including optical coherence tomography (OCT) should be performed prior to starting pemigatinib and throughout treatment. Consult the SmPC for full details of OCT requirements and dose modification guidelines for serous retinal detachment reactions.
Dry eye: Pemigatinib can cause dry eye. Treat with ocular demulcents as needed.
Blood creatinine increase: Pemigatinib may increase serum creatinine by decreasing renal tubular secretion of creatinine. Alternative markers of renal function should be considered if persistent elevations in serum creatinine are observed.
Hepatic or renal impairment: Dose adjustment is recommended when administering pemigatinib to patients with severe hepatic or renal impairment.
Central nervous system (CNS) metastasis: 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 pemigatinib is expected to be low.
Driving and operating machinery: Adverse reactions of fatigue and symptoms associated with retinal detachment may influence the ability to drive and operate machinery.
Drug interactions: If concurrent use of strong CYP3A4 inhibitors is necessary, the daily dose of pemigatinib should be reduced. Consult the SmPC for full details and for information on all potential drug interactions.
Pregnancy and breast-feeding: Pemigatinib can cause foetal harm when administered during pregnancy. Women of childbearing potential, including partners of male patients, should use effective contraception during treatment with pemigatinib and for 1 week after the last dose. Discontinue breast-feeding during treatment with pemigatinib and for 1 week following last dose.
Undesirable effects: The most common adverse drug reactions (ADRs) were hyperphosphataemia, alopecia, diarrhoea, nail toxicity, fatigue, nausea, dysgeusia, stomatitis, constipation, dry mouth, dry eye, arthralgia, hypophosphataemia, dry skin, and palmar-plantar erythrodysaesthesia syndrome. The most common serious adverse reactions were hyponatraemia and blood creatinine increase (see SmPC for details of all ADRs).
Quantities and marketing authorisation numbers:
4.5 mg dose (14 or 28 tablets) EU/1/21/1535/001 002, PLGB 42338/0008
9 mg dose (14 or 28 tablets) EU/1/21/1535/003 004, PLGB 42338/0009
13.5 mg dose (14 or 28 tablets) EU/1/21/1535/005 006, PLGB 42338/0010
Cost (ex. VAT): 4.5 mg x 14 tablets £7,159; 9 mg x 14 tablets £7,159; 13.5 mg x 14 tablets £7,159.
Legal categorisation: POM (prescription only medicine).
Marketing authorisation holder:
Great Britain: Incyte Biosciences UK Ltd, First Floor Q1, The Square, Randalls Way, Leatherhead, KT22 7TW, UK.
United Kingdom (Northern Ireland): Incyte Biosciences Distribution B.V. Paasheuvelweg 25, 1105 BP Amsterdam, Netherlands.
Date of preparation: April 2021.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Incyte immediately by phoning 0330-100-3677 (Great Britain) or 00-800-0002-7423 (United Kingdom [Northern Ireland]).
Resources and support
For further information, please refer to the PEMAZYRE Summary of Product Characteristics.1
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