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Prescribing Information Summary of Product Characteristics (SmPC) – Great Britain Summary of Product Characteristics (SmPC) – Northern Ireland Report an adverse event

▼ 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 medicinal product has been authorised under a 'conditional approval' scheme

Safety

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The safety of PEMAZYRE®▼ (pemigatinib) was investigated in the FIGHT–202 clinical study (N=147)1,2

The safety of PEMAZYRE®▼ (pemigatinib) was investigated in the FIGHT–202 clinical study (N=147)1,2

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Table 1. Most common adverse reactions

Table 2. Adverse reactions observed in FIGHT–202 study — frequency reported by incidence of treatment-emergent events

Please refer to the SmPC for full safety information and special warnings before prescribing.

FIGHT–202 was a multicentre, open-label, single-arm study to evaluate the efficacy and safety of PEMAZYRE in previously treated patients with locally advanced/metastatic or surgically unresectable cholangiocarcinoma (CCA).1

Patients received PEMAZYRE in 21-day cycles, consisting of 13.5 mg once-daily oral dosing for 14 days, followed by 7 days off therapy. PEMAZYRE was administered until disease progression or unacceptable toxicity.1

The most common adverse reactions were hyperphosphataemia, alopecia, diarrhoea, nail toxicity, fatigue, nausea, stomatitis, constipation, dysgeusia, dry mouth, arthralgia, dry eye, hypophosphataemia, dry skin and palmar-plantar erythrodysaesthesia syndrome (Table 1).1

The most common serious adverse reactions were hyponatraemia (2.0% [n=3]) and blood creatinine increase (1.4% [n=2]). No serious adverse reaction led to PEMAZYRE dose reduction. One serious adverse reaction of hyponatraemia (0.7%) led to dose interruption. One serious adverse reaction of blood creatinine increase (0.7%) led to dose discontinuation.1,2

Adverse reactions observed in the FIGHT–202 study are presented in Table 2. Frequency categories are very common (≥1/10), common (≥1/100 to <1/10) and uncommon (≥1/1,000 to <1/100). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.1

Hyperphosphataemia
Hypophosphataemia
Serous retinal detachment
Blood creatinine increase
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Hyperphosphataemia was observed in patients treated with PEMAZYRE

Hyperphosphataemia was observed in patients treated with PEMAZYRE

Hyperphosphataemia is a pharmacodynamic effect expected with PEMAZYRE administration. 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, calcinosis and non-uraemic calciphylaxis, have been observed with PEMAZYRE treatment.1

Hyperphosphataemia was reported in 60.5% of all patients treated with PEMAZYRE. Hyperphosphataemia above 7 mg/dL and 10 mg/dL was experienced by 27.2% and 0.7% of patients, respectively. Hyperphosphataemia usually develops within the first 15 days. None of the reactions were ≥ Grade 3 in severity, serious or led to discontinuation of PEMAZYRE. Dose interruption occurred in 1.4% (n=2) of patients and reduction in 0.7% (n=1) of patients.1,2

Recommendations for management of hyperphosphataemia

Recommendations include dietary phosphate restriction, administration of phosphate-lowering therapy and dose modification when required (Table 3). Phosphate-lowering therapy was used by 19% of patients during treatment with PEMAZYRE.1

In all patients, a low-phosphate diet should be initiated when serum phosphate level is >5.5 mg/dL, and adding a phosphate-lowering therapy should be considered when level is >7 mg/dL. The dose of phosphate-lowering therapy should be adjusted until serum phosphate level returns to <7 mg/dL.1

Table 3. Dose modifications for hyperphosphataemia

Discontinuing phosphate-lowering therapy and diet should be considered during PEMAZYRE treatment breaks or if serum phosphate level falls below normal range. Severe hypophosphataemia may present with confusion, seizures, focal neurological findings, heart failure, respiratory failure, muscle weakness, rhabdomyolysis and haemolytic anaemia.1

For patients presenting with hyperphosphataemia or hypophosphataemia, additional close monitoring and follow-up is recommended regarding dysregulation of bone mineralisation.1

Results from the FIGHT–202 clinical study 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 PEMAZYRE.1

Hypophosphataemia

Hypophosphataemia

Discontinuing phosphate-lowering therapy and diet should be considered during PEMAZYRE treatment breaks or if serum phosphate level falls below normal range. Severe hypophosphataemia may present with confusion, seizures, focal neurological findings, heart failure, respiratory failure, muscle weakness, rhabdomyolysis and haemolytic anaemia. In the FIGHT–202 study, hypophosphataemia reactions were ≥ Grade 3 in 14.3% (n=21) of participants. None of the events were serious, led to discontinuation or to dose reduction. Dose interruption occurred in 1.4% (n=2) of participants.1,2

For patients presenting with hyperphosphataemia or hypophosphataemia, additional close monitoring and follow-up is recommended regarding dysregulation of bone mineralisation.1

Serous retinal detachment was observed in patients treated with PEMAZYRE

Serous retinal detachment was observed in patients treated with PEMAZYRE

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 machines.1

Serous retinal detachment occurred in 4.8% (n=7) of all patients treated with PEMAZYRE. Reactions were generally Grade 1 or 2 (4.1% [n=6]) in severity; ≥ Grade 3 and serious reactions included retinal detachment in 1 patient (0.7%). Two adverse reactions 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 discontinuation.1,2

Recommendations for management of serous retinal detachment

Ophthalmological examination, including optical coherence tomography, 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 followed (Table 4).1

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 detachment.1

Dry eye

PEMAZYRE can cause dry eye. Patients should use ocular demulcents, in order to prevent or treat dry eye, as needed.1

Table 4. Dose modifications for serous retinal detachment

Blood creatinine increase

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 function. 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 observed.1

Embryo-foetal toxicity

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 foetus.1

  • Women of childbearing potential should be advised to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose.1
  • 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 dose.1

A pregnancy test should be performed before treatment initiation to exclude pregnancy.1

Central nervous system (CNS) metastasis

Since untreated or progressing brain/CNS metastasis were not allowed in FIGHT-202, 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 low.1

References:
1. PEMAZYRE® (pemigatinib). Summary of Product Characteristics.
2. Incyte Data on File.

Table 1. Most common adverse reactions1,2

Adverse reaction Incidence, n (%)
Hyperphosphataemia 89 (60.5)
Alopecia 73 (49.7)
Diarrhoea 70 (47.6)
Nail toxicity 66 (44.9)
Fatigue 64 (43.5)
Nausea 61 (41.5)
Stomatitis 56 (38.1)
Constipation 54 (36.7)
Dysgeusia 53 (36.1)
Dry mouth 50 (34.0)
Arthralgia 44 (29.9)
Dry eye 41 (27.9)
Hypophosphataemia 35 (23.8)
Dry skin 32 (21.8)
Palmar-plantar erythrodysaesthesia syndrome 24 (16.3)

References:
1. PEMAZYRE® (pemigatinib). Summary of Product Characteristics.
2. Incyte Data on File.

Table 2. Adverse reactions observed in FIGHT–202 study – frequency reported by incidence of treatment-emergent events. Frequency categories are very common (≥1/10), common (≥1/100 to <1/10) and uncommon (≥1/1,000 to <1/100). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.1

System organ class Frequency Adverse reactions
Metabolism and nutrition disorders Very common Hyponatraemia, Hyperphosphataemia,a Hypophosphataemiab
Nervous system disorders Very common Dysgeusia
Eye disorders Very common Dry eye
Common Serous retinal detachment,c Punctate keratitis, Vision blurred, Trichiasis
Gastrointestinal disorders Very common Nausea, Stomatitis, Diarrhoea, Constipation, Dry mouth
Skin and subcutaneous tissue disorders Very common Palmar-plantar erythrodysaesthesia syndrome, Nail toxicity,d Alopecia, Dry skin
Common Hair growth abnormal
Uncommon Cutaneous calcification
Musculoskeletal and connective tissue disorders Very common Arthralgia
General disorders and administration site conditions Very common Fatigue
Investigations Very common Blood creatinine increased

aIncludes hyperphosphataemia and blood phosphorous increased.
bIncludes hypophosphataemia and blood phosphorous decreased.
cIncludes serous retinal detachment, retinal detachment, detachment of retinal pigmented epithelium, retinal thickening, subretinal fluid, chorioretinal folds, chorioretinal scar and maculopathy.
d Includes nail toxicity, nail disorder, nail discolouration, nail dystrophy, nail hypertrophy, nail ridging, nail infection, onychalgia, onychoclasis, onycholysis, onychomadesis, onychomycosis and paronychia.

Reference:
1. PEMAZYRE® (pemigatinib). Summary of Product Characteristics.

Table 3. Dose modifications for hyperphosphataemia1

Serum phosphate Dose modification
>5.5–≤7 mg/dL
  • PEMAZYRE should be continued at current dose.
>7–≤10 mg/dL
  • PEMAZYRE should be continued at current dose, phosphate-lowering therapy should be initiated, serum phosphate should be monitored weekly, dose of phosphate-lowering therapy should be adjusted as needed until level returns to <7 mg/dL.
  • PEMAZYRE should be withheld if levels do not return to <7 mg/dL within 2 weeks of starting a phosphate-lowering therapy. PEMAZYRE and phosphate-lowering therapy should be restarted at the same dose when level returns to <7 mg/dL.
  • Upon recurrence of serum phosphate at >7 mg/dL with phosphate-lowering therapy, PEMAZYRE should be reduced 1 dose level.
>10 mg/dL
  • PEMAZYRE should be continued at current dose, phosphate-lowering therapy should be initiated, serum phosphate should be monitored weekly and dose of phosphate-lowering therapy should be adjusted as needed until level returns to <7 mg/dL.
  • PEMAZYRE should be withheld if levels continue >10 mg/dL for 1 week. PEMAZYRE and phosphate-lowering therapy should be restarted 1 dose level lower when serum phosphate is <7 mg/dL.
  • If there is recurrence of serum phosphate >10 mg/dL following 2 dose reductions, PEMAZYRE should be permanently discontinued.

Reference:
1. PEMAZYRE® (pemigatinib). Summary of Product Characteristics.

Table 4. Dose modifications for serous retinal detachment1

Adverse reaction Dose modification
Asymptomatic
  • PEMAZYRE should be continued at current dose. Monitoring should be performed as described in section 4.4 of the SmPC.
Moderate decrease in visual acuity (best corrected visual acuity 20/40 or better or ≤3 lines of decreased vision from baseline); limiting instrumental activities of daily living
  • PEMAZYRE should be withheld until resolution. If improved on subsequent examination, PEMAZYRE should be resumed at the next lower dose level.
  • If it recurs, symptoms persist or examination does not improve, permanent discontinuation of PEMAZYRE should be considered based on clinical status.
Marked decrease in visual acuity (best corrected visual acuity worse than 20/40 or >3 lines decreased vision from baseline up to 20/200); limiting activities of daily living
  • PEMAZYRE should be withheld until resolution. If improved on subsequent examination, PEMAZYRE may be resumed at 2 dose levels lower.
  • If it recurs, symptoms persist or examination does not improve, permanent discontinuation of PEMAZYRE should be considered, based on clinical status.
Visual acuity worse than 20/200 in affected eye; limiting activities of daily living
  • PEMAZYRE should be withheld until resolution. If improved on subsequent examination, PEMAZYRE may be resumed at 2 dose levels lower.
  • If it recurs, symptoms persist or examination does not improve, permanent discontinuation of PEMAZYRE should be considered, based on clinical status

Reference:
1. PEMAZYRE® (pemigatinib). Summary of Product Characteristics.

Learn more about PEMAZYRE (pemigatinib):

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Discover more about ESMO guideline recommendations for patients with CCA.

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PEMAZYRE self-directed learning

A self-directed learning material on PEMAZYRE is available to complete in your own time. With the PEMAZYRE learning module, you can learn about the clinical unmet needs in the treatment of CCA, discuss the need for molecular profiling for early patient identification and learn more about PEMAZYRE.

Learn about PEMAZYRE

PEMAZYRE eDetail
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Great Britain:
Incyte Biosciences UK Ltd,
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Randalls Way, Leatherhead,
KT22 7TW, UK

Northern Ireland:
Incyte Biosciences Distribution B.V.
Paasheuvelweg 25,
1105 BP Amsterdam, Netherlands

▼ 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.

Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk. 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]).

This medicinal product has been authorised under a 'conditional approval' scheme. This means that further evidence on this medicinal product is awaited. The Medicines and Healthcare products Regulatory Agency will review new information on this medicinal product at least every year and the Summary of Product Characteristics will be updated as necessary.

UK/PEMA/P/23/0039
Date of preparation: November 2023
Developed and funded by Incyte Biosciences International Sàrl.
© 2023, Incyte. All rights reserved.
PEMAZYRE, the PEMAZYRE logo and the Incyte logo are registered trademarks of Incyte.

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