ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS

1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 section 4.8 for how to report adverse reactions.
1.

NAME OF THE MEDICINAL PRODUCTPemazyre 4.5 mg tablets
Pemazyre 9 mg tablets
Pemazyre 13.5 mg tablets
2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Pemazyre 4.5 mg tablets
Each tablet contains 4.5 mg of pemigatinib.
Pemazyre 9 mg tablets
Each tablet contains 9 mg of pemigatinib.
Pemazyre 13.5 mg tablets
Each tablet contains 13.5 mg of pemigatinib.
For the full list of excipients, see section 6.1.
3.

PHARMACEUTICAL FORM

Tablet.
Pemazyre 4.5 mg tablets
Round (5.8 mm), white to off-white tablet debossed on one side with "I" and "4.5" on the reverse.
Pemazyre 9 mg tablets
Oval (10 × 5 mm), white to off-white tablet debossed on one side with "I" and "9" on the reverse.
Pemazyre 13.5 mg tablets
Round (8.5 mm), white to off-white tablet debossed on one side with "I" and "13.5" on the reverse.
4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

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 thathave progressed after at least one prior line of systemic therapy.
4.2

Posology and method of administration

Therapy should be initiated by a physician experienced in the diagnosis and treatment of patients withbiliary tract cancer.
FGFR 2 fusion positivity status must be known prior to initiation of Pemazyre therapy. Assessment for
FGFR 2 fusion positivity in tumor specimen should be performed with an appropriate diagnostic test.

2

Posology
The recommended dose is 13.5 mg pemigatinib taken once daily for 14 days followed by 7 days off
therapy.
If a dose of pemigatinib is missed by 4 or more hours or vomiting occurs after taking a dose, anadditional dose should not be administered and dosing should be resumed with the next scheduled
dose.
Treatment should be continued as long as the patient does not show evidence of disease progression or
unacceptable toxicity.
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 ofphosphate-lowering therapy should be adjusted until serum phosphate level returns to < 7 mg/dL.
Prolonged hyperphosphataemia can cause precipitation of calcium-phosphate crystals that can lead tohypocalcaemia, soft tissue mineralization, muscle cramps, seizure activity, QT interval prolongation,
and arrhythmias (see section 4.4).
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 neurologic findings, heart failure, respiratory failure, muscle weakness,
rhabdomyolysis, and haemolytic anemia (see section 4.4).
Dose adjustment due to drug interaction
Concomitant use of pemigatinib with strong CYP3A4 inhibitors
Concurrent use of strong CYP3A4 inhibitors, including grapefruit juice, should be avoided during
treatment with pemigatinib. If co-administration with a strong CYP3A4 inhibitor is necessary, thedose of patients who are taking 13.5 mg pemigatinib once daily should be reduced to 9 mg once daily
and the dose of patients who are taking 9 mg pemigatinib once daily should be reduced to 4.5 mg once
daily (see sections 4.4 and 4.5).
Management of toxicities
Dose modifications or interruption of dosing should be considered for the management of toxicities.
Pemigatinib dose reductions levels are summarised in table 1.
Table 1:

Recommended pemigatinib dose reduction levels
Dose
Dose reduction levels
First
Second13.5 mg taken orally once daily 9 mg taken orally once daily
4.5 mg taken orally once dailyfor 14 days followed by 7 days for 14 days on, followed byfor 14 days on, followed by
off therapy
7 days off therapy
7 days off therapy

Treatment should be permanently discontinued if patient is unable to tolerate 4.5 mg pemigatinib once
daily.
Dose modifications for hyperphosphataemia are provided in table 2.

3

Table 2:
Dose modifications for hyperphosphataemia
Adverse reaction
pemigatinib dose modification> 5.5 mg/dL - ≤ 7 mg/dL•
pemigatinib should be continued at current dose.
> 7 mg/dL - ≤ 10 mg/dL•••> 10 mg/dL

•

•

•

pemigatinib should be continued at current dose, phosphatelowering 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.
pemigatinib should be withheld if levels do not return to<7 mg/dL within 2 weeks of starting a phosphate lowering
therapy. pemigatinib and phosphate-lowering therapy should berestarted at the same dose when level returns to < 7 mg/dL.
Upon recurrence of serum phosphate at > 7 mg/dL withphosphate-lowering therapy, pemigatinib should be reduced 1
dose level.
pemigatinib should be continued at current dose, phosphatelowering 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.
pemigatinib should be withheld if levels continue > 10 mg/dL
for 1 week. pemigatinib 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, pemigatinib should be permanently
discontinued.

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

4Special populations
Elderly patients
The dose of pemigatinib is the same in elderly patients as younger adult patients (see section 5.1).
Renal impairment
Dose adjustment is not required for patients with mild, moderate renal impairment or End Stage Renal
Disease (ESRD) on haemodialysis. For patients with severe renal impairment, the dose of patients who
are taking 13.5 mg pemigatinib once daily should be reduced to 9 mg once daily and the dose ofpatients who are taking 9 mg pemigatinib once daily should be reduced to 4.5 mg once daily (seesection 5.2).
Hepatic impairment
Dose adjustment is not required for patients with mild or moderate hepatic impairment. For patientswith severe hepatic impairment, the dose of patients who are taking 13.5 mg pemigatinib once daily
should be reduced to 9 mg once daily and the dose of patients who are taking 9 mg pemigatinib once
daily should be reduced to 4.5 mg once daily (see section 5.2).
Paediatric population
The safety and efficacy of Pemazyre in patients less than 18 years of age have not been established.
No data are available.
Method of administration
Pemazyre is for oral use. The tablets should be taken at approximately the same time every day.
Patients should not crush, chew, split or dissolve the tablets. Pemigatinib may be taken with or without
food.
4.3

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Concomitant use with St John’s wort (see section 4.5).
4.4

Special warnings and precautions for use

Hyperphosphataemia
Hyperphosphataemia is a pharmacodynamic effect expected with pemigatinib administration (seesection 5.1). Prolonged hyperphosphataemia can cause precipitation of calcium-phosphate crystals thatcan lead to hypocalcaemia, soft tissue mineralization, anemia, secondary hyperparathyroidism, muscle
cramps, seizure activity, QT interval prolongation, and arrhythmias (see section 4.2). Soft tissue
mineralization, including cutaneous calcification, calcinosis and non-uraemic calciphylaxis have been
observed with pemigatinib treatment.
Recommendations for management of hyperphosphataemia include dietary phosphate restriction,
administration of phosphate-lowering therapy, and dose modification when required (see section 4.2).
Phosphate-lowering therapy was used by 19 % of patients during treatment with pemigatinib (seesection 4.8).
Hypophosphataemia
Discontinuing phosphate-lowering therapy and diet should be considered during pemigatinib treatment
breaks or if serum phosphate level falls below normal range. Severe hypophosphataemia may present
with confusion, seizures, focal neurologic findings, heart failure, respiratory failure, muscle weakness,
rhabdomyolysis, and haemolytic anemia (see section 4.2). Hypophosphataemia reactions were ≥ Grade
3 in 14.3 % of participants. None of the events were serious, led to discontinuation or to dose
reduction. Dose interruption occurred in 1.4 % of participants.

5

For patients presenting with hyperphosphataemia or hypophosphataemia, additional close monitoring
and follow-up is recommended regarding dysregulation of bone mineralization.
Serous retinal detachment
Pemigatinib can cause serous retinal detachment reactions, which may present with symptoms such as
blurred vision, visual floaters, or photopsia (see section 4.8). This can moderately influence the ability
to drive and use machines (see section 4.7).
Ophthalmological examination, including optical coherence tomography (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, thedose modification guidelines should be followed (see section 4.2).
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 pemigatinib 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 detachment.
Dry eyePemigatinib can cause dry eye (see section 4.8). Patients should use ocular demulcents, in order toprevent or treat dry eye, as needed.
Embryo-foetal toxicity
Based on the mechanism of action and findings in an animal reproduction study (see section 5.3),
pemigatinib can cause foetal harm when administered to a pregnant woman. Pregnant women should
be advised of the potential risk to the foetus. Women of childbearing potential should be advised touse effective contraception during treatment with pemigatinib and for 1 week after the last dose.
Male patients with female partners of childbearing potential should be advised to use effective
contraception during treatment with pemigatinib and for at least 1 week after the last dose (see section
4.6).
Blood creatinine increase
Pemigatinib may increase serum creatinine by decreasing renal tubular secretion of creatinine; thismay occur due to inhibition of renal transporters OCT2 and MATE1 and may not affect glomerularfunction. Within the first cycle, serum creatinine increased (mean increase of 0.2 mg/dL) and reachedsteady state by Day 8, and then decreased during the 7 days off therapy (see section 4.8). Alternative
markers of renal function should be considered if persistent elevations in serum creatinine areobserved.
Combination with proton pump inhibitors
Concomitant use of pemigatinib with proton pump inhibitors should be avoided (see section 4.5).
Combination with strong CYP3A4 inhibitors
Concomitant use of pemigatinib with strong CYP3A4 inhibitors requires dose adjustment (see sections
4.2 and 4.5). Patients should be advised to avoid eating grapefruit or drinking grapefruit juice while
taking pemigatinib.
Combination with strong or moderate CYP3A4 inducers
Concomitant use of pemigatinib with strong or moderate CYP3A4 inducers is not recommended (seesection 4.5).

6

CNS metastasis
Since untreated or progressing brain/CNS metastasis were not allowed in the study, efficacy in thispopulation has not been evaluated and no dose recommendations can be made, however the
blood-brain barrier penetration of pemigatinib is expected to be low (see section 5.3).
Contraception
Based on findings in an animal study and its mechanism of action, Pemazyre can cause foetal harmwhen administered to a pregnant woman. Women of childbearing age being treated with Pemazyre
should be advised not to become pregnant and men being treated with Pemazyre should be advised not
to father a child during treatment. An effective method of contraception should be used in women ofchildbearing potential and in men with women partners of childbearing potential during treatment with
Pemazyre and for 1 week following completion of therapy (see section 4.6).
Pregnancy test
A pregnancy test should be performed before treatment initiation to exclude pregnancy.
4.5

Interaction with other medicinal products and other forms of interaction

Effects of other medicinal products on pemigatinib
Strong CYP3A4 inhibitors
A strong CYP3A4 inhibitor (itraconazole 200 mg once daily) increased pemigatinib AUC geometricmean by 88 % (90 % CI of 75 %, 103 %), which may increase the incidence and severity of adverse
reactions with pemigatinib. Patients who are taking 13.5 mg pemigatinib once daily should have theirdose reduced to 9 mg once daily and patients who are taking 9 mg pemigatinib once daily should havetheir dose reduced to 4.5 mg once daily (see section 4.2).
CYP3A4 inducers
A strong CYP3A4 inducer (rifampin 600 mg once daily) decreased pemigatinib AUC geometric meanby 85 % (90 % CI of 84 %, 86 %), which may decrease the efficacy of pemigatinib. Concurrent use ofstrong CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbital, rifampicin) should be
avoided during treatment with pemigatinib (see section 4.4). Concomitant use of pemigatinib with St
John’s wort is contra-indicated (see section 4.3). If needed, other enzyme inducers (e.g. efavirenz)
should be used under close surveillance.
Proton pump inhibitors
Pemigatinib geometric mean ratios (90 % CI) for Cmax and AUC were 65.3 % (54.7, 78.0) and 92.1 %(88.6, 95.8), respectively, when co-administered in healthy subjects with esomeprazole (a proton
pump inhibitor) relative to pemigatinib alone. Co-administration of a proton pump inhibitor(esomeprazole) did not result in a clinically important change in pemigatinib exposure.
However, in more than one third of patients given PPIs, a significant reduction of the exposure ofpemigatinib was observed. PPIs should be avoided in patients receiving pemigatinib (see section 4.4).
H2-receptors antagonists
Co-administration of ranitidine did not result in a clinically important change in pemigatinib exposure.
Effects of pemigatinib on other medicinal products
Effect of pemigatinib on CYP2B6 substrates
In vitro studies indicate that pemigatinib induces CYP2B6. Co-administration of pemigatinib withCYP2B6 substrates (e.g. cyclophosphamide, ifosfamide, methadone, efavirenz) may decrease their
exposure. Close clinical surveillance is recommended when pemigatinib is administered with these
medicinal products or any CYP2B6 substrate having a narrow therapeutic index.
Effect of pemigatinib on P-gp substrates
In vitro, pemigatinib is an inhibitor of P-gp. Co-administration of pemigatinib with P-gp substrates(e.g. digoxin, dabigatran, colchicine) may increase their exposure and thus their toxicity. Pemigatinib
7

administration should be separated by at least 6 hours before or after administration of P-gp substrates
with a narrow therapeutic index.
4.6

Fertility, pregnancy and lactation

Contraception in men and women/women of childbearing potential
Based on findings in an animal study and its mechanism of action, pemigatinib can cause foetal harmwhen administered to a pregnant woman. Women of childbearing potential being treated withpemigatinib should be advised not to become pregnant and men being treated with pemigatinib should
be advised not to father a child during treatment. An effective method of contraception should be usedin women of childbearing potential and in men with women partners of childbearing potential during
treatment with pemigatinib and for 1 week following completion of therapy. Since the effect ofpemigatinib on the metabolism and efficacy of contraceptives has not been investigated, barrier
methods should be applied as a second form of contraception, to avoid pregnancy.
Pregnancy
There are no available data from the use of pemigatinib in pregnant women. Studies in animals haveshown reproductive toxicity (see section 5.3). Based on animal data and pharmacology of pemigatinib,
Pemazyre should not be used during pregnancy unless the clinical condition of the women requires
treatment with pemigatinib. A pregnancy test should be performed before treatment initiation to
exclude pregnancy.
Breast-feeding
It is unknown whether pemigatinib or its metabolites are excreted in human milk. A risk to the breastfed child cannot be excluded. Breast-feeding should be discontinued during treatment with Pemazyre
and for 1 week following completion of therapy.
Fertility
There are no data on the impact of pemigatinib on human fertility. Animal fertility studies have notbeen conducted with pemigatinib (see section 5.3). Based on the pharmacology of pemigatinib,
impairment of male and female fertility cannot be excluded.
4.7

Effects on ability to drive and use machines

Pemigatinib has moderate influence on the ability to drive and use machines. Adverse reactions suchas fatigue and visual disturbances have been associated with pemigatinib. Therefore, caution should berecommended when driving or operating machines (see section 4.4).
4.8

Undesirable effects

Summary of the safety profile
The most common adverse reactions were hyperphosphataemia (60.5 %), alopecia (49.7 %), diarrhoea(47.6 %), nail toxicity (44.9 %), fatigue (43.5 %), nausea (41.5 %), stomatitis (38.1 %), constipation(36.7 %), dysgeusia (36.1 %), dry mouth (34.0 %), arthralgia (29.9 %), dry eye (27.9 %),hypophosphataemia (23.8 %), dry skin (21.8 %), and palmar-plantar erythrodysaesthesia syndrome(16.3 %).
The most common serious adverse reactions were hyponatremia (2.0 %) and blood creatinine increase(1.4 %). No serious adverse reaction led to pemigatinib dose reduction. One serious adverse reactionof hyponatremia (0.7 %) led to dose interruption. One serious adverse reaction of blood creatinine
increase (0.7 %) led to dose discontinuation.
Eye disorders serious adverse reactions were retinal detachment (0.7 %), non-arteritic optic ischemic
neuropathy (0.7 %) and retinal artery occlusion (0.7 %).

8Tabulated list of adverse reactions
Adverse reactions are presented in table 4. 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.
Table 4:Adverse reactions reported in clinical studies
System organ classFrequency
Adverse reactions
Metabolism and nutrition
Hyponatraemia, Hyperphosphataemiaa,
Very common
disorders
Hypophosphataemiab
Nervous system disorders
Very common
Dysgeusia
Very common
Dry eyeEye disorders
Serous retinal detachmentc, Punctate
Commonkeratitis, Vision blurred, Trichiasis
Nausea, Stomatitis, Diarrhoea,
Gastrointestinal disorders
Very common
Constipation, Dry mouth
Palmar-plantar erythrodysaesthesia
Very common
syndrome, Nail toxicityd, Alopecia, Dry
Skin and subcutaneous tissue
skindisordersCommonHair growth abnormal
UncommonCutaneous calcification
Musculoskeletal and connective
Very common
Arthralgia
tissue disorders
General disorders andVery common
Fatigueadministration site conditions
Investigations
Very common
Blood creatinine increaseda Includes Hyperphosphataemia and Blood phosphorous increased. See below “Hyperphosphataemia”.
b Includes Hypophosphataemia and Blood phosphorous decreasedc Includes Serous retinal detachment, Retinal detachment, Detachment of retinal pigmented epithelium, Retinal thickening,
Subretinal fluid, Chorioretinal folds, Chorioretinal scar, and Maculopathy. See below “Serous retinal detachment”.
d Includes Nail toxicity, Nail disorder, Nail discolouration, Nail dystrophy, Nail hypertrophy, Nail ridging, Nail infection,
Onychalgia, Onychoclasis, Onycholysis, Onychomadesis, Onychomycosis and Paronychia

Description of selected adverse reactions
Hyperphosphataemia
Hyperphosphataemia was reported in 60.5 % of all patients treated with pemigatinib.
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 pemigatinib.
Dose interruption occurred in 1.4 % patients and reduction in 0.7 % of patients. These results suggestthat 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 pemigatinib.
Recommendations for management of hyperphosphataemia are provided in sections 4.2 and 4.4.
Serous retinal detachment
Serous retinal detachment occurred in 4.8 % of all patients treated with pemigatinib. Reactions weregenerally Grade 1 or 2 (4.1 %) in severity; ≥ Grade 3 and serious reactions included retinal detachment
in 1 patient (0.7 %). Two adverse reactions 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
discontinuation.
Recommendations for management of serous retinal detachment are provided in sections 4.2 and 4.4.
Reporting of suspected adverse reactions
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. Healthcare9

professionals are asked to report any suspected adverse reactions via the national reporting system
listed in Appendix V.
4.9

Overdose

There is no information on overdose of pemigatinib.
5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: antineoplastic agents, protein kinase inhibitors, ATC code: L01EN02
Pemigatinib is a kinase inhibitor of FGFR1, 2 and 3 which inhibits FGFR phosphorylation andsignalling and decreases cell viability in cells expressing FGFR genetic alterations, including point
mutations, amplifications, and fusions or rearrangements. FGFR2 fusions/rearrangements are strong
oncogenic drivers and are the most common FGFR alteration occurring, almost exclusively, in 1016 % of intrahepatic cholangiocarcinoma (CCA).
Pharmacodynamic effects
Serum phosphate
Pemigatinib increased serum phosphate level as a consequence of FGFR inhibition. In pemigatinib
clinical studies, phosphate-lowering therapy and dose modifications were permitted to manage
hyperphosphataemia (see sections 4.2, 4.4 and 4.8).
Clinical studies
FIGHT-202 was a multicentre, open-label, single-arm study to evaluate the efficacy and safety ofPemazyre in previously treated patients with locally advanced/metastatic or surgically unresectablecholangiocarcinoma. The efficacy population consists of 108 patients (107 patients with intrahepaticdisease) that had progressed after at least 1 prior therapy and who had FGFR2 fusion or
rearrangement, as determined by the test performed at a central laboratory.
Patients received Pemazyre in 21-days 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 unacceptabletoxicity. The major efficacy outcome measures were objective response rate (ORR) and duration of
response (DoR), as determined by independent review committee (IRC) according to RECIST v1.1.
The median age was 55.5 years (range: 26 to 77 years), 23.1 % were ≥65 years, 61.1 % were female,and 73.1 % were Caucasian. Most (95.4 %) patients had a baseline Eastern Cooperative Oncology
Group (ECOG) performance status of 0 (42.6 %) or 1 (52.8 %). All patients had at least 1 prior line ofsystemic therapy, 27.8 % had 2 prior lines of therapy, and 12.0 % had 3 or more prior lines of therapy.
Ninety-six percent of patients had received prior platinum-based therapy including 78 % with priorgemcitabine/cisplatin.
Efficacy results are summarised in table 5.
The median time to response was 2.69 months (range 0.7 – 16.6 months).

10

Table 5:

Efficacy results

Cohort A (FGFR2 fusion or rearrangement)
Efficacy Evaluable Population(N = 108)37.0 % (27.94, 46.86)
2.8 % (3)34.3 % (37)9.13 (6.01, 14.49)

ORR (95 % CI)
Complete response (N)Partial response (N)Median duration of response (months) (95 %CI)aKaplan-Meier estimates of duration of
response (95 % CI)
3 months
6 months
9 months
12 months

100.0 (100.0, 100.0)
67.8 (50.4, 80.3)
50.5 (33.3, 65.4)
41.2 (24.8, 56.8)

ORR- CR+PR
CI= Confidence Interval
Note: Data are from IRC per RECIST v1.1, and complete and partial responses are confirmed.
a The 95 % CI was calculated using the Brookmeyer and Crowley's method

Elderly patients
In the clinical study of pemigatinib, 23.1 % of patients were 65 years and older, and 4.6 % of patientswere 75 years and older. No difference in efficacy response was detected between these patients and inpatients < 65 years of age.
Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with
Pemazyre in all subsets of the paediatric population in the treatment of cholangiocarcinoma. See
section 4.2 for information in pediatric use.
This medicinal product has been authorised under a so-called ‘conditional approval’ scheme. Thismeans that further evidence on this medicinal product is awaited. The European Medicines Agency
will review new information on this medicinal product at least every year and this SmPC will be
updated as necessary.
5.2

Pharmacokinetic properties

Pemigatinib exhibits linear pharmacokinetics in the dose range of 1 to 20 mg. Following oral
administration of Pemazyre 13.5 mg once daily, steady-state was reached by 4 days with a geometricmean accumulation ratio of 1.6. The geometric mean steady-state AUC0-24h was 2620 nM·h (54 % CV)
and Cmax was 236 nM (56 % CV) for 13.5 mg once daily.
Absorption
Median time to achieve peak plasma concentration (tmax) was 1 to 2 hours.
No clinically meaningful differences with pemigatinib pharmacokinetics were observed following
administration of a high-fat and high-calorie meal (800 calories to 1,000 calories with approximately
50 % of total caloric content of the meal from fat) in patients with cancer.
Distribution
Pemigatinib is 90.6 % bound to human plasma proteins, predominantly to albumin. The estimatedapparent volume of distribution was 235 L (60.8 %) in patients with cancer.
Biotransformation
Pemigatinib is predominantly metabolised by CYP3A4 in vitro. Following oral administration of asingle 13.5 mg radiolabeled pemigatinib dose, unchanged pemigatinib was the major drug-related
moiety in plasma, and no metabolites > 10 % of total circulating radioactivity were observed.

11

Elimination
Following oral administration of pemigatinib 13.5 mg once daily in patients with cancer, the geometricmean elimination half-life (t½) was 15.4 (51.6 % CV) hours and the geometric mean apparent
clearance (CL/F) was 10.6 L/h (54 % CV).
Excretion
Following a single oral dose of radiolabeled pemigatinib, 82.4 % of the dose was recovered in faeces(1.4 % as unchanged) and 12.6 % in urine (1 % as unchanged).
Renal impairment
The effect of renal impairment on the pharmacokinetics of pemigatinib was evaluated in a renal
impairment study in subjects with normal renal function (GFR ≥ 90 mL/min), severe renal function(GFR < 30 mL/min and not on hemodialysis) and End Stage Renal Disease (ESRD) (GFR < 30
mL/min and on hemodialysis). In subjects with the severe renal impairment, the geometric mean ratios(90 % CI) compared to normal controls were 64.6 % (44.1 %, 94.4 %) for Cmax and 159 % (95.4 %,264 %) for AUC0-∞. In the subjects with ESRD before hemodialysis, the geometric mean ratios (90 %CI) was 77.5 % (51.2 %, 118 %) for Cmax and 76.8 % (54.0 %, 109 %) for AUC0-∞. Besides, inparticipants with ESRD after hemodialysis, the geometric mean ratios (90 % CI) were 90.0 % (59.3 %,137 %) for Cmax and 91.3 % (64.1 %, 130 %) for AUC0-∞. Based on these results, pemigatinib doseshould be reduced for patients with severe renal impairment (see section 4.2).
Hepatic impairment
The effect of hepatic impairment on the pharmacokinetics of pemigatinib was evaluated in a hepatic
impairment study in subjects with normal hepatic function, moderate (Child-Pugh class B) and severe(Child-Pugh class C) hepatic impairment. In subjects with moderate hepatic impairment, the geometricmean ratios (90 % CI) compared to normal controls, were 96.7 % (59.4 %, 157 %) for Cmax and 146 %(100 %, 212 %) for AUC0-∞. In subjects with severe hepatic impairment, the GMR (90 % CI) was
94.2 % (68.9 %, 129 %) for Cmax and 174 % (116 %, 261 %) for AUC0-∞. Based on these results, nodose adjustment is recommended for patients with mild and moderate hepatic impairment. However,pemigatinib dose should be reduced for patients with severe hepatic impairment (see section 4.2).
Interactions
CYP substrates
Pemigatinib at clinically relevant concentrations is not an inhibitor of CYP1A2, CYP2B6, CYP2C8,CYP2C9, CYP2C19, CYP2D6 and CYP3A4 or an inducer of CYP1A2 and CYP3A4.
Transporters
Pemigatinib is a substrate of both P-gp and BCRP. P-gp or BCRP inhibitors are not expected to affectpemigatinib exposure at clinically relevant concentrations.
In vitro, pemigatinib is an inhibitor of OATP1B3, OCT2, and MATE1. Inhibition of OCT2 may
increase serum creatinine.
5.3

Preclinical safety data

Systemic toxicity
The most prominent findings following repeat-dose administration of pemigatinib in both rats andmonkeys were attributed to the intended pharmacology of pemigatinib (FGFR1, FGFR2, and FGFR3
inhibition), including hyperphosphataemia, physeal dysplasia, and soft tissue mineralization; some ofthese findings were observed at exposures (AUC) lower than therapeutic. Mineralization was observedin numerous tissues including kidneys, stomach, arteries, ovaries (monkey only), and eyes (cornea, ratonly). Soft tissue mineralization was not reversible, while physeal and cartilage findings werereversible. In addition, changes of the bone marrow (rats) and kidney lesions were observed.

12

Genotoxicity
Pemigatinib was not mutagenic in a bacterial mutagenicity assay, nor clastogenic in an in vitro
chromosome aberration assay, and did not result in induction of bone marrow micronuclei in an invivo micronucleus assay in rats.
Carcinogenicity
Carcinogenicity studies with pemigatinib have not been conducted.
Impairment of fertility
No specific animal studies with pemigatinib have been conducted to evaluate the effects of pemigatinib
on fertility. In repeated dose toxicity studies, oral administration of pemigatinib did not result in any
dose-related adverse effects on male and female reproductive organs.
Developmental toxicity
In rats, administration of pemigatinib at ≥ 0.3 mg/kg/day during the period of organogenesis resulted
in 100 % postimplantation loss. At 0.1 mg/kg/day, an increase in foetal skeletal malformations andmajor blood vessels variations, reduced ossification, and decrease foetal body weight were observed.
Exposure at that dose is approximately 20 % of the clinical exposure at the maximum recommended
human dose of 13.5 mg based on AUC.
Safety pharmacology
In vitro, pemigatinib showed an IC50 for hERG inhibition > 8 μM (the highest feasible concentration
based on solubility), that is > 360-fold higher than the clinical steady-state unbound Cmax at the dose of
13.5 mg. In vivo, there were no adverse findings in safety pharmacology assessments of pemigatinib,
including in vivo respiratory and central nervous system function studies in rats and cardiovascularstudy in monkeys.
6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Microcrystalline cellulose (E-460)
Sodium starch glycolate (Type A)
Magnesium stearate (E-572)
6.2

Incompatibilities

Not applicable.
6.3

Shelf life

4 years.
6.4

Special precautions for storage

This medicinal product does not require any special storage conditions.
6.5

Nature and contents of container

PVC/Al blister containing 14 tablets. Carton box containing 14 or 28 tablets.
Not all pack sizes may be marketed.
6.6

Special precautions for disposal

No special requirements for disposal.
13

7.

MARKETING AUTHORISATION HOLDER

Incyte Biosciences Distribution B.V.
Paasheuvelweg 251105 BP Amsterdam
Netherlands
8.

MARKETING AUTHORISATION NUMBER(S)Pemazyre 4.5 mg tablets
EU/1/21/1535/001
EU/1/21/1535/002
Pemazyre 9 mg tablets
EU/1/21/1535/003
EU/1/21/1535/004
Pemazyre 13.5 mg tablets
EU/1/21/1535/005
EU/1/21/1535/006
9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 26 March 2021
Date of latest renewal: 23 February 2023
10.

DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines
Agency http://www.ema.europa.eu.

14

ANNEX IIA.

MANUFACTURER(S) RESPONSIBLE FOR BATCH
RELEASEB.

CONDITIONS OR RESTRICTIONS REGARDING SUPPLYAND USEC.

OTHER CONDITIONS AND REQUIREMENTS OF THE
MARKETING AUTHORISATION

D.

CONDITIONS OR RESTRICTIONS WITH REGARD TO
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL
PRODUCTE.

SPECIFIC OBLIGATION TO COMPLETE POSTAUTHORISATION MEASURES FOR THE CONDITIONAL
MARKETING AUTHORISATION

15

A.

MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers responsible for batch release
Incyte Biosciences Distribution B.V.
Paasheuvelweg 251105 BP Amsterdam
Netherlands
Tjoapack Netherlands B.V.
Nieuwe Donk 94879 AC Etten-Leur
Netherlands
The printed package leaflet of the medicinal product must state the name and address of the
manufacturer responsible for the release of the concerned batch.
B.

CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to restricted medical prescription (see Annex I: Summary of ProductCharacteristics, section 4.2).
C.

OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING
AUTHORISATION•

Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list ofUnion reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC
and any subsequent updates published on the European medicines web-portal.
The marketing authorisation holder shall submit the first periodic safety update report for this productwithin 6 months following authorisation.
D.

CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT•Risk management plan (RMP)

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of themarketing authorisation and any agreed subsequent updates of the RMP.
An updated RMP should be submitted:• At the request of the European Medicines Agency;• Whenever the risk management system is modified, especially as the result of new information
being received that may lead to a significant change to the benefit/risk profile or as the result of
an important (pharmacovigilance or risk minimisation) milestone being reached.
E.

SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURESFOR THE CONDITIONAL MARKETING AUTHORISATIONThis being a conditional marketing authorisation and pursuant to Article 14-a of Regulation (EC) No
726/2004, the MAH shall complete, within the stated timeframe, the following measures:16Description
In order to confirm the efficacy and safety of Pemazyre in adults with locallyadvanced 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, the MAH should submit the results of FIGHT302 (INCB 54828-302), a phase 3 study comparing the efficacy and safety ofpemigatinib vs. gemcitabine plus cisplatin chemotherapy in adults withunresectable or metastatic cholangiocarcinoma with FGFR2 rearrangement.

17

Due date
December
2026

ANNEX III
LABELLING AND PACKAGE LEAFLET

18

A. LABELLING

19

PARTICULARS TO APPEAR ON THE OUTER PACKAGINGOUTER CARTON FOR BLISTER
1.

NAME OF THE MEDICINAL PRODUCTPemazyre 4.5 mg tablets
pemigatinib
2.

STATEMENT OF ACTIVE SUBSTANCE(S)Each tablet contains 4.5 mg pemigatinib.
3.

LIST OF EXCIPIENTS

4.

PHARMACEUTICAL FORM AND CONTENTS

14 tablets
28 tablets
5.

METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.
6.

SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.
7.

OTHER SPECIAL WARNING(S), IF NECESSARY8.

EXPIRY DATEEXP
9.

SPECIAL STORAGE CONDITIONS

10.

SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE

20

11.

NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Incyte Biosciences Distribution B.V.
Paasheuvelweg 251105 BP Amsterdam
Netherlands
12.

MARKETING AUTHORISATION NUMBER(S)EU/1/21/1535/001
EU/1/21/1535/002
13.

14 tablets
28 tablets

BATCH NUMBER

Lot
14.

GENERAL CLASSIFICATION FOR SUPPLY

15.

INSTRUCTIONS ON USE

16.

INFORMATION IN BRAILLE

Pemazyre 4.5 mg
17.

UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.
18.

UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN

21

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPSBLISTER
1.

NAME OF THE MEDICINAL PRODUCTPemazyre 4.5 mg tablets
pemigatinib
2.

NAME OF THE MARKETING AUTHORISATION HOLDER

Incyte Biosciences Distribution B.V. (as Incyte logo)
3.

EXPIRY DATEEXP
4.

BATCH NUMBER

Lot
5.

OTHER

Mon.
Tue.
Wed.
Thu.
Fri.
Sat.
Sun.

22

PARTICULARS TO APPEAR ON THE OUTER PACKAGINGOUTER CARTON FOR BLISTER
1.

NAME OF THE MEDICINAL PRODUCTPemazyre 9 mg tablets
pemigatinib
2.

STATEMENT OF ACTIVE SUBSTANCE(S)Each tablet contains 9 mg pemigatinib.
3.

LIST OF EXCIPIENTS

4.

PHARMACEUTICAL FORM AND CONTENTS

14 tablets
28 tablets
5.

METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.
6.

SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.
7.

OTHER SPECIAL WARNING(S), IF NECESSARY8.

EXPIRY DATEEXP
9.

SPECIAL STORAGE CONDITIONS

10.

SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE

23

11.

NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Incyte Biosciences Distribution B.V.
Paasheuvelweg 251105 BP Amsterdam
Netherlands
12.

MARKETING AUTHORISATION NUMBER(S)EU/1/21/1535/003
EU/1/21/1535/004
13.

14 tablets
28 tablets

BATCH NUMBER

Lot
14.

GENERAL CLASSIFICATION FOR SUPPLY

15.

INSTRUCTIONS ON USE

16.

INFORMATION IN BRAILLE

Pemazyre 9 mg
17.

UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.
18.

UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN

24

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPSBLISTER
1.

NAME OF THE MEDICINAL PRODUCTPemazyre 9 mg tablets
pemigatinib
2.

NAME OF THE MARKETING AUTHORISATION HOLDER

Incyte Biosciences Distribution B.V. (as Incyte logo)
3.

EXPIRY DATEEXP
4.

BATCH NUMBER

Lot
5.

OTHER

Mon.
Tue.
Wed.
Thu.
Fri.
Sat.
Sun.

25

PARTICULARS TO APPEAR ON THE OUTER PACKAGINGOUTER CARTON FOR BLISTER
1.

NAME OF THE MEDICINAL PRODUCTPemazyre 13.5 mg tablets
pemigatinib
2.

STATEMENT OF ACTIVE SUBSTANCE(S)Each tablet contains 13.5 mg pemigatinib.
3.

LIST OF EXCIPIENTS

4.

PHARMACEUTICAL FORM AND CONTENTS

14 tablets
28 tablets
5.

METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.
6.

SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.
7.

OTHER SPECIAL WARNING(S), IF NECESSARY8.

EXPIRY DATEEXP
9.

SPECIAL STORAGE CONDITIONS

10.

SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE

26

11.

NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Incyte Biosciences Distribution B.V.
Paasheuvelweg 251105 BP Amsterdam
Netherlands
12.

MARKETING AUTHORISATION NUMBER(S)EU/1/21/1535/005
EU/1/21/1535/006
13.

14 tablets
28 tablets

BATCH NUMBER

Lot
14.

GENERAL CLASSIFICATION FOR SUPPLY

15.

INSTRUCTIONS ON USE

16.

INFORMATION IN BRAILLE

Pemazyre 13.5 mg
17.

UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.
18.

UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN

27

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPSBLISTER
1.

NAME OF THE MEDICINAL PRODUCTPemazyre 13.5 mg tablets
pemigatinib
2.

NAME OF THE MARKETING AUTHORISATION HOLDER

Incyte Biosciences Distribution B.V. (as Incyte logo)
3.

EXPIRY DATEEXP
4.

BATCH NUMBER

Lot
5.

OTHER

Mon.
Tue.
Wed.
Thu.
Fri.
Sat.
Sun.

28

B. PACKAGE LEAFLET

29

Package leaflet: Information for the patient
Pemazyre 4.5 mg tablets
Pemazyre 9 mg tablets
Pemazyre 13.5 mg tablets
pemigatinib
This medicine is subject to additional monitoring. This will allow quick identification of new safety
information. You can help by reporting any side effects you may get. See the end of section 4 for how
to report side effects.
Read all of this leaflet carefully before you start taking this medicine because it contains
important information for you.
•
Keep this leaflet. You may need to read it again.
•
If you have any further questions, ask your doctor or pharmacist.
•
This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,even if their signs of illness are the same as yours.
•
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side
effects not listed in this leaflet. See section 4.
What is in this leaflet
1.
2.
3.
4.
5.
6.

What Pemazyre is and what it is used for
What you need to know before you take Pemazyre
How to take Pemazyre
Possible side effects
How to store Pemazyre
Contents of the pack and other information

1.

What Pemazyre is and what it is used for

Pemazyre contains the active substance pemigatinib, which belongs to a group of cancer medicines
called tyrosine kinase inhibitors. It blocks the action of proteins in the cell called fibroblast growth
factor receptor types 1, 2 and 3 (FGFR1, FGFR2, and FGFR3) that help regulate cell growth. Cancer
cells may have an abnormal form of this protein. By blocking FGFR, pemigatinib can prevent thegrowth of such cancer cells.
Pemazyre is used:• to treat adults with bile duct cancer (also known as cholangiocarcinoma) whose cancer cells
have an abnormal form of the FGFR2 protein, and• when the cancer has spread to other parts of the body or cannot be removed by surgery, and• when treatment with other medicines is no longer working.
2.

What you need to know before you take Pemazyre

Do not take Pemazyre if you are•allergic to pemigatinib or any of the other ingredients of this medicine (listed in section 6)•
using St John’s wort, a medicine to treat depression
Warnings and precautions
Talk to your doctor or pharmacist before taking Pemazyre if you have:•been told you have an increase or decrease of a mineral in your blood called phosphorus•
vision or eye problems•
severely reduced liver function. Your treatment may need to be adjusted•
severely reduced kidney function. Your treatment may need to be adjusted30

•cancer cells that have spread into the brain or spinal cord

Eye examinations are recommended:•
before starting treatment with Pemazyre•
every 2 months for the first 6 months of treatment•
every 3 months thereafter or immediately if any visual symptoms occur, including flashes oflight, visual disturbances or dark spots.
Tell your doctor straight away if you get any symptoms with your vision.
You should also use lubricating or hydrating eye drops or gels to help prevent or treat dry eyes.
Pemazyre may harm the unborn baby. An effective contraception must be used during treatment andfor at least 1 week after the last dose of Pemazyre in women of childbearing age and in men withwomen partners of childbearing age.
Children and adolescents
Pemazyre should not be given to children or adolescents under 18 years. It is not known whether it issafe and effective in this age group.
Other medicines and Pemazyre
Tell your doctor or pharmacist if you are taking, have recently taken or might take any othermedicines.
In particular, you should tell your doctor if you are taking any of the following medicines so that thedoctor can decide if your treatment needs to change:•
St John’s wort: a medicine to treat depression. You must not take St John’s wort during
treatment with Pemazyre.
•
medicines with active substance names ending with “prazole”: they are used to reduce therelease of stomach acid. Avoid using these medicines during treatment with Pemazyre•
itraconazole: a medicine to treat fungal infections•
rifampicin: a medicine to treat tuberculosis or certain other infections•
carbamazepine, phenytoin, phenobarbital, primidone: medicines to treat epilepsy•
efavirenz: medicine to treat HIV infection•
cyclophosphamide, ifosfamide: other medicines to treat cancer•
methadone: a medicine to treat severe pain or for managing addiction•
digoxin: a medicine to treat heart disease•
dabigatran: a medicine to prevent blood clots•
colchicine: a medicine to treat gout attacks
Pemazyre with food and drink
Avoid eating grapefruit or drinking grapefruit juice while using this medication.
Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask
your doctor or pharmacist for advice before taking this medicine.
••

Pregnancy
Pemazyre may harm the unborn baby and should not be used during pregnancy unless you are
told otherwise by your doctor. A pregnancy test should be performed before initiating treatment.
Contraception advice for men and women
Women being treated with Pemazyre should not become pregnant. Therefore, women who
could become pregnant must use effective contraception during treatment and for at least 1
week after the last dose of Pemazyre. Talk to your doctor about the most suitable contraception
for you.
Men should avoid fathering a child. They must use effective contraception during treatment andfor at least 1 week after the last dose of Pemazyre.
31

•Breast-feeding
Do not breast-feed during treatment with Pemazyre and for at least 1 week after the last dose.

Driving and using machines
Pemazyre can cause side effects such as fatigue or visual disturbances. Do not drive or operatemachinery if this happens.
3.

How to take Pemazyre

Pemazyre treatment should be started by a doctor who is experienced in the diagnosis and treatment ofbile duct cancer. Always take this medicine exactly as your doctor or pharmacist has told you. Check
with your doctor or pharmacist if you are not sure.
The recommended dose is
1 tablet of Pemazyre 13.5 mg taken once daily for 14 days, followed by 7 days without taking
Pemazyre.
Treatment is continued with the same pattern of 14 days of Pemazyre once daily, followed by 7 days
off therapy. Do not take Pemazyre during the 7 days off therapy. Your doctor will adjust the dose orstop treatment if needed.
Method of use
Swallow the tablet whole with one glass of water at the same time every day. Pemazyre may be takenwith food or between meals.
Do not crush, chew, split or dissolve the tablets.
Duration of use
Take Pemazyre for as long as it is prescribed by the doctor.
If you take more Pemazyre than you should
Tell your doctor if you have taken more Pemazyre than you should have.
If you forget to take Pemazyre
If you miss a dose of Pemazyre by 4 hours or more, or if you vomit after taking Pemazyre, do not takeanother Pemazyre tablet to make up for the missed dose. Take your next dose of Pemazyre at thescheduled time.
If you stop taking Pemazyre
Do not stop taking Pemazyre without discussing it with your doctor, as this could reduce the successof therapy.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor immediately if you have any of the serious side effects below. These side effects
may occur with the following frequency:
Very common (may affect more than 1 in 10 people):•low sodium in blood; symptoms include decreased ability to think, headache, nausea, poor
balance, confusion, seizures, coma32•blood tests showing increase of creatinine, which can suggest kidney problems; usually raised
creatinine does not cause symptoms, but symptoms of kidney problems may include nausea andchanges in urination

Other side effects may occur with the following frequencies:
Very common (may affect more than 1 in 10 people)•
high or low phosphate levels seen in blood tests•
taste disturbance•dry eye•nausea•inflammation of the inner lining of the mouth•
diarrhoea•
constipation•
dry mouth•skin reactions with redness, swelling and pain on palms of the hands and soles of the feet, called
hand-foot syndrome•
nail toxicity, including nails separating from the nail bed, nail pain, nail bleeding, breaking of
the nails, colour or texture changes in your nails, infected skin around the nail•hair loss•
dry skin•joint pain•
fatigue
Common (may affect up to 1 in 10 people)•
fluid build-up under the retina (the light-sensitive layer at the back of the eye)•inflammation of the cornea (the clear outer layer of the eye)•reduced vision•
eyelash changes including abnormally long eyelashes, ingrown eyelashes•
abnormal hair growth
Uncommon (may affect up to 1 in 100 people)•
deposition of calcium salts that appears as hard papules, nodules, or plaques in or under the skinin any area of the body and can cause pain and ulcers
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects
not listed in this leaflet. You can also report side effects directly via the national reporting system
listed in Appendix V. By reporting side effects you can help provide more information on the safety ofthis medicine.
5.

How to store Pemazyre

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and the blister after EXP.
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how tothrow away medicines you no longer use. These measures will help protect the environment.

33

6.

Contents of the pack and other information

What Pemazyre contains•
The active substance is pemigatinib.
Each 4.5 mg tablet contains 4.5 mg pemigatinib.
Each 9 mg tablet contains 9 mg pemigatinib.
Each 13.5 mg tablet contains 13.5 mg pemigatinib.
•
The other ingredients are microcrystalline cellulose, sodium starch glycolate (Type A),
magnesium stearate.
What Pemazyre looks like and contents of the packPemazyre 4.5 mg tablets are round, white to off-white, debossed on one side with “I” and “4.5” on thereverse.
Pemazyre 9 mg tablets are oval, white to off-white, debossed on one side with “I” and “9” on thereverse.
Pemazyre 13.5 mg tablets are round, white to off-white, debossed on one side with “I” and “13.5” on
the reverse.
The tablets are provided in blisters containing 14 tablets. The carton contains 14 or 28 tablets.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Incyte Biosciences Distribution B.V.
Paasheuvelweg 251105 BP Amsterdam
Netherlands
Manufacturer
Incyte Biosciences Distribution B.V.
Paasheuvelweg 251105 BP Amsterdam
Netherlands
Tjoapack Netherlands B.V.
Nieuwe Donk 94879 AC Etten-Leur
Netherlands
This leaflet was last revised in {MM/YYYY}.
This medicine has been given ‘conditional approval’. This means that there is more evidence to comeabout this medicine.
The European Medicines Agency will review new information on this medicine at least every year andthis leaflet will be updated as necessary.
Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu.

34

ANNEX IVSCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS
OF THE MARKETING AUTHORISATION(S)35

Scientific conclusions
Taking into account the PRAC Assessment Report on the PSUR(s) for pemigatinib, the scientificconclusions of CHMP are as follows:
In view of available data on cutaneous calcification from clinical trials, including in some cases a
close temporal relationship, and in view of a plausible mechanism of action, the PRAC considers acausal relationship between pemigatinib and cutaneous calcification is at least a reasonable
possibility. The PRAC concluded that the product information of products containing pemigatinib
should be amended accordingly.
The CHMP agrees with the scientific conclusions made by the PRAC.

Grounds for the variation to the terms of the marketing authorisation(s)On the basis of the scientific conclusions for pemigatinib the CHMP is of the opinion that thebenefit-risk balance of the medicinal product(s) containing pemigatinib is unchanged subject to the
proposed changes to the product information
The CHMP recommends that the terms of the marketing authorisation(s) should be varied.

36