PEMAZYRE is a kinase inhibitor indicated: for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. ( 1 , 2.1 ) This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
( 1 , 2.1 ) For the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement. ( 1 , 2.1 )
1.1Cholangiocarcinoma
PEMAZYRE is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test [see Dosage and Administration ( 2.1 )] . This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies ( 14.1 )].
Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
1.2Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement
PEMAZYRE is indicated for the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with fibroblast growth factor receptor 1 (FGFR1) rearrangement.
Contraindications
None. None. ( 4 )
Warnings and precautions
Ocular Toxicity : PEMAZYRE can cause retinal pigment epithelial detachment. Perform ophthalmological examination including optical coherence tomography (OCT) prior to initiation of therapy, every 2 months for the first 6 months of treatment and every 3 months thereafter, and urgently at any time for visual symptoms. ( 2.3 , 5.1 ) Hyperphosphatemia and Soft Tissue Mineralization : PEMAZYRE can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcification, calcinosis, and non-uremic calciphylaxis.
Monitor for hyperphosphatemia and withhold, reduce the dose, or permanently discontinue based on duration and severity of hyperphosphatemia. ( 2.3 , 5.2 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of reproductive potential of the potential risk to the fetus and use effective contraception. ( 5.3 , 8.1 , 8.3 )
PEMAZYRE can cause RPED, which may cause symptoms such as blurred vision, visual floaters, or photopsia. Clinical trials of PEMAZYRE did not conduct routine monitoring including optical coherence tomography (OCT) to detect asymptomatic RPED; therefore, the incidence of asymptomatic RPED with PEMAZYRE is unknown. Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, RPED occurred in 11% of patients, including Grade 3-4 RPED in 1.3%.
The median time to first onset of RPED was 56 days. RPED led to dose interruption of PEMAZYRE in 3.1% of patients, and dose reduction and permanent discontinuation in 1.3% and in 0.2% of patients, respectively. RPED resolved or improved to Grade 1 levels in 76% of patients who required dosage modification of PEMAZYRE for RPED. Perform a comprehensive ophthalmological examination including OCT prior to initiation of PEMAZYRE and every 2 months for the first 6 months and every 3 months thereafter during treatment.
For onset of visual symptoms, refer patients for ophthalmologic evaluation urgently, with follow-up every 3 weeks until resolution or discontinuation of PEMAZYRE. Modify the dose or permanently discontinue PEMAZYRE as recommended [see Dosage and Administration ( 2.3 )] . Dry Eye Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, dry eye occurred in 31% of patients, including Grade 3-4 in 1.6% of patients.
Treat patients with ocular demulcents as needed.
5.2Hyperphosphatemia and Soft Tissue Mineralization
PEMAZYRE can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcification, calcinosis, and non-uremic calciphylaxis. Increases in phosphate levels are a pharmacodynamic effect of PEMAZYRE [see Clinical Pharmacology ( 12.2 )] . Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, hyperphosphatemia was reported in 93% of patients based on laboratory values above the upper limit of normal.
The median time to onset of hyperphosphatemia was 8 days (range 1-169). Phosphate lowering therapy was required in 33% of patients receiving PEMAZYRE. Monitor for hyperphosphatemia and initiate a low phosphate diet when serum phosphate level is > 5.5 mg/dL. For serum phosphate levels > 7 mg/dL, initiate phosphate lowering therapy and withhold, reduce the dose, or permanently discontinue PEMAZYRE based on duration and severity of hyperphosphatemia [see Dosage and Administration ( 2.3 )].
5.3Embryo-Fetal Toxicity Based
on findings in an animal study and its mechanism of action, PEMAZYRE can cause fetal harm when administered to a pregnant woman. Oral administration of pemigatinib to pregnant rats during the period of organogenesis caused fetal malformations, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure based on area under the curve (AUC) at the clinical dose of 13.5 mg. Advise pregnant women of the potential risk to the fetus.
Advise female patients of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose [see Use in Specific Populations ( 8.1 , 8.3 )] .
Interactions
Strong and Moderate CYP3A Inducers: Avoid concomitant use of PEMAZYRE. ( 7.1 ) Strong and Moderate CYP3A Inhibitors: Avoid concomitant use. If concomitant use cannot be avoided, reduce PEMAZYRE dosage. ( 2.4 , 7.1 )
7.1Effect of Other Drugs on
PEMAZYRE Strong and Moderate CYP3A Inducers Concomitant use of PEMAZYRE with a strong or moderate CYP3A inducer decreases pemigatinib plasma concentrations [ see Clinical Pharmacology ( 12.3 )], which may reduce the efficacy of PEMAZYRE. Avoid concomitant use of strong and moderate CYP3A inducers with PEMAZYRE. Strong and Moderate CYP3A Inhibitors Concomitant use of a strong or moderate CYP3A inhibitor with PEMAZYRE increases pemigatinib plasma concentrations [see Clinical Pharmacology ( 12.3 )], which may increase the incidence and severity of adverse reactions.
Avoid concomitant use of strong and moderate CYP3A inhibitors with PEMAZYRE. Reduce PEMAZYRE dosage if concomitant use of strong and moderate CYP3A inhibitors cannot be avoided [see Dosage and Administration ( 2.4 )] .
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary Based
on findings in an animal study and its mechanism of action, PEMAZYRE can cause fetal harm or loss of pregnancy when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data on the use of PEMAZYRE in pregnant women. Oral administration of pemigatinib to pregnant rats during the period of organogenesis at maternal plasma exposures below the human exposure at the clinical dose of 13.5 mg resulted in fetal malformations, fetal growth retardation, and embryo-fetal death (see Data) .
Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Once daily oral administration of pemigatinib to pregnant rats during the period of organogenesis resulted in 100% embryofetal mortality due to post-implantation loss at doses ≥ 0.3 mg/kg (approximately 0.6 times the human exposure based on AUC at the clinical dose of 13.5 mg).
Fetal survival was unaffected at 0.1 mg/kg per day; however, once daily oral administration of pemigatinib at the 0.1 mg/kg dose level (approximately 0.2 times the human exposure based on AUC at the clinical dose of 13.5 mg) resulted in reduced mean fetal body weight and an increase in fetal skeletal and visceral malformations, major blood vessel variations, and reduced ossification.
Adverse reactions
The following adverse reactions are discussed elsewhere in the labeling: Ocular Toxicity [see Warnings and Precautions ( 5.1 )] Hyperphosphatemia and Soft Tissue Mineralization [see Warnings and Precautions ( 5.2 )] Cholangiocarcinoma: The most common adverse reactions (incidence ≥ 20%) are hyperphosphatemia, alopecia, diarrhea, nail toxicity, fatigue, dysgeusia, nausea, constipation, stomatitis, dry eye, dry mouth, decreased appetite, vomiting, arthralgia, abdominal pain, hypophosphatemia, back pain, and dry skin.
( 6.1 ) Myeloid/lymphoid neoplasms with FGFR1 rearrangement: The most common (≥ 20%) adverse reactions are hyperphosphatemia, nail toxicity, alopecia, stomatitis, diarrhea, dry eye, fatigue, rash, abdominal pain, anemia, constipation, dry mouth, epistaxis, serous retinal detachment, extremity pain, decreased appetite, dry skin, dyspepsia, back pain, nausea, blurred vision, peripheral edema, and dizziness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Incyte Corporation at 1-855-463-3463 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in the WARNINGS AND PRECAUTIONS section reflects exposure to PEMAZYRE at a starting dose of 13.5 mg orally once daily (intermittent or continuous administration) in 635 patients with advanced malignancies.
Among the 635 patients, 31% were exposed for 6 months or longer and 11% were exposed greater than one year, including patients with previously treated, advanced, or metastatic cholangiocarcinoma in FIGHT-202 and patients with MLNs with FGFR1 rearrangement in FIGHT-203. Cholangiocarcinoma FIGHT-202 The safety of PEMAZYRE was evaluated in FIGHT-202, which included 146 patients with previously treated, locally advanced or metastatic cholangiocarcinoma [see Clinical Studies ( 14.1 )].
Patients were treated orally with PEMAZYRE 13.5 mg once daily for 14 days on followed by 7 days off therapy until disease progression or unacceptable toxicity. The median duration of treatment was 181 days (range: 7 to 730 days). The median age of PEMAZYRE-treated patients was 59 years (range 26-78), 58% were females, and 71% were White. Serious adverse reactions occurred in 45% of patients receiving PEMAZYRE. Serious adverse reactions in ≥ 2% of patients who received PEMAZYRE included abdominal pain, pyrexia, cholangitis, pleural effusion, acute kidney injury, cholangitis infective, failure to thrive, hypercalcemia, hyponatremia, small intestinal obstruction, and urinary tract infection.
Fatal adverse reactions occurred in 4.1% of patients, including failure to thrive, bile duct obstruction, cholangitis, sepsis, and pleural effusion. Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received PEMAZYRE. Adverse reactions requiring permanent discontinuation in ≥ 1% of patients included intestinal obstruction and acute kidney injury. Dosage interruptions due to an adverse reaction occurred in 43% of patients who received PEMAZYRE.
Adverse reactions requiring dosage interruption in ≥ 1% of patients included stomatitis, palmar-plantar erythrodysesthesia syndrome, arthralgia, fatigue, abdominal pain, AST increased, asthenia, pyrexia, ALT increased, cholangitis, small intestinal obstruction, alkaline phosphatase increased, diarrhea, hyperbilirubinemia, electrocardiogram QT prolonged, decreased appetite, dehydration, hypercalcemia, hyperphosphatemia, hypophosphatemia, back pain, pain in extremity, syncope, acute kidney injury, onychomadesis, and hypotension.
Dose reductions due to an adverse reaction occurred in 14% of patients who received PEMAZYRE. Adverse reactions requiring dosage reductions in ≥ 1% of patients who received PEMAZYRE included stomatitis, arthralgia, palmar-plantar erythrodysesthesia syndrome, asthenia, and onychomadesis. Table 3 summarizes the adverse reactions in FIGHT-202. Table 4 summarizes laboratory abnormalities in FIGHT-202. Table 3: Adverse Reactions (≥ 15%) in Patients Receiving PEMAZYRE in FIGHT-202 Adverse Reaction PEMAZYRE N=146 All Grades Graded per NCI CTCAE 4.03.
(%) Grades 3 or 4 (%) Metabolism and nutrition disorders Hyperphosphatemia Includes hyperphosphatemia and blood phosphorous increased; graded based on clinical severity and medical interventions taken according to the "investigations-other, specify" category in NCI CTCAE v4.03. 60 0 Decreased appetite 33
1.4Hypophosphatemia
Includes hypophosphatemia and blood phosphorous decreased. 23 12 Dehydration 15
3.4Skin
and subcutaneous tissue disorders Alopecia 49 0 Nail toxicity Includes nail toxicity, nail disorder, nail discoloration, nail dystrophy, nail hypertrophy, nail ridging, nail infection, onychalgia, onychoclasis, onycholysis, onychomadesis, onychomycosis, and paronychia. 43
2.1 Dry skin 20
0.7 Palmar-plantar erythrodysesthesia syndrome 15
4.1 Gastrointestinal disorders Diarrhea 47
2.7 Nausea 40
2.1 Constipation 35
0.7Stomatitis 35 5
Dry mouth 34 0 Vomiting 27
1.4 Abdominal pain 23
4.8 General disorders Fatigue 42
4.8 Edema peripheral 18
0.7 Nervous system disorders Dysgeusia 40 0 Headache 16 0 Eye disorders Dry eye Includes dry eye, keratitis, lacrimation increased, pinguecula, and punctate keratitis. 35
0.7Musculoskeletal
and connective tissue disorders Arthralgia 25 6 Back pain 20
2.7Pain
in extremity 19
2.1Infections
and infestations Urinary tract infection 16
2.7Investigations
Weight loss 16
2.1 Clinically relevant adverse reactions occurring in ≤ 10% of patients included fractures (2.1%). In all patients treated with pemigatinib, 0.5% experienced pathologic fractures (which included patients with and without cholangiocarcinoma [N=635]). Soft tissue mineralization, including cutaneous calcification, calcinosis, and non-uremic calciphylaxis associated with hyperphosphatemia were observed with PEMAZYRE treatment.
Table 4: Select Laboratory Abnormalities (≥ 10%) Worsening from Baseline in Patients Receiving PEMAZYRE in FIGHT-202 PEMAZYRE The denominator used to calculate the rate varied from 142-146 based on the number of patients with a baseline value and at least one post-treatment value. N=146 Laboratory Abnormality All Grades Graded per NCI CTCAE 4.03. (%) Grades 3 or 4 (%) Hematology Decreased hemoglobin 43 6 Decreased lymphocytes 36 8 Decreased platelets 28
3.4 Increased leukocytes 27
0.7 Decreased leukocytes 18
1.4Chemistry
Increased phosphate Based on CTCAE 5.0 grading. 94 0 Decreased phosphate 68 38 Increased alanine aminotransferase 43
the first 21-day cycle of PEMAZYRE dosing, 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. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed [see Clinical Pharmacology ( 12.3 )]. Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement FIGHT-203 The safety of PEMAZYRE was evaluated in FIGHT-203, which included 34 patients who were treated for MLN with FGFR1 rearrangement [see Clinical Studies ( 14.2 )] .
Patients were treated with PEMAZYRE 13.5 mg once daily on a continuous schedule (the approved recommended starting dosage) or for 14 days on followed by 7 days off therapy (an unapproved dosage regimen in MLN with FGFR1 rearrange
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
PEMIGATINIB 13.5MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
