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One pill, once daily that can be taken at home, with or without food1

  • Instruct patients to take their dose of PEMAZYRE at approximately the same time every day
  • Swallow tablets whole. Do not crush, chew, split, or dissolve tablets
  • If the patient misses a dose by 4 or more hours or if vomiting occurs, resume dosing with the next scheduled dose
 
 
Pill bottle icon

Refer to the Dosing and Administration Guide
for more information on dose modifications.

 

PEMAZYRE Safety and Dosing in Cholangiocarcinoma

Hear from Dr Richard Kim as he presents safety and dosing information for PEMAZYRE.

PEMAZYRE Safety
and Dosing in Cholangiocarcinoma

Hear from Dr Richard Kim as he presents safety and dosing information for PEMAZYRE.

 
 
Pill bottle icon

Refer to the Dosing and Administration Guide
for more information on dose modifications.

Dosage modifications1

  • PEMAZYRE is available in 3 strengths to enable dose modifications as needed—13 .5 mg, 9 mg, and 4 .5 mg

    Image showing the 3 strengths of PEMAZYRE to enable dose modifications as needed – 13.5mg Starting dose > 9mg First dose reduction > 4.5mg Second dose reduction
    • Permanently discontinue PEMAZYRE if unable to tolerate 4.5 mg once daily for 14 days of each 21-day cycle.
  • Reduce the dose of PEMAZYRE for adverse reactions
    • RPED: If asymptomatic and stable on serial examination, continue PEMAZYRE. If symptomatic or worsening on serial examination, withhold PEMAZYRE; if asymptomatic and improved on subsequent examination, resume PEMAZYRE at a lower dose. If symptoms persist or examination does not improve, consider permanent discontinuation of PEMAZYRE, based on clinical status.
    • Hyperphosphatemia: If serum phosphate >7 mg/dL to ≤10 mg/dL, initiate phosphate lowering therapy and monitor serum phosphate weekly. Withhold PEMAZYRE if levels are not <7 mg/dL within 2 weeks of starting phosphate lowering therapy, and resume PEMAZYRE at the same dose when phosphate levels are <7 mg/dL for first occurrence. Resume at a lower dose level for subsequent recurrences. If serum phosphate >10 mg/dL, initiate phosphate lowering therapy and monitor serum phosphate weekly, withhold PEMAZYRE if levels are not ≤10 mg/dL within 1 week after starting phosphate lowering therapy, and resume PEMAZYRE at the next lower dose level when phosphate levels are <7 mg/dL. Permanently discontinue PEMAZYRE for recurrence of serum phosphate >10 mg/dL following 2 dose reductions.
    • Other adverse reactions: For Grade 3, withhold PEMAZYRE until resolves to Grade 1 or baseline. Resume PEMAZYRE at next lower dose if resolves within 2 weeks, and permanently discontinue PEMAZYRE if does not resolve within 2 weeks. Permanently discontinue PEMAZYRE for recurrent Grade 3 after 2 dose reductions. For Grade 4, permanently discontinue PEMAZYRE.
  • Avoid concomitant use of strong and moderate CYP3A inhibitors during treatment with PEMAZYRE
    • If concomitant use with a strong or moderate CYP3A inhibitor cannot be avoided, reduce the dose of PEMAZYRE
  • Avoid concomitant use of strong and moderate CYP3A inducers with PEMAZYRE
  • The recommended dosage of PEMAZYRE for patients with severe renal impairment (eGFR estimated by Modification of Diet in Renal Disease [MDRD] 15 to 29 mL/min/1.73 m2) is 9 mg with the schedule (intermittent or continuous) designated for the indication
  • The recommended dosage of PEMAZYRE for patients with severe hepatic impairment (total bilirubin > 3 × upper limit normal [ULN] with any AST) is 9 mg with the schedule (intermittent or continuous) designated for the indication
 

Refer to the Dosing and Administration

Guide for more information on dose modifications.

Reference:

1. PEMAZYRE Prescribing Information. Incyte Corporation.

INDICATIONS AND USAGE

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.

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).

IMPORTANT SAFETY INFORMATION

Ocular Toxicity

Retinal Pigment Epithelial Detachment (RPED): 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 in the prescribing information for PEMAZYRE.

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.

Hyperphosphatemia 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. 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 as recommended in the prescribing information.

Embryo-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.

Adverse Reactions: Cholangiocarcinoma

Serious adverse reactions occurred in 45% of patients receiving PEMAZYRE (n=146). 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.

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.

Within 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.

In cholangiocarcinoma (n=146) the most common adverse reactions (incidence ≥20%) were hyperphosphatemia (60%), alopecia (49%), diarrhea (47%), nail toxicity (43%), fatigue (42%), dysgeusia (40%), nausea (40%), constipation (35%), stomatitis (35%), dry eye (35%), dry mouth (34%), decreased appetite (33%), vomiting (27%), arthralgia (25%), abdominal pain (23%), hypophosphatemia (23%), back pain (20%), and dry skin (20%).

Drug Interactions

Avoid concomitant use of strong and moderate CYP3A inhibitors with PEMAZYRE. Reduce the dose of PEMAZYRE if concomitant use with a strong or moderate CYP3A inhibitor cannot be avoided. Avoid concomitant use of strong and moderate CYP3A inducers with PEMAZYRE.

Special Populations

Advise lactating women not to breastfeed during treatment with PEMAZYRE and for 1 week after the last dose.

Reduce the recommended dose of PEMAZYRE for patients with severe renal impairment as described in the prescribing information.

Reduce the recommended dose of PEMAZYRE for patients with severe hepatic impairment as described in the prescribing information.

INDICATIONS AND USAGE

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.

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).