Pemazyre® (pemigatinib) tablets - Incyte Corporation



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Indications & Usage

INDICATIONS AND USAGE

 

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.

 

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).

 

 

Please see Full Prescribing Information for PEMAZYRE.

Dosage & Administration

DOSAGE AND ADMINISTRATION

 

·        Confirm the presence of an FGFR2 fusion or rearrangement prior to initiation of treatment with PEMAZYRE.

·        Recommended dose is 13.5 mg orally once daily for 14 consecutive days followed by 7 days off therapy in 21-day cycles. Continue treatment until disease progression or unacceptable toxicity occurs.

·        Swallow tablet whole, with or without food.

·        Severe renal impairment: the recommended dosage of PEMAZYRE is 9 mg orally once daily for 14 consecutive days followed by 7 days off therapy in 21-day cycles.

·        Severe Hepatic Impairment: the recommended dosage of PEMAZYRE is 9 mg orally once daily for 14 consecutive days followed by 7 days off therapy in 21-day cycles.

 

DOSAGE FORMS AND STRENGTHS

 

Tablets:  4.5 mg, 9 mg, and 13.5 mg.

 

 

Please see Full Prescribing Information for PEMAZYRE.

Contraindications

CONTRAINDICATIONS

 

None.

 

 

Please see Full Prescribing Information for PEMAZYRE.

Warnings & Precautions

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.

·        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.

·        Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to the fetus and use effective contraception.

 

 

Please see Full Prescribing Information for PEMAZYRE.

Adverse Reactions

ADVERSE REACTIONS

 

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.

 

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.

 

 

Please see Full Prescribing Information for PEMAZYRE.

Drug Interactions

DRUG INTERACTIONS

 

·        Strong and moderate CYP3A Inducers: Avoid concomitant use of PEMAZYRE.

·        Strong and moderate CYP3A inhibitors: Reduce the dose of PEMAZYRE, if concomitant use cannot be avoided.

 

 

Please see Full Prescribing Information for PEMAZYRE.

Use in Specific Populations

USE IN SPECIFIC POPULATIONS

 

·        Lactation: Advise not to breastfeed.

 

See section 17 of the Full Prescribing Information for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

 

 

Please see Full Prescribing Information for PEMAZYRE.

ICD Codes

ICD Codes

C22.1

Intrahepatic Bile Duct Carcinoma

C24.0

Malignant Neoplasm of Extrahepatic Bile Duct

 

 

  PEMAZYRE and the Incyte logo are registered trademarks of Incyte.
  The PEMAZYRE logo is a trademark of Incyte.
  ©2021, Incyte Corporation. MAT-PEM-00215 06/21

Please see Full Prescribing Information for PEMAZYRE



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 466 patients who received PEMAZYRE across clinical trials, RPED occurred in 6% of patients, including Grade 3-4 RPED in 0.6%. The median time to first onset of RPED was 62 days. RPED led to dose interruption of PEMAZYRE in 1.7% of patients, and dose reduction and permanent discontinuation in 0.4% and in 0.4% of patients, respectively. RPED resolved or improved to Grade 1 levels in 87.5% 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 466 patients who received PEMAZYRE across clinical trials, dry eye occurred in 27% of patients, including Grade 3-4 in 0.6% 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 466 patients who received PEMAZYRE across clinical trials, hyperphosphatemia was reported in 92% 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 29% 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 final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the final dose.

 

Adverse Reactions

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.

 

Clinically relevant adverse reactions occurring in 10% of patients included fractures (2.1%). In all patients treated with pemigatinib, 1.3% experienced pathologic fractures (which included patients with and without cholangiocarcinoma [N = 466]). 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.

 

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 final 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.

 

Please see Full Prescribing Information for PEMAZYRE.