pemigatinib

Absorption: Rapidly absorbed; extent of absorption unknown.

Distribution: Extensively distributed to tissues.

Protein Binding: 90.6%.

Metabolism/Excretion: Primarily metabolized in the liver via CYP3A4 isoenzyme. Primarily excreted in feces (82%; 1.4% unchanged), with 12.6% excreted in urine (1% unchanged).

Half-Life: 15.4 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1.1 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Severe renal impairment (dose ↓ required);
Severe hepatic impairment (dose ↓ required);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: peripheral edema

Derm: alopecia, dry skin, nail discoloration, nail hypertrophy, nail infection, palmar-plantar erythrodysesthesia syndrome

EENT: dry eyes, retinal pigment epithelial detachment, blurred vision, visual floaters

Endo: hyperglycemia, hypoglycemia

F and E: dehydration, hypercalcemia, hyperkalemia, hyperphosphatemia, hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia

GI: ↑liver enzymes, abdominal pain, constipation, diarrhea, dry mouth, hyperbilirubinemia, hypoalbuminemia, nausea, stomatitis, vomiting

GU: ↑serum creatinine, urinary tract infection

Hemat: anemia, leukocytosis, leukopenia, lymphocytopenia, thrombocytopenia

Metab: ↓appetite, ↓weight, hyperuricemia

MS: arthralgia, fractures

Neuro: dysgeusia, headache

Misc: fatigue

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including itraconazole, and moderate CYP3A4 inhibitors, may ↑ levels and risk of toxicity; avoid concurrent use, if possible; if must use concurrently, ↓ pemigatinib dose.
Strong CYP3A4 inducers, including rifampin, and moderate CYP3A4 inducers may ↓ levels and effectiveness; avoid concurrent use.

Route/Dosage ⬆ ⬇

Cholangiocarcinoma

PO (Adults ): 13.5 mg once daily for 14 days, followed by 7 days off of therapy (21-day cycle). Continue 21-day cycles of therapy until disease progression or unacceptable toxicity. Concurrent use of strong or moderate CYP3A4 inhibitors: If previously taking 13.5 mg once daily, ↓ to 9 mg once daily. If previously taking 9 mg once daily, ↓ to 4.5 mg once daily.

Renal Impairment

PO (Adults ): eGFR 15–29 mL/min/1.73 m²: 9 mg once daily for 14 days, followed by 7 days off of therapy (21-day cycle). Continue 21-day cycles of therapy until disease progression or unacceptable toxicity.

Hepatic Impairment

PO (Adults ): Severe hepatic impairment (total bilirubin >3 times upper limit of normal [ULN]): 9 mg once daily for 14 days, followed by 7 days off of therapy (21-day cycle). Continue 21-day cycles of therapy until disease progression or unacceptable toxicity.

Myeloid/Lymphoid Neoplasms

PO (Adults ): 13.5 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong or moderate CYP3A4 inhibitors: If previously taking 13.5 mg once daily, ↓ to 9 mg once daily. If previously taking 9 mg once daily, ↓ to 4.5 mg once daily.

Renal Impairment

PO (Adults ): eGFR 15–29 mL/min/1.73 m²: 9 mg once daily until disease progression or unacceptable toxicity.

Hepatic Impairment

PO (Adults ): Severe hepatic impairment (total bilirubin >3 times ULN): 9 mg once daily until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Tablets: 4.5 mg; 9 mg; 13.5 mg

Assessment ⬆ ⬇

Perform comprehensive ophthalmological exam, including OCT, before starting pemigatinib, every 2 mo for first 6 mo, and every 3 mo thereafter during therapy. If visual symptoms of retinal pigment epithelial detachment (blurred vision, visual floaters, photopsia) occur, refer patient for ophthalmologic evaluation urgently, with follow-up every 3 wk until resolution or discontinuation of pemigatinib. If asymptomatic and stable on serial examination, continue pemigatinib. If symptomatic or worsening on serial examination, hold pemigatinib. If asymptomatic and improved on subsequent examination, resume at a ↓ dose. If symptoms persist or do not improve, consider permanent discontinuation of pemigatinib.
Assess for dry eyes. Occurs frequently. Treat with ocular demulcents.

Lab Test Considerations:

Verify a negative pregnancy test before starting therapy.
- Patient selection is based on presence of an FGFR2 fusion or rearrangement as detected by an FDA-approved test. Information is available athttp://www.fda.gov/CompanionDiagnostics .
- Monitor for hyperphosphatemia periodically during therapy. Begin a low-phosphate diet when serum phosphate level >5.5 mg/dL. For serum phosphate level >7 mg/dL to ≤10 mg/dL, start phosphate-lowering therapy and monitor serum phosphate level weekly. If serum phosphate level ≥7 mg/dL within 2 wk of starting phosphate-lowering therapy, hold pemigatinib. When serum phosphate level <7 mg/dL, resume pemigatinib at same dose for 1st occurrence or at ↓ doses for subsequent occurrences. If serum phosphate level >10 mg/dL, start phosphate-lowering therapy and monitor serum phosphate level weekly. If serum phosphate level ≥10 mg/dL within 1 wk after starting phosphate-lowering therapy, hold pemigatinib. When serum phosphate level <7 mg/dL, resume pemigatinib at next lower dose. If serum phosphate level >10 mg/dL after two dose ↓, discontinue pemigatinib permanently.
- May cause ↑ or ↓ leukocytes and ↓ hemoglobin, lymphocytes, and platelets.
- May cause ↑ AST, ALT, alkaline phosphatase, and bilirubin and ↓ albumin.
- May cause ↑ or ↓ calcium, glucose, and potassium, and ↓ sodium.
- May cause ↑ uric acid and serum creatinine. Within first 21-day cycle, serum creatinine ↑ by a mean of 0.2 mg/dL, reached steady state by Day 8, and ↓ during 7 days off therapy. If ↑ serum creatinine persist, consider alternate measures of renal function. Calculate CCr using MDRD equation for dose adjustment.

Implementation ⬆ ⬇

Recommended dose reductions: Cholangiocarcinoma with FGFR2 fusion or rearrangement1st reduction:9 mg once daily for first 14 days of each 21-day cycle; 2nd reduction:4.5 mg once daily for first 14 days of each 21-day cycle; 3rd reduction:discontinue. Myeloid/lymphoid neoplasms with FGFR1 rearrangement1st reduction:9 mg once daily; 2nd reduction:4.5 mg once daily; 3rd reduction:4.5 mg once daily for first 14 days of each 21-day cycle. Permanently discontinue pemigatinib if unable to tolerate 4.5 mg once daily for 14 days of each 21-day cycle.
PO: Administer once daily at the same time each day, without regard to food. DNC: Swallow tablet whole; do not break, crush, chew, or dissolve.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Instruct patient to take pemigatinib as directed at same time each day. If patient vomits or dose is missed by ≥4 hr, take next dose at scheduled time. Emphasize importance of frequent eye exams and lab test to monitor for side effects.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications. Advise patient to avoid grapefruit products.
Advise patient to notify health care professional immediately if visual changes (blurred vision, flashes of light, seeing black spots) or signs and symptoms of hyperphosphatemia (muscle cramps, numbness, tingling around mouth) occur.
Inform patient that nail disorders and dry eyes may occur. Artificial tear or substitutes and hydrating or lubricating eye gels may be used prevent or treat dry eyes.
Rep: May cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception and to avoid breastfeeding during therapy and for 1 wk after last dose.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇