Pemigatinib

Pemigatinib (brand name Pemazyre) is a targeted cancer treatment approved for two distinct types of cancer that carry specific FGFR gene changes.

• Pemazyre is approved to treat adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma (bile duct cancer) whose tumors have an FGFR2 fusion or rearrangement, confirmed by an FDA-approved diagnostic test. This approval is based on tumor response rates and duration of response; continued approval may depend on confirmatory trial results.
• Pemazyre is also approved for adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement — blood and bone marrow cancers that have come back or no longer respond to prior therapy.

Pemigatinib is a small molecule kinase inhibitor — it works by blocking proteins called FGFR1, FGFR2, and FGFR3. In certain cancers, gene fusions or rearrangements keep these proteins switched on all the time, continuously sending signals that tell cancer cells to grow and survive. By precisely blocking those overactive FGFR proteins, pemigatinib cuts off those growth signals, reducing cancer cell viability and slowing tumor growth.

Because of how it works, pemigatinib raises phosphate levels in the blood as an expected on-target effect — blocking FGFR also affects how the body handles phosphate. This is why monitoring and managing phosphate is a routine and important part of treatment.

Pemazyre comes as an oral tablet taken once daily. It can be taken with or without food, and should be taken at roughly the same time each day. Tablets must be swallowed whole — never crushed, chewed, split, or dissolved.

• For cholangiocarcinoma: Pemazyre is taken for 14 consecutive days, followed by 7 days off, repeating in 21-day cycles.
• For myeloid/lymphoid neoplasms with FGFR1 rearrangement: Pemazyre is taken once daily on a continuous (uninterrupted) schedule.
• If you miss a dose by 4 or more hours, or if you vomit after taking a dose, skip it and take the next dose at the usual time — do not double up.

Dose adjustments may be needed if you have severe kidney or liver disease, or if you take certain other medicines. Always follow your prescriber's instructions exactly.

Most people taking Pemazyre experience some side effects; the most common ones are manageable with supportive care and dose adjustments.

Serious reactions that require prompt medical attention include vision changes (possible retinal detachment), skin calcifications or lumps related to high phosphate, and signs of severe infection or organ problems. Contact your care team right away if any of these occur.

• Eye toxicity (RPED): Pemazyre can cause retinal pigment epithelial detachment — a separation of layers at the back of the eye — which may cause blurred vision, floaters, or light flashes. Regular eye exams including OCT (optical coherence tomography — a detailed eye scan) are required before starting treatment, every 2 months for the first 6 months, then every 3 months. Report any vision changes to your doctor immediately.
• High phosphate and soft tissue mineralization: Almost all patients develop elevated blood phosphate on this medicine. If not managed, phosphate can deposit in soft tissues, causing skin calcifications, calcinosis, or a rare dangerous skin condition called non-uremic calciphylaxis. Your doctor will monitor phosphate levels, recommend a low-phosphate diet when needed, and may prescribe phosphate-lowering medication.
• Embryo-fetal toxicity: This medicine can cause fetal harm, birth defects, or pregnancy loss. It must not be used during pregnancy. Both women and men of reproductive potential must use effective contraception during treatment and for 1 week after the last dose.

Pemigatinib is broken down mainly by a liver enzyme called CYP3A4, so medicines that affect this enzyme can significantly raise or lower pemigatinib levels in your blood.

• Strong or moderate CYP3A inhibitors (e.g., itraconazole, certain antifungals, some HIV medicines, some antibiotics) — raise pemigatinib blood levels, increasing the risk of serious side effects. Avoid combining if possible; if unavoidable, your Pemazyre dose will need to be reduced.
• Strong or moderate CYP3A inducers (e.g., rifampin, certain seizure or tuberculosis medicines) — lower pemigatinib blood levels significantly, potentially making the medicine less effective. Avoid combining.
• Pemigatinib can affect creatinine levels in blood tests by interfering with how the kidneys handle this waste product — this does not necessarily mean actual kidney damage, but your doctor should be aware of it when interpreting lab results.

Not a complete list. The label covers the interactions the manufacturer studied or reported, and our own interaction database does not cover every medicine either. Bring your full medication list, including vitamins and herbal products, to your pharmacist.

• Pregnancy: Do not take pemigatinib if you are pregnant. It can cause serious fetal harm, birth defects, or pregnancy loss. A pregnancy test should be done before starting treatment.
• Breastfeeding: Do not breastfeed during treatment or for 1 week after your last dose. The potential risk to a nursing infant is not known.
• Contraception: Women of childbearing potential must use effective contraception during treatment and for 1 week after the last dose. Men with female partners who could become pregnant must also use contraception during treatment and for 1 week after the last dose.
• Children: Safety and effectiveness have not been established in pediatric patients. Animal studies showed concerning effects on bone and tooth development.
• Severe kidney disease: A dose reduction is recommended for severe renal impairment. No adjustment is needed for mild-to-moderate kidney disease.
• Severe liver disease: A dose reduction is recommended for severe hepatic impairment. No adjustment is needed for mild-to-moderate liver disease.
• Older adults: No meaningful differences in safety or effectiveness were observed in patients 65 and older compared to younger patients.
• All medicines and supplements: Tell your doctor about all medicines, herbal products, and supplements you take before starting Pemazyre.

Because pemigatinib blocks FGFR proteins, one predictable effect is a rise in blood phosphate levels — this happens as a direct consequence of FGFR inhibition and occurs in the vast majority of patients. Higher doses produce higher phosphate levels and a greater risk of hyperphosphatemia. At doses up to 1.5 times the maximum recommended dose, pemigatinib does not cause a clinically meaningful change in the heart's electrical rhythm (QTc interval).

After an oral dose, pemigatinib is absorbed quickly, reaching peak blood levels in about 1 hour. Food — including a high-fat, high-calorie meal — does not meaningfully affect how much of the drug the body absorbs, so it can be taken with or without food. The drug is about 91% bound to proteins in the blood and is broken down mainly by the liver enzyme CYP3A4, with most of the drug leaving the body through the stool. The half-life (time for blood levels to drop by half) is approximately 15 hours, and steady blood levels are reached within about 4 days of once-daily dosing. People with severe liver impairment have significantly higher drug exposure, which is why a dose reduction is recommended for them.

Store PEMAZYRE tablets at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).