Pemazyre (pemigatinib)

• Eye problems. Certain eye problems are common with Pemazyre but can also be serious. Eye problems include dry eye or inflamed eyes, inflamed cornea (front part of the eye), increased tears, and a disorder of the retina (an internal part of the eye). You will need to see an eye specialist for a complete eye exam before you begin treatment with Pemazyre, every 2 months for the first 6 months, and then every 3 months during treatment with Pemazyre.
  • You should use artificial tears or substitutes, hydrating or lubricating eye gels as needed, to help prevent or treat dry eyes.
  • Tell your healthcare provider right away if you develop any changes in your vision during treatment with Pemazyre, including: blurred vision, flashes of light, or see black spots. You may need to see an eye specialist right away.
• High phosphate levels in your blood (hyperphosphatemia). Hyperphosphatemia is common with Pemazyre but can also be serious. Your healthcare provider will check your blood phosphate levels during treatment with Pemazyre.
  • Your healthcare provider may prescribe changes in your diet or phosphate lowering therapy, or change, interrupt or stop Pemazyre if needed.
  • Tell your healthcare provider right away if you develop any muscle cramps, or numbness or tingling around your mouth.

The most common side effects of Pemazyre include:

• hair loss
• diarrhea
• nails separate from the bed or poor formation of the nail
• feeling tired
• change in sense of taste
• nausea
• constipation
• mouth sores
• dry eyes
• dry mouth
• decrease in appetite
• vomiting
• joint pain
• stomach-area (abdominal) pain
• low phosphate in blood
• back pain
• dry skin

These are not all the possible side effects of Pemazyre. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Patient Selection

Select patients for the treatment of locally advanced or metastatic cholangiocarcinoma with Pemazyre based on the presence of an FGFR2 fusion or rearrangement as detected by an FDA-approved test.

Information on FDA-approved test(s) for the detection of an FGFR2 fusion or rearrangement in cholangiocarcinoma is available at http://www.fda.gov/CompanionDiagnostics.

Recommended Dosage

• The recommended dosage of Pemazyre 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.
• Take Pemazyre with or without food at approximately the same time every day.
• Swallow tablets whole. Do not crush, chew, split, or dissolve tablets.
• If the patient misses a dose of Pemazyre by 4 or more hours or if vomiting occurs, resume dosing with the next scheduled dose.

Dosage Modification For Adverse Reactions

• The recommended dose reductions for adverse reactions are provided in Table 1.

Table 1: Recommended Dose Reductions for Pemazyre for Adverse Reactions

• The recommended dosage modifications for adverse reactions are provided in Table 2.

Table 2: Recommended Dosage Modifications for Pemazyre Adverse Reactions

Dosage Modification For Concomitant Use With Strong Or Moderate CYP3A Inhibitors

Avoid concomitant use of strong and moderate CYP3A inhibitors with Pemazyre . If concomitant use with a strong or moderate CYP3A inhibitor cannot be avoided:

• Reduce Pemazyre dosage from 13.5 mg to 9 mg.
• Reduce Pemazyre dosage from 9 mg to 4.5 mg.

If concomitant use of a strong or moderate CYP3A inhibitor is discontinued, increase the Pemazyre dosage (after 3 plasma half-lives of the CYP3A inhibitor) to the dosage that was used before starting the strong or moderate inhibitor.

Recommended Dosage For Severe Renal Impairment

• The recommended dosage of Pemazyre for patients with severe renal impairment (eGFR estimated by MDRD 15 to 29 mL/min/1.73 m²) is 9 mg orally once daily for 14 consecutive days followed by 7 days off therapy, in 21-day cycles.

Recommended Dosage For Severe Hepatic Impairment

• The recommended dosage of Pemazyre for patients with severe hepatic impairment (total bilirubin > 3 × ULN with any AST) is 9 mg orally once daily for 14 consecutive days followed by 7 days off therapy, in 21-day cycles.

Effect 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, 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, 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.

• 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.
• There are no available data on the use of Pemazyre in pregnant women.
• There are no data on the presence of pemigatinib or its metabolites in human milk or their effects on either the breastfed child or on milk production.
• Because of the potential for serious adverse reactions in breastfed children from Pemazyre, women should not breastfeed during treatment and for 1 week after the final dose.