Pemazyre (pemigatinib): Cancer Medication Side Effects & Dosage

Generic drug: pemigatinib

Brand name: Pemazyre

What is Pemazyre (pemigatinib), and how does it work?

Pemazyre (pemigatinib) is a prescription medicine that is used to treat adults with bile duct cancer (cholangiocarcinoma) that has spread or cannot be removed by surgery:

• who have already received a previous treatment, and
• whose tumor has a certain type of abnormal "FGFR2" gene.

Your healthcare provider will test your cancer for a certain type of abnormal FGFR2 gene and make sure that Pemazyre is right for you.

It is not known if Pemazyre is safe and effective in children.

What are the side effects of Pemazyre?

Pemazyre may cause serious side effects, including:

• 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.

What is the dosage for Pemazyre?

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

Dose ReductionRecommended DosageFirst9 mg once daily for first 14 days of each 21-day cycleSecond*4.5 mg once daily for first 14 days of each 21-day cycle* Permanently discontinue
Pemazyre if unable to tolerate 4.5 mg once daily.

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

Table 2: Recommended Dosage Modifications for Pemazyre Adverse Reactions

Adverse ReactionSeverity*
Pemazyre Dosage ModificationRetinal Pigment Epithelial
Detachment (RPED)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 Serum phosphate > 7 mg/dL- ≤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.
• 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.

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.
• 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 ReactionsGrade 3

• Withhold
  Pemazyre until resolves to Grade 1 or baseline.
• Resume Pemazyre at next lower dose if resolves within 2 weeks.
• Permanently discontinue
  Pemazyre if does not resolve within 2 weeks.
• Permanently discontinue
  Pemazyre for recurrent Grade 3 after 2 dose reductions.

Grade 4

• Permanently discontinue
  Pemazyre.

*Severity as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

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.

What drugs interact with Pemazyre?

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.

Is Pemazyre safe to use while pregnant or breastfeeding?

• 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.