pemigatinib (Rx)

Brand and Other Names:Pemazyre
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 4.5mg
  • 9mg
  • 13.5mg

Cholangiocarcinoma

Indicated for unresectable locally advanced or metastatic cholangiocarcinoma in previously treated patients with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement

Each cycle is 21 days

13.5 mg PO qDay for 14 consecutive days followed by 7 days off therapy

Continue until disease progression or unacceptable toxicity occurs

Dosage Modifications

Dose reductions for adverse reactions

  • First dose reduction: 9 mg qDay for first 14 days of each 21-day cycle
  • Second dose reduction: 4.5 mg qDay for first 14 days of each 21-day cycle
  • Patients unable to tolerate 4.5 mg qDay: Permanently discontinue

Retinal pigment epithelial detachment (RPED)

  • Asymptomatic and stable on serial examination: Continue treatment
  • Symptomatic OR worsening on serial examination
    • Withhold; resume at a lower dose if asymptomatic and improved on subsequent examination
    • Symptoms persist or examination does not improve: Consider permanent discontinuation based on clinical status

Hyperphosphatemia

  • Initiate phosphate lowering therapy and monitor serum phosphate weekly
  • Serum phosphate >7 to ≤10 mg/dL
    • Withhold if levels are still ≥7 mg/dL within 2 weeks of starting phosphate lowering therapy
    • Resume 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
    • Withhold if levels are still >10 mg/dL within 1 week of starting phosphate lowering therapy
    • Resume at the next lower dose level when phosphate levels are <7 mg/dL
    • Permanently discontinue for recurrence of serum phosphate >10 mg/dL following 2 dose reductions

Other adverse reactions

  • Grade 3
    • Withhold until resolves to Grade ≤1; resume at next lower dose if resolves within 2 weeks
    • Permanently discontinue if unresolved within 2 weeks OR for recurrent Grade 3 after 2 dose reductions
  • Grade 4
    • Permanently discontinue

Coadministration with CYP3A inhibitors

  • Avoid coadministration
  • If use cannot be avoided, reduce dose (ie, 13.5 mg to 9 mg, 9 mg to 4.5 mg)
  • If strong or moderate CYP3A inhibitor is discontinued, increase pemigatinib dose (after 3 plasma half-lives of the CYP3A inhibitor) to dose taken before initiating inhibitor

Renal impairment

  • Mild or moderate (GFR ≥30 to <89 mL/min/1.73 m2): No dosage adjustment necessary
  • Severe (GFR <30 mL/min/1.73 m2): Reduce to 9 mg PO qDay for 14 consecutive days followed by 7 days off therapy for each 21-day cycle
  • End-stage renal disease (eGFR <15 mL/min/1.73 m2) who are receiving intermittent hemodialysis: No dosage adjustment necessary

Hepatic impairment

  • Mild or moderate (total bilirubin ≤3x ULN with any AST): No dosage adjustment necessary
  • Severe (total bilirubin >3x with any AST): Reduce to 9 mg PO qDay for 14 consecutive days followed by 7 days off therapy for each 21-day cycle

Dosing Considerations

Verify pregnancy status of females of reproductive potential before initiation

Patient selection

Safety and efficacy not established

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Interactions

Interaction Checker

and pemigatinib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            All grades

            • Increased phosphate (94%)
            • Decreased phosphate (68%)
            • Hyperphosphatemia (60%)
            • Alopecia (49%)
            • Diarrhea (47%)
            • Nail toxicity (43%)
            • Increased AST/ALT (43%)
            • Increased calcium (43%)
            • Decreased hemoglobin (43%)
            • Fatigue (42%)
            • Increased alkaline phosphatase (41%)
            • Increased creatinine (41%)
            • Nausea (40%)
            • Dysgeusia (40%)
            • Decreased sodium (39%)
            • Increased glucose (36%)
            • Decreased lymphocytes (36%)
            • Constipation (35%)
            • Stomatitis (35%)
            • Dry eye (35%)
            • Dry mouth (34%)
            • Decreased albumin (34%)
            • Decreased appetite (33%)
            • Increased urate (30%)
            • Decreased platelets (28%)
            • Increased leukocytes (27%)
            • Vomiting (27%)
            • Increased bilirubin (26%)
            • Decreased potassium (26%)
            • Arthralgia (25%)
            • Hypophosphatemia (23%)
            • Abdominal pain (23%)
            • Dry skin (20%)
            • Back pain (20%)
            • Pain in extremity (19%)
            • Decreased leukocytes (18%)
            • Peripheral edema (18%)
            • Decreased calcium (17%)
            • Headache (16%)
            • Urinary tract infection (16%)
            • Weight loss (16%)
            • Dehydration (15%)
            • Palmoplantar erythrodysesthesia syndrome (15%)
            • Increased potassium (12%)
            • Decreased glucose (11%)

            Grade ≥3

            • Decreased phosphate (38%)
            • Hypophosphatemia (12%)
            • Decreased sodium (12%)
            • Increased alkaline phosphatase (11%)

            1-10%

            Grade ≥3

            • Increased urate (10%)
            • Decreased lymphocytes (8%)
            • Decreased hemoglobin (6%)
            • Increased bilirubin (6%)
            • Increased AST (6%)
            • Arthralgia (6%)
            • Decreased potassium (5%)
            • Stomatitis (5%)
            • Abdominal pain (4.8%)
            • Fatigue (4.8%)
            • Increased calcium (4.1%)
            • Increased ALT (4.1%)
            • Palmoplantar erythrodysesthesia syndrome (4.1%)
            • Decreased platelets (3.4%)
            • Dehydration (3.4%)
            • Decreased calcium (2.7%)
            • Diarrhea (2.7%)
            • Back pain (2.7%)
            • Urinary tract infection (2.7%)
            • Increased potassium (2.1%)
            • Nail toxicity (2.1%)
            • Pain in extremity (2.1%)
            • Weight loss (2.1%)
            • Decreased leukocytes (1.4%)
            • Increased creatinine (1.4%)
            • Decreased glucose (1.4%)
            • Decreased appetite (1.4%)
            • Vomiting (1.4%)

            <1%

            Grade ≥3

            • Increased leukocytes (0.7%)
            • Increased glucose (0.7%)
            • Dry skin (0.7%)
            • Constipation (0.7%)
            • Peripheral edema (0.7%)
            • Dry eye (0.7%)
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            Warnings

            Contraindications

            None

            Cautions

            May cause RPED; symptoms include blurred vision, visual floaters, or photopsia; perform ophthalmological examination including optical coherence tomography before initiation, every 2 months for the first 6 months of therapy, and every 3 months thereafter, and, urgently at any time for visual symptoms

            Hyperphosphatemia reported; can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcification, calcinosis, and nonuremic calciphylaxis; monitor for hyperphosphatemia and initiate a low phosphate diet when serum phosphate level is >5.5 mg/dL

            Can cause fetal harm

            Drug interaction overview

            CYP3A4 substrate

            Also inhibits P-glycoprotein (P-gp), OCT2, and MATE1 in vitro; no clinically significant difference in glucose levels were observed when coadministered with metformin (OCT2/MATE1 substrate)

            Strong or moderate CYP3A inducers
            • Avoid coadministration
            • Strong or moderate CYP3A inducers decrease pemigatinib plasma concentrations, which may reduce the efficacy of pemigatinib
            Strong and moderate CYP3A4 inhibitors
            • Avoid coadministration; reduce pemigatinib dose, if concomitant use cannot be avoided
            • Strong or moderate CYP3A inhibitors increase pemigatinib plasma concentrations, which may increase the risk and severity of adverse reactions
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            Pregnancy & Lactation

            Pregnancy

            Based on animal data and its mechanism of action, fetal harm or loss of pregnancy may occur when administered to a pregnant females

            No data available on use in pregnant females

            Verify pregnancy status of females of reproductive potential before initiation

            Contraception

            • Females of reproductive potential or males with female partners of reproductive potential: Use effective contraception during treatment and for at least 1 week after final dose

            Animal data

            • Oral administration to pregnant rats during organogenesis at maternal plasma exposures below the human exposure at the 13.5-mg dose resulted in fetal malformations, fetal growth retardation, and embryofetal death
            • Advise pregnant women of the potential risk to a fetus

            Lactation

            No data available on the presence of pemigatinib or its metabolites in human milk or their effects on either the breastfed child or on milk production

            Advise females not to breastfeed during treatment and for 1 week after the final dose

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Orally bioavailable inhibitor of the FGFR types 1, 2, and 3 (FGFR1/2/3)

            Pemigatinib inhibits FGFR 1/2/3 phosphorylation and signaling, and decreases cell viability in cancer cell lines with activating FGFR amplifications and fusions

            Absorption

            Steady-state reached within 4 days following repeated once-daily dosing

            Peak plasma time: 1.13 hr

            Distribution

            Protein bound: 90.6%

            Vd: 235 L

            Metabolism

            Primarily metabolized by CYP3A4

            Elimination

            Half-life: 15.4 hr

            Clearance: 10.6 L/hr

            Excretion: Feces (82.4% [1.4% unchanged]); urine (12.6% [1% unchanged])

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            Administration

            Oral Administration

            Take with or without food at around the same time every day

            Swallow tablet whole; do not crush, chew, split, or dissolve tablet

            Missed dose by ≥4 hr or vomited dose: Resume dosing at next scheduled dose

            Storage

            Store at room temperature, 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

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            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.