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  • CLASSES

    Small Molecule Antineoplastic Fibroblast Growth Factor Receptor (FGFR) Inhibitors

    DEA CLASS

    Rx

    DESCRIPTION

    Kinase inhibitor that inhibits FGFR1, FGFR2, FGFR3, and FGFR4
    Used for certain types of locally advanced or metastatic urothelial carcinoma
    Adjust doses based on serum phosphate levels and perform regular ophthalmological examinations

    COMMON BRAND NAMES

    Balversa

    HOW SUPPLIED

    BALVERSA/Erdafitinib Oral Tab: 3mg, 4mg, 5mg

    DOSAGE & INDICATIONS

    For the treatment urothelial carcinoma.
    NOTE: Select patients for treatment based on the presence of susceptible FGFR genetic alterations in tumor specimens. Information on FDA-approved tests for the detection of FGFR genetic alterations in urothelial cancer is available at http://www.fda.gov/CompanionDiagnostics.
    For the treatment of locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 or FGFR2 genetic alterations, that has progressed during or following at least one prior line of platinum-based chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-based chemotherapy.
    Oral dosage
    Adults

    8 mg PO once daily initially. After 14 to 21 days of treatment, increase the dose to 9 mg PO once daily if the serum phosphate level is less than 5.5 mg/dL and there are no ocular disorders or grade 2 or higher adverse reactions. Continue treatment until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Treatment of progressive, locally advanced or metastatic urothelial carcinoma with FGFR3 gene mutations or FGFR gene fusions with erdafitinib (n = 87) resulted in a confirmed objective response rate (ORR) of 40%, with 3% complete responses; the median duration of response was 5.6 months. Responders included patients who had previously not responded to anti-PD-L1/PD-1 therapy. In a subgroup analysis by FGFR genetic alterations, the ORR was 49% in patients with an FGFR3 point mutation (n = 74), 16% in patients with an FGFR2/3 fusion (n = 25), and 0% in patients with an FGFR2 fusion.[64064]

    MAXIMUM DOSAGE

    Adults

    9 mg PO once daily.

    Geriatric

    9 mg PO once daily.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Oral Administration

    Swallow tablets whole, with or without food.
    If vomiting occurs, do not replace the dose; the next dose should be taken the next day.
    If a dose is missed, it can be taken as soon as possible on the same day; do not take extra tablets to make up for the missed dose. Resume the regular daily schedule on the next day.

    STORAGE

    Balversa:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Hyperphosphatemia

    Avoid coadministration with agents that alter serum phosphate levels before the initial dose increase period (days 14 to 21), as this may interfere with the determination of the initial dose of erdafitinib. Monitor phosphate levels monthly for hyperphosphatemia and follow dose modification guidelines when required. In patients with hyperphosphatemia, restrict phosphate intake to 600 mg to 800 mg daily. If serum phosphate is above 7 mg/dL, consider adding an oral phosphate binder until the serum phosphate level returns to less than 5.5 mg/dL. Hyperphosphatemia is a commonly reported adverse reaction in patients treated with erdafitinib, as increases in phosphate levels are a pharmacodynamic effect of erdafitinib.[64064]

    Ocular disease, visual disturbance

    Use erdafitinib with caution in patients with a history of ocular disease. Erdafitinib can cause ocular disorders, including central serous retinopathy (CSR)/retinal pigment epithelial detachment (RPED) resulting in visual field defect. Dry eye symptoms were also commonly reported; all patients should receive dry eye prophylaxis with ocular demulcents as needed. Perform monthly ophthalmological examinations during the first 4 months of treatment and every 3 months thereafter, and urgently at any time for visual disturbance; examinations should include an assessment of visual acuity, slit lamp examination, fundoscopy, and optical coherence tomography. An interruption of therapy, discontinuation of therapy, or dose reduction may be necessary for ocular adverse reactions.[64064]

    Poor metabolizers

    Monitor for increased erdafitinib-related adverse reactions in patients who are known or suspected to be poor metabolizers with the CYP2C9*3/*3 genotype; erdafitinib plasma concentrations were predicted to be higher in patients with this genotype.

    Pregnancy

    Pregnancy should be avoided by females of reproductive potential during erdafitinib treatment and for at least 1 month after the last dose. Although there are no adequately controlled studies in pregnant women, erdafitinib can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving erdafitinib should be apprised of the potential hazard to the fetus. In an embryo-fetal toxicity study, oral administration of erdafitinib to pregnant rats during organogenesis caused malformations and embryofetal death at less than 0.1% of total human exposures at the maximum recommended human dose based on AUC, including embryo-fetal death, major blood vessel malformations and other vascular anomalies, limb malformations (e.g., ectrodactyly, absent or misshapen long bones), an increased incidence of skeletal anomalies in multiple bones (e.g., vertebrae, sternebrae, ribs), and decreased fetal weight.

    Contraception requirements, infertility, male-mediated teratogenicity, pregnancy testing, reproductive risk

    Counsel patients about the reproductive risk and contraception requirements during erdafitinib treatment. Erdafitinib can be teratogenic if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during and for 1 month after the last dose of erdafitinib. Due to the risk of male-mediated teratogenicity, men with female partners of reproductive potential should also use effective contraception during treatment and for 1 month after the last dose. Females of reproductive potential should undergo pregnancy testing prior to initiation of erdafitinib. Women who become pregnant while receiving erdafitinib should be apprised of the potential hazard to the fetus. Although there are no data regarding the effect of erdafitinib on human fertility, female infertility has been observed in animal studies.

    Breast-feeding

    Due to the potential for serious adverse reactions in nursing infants from erdafitinib, advise women to discontinue breast-feeding during treatment and for 1 month after the final dose. It is not known whether erdafitinib is present in human milk, although many drugs are excreted in human milk.

    ADVERSE REACTIONS

    Severe

    infection / Delayed / 20.0-20.0
    hyponatremia / Delayed / 16.0-16.0
    hyperkalemia / Delayed / 16.0-16.0
    fatigue / Early / 10.0-10.0
    onycholysis / Delayed / 10.0-10.0
    hypophosphatemia / Delayed / 9.0-9.0
    stomatitis / Delayed / 9.0-9.0
    xerophthalmia / Early / 6.0-6.0
    palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / 6.0-6.0
    renal failure (unspecified) / Delayed / 5.0-5.0
    hypercalcemia / Delayed / 3.0-3.0
    retinopathy / Delayed / 3.0-3.0
    retinal detachment / Delayed / 3.0-3.0
    anemia / Delayed / 3.0-3.0
    vomiting / Early / 2.0-2.0
    abdominal pain / Early / 2.0-2.0
    diarrhea / Early / 2.0-2.0
    dyspnea / Early / 2.0-2.0
    hematuria / Delayed / 2.0-2.0
    neutropenia / Delayed / 2.0-2.0
    hypomagnesemia / Delayed / 1.0-1.0
    hyperphosphatemia / Delayed / 1.0-1.0
    constipation / Delayed / 1.0-1.0
    nausea / Early / 1.0-1.0
    dysgeusia / Early / 1.0-1.0
    fever / Early / 1.0-1.0
    thrombocytopenia / Delayed / 1.0-1.0
    elevated hepatic enzymes / Delayed / 0-1.0
    keratitis / Delayed / 1.0
    corneal erosion / Delayed / Incidence not known

    Moderate

    hypoalbuminemia / Delayed / 37.0-37.0
    blurred vision / Early / 17.0-17.0
    leukopenia / Delayed / 17.0-17.0
    conjunctivitis / Delayed / 11.0-11.0
    hyperglycemia / Delayed / 10.0-10.0

    Mild

    xerostomia / Early / 45.0-45.0
    anorexia / Delayed / 38.0-38.0
    xerosis / Delayed / 34.0-34.0
    alopecia / Delayed / 26.0-26.0
    musculoskeletal pain / Early / 20.0-20.0
    weight loss / Delayed / 16.0-16.0
    nail discoloration / Delayed / 11.0-11.0
    arthralgia / Delayed / 11.0-11.0
    lacrimation / Early / 10.0-10.0
    foreign body sensation / Rapid / Incidence not known
    malaise / Early / Incidence not known
    lethargy / Early / Incidence not known
    asthenia / Delayed / Incidence not known
    back pain / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Butalbital: (Major) If coadministration of erdafitinib and butalbital is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If butalbital must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If butalbital is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer.
    Acetaminophen; Butalbital; Caffeine: (Major) If coadministration of erdafitinib and butalbital is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If butalbital must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If butalbital is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Major) If coadministration of erdafitinib and butalbital is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If butalbital must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If butalbital is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer.
    Alfentanil: (Major) Avoid coadministration of erdafitinib with alfentanil due to the potential for altered plasma concentrations of alfentanil which may lead to loss of activity or increased toxicity of alfentanil. Alfentanil is a sensitive CYP3A4 substrate with a narrow therapeutic range. Erdafitinib is a time dependent inhibitor and inducer of CYP3A4; the effect of erdafitinib on a sensitive CYP3A4 substrate is unknown.
    Alogliptin; Metformin: (Moderate) Consider the benefits and risks of concomitant treatment with metformin and erdafitinib. Metformin is a substrate of organic cationic transporter-2 (OCT2). Erdafitinib is an OCT2 inhibitor. Coadministration with OCT2 inhibitors could increase systemic exposure to metformin and increase the risk for lactic acidosis.
    Aluminum Hydroxide: (Major) Avoid coadministration of aluminum hydroxide with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Aluminum hydroxide decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by aluminum hydroxide may interfere with the determination of this initial dose increase.
    Aluminum Hydroxide; Magnesium Carbonate: (Major) Avoid coadministration of aluminum hydroxide with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Aluminum hydroxide decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by aluminum hydroxide may interfere with the determination of this initial dose increase.
    Aluminum Hydroxide; Magnesium Hydroxide: (Major) Avoid coadministration of aluminum hydroxide with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Aluminum hydroxide decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by aluminum hydroxide may interfere with the determination of this initial dose increase.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Major) Avoid coadministration of aluminum hydroxide with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Aluminum hydroxide decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by aluminum hydroxide may interfere with the determination of this initial dose increase.
    Aluminum Hydroxide; Magnesium Trisilicate: (Major) Avoid coadministration of aluminum hydroxide with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Aluminum hydroxide decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by aluminum hydroxide may interfere with the determination of this initial dose increase.
    Amobarbital: (Major) If coadministration of erdafitinib and amobarbital is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If amobarbital must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If amobarbital is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and amobarbital is a moderate CYP3A4 inducer.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Avoid coadministration of erdafitinib and clarithromycin due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If clarithromycin is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of erdafitinib and clarithromycin due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If clarithromycin is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Apalutamide: (Major) Avoid coadministration of erdafitinib and apalutamide due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer.
    Aspirin, ASA; Butalbital; Caffeine: (Major) If coadministration of erdafitinib and butalbital is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If butalbital must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If butalbital is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) If coadministration of erdafitinib and butalbital is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If butalbital must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If butalbital is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer.
    Atazanavir: (Major) Avoid coadministration of erdafitinib and atazanavir due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If atazanavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Atazanavir; Cobicistat: (Major) Avoid coadministration of erdafitinib and atazanavir due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If atazanavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor. (Major) Avoid coadministration of erdafitinib and cobicistat due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If cobicistat is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Major) Avoid coadministration of erdafitinib and phenobarbital due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Avoid coadministration of erdafitinib and phenobarbital due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer.
    Bexarotene: (Major) If coadministration of erdafitinib and bexarotene is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If bexarotene must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If bexarotene is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer.
    Bosentan: (Major) If coadministration of erdafitinib and bosentan is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If bosentan must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If bosentan is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 and CYP2C9 substrate. Bosentan is a moderate CYP3A4 and CYP2C9 inducer.
    Burosumab: (Major) Avoid coadministration of burosumab with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Burosumab increases serum phosphate levels. Erdafitinib causes hyperphosphatemia as a consequence of FGFR inhibition. Changes in serum phosphate levels by burosumab may interfere with the determination of this initial dose increase and may cause additive hyperphosphatemia.
    Butabarbital: (Major) If coadministration of erdafitinib and butabarbital is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If butabarbital must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If butabarbital is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and butabarbital is a moderate CYP3A4 inducer.
    Calcitriol: (Major) Avoid coadministration of calcitriol with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Calcitriol can increase serum phosphate levels. Erdafitinib causes hyperphosphatemia as a consequence of FGFR inhibition; additionally, the initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels. Changes in serum phosphate levels by calcitriol may interfere with the determination of this initial dose increase and may cause additive hyperphosphatemia.
    Calcium Acetate: (Major) Avoid coadministration of calcium acetate with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Calcium acetate decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by calcium acetate may interfere with the determination of this initial dose increase.
    Calcium Carbonate: (Major) Avoid coadministration of calcium carbonate with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Calcium carbonate decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by calcium carbonate may interfere with the determination of this initial dose increase.
    Calcium Carbonate; Magnesium Hydroxide: (Major) Avoid coadministration of calcium carbonate with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Calcium carbonate decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by calcium carbonate may interfere with the determination of this initial dose increase.
    Calcium Carbonate; Risedronate: (Major) Avoid coadministration of calcium carbonate with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Calcium carbonate decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by calcium carbonate may interfere with the determination of this initial dose increase.
    Calcium Carbonate; Simethicone: (Major) Avoid coadministration of calcium carbonate with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Calcium carbonate decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by calcium carbonate may interfere with the determination of this initial dose increase.
    Canagliflozin; Metformin: (Moderate) Consider the benefits and risks of concomitant treatment with metformin and erdafitinib. Metformin is a substrate of organic cationic transporter-2 (OCT2). Erdafitinib is an OCT2 inhibitor. Coadministration with OCT2 inhibitors could increase systemic exposure to metformin and increase the risk for lactic acidosis.
    Carbamazepine: (Major) Avoid coadministration of erdafitinib and carbamazepine due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 and CYP2C9 substrate; carbamazepine is a strong CYP3A4 inducer as well as a CYP2C9 inducer.
    Ceritinib: (Major) Avoid coadministration of erdafitinib and ceritinib due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If ceritinib is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Chloramphenicol: (Major) Avoid coadministration of erdafitinib and chloramphenicol due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If chloramphenicol is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Clarithromycin: (Major) Avoid coadministration of erdafitinib and clarithromycin due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If clarithromycin is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Cobicistat: (Major) Avoid coadministration of erdafitinib and cobicistat due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If cobicistat is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Conivaptan: (Major) Avoid coadministration of erdafitinib and conivaptan due to the risk of increased plasma concentrations of erdafitinib; subsequent treatment with erdafitinib should be initiated no sooner than 1 week after the infusion of conivaptan is completed. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If conivaptan is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and conivaptan is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Cyclosporine: (Major) Avoid coadministration of cyclosporine with erdafitinib due to the risk of increased plasma concentrations of cyclosporine. If concomitant use is unavoidable, separate erdafitinib administration by at least 6 hours before or after administration of cyclosporine; monitor cyclosporine levels. Cyclosporine is a P-glycoprotein (P-gp) substrate with a narrow therapeutic index and erdafitinib is a P-gp inhibitor.
    Dabrafenib: (Major) If coadministration of erdafitinib and dabrafenib is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If dabrafenib must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If dabrafenib is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer.
    Dapagliflozin; Metformin: (Moderate) Consider the benefits and risks of concomitant treatment with metformin and erdafitinib. Metformin is a substrate of organic cationic transporter-2 (OCT2). Erdafitinib is an OCT2 inhibitor. Coadministration with OCT2 inhibitors could increase systemic exposure to metformin and increase the risk for lactic acidosis.
    Darunavir: (Major) Avoid coadministration of erdafitinib and darunavir due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If darunavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Darunavir; Cobicistat: (Major) Avoid coadministration of erdafitinib and cobicistat due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If cobicistat is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor. (Major) Avoid coadministration of erdafitinib and darunavir due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If darunavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of erdafitinib and cobicistat due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If cobicistat is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor. (Major) Avoid coadministration of erdafitinib and darunavir due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If darunavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of erdafitinib and ritonavir due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If ritonavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Delavirdine: (Major) Avoid coadministration of erdafitinib and delavirdine due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If delavirdine is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Dexamethasone: (Major) If coadministration of erdafitinib and dexamethasone is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If dexamethasone must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If dexamethasone is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and dexamethasone is a moderate CYP3A4 inducer.
    Digoxin: (Major) Avoid coadministration of digoxin with erdafitinib due to the risk of increased plasma concentrations of digoxin. If concomitant use is unavoidable, separate erdafitinib administration by at least 6 hours before or after administration of digoxin; monitor digoxin levels. Digoxin is a P-glycoprotein (P-gp) substrate with a narrow therapeutic index and erdafitinib is a P-gp inhibitor.
    Dihydrotachysterol: (Major) Avoid coadministration of dihydrotachysterol with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Dihydrotachysterol can increase serum phosphate levels. Erdafitinib causes hyperphosphatemia as a consequence of FGFR inhibition. Changes in serum phosphate levels by dihydrotachysterol may interfere with the determination of this initial dose increase and may cause additive hyperphosphatemia.
    Dofetilide: (Severe) Coadministration of dofetilide with erdafitinib is contraindicated due to the risk of increased dofetilide exposure which may be associated with QT prolongation. Dofetilide is eliminated in the kidney by cationic secretion. Erdafitinib is an inhibitor of the renal uptake transporter organic cation transporter 2 (OCT2).
    Efavirenz: (Major) If coadministration of erdafitinib and efavirenz is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If efavirenz must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If efavirenz is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer.
    Efavirenz; Emtricitabine; Tenofovir: (Major) If coadministration of erdafitinib and efavirenz is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If efavirenz must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If efavirenz is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) If coadministration of erdafitinib and efavirenz is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If efavirenz must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If efavirenz is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer.
    Elagolix: (Major) If coadministration of erdafitinib and elagolix is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If elagolix must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If elagolix is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and elagolix is a moderate CYP3A4 inducer.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of erdafitinib and cobicistat due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If cobicistat is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of erdafitinib and cobicistat due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If cobicistat is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Empagliflozin; Metformin: (Moderate) Consider the benefits and risks of concomitant treatment with metformin and erdafitinib. Metformin is a substrate of organic cationic transporter-2 (OCT2). Erdafitinib is an OCT2 inhibitor. Coadministration with OCT2 inhibitors could increase systemic exposure to metformin and increase the risk for lactic acidosis.
    Enzalutamide: (Major) Avoid coadministration of erdafitinib and enzalutamide due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 and CYP2C9 substrate; enzalutamide is a strong CYP3A4 inducer as well as a CYP2C9 inducer.
    Ertugliflozin; Metformin: (Moderate) Consider the benefits and risks of concomitant treatment with metformin and erdafitinib. Metformin is a substrate of organic cationic transporter-2 (OCT2). Erdafitinib is an OCT2 inhibitor. Coadministration with OCT2 inhibitors could increase systemic exposure to metformin and increase the risk for lactic acidosis.
    Eslicarbazepine: (Major) If coadministration of erdafitinib and eslicarbazepine is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If eslicarbazepine must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If eslicarbazepine is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer.
    Etravirine: (Major) If coadministration of erdafitinib and etravirine is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If etravirine must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If etravirine is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer.
    Everolimus: (Major) Avoid coadministration of erdafitinib with everolimus due to the potential for altered plasma concentrations of everolimus which may lead to loss of activity or increased toxicity of everolimus. Everolimus is a sensitive CYP3A4 substrate with a narrow therapeutic range. Erdafitinib is a time dependent inhibitor and inducer of CYP3A4; the effect of erdafitinib on a sensitive CYP3A4 substrate is unknown. Everolimus is also a P-glycoprotein (P-gp) substrate and erdafitinib is a P-gp inhibitor.
    Fluconazole: (Major) Avoid coadministration of erdafitinib and fluconazole due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If fluconazole is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 and CYP2C9 substrate; fluconazole is a CYP2C9 and CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 121% and 148%, respectively, when coadministered with fluconazole.
    Fosamprenavir: (Major) Avoid coadministration of erdafitinib and fosamprenavir due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If fosamprenavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and fosamprenavir is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Fosphenytoin: (Major) Avoid coadministration of erdafitinib and fosphenytoin due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer.
    Glipizide; Metformin: (Moderate) Consider the benefits and risks of concomitant treatment with metformin and erdafitinib. Metformin is a substrate of organic cationic transporter-2 (OCT2). Erdafitinib is an OCT2 inhibitor. Coadministration with OCT2 inhibitors could increase systemic exposure to metformin and increase the risk for lactic acidosis.
    Glyburide; Metformin: (Moderate) Consider the benefits and risks of concomitant treatment with metformin and erdafitinib. Metformin is a substrate of organic cationic transporter-2 (OCT2). Erdafitinib is an OCT2 inhibitor. Coadministration with OCT2 inhibitors could increase systemic exposure to metformin and increase the risk for lactic acidosis.
    Grapefruit juice: (Major) Advise patients to avoid grapefruit juice while taking erdafitinib due to increased erdafitinib exposure. Erdafitinib is a CYP3A4 substrate and grapefruit juice is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Avoid coadministration of sodium phosphates with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Sodium phosphates increase serum phosphate levels. Erdafitinib causes hyperphosphatemia as a consequence of FGFR inhibition. Changes in serum phosphate levels by sodium phosphate may interfere with the determination of this initial dose increase and may cause additive hyperphosphatemia.
    Ibritumomab Tiuxetan: (Major) Avoid coadministration of potassium phosphate with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Potassium phosphate increases serum phosphate levels. Erdafitinib causes hyperphosphatemia as a consequence of FGFR inhibition. Changes in serum phosphate levels by potassium phosphate may interfere with the determination of this initial dose increase and may cause additive hyperphosphatemia. (Major) Avoid coadministration of sodium phosphates with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Sodium phosphates increase serum phosphate levels. Erdafitinib causes hyperphosphatemia as a consequence of FGFR inhibition. Changes in serum phosphate levels by sodium phosphate may interfere with the determination of this initial dose increase and may cause additive hyperphosphatemia.
    Idelalisib: (Major) Avoid coadministration of erdafitinib and idelalisib due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If idelalisib is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Indinavir: (Major) Avoid coadministration of erdafitinib and indinavir due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If indinavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and indinavir is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Iron Sucrose, Sucroferric Oxyhydroxide: (Major) Avoid coadministration of iron sucrose; sucroferric oxyhydroxide with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Iron sucrose; sucroferric oxyhydroxide decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by iron sucrose; sucroferric oxyhydroxide may interfere with the determination of this initial dose increase.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid the concomitant use of erdafitinib and rifampin due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 and CYP2C9 substrate; rifampin is a strong CYP3A4 and CYP2C9 inducer. Simulations suggested that rifampin may significantly decrease erdafitinib Cmax and AUC.
    Isoniazid, INH; Rifampin: (Major) Avoid the concomitant use of erdafitinib and rifampin due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 and CYP2C9 substrate; rifampin is a strong CYP3A4 and CYP2C9 inducer. Simulations suggested that rifampin may significantly decrease erdafitinib Cmax and AUC.
    Itraconazole: (Major) Avoid the concomitant use of erdafitinib and itraconazole due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If itraconazole is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and itraconazole is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with itraconazole.
    Ketoconazole: (Major) Avoid coadministration of erdafitinib and ketoconazole due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If ketoconazole is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Lanthanum Carbonate: (Major) Avoid coadministration of lanthanum carbonate with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Lanthanum carbonate decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by lanthanum carbonate may interfere with the determination of this initial dose increase.
    Linagliptin; Metformin: (Moderate) Consider the benefits and risks of concomitant treatment with metformin and erdafitinib. Metformin is a substrate of organic cationic transporter-2 (OCT2). Erdafitinib is an OCT2 inhibitor. Coadministration with OCT2 inhibitors could increase systemic exposure to metformin and increase the risk for lactic acidosis.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of erdafitinib and lopinavir due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If lopinavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and lopinavir is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor. (Major) Avoid coadministration of erdafitinib and ritonavir due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If ritonavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Lorlatinib: (Major) If coadministration of erdafitinib and lorlatinib is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If lorlatinib must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If lorlatinib is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer.
    Lumacaftor; Ivacaftor: (Major) Avoid coadministration of erdafitinib and lumacaftor; ivacaftor due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer.
    Lumacaftor; Ivacaftor: (Major) Avoid coadministration of erdafitinib and lumacaftor; ivacaftor due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer.
    Mephobarbital: (Major) Avoid coadministration of erdafitinib and mephobarbital due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 substrate and mephobarbital is a strong CYP3A4 inducer.
    Metformin: (Moderate) Consider the benefits and risks of concomitant treatment with metformin and erdafitinib. Metformin is a substrate of organic cationic transporter-2 (OCT2). Erdafitinib is an OCT2 inhibitor. Coadministration with OCT2 inhibitors could increase systemic exposure to metformin and increase the risk for lactic acidosis.
    Metformin; Pioglitazone: (Moderate) Consider the benefits and risks of concomitant treatment with metformin and erdafitinib. Metformin is a substrate of organic cationic transporter-2 (OCT2). Erdafitinib is an OCT2 inhibitor. Coadministration with OCT2 inhibitors could increase systemic exposure to metformin and increase the risk for lactic acidosis.
    Metformin; Repaglinide: (Moderate) Consider the benefits and risks of concomitant treatment with metformin and erdafitinib. Metformin is a substrate of organic cationic transporter-2 (OCT2). Erdafitinib is an OCT2 inhibitor. Coadministration with OCT2 inhibitors could increase systemic exposure to metformin and increase the risk for lactic acidosis.
    Metformin; Rosiglitazone: (Moderate) Consider the benefits and risks of concomitant treatment with metformin and erdafitinib. Metformin is a substrate of organic cationic transporter-2 (OCT2). Erdafitinib is an OCT2 inhibitor. Coadministration with OCT2 inhibitors could increase systemic exposure to metformin and increase the risk for lactic acidosis.
    Metformin; Saxagliptin: (Moderate) Consider the benefits and risks of concomitant treatment with metformin and erdafitinib. Metformin is a substrate of organic cationic transporter-2 (OCT2). Erdafitinib is an OCT2 inhibitor. Coadministration with OCT2 inhibitors could increase systemic exposure to metformin and increase the risk for lactic acidosis.
    Metformin; Sitagliptin: (Moderate) Consider the benefits and risks of concomitant treatment with metformin and erdafitinib. Metformin is a substrate of organic cationic transporter-2 (OCT2). Erdafitinib is an OCT2 inhibitor. Coadministration with OCT2 inhibitors could increase systemic exposure to metformin and increase the risk for lactic acidosis.
    Methenamine; Sodium Acid Phosphate: (Major) Avoid coadministration of sodium phosphates with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Sodium phosphates increase serum phosphate levels. Erdafitinib causes hyperphosphatemia as a consequence of FGFR inhibition. Changes in serum phosphate levels by sodium phosphate may interfere with the determination of this initial dose increase and may cause additive hyperphosphatemia.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Avoid coadministration of sodium phosphates with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Sodium phosphates increase serum phosphate levels. Erdafitinib causes hyperphosphatemia as a consequence of FGFR inhibition. Changes in serum phosphate levels by sodium phosphate may interfere with the determination of this initial dose increase and may cause additive hyperphosphatemia.
    Methohexital: (Major) If coadministration of erdafitinib and methohexital is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If methohexital must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If methohexital is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and methohexital is a moderate CYP3A4 inducer.
    Mifepristone: (Major) Avoid coadministration of erdafitinib and chronic mifepristone therapy due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If mifepristone is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Mitotane: (Major) Avoid coadministration of erdafitinib and mitotane due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer.
    Modafinil: (Major) If coadministration of erdafitinib and modafinil is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If modafinil must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If modafinil is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and modafinil is a moderate CYP3A4 inducer.
    Nafcillin: (Major) If coadministration of erdafitinib and nafcillin is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If nafcillin must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If nafcillin is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and nafcillin is a moderate CYP3A4 inducer.
    Nefazodone: (Major) Avoid coadministration of erdafitinib and nefazodone due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If nefazodone is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and nefazodone is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Nelfinavir: (Major) Avoid coadministration of erdafitinib and nelfinavir due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If nelfinavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and nelfinavir is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Nevirapine: (Major) If coadministration of erdafitinib and nevirapine is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If nevirapine must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If nevirapine is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of erdafitinib and ritonavir due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If ritonavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Pentobarbital: (Major) If coadministration of erdafitinib and pentobarbital is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If pentobarbital must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If pentobarbital is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and pentobarbital is a moderate CYP3A4 inducer.
    Phenobarbital: (Major) Avoid coadministration of erdafitinib and phenobarbital due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer.
    Phenytoin: (Major) Avoid coadministration of erdafitinib and phenytoin due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer.
    Posaconazole: (Major) Avoid coadministration of erdafitinib and posaconazole due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If posaconazole is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Potassium Phosphate: (Major) Avoid coadministration of potassium phosphate with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Potassium phosphate increases serum phosphate levels. Erdafitinib causes hyperphosphatemia as a consequence of FGFR inhibition. Changes in serum phosphate levels by potassium phosphate may interfere with the determination of this initial dose increase and may cause additive hyperphosphatemia.
    Potassium Phosphate; Sodium Phosphate: (Major) Avoid coadministration of potassium phosphate with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Potassium phosphate increases serum phosphate levels. Erdafitinib causes hyperphosphatemia as a consequence of FGFR inhibition. Changes in serum phosphate levels by potassium phosphate may interfere with the determination of this initial dose increase and may cause additive hyperphosphatemia. (Major) Avoid coadministration of sodium phosphates with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Sodium phosphates increase serum phosphate levels. Erdafitinib causes hyperphosphatemia as a consequence of FGFR inhibition. Changes in serum phosphate levels by sodium phosphate may interfere with the determination of this initial dose increase and may cause additive hyperphosphatemia.
    Primidone: (Major) Avoid coadministration of erdafitinib and primidone due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer.
    Ribociclib: (Major) Avoid coadministration of erdafitinib and ribociclib due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If ribociclib is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Ribociclib; Letrozole: (Major) Avoid coadministration of erdafitinib and ribociclib due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If ribociclib is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Rifabutin: (Major) If coadministration of erdafitinib and rifabutin is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If rifabutin must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If rifabutin is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer.
    Rifampin: (Major) Avoid the concomitant use of erdafitinib and rifampin due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 and CYP2C9 substrate; rifampin is a strong CYP3A4 and CYP2C9 inducer. Simulations suggested that rifampin may significantly decrease erdafitinib Cmax and AUC.
    Rifapentine: (Major) If coadministration of erdafitinib and rifapentine is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If rifapentine must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If rifapentine is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and rifapentine is a moderate CYP3A4 inducer.
    Rifaximin: (Major) If coadministration of erdafitinib and rifaximin is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If rifaximin must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21) in patients with hepatic impairment, increase the dose of erdafitinib up to 9 mg. If rifaximin is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate. In patients with normal liver function, rifaximin at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.
    Ritonavir: (Major) Avoid coadministration of erdafitinib and ritonavir due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If ritonavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Saquinavir: (Major) Avoid coadministration of erdafitinib and saquinavir due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If saquinavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and saquinavir is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Secobarbital: (Major) If coadministration of erdafitinib and secobarbital is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If secobarbital must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If secobarbital is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and secobarbital is a moderate CYP3A4 inducer.
    Sevelamer: (Major) Avoid coadministration of sevelamer with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Sevelamer decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by sevelamer may interfere with the determination of this initial dose increase.
    Sirolimus: (Major) Avoid coadministration of erdafitinib with sirolimus due to the potential for altered plasma concentrations of sirolimus which may lead to loss of activity or increased toxicity of sirolimus. Sirolimus is a sensitive CYP3A4 substrate with a narrow therapeutic range. Erdafitinib is a time dependent inhibitor and inducer of CYP3A4; the effect of erdafitinib on a sensitive CYP3A4 substrate is unknown. Sirolimus is also a P-glycoprotein (P-gp) substrate and erdafitinib is a P-gp inhibitor.
    Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Major) Avoid coadministration of sodium phosphates with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Sodium phosphates increase serum phosphate levels. Erdafitinib causes hyperphosphatemia as a consequence of FGFR inhibition. Changes in serum phosphate levels by sodium phosphate may interfere with the determination of this initial dose increase and may cause additive hyperphosphatemia.
    St. John's Wort, Hypericum perforatum: (Major) Avoid the concomitant use of erdafitinib and St. John's Wort due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 and CYP2C9 substrate; St. John's Wort is a strong CYP3A4 and CYP2C9 inducer.
    Tacrolimus: (Major) Avoid coadministration of erdafitinib with tacrolimus due to the potential for altered plasma concentrations of tacrolimus which may lead to loss of activity or increased toxicity of tacrolimus. Tacrolimus is a sensitive CYP3A4 substrate with a narrow therapeutic range. Erdafitinib is a time dependent inhibitor and inducer of CYP3A4; the effect of erdafitinib on a sensitive CYP3A4 substrate is unknown.
    Telithromycin: (Major) Avoid coadministration of erdafitinib and telithromycin due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If telithromycin is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Thiopental: (Major) If coadministration of erdafitinib and thiopental is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If thiopental must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If thiopental is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and thiopental is a moderate CYP3A4 inducer.
    Tipranavir: (Major) Avoid coadministration of erdafitinib and tipranavir due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If tipranavir is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and tipranavir is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
    Vincristine Liposomal: (Major) Avoid coadministration of sodium phosphates with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Sodium phosphates increase serum phosphate levels. Erdafitinib causes hyperphosphatemia as a consequence of FGFR inhibition. Changes in serum phosphate levels by sodium phosphate may interfere with the determination of this initial dose increase and may cause additive hyperphosphatemia.
    Voriconazole: (Major) Avoid coadministration of erdafitinib and voriconazole due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If voriconazole is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.

    PREGNANCY AND LACTATION

    Pregnancy

    Pregnancy should be avoided by females of reproductive potential during erdafitinib treatment and for at least 1 month after the last dose. Although there are no adequately controlled studies in pregnant women, erdafitinib can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving erdafitinib should be apprised of the potential hazard to the fetus. In an embryo-fetal toxicity study, oral administration of erdafitinib to pregnant rats during organogenesis caused malformations and embryofetal death at less than 0.1% of total human exposures at the maximum recommended human dose based on AUC, including embryo-fetal death, major blood vessel malformations and other vascular anomalies, limb malformations (e.g., ectrodactyly, absent or misshapen long bones), an increased incidence of skeletal anomalies in multiple bones (e.g., vertebrae, sternebrae, ribs), and decreased fetal weight.

    Due to the potential for serious adverse reactions in nursing infants from erdafitinib, advise women to discontinue breast-feeding during treatment and for 1 month after the final dose. It is not known whether erdafitinib is present in human milk, although many drugs are excreted in human milk.

    MECHANISM OF ACTION

    Erdafitinib is a kinase inhibitor that binds to and inhibits the enzymatic activity of FGFR1, FGFR2, FGFR3, and FGFR4 based on in vitro data. It also binds to RET, CSF1R, PDGFRA, PDGFRB, FLT4, KIT, and VEGF2. Erdafitinib inhibited FGFR phosphorylation and signaling and decreased cell viability in cell lines expressing FGFR genetic alterations including point mutations, amplifications, and fusions. It demonstrated antitumor activity in FGFR-expressing cell lines and xenograft models derived from tumor types, including bladder cancer.

    PHARMACOKINETICS

    Erdafitinib is administered orally. It is 99.8% protein bound, primarily to alpha-1-acid glycoprotein. The mean apparent volume of distribution (Vd) of erdafitinib is 29 liters. The mean total apparent clearance (CL/F) was 0.362 L/hour, with a mean effective half-life of 59 hours. Steady-state was achieved after 2 weeks with once-daily dosing, and the mean accumulation ratio was 4-fold. Following a single oral dose of radiolabeled erdafitinib, approximately 69% of the dose was recovered in feces (19% as unchanged drug) and 19% in urine (13% as unchanged drug).[64064]
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP2C9, CYP3A4, P-glycoprotein (P-gp)
    Erdafitinib is primarily metabolized by CYP2C9 (39%) and CYP3A4 (20%); unchanged erdafitinib was the major drug-related moiety in plasma and there were no circulating metabolites. Erdafitinib is a time-dependent inhibitor and inducer of CYP3A4 in vitro; however, the effect of erdafitinib on a sensitive CYP3A4 substrate is unknown. Erdafitinib is also a substrate and inhibitor of P-gp in vitro, although P-gp inhibitors are not expected to affect erdafitinib exposure to a clinically relevant extent; erdafitinib may increase plasma concentrations of P-gp substrates. Erdafitinib is an inhibitor of OCT2 in vitro.[64064]

    Oral Route

    Following administration of erdafitinib 8 mg once daily, the mean steady-state maximum observed plasma concentration (Cmax) was 1,399 ng/mL (CV, 51%), mean area under the curve (AUC) was 29,268 ng x hour/mL (CV, 60%), and mean minimum observed plasma concentration (Cmin) was 936 ng/mL (CV, 65%). The median time to achieve peak plasma concentration (Tmax) was 2.5 hours (range, 2 to 6 hours). Following single and repeat once daily dosing, erdafitinib exposure (Cmax and AUC) increased proportionally across the dose range of 0.5 mg to 12 mg (0.06 to 1.3 times the maximum approved recommended dose). Food did not have a clinically meaningful effect on erdafitinib pharmacokinetics.[64064]