Erdafitinib is a kinase inhibitor that inhibits FGFR1, FGFR2, FGFR3, and FGFR4. It is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma that has susceptible FGFR3 genetic alterations and has progressed during or following at least 1 line of systemic therapy; erdafitinib is not recommended for patients who are eligible for and have not received treatment with a PD-1 or PD-L1 inhibitor. As a consequence of FGFR inhibition, erdafitinib is associated with hyperphosphatemia; dose adjustments are necessary based on the serum phosphate level. Ocular disorders including central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED) are also common; ophthalmological examinations should be performed regularly.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Emetic Risk
-Minimal/Low
-Administer prn antiemetics as necessary.
Route-Specific 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.
Increases in phosphate levels are a pharmacodynamic effect of erdafitinib as a consequence of FGFR inhibition. Hyperphosphatemia was reported in 73% of patients with advanced urothelial carcinoma and FGFR alteration who received erdafitinib based on a pooled safety population (n = 479), with a median time to onset of 16 days; grade 3 or 4 increase in phosphate levels occurred in 1.2% to 5% of patients in 2 clinical trials. Phosphate binders were used in 24% of patients with hyperphosphatemia. Vascular calcification occurred in 0.2% of erdafitinib-treated patients. Restrict daily phosphate intake to 600 mg to 800 mg. Monitor serum phosphate throughout treatment course; erdafitinib dose reduction, interruption, or discontinuation may be necessary. Consider starting oral phosphate binder in patients with serum phosphate greater than 7 mg/dL. Hypophosphatemia, hyponatremia, hypomagnesemia, hypercalcemia, and hyperkalemia were also reported in clinical trials, with decreases from baseline in phosphorous (24% to 34%; grade 3 or 4, 8% to 9%), sodium (40% to 44%; grade 3 or 4, 16%), and magnesium (31% or less; grade 3 or 4, 1.2% or less). Increases from baseline were reported with serum calcium (22% to 27%; grade 3 or 4, 3.5% to 8%) and potassium (24% or less).
Central serous retinopathy (CSR)/retinal pigment epithelial detachment (RPED; retinal detachment) resulting in visual field defect was reported in 22% of patients with advanced urothelial carcinoma and FGFR alteration who received erdafitinib based on a pooled safety population (n = 479), with a median time to first onset of 46 days; grade 3 or 4 CSR were reported in 2.2% to 4.6% of patients in 2 clinical trials. CSR/RPED occurred in 104 erdafitinib-treated patients which led to an interruption of therapy in 40% of patients, a dose reduction in 56% of patients, and discontinuation of therapy in 3% of patients. Twenty-four patients restarted erdafitinib with or without a dose reduction, 67% had worsening or recurring CSR. CSR/RPED was ongoing at the time of last evaluation in 41% of the 104 patients. Monitor patients for ocular symptoms and perform opthalmic evaluation as needed; dose interruption, or discontinuation may be necessary. Dry eye (xerophthalmia) symptoms occurred in 25% to 29% (grade 3 or 4; 0.7% to 1.1%) of erdafitinib-treated patients. All patients should receive dry eye prophylaxis with ocular demulcents as needed. A nonrandomized clinical trial (n = 87) reported blurred vision in 17% of patients.
Gastrointestinal adverse reactions were commonly reported in patients with locally advanced or metastatic urothelial carcinoma who received erdafitinib in clinical trials, including stomatitis (56% to 62%; grade 3 or 4, 10% to 11%), diarrhea (48% to 63%; grade 3 or 4, 3% to 4.6%), xerostomia (39% to 45%), constipation (27% to 28%; grade 3 or 4, 1.1% or less), nausea (15% to 21%; grade 3 or 4, 1.1% or less), and vomiting (10% to 13%).
Metabolism and nutrition disorders were reported in patients with locally advanced or metastatic urothelial carcinoma who received erdafitinib during clinical trials, including decreased appetite/anorexia (27% to 38%; grade 3 or 4, 3% or less) and weight loss (16% to 22%; grade 3 or 4, 2% or less).
Dysgeusia was reported in 30% to 38% of patients with locally advanced or metastatic urothelial carcinoma who received erdafitinib in clinical trials (grade 3 or 4, 0.7% to 1.1%).
Fatigue (29% to 54%; grade 3 or 4, 1.5% to 8%) and fever (14% to 15%) were reported in patients with locally advanced or metastatic urothelial carcinoma who received erdafitinib in clinical trials. A nonrandomized clinical trial (n = 87) reported 2 fatal adverse events related to fatigue.
Skin and subcutaneous disorders were reported in patients with locally advanced or metastatic urothelial carcinoma who received erdafitinib in clinical trials, including nail disorders (62% to 70%; grade 3 or 4, 12% to 14%), xerosis (27% to 37%; grade 3 or 4, 1.5% or less), palmar-plantar erythrodysesthesia (hand and foot syndrome) (26% to 30%; grade 3 or 4, 6% to 10%), and alopecia (25% to 26%; grade 3 or 4, 0.7% or less).
Urinary tract infection was reported in 17% of patients with locally advanced or metastatic urothelial carcinoma who received erdafitinib in a nonrandomized trial (n = 87) (grade 3 or 4, 6%).
Epistaxis (13%) and hematuria (3.7%) were reported in patients receiving erdafitinib for locally advanced or metastatic urothelial carcinoma in a randomized clinical trial (n = 135).
Increased serum creatinine was reported in 43% to 52% of patients with locally advanced or metastatic urothelial carcinoma who received erdafitinib in clinical trials (grade 3 or 4, 1.5% to 4.7%). In a randomized trial (n = 135), 2.2% of patients developed an acute kidney injury. Renal failure resulted in fatality in 0.7% of patients.
Arthralgia occurred in 10% of patients receiving erdafitinib for locally advanced or metastatic urothelial carcinoma in a randomized clinical trial (n = 135). Extremity pain was also reported in 13% of patients in a nonrandomized clinical trial (n = 87).
Hematologic adverse reactions were reported in patients with locally advanced or metastatic urothelial carcinoma who received erdafitinib in clinical trials, including decreased hemoglobin (anemia) (35% to 50%; grade 3 or 4, 3.5% to 12%), decreased platelets (thrombocytopenia) (17% to 19%; grade 3 or 4, 1.2% to 1.5%), decreased leukocytes (leukopenia) (17%), and decreased neutrophils (neutropenia) (16% or less; grade 3 or 4, 0.8% or less).
Elevated hepatic enzymes were reported in patients with locally advanced or metastatic urothelial carcinoma who received erdafitinib in clinical trials, including increased ALT (41% to 46%; grade 3 or 4, 1.2% to 3.8%), increased alkaline phosphatase (41% to 54%; grade 3 or 4, 1.2% to 4.7%), and increased AST (30% to 44%; grade 3 or 4, 3.1% or less).
Peripheral edema occurred in 10% of patients receiving erdafitinib for locally advanced or metastatic urothelial carcinoma in a nonrandomized clinical trial (n = 87).
Erdafitinib can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis and vascular calcification. 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. Avoid concomitant use with agents that can increase serum phosphate levels. If serum phosphate is above 7 mg/dL, add an oral phosphate binder until the serum phosphate level returns to less than 7 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.
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.
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 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.
Patients 65 years of age and older (geriatric) had a higher incidence of adverse reactions requiring discontinuation of erdafitinib compared to younger patients. In clinical trials, the incidence of treatment discontinuation of erdafitinib due to adverse reactions was 10% in patients younger than 65 years, 20% in patients ages 65 to 75 years, and 35% for patients 75 years and older.
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.
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.
For the treatment urothelial carcinoma:
NOTE: Erdafitinib is not recommended for patients who are eligible for and have not received prior PD-1 or PD-L1 inhibitor therapy.
NOTE: Select patients for treatment based on the presence of susceptible FGFR3 genetic alterations in tumor specimens. Information on FDA-approved tests for the detection of FGFR3 genetic alterations in urothelial cancer is available at www.fda.gov/CompanionDiagnostics.
-for the treatment of locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 genetic alterations, that has progressed during or following at least one prior line of systemic therapy:
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 9 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 resulted in a confirmed objective response rate (ORR) of 40% in an open-label, phase 2 clinical trial (BLC2001), with 3% complete responses (CR); 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. In Cohort 1 of a multicenter, randomized, phase 3 trial (THOR), treatment with erdafitinib significantly improved median overall survival (12.1 months vs. 7.8 months), median progression-free survival (5.6 months vs. 2.7 months), and ORR (35.3% vs. 8.5%; CR, 5.1% vs. 0.8%) in patients with FGFR3-positive advanced urothelial cancer compared with chemotherapy; all patients had received prior treatment with a PD-1 or PD-L1 inhibitor. Treatment with erdafitinib was not superior to pembrolizumab at the final analysis of Cohort 2 of this study, with a median overall survival of 10.9 months versus 11.1 months, respectively.
Therapeutic Drug Monitoring:
Dosage Adjustments for Treatment-Related Toxicities:
Daily dose: 9 mg
-1st dose reduction: 8 mg
-2nd dose reduction: 6 mg
-3rd dose reduction: 5 mg
-4th dose reduction: 4 mg
-5th dose reduction: Discontinue erdafitinib therapy.
Daily dose: 8 mg
-1st dose reduction: 6 mg
-2nd dose reduction: 5 mg
-3rd dose reduction: 4 mg
-4th dose reduction: Discontinue erdafitinib therapy.
Hyperphosphatemia
-In all patients, restrict phosphate intake to 600 to 800 mg daily.
-Serum phosphate level less than 6.99 mg/dL: Continue erdafitinib at the current dose.
-Serum phosphate level 7 to 8.99 mg/dL: Continue current dose of erdafitinib. Start an oral phosphate binder with food until the serum phosphate level is less than 7 mg/dL. Reduce the erdafitinib dose if serum phosphate remains greater than 7 mg/dL for 2 months or if clinically necessary.
-Serum phosphate level 9 to 10 mg/dL: Hold erdafitinib. Reassess serum phosphate level weekly until it returns to less than 7 mg/dL, then restart erdafitinib therapy at the same dose level. Start an oral phosphate binder until the serum phosphate level returns to less than 7 mg/dL. Reduce the erdafitinib dose if serum phosphate is greater than 9 mg/dL for at least 1 month or if clinically necessary.
-Serum phosphate greater than 10 mg/dL: Hold erdafitinib. Reassess serum phosphate level weekly until level returns to less than 7 mg/dL, then restart therapy at first reduced dose level. If serum phosphate is greater than or equal to 10 mg/dL for more than 2 weeks, permanently discontinue erdafitinib. Medically manage hyperphosphatemia symptoms.
-Serum phosphate with life-threatening consequences: Permanently discontinue erdafitinib.
Central Serous Retinopathy (CSR)
-All grades: Hold erdafitinib and perform ophthalmic evaluation within 2 weeks. If symptoms improve within 14 days, then restart erdafitinib at the current dose. If no improvement within 14 days, continuing holding erdafitinib until improvement seen; once improving resume erdafitinib at the next lower dose level. Upon restarting, monitor for recurrence every 1 to 2 weeks for a month. If there is a recurrence or no improvement after holding erdafitinib for at least 4 weeks, consider permanent discontinuation of therapy.
Other Treatment-Related Adverse Reactions
-Grade 3: Hold erdafitinib until resolution to grade 1 or baseline, then may resume erdafitinib at the next lower dose level, as specified above.
-Grade 4: Permanently discontinue therapy.
Maximum Dosage Limits:
-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.
Patients with Hepatic Impairment Dosing
-Mild or moderate hepatic impairment (Child-Pugh A or B): No dose adjustment is recommended.
-Severe hepatic impairment (Child-Pugh C): Limited data are available.
Patients with Renal Impairment Dosing
-Mild or moderate renal impairment (CrCl 30 to 89 mL/min): No dosage adjustment is recommended.
-Severe renal impairment (CrCl less than 30 mL/min): Limited data are available.
-Renal impairment requiring dialysis: No data are available.
*non-FDA-approved indication
Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with erdafitinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Adagrasib: (Major) Avoid coadministration of erdafitinib and adagrasib 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 adagrasib is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A and CYP2C9 substrate and adagrasib is a strong CYP3A and moderate CYP2C9 inhibitor. The mean ratio for the AUC of erdafitinib was 134% when coadministered with another strong CYP3A inhibitor.
Afatinib: (Moderate) If the concomitant use of erdafitinib and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of erdafitinib. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-gp substrate and erdafitinib is a P-gp inhibitor. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC of afatinib was 119% when coadministered with the same P-gp inhibitor, and 111% when the inhibitor was administered 6 hours after afatinib.
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.
Amiodarone: (Major) Avoid coadministration of erdafitinib and amiodarone due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP2C9 substrate and amiodarone is a moderate CYP2C9 inhibitor.
Amlodipine; Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with erdafitinib is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a P-gp substrate; erdafitinib is a P-gp inhibitor.
Amobarbital: (Major) Avoid coadministration of erdafitinib and barbiturates due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of erdafitinib and clarithromycin due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
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 CYP3A substrate and apalutamide is a strong CYP3A inducer.
Asciminib: (Major) Avoid coadministration of erdafitinib and asciminib 200 mg bid due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP2C9 substrate and asciminib 200 mg bid is a moderate CYP2C9 inhibitor.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid coadministration of erdafitinib and barbiturates due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Atazanavir: (Major) Avoid coadministration of erdafitinib and atazanavir due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Atazanavir; Cobicistat: (Major) Avoid coadministration of erdafitinib and atazanavir due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%. (Major) Avoid coadministration of erdafitinib and cobicistat due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with erdafitinib is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a P-gp substrate; erdafitinib is a P-gp inhibitor.
Barbiturates: (Major) Avoid coadministration of erdafitinib and barbiturates due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving erdafitinib. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving erdafitinib. Concurrent use may increase betrixaban exposure resulting in an increased bleeding risk; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a P-gp substrate and erdafitinib is a P-gp inhibitor. Coadministration of other P-gp inhibitors increased betrixaban exposure by 2 to 3-fold.
Bexarotene: (Major) If coadministration of erdafitinib and bexarotene is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with erdafitinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Bosentan: (Major) If coadministration of erdafitinib and bosentan is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and bosentan is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Brodalumab: (Major) Avoid coadministration of erdafitinib and brodalumab 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 brodalumab is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP2C9 substrate and brodalumab is a moderate CYP2C9 inhibitor.
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.
Butalbital; Acetaminophen: (Major) Avoid coadministration of erdafitinib and barbiturates due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid coadministration of erdafitinib and barbiturates due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid coadministration of erdafitinib and barbiturates due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid coadministration of erdafitinib and barbiturates due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and barbiturates are strong CYP3A inducers.
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; Famotidine; 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; 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; Magnesium Hydroxide; 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.
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.
Calcium; Vitamin D: (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.
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 CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Cenobamate: (Major) If coadministration of erdafitinib and cenobamate is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and cenobamate is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Ceritinib: (Major) Avoid coadministration of erdafitinib and ceritinib due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Chloramphenicol: (Major) Avoid coadministration of erdafitinib and chloramphenicol due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Clarithromycin: (Major) Avoid coadministration of erdafitinib and clarithromycin due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Cobicistat: (Major) Avoid coadministration of erdafitinib and cobicistat due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Cobimetinib: (Moderate) Monitor for an increase in cobimetinib-related adverse reactions if coadministration with erdafitinib is necessary. Concomitant use may increase cobimetinib exposure. In vitro, cobimetinib is a P-gp substrate; erdafitinib is a P-gp inhibitor.
Colchicine: (Major) Avoid concomitant use of colchicine and erdafitinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and erdafitinib is a P-gp 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.
Dabigatran: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with erdafitinib is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Dabrafenib: (Major) If coadministration of erdafitinib and dabrafenib is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Darunavir: (Major) Avoid coadministration of erdafitinib and darunavir due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Darunavir; Cobicistat: (Major) Avoid coadministration of erdafitinib and cobicistat due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%. (Major) Avoid coadministration of erdafitinib and darunavir due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of erdafitinib and cobicistat due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%. (Major) Avoid coadministration of erdafitinib and darunavir due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%. (Moderate) Coadministration of tenofovir alafenamide with erdafitinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Delavirdine: (Major) Avoid coadministration of erdafitinib and delavirdine due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and delavirdine is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
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.
Dolutegravir: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with erdafitinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with erdafitinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Dolutegravir; Rilpivirine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with erdafitinib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with erdafitinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Doxorubicin Liposomal: (Major) Avoid coadministration of erdafitinib with doxorubicin due to the risk for increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Doxorubicin is a P-gp substrate and erdafitinib is a P-gp inhibitor. Concurrent use of P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of erdafitinib with doxorubicin due to the risk for increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Doxorubicin is a P-gp substrate and erdafitinib is a P-gp inhibitor. Concurrent use of P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Edoxaban: (Major) Consider an edoxaban dosage reduction for patients being treated for deep venous thrombosis (DVT) or pulmonary embolism (PE) if concomitant use of erdafitinib is necessary. Concomitant use may increase edoxaban exposure; edoxaban is a P-gp substrate and erdafitinib is a P-gp inhibitor. An edoxaban dose reduction to 30 mg PO once daily is recommended by the manufacturer for use with certain P-gp inhibitors; however, because use of concomitant P-gp inhibitors was limited to only certain drugs that inhibit P-gp in DVT/PE clinical trials, clinicians should use professional judgment and guide edoxaban dose adjustments based on patient response if coadministered with erdafitinib. Based on clinical experience in patients with non-valvular atrial fibrillation no dose reduction is recommended for concomitant use of erdafitinib. Increased concentrations of edoxaban may occur during concomitant use of erdafitinib; monitor for increased adverse effects of edoxaban.
Efavirenz: (Major) If coadministration of erdafitinib and efavirenz is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) If coadministration of erdafitinib and efavirenz is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%. (Moderate) Coadministration of tenofovir disoproxil fumarate with erdafitinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) If coadministration of erdafitinib and efavirenz is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%. (Moderate) Coadministration of tenofovir disoproxil fumarate with erdafitinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Elagolix: (Major) If coadministration of erdafitinib and elagolix is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Elagolix; Estradiol; Norethindrone acetate: (Major) If coadministration of erdafitinib and elagolix is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of erdafitinib and cobicistat due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%. (Moderate) Coadministration of tenofovir alafenamide with erdafitinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of erdafitinib and cobicistat due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%. (Moderate) Coadministration of tenofovir disoproxil fumarate with erdafitinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with erdafitinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with erdafitinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Emtricitabine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with erdafitinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with erdafitinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Encorafenib: (Major) Avoid coadministration of erdafitinib and encorafenib due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and encorafenib is a strong CYP3A inducer.
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 CYP3A substrate and enzalutamide is a strong CYP3A inducer.
Eslicarbazepine: (Major) If coadministration of erdafitinib and eslicarbazepine is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Etravirine: (Major) If coadministration of erdafitinib and etravirine is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and etravirine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with erdafitinib is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-glycoprotein (P-gp) substrate and erdafitinib is a P-gp inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations.
Ezetimibe; Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with erdafitinib is necessary. Concomitant use may increase simvastatin exposure. Simvastatin is a P-gp substrate; erdafitinib is a P-gp inhibitor.
Fluconazole: (Major) Avoid coadministration of erdafitinib and fluconazole due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP2C9 substrate and fluconazole is a moderate CYP2C9 inhibitor.
Fluorouracil, 5-FU: (Major) Avoid coadministration of erdafitinib and fluorouracil due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP2C9 substrate and fluorouracil is a moderate CYP2C9 inhibitor.
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 phenytoin/fosphenytoin due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and phenytoin/fosphenytoin is a strong CYP3A inducer.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with coadministration of glecaprevir and erdafitinib as increased plasma concentrations of glecaprevir may occur resulting in increased risk of glecaprevir-related adverse events. Glecaprevir is a substrate of P-gp and erdafitinib is a P-gp inhibitor. (Moderate) Monitor for an increase in pibrentasvir-related adverse effects if concomitant use of erdafitinib is necessary. Concomitant use may increase pibrentasvir exposure. Pibrentasvir is a substrate of P-gp and erdafitinib is a P-gp inhibitor.
Grapefruit juice: (Major) Advise patients to avoid grapefruit juice while taking erdafitinib due to increased erdafitinib exposure. Erdafitinib is a substrate of CYP2C9 and CYP3A4. Grapefruit juice is a moderate CYP2C9 inhibitor and 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 for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Indinavir: (Major) Avoid coadministration of erdafitinib and indinavir due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and indinavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
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 coadministration of erdafitinib and rifampin due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and rifampin is a strong CYP3A inducer.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of erdafitinib and rifampin due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and rifampin is a strong CYP3A inducer.
Itraconazole: (Major) Avoid coadministration of erdafitinib and itraconazole due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and itraconazole is a strong CYP3A inhibitor. Concomitant use with itraconazole increased erdafitinib overall exposure by 134%.
Ketoconazole: (Major) Avoid coadministration of erdafitinib and ketoconazole due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with erdafitinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of erdafitinib and clarithromycin due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
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.
Lapatinib: (Moderate) Monitor for an increase in lapatinib-related adverse reactions if coadministration with erdafitinib is necessary. Lapatinib is a P-gp substrate and erdafitinib is a P-gp inhibitor. Increased plasma concentrations of lapatinib are likely.
Lefamulin: (Major) Avoid coadministration of erdafitinib with oral lefamulin as concurrent use may increase lefamulin exposure and adverse effects. If coadministration of erdafitinib with oral lefamulin is unavoidable, separate erdafitinib and lefamulin doses by at least 6 hours. Erdafitinib may be administered with intravenous lefamulin. Lefamulin is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Levoketoconazole: (Major) Avoid coadministration of erdafitinib and ketoconazole due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Lonafarnib: (Major) Avoid coadministration of erdafitinib and lonafarnib due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and lonafarnib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with erdafitinib. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and erdafitinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with erdafitinib. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and erdafitinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Major) Avoid coadministration of erdafitinib and ritonavir due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Lorlatinib: (Major) If coadministration of erdafitinib and lorlatinib is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and lorlatinib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Lovastatin: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with erdafitinib is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; erdafitinib is a P-gp inhibitor.
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 CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A 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 CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer.
Maraviroc: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with erdafitinib is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; erdafitinib is a P-gp inhibitor.
Mavacamten: (Major) If coadministration of erdafitinib and mavacamten is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Mefloquine: (Moderate) Monitor for an increase in mefloquine-related adverse effects if concomitant use of erdafitinib is necessary. Concomitant use may increase mefloquine exposure. Mefloquine is a P-gp substrate and erdafitinib is a P-gp inhibitor.
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) Avoid coadministration of erdafitinib and barbiturates due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Mifepristone: (Major) Avoid coadministration of erdafitinib and mifepristone due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A and CYP2C9 substrate and mifepristone is a strong CYP3A and moderate CYP2C9 inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
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 CYP3A substrate and mitotane is a strong CYP3A 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.
Morphine: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with erdafitinib is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and erdafitinib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold.
Morphine; Naltrexone: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with erdafitinib is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and erdafitinib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold.
Nafcillin: (Major) If coadministration of erdafitinib and nafcillin is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and nafcillin is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Naldemedine: (Moderate) Monitor for naldemedine-related adverse reactions if coadministered with erdafitinib. Naldemedine plasma concentrations may increase during concomitant use. Naldemedine is a P-gp substrate; erdafitinib is a P-gp inhibitor.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and erdafitinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Nefazodone: (Major) Avoid coadministration of erdafitinib and nefazodone due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Nelfinavir: (Major) Avoid coadministration of erdafitinib and nelfinavir due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and nelfinavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Nirmatrelvir; Ritonavir: (Major) Avoid coadministration of erdafitinib and ritonavir due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Omeprazole; Amoxicillin; Rifabutin: (Major) If coadministration of erdafitinib and rifabutin is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and rifabutin is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Pazopanib: (Major) Avoid coadministration of pazopanib and erdafitinib due to the potential for increased pazopanib exposure. If coadministration of erdafitinib with pazopanib is necessary, separate erdafitinib and pazopanib doses by at least 6 hours. Pazopanib is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Pentobarbital: (Major) Avoid coadministration of erdafitinib and barbiturates due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Pexidartinib: (Major) If coadministration of erdafitinib and pexidartinib is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Phenobarbital: (Major) Avoid coadministration of erdafitinib and barbiturates due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of erdafitinib and barbiturates due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Phenytoin: (Major) Avoid coadministration of erdafitinib and phenytoin/fosphenytoin due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and phenytoin/fosphenytoin is a strong CYP3A inducer.
Pitavastatin: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with erdafitinib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; erdafitinib is a P-gp inhibitor.
Posaconazole: (Major) Avoid coadministration of erdafitinib and posaconazole due to the risk for increased plasma concentrations of erdafitinib. Concomitant use may also increase posaconazole exposure. If concomitant use is necessary, closely monitor for adverse reactions and consider dose modifications as clinically appropriate based on response. Erdafitinib is a CYP3A substrate and P-gp inhibitor and posaconazole is a P-gp substrate and strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
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.
Pralsetinib: (Major) Avoid concomitant use of erdafitinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and erdafitinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Primidone: (Major) Avoid coadministration of erdafitinib and barbiturates due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and erdafitinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Ranolazine: (Moderate) Monitor for an increase in ranolazine-related adverse reactions if coadministration with erdafitinib is necessary and consider a ranolazine dosage adjustment. Concomitant use may increase ranolazine exposure. Ranolazine is a P-gp substrate; erdafitinib is a P-gp inhibitor.
Relugolix: (Major) Avoid concomitant use of relugolix and oral erdafitinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer erdafitinib at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral erdafitinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer erdafitinib at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Repotrectinib: (Major) Avoid coadministration of repotrectinib with erdafitinib. Concomitant use may increase repotrectinib exposure and risk for repotrectinib-related adverse effects and decrease erdafitinib exposure and efficacy. While use is not recommended, if combination therapy is necessary, an erdafitinib dosage increase is required. If coadministration of erdafitinib and repotrectinib is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Repotrectinib is a P-gp substrate and moderate CYP3A inducer; erdafitinib is a CYP3A substrate and P-gp inhibitor. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Ribociclib: (Major) Avoid coadministration of erdafitinib and ribociclib due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Ribociclib; Letrozole: (Major) Avoid coadministration of erdafitinib and ribociclib due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Rifabutin: (Major) If coadministration of erdafitinib and rifabutin is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and rifabutin is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Rifampin: (Major) Avoid coadministration of erdafitinib and rifampin due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and rifampin is a strong CYP3A inducer.
Rifapentine: (Major) Avoid coadministration of erdafitinib and rifapentine due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with erdafitinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and erdafitinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with erdafitinib; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Ritonavir: (Major) Avoid coadministration of erdafitinib and ritonavir due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Saquinavir: (Major) Avoid coadministration of erdafitinib and saquinavir due to the risk for increased plasma concentrations of erdafitinib. Concomitant use may also increase saquinavir exposure. If concomitant use is necessary, closely monitor for adverse reactions and consider dose modifications as clinically appropriate based on response. Erdafitinib is a CYP3A substrate and P-gp inhibitor and saquinavir is a P-gp substrate and strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Secobarbital: (Major) Avoid coadministration of erdafitinib and barbiturates due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and barbiturates are strong CYP3A inducers.
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.
Silodosin: (Major) Avoid coadministration of silodosin and erdafitinib due to the potential for increased silodosin exposure. If coadministration of erdafitinib with silodosin is necessary, separate erdafitinib and silodosin doses by at least 6 hours. In vitro data indicate that silodosin is a P-gp substrate; erdafitinib is a P-gp inhibitor.
Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with erdafitinib is necessary. Concomitant use may increase simvastatin exposure. Simvastatin is a P-gp substrate; erdafitinib is a P-gp inhibitor.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of erdafitinib. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a 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.
Sotorasib: (Major) If coadministration of erdafitinib and sotorasib is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and sotorasib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of erdafitinib and St. John's wort due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and St. John's wort is a strong CYP3A inducer.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) Avoid coadministration of erdafitinib and sulfamethoxazole due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP2C9 substrate and sulfamethoxazole is a moderate CYP2C9 inhibitor.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with erdafitinib is necessary. Talazoparib is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Temsirolimus: (Moderate) Monitor for an increase in temsirolimus-related adverse reactions if coadministration with erdafitinib is necessary due to the risk of increased temsirolimus exposure. Temsirolimus is a P-gp substrate and erdafitinib is a P-gp inhibitor. Coadministration is likely to increase plasma concentrations of temsirolimus.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with erdafitinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with erdafitinib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with erdafitinib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Ticagrelor: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with erdafitinib as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Tipranavir: (Major) Avoid coadministration of erdafitinib and tipranavir due to the risk for increased plasma concentrations of erdafitinib. Concomitant use may also increase tipranavir exposure. If concomitant use is necessary, closely monitor for adverse reactions and consider dose modifications as clinically appropriate based on response. Erdafitinib is a CYP3A substrate and P-gp inhibitor and tipranavir is a P-gp substrate and strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Topotecan: (Major) Avoid coadministration of erdafitinib with oral topotecan due to increased topotecan exposure. If coadministration of erdafitinib with oral topotecan is necessary, separate erdafitinib and topotecan doses by at least 6 hours. Erdafitinib may be administered with intravenous topotecan. Coadministration increases the risk of topotecan-related adverse reactions. Oral topotecan is a P-gp substrate and erdafitinib is a P-gp inhibitor. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
Tucatinib: (Major) Avoid coadministration of erdafitinib and tucatinib due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and tucatinib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with erdafitinib. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Valproic Acid, Divalproex Sodium: (Major) Avoid coadministration of erdafitinib and valproic acid 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 valproic acid is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP2C9 substrate and valproic acid is a moderate CYP2C9 inhibitor.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with erdafitinib due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of erdafitinib. Venetoclax is a P-gp substrate; erdafitinib is a P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
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. (Moderate) Monitor for vincristine-related adverse reactions if coadministration of erdafitinib is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Vincristine: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of erdafitinib is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of erdafitinib and clarithromycin due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Voriconazole: (Major) Avoid coadministration of erdafitinib and voriconazole due to the risk for increased plasma concentrations of erdafitinib. If concomitant use is necessary, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. Erdafitinib is a CYP3A substrate and voriconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased erdafitinib overall exposure by 134%.
Erdafitinib is a kinase inhibitor that binds to and inhibits the enzymatic activity of FGFR1, FGFR2, FGFR3, and FGFR4 based on in vitro data. 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.
Erdafitinib is administered orally. It is 99.7% 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).
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. 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.
-Route-Specific Pharmacokinetics
Oral Route
Following administration of erdafitinib 8 mg once daily, the mean steady-state maximum 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 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.
-Special Populations
Hepatic Impairment
Mild and moderate hepatic impairment (Child-Pugh A or B) did not have a clinically meaningful effect on erdafitinib exposure. Limited data are available in patients with severe (Child-Pugh C) hepatic impairment.
Renal Impairment
Mild or moderate renal impairment (eGFR 30 to 89 mL/min/1.73 m2) did not have a clinically meaningful effect on erdafitinib exposure. Limited data are available in patients with severe renal impairment. The pharmacokinetics of erdafitinib in patients with renal impairment requiring dialysis is unknown.
Geriatric
Age (range, 21 to 92 years) did not have a clinically meaningful effect on erdafitinib exposure.
Gender Differences
Gender did not have a clinically meaningful effect on erdafitinib exposure.
Ethnic Differences
Ethnicity did not have a clinically meaningful effect on erdafitinib exposure.
Obesity
Body weight (range, 36 kg to 166 kg) did not have a clinically meaningful effect on erdafitinib exposure.
Other
CYP2C9 activity
Genetic variants of CYP2C9 such as CYP2C9*2 and CYP2C9*3 polymorphisms have reduced CYP2C9 activity. Erdafitinib exposure was similar in subjects with CYP2C9*1/*2 and *1*3 genotypes relative to subjects with CYP2C9*1*1 genotype (wild type). No data are available in subjects with other genotypes (e.g., *2/*2, *2/*3, *3/*3). Simulation suggested no clinically meaningful differences in erdafitinib exposure in subjects with CYP2C9*2/*2 and *2/*3 genotypes. The exposure of erdafitinib is predicted to be 50% higher in subjects with the CYP2C9*3/*3 genotype, which is estimated to be present in 0.4% to 3% of the population among various ethnic groups.