BALVERSA (Page 3 of 6)

7 DRUG INTERACTIONS

7.1 Effect of Other Drugs on BALVERSA

Table 5 summarizes drug interactions that affect the exposure of BALVERSA or serum phosphate level and their clinical management.

Table 5: Drug Interactions that Affect BALVERSA
Moderate CYP2C9 or Strong CYP3A4 Inhibitors
Clinical Impact
  • Co-administration of BALVERSA with moderate CYP2C9 or strong CYP3A4 inhibitors increased erdafitinib plasma concentrations [see Clinical Pharmacology (12.3)].
  • Increased erdafitinib plasma concentrations may lead to increased drug-related toxicity [see Warnings and Precautions (5)].
Clinical Management
  • Consider alternative therapies that are not moderate CYP2C9 or strong CYP3A4 inhibitors during treatment with BALVERSA.
  • If co-administration of moderate CYP2C9 or strong CYP3A4 inhibitor is unavoidable, monitor closely for adverse reactions and consider dose modifications accordingly [see Dosage and Administration (2.3)]. If the moderate CYP2C9 or strong CYP3A4 inhibitor is discontinued, the BALVERSA dose may be increased in the absence of drug-related toxicity.
Strong CYP2C9 or CYP3A4 Inducers
Clinical Impact
  • Co-administration of BALVERSA with strong inducers of CYP2C9 or CYP3A4 may decrease erdafitinib plasma concentrations significantly [see Clinical Pharmacology (12.3)].
  • Decreased erdafitinib plasma concentrations may lead to decreased activity.
Clinical Management
  • Avoid co-administration of strong inducers of CYP2C9 or CYP3A4 with BALVERSA.
Moderate CYP2C9 or CYP3A4 Inducers
Clinical Impact
  • Co-administration of BALVERSA with moderate inducers of CYP2C9 or CYP3A4 may decrease erdafitinib plasma concentrations [see Clinical Pharmacology (12.3)].
  • Decreased erdafitinib plasma concentrations may lead to decreased activity.
Clinical Management
  • If a moderate CYP2C9 or CYP3A4 inducer must be co-administered at the start of BALVERSA treatment, administer BALVERSA dose as recommended (8 mg once daily with potential to increase to 9 mg once daily based on serum phosphate levels on Days 14 to 21 and tolerability).
  • If a moderate CYP2C9 or CYP3A4 inducer must be co-administered after the initial dose increase period based on serum phosphate levels and tolerability, increase BALVERSA dose up to 9 mg.
  • When a moderate inducer of CYP2C9 or CYP3A4 is discontinued, continue BALVERSA at the same dose, in the absence of drug-related toxicity.
Serum Phosphate Level-Altering Agents
Clinical Impact
  • Co-administration of BALVERSA with other serum phosphate level-altering agents may increase or decrease serum phosphate levels [see Pharmacodynamics (12.2)].
  • Changes in serum phosphate levels due to serum phosphate level-altering agents (other than erdafitinib) may interfere with serum phosphate levels needed for the determination of initial dose increased based on serum phosphate levels [see Dosage and Administration (2.3)].
Clinical Management
  • Avoid co-administration of serum phosphate level-altering agents with BALVERSA before initial dose increase period based on serum phosphate levels (Days 14 to 21) [see Dosage and Administration (2.3)].

7.2 Effect of BALVERSA on Other Drugs

Table 6 summarizes the effect of BALVERSA on other drugs and their clinical management.

Table 6: BALVERSA Drug Interactions that Affect Other Drugs
CYP3A4 Substrates
Clinical Impact
  • Co-administration of BALVERSA with CYP3A4 substrates may alter the plasma concentrations of CYP3A4 substrates [see Clinical Pharmacology (12.3)].
  • Altered plasma concentrations of CYP3A4 substrates may lead to loss of activity or increased toxicity of the CYP3A4 substrates.
Clinical Management
  • Avoid co-administration of BALVERSA with sensitive substrates of CYP3A4 with narrow therapeutic indices.
OCT2 Substrates
Clinical Impact
  • Co-administration of BALVERSA with OCT2 substrates may increase the plasma concentrations of OCT2 substrates [see Clinical Pharmacology (12.3)].
  • Increased plasma concentrations of OCT2 substrates may lead to increased toxicity of the OCT2 substrates.
Clinical Management
  • Consider alternative therapies that are not OCT2 substrates or consider reducing the dose of OCT2 substrates (e.g., metformin) based on tolerability.
P-glycoprotein (P-gp) Substrates
Clinical Impact
  • Co-administration of BALVERSA with P-gp substrates may increase the plasma concentrations of P-gp substrates [see Clinical Pharmacology (12.3)].
  • Increased plasma concentrations of P-gp substrates may lead to increased toxicity of the P-gp substrates.
Clinical Management
  • If co-administration of BALVERSA with P-gp substrates is unavoidable, separate BALVERSA administration by at least 6 hours before or after administration of P-gp substrates with narrow therapeutic index.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Based on the mechanism of action and findings in animal reproduction studies, BALVERSA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on BALVERSA use in pregnant women to inform a drug-associated risk. Oral administration of erdafitinib to pregnant rats during organogenesis caused malformations and embryo-fetal death at maternal exposures that were less than the human exposures at the maximum recommended human dose based on AUC (see Data). Advise pregnant women and females of reproductive potential of the potential risk to the fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.

Data

Animal Data

In an embryo-fetal toxicity study, erdafitinib was orally administered to pregnant rats during the period of organogenesis. Doses ≥4mg/kg/day (at total maternal exposures <0.1% of total human exposures at the maximum recommended human dose based on AUC) produced embryo-fetal death, major blood vessel malformations and other vascular anomalies, limb malformations (ectrodactyly, absent or misshapen long bones), an increased incidence of skeletal anomalies in multiple bones (vertebrae, sternebrae, ribs), and decreased fetal weight.

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