scontinued, continueBALVERSA 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-alteringagents may increase or decrease serum phosphate levels [seePharmacodynamics (12.2)].
• Changes in serum phosphate levels due to serum phosphate level-alteringagents (other than erdafitinib) may interfere with serum phosphate levelsneeded for the determination of initial dose increased based on serumphosphate levels [see Dosage and Administration (2.3)].
Clinical Management
• Avoid co-administration of serum phosphate level-altering agents withBALVERSA before initial dose increase period based on serum phosphatelevels (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 theplasma concentrations of CYP3A4 substrates [see Clinical Pharmacology(12.3)].
• Altered plasma concentrations of CYP3A4 substrates may lead to loss ofactivity or increased toxicity of the CYP3A4 substrates.
Clinical Management • Avoid co-administration of BALVERSA with sensitive substrates of CYP3A4with narrow therapeutic indices.
OCT2 Substrates
Clinical Impact
• Co-administration of BALVERSA with OCT2 substrates may increase theplasma concentrations of OCT2 substrates [see Clinical Pharmacology (12.3)].
• Increased plasma concentrations of OCT2 substrates may lead to increasedtoxicity of the OCT2 substrates.
Clinical Management • Consider alternative therapies that are not OCT2 substrates or considerreducing 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 theplasma 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 afteradministration 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 causefetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)].
There are noavailable data on BALVERSA use in pregnant women to inform a drug-associated risk. Oraladministration of erdafitinib to pregnant rats during organogenesis caused malformations and embryofetaldeath at maternal exposures that were less than the human exposures at the maximumrecommended 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 isunknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In theU.S. general popula |
