Interactions : אינטראקציות

9     DRUG INTERACTIONS
9.1       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
• Co-administration of BALVERSA with moderate CYP2C9 or strong
CYP3A4 inhibitors increased erdafitinib plasma concentrations [see
Clinical Impact               Clinical Pharmacology (12.3)].
• Increased erdafitinib plasma concentrations may lead to increased drug- related toxicity [see Warnings and Precautions (7)].
• Consider alternative therapies that are not moderate CYP2C9 or strong CYP3A4 inhibitors during treatment with BALVERSA.
• If co-administration of a moderate CYP2C9 or strong CYP3A4 inhibitor is unavoidable, monitor closely for adverse reactions and
Clinical Management consider dose modifications accordingly [see Dosage and
Administration (5.3)]. If the moderate CYP2C9 or strong CYP3A4 inhibitor is discontinued, the BALVERSA dose may be increased in the absence of drug-related toxicity.
Dual CYP2C9 and Strong CYP3A4 Inducers
• Co-administration of BALVERSA with a dual CYP2C9 and strong
CYP3A4 inducer decreased erdafitinib plasma concentrations
Clinical Impact              significantly [see Clinical Pharmacology (12.3)].
• Decreased erdafitinib plasma concentrations may lead to decreased activity.
• Avoid co-administration of dual CYP2C9 and strong CYP3A4 inducers Clinical Management with BALVERSA.
Strong/Moderate CYP2C9 or CYP3A4 Inducers
• Co-administration of BALVERSA with strong/moderate CYP2C9 or
CYP3A4 inducers may decrease erdafitinib plasma concentrations [see
Clinical Impact              Clinical Pharmacology (12.3)].
• Decreased erdafitinib plasma concentrations may lead to decreased activity.
• If a strong/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 strong/moderate CYP2C9 or CYP3A4 inducer must be co-
Clinical Management administered after the initial dose increase period based on serum phosphate levels and tolerability, increase BALVERSA dose up to 9 mg.
• When a strong/moderate CYP2C9 or CYP3A4 inducer is discontinued,
continue BALVERSA at the same dose, in the absence of drug-related toxicity.
Serum Phosphate Level-Altering Agents
• 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-
Clinical Impact 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
(5.3)].
• Avoid co-administration of serum phosphate level-altering agents with BALVERSA before initial dose increase period based on serum
Clinical Management phosphate levels (Days 14 to 21) [see Dosage and Administration
(5.3)].



9.2     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
P-glycoprotein (P-gp) Substrates
• Co-administration of BALVERSA with P-gp substrates may increase the plasma concentrations of P-gp substrates [see Clinical Pharmacology
Clinical Impact                    (12.3)].
• Increased plasma concentrations of P-gp substrates may lead to increased toxicity of the P-gp substrates.
• If co-administration of BALVERSA with P-gp substrates is unavoidable, Clinical Management                separate BALVERSA administration by at least 6 hours before or after administration of P-gp substrates with narrow therapeutic index.