BAXFENDY Ref.[116676] Active ingredients:

5.1 Hyperkalemia

BAXFENDY can cause hyperkalemia [see Adverse Reactions (6.1)].

Assess serum potassium prior to initiation of BAXFENDY and monitor periodically during treatment. Correct serum potassium abnormalities prior to initiation of BAXFENDY [see Dosage and Administration (2.1, 2.2)]. More frequent monitoring is recommended for patients at increased risk of hyperkalemia (e.g., patients ≥65 years of age, those with diabetes mellitus or chronic kidney disease, and those receiving concomitant medications that increase serum potassium) [see Drug Interactions (7.1) and Geriatric Use (8.5)].

If hyperkalemia occurs, treat hyperkalemia and consider interrupting or discontinuing BAXFENDY. Consider more frequent monitoring of serum potassium in patients who restart BAXFENDY after experiencing hyperkalemia. Permanently discontinue BAXFENDY if clinically significant hyperkalemia recurs.

5.2 Hyponatremia

BAXFENDY can cause hyponatremia [see Adverse Reactions (6.1)].

Assess serum sodium prior to initiation of BAXFENDY and monitor periodically during treatment. Correct serum sodium abnormalities prior to initiation of BAXFENDY [see Dosage and Administration (2.1, 2.2)]. More frequent monitoring is recommended for patients with low baseline serum sodium concentrations and those at risk of hyponatremia, such as those receiving concomitant medications that may cause hyponatremia.

If clinically significant hyponatremia occurs, treat the hyponatremia and consider interrupting or discontinuing BAXFENDY. Consider more frequent monitoring of serum sodium in patients who restart BAXFENDY after experiencing hyponatremia. Permanently discontinue BAXFENDY if clinically significant hyponatremia recurs.

The following clinically significant adverse reactions are also discussed elsewhere in the labeling:

• Hyperkalemia [see Warnings and Precautions (5.1)]
• Hyponatremia [see Warnings and Precautions (5.2)]

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of BAXFENDY was evaluated over 12 weeks using the randomized, double-blind, placebo-controlled periods from three clinical trials in patients with hypertension not adequately controlled on other antihypertensive medications. Three of these trials [BaxHTN (NCT06034743), BrigHTN (NCT04519658), Bax24 (NCT06168409)] evaluated BAXFENDY 2 mg as add-on treatment and two trials [BaxHTN, BrigHTN] evaluated BAXFENDY 1 mg as add-on treatment. These data reflect exposure of 441 patients to BAXFENDY 2 mg and 333 patients to BAXFENDY 1 mg, with a mean treatment duration of 80 days for both BAXFENDY 2 mg and 1 mg. Analyses in this section are based on the 12‑week periods in these three trials. Uncontrolled, long-term safety data from 192 patients exposed to BAXFENDY 1 mg or 2 mg for a mean of 293 days and 172 patients exposed to BAXFENDY 2 mg for a mean of 327 days, were consistent with the safety profile observed during the 12-week, randomized, double-blind, placebo-controlled periods.

Hyperkalemia was the most frequently reported adverse reaction to BAXFENDY in the three clinical trials [see Warnings and Precautions (5.1)]. Hyperkalemia led to permanent discontinuation of treatment in 8 (1.8%) patients in the BAXFENDY 2 mg group, 2 (0.6%) patients in the BAXFENDY 1 mg group, and none in the placebo group.

Table 1 shows the most frequently reported adverse reactions to BAXFENDY during the 12-week period in the three clinical trials.

Table 1. Adverse Reactions Reported in ≥2% of Patients Treated with BAXFENDY and Greater (≥1%) than Placebo During the 12-Week, Randomized, Double-Blind Periods from Three Clinical Trials in Patients with Hypertension:

Laboratory Tests

Serum Potassium

During the 12-week, randomized, double-blind periods from BAXFENDY clinical trials in patients with hypertension, increases in serum potassium (>5.5 mEq/L) were reported for 12.2% of patients administered BAXFENDY 2 mg, 6.3% of patients administered BAXFENDY 1 mg, and 0.9% of placebo-treated patients.

Serum Sodium

During the 12-week, randomized, double-blind periods from BAXFENDY clinical trials in patients with hypertension, decreases in serum sodium (<130 mEq/L) were reported for 3.7% of patients administered BAXFENDY 2 mg, 3.3% of patients administered BAXFENDY 1 mg, and 0.9% of placebo-treated patients.

Estimated Glomerular Filtration Rate (eGFR)

A decrease in mean eGFR was observed in BAXFENDY clinical trials in patients with hypertension. At Week 12, the mean placebo-corrected decrease in eGFR was 8.0 mL/min/1.73 m² in the BAXFENDY 2 mg group and 7.1 mL/min/1.73 m² in the BAXFENDY 1 mg group. In BAXFENDY-treated patients, the mean reduction in eGFR appeared to plateau by Week 12 and the mean eGFR increased after BAXFENDY discontinuation, suggesting a hemodynamic effect on renal function.

7.1 Drugs That Increase Serum Potassium

Monitor serum potassium more frequently when BAXFENDY is used concomitantly with drugs that impair potassium excretion or increase serum potassium. Concomitant use may increase the risk of hyperkalemia [see Warnings and Precautions (5.1)].

7.2 Effect of Other Drugs on BAXFENDY

Strong and Moderate CYP3A Inducers

Monitor the therapeutic effect of BAXFENDY more frequently when concomitantly used with strong or moderate CYP3A inducers.

Baxdrostat is a CYP3A substrate. Strong or moderate CYP3A inducers may decrease baxdrostat plasma concentration, which may reduce the efficacy of BAXFENDY.

Risk Summary

There are no available data on the use of BAXFENDY during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcome. Hypertension during pregnancy poses a risk to the mother and fetus (see Clinical Considerations). Although studies in animals have shown embryo-fetal toxicity at baxdrostat exposures >29 times the human exposure at the clinical dose of 2 mg, the clinical significance of these findings is unclear (see Data).

The 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% to 4% and 15% to 20%, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Hypertension in pregnancy increases the risk for adverse maternal outcomes including pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension also increases the risk of adverse fetal outcomes including intrauterine growth restriction and stillbirth. Pregnant women with hypertension should be carefully monitored and managed accordingly.

Data

Animal Data

While baxdrostat had no effects on embryo-fetal development in rats or rabbits dosed through organogenesis at exposures up to 54‑fold (rat) and 29-fold (rabbit) the human dose of 2 mg, baxdrostat showed greatly reduced potency in rats compared to humans, which limits the interpretability of the rodent data. Higher baxdrostat doses were associated with increased incidence of adverse skeletal malformations in the rat and adverse decrease in rabbit fetal weights.

No adverse effects were noted in a pre- and postnatal study in rats dosed from gestation day 6 through lactation day 20 at exposures up to 65-fold the human exposure at 2 mg.

Risk Summary

There are no data on the presence of baxdrostat in human milk, the effects on the breastfed infant, or the effects on milk production. Baxdrostat transfers to milk in lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for BAXFENDY and any potential adverse effects on the breastfed infant from BAXFENDY or from the underlying maternal condition.

The safety and effectiveness of BAXFENDY in pediatric patients under 18 years of age have not been established.

No dose adjustment is required based on age [see Clinical Pharmacology (12.3)]. In the BaxHTN trial [see Clinical Studies (14)], 88 (33%) patients were 65 to 74 years of age, and 33 (12%) patients were ≥75 years of age in the BAXFENDY 2 mg group; and 71 (27%) patients were 65 to 74 years of age, and 25 (10%) patients were ≥75 years of age in the BAXFENDY 1 mg group. No overall differences in effectiveness were observed between these patients and younger adult patients. Hyperkalemia occurred at a higher incidence in patients ≥65 years of age [see Warnings and Precautions (5.1)]. Among patients 65 to 74 years of age, hyperkalemia occurred in 12 (14%) patients treated with BAXFENDY 2 mg, 7 (10%) patients treated with BAXFENDY 1 mg, and 3 (3%) patients treated with placebo. Among patients ≥75 years of age, hyperkalemia occurred in 7 (21%) patients treated with BAXFENDY 2 mg, none of the patients treated with BAXFENDY 1 mg, and none of the patients treated with placebo.

Safety and effectiveness of BAXFENDY initiated in patients with eGFR < 45 mL/min/1.73 m² have not been established [see Clinical Studies (14)]. No dosage adjustment is required in patients with an eGFR ≥45 mL/min, unless assessed to be at risk of hyperkalemia [see Dosage and Administration (2.2) and Warnings and Precautions (5.1)].