Tarpeyo Drug Information

is indicated to reduce the loss of kidney function in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression. TARPEYO is a corticosteroid indicated to reduce the loss of kidney function in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression.

The recommended duration of therapy is 9 months, with a dosage of 16 mg administered orally once daily . When discontinuing therapy, reduce the dosage to 8 mg once daily for the last 2 weeks of therapy . The delayed release capsules should be swallowed whole in the morning, at least 1 hour before a meal. Do not open, crush or chew. If a dose is missed, take the prescribed dose at the next scheduled time.

Do not double the next dose. Safety and efficacy of treatment with subsequent courses of TARPEYO have not been established. The recommended dosage is 16 mg administered orally once daily, in the morning at least 1 hour before a meal.

Swallow whole. Do not open, crush or chew. When discontinuing, reduce dosage to 8 mg once daily for the last two weeks.

Clinical Trials Experience

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 TARPEYO was evaluated in 389 patients in the randomized, double-blind, placebo-controlled study, NefIgArd (NCT: 03643965, Phase 3 clinical study in adults with primary IgAN). The data below reflect TARPEYO exposure in 195 patients with a median duration of 41 weeks, compared with comparable exposure to placebo in 194 patients. The most common adverse reactions, reported in greater than or equal to 5% of TARPEYO-treated patients and greater than or equal to 2% higher than placebo, in the 9-month treatment period are listed in Table 1. Most adverse reactions that occurred at a greater incidence for TARPEYO compared to placebo were consistent with hypercortisolism and reversible, resolving within 3 months after discontinuation.

Table 1: Reported adverse reactions occurring in greater than or equal to 5% of TARPEYO treated patients, and greater than or equal to 2% higher than Placebo Adverse Reaction TARPEYO 16 mg (N=195) Placebo (N=194) n (%) n (%) Peripheral edema 33 10 Hypertension 23 6 Muscle spasms 23 8 Acne 22 2 Headache 19 14 Upper respiratory tract infection 16 12 Face edema 15 1 Weight increased 13 6 Dyspepsia 13 4 Dermatitis 12 2 Arthralgia 12 4 White blood cell count increased 11 1

Interaction with

CYP3A4 Inhibitors Budesonide is a substrate for CYP3A4. Avoid use with potent CYP3A4 inhibitors; e.g. ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, and cyclosporine . Avoid ingestion of grapefruit juice with TARPEYO. Intake of grapefruit juice, which inhibits CYP3A4 activity, can increase the systemic exposure to budesonide .

Pregnancy Risk Summary The available data from published case series, epidemiological studies and reviews with oral budesonide use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with IgA Nephropathy. Infants exposed to in utero corticosteroids, including budesonide, are at risk for hypoadrenalism (see Clinical Considerations ). In animal reproduction studies with pregnant rats and rabbits, administration of subcutaneous budesonide during organogenesis at doses approximately 0.3 times or 0.03 times, respectively, the maximum recommended human dose (MRHD), resulted in increased fetal loss, decreased pup weights, and skeletal abnormalities.

Maternal toxicity was observed in both rats and rabbits at these dose levels (see Data ). The estimated background risk of major birth defects and miscarriage of the indicated population is unknown. All pregnancies have a background risk of birth defects, 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 IgA nephropathy in pregnancy is associated with adverse maternal outcomes, including increased rates of cesarean section, pregnancy-induced hypertension, pre-eclampsia and preterm delivery, and adverse fetal/neonatal outcomes, including stillbirth and low birth weight. Fetal/Neonatal Adverse Reactions Hypoadrenalism may occur in infants born to mothers receiving corticosteroids during pregnancy. Infants should be carefully observed for signs of hypoadrenalism, such as poor feeding, irritability, weakness, and vomiting, and managed accordingly.

Data Animal Data Budesonide was teratogenic and embryo-lethal in rabbits and rats. In an embryo-fetal development study in pregnant rats dosed subcutaneously with budesonide during the period of organogenesis on gestation days 6 to 15 there were effects on fetal development and survival at subcutaneous doses up to approximately 500 mcg/kg in rats (approximately 0.3 times the maximum recommended human dose (MRHD) on a body surface area basis). In an embryo-fetal development study in pregnant rabbits dosed during the period of organogenesis on gestation days 6 to 18, there was an increase in maternal abortion, and effects on fetal development and reduction in litter weights at subcutaneous doses from approximately 25 mcg/kg (approximately 0.03 times the MRHD on a body surface area basis). Maternal toxicity, including reduction in body weight gain, was observed at subcutaneous doses of 5 mcg/kg in rabbits (approximately 0.006 times the maximum recommended human dose on a body surface area basis) and 500 mcg/kg in rats (approximately 0.3 times the maximum recommended human dose on a body surface area basis). In a peri- and post-natal development study, subcutaneous treatment of pregnant rats with budesonide during the period from Day 15 post coitum to Day 21 post partum, budesonide had no effects on delivery, but did have an effect on growth and development of offspring. In addition, offspring survival was reduced and surviving offspring had decreased mean body weights at birth and during lactation at exposures ≥ 0.012 times the MRHD (on a mg/m 2 basis at maternal subcutaneous doses of 20 mcg/kg/day and higher). These findings occurred in the presence of maternal toxicity.

Pediatric Use The safety and efficacy of TARPEYO in pediatric patients have not been established.

is contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of TARPEYO. Serious hypersensitivity reactions, including anaphylaxis have occurred with other budesonide formulations. Hypersensitivity to budesonide or any of the ingredients in TARPEYO.

Reports of acute toxicity and/or death following overdosage of corticoids are rare. In the event of acute overdosage, no specific antidote is available. Treatment consists of supportive and symptomatic therapy.