Corticosteroid

Tarpeyo

Approved 15 Dec 2021OralCapsule, delayed release

Indications

TARPEYO 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. ( 1 )

Contraindications

TARPEYO 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. ( 4 )

Warnings and precautions

Hypercorticism and Adrenal Axis Suppression: Follow general warnings concerning corticosteroids, patients with hepatic impairment may be at increased risk. Taper upon discontinuation. ( 2 , 5.1 , 8.6 , 12.3 ) Immunosuppression and Increased Risk of Infection: Avoid use in patients with active or quiescent tuberculosis infection, untreated fungal, bacterial, systemic viral or parasitic infections, or ocular herpes simplex.

May affect vaccine efficacy. ( 5.2 ) Other Corticosteroid Effects: Monitor patients with concomitant conditions where corticosteroids may have unwanted effects (e.g., hypertension, diabetes mellitus). ( 5.3 )

5.1Hypercorticism and Adrenal Axis Suppression

When corticosteroids are used chronically, systemic effects such as hypercorticism and adrenal suppression may occur. Corticosteroids can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to surgery or other stress situations, supplementation with a systemic corticosteroid is recommended. When discontinuing therapy [see Dosing and Administration ( 2 )] or switching between corticosteroids, monitor for signs of adrenal axis suppression.

Patients with moderate to severe hepatic impairment (Child-Pugh Class B and C respectively) could be at an increased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure of oral budesonide. Avoid use in patients with severe hepatic impairment (Child-Pugh Class C). Monitor for increased signs and/or symptoms of hypercorticism in patients with moderate hepatic impairment (Child-Pugh Class B) [see Use in Specific Populations ( 8.6 ), Clinical Pharmacology ( 12.3 )] .

Pregnancy and breastfeeding

8.1Pregnancy 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 [see Warnings and Precautions ( 5.1 )]. 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.

Adverse reactions

The following clinically significant adverse reactions are described elsewhere in the labeling: Hypercorticism and adrenal axis suppression [see Warnings and Precautions ( 5.1 )] Risks of immunosuppression [see Warnings and Precautions ( 5.2 )] Other corticosteroid effects [see Warnings and Precautions ( 5.3 )] Most common adverse reactions ( ≥5%) are peripheral edema, hypertension, muscle spasms, acne, headache, upper respiratory tract infection, face edema, weight increased, dyspepsia, dermatitis, arthralgia, white blood cell count increased.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Calliditas Therapeutics at 1-844-IGA-0011 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical 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 (17) 10 (5) Hypertension 23 (12) 6 (3) Muscle spasms 23 (12) 8 (4) Acne 22 (11) 2 (1) Headache 19 (10) 14 (7) Upper respiratory tract infection 16 (8) 12 (6) Face edema 15 (8) 1 (0.5) Weight increased 13 (7) 6 (3) Dyspepsia 13 (7) 4 (2) Dermatitis 12 (6) 2 (1) Arthralgia 12 (6) 4 (2) White blood cell count increased 11 (6) 1 (0.5)

Tarpeyo

Indications

Contraindications

Warnings and precautions

5.1Hypercorticism and Adrenal Axis Suppression

Two medicines in one question?

5.2Immunosuppression and Increased Risk of Infection

5.3Other Corticosteroid Effects

Interactions

7.1Interaction with CYP3A4 Inhibitors

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

Composition

Official product information

At a glance

Guidelines