Tarpeyo

Description

TARPEYO (budesonide) delayed release capsules contain budesonide, a synthetic corticosteroid, as the active ingredient. Budesonide is chemically designated as 16α, 17α-(1RS)-Butylidenebis(oxy)-11β, 21-dihydroxypregna-1,4-diene-3,20-dione and is provided as a mixture of two epimers (22R and 22S). The empirical formula of budesonide is C25H34O6, with a molecular weight of 430.5 g/mol. Budesonide appears as a white to off-white, tasteless, and odorless powder that is practically insoluble in water, sparingly soluble in alcohol, and freely soluble in chloroform.

Each capsule contains beads with inactive ingredients, including sugar spheres (sucrose and starch), hypromellose, polyethylene glycol, citric acid monohydrate, ethyl cellulose, medium chain triglycerides, and oleic acid. The capsule shells are composed of hypromellose and titanium oxide (E171), while the printing ink on the capsules includes shellac, propylene glycol, and black iron oxide (E172). The enteric coating of the capsules consists of methacrylic acid and methacrylate copolymer, talc, and dibutyl sebacate.

Uses and Indications

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.

There are no teratogenic or nonteratogenic effects associated with TARPEYO.

Dosage and Administration

The recommended dosage for the medication is 16 mg, administered orally once daily in the morning, at least one hour before a meal. It is essential that the tablet is swallowed whole; the tablet should not be opened, crushed, or chewed to ensure proper release and absorption of the active ingredient.

In cases where discontinuation of therapy is necessary, it is advised to taper the dosage to 8 mg once daily for the final two weeks to minimize potential withdrawal effects.

Contraindications

Use of TARPEYO is contraindicated in patients with hypersensitivity to budesonide or any of the components of the formulation. This contraindication is based on the potential for severe allergic reactions, which may pose significant health risks to affected individuals.

Warnings and Precautions

Patients receiving corticosteroid therapy should be closely monitored for potential adverse effects, particularly those related to hypercorticism and adrenal axis suppression. It is essential to adhere to established guidelines regarding corticosteroid use, especially in individuals with hepatic impairment, as they may be at an increased risk for these complications. A gradual tapering of the medication is recommended upon discontinuation to mitigate withdrawal symptoms and adrenal insufficiency.

Immunosuppression is another significant concern associated with corticosteroid therapy. Healthcare professionals should exercise caution when prescribing these medications to patients with active or quiescent tuberculosis infections, as well as those with untreated fungal, bacterial, systemic viral, or parasitic infections, including ocular herpes simplex. The use of corticosteroids may also diminish the efficacy of vaccines, necessitating careful consideration of vaccination status prior to initiation of therapy.

Additionally, it is crucial to monitor patients who have concomitant conditions that may be exacerbated by corticosteroid use, such as hypertension and diabetes mellitus. Regular assessments of these conditions can help prevent potential complications and ensure optimal management of the patient's overall health.

Side Effects

In clinical trials, the most common adverse reactions observed in patients receiving TARPEYO, occurring at a frequency of 5% or greater, included peripheral edema, hypertension, muscle spasms, acne, headache, upper respiratory tract infection, face edema, weight increase, dyspepsia, dermatitis, arthralgia, and increased white blood cell count.

Specifically, peripheral edema was reported in 33 patients (17%) in the TARPEYO group compared to 10 patients (5%) in the placebo group. Hypertension occurred in 23 patients (12%) receiving TARPEYO versus 6 patients (3%) in the placebo group. Muscle spasms were noted in 23 patients (12%) in the TARPEYO group, while only 8 patients (4%) in the placebo group experienced this reaction. Acne was reported in 22 patients (11%) receiving TARPEYO compared to 2 patients (1%) in the placebo group. Headache was experienced by 19 patients (10%) in the TARPEYO group, compared to 14 patients (7%) in the placebo group. Upper respiratory tract infections were reported in 16 patients (8%) receiving TARPEYO versus 12 patients (6%) in the placebo group. Face edema was noted in 15 patients (8%) in the TARPEYO group, while only 1 patient (0.5%) in the placebo group reported this reaction. Weight increase was observed in 13 patients (7%) receiving TARPEYO compared to 6 patients (3%) in the placebo group. Dyspepsia and dermatitis were reported in 13 (7%) and 12 (6%) patients, respectively, in the TARPEYO group, compared to 4 (2%) and 2 (1%) in the placebo group. Lastly, arthralgia was noted in 12 patients (6%) receiving TARPEYO versus 4 patients (2%) in the placebo group, and an increased white blood cell count was observed in 11 patients (6%) in the TARPEYO group compared to 1 patient (0.5%) in the placebo group.

Additional adverse reactions of clinical significance include hypercorticism and adrenal axis suppression, particularly in patients with hepatic impairment, who may be at increased risk. It is recommended to taper the dosage upon discontinuation. Immunosuppression and an increased risk of infection are also concerns; therefore, TARPEYO should be avoided in patients with active or quiescent tuberculosis, untreated fungal, bacterial, systemic viral, or parasitic infections, or ocular herpes simplex. The use of TARPEYO may also affect vaccine efficacy. Furthermore, patients with concomitant conditions where corticosteroids may have unwanted effects, such as hypertension or diabetes mellitus, should be monitored closely. Hypersensitivity reactions to budesonide or any of the ingredients in TARPEYO have also been reported.

Drug Interactions

Concomitant use of potent CYP3A4 inhibitors, such as ketoconazole and grapefruit juice, is contraindicated due to the potential for increased systemic concentrations of budesonide. This interaction may lead to an enhanced pharmacological effect and an increased risk of adverse reactions. It is advisable to avoid the use of these inhibitors while administering budesonide to ensure patient safety and therapeutic efficacy. Monitoring for signs of increased systemic effects is recommended if such interactions cannot be avoided.

Packaging & NDC

The table below lists all NDC Code configurations of Tarpeyo (budesonide), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and efficacy of TARPEYO in pediatric patients have not been established. There are currently no data available to support its use in children or adolescents. Healthcare professionals should exercise caution when considering TARPEYO for this population, as the lack of established guidelines may impact treatment decisions.

Geriatric Use

Clinical studies of TARPEYO did not include a sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, other reported clinical experience has not identified significant differences in responses between elderly patients and younger patients.

In general, dose selection for geriatric patients should be approached with caution. This is particularly important due to the increased likelihood of decreased hepatic, renal, or cardiac function in this population, as well as the potential for concomitant diseases or other drug therapies that may affect treatment outcomes. Therefore, healthcare providers are advised to carefully consider these factors when prescribing TARPEYO to elderly patients, ensuring appropriate monitoring and adjustments as necessary.

Pregnancy

The available data from published case series, epidemiological studies, and reviews indicate that oral budesonide use in pregnant women has not been associated with an increased risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. However, it is important to note that there are inherent risks to both the mother and fetus associated with IgA nephropathy, which may lead to adverse maternal outcomes such as increased rates of cesarean section, pregnancy-induced hypertension, pre-eclampsia, and preterm delivery, as well as adverse fetal/neonatal outcomes including stillbirth and low birth weight.

Infants exposed to corticosteroids, including budesonide, in utero may be at risk for hypoadrenalism. Healthcare professionals should carefully monitor these infants for signs of hypoadrenalism, such as poor feeding, irritability, weakness, and vomiting, and manage them accordingly.

Animal reproduction studies have demonstrated that budesonide is teratogenic and embryo-lethal in pregnant rats and rabbits. In studies where pregnant rats were administered subcutaneous budesonide during organogenesis, doses approximately 0.3 times the maximum recommended human dose (MRHD) resulted in increased fetal loss, decreased pup weights, and skeletal abnormalities. Maternal toxicity was also observed at these dose levels. Similarly, in pregnant rabbits, subcutaneous doses starting at approximately 0.03 times the MRHD led to increased maternal abortion rates and adverse effects on fetal development, including reduced litter weights.

In a peri- and post-natal development study, treatment of pregnant rats with budesonide from Day 15 post coitum to Day 21 post partum did not affect delivery but did impact the growth and development of offspring. Notably, offspring survival was reduced, and surviving offspring exhibited decreased mean body weights at birth and during lactation at exposures equal to or greater than 0.012 times the MRHD, with these findings occurring in the context of maternal toxicity.

The estimated background risk of major birth defects and miscarriage in the U.S. general population is 2% to 4% and 15% to 20%, respectively. All pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. Given these considerations, healthcare professionals should weigh the potential benefits and risks of budesonide use in pregnant patients, particularly those with IgA nephropathy, and counsel patients accordingly.

Lactation

Breastfeeding is not expected to result in significant exposure of the infant to TARPEYO. Lactation studies have not been conducted with oral budesonide, including TARPEYO, and no information is available on the effects of the drug on the breastfed infant or on milk production.

One published study indicates that budesonide is present in human milk following maternal inhalation, with infant doses estimated to be approximately 0.3% to 1% of the maternal weight-adjusted dosage. The milk to plasma ratio was approximately 0.5. Budesonide was not detected in plasma, and no adverse events were noted in breastfed infants following maternal use of inhaled budesonide.

Assuming a daily average milk intake of about 150 mL/kg/day and a milk to plasma ratio of 0.5, the estimated oral dose of budesonide for a 5 kg infant is expected to be less than 2 mcg/day for a maternal dose of 16 mg TARPEYO. This represents about 0.1% of the maternal dose and approximately 3% of the highest inhaled dose used clinically for asthma in infants.

Routine monitoring of linear growth in infants is recommended with chronic use of budesonide in the nursing mother. The developmental and health benefits of breastfeeding should be considered alongside the mother's clinical need for TARPEYO and any potential adverse effects on the breastfed infant from TARPEYO or from the underlying maternal condition.

Renal Impairment

There is no specific information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

Hepatic Impairment

Patients with moderate to severe hepatic impairment (Child-Pugh Class B and C, respectively) may experience an increased risk of hypercorticism and adrenal axis suppression due to elevated systemic exposure to budesonide. Therefore, the use of budesonide is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C).

For patients with moderate hepatic impairment (Child-Pugh Class B), it is essential to monitor for increased signs and/or symptoms of hypercorticism. Regular assessment of liver function and clinical symptoms is recommended to ensure patient safety and to adjust treatment as necessary.

Overdosage

Acute overdosage of corticoids is infrequently associated with reports of acute toxicity or fatal outcomes. In cases of suspected overdosage, it is crucial to note that there is no specific antidote available.

Management of an overdosage situation should focus on supportive and symptomatic therapy. Healthcare professionals are advised to monitor the patient closely and provide appropriate interventions based on the symptoms presented. This may include managing any adverse effects and ensuring the patient's stability throughout the treatment process.

In summary, while the occurrence of severe toxicity or death from corticoid overdosage is rare, prompt recognition and supportive care are essential in managing such cases effectively.

Nonclinical Toxicology

Budesonide has been evaluated for its nonclinical toxicology profile, with specific attention to teratogenic effects, non-teratogenic effects, carcinogenicity, and mutagenicity.

No teratogenic effects were observed in the studies conducted. In terms of non-teratogenic effects, budesonide did not impact fertility in rats at subcutaneous doses up to 80 mcg/kg, which is approximately 0.05 times the maximum recommended human dose (MRHD) on a body surface area basis. However, at subcutaneous doses of 20 mcg/kg (approximately 0.012 times the MRHD) and above, there was a noted decrease in prenatal viability and viability of pups at birth and during lactation, alongside a reduction in maternal food consumption and body weight gain. No adverse effects were recorded at a dose of 5 mcg/kg (approximately 0.003 times the MRHD).

Carcinogenicity studies involving budesonide were performed in both rats and mice. A two-year study in Sprague-Dawley rats revealed a statistically significant increase in the incidence of gliomas in male rats at an oral dose of 50 mcg/kg (approximately 0.03 times the MRHD). Additionally, there were increased incidences of primary hepatocellular tumors in male rats at doses of 25 mcg/kg (approximately 0.015 times the MRHD) and higher. No tumorigenicity was observed in female rats at oral doses up to 50 mcg/kg. In a separate two-year study in male Sprague-Dawley rats, no gliomas were detected at the same oral dose of 50 mcg/kg, although a statistically significant increase in hepatocellular tumors was noted. Similar findings were reported with concurrent reference corticosteroids, prednisolone and triamcinolone acetonide. In a 91-week study in mice, budesonide did not demonstrate treatment-related carcinogenicity at oral doses up to 200 mcg/kg (approximately 0.06 times the MRHD).

Budesonide was also assessed for genotoxicity and was found to be non-genotoxic in several tests, including the Ames test, the mouse lymphoma cell forward gene mutation test, the human lymphocyte chromosome aberration test, the Drosophila melanogaster sex-linked recessive lethal test, the rat hepatocyte UDS test, and the mouse micronucleus test.

Postmarketing Experience

Postmarketing experience with TARPEYO has identified several important considerations for healthcare providers and patients. Reports indicate that TARPEYO may lead to hypercorticism and adrenal axis suppression; therefore, it is essential for patients to follow a taper schedule as instructed by their healthcare provider upon discontinuation of therapy.

Additionally, TARPEYO is associated with immunosuppression, which necessitates caution regarding exposure to infectious diseases. Patients are advised to avoid contact with individuals who have chicken pox or measles and to seek immediate consultation with their healthcare provider if exposed. There is an increased risk of developing various infections, including exacerbation of existing tuberculosis, as well as fungal, bacterial, viral, or parasitic infections, and ocular herpes simplex. Patients should contact their healthcare provider if they experience any symptoms indicative of infection.

The most frequently reported side effects of TARPEYO include peripheral edema (swelling of the lower legs, ankles, and feet), facial swelling, weight gain, hypertension, dyspepsia, muscle spasms, skin irritation or inflammation, acne, arthralgia, headache, elevated white blood cell count, and upper respiratory tract infections.

Patients are encouraged to consult their healthcare provider for medical advice regarding side effects and may report adverse events to the FDA at 1-800-FDA-1088.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling (Patient Information) to understand the medication fully. It is important to inform patients that TARPEYO may cause hypercorticism and adrenal axis suppression. They should be instructed to follow a taper schedule as directed by their healthcare provider if they need to discontinue therapy.

Healthcare providers should discuss the immunosuppressive effects of TARPEYO with patients, emphasizing the need to avoid exposure to individuals with chicken pox or measles. Patients should be advised to consult their healthcare provider immediately if they are exposed to these infections. Additionally, they should be made aware of the increased risk of developing various infections, including the worsening of existing tuberculosis, and other fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex. Patients must be instructed to contact their healthcare provider if they experience any symptoms of infection.

Providers should also offer guidance regarding vaccination schedules for immunocompromised patients to ensure appropriate preventive measures are taken.

Patients should be informed that TARPEYO delayed release capsules must be swallowed whole and should not be chewed, crushed, or broken. They should take TARPEYO in the morning, at least 1 hour before a meal, to ensure optimal absorption.

Lastly, it is essential to advise patients to avoid the consumption of grapefruit juice during their TARPEYO therapy, as it may interact with the medication.

Storage and Handling

The product is supplied in a container that must be kept tightly closed to maintain its integrity. It should be stored at a temperature range of 20-25°C (68-77°F), with permissible excursions between 15° to 30°C (59° to 86°F). Additionally, it is essential to protect the product from moisture to ensure optimal stability and efficacy.

Additional Clinical Information

Clinicians should counsel patients on the importance of monitoring for signs of adrenal axis suppression when discontinuing therapy or switching between corticosteroids. In patients with moderate hepatic impairment (Child-Pugh Class B), increased signs and/or symptoms of hypercorticism should be closely observed. Additionally, clinicians should monitor for the development of infections and consider the withdrawal of TARPEYO as necessary.

Before initiating immunosuppressive treatment with TARPEYO, it is essential to screen patients for hepatitis B infection. Consultation with healthcare professionals experienced in managing hepatitis B is recommended for monitoring and potential antiviral therapy considerations.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Tarpeyo as submitted by Calliditas Therapeutics AB. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)