布地奈德缓释胶囊(Tarpeyo)的详细说明书：作用与功效,用法用量,副作用,注意事项等

The R&D company of Budesonide Sustained-Release Capsules (Tarpeyo) is Calliditas, Sweden. On December 17, 2021, the U.S. FDA approved the marketing of Budesonide Sustained-Release Capsules.

Indications of Budesonide Sustained-Release Capsules (Tarpeyo)

It is suitable for adults who are at risk of disease progression to reduce the risk of primary disease. Loss of renal function in patients with immunoglobulin A nephropathy (IgAN).

Budesonide extended-release capsules (Tarpeyo) dosage

1. Dosage: 16 mg orally once daily. When treatment is stopped, reduce the dose to 8 mg once daily during the last 2 weeks of treatment.

2. Dosage

Desonide extended-release capsules should be swallowed whole in the morning, at least 1 hour before meals. Do not open, crush or chew them.

3. Missed dose handling German. White-coated opaque capsules with black words "CAL104MG" printed on the capsule body.

5. Overdose

Acute poisoning and/or death are rarely reported. In the event of acute overdose, there is no specific antidote.

6. Recommended course of treatment

The recommended course of treatment is 9 months. style="text-align:center">

The pictures are from public channels (such as the official website of the FDA, the official website of the original drug manufacturer, etc.) and are for reference only.

Contraindications of Budesonide Extended-Release Capsules (Tarpeyo)

Budesonide is contraindicated in patients who are allergic to budesonide or any of its ingredients. De sustained-release capsules. Severe hypersensitivity reactions, including allergic reactions, have occurred when using other budesonide preparations.

Precautions for budesonide sustained-release capsules (Tarpeyo)

1. Cushing's syndrome and adrenal axis suppression

When Systemic effects such as Cushing's syndrome and adrenal suppression may occur with long-term use of corticosteroids. Corticosteroids can reduce the ability of the hypothalamic-pituitary-adrenal (HPA) axis to respond to stress.

Supplementation is recommended when patients are facing surgery or other stressful situations. Systemic corticosteroids.

Avoid use in patients with severe hepatic impairment (Child-Pugh Class C)

Monitor patients with moderate hepatic impairment (Child-Pugh Class B) for increased signs and/or symptoms of Cushing syndrome.

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2. Immunosuppression and increased risk of infection

Corticosteroids, including budesonide extended-release capsules, can suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoal or helminthic pathogens. Corticosteroids can. : Decreases resistance to new infections, aggravates existing infections, increases risk of disseminated infection, increases risk of reactivation or exacerbation of latent infection, masks certain signs of infection.

Infections associated with corticosteroids can be mild but can also be severe and sometimes fatal. The incidence of infectious complications increases with increasing doses of corticosteroids

Monitor the development of infection and consider discontinuing budesonide extended-release capsules as needed

3. Pulmonary tuberculosis

If positive for latent tuberculosis or tuberculin. Use of budesonide extended-release capsules to treat certain diseases may lead to recurrence of tuberculosis. For patients with latent tuberculosis or positive tuberculin reaction, budesonide extended-release capsules should be discontinued.

4. Varicella zoster virus and measles virus infections

Chickenpox and measles can have a serious or even fatal course in nonimmune patients who are taking corticosteroids, including budesonide extended-release capsules. For patients who have not suffered from these diseases or lack immunity and are receiving corticosteroid treatment, special attention should be paid to avoid exposure to chickenpox and measles:

(1) If patients receiving budesonide extended-release capsules are exposed to chickenpox, varicella zoster immunoglobulin prophylaxis may be required. If chickenpox occurs, treatment with antiviral medications may be considered.

(2) If patients receiving budesonide extended-release capsules are exposed to measles, immune globulin prophylaxis may be required.

5. Hepatitis B virus reactivation

Reactivation of hepatitis B virus may occur in hepatitis B virus carriers treated with immunosuppressive doses of corticosteroids, including budesonide extended-release capsules. Reactivation may also occur occasionally in patients receiving corticosteroids from apparently resolved hepatitis B infection.

Before starting immunosuppressive therapy with budesonide extended-release capsules, patients should be screened for hepatitis B virus infection. For patients who show evidence of hepatitis B virus infection, consultation with a physician with expertise in hepatitis B management is recommended for monitoring and consideration of hepatitis B antiviral therapy.

6. Fungal infections

Corticosteroids, including budesonide extended-release capsules, may aggravate systemic fungal infections; therefore, avoid using budesonide extended-release capsules in the presence of such infections.

7. Amebiasis

Corticosteroids, including budesonide extended-release capsules, may activate latent amebiasis. Therefore, it is recommended that latent or active amebiasis be ruled out before initiating therapy with budesonide extended-release capsules in patients who have spent time in tropical areas or in patients with unexplained diarrhea.

8. Cerebral malaria

Avoid the use of corticosteroids, including budesonide extended-release capsules, in patients with cerebral malaria.

9. Ocular Herpes Simplex Virus Infection

Corticosteroids, including budesonide extended-release capsules, may aggravate ocular herpes simplex virus infection; therefore, avoid using budesonide extended-release capsules in the presence of such infections.

10. Kaposi's sarcoma

Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy (most commonly for chronic diseases). Discontinuation of corticosteroids may result in clinical improvement in Kaposi's sarcoma.

11. Immunization

Corticosteroid treatment, including budesonide extended-release capsules, may reduce the immune response to some vaccines.

12. Other corticosteroid effects

Budesonide extended-release capsule is a corticosteroid with systemic bioavailability and is expected to cause related adverse reactions. Monitor patients with hypertension, prediabetes, diabetes, osteoporosis, peptic ulcers, glaucoma, or cataracts, or a family history of diabetes or glaucoma, or any other condition in which corticosteroids may have adverse effects.

Adverse reactions of Budesonide extended-release capsules (Tarpeyo)

The most common adverse reactions with an incidence rate ≥2% higher than the placebo group are as follows: hypertension, mania/hypomania, acne, bruising, weight gain, peripheral edema, abnormal hair growth, indigestion, dyspnea, dizziness and muscle spasm.

Drug interactions of Budesonide extended-release capsules (Tarpeyo)

Interactions with CYP3A4 inhibitors

1. Budesonide is a substrate of CYP3A4. Avoid coadministration with strong CYP3A4 inhibitors, such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin and cyclosporine.

2. Avoid consuming grapefruit juice while taking TARPEYO. Ingestion of grapefruit juice, which inhibits CYP3A4 activity, may increase systemic exposure of budesonide.

Budesonide Extended-Release Capsules (Tarpeyo) Medication for Special Populations

1. Pregnancy

IgA nephropathy during pregnancy is associated with adverse maternal outcomes, including increased rates of cesarean section, pregnancy-induced hypertension, preeclampsia, and preterm birth, as well as adverse fetal/neonatal outcomes, including stillbirth and low birth weight.

2. Lactation period

Breastfeeding is not expected to result in significant infant exposure to budesonide extended-release capsules, lactation studies with oral budesonide have not been conducted, and there is no information on the effects of this drug on breastfed infants or on milk.

3. Pediatric use

The safety and effectiveness of budesonide extended-release capsules in pediatric patients has not been determined.

4. Elderly use

Clinical studies of budesonide extended-release capsules did not include a sufficient number of subjects aged 65 and above to determine whether their responses were different from those of younger subjects. Other reported clinical experiences did not find any difference in response between elderly patients and younger patients.

Dose selection in elderly patients should be cautious and reflect reduced hepatic, renal, or cardiac function, as well as a greater frequency of concurrent disease or other drug therapy.

5. Hepatic insufficiency

Patients with moderate to severe hepatic impairment (Child-Pugh class B and C, respectively) may be at higher risk of Cushing's syndrome and adrenal axis suppression due to increased systemic exposure of budesonide.

Avoid use in patients with severe hepatic impairment (Child-Pugh Class C). Monitor patients with moderate hepatic impairment (Child-Pugh class B) for an increase in signs and/or symptoms of Cushing's syndrome.

Mechanism of action of Budesonide extended-release capsules (Tarpeyo)

Budesonide is a corticosteroid with strong glucocorticoid activity and weak mineralocorticoid activity, and undergoes significant first-pass metabolism. Mucosal B cells in the ileum (including Peyer's patches) express glucocorticoid receptors and are responsible for the production of galactose-deficient IgA1 antibodies (Gd-Ag1) that cause IgA nephropathy.

Through their anti-inflammatory and immunosuppressive effects on the glucocorticoid receptor, corticosteroids can regulate the number and activity of B cells. The extent to which the efficacy of budesonide extended-release capsules is mediated through local effects in the ileum versus systemic effects has not been determined.

Budesonide extended-release capsules (Tarpeyo) pharmacokinetics

1. Absorption

After a single oral administration of TARPEYO 16mg to healthy subjects, the average geometric mean Cmax (CV%) was 4.4ng/mL (58.3), and the AUC0-24 was 24.1h*ng/mL (49.7). The median Tlag (minimum, maximum) is 3.1 hours (0,6), while the median Tmax (minimum, maximum) is 5.1 hours (4.5,10).

Food Effects: No clinically relevant food effects on overall systemic exposure to budesonide were observed when a moderate or high-fat meal was ingested 1 hour after administration of budesonide extended-release capsules.

2. Distribution

In the concentration range of 0.43 to 99ng/mL, budesonide is approximately 85%-90% bound to plasma proteins in the blood, and the steady-state distribution volume reported in the literature is 3-4L/kg.

3. Metabolism

Budesonide is metabolized mainly in the liver (and to a lesser extent the intestine) through the oxidative pathway of CYP3A4 into two major metabolites: 16α-hydroxyprednisolone and 6β-hydroxybudesonide, whose corticosteroid activity is less than 1% of budesonide.

4. Elimination

Budesonide has a high plasma clearance rate, ranging from 0.9 to 1.8L/min in healthy adults, which is close to the estimated liver blood flow, thus indicating that budesonide is a drug with high hepatic clearance.

After a single oral administration of 16 mg of budesonide extended-release capsules to healthy subjects, the elimination half-life (t½) of TARPEYO ranged from 5.0 to 6.8 hours.

5. Excretion

Budesonide is excreted in the form of metabolites through urine and feces. Approximately 60% of the recovered radioactivity is found in urine after oral and intravenous administration of micronized [3H]-budesonide. The major metabolites, including 16α-hydroxyprednisolone and 6β-hydroxybudesonide, are primarily excreted via the kidneys in intact or conjugated forms. Unchanged budesonide was not detected in urine.

Pharmacokinetics of budesonide extended-release capsules (Tarpeyo) in special populations

1. Age, race and weight

The effects of age, race and weight on the pharmacokinetics of budesonide extended-release capsules have not been determined.

2. Gender

Among the 143 healthy volunteers included in the phase 1 study, 29% were women. The pharmacokinetics of budesonide were similar between men and women.

3. Hepatic insufficiency

The AUC of budesonide in subjects with moderate hepatic impairment (Child-Pugh Class B) is 3.5 times that of healthy volunteers, while the AUC of budesonide in subjects with mild hepatic impairment (Child-Pugh Class A) is approximately 1.4 times that of healthy volunteers.

Patients with severe hepatic impairment (Child-Pugh class C) have not been studied.

4. Renal insufficiency

Intact budesonide is not excreted by the kidneys. The major metabolite of budesonide, which has negligible corticosteroid activity, is mostly (60%) excreted in the urine.

Storage of Budesonide extended-release capsules (Tarpeyo)

Store at 20°C-25°C (68-77°F), with an allowed excursion between 15°C-30°C (59° to 86°F). Keep container tightly closed to prevent moisture.