Budenofalk (Capsules, Granules, Foam) Instructions for Use

ATC Code

A07EA06 (Budesonide)

Active Substance

Budesonide (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Corticosteroids for oral administration. A drug for the treatment of Crohn’s disease

Pharmacotherapeutic Group

Antidiarrheals, intestinal anti-inflammatory/antimicrobial agents; intestinal anti-inflammatory agents; topical corticosteroids

Pharmacological Action

Glucocorticosteroid for oral administration. The exact mechanism of action of budesonide in inflammatory bowel diseases has not been fully elucidated. Data from clinical-pharmacological and controlled clinical studies clearly indicate that the mechanism of action of budesonide is primarily based on its local action in the intestine.

When taken orally in doses clinically equivalent to systemic glucocorticosteroids, Budesonide causes significantly less suppression of the hypothalamic-pituitary-adrenal system and has a lesser effect on markers of inflammation.

Pharmacokinetics

After oral administration, the average C_max is 1-2 ng/ml. The V_d is about 3 L/kg. Plasma protein binding is 85-90%. About 90% of budesonide undergoes intensive biotransformation in the liver with the participation of CYP3A isoenzymes. The resulting metabolites (6-β-hydroxybudesonide and 16-α-hydroxyprednisolone) have low biological activity (no more than 1% of the activity of budesonide). Depending on the type and severity of liver disease, the metabolism of budesonide involving CYP3A isoenzymes may be reduced.

The mean T_1/2 of budesonide is approximately 3-4 hours. The systemic bioavailability in healthy volunteers and in patients with inflammatory bowel disease after fasting is about 9-13%. The mean clearance of budesonide is about 10 L/min. Budesonide is eliminated by the kidneys only to a limited extent.

Indications

Mild to moderate Crohn’s disease involving the ileum and/or ascending colon; collagenous colitis; autoimmune hepatitis without histological signs of liver cirrhosis.

ICD codes

Dosage Regimen

For Capsules and Granules, administer the total daily dose of 6 mg to 9 mg orally.

Take the entire daily dose once in the morning on an empty stomach.

Swallow the capsules or granules whole; do not chew or crush them.

For the treatment of mild to moderate Crohn’s disease involving the ileum and/or ascending colon, continue therapy until remission is achieved, typically for a duration of up to 8 weeks.

For maintenance of remission, do not use; taper and discontinue the drug after the acute episode.

For autoimmune hepatitis, use an initial dose of 6 mg to 9 mg daily, divided into two or three doses.

Taper the dose gradually based on clinical response and biochemical markers; individualize the maintenance dose.

For collagenous colitis, follow the dosing schedule as for Crohn’s disease.

For rectal Foam, administer one 2 mg applicatorful rectally once daily at bedtime.

Use for the treatment of ulcerative colitis affecting the rectum and sigmoid colon.

Continue treatment for 6 to 8 weeks or as directed for the control of exacerbations.

In all cases, use the lowest effective dose for the shortest possible duration to minimize systemic effects.

Do not abruptly discontinue therapy after prolonged use; always taper the dose.

Adverse Reactions

Metabolism disorders often – Cushing’s syndrome, e.g., moon face, abdominal obesity, decreased glucose tolerance, diabetes mellitus, arterial hypertension, sodium retention with edema development, increased potassium excretion, decreased function or atrophy of the adrenal cortex, red striae, steroid acne, disorder of sex hormone secretion (e.g., amenorrhea, hirsutism, impotence); rarely – growth retardation in children.

Organ of vision glaucoma, cataract, blurred vision.

Digestive system often – indigestion; infrequently – gastric or duodenal ulcers; rarely – pancreatitis; very rarely – constipation.

Immune system often – increased risk of infectious diseases.

Nervous system often – headache; rarely – benign intracranial hypertension (pseudotumor cerebri), including optic disc edema in adolescents.

Psychiatric disorders often – depression, irritability, euphoria; infrequently – psychomotor hyperactivity, anxiety; rarely – aggression.

Musculoskeletal system often – muscle and joint pain, muscle weakness and muscle twitching (contractions), osteoporosis; rarely – osteonecrosis.

Skin and subcutaneous tissues often – allergic exanthema, petechiae, delayed wound healing, contact dermatitis; rarely – ecchymoses.

Cardiovascular system very rarely – increased risk of thrombosis, vasculitis (withdrawal syndrome after long-term therapy).

General reactions very rarely – fatigue, tiredness, general malaise.

Contraindications

Hypersensitivity to budesonide, liver cirrhosis, children and adolescents under 18 years of age.

With caution

Tuberculosis, arterial hypertension, diabetes mellitus, osteoporosis, gastric and duodenal ulcer, glaucoma, cataract, family history of diabetes mellitus or glaucoma, pregnancy, breastfeeding period, any other conditions in which the use of glucocorticosteroids may lead to undesirable effects.

The risk of worsening the course of bacterial, fungal, amoebic, and viral infections during glucocorticosteroid treatment should be carefully assessed.

Use in Pregnancy and Lactation

During pregnancy, use is possible only in cases where the expected benefit to the mother outweighs the potential risk to the fetus.

Budesonide is excreted in breast milk. However, exposure to a breastfed infant after maternal intake of budesonide in the therapeutic range is expected to be low. The decision to either discontinue breastfeeding or discontinue or not initiate budesonide therapy should be made taking into account the benefit of breastfeeding for the child and the benefit of budesonide therapy for the woman.

Use in Hepatic Impairment

Use in liver cirrhosis is contraindicated. There is no reason to believe that dose adjustment is required for patients with non-cirrhotic liver disease or mild hepatic impairment.

Use in Renal Impairment

There are no specific dosing recommendations for patients with renal failure. The duration and frequency of drug administration is determined by the attending physician.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Use with caution in elderly patients to avoid exacerbation of chronic diseases.

Special Precautions

Suppression of the inflammatory response and immune function during budesonide intake increases the susceptibility to severe infections.

Particular concern is varicella, as this usually mild disease can be fatal in immunocompromised patients. Patients who have not previously had varicella should avoid contact with patients with varicella or herpes zoster, and in case of contact, they should seek urgent medical attention.

Immunocompromised patients exposed to measles should receive normal immunoglobulin as soon as possible.

Patients continuously taking Budesonide should not be given live vaccines, due to the possible suppression of the antibody response to such vaccines.

Based on experience in treating patients with late-stage primary biliary cirrhosis suffering from liver cirrhosis, an increase in the systemic availability of budesonide should be expected in all patients with severe liver dysfunction.

Effect on ability to drive vehicles and operate machinery

Patients should be warned about the possibility of blurred vision. If the described adverse reactions occur, one should refrain from performing these activities.

Drug Interactions

The effect of cardiac glycosides may be enhanced due to potassium deficiency.

With simultaneous use with diuretics, potassium excretion may increase.

There is reason to believe that concomitant use with inhibitors of the CYP3A4 isoenzyme, including drugs containing cobicistat, will lead to an increased risk of systemic adverse events. Simultaneous use of such drugs should be avoided, except in cases where the expected benefit outweighs the increased risk of systemic glucocorticosteroid adverse events; in this case, patients should be carefully monitored for the occurrence of systemic glucocorticosteroid adverse events.

With simultaneous use of ketoconazole 200 mg once a day orally, plasma concentrations of budesonide (single dose 3 mg) increased approximately 6-fold. When ketoconazole was administered 12 hours after budesonide, concentrations increased approximately 3-fold. Since the available data are insufficient to provide dose recommendations, simultaneous use of budesonide with ketoconazole should be avoided.

Other strong inhibitors of the CYP3A4 isoenzyme, such as ritonavir, itraconazole, clarithromycin, and grapefruit juice, can also cause a significant increase in plasma concentrations of budesonide. Therefore, their use simultaneously with budesonide should be avoided.

Inducers of the CYP3A4 isoenzyme, including carbamazepine and rifampicin, may reduce the systemic as well as the local effect of budesonide on the intestinal mucosa. In this case, dose adjustment of budesonide is necessary.

Substrates of the CYP3A4 isoenzyme may compete with budesonide. Compounds and drugs that are metabolized with the participation of CYP3A4 may lead to an increase in plasma concentrations of budesonide if the competing substance has a greater affinity for CYP3A4, or, if Budesonide has a greater affinity for CYP3A4, then an increase in the plasma concentration of the competing substance is possible; in such cases, dose adjustment/reduction of such a drug may be required.

There are data on increased plasma estrogen concentrations and enhanced effects of glucocorticosteroids in women taking estrogens or oral contraceptives in combination with budesonide. However, this effect was not observed with low-dose oral contraceptives.

Theoretically, interaction with ion-exchange resins capable of binding steroids (e.g., cholestyramine), as well as antacids, cannot be excluded. With simultaneous administration of these drugs with budesonide, the therapeutic effect of budesonide may decrease as a result of the interaction. Therefore, an interval of 2 hours should be observed between taking these drugs.

Since Budesonide can suppress the function of the adrenal cortex, the ACTH stimulation test for the diagnosis of pituitary insufficiency may show false results (low values).

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.