Budesonide for Inflammatory Bowel Disease

Budesonide is a glucocorticoid with high topical potency and about 85% to 90% first-pass hepatic metabolism, so systemic effects are far less than with prednisolone. It is used for mild to moderate ileocaecal Crohn disease and, as a colonic-release preparation, for mild to moderate ulcerative colitis.

Classification. Corticosteroid; locally acting glucocorticoid.

Mechanism. Binds glucocorticoid receptors with high affinity, suppressing inflammatory gene transcription and cytokine release in the gut lining.

Pharmacodynamics. Response in active Crohn disease at 2 to 4 weeks; remission rates are lower than with systemic steroids, but with fewer adverse effects.

Pharmacokinetics. Release depends on formulation: the ileocaecal capsule releases from the terminal ileum to the right colon; the colonic-release tablet releases throughout the colon. Systemic bioavailability about 10% to 15%. Half-life 2 to 4 hours.

Metabolism. Extensive first-pass metabolism by CYP3A4 to inactive metabolites; excreted in urine and faeces.

Adult oral doses unless stated.

Active mild to moderate Crohn disease affecting the ileum or ascending colon.

• 9 mg once daily in the morning, for up to 8 weeks.

• Then taper: 6 mg daily for 2 weeks, then 3 mg daily for 2 weeks, then stop.

Maintenance of remission in Crohn disease. 6 mg daily has been used for up to 12 months, but evidence of benefit is weak and bone and adrenal effects accumulate; usually avoided.

Active mild to moderate ulcerative colitis (colonic-release tablets).

• 9 mg once daily in the morning, for up to 8 weeks.

• Stop without taper in many labels.

Distal ulcerative colitis (rectal).

• Foam 2 mg in each actuation: 2 mg twice daily for 2 weeks, then once daily for 4 weeks.

• Enema 2 mg in 100 mL at bedtime for 4 to 6 weeks.

Eosinophilic oesophagitis (reference). Orodispersible tablet 1 mg twice daily or viscous suspension 1 mg twice daily; use local labels for doses.

Children. Use under specialist care only, with doses of 6 to 9 mg daily in Crohn disease for ages 8 years and over; limited labelled data.

Kidney and liver adjustment.

• Kidney impairment: no adjustment.

• Liver impairment: moderate to severe impairment increases systemic exposure; avoid in cirrhosis or use with caution at the lowest dose.

Contraindications. Hypersensitivity; untreated systemic infection, tuberculosis or fungal infection; severe liver impairment.

Common adverse effects. Headache, acne, moon face, insomnia, mood changes, dyspepsia, abdominal pain and fluid retention. Systemic steroid effects are less than with prednisolone but still occur.

Serious adverse effects.

• Adrenal suppression, mainly after prolonged or high-dose use or when switching from systemic steroids.

• Infections, including reactivation of latent tuberculosis, and masking of infection.

• Osteoporosis, cataract and glaucoma with prolonged use.

• Hyperglycaemia and hypertension.

• Psychiatric reactions including depression and euphoria.

Major interactions.

• Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, cobicistat): large increases in budesonide levels, causing Cushing syndrome and adrenal suppression; avoid.

• Grapefruit juice: increases levels; avoid.

• CYP3A4 inducers (rifampicin, carbamazepine, phenytoin): reduce efficacy.

• Oestrogen-containing contraceptives: may modestly raise levels.

• Antacids and acid suppressants may alter release of pH-dependent formulations.

• Live vaccines: avoid with significant immunosuppression.

Special groups.

• Pregnancy: limited data; use if benefit outweighs risk.

• Breastfeeding: low systemic levels; acceptable.

• Children: specialist use only.

• Older adults: monitor bone density, glucose and blood pressure.

• Kidney impairment: no adjustment.

• Liver impairment: avoid in severe impairment.

• Regional: limited availability in East Africa; prednisolone is often used instead, with more systemic effects.

Formulations. Capsules 3 mg (ileocaecal release); tablets 9 mg (colonic release); foam 2 mg in each dose; enema 2 mg in 100 mL.

Administration.

• Swallow capsules or tablets whole in the morning, with or without food.

• Do not take with grapefruit juice.

• Rectal products: empty the bowel first and administer at bedtime.

Baseline. Blood pressure, glucose, bone risk and infection screening (including tuberculosis risk).

Monitoring.

• Symptoms and disease activity at 2 to 4 weeks.

• Blood pressure and glucose.

• Bone density if repeated or prolonged courses.

• Signs of adrenal suppression, such as fatigue, hypotension and hypoglycaemia, when stopping.

Therapeutic drug monitoring. Not applicable.

Stopping. Taper the Crohn disease capsule over 4 weeks. Do not stop abruptly after switching from systemic steroids.

Referral and escalation. Refer for steroid-dependent disease or failure of response by 4 weeks, as it indicates the need for an immunomodulator or biologic. Urgent admission for acute severe colitis.