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Colonic-release Budesonide

Colonic-release Budesonide

The information below is based on the summary of product characteristics approved by regulatory authorities. For full details from the SmPC please click here: https://www.medicines.org.uk/emc/product/1740/smpc#PRODUCTINFO; ECCO Consensus on UC, 2017; ECCO Consensus on Crohn’s Disease 2013; ECCO Toolkit

Additional related ECCO e-Learning resources can be found under IBD Curriculum Topic 6.1-6.11

Introduction and Mechanism of Action

Budesonide is considered as a low-bioavailability steroid with similar efficacy than systemic steroids in mild-to-moderate Crohn’s disease limited to the ileum and/or the right colon. The exact mechanism of budesonide in the treatment of ulcerative colitis is not fully understood. Budesonide is a glucocorticosteroid with a high local anti-inflammatory effect. At doses clinically equivalent to systemically acting glucocorticosteroids, budesonide gives significantly less HPA axis suppression and has a lower impact on inflammatory markers. It has a topical anti-inflammatory activity, but does not reduce cortisol levels to the same extent as systemic glucocorticoids.

 

MMX extended release technology is characterised by a multi-matrix structure covered by a gastro-resistant coating that dissolves in intestinal fluids having a pH greater than 7. When the dosage form is administered, the gastro-protective layer protects the dosage form during transit through the stomach and duodenum up to the lower part of the intestine. When the protective layer is lost, the intestinal fluid then comes into contact with the hydrophilic matrix polymers, which start to swell until a viscous gel matrix is formed. The solvent that penetrates into the gel matrix dissolves the active ingredient from the lipophilic matrices. Budesonide is then released into the intestinal tract at a controlled rate throughout the colon.

Therapeutic indications

In ulcerative colitis, it is appropriate for the induction of remission in patients with mild to moderate active disease, where 5-ASA treatment is not sufficient

Dosing, administration

The recommended daily dose is 9 mg/day for 8 weeks. When treatment is discontinued, it may be useful to gradually reduce the dose, although no specific data are available on how to reduce the dose before discontinuation.

Contraindications

Hypersensitivity to the active substance

Adverse effects

Common

  • Nausea
  • Abdominal pain
  • Abdominal distension
  • Dry mouth
  • Dyspepsia
  • Headache
  • Insomnia
  • Acne
  • Fatigue
  • Myalgia
  • Blood cortisol decreased

Uncommon

  • Flatulence
  • Dizziness
  • Mood altered
  • Oedema peripheral
  • Back pain
  • Muscle spasms
  • Influenza
  • Leukocytosis

Laboratory parameters and Monitoring

No particular parameters or monitoring strategies are recommended.

Interactions with other Drugs

No specific data on interactions between budesonide MMX and other drugs are available. Therefore, the same recommendation valid for budesonide can be applied.

 

  • Co-treatment with CYP3A inhibitors is expected to increase the risk of systemic side-effects
  • Compounds or drugs such as carbamazepine and rifampicin, which induce CYP3A4, might reduce the systemic but also the local exposure of budesonide at the gut mucosa. An adjustment of the budesonide dose might be necessary.
  • Compounds or drugs which are metabolized by CYP3A4 might be in competition with budesonide. This might lead to an increased budesonide plasma concentration if the competing substance has a stronger affinity to CYP3A4, or – if budesonide binds stronger to CYP3A4 – the competing substance might be increased in plasma and a dose-adaption/reduction of this drug might be required.
  • Potential interactions with steroid-binding synthetic resins such as cholestyramine, and with antacids cannot be ruled out. These preparations should not be taken simultaneously, but at least two hours apart.

Special situations (e.g. pregnancy)

No specific data on the use of budesonide MMX during pregnancy and lactation are available. Therefore, the same recommendation valid for budesonide can be applied.

 

  • Administration during pregnancy should be avoided unless there are compelling reasons for therapy with budesonide. There are few data of pregnancy outcomes after oral administration of budesonide in humans. The maximal concentration of budesonide in plasma has to be expected to be higher in the treatment with oral budesonide compared to inhaled budesonide. In pregnant animals, budesonide, like other glucocorticosteroids, has been shown to cause abnormalities of foetal development. The relevance of this to man has not been established.
  • Budesonide is excreted in human milk (data on excretion after inhalative use is available). However, only minor effects on the breast-fed child are anticipated after budesonide intake within the therapeutic range. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from budesonide therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.