Budesonide

 Budesonide: Uses, Dosage and Side Effects

Overview

Budesonide is a potent glucocorticoid, about 15 times stronger than prednisolone,
with strong topical anti-inflammatory activity and minimal mineralocorticoid activity.
Enteric-coated formulations delay dissolution until the duodenum, allowing the drug
to act directly on intestinal tissue.

Although budesonide is absorbed from the gut, it undergoes significant first-pass metabolism
in the liver, which lowers systemic glucocorticoid effects. Despite this, HPA axis suppression
has been observed in dogs, cats, and horses.

Uses of Budesonide

In dogs

• In dogs with chronic inflammatory enteropathies, commercial
  budesonide capsules led to modest clinical or histologic improvement, while
  placebo-treated dogs showed disease progression.

In cats

• Anecdotally, budesonide may be helpful in some cats with chronic inflammatory enteropathies.
• Inhaled budesonide has improved signs of asthma and chronic bronchitis.

In horses

• It significantly improved pulmonary function in severe equine asthma (SEA),
  formerly known as recurrent airway obstruction (RAO).

Dose of Budesonide

1. DOGS

Adjunctive treatment of chronic inflammatory enteropathies:

• 1 mg (must be compounded) for body weight 3 to 7 kg, PO once daily.
• 2 mg (must be compounded) for 7.1 to 15 kg, PO once daily.
• 3 mg (commercially available) for 15.1 to 30 kg, PO once daily.
• 5 mg (must be compounded) for greater than 30 kg, PO once daily.
• Once adequately controlled, gradual reductions in dosage amounts or frequency (every other day) are desirable.

2. CATS:

Adjunctive treatment of chronic inflammatory enteropathies:

• Most cats tolerate oral glucocorticoids, but in those that cannot and especially in diabetic cats, budesonide can be considered.
• 0.5 – 0.75 mg/cat PO once daily.
• NOTE: These dosages require reformulation to provide the appropriate dose.

3. HORSES

Adjunctive treatment of severe equine asthma:

• 1.8 mg total dose twice daily.
• The drug was delivered as 8 actuations via Respimat® inhalation device and using an equine-specific nostril adapter.

Popular Dosage Forms

• No veterinary-labeled budesonide products are currently available.
• The Association of Racing Commissioners International (ARCI) classifies budesonide as a
  Class 4 substance.
• Human-labeled budesonide products include extended-release capsules (3 mg and 9 mg, micronized),
  available under brand names such as Entocort EC®, Uceris®, and as
  generics (prescription only).

Precautions

• Budesonide may cause systemic corticosteroid effects, so it should be used
  with caution in patients where glucocorticoid use is risky.
• Conditions of concern include gastrointestinal ulcers,
  active infections, diabetes mellitus, and cataracts.
• Patients with hepatic impairment may be at higher risk for systemic effects,
  and dosage reduction may be necessary.
• Because budesonide suppresses the HPA axis, exogenous steroids should
  be considered during stressful procedures, such as surgery.

Drug Interactions

• Aspirin increases the risk of gastrointestinal erosion, ulceration, or perforation
  when used with budesonide.
• NSAIDs (e.g., carprofen, meloxicam, robenacoxib) also increase the risk for
  GI complications when combined with budesonide.
• Oral antacids may interfere with budesonide’s pH-dependent coating;
  administer budesonide at least 2 hours apart from oral antacids.
• Other acid-reducing drugs (e.g., famotidine, omeprazole)
  do not significantly affect budesonide’s pharmacokinetics.
• Budesonide is extensively metabolized by the CYP3A enzyme;
  drugs that inhibit CYP3A can significantly increase systemic exposure.
• Azole antifungals (e.g., fluconazole, itraconazole, ketoconazole),
  especially ketoconazole, can increase budesonide AUC by up to 8-fold.

Contraindications of Budesonide

• Budesonide is contraindicated in patients hypersensitive to it.

Side Effects of Budesonide

• It has been demonstrated that compounded budesonide powder and commercial formulations
  significantly reduce the HPA axis in dogs.
• Budesonide can cause GI erosion, ulceration, or perforation
  if taken in excess because it is a strong glucocorticoid with local GI activity.
• It has been demonstrated that inhaled budesonide lowers cortisol levels in horses
  and suppresses the HPA axis in cats.

Overdose

• Budesonide doses of 200 mg/kg were fatal to mice.
• Although glucocorticoid overdoses by themselves are usually not likely to result in significant injury,
  dogs may experience severe gastrointestinal symptoms.
• As needed, supportive treatment should be given if clinical symptoms appear.

Some Notes:

• Up to 80 µg/kg of budesonide administered subcutaneously did not affect rat fertility.
• It has been demonstrated to be teratogenic and embryocidal in rats and rabbits,
  just like other corticosteroids.
• Budesonide should only be administered when the benefit to the mother surpasses
  the possible risk to the fetus, as safety in veterinary species has not been proven.