Budesonide

BUDESONIDE- budesonide aerosol, foam
Oceanside Pharmaceuticals

1 INDICATIONS AND USAGE

Budesonide rectal foam is indicated for the induction of remission in patients with active mild to moderate distal ulcerative colitis extending up to 40 cm from the anal verge.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

The recommended dosage regimen is 1 metered dose administered rectally twice daily for 2 weeks followed by 1 metered dose administered rectally once daily for 4 weeks.

2.2 Administration Instructions

Advise patients:

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Budesonide rectal foam is only to be applied rectally. It is not for oral use.

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Before using budesonide rectal foam, use the bathroom to empty your bowels.

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Each applicator is coated with a lubricant. If additional lubrication is needed, petrolatum or petroleum jelly can also be used.

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Warm the canister in the hands while shaking it vigorously for 10 to 15 seconds prior to use.

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Budesonide rectal foam can be used in a standing, lying or sitting position (e.g., while using the toilet).

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Apply budesonide rectal foam in the morning and the evening for the first 2 weeks of treatment; then once daily in the evening for the next 4 weeks. When applied in the evening, use immediately prior to bedtime. Try not to empty your bowels again until the next morning.

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Avoid concomitant use of CYP3A4 inhibitors (e.g., ketoconazole, grapefruit juice) during treatment with budesonide rectal foam.

3 DOSAGE FORMS AND STRENGTHS

Budesonide rectal foam is formulated as an emulsion which is filled into an aluminum canister with an aerosol propellant. It is available in 1 strength: 2 mg budesonide per metered dose.

4 CONTRAINDICATIONS

Budesonide rectal foam is contraindicated in patients with a history of a known hypersensitivity to budesonide or any of the ingredients of budesonide rectal foam. Reactions have included anaphylaxis [see Adverse Reactions (6.2)].

5 WARNINGS AND PRECAUTIONS

5.1 Hypercorticism and Adrenal Axis Suppression

When glucocorticosteroids are used chronically, systemic effects such as hypercorticism and adrenal suppression may occur. Glucocorticosteroids can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to surgery or other stress situations, supplementation with a systemic glucocorticosteroid is recommended. Since budesonide rectal foam contains a glucocorticosteroid, general warnings concerning glucocorticoids should be followed [see Clinical Pharmacology (12.2)].

Reduced liver function affects the elimination of glucocorticosteroids, and increased systemic availability of oral budesonide has been demonstrated in patients with liver cirrhosis [see Use in Specific Populations (8.6)].

5.2 Impaired Adrenal Suppression in Patients Transferred from Other Glucocorticoids

Monitor patients who are transferred from glucocorticosteroid treatment with higher systemic effects to glucocorticosteroids with lower systemic effects, such as budesonide rectal foam, since symptoms attributed to withdrawal of steroid therapy, including those of acute adrenal suppression or benign intracranial hypertension, may develop. Adrenocortical function monitoring may be required in these patients and the dose of glucocorticosteroid treatment with high systemic effects should be reduced cautiously.

Replacement of systemic glucocorticosteroids with budesonide rectal foam may unmask allergies (e.g., rhinitis and eczema), which were previously controlled by the systemic drug.

5.3 Increased Risk of Infection

Patients who are on drugs that suppress the immune system are more susceptible to infection than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in susceptible patients or patients on immunosuppressant doses of glucocorticosteroids. In patients who have not had these diseases, particular care should be taken to avoid exposure.

How the dose, route and duration of glucocorticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior glucocorticosteroid treatment to the risk is also not known. If exposed, therapy with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG), as appropriate, may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated (see prescribing information for VZIG and IG). If chicken pox develops, treatment with antiviral agents may be considered.

Glucocorticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infection, untreated fungal, bacterial, systemic viral or parasitic infections, or ocular herpes simplex.

5.4 Other Glucocorticosteroid Effects

Monitor patients with hypertension, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma or cataracts, or with a family history of diabetes or glaucoma, or with any other condition where glucocorticosteroids may have unwanted effects.

5.5 Flammable Contents

The contents of budesonide rectal foam include n-butane, isobutane and propane as propellants which are flammable. Instruct the patient to avoid fire, flame, and smoking during and immediately following administration. Patients should temporarily discontinue use of budesonide rectal foam before initiation of bowel preparation for colonoscopy and consult their healthcare provider before resuming therapy.

6 ADVERSE REACTIONS

Serious and important adverse reactions include:

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Hypercorticism and adrenal axis suppression [see Warnings and Precautions (5.1)]

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Symptoms of steroid withdrawal in those patients transferring from systemic glucocorticosteroid therapy [see Warnings and Precautions (5.2)]

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Increased susceptibility to infection [see Warnings and Precautions (5.3)]

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Other glucocorticosteroid effects [see Warnings and Precautions (5.4)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to budesonide rectal foam in 332 patients with active mild to moderate distal ulcerative colitis extending up to 40 cm from the anal verge. The median duration of exposure was 42 days. This included 14 patients exposed for at least 6 months.

Budesonide rectal foam was studied primarily in 2 placebo-controlled, 6-week trials in patients with active disease (Study 1 and Study 2). In these trials, 268 patients received budesonide rectal foam 2 mg twice a day for 2 weeks followed by 2 mg once a day for 4 weeks [see Clinical Studies (14)].

The most common adverse reactions (≥ 2% of the budesonide rectal foam or Placebo group and at higher frequency in the budesonide rectal foam group) were decreased blood cortisol, adrenal insufficiency, and nausea (Table 1). Decreased blood cortisol was defined as a morning cortisol level of <5 mcg/dL. Adrenal insufficiency was defined as a cortisol level of <18 mcg/dL at 30 minutes post-challenge with adrenocorticotropic hormone (ACTH).

A total of 10% of budesonide rectal foam-treated patients discontinued treatment due to an adverse reaction compared with 4% of placebo-treated patients.

Table 1: Summary of Adverse Reactions in 2 Placebo-Controlled Trials * (Studies 1 and 2)

* Experienced by ≥ 2% of the budesonide rectal foam or Placebo group and at higher frequency in the budesonide rectal foam group. † Decreased blood cortisol was defined as a morning cortisol level of <5 mcg/dL. ‡ Adrenal insufficiency was defined as a cortisol level of <18 mcg/dL at 30 minutes post-challenge with ACTH.
Adverse Reaction	Budesonide Rectal Foam 2 mg/25 mL N=268 n (%)	Placebo N=278 n (%)
Decreased blood cortisol †	46 (17)	6 (2)
Adrenal insufficiency ‡	10 (4)	2 (1)
Nausea	6 (2)	2 (1)

Of the 46 budesonide rectal foam treated patients with decreased blood cortisol (defined as a morning cortisol level of <5 mcg/dL) reported as an adverse event, none had adrenal insufficiency (defined as a cortisol level of <18 mcg/dL at 30 minutes post-challenge with ACTH) (see Table 2). All cases of adrenal insufficiency resolved.

Table 2 summarizes the percentages of patients reporting glucocorticoid related effects in the 2 placebo-controlled trials (Studies 1 and 2).

Table 2: Summary of Glucocorticoid Related Effects in Two Placebo-Controlled Trials (Studies 1 and 2)

* Decreases in serum cortisol levels associated with budesonide treatment were seen at Weeks 1 and 2 (twice daily treatment) in the budesonide rectal foam group, but gradually returned to baseline levels during the 4 weeks of once daily treatment.
Adverse Reaction	Budesonide Rectal Foam 2 mg/25 mL N=268 n (%)	Placebo N=278 n (%)
Overall	60 (22)	10 (4)
Blood cortisol decreased	46 (17)*	6 (2)
Adrenal insufficiency	10 (4)	2 (1)
Insomnia	1 (0.4)	1 (0.4)
Sleep disorder	1 (0.4)	0
Acne	1 (0.4)	0
Depression	1 (0.4)	1 (0.4)
Hyperglycemia	1 (0.4)	0

No clinically significant differences were observed with respect to the overall percentages of patients with any glucocorticoid related effects between budesonide rectal foam and placebo after 6 weeks of therapy.

For additional details on morning cortisol levels and the response to the ACTH stimulation test, see Clinical Pharmacology (12.2).