UCERIS- budesonide aerosol, foam
Salix Pharmaceuticals, Inc.
1 INDICATIONS AND USAGE
UCERIS 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 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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UCERIS rectal foam is only to be applied rectally. It is not for oral use.
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Before using UCERIS 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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UCERIS rectal foam can be used in a standing, lying or sitting position (e.g., while using the toilet).
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Apply UCERIS 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 UCERIS rectal foam.
3 DOSAGE FORMS AND STRENGTHS
UCERIS 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
UCERIS rectal foam is contraindicated in patients with a history of a known hypersensitivity to budesonide or any of the ingredients of UCERIS 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 UCERIS 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 UCERIS 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 UCERIS 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 UCERIS 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 UCERIS 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 UCERIS 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.
UCERIS 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 UCERIS 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 UCERIS rectal foam or Placebo group and at higher frequency in the UCERIS 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 UCERIS rectal foam-treated patients discontinued treatment due to an adverse reaction compared with 4% of placebo-treated patients.
DRUG INTERACTIONS
7.1 CYP3A4 Inhibitors
The active ingredient of UCERIS rectal foam, budesonide, is metabolized by CYP3A4. Inhibitors of CYP3A4 activity (such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, cyclosporine and grapefruit juice) can increase systemic budesonide concentrations. Avoid concomitant use of CYP3A4 inhibitors with UCERIS rectal foam [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C
OVERDOSAGE
Acute overdosage with UCERIS rectal foam is unlikely. However, UCERIS rectal foam is absorbed systemically and chronic overdosage may result in signs/symptoms of hypercorticism [see Warnings and Precautions (5.1)].
11 DESCRIPTION
UCERIS rectal foam contains budesonide, a non-halogenated synthetic glucocorticoid, as the active ingredient. It is a mixture of the 2 epimers (22R and 22S) differing in the position of an acetal chain. Both epimers are active glucocorticoids applied in a mixture of approximately 1:1.
Budesonide is designated chemically as (RS)-11β, 16α, 17,21 tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with butyraldehyde. The empirical formula of budesonide is C25 H34 O6 and its molecular weight is 430.5
UCERIS rectal foam contains 2 mg budesonide per metered dose.
Inactive ingredients: cetyl alcohol, citric acid monohydrate, edetate disodium, emulsifying wax, polyoxyl (10) stearyl ether, propylene glycol, and purified water.
Propellant: n-butane, isobutane, and propane.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Budesonide has glucocorticosteroid (GCS) activity.
PATIENT AND COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use)
Administration
Advise patients:
�
UCERIS rectal foam is only to be applied rectally. It is not for oral use.
�
Before using UCERIS rectal foam, use the bathroom to empty your bowels.
�
Each applicator is coated with a lubricant. If additional lubrication is needed, petrolatum or petroleum jelly can also be used.
�
Warm the canister in the hands while shaking it vigorously for 10 to 15 seconds prior to use.
�
UCERIS rectal foam can be used in a standing, lying or sitting position (e.g., while using the toilet).
�
Apply UCERIS 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.
�
Avoid consumption of grapefruit or grapefruit juice during treatment with UCERIS rectal foam.
�
Avoid fire, flame, and smoking during and immediately following administration since UCERIS rectal foam is flammable.
Hypercorticism and Adrenal Suppression
Advise patients that UCERIS rectal foam may cause hypercorticism and adrenal suppression and that they should taper slowly from systemic corticosteroids if transferring to UCERIS rectal foam [see Warnings and Precautions (5.1) ,(5.2)]. Advise patients that replacement of systemic glucocorticosteroids with UCERIS rectal foam may unmask allergies (e.g., rhinitis and eczema), which were previously controlled by the systemic drug.
Increased Risk of Infection
Advise patients to avoid exposure to people with chicken pox or measles and if exposed, consult a physician. Also, inform patients that they are at increased risk of developing a variety of infections, including worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infections, or ocular herpes simplex and to contact their physician if they develop any symptoms of infection [see Warnings and Precautions (5.3)].
Manufactured for:
Salix Pharmaceuticals, a division of
Valeant Pharmaceuticals North America LLC
Bridgewater, NJ 08807 USA
Product marketed and distributed under license from Dr. Falk Pharma.
UCERIS is a trademark of Valeant Pharmaceuticals International, Inc. or its affiliates.
� Valeant Pharmaceuticals North America LLC
