Corticosteroid

Uceris

Approved 7 Oct 2014RectalAerosol, foam

The FDA lists this product in 2 strengths and forms.

Indications

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. UCERIS rectal foam is a glucocorticosteroid 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. ( 1 )

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 )] . Known hypersensitivity to budesonide or any of the ingredients in UCERIS rectal foam. ( 4 )

Warnings and precautions

Hypercorticism and adrenal suppression: Follow general warnings concerning glucocorticosteroids. ( 5.1 )
Impaired Adrenal Function in Patients Transferred from Other Glucocorticoids: Taper slowly from glucocorticosteroids with high systemic effects; monitor for withdrawal symptoms and unmasking of allergies (rhinitis, eczema). ( 5.2 )
Increased Risk of Infection, including serious and fatal chicken pox and measles: Monitor patients with active or quiescent tuberculosis infection, untreated fungal, bacterial, systemic viral or parasitic infections, or ocular herpes simplex. ( 5.3 )
Other Glucocorticosteroid Effects: Monitor patients with other conditions where glucocorticoids may have unwanted effects. ( 5.4 )
Flammable Contents: The contents of UCERIS rectal foam are flammable. Instruct the patient to avoid fire, flame and smoking during and immediately following administration. ( 5.5 )

5.1Hypercorticism 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 )].

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Limited published studies report on the use of budesonide in pregnant women; however, the data are insufficient to inform a drug-associated risk for major birth defects and miscarriage. There are clinical considerations (see Clinical Considerations) . In animal reproduction studies with pregnant rats and rabbits, subcutaneous administration of budesonide during organogenesis at doses 1.2 times and 0.12 times, respectively, the human intrarectal dose of 4 mg/day, resulted in increased fetal loss, decreased pup weights, and skeletal abnormalities.

Maternal toxicity was observed in both rats and rabbits at these dose levels (see Data). Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage of the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is of 2% to 4%, and 15% to 20%, respectively.

Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with ulcerative colitis. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth. Fetal/Neonatal Adverse Reactions Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy.

Infants should be carefully observed for signs of hypoadrenalism, such as poor feeding, irritability, weakness, and vomiting, and managed accordingly [see Warnings and Precautions (5.1)] . Data Animal Data Budesonide was teratogenic and embryolethal in rabbits and rats. In an embryo-fetal development study in pregnant rats dosed subcutaneously with budesonide during the period of organogenesis from gestation days 6-15 there were effects on fetal development and survival at subcutaneous doses up to approximately 500 mcg/kg in rats (approximately 1.2 times the recommended human intrarectal dose on a body surface area basis).

In an embryo-fetal development study in pregnant rabbits dosed during the period of organogenesis from gestation days 6-18, there was an increase in maternal abortion, and effects on fetal development and reduction in litter weights at subcutaneous doses up to approximately 25 mcg/kg in rabbits (approximately 0.12 times the recommended human intrarectal dose of 4 mg/day on a body surface area basis). Maternal toxicity, including reduction in body weight gain, was observed at subcutaneous doses of 5 mcg/kg in rabbits (approximately 0.02 times the recommended human intrarectal dose on a body surface area basis) and 500 mcg/kg in rats (approximately 1.2 times the recommended human intrarectal dose of 4 mg/day on a body surface area basis).

In a pre-and post-natal development study, rats dosed subcutaneously with budesonide during the period of Day 15 post coitum to Day 21 postpartum, budesonide had no effects on delivery but did have an effect on growth and development of offspring. In addition, offspring survival was reduced, and surviving offspring had decreased mean body weights at birth and during lactation at exposures 0.05 times the MRHD (on a mg/m 2 basis at maternal subcutaneous doses of 20 mcg/kg/day and higher).

These findings occurred in the presence of maternal toxicity.

Adverse reactions

Serious and important adverse reactions include:

Hypercorticism and adrenal axis suppression [see Warnings and Precautions ( 5.1 )]
Symptoms of steroid withdrawal in those patients transferring from systemic glucocorticosteroid therapy [see Warnings and Precautions ( 5.2 )]
Increased susceptibility to infection [see Warnings and Precautions ( 5.3 )]
Other glucocorticosteroid effects [see Warnings and Precautions ( 5.4 )] Most common adverse reactions (≥ 2%) are decreased blood cortisol, adrenal insufficiency, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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. Table 1:Summary of Adverse Reactions in 2 Placebo-Controlled Trials* (Studies 1 and 2) Adverse Reaction UCERIS 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 UCERIS 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) Adverse Reaction UCERIS 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 UCERIS 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 ) .

6.2Postmarketing Experience

In addition to adverse reactions reported from clinical trials for UCERIS rectal foam, the following adverse reactions have been identified during post-approval use of other oral and rectal formulations of budesonide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac disorders: hypertension Gastrointestinal disorders: pancreatitis General disorders and administration site conditions: pyrexia, peripheral edema Immune system disorders: anaphylactic reactions Nervous system disorders: dizziness, benign intracranial hypertension Psychiatric disorders: mood swings Skin and subcutaneous tissue disorders: pruritus, maculopapular rash, allergic dermatitis

Uceris

Indications

Contraindications

Warnings and precautions

5.1Hypercorticism and Adrenal Axis Suppression

Two medicines in one question?

5.2Impaired Adrenal Suppression in Patients Transferred from Other Glucocorticoids

5.3Increased Risk of Infection

5.4Other Glucocorticosteroid Effects

5.5Flammable Contents

Interactions

7.1CYP3A4 Inhibitors

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information

At a glance

Guidelines