"An experimental oral lymphocyte trafficking agent, ozanimod (Receptos), showed modest activity against ulcerative colitis (UC) in a small, early-stage clinical trial.
In the double-blind, placebo-controlled phase 2 trial in adults wit"...
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].
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].
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.
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.
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.
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 health care provider before resuming therapy.
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION and Instructions for Use)
- 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]. 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].
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Carcinogenicity studies with budesonide were conducted in rats and mice. In a 2-year study in Sprague-Dawley rats, budesonide caused a statistically significant increase in the incidence of gliomas in male rats at an oral dose of 50 mcg/kg (approximately 0.12 times the recommended intrarectal dose of 4 mg/day in humans, based on the body surface area). In addition, there were increased incidences of primary hepatocellular tumors in male rats at 25 mcg/kg (approximately 0.06 times the recommended intrarectal dose of 4 mg/day in humans, based on the body surface area) and above. No tumorigenicity was seen in female rats at oral doses up to 50 mcg/kg (approximately 0.12 times the recommended intrarectal dose of 4 mg/day in humans, based on the body surface area).
In an additional 2-year study in male Sprague-Dawley rats, budesonide caused no gliomas at an oral dose of 50 mcg/kg (approximately 0.12 times the recommended intrarectal dose of 4 mg/day in humans, based on the body surface area). However, it caused a statistically significant increase in the incidence of hepatocellular tumors at an oral dose of 50 mcg/kg (approximately 0.12 times the recommended intrarectal dose of 4 mg/day in humans, based on the body surface area). The concurrent reference glucocorticosteroids (prednisolone and triamcinolone acetonide) showed similar findings. In a 91-week study in mice, budesonide caused no treatment-related carcinogenicity at oral doses up to 200 mcg/kg (approximately 0.24 times the recommended intrarectal dose of 4 mg/day in humans, based on the body surface area).
Budesonide showed no evidence of mutagenic potential in the Ames test, the mouse lymphoma cell forward gene mutation (TK+/-) test, the human lymphocyte chromosome aberration test, the Drosophila melanogaster sex-linked recessive lethality test, the rat hepatocyte UDS test or the mouse micronucleus test.
Impairment of Fertility
In rats, budesonide had no effect on fertility at subcutaneous doses up to 80 mcg/kg (approximately 0.20 times recommended intrarectal dose of 4 mg/day in humans, based on the body surface area). However, it caused a decrease in prenatal viability and viability in pups at birth and during lactation, along with a decrease in maternal body-weight gain, at subcutaneous doses of 20 mcg/kg (approximately 0.05 times recommended intrarectal dose of 4 mg/day in humans, based on the body surface area) and above. No such effects were noted at 5 mcg/kg.
Use In Specific Populations
Pregnancy Category C
There are no adequate and well controlled studies with UCERIS rectal foam in pregnant women. Animal reproduction studies have been conducted with budesonide. In these studies, subcutaneous administration of budesonide to rats and rabbits at doses 1.2 times and 0.12 times, respectively, the human intrarectal dose of 4 mg/day, produced skeletal abnormalities, fetal loss and decreased pup weight. UCERIS rectal foam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. All pregnancies, regardless of drug exposure, have a background rate of 2 to 4 percent for major malformations, and 15 to 20 percent for pregnancy loss.
Fetal/neonatal Adverse Reactions
Hypoadrenalism may occur in neonates exposed to glucocorticosteroids in-utero. Carefully observe these neonates for signs and symptoms of hypoadrenalism.
Budesonide is teratogenic and embryocidal in rabbits and rats. In subcutaneous embryofetal development studies, fetal loss, decreased pup weights, and skeletal abnormalities were observed at a subcutaneous dose of 25 mcg/kg in rabbits (approximately 0.12 times the recommended human intrarectal dose of 4 mg/day, based on the body surface area) and 500 mcg/kg in rats (approximately 1.2 times the recommended human intrarectal dose of 4 mg/day, based on the body surface area).
Use of UCERIS rectal foam is likely to result in budesonide in human milk as budesonide delivered by inhalation from a dry powder inhaler is present in human milk at low concentrations. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for UCERIS rectal foam and any potential adverse effects on the breastfed child from UCERIS rectal foam or from the underlying maternal condition. Exercise caution when administering UCERIS rectal foam to a nursing woman.
The safety and effectiveness of UCERIS rectal foam has not been established in pediatric patients.
Children who are treated with corticosteroids by any route may experience a decrease in their growth velocity. This negative impact of corticosteroids on growth has been in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression. The long-term effects of this reduction in growth velocity associated with corticosteroid treatment, including the impact on final adult height, are unknown. Growth velocity may therefore be a more sensitive indicator of systemic corticosteroid exposure in children than some commonly used tests of HPA axis function. The linear growth of children treated with corticosteroids by any route should be monitored (e.g., via stadiometry), and the potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the availability of other treatment alternatives. In order to minimize the potential growth effects of corticosteroids, children should be titrated to the lowest effective dose.
Clinical studies with UCERIS rectal foam did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
No dosage adjustment is needed for patients with mild (Child-Pugh Class A) hepatic impairment. Patients with moderate to severe hepatic impairment (Child-Pugh Class B or C) should be monitored for increased signs and/or symptoms of hypercorticism. Discontinuing the use of UCERIS rectal foam should be considered in these patients if signs of hypercorticism are observed [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 11/17/2014
Additional Uceris Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.