Uceris

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.

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.

Pregnancy

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/m2 basis at maternal subcutaneous doses of 20 mcg/kg/day and higher). These findings occurred in the presence of maternal toxicity.

Lactation

Risk Summary

Lactation studies have not been conducted with UCERIS rectal foam or other rectally administered budesonide products and no information is available on the effects of budesonide on the breastfed infant or the effects of the drug on milk production. One published study reports that budesonide is present in human milk following maternal inhalation of budesonide (see Data). 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. Data

One published study reports that budesonide is present in human milk following maternal inhalation of budesonide and the milk/plasma ratio ranged between 0.4 and 0.5. Budesonide plasma concentrations were not detected, and no adverse events were noted in the breastfed infants following maternal use of inhaled budesonide. The systemic exposure (AUC0-12) following administration of 400 mcg twice a day of inhaled budesonide ranged from 1.27 to 2.26 ng*hr/mL. The estimated budesonide AUC0-12 following rectal administration of 2 mg twice a day UCERIS was 4.31 ng*hr/mL [see Clinical Pharmacology ]. Budesonide exposure to the nursing child may be higher with maternal rectal administration of UCERIS than with maternal inhaled administration of budesonide.

Pediatric Use

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.

Geriatric Use

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.

Hepatic Impairment

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 ].

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.

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

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.

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.