March 27, 2017
Recommended Topic Related To:

Entocort

"The US Food and Drug Administration (FDA) has approved ustekinumab (Stelara, Janssen Biotech, Inc) for the treatment of moderately to severely active Crohn's disease in patients aged 18 years or older.

Specifically, the interle"...

A A A

Entocort EC




Warnings
Precautions

WARNINGS

Included as part of the "PRECAUTIONS" Section

PRECAUTIONS

Hypercorticism And Adrenal Axis Suppression

When corticosteroids are used chronically, systemic effects such as hypercorticism and adrenal axis suppression may occur. Corticosteroids 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 corticosteroid is recommended. Since ENTOCORT EC contains a corticosteroid, general warnings concerning corticosteroids should be followed [see Symptoms Of Steroid Withdrawal In Patients Transferred From Other Systemic Corticosteroids, Increased Risk Of Infection, Other Corticosteroid Effects].

Pediatric patients with Crohn’s disease have a slightly higher systemic exposure of budesonide and increased cortisol suppression than adults with Crohn’s disease [see Use In Specific Populations, CLINICAL PHARMACOLOGY]. Patients with moderate to severe hepatic impairment (Child-Pugh Class B and C respectively) could be at an increased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure of oral budesonide. Avoid use in patients with severe hepatic impairment (Child-Pugh Class C). Monitor for increased signs and/or symptoms of hypercorticism and consider reducing the dosage in patients with moderate hepatic impairment (Child-Pugh Class B) [see DOSAGE AND ADMINISTRATION, Use In Specific Populations, CLINICAL PHARMACOLOGY].

Symptoms Of Steroid Withdrawal In Patients Transferred From Other Systemic Corticosteroids

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

Replacement of systemic corticosteroids with ENTOCORT EC 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 corticosteroids. In patients who have not had these diseases, particular care should be taken to avoid exposure.

How the dose, route and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid 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.

Corticosteroids 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 Corticosteroid 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 corticosteroids may have unwanted effects.

Patient Counseling Information

Advise Patients to read the FDA-Approved patient labeling (Patient Information).

Hypercorticism And Adrenal Axis Suppression

Advise patients that ENTOCORT EC Capsules may cause hypercorticism and adrenal axis suppression and to follow a taper schedule, as instructed by their healthcare provider if transferring to ENTOCORT EC from systemic corticosteroids [see WARNINGS AND PRECAUTIONS]. Advise patients that replacement of systemic corticosteroids with ENTOCORT EC 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, to consult their healthcare provider immediately. 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 healthcare provider if they develop any symptoms of infection [see WARNINGS AND PRECAUTIONS].

Pregnancy

Advise female patients that ENTOCORT EC may cause fetal harm and to inform their healthcare provider with a known or suspected pregnancy [see Use In Specific Populations].

Administration

Advise patients to:

  • Take ENTOCORT EC capsules once daily in the morning.
  • Swallow ENTOCORT EC capsules whole. Do not chew or crush.
  • Avoid consumption of grapefruit juice for the duration of their ENTOCORT EC therapy [see DRUG INTERACTIONS].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenicity studies with budesonide were conducted in rats and mice. In a two-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 0.05 times the maximum recommended human dose on a body surface area basis). In addition, there were increased incidences of primary hepatocellular tumors in male rats at 25 mcg/kg (approximately 0.023 times the maximum recommended human dose on a body surface area basis) and above. No tumorigenicity was seen in female rats at oral doses up to 50 mcg/kg (approximately 0.05 times the maximum recommended human dose on a body surface area basis). In an additional two-year study in male Sprague-Dawley rats, budesonide caused no gliomas at an oral dose of 50 mcg/kg (approximately 0.05 times the maximum recommended human dose on a body surface area basis). However, it caused a statistically significant increase in the incidence of hepatocellular tumors at an oral dose of 50 mcg/kg (approximately 0.05 times the maximum recommended human dose on a body surface area basis). The concurrent reference corticosteroids (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 0.1 times the maximum recommended human dose on a body surface area basis).

Budesonide was not genotoxic 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 and the mouse micronucleus test.

In rats, budesonide had no effect on fertility at subcutaneous doses up to 80 mcg/kg (approximately 0.07 times the maximum recommended human dose on a body surface area basis). 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 0.02 times the maximum recommended human dose on a body surface area basis) and above. No such effects were noted at 5 mcg/kg (approximately 0.005 times the maximum recommended human dose on a body surface area basis).

Use In Specific Populations

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, administration of subcutaneous budesonide during organogenesis at doses approximately 0.5 times or 0.05 times, respectively, the maximum recommended human dose, 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. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Some published epidemiological studies show an association of adverse pregnancy outcomes in women with Crohn’s disease, including preterm birth and low birth weight infants, during periods of increased disease activity (including increased stool frequency and abdominal pain). Pregnant women with Crohn’s disease should be counseled regarding the importance of controlling disease.

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].

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 6-17 there was a prolonged duration of pregnancy in dams and effects on fetal development and survival at subcutaneous doses up to approximately 500 mcg/kg in rats (approximately 0.5 times the maximum recommended human 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 7 to 20, 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 0.05 times the maximum recommended human dose 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 0.01 times the maximum recommended human dose on a body surface area basis) and 500 mcg/kg in rats (approximately 0.5 times the maximum recommended human dose on a body surface area basis).

In a peri-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 along with delayed sexual maturation at exposures ≥ 0.5 times the MRHD (on a mg/m2 basis at maternal subcutaneous doses of 500 mcg/kg/day and higher). These findings occurred in the presence of maternal toxicity.

Lactation

Risk Summary

Lactation studies have not been conducted with oral budesonide, including ENTOCORT EC, and no information is available on the effects of the drug 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 ENTOCORT EC and any potential adverse effects on the breastfed infant from ENTOCORT EC, or from the underlying maternal condition.

Data

One published study reports that budesonide is present in human milk following maternal inhalation of budesonide which resulted in infant doses approximately 0.3% to 1% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging 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 recommended daily dose of ENTOCORT EC capsules is higher (up to 9 mg daily) compared with inhaled budesonide (up to 800 mcg daily) given to mothers in the above described study. The maximum budesonide plasma concentration following a 9 mg daily dose (in both single-and repeated-dose pharmacokinetic studies) of oral budesonide is approximately 5 to 10 nmol/L which is up to 10 times higher than the 1 to 2 nmol/L for a 800 mcg daily dose of inhaled budesonide at steady state in the above inhalation study. Assuming the coefficient of extrapolation between the inhaled and oral doses is constant across all dose levels, at therapeutic doses of ENTOCORT EC, budesonide exposure to the nursing child may be up to 10 times higher than that by budesonide inhalation.

Pediatric Use

The safety and effectiveness of ENTOCORT EC have been established in pediatric patients 8 to 17 years of age who weigh more than 25 kg for the treatment of mild to moderate active Crohn’s disease involving the ileum and/or the ascending colon. Use of ENTOCORT EC in this age group is supported by evidence from adequate and well controlled studies of ENTOCORT EC in adults, with additional data from 2 clinical studies in 149 pediatric patients treated up to 8 weeks and one pharmacokinetic study in 8 pediatric patients [see ADVERSE REACTIONS, CLINICAL PHARMACOLOGY, and Clinical Studies].

The observed safety profile of ENTOCORT EC in pediatric patients is consistent with its known safety profile in adults and no new safety concerns were identified [see ADVERSE REACTIONS].

Systemic corticosteroids, including ENTOCORT EC, may cause a reduction of growth velocity in pediatric patients. Pediatric patients with Crohn’s disease have a 17% higher mean systemic exposure and cortisol suppression than adults with Crohn’s disease [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

The safety and effectiveness of ENTOCORT EC have not been established in pediatric patients less than 8 years of age for the treatment of mild to moderate active Crohn’s disease involving the ileum and/or the ascending colon.

The safety and effectiveness of ENTOCORT EC have not been established in pediatric patients for the maintenance of clinical remission of mild to moderate Crohn’s disease. An open-label study to evaluate the safety and tolerability of ENTOCORT EC as maintenance treatment in pediatric patients aged 5 to 17 years was conducted, and did not establish the safety and efficacy of maintenance of clinical remission.

Geriatric Use

Clinical studies of ENTOCORT EC did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Of the 651 patients treated with ENTOCORT EC in clinical studies, 17 (3%) were greater than or equal to 65 years of age and none were greater than 74 years of age. 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

Patients with moderate to severe hepatic impairment (Child-Pugh Class B and C, respectively) could be at an increased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure to budesonide [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Avoid use in patients with severe hepatic impairment (Child-Pugh Class C). Monitor for increased signs and/or symptoms of hypercorticism and consider dosage reduction in patients with moderate hepatic impairment (Child-Pugh Class B) [see DOSAGE AND ADMINISTRATION]. No dosage adjustment is needed in patients with mild hepatic impairment (Child-Pugh Class A).

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 8/1/2016

Warnings
Precautions

Entocort EC - User Reviews

Entocort EC User Reviews

Now you can gain knowledge and insight about a drug treatment with Patient Discussions.

Here is a collection of user reviews for the medication Entocort EC sorted by most helpful. Patient Discussions FAQs

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.


Women's Health

Find out what women really need.