Budesonide (Entocort EC)
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Budesonide (Entocort EC)

ENTOCORT® EC
(budesonide)

DRUG DESCRIPTION

Budesonide, the active ingredient of ENTOCORT EC capsules, is a synthetic corticosteroid. Budesonide is designated chemically as (RS)-11β, 16α, 17,21tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with butyraldehyde. Budesonide is provided as a mixture of two epimers (22R and 22S). The empirical formula of budesonide is C25H34O6 and its molecular weight is 430.5. Its structural formula is:

ENTOCORT® EC (budesonide) Structural Formula Illustration

Budesonide is a white to off-white, tasteless, odorless powder that is practically insoluble in water and heptane, sparingly soluble in ethanol, and freely soluble in chloroform. Its partition coefficient between octanol and water at pH 5 is 1.6 x 103 ionic strength 0.01.

Each capsule for oral administration contains 3 mg of micronized budesonide with the following inactive ingredients: ethylcellulose, acetyltributyl citrate, methacrylic acid copolymer type C, triethyl citrate, antifoam M, polysorbate 80, talc, and sugar spheres. The capsule shells have the following inactive ingredients: gelatin, iron oxide, and titanium dioxide.

What are the possible side effects of budesonide (Entocort EC)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist);
  • increased blood pressure (severe headache, fast or uneven heart rate, blurred vision); or
  • general ill feeling with headache, tiredness, nausea, and vomiting.

Less serious side effects may...

Read All Potential Side Effects and See Pictures of Entocort EC »

What are the precautions when taking budesonide (Entocort EC)?

Before taking budesonide, tell your doctor if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: eye disease (such as cataracts, glaucoma), high blood pressure, liver disease, thyroid problems, diabetes, stomach/intestinal problems (such as diverticulitis, ulcer), brittle bones (osteoporosis), current/past infections (such as tuberculosis, positive tuberculosis test, herpes, fungal), bleeding problems, mental/mood conditions (such as psychosis, anxiety, depression).

Using corticosteroid medications for a long time can make it...

Read All Potential Precautions of Entocort EC »

Last reviewed on RxList: 1/10/2012
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Mild to Moderate Active Crohn's Disease

ENTOCORT EC is indicated for the treatment of mild to moderate active Crohn's disease involving the ileum and/or the ascending colon.

Maintenance of Clinical Remission of Mild to Moderate Crohn's Disease

ENTOCORT EC is indicated for the maintenance of clinical remission of mild to moderate Crohn's disease involving the ileum and/or the ascending colon for up to 3 months.

DOSAGE AND ADMINISTRATION

Mild to Moderate Active Crohn's Disease

The recommended adult dosage for the treatment of mild to moderate active Crohn's disease involving the ileum and/or the ascending colon is 9 mg orally taken once daily in the morning for up to 8 weeks. Repeated 8 week courses of ENTOCORT EC can be given for recurring episodes of active disease.

Maintenance of Clinical Remission of Mild to Moderate Crohn's Disease

Following an 8 week course(s) of treatment for active disease and once the patient's symptoms are controlled (CDAI less than 150), ENTOCORT EC 6 mg orally is recommended once daily for maintenance of clinical remission up to 3 months. If symptom control is still maintained at 3 months an attempt to taper to complete cessation is recommended. Continued treatment with ENTOCORT EC 6 mg for more than 3 months has not been shown to provide substantial clinical benefit.

Patients with mild to moderate active Crohn's disease involving the ileum and/or ascending colon have been switched from oral prednisolone to ENTOCORT EC with no reported episodes of adrenal insufficiency. Since prednisolone should not be stopped abruptly, tapering should begin concomitantly with initiating ENTOCORT EC treatment.

CYP3A4 inhibitors

If concomitant administration with ketoconazole, or any other CYP3A4 inhibitor, is indicated, patients should be closely monitored for increased signs and/or symptoms of hypercorticism. Grapefruit juice, which is known to inhibit CYP3A4, should also be avoided when taking ENTOCORT EC. In these cases, reduction in the dose of ENTOCORT EC capsules should be considered [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].

HOW SUPPLIED

Dosage Forms And Strengths

ENTOCORT EC 3 mg capsules are hard gelatin capsules with an opaque light grey body and an opaque pink cap, coded with ENTOCORT EC 3 mg on the capsule.

Storage And Handling

ENTOCORT EC 3 mg capsules are hard gelatin capsules with an opaque light grey body and an opaque pink cap, coded with ENTOCORT EC 3 mg on the capsule and are supplied as follows:

NDC 65483-702-10 Bottles of 100 17

Store at 25°C (77°F); excursions permitted to 15-30°C (5986°F) [See USP Controlled Room Temperature].

Keep container tightly closed.

Manufactured by: AstraZeneca AB, S-151 85 Södertälje, Sweden. Distributed by: Prometheus Laboratories Inc. San Diego, CA 92121. Revised: 12/2011

Last reviewed on RxList: 1/10/2012
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

Systemic glucocorticosteroid use may result in the following:

  • Hypercorticism and Adrenal Suppression [see WARNINGS AND PRECAUTIONS]
  • Symptoms of steroid withdrawal in those patients transferring from Systemic Glucocorticosteroid Therapy [see WARNINGS AND PRECAUTIONS]
  • Immunosuppression [see WARNINGS AND PRECAUTIONS]
  • Increased Systemic Glucocorticosteroid Susceptibilty [see WARNINGS AND PRECAUTIONS]
  • Other Glucocorticosteroid Effects [see WARNINGS AND PRECAUTIONS]

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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice

The safety of ENTOCORT EC was evaluated in 651 patients in five short-term, active disease state studies. They ranged in age from 17 to 74 (mean 35), 40% were male and 97% were white, 2.6% were greater than or equal to 65 years of age. Five hundred and twenty patients were treated with ENTOCORT EC 9 mg (total daily dose). The most common adverse reactions reported were headache, respiratory infection, nausea, and symptoms of hypercorticism. Clinical studies have shown that the frequency of glucocorticosteroidassociated adverse reactions was substantially reduced with ENTOCORT EC capsules compared with prednisolone at therapeutically equivalent doses. Adverse reactions occurring in greater than or equal to 5% of the patients are listed in Table 1:

Table 1 : Adverse Reactions Occurring in greater than or equal to 5% of the Patients in any treated group

Adverse Reaction ENTOCORT EC 9 mg
n=520
Number (%)
Placebo
n=107
Number (%)
Prednisolone 40 mg
n=145
Number (%)
Comparator*
n=88
Number (%)
Headache 107(21) 19(18) 31(21) 11(13)
Respiratory Infection 55 (11) 7(7) 20(14) 5(6)
Nausea 57(11) 10(9) 18(12) 7(8)
Back Pain 36(7) 10(9) 17(12) 5(6)
Dyspepsia 31(6) 4(4) 17(12) 3(3)
Dizziness 38(7) 5(5) 18(12) 5(6)
Abdominal Pain 32(6) 18(17) 6(4) 10(11)
Flatulence 30(6) 6(6) 12(8) 5(6)
Vomiting 29(6) 6(6) 6(4) 6(7)
Fatigue 25(5) 8(7) 11(8) 0(0)
Pain 24(5) 8(7) 17(12) 2(2)
*This drug is not approved for the treatment of Crohn's disease in the United States.

The safety of ENTOCORT EC was evaluated in 233 patients in four long-term clinical trials (52 weeks). A total of 145 patients were treated with ENTOCORT EC 6 mg. A total of 8% of ENTOCORT EC patients discontinued treatment due to adverse reactions compared with 10% in the placebo group. The adverse reaction profile in long-term treatment of Crohn's disease was similar to that of short-term treatment with ENTOCORT EC 9 mg in active Crohn's disease.

In the long-term clinical trials, the following adverse reactions occurred in greater than or equal to 5% of the 6 mg ENTOCORT EC patients and are not listed in (Table 1) or by body system below: diarrhea (10%); sinusitis (8%); infection viral (6%); and arthralgia (5%).

Adverse reactions, occurring in patients treated with ENTOCORT EC 9 mg (total daily dose) in short-term active disease state studies and/or ENTOCORT EC 6 mg (total daily dose) long-term, with an incidence less than 5% and greater than placebo are listed below by system organ class:

Blood and lymphatic system disorders: leukocytosis

Cardiac disorders: palpitation, tachycardia, Eye disorders: eye abnormality, vision abnormal

General disorders and administration site conditions: asthenia, chest pain, dependent edema, face edema, flu-like disorder, malaise, fever

Gastrointestinal disorders: anus disorder, Crohn's disease aggravated, enteritis, epigastric pain, gastrointestinal fistula, glossitis, hemorrhoids, intestinal obstruction, tongue edema, tooth disorder

Infections and infestations: Ear infection-not otherwise specified, bronchitis, abscess, rhinitis, urinary tract infection, thrush

Investigations: c-reactive protein increased, weight increased

Metabolism and nutrition disorders: appetite increased, hypokalemia

Musculoskeletal and connective tissue disorders: arthritis, cramps, myalgia

Nervous system disorders: hyperkinesia, parasthesia, tremor, vertigo, dizziness, somnolence, amnesia

Psychiatric disorders: agitation, confusion, insomnia, nervousness, sleep disorder

Renal and urinary disorders: dysuria, micturition frequency, nocturia

Reproductive system and breast disorders: intermenstrual bleeding, menstrual disorder

Respiratory, thoracic and mediastinal disorders: dyspnea, pharynx disorder

Skin and subcutaneous tissue disorders: acne, alopecia, dermatitis, eczema, skin disorder, sweating increased, purpura

Vascular disorders: flushing, hypertension

Table 2 displays the frequency and incidence of signs/symptoms of hypercorticism by active questioning of patients in short-term clinical trials.

Table 2 : Summary and Incidence of Signs/Symptoms of Hypercorticism in Short-Term Studies

Signs/Symptom ENTOCORT EC 9 mg
n=427
Number (%)
Placebo
n=107
Number (%)
Prednisolone Taper 40 mg
n=145
Number (%)
Acne 63 (15) 14 (13) 33 (23) *
Bruising Easily 63 (15) 12 (11) 13 (9)
Moon Face 46 (11) 4 (4) 53 (37) *
Swollen Ankles 32 (7) 6 (6) 13 (9)
Hirsutism† 22 (5) 2 (2) 5 (3)
Buffalo Hump 6 (1) 2 (2) 5 (3)
Skin Striae 4 (1) 2 (2) 0 (0)
* Statistically significantly different from ENTOCORT EC 9 mg
† Adverse reaction dictionary included term hair growth increased, local and hair growth increased, general.

Table 3 displays the frequency and incidence of signs/symptoms of hypercorticism by active questioning of patients in long-term clinical trials.

Table 3 : Summary and Incidence of Symptoms of Hypercorticism in Long-Term Studies

Signs/Symptom ENTOCORT EC 3 mg
n=88
Number (%)
ENTOCORT EC 6 mg
n=145
Number (%)
Placebo
n=143
Number (%)
Bruising easily 4 (5) 15 (10) 5 (4)
Acne 4 (5) 14(10) 3 (2)
Moon face 3 (3) 6 (4) 0
Hirsutism 2 (2) 5 (3) 1 (1)
Swollen ankles 2 (2) 3(2) 3(2)
Buffalo hump 1 (1) 1 (1) 0
Skin striae 2 (2) 0 0

The incidence of signs/symptoms of hypercorticism as described above in long-term clinical trials was similar to that seen in the short-term clinical trials.

A randomized, open, parallel-group multicenter safety study specifically compared the effect of ENTOCORT EC (less than 9 mg per day) and prednisolone (less than 40 mg per day) on bone mineral density over 2 years when used at doses adjusted to disease severity. Bone mineral density decreased significantly less with ENTOCORT EC than with prednisolone in steroid-naïve patients, whereas no difference could be detected between treatment groups for steroid-dependent patients and previous steroid users. The incidence of symptoms associated with hypercorticism was significantly higher with prednisolone treatment.

Clinical Laboratory Test Findings

The following potentially clinically significant laboratory changes in clinical trials, irrespective of relationship to ENTOCORT EC, were reported in greater than or equal to 1% of patients: hypokalemia, leukocytosis, anemia, hematuria, pyuria, erythrocyte sedimentation rate increased, alkaline phosphatase increased, atypical neutrophils, C-reactive protein increased, and adrenal insufficiency.

Postmarketing Experience

The following adverse reactions have been reported during post-approval use of ENTOCORT EC. 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.

Immune System Disorders: Anaphylactic reactions

Nervous System Disorders: Benign intracranial hypertension

Psychiatric Disorders: Mood swings

Read the Entocort EC (budesonide) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

Concomitant oral administration of ketoconazole (a known inhibitor of CYP3A4 activity in the liver and in the intestinal mucosa) caused an eight-fold increase of the systemic exposure to oral budesonide. If treatment with inhibitors of CYP3A4 activity (such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, etc.) is indicated, reduction of the budesonide dose should be considered. After extensive intake of grapefruit juice (which inhibits CYP3A4 activity predominantly in the intestinal mucosa), the systemic exposure for oral budesonide increased about two times. Ingestion of grapefruit or grapefruit juice should be avoided in connection with budesonide administration [see CLINICAL PHARMACOLOGY].

Last reviewed on RxList: 1/10/2012
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Hypercorticism and Adrenal 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 ENTOCORT EC is a glucocorticosteroid, general warnings concerning glucocorticoids should be followed.

Transferring Patients from Systemic Glucocorticosteroid Therapy

Care is needed in patients who are transferred from glucocorticosteroid 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 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.

Immunosuppression

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.

Replacement of systemic glucocorticosteroids with ENTOCORT EC capsules may unmask allergies (e.g., rhinitis and eczema), which were previously controlled by the systemic drug.

Increased Systemic Glucocorticosteroid Susceptibility

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].

Other Glucocorticosteroid Effects

Caution should be taken in 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.

Patient Counseling Information

“See FDA-Approved Patient Labeling (PATIENT INFORMATION)”

Patients being treated with ENTOCORT EC Capsules should receive the following information and instructions. This information is intended to aid the patient in the safe and effective use of the medication. It is not a disclosure of all possible adverse or intended effects. For proper use of ENTOCORT EC Capsules and to attain maximum improvement, the patient should read and follow the accompanying FDA-Approved Patient Labeling.

Hypercorticism and Adrenal Suppression

Patients should be advised that ENTOCORT EC Capsules may cause systemic glucocorticosteroid effects of hypercorticism and adrenal suppression. Patients should taper slowly from systemic glucocorticosteroids if transferring to ENTOCORT EC Capsules [see W WARNINGS AND PRECAUTIONS].

Immunosuppression

Patients who are on immunosuppressant doses of glucocorticosteroids should be warned to avoid exposure to chicken pox or measles and, if exposed, to consult their physician without delay. Patients should be informed of potential worsening of existing tuberculosis, fungal, bacterial, viral or parasitic infections [see WARNINGS AND PRECAUTIONS].

How to Take ENTOCORT EC Capsules

ENTOCORT EC Capsules should be swallowed whole and NOT CHEWED OR BROKEN. Patients should be advised to avoid the consumption of grapefruit juice for the duration of their ENTOCORT EC therapy.

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 91week 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

Teratogenic Effects -Pregnancy Category C

Budesonide was teratogenic and embryocidal in rabbits and rats. Budesonide produced fetal loss, decreased pup weights, and skeletal abnormalities at subcutaneous doses of 25 mcg/kg in rabbits (approximately 0.05 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).

There are no adequate and well-controlled studies in pregnant women. Budesonide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Such infants should be carefully observed.

Nursing Mothers

The disposition of budesonide when delivered by inhalation from a dry powder inhaler at doses of 200 or 400 mcg twice daily for at least 3 months was studied in eight lactating women with asthma from 1 to 6 months postpartum1. Systemic exposure to budesonide in these women appears to be comparable to that in non-lactating women with asthma from other studies. Breast milk obtained over eight hours post-dose revealed that the maximum budesonide concentration for the 400 and 800 mcg total daily doses was 0.39 and 0.78 nmol/L, respectively, and occurred within 45 minutes after inhalation. The estimated oral daily dose of budesonide from breast milk to the infant is approximately 0.007 and 0.014 mcg/kg per day for the two dose regimens used in this study, which represents approximately 0.3% to 1% of the dose inhaled by the mother. Budesonide plasma concentrations obtained from five infants at about 90 minutes after breast feeding (and about 140 minutes after drug administration to the mother) were below quantifiable levels (less than 0.02 nmol/L in four infants and less than 0.04 nmol/L in one infant).

The recommended daily dose of ENTOCORT EC capsules is higher (up to 9 mg daily) compared with inhaled budesonide (up to 800 mg daily) given to mothers in the above 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 5-10 nmol/L which is up to 10 times higher than the 1-2 nmol/L for a 800 mg daily dose of inhaled budesonide at steady state in the above inhalation study.

Since there are no data from controlled trials on the use of ENTOCORT EC by nursing mothers or their infants, and because of the potential for serious adverse reactions in nursing infants from ENTOCORT EC, a decision should be made whether to discontinue nursing or to discontinue ENTOCORT EC, taking into account the clinical importance of ENTOCORT EC to the mother.

Budesonide is secreted in human milk. Data from budesonide delivered via dry powder inhaler indicates that the total daily oral dose of budesonide available in breast milk to the infant is approximately 0.3% to 1% of the dose inhaled by the mother. 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

Safety and effectiveness in pediatric patients have not been established. Systemic and inhaled corticosteroids, including ENTOCORT EC, may cause a reduction of growth velocity in pediatric patients.

Geriatric Use

Clinical studies of ENTOCORT EC did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. 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 Insufficiency

Patients with moderate to severe liver disease should be monitored for increased signs and/or symptoms of hypercorticism. Reducing the dose of ENTOCORT EC capsules should be considered in these patients [see WARNINGS AND PRECAUTIONS].

Last reviewed on RxList: 1/10/2012
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

Reports of acute toxicity and/or death following overdosage of glucocorticosteroids are rare. Treatment consists of immediate gastric lavage or emesis followed by supportive and symptomatic therapy.

If glucocorticosteroids are used at excessive doses for prolonged periods, systemic glucocorticosteroid effects such as hypercorticism and adrenal suppression may occur. For chronic overdosage in the face of severe disease requiring continuous steroid therapy, the dosage may be reduced temporarily.

Single oral doses of 200 and 400 mg/kg were lethal in female and male mice, respectively. The signs of acute toxicity were decreased motor activity, piloerection and generalized edema.

CONTRAINDICATIONS

ENTOCORT EC is contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of ENTOCORT EC. Anaphylactic reactions have occurred [see ADVERSE REACTIONS].

Last reviewed on RxList: 1/10/2012
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Budesonide has a high topical glucocorticosteroid (GCS) activity and a substantial first pass elimination. The formulation contains granules which are coated to protect dissolution in gastric juice, but which dissolve at pH greater than 5.5, ie, normally when the granules reach the duodenum. Thereafter, a matrix of ethylcellulose with budesonide controls the release of the drug into the intestinal lumen in a time-dependent manner.

Pharmacodynamics

Budesonide has a high glucocorticoid effect and a weak mineralocorticoid effect, and the affinity of budesonide to GCS receptors, which reflects the intrinsic potency of the drug, is about 200-fold that of cortisol and 15-fold that of prednisolone.

Treatment with systemically active GCS is associated with a suppression of endogenous cortisol concentrations and an impairment of the hypothalamus-pituitary-adrenal (HPA) axis function. Markers, indirect and direct, of this are cortisol levels in plasma or urine and response to ACTH stimulation.

Plasma cortisol suppression was compared following five days' administration of ENTOCORT EC capsules and prednisolone in a crossover study in healthy volunteers. The mean decrease in the integrated 0-24 hour plasma cortisol concentration was greater (78%) with prednisolone 20 mg per day compared to 45% with ENTOCORT EC 9 mg per day.

Pharmacokinetics

Absorption

The absorption of ENTOCORT EC seems to be complete, although Cmax and Tmax are variable. Time to peak concentration varies in individual patients between 30 and 600 minutes. Following oral administration of 9 mg of budesonide in healthy subjects, a peak plasma concentration of approximately 5 nmol/L is observed and the area under the plasma concentration time curve is approximately 30 nmol•hr/L. The systemic availability after a single dose is higher in patients with Crohn's disease compared to healthy volunteers, (21% vs 9%) but approaches that in healthy volunteers after repeated dosing.

Distribution

The mean volume of distribution (Vss) of budesonide varies between 2.2 and 3.9 L/kg in healthy subjects and in patients. Plasma protein binding is estimated to be 85 to 90% in the concentration range 1 to 230 nmol/L, independent of gender. The erythrocyte/plasma partition ratio at clinically relevant concentrations is about 0.8.

Metabolism

Following absorption, budesonide is subject to high first pass metabolism (80-90%). In vitro experiments in human liver microsomes demonstrate that budesonide is rapidly and extensively biotransformed, mainly by CYP3A4, to its 2 major metabolites, 6β-hydroxy budesonide and 16α-hydroxy prednisolone. The glucocorticoid activity of these metabolites is negligible (less than 1/100) in relation to that of the parent compound.

In vivo investigations with intravenous doses in healthy subjects are in agreement with the in vitro findings and demonstrate that budesonide has a high plasma clearance, 0.9-1.8 L/min. Similarly, high plasma clearance values have been shown in patients with Crohn's disease. These high plasma clearance values approach the estimated liver blood flow, and, accordingly, suggest that budesonide is a high hepatic clearance drug.

The plasma elimination half-life, t½, after administration of intravenous doses ranges between 2 and 3.6 hours, and does not differ between healthy adults and patients with Crohn's disease.

Excretion

Budesonide is excreted in urine and feces in the form of metabolites. After oral as well as intravenous administration of micronized [3H]-budesonide, approximately 60% of the recovered radioactivity is found in urine. The major metabolites, including 6β-hydroxy budesonide and 16αhydroxy prednisolone, are mainly renally excreted, intact or in conjugated forms. No unchanged budesonide is detected in urine.

Special Populations

Gender

No significant pharmacokinetic differences have been identified due to gender.

Hepatic Insufficiency

In patients with liver cirrhosis, systemic availability of orally administered budesonide correlates with disease severity and is, on average, 2.5-fold higher compared with healthy controls. Patients with mild liver disease are minimally affected. Patients with severe liver dysfunction were not studied. Absorption parameters are not altered, and for the intravenous dose, no significant differences in CL or Vss are observed.

Renal Insufficiency

The pharmacokinetics of budesonide in patients with renal impairment has not been studied. Intact budesonide is not renally excreted, but metabolites are to a large extent, and might therefore reach higher levels in patients with impaired renal function. However, these metabolites have negligible corticosteroid activity as compared with budesonide (less than 1/100).

Drug-Drug Interactions

Budesonide is metabolized via CYP3A4. Potent inhibitors of CYP3A4 can increase the plasma levels of budesonide several-fold. Co-administration of ketoconazole results in an eight-fold increase in AUC of budesonide, compared to budesonide alone. Grapefruit juice, an inhibitor of gut mucosal CYP3A, approximately doubles the systemic exposure of oral budesonide. Conversely, induction of CYP3A4 can result in the lowering of budesonide plasma levels.

Oral contraceptives containing ethinyl estradiol, which are also metabolized by CYP3A4, do not affect the pharmacokinetics of budesonide. Budesonide does not affect the plasma levels of oral contraceptives (ie, ethinyl estradiol) [see DRUG INTERACTIONS].

Since the dissolution of the coating of ENTOCORT EC is pH dependent (dissolves at pH greater than 5.5), the release properties and uptake of the compound may be altered after treatment with drugs that change the gastrointestinal pH. However, the gastric acid inhibitory drug omeprazole, 20 mg once daily does not affect the absorption or pharmacokinetics of ENTOCORT EC. When an uncoated oral formulation of budesonide is co-administered with a daily dose of cimetidine 1 g, a slight increase in the budesonide peak plasma concentration and rate of absorption occurs, resulting in significant cortisol suppression.

Food Effects

A mean delay in time to peak concentration of 2.5 hours is observed with the intake of a high-fat meal, with no significant differences in AUC.

Clinical Studies

The safety and efficacy of ENTOCORT EC were evaluated in 994 patients with mild to moderate active Crohn's disease of the ileum and/or ascending colon in 5 randomized and double-blind studies. The study patients ranged in age from 17 to 85 (mean 35), 40% were male and 97% were white. Of the 651 patients treated with ENTOCORT EC, 17 (2.6%) were greater than or equal to 65 years of age and none were greater than 74 years of age. The Crohn's Disease Activity Index (CDAI) was the main clinical assessment used for determining efficacy in these 5 studies. The CDAI is a validated index based on subjective aspects rated by the patient (frequency of liquid or very soft stools, abdominal pain rating and general well-being) and objective observations (number of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal mass, body weight and hematocrit). Clinical improvement, defined as a CDAI score of less than or equal to 150 assessed after 8 weeks of treatment, was the primary efficacy variable in these 5 comparative efficacy studies of ENTOCORT EC capsules. Safety assessments in these studies included monitoring of adverse reactions. A checklist of potential symptoms of hypercorticism was used.

One study (Study 1) compared the safety and efficacy of ENTOCORT EC 9 mg daily in the morning to a comparator. At baseline, the median CDAI was 272. ENTOCORT EC 9 mg daily resulted in a significantly higher clinical improvement rate at Week 8 than the comparator. See Table 4.

Table 4 : Clinical Improvement Rates (CDAI less than or equal to 150) After 8 weeks of Treatment

Clinical Study ENTOCORT EC Comparator* Placebo Prednisolone
9 mg Daily 4.5 mg Twice Daily
1 62/91
(69%)
  37/83
(45%)
   
2   31/61
(51%)
  13/64
(20%)
 
3 38/79
(48%)
41/78
(53%)
  13/40
(33%)
 
4 35/58
(60%)
25/60
(42%)
    35/58
(60%)
5 45/86
(52%)
      56/85
(65%)
* This drug is not approved for the treatment of Crohn's disease in the United States.

Two placebo-controlled clinical trials (Studies 2 and 3) were conducted. Study 2 involved 258 patients and tested the effects of graded doses of ENTOCORT EC (1.5 mg twice daily, 4.5 mg twice daily, or 7.5 mg twice daily) versus placebo. At baseline, the median CDAI was 290. The 3 mg per day dose level (data not shown) could not be differentiated from placebo. The 9 mg per day arm was statistically different from placebo (Table 4), while no additional benefit was seen when the daily ENTOCORT EC dose was increased to 15 mg per day (data not shown). In Study 3, the median CDAI at baseline was 263. Neither 9 mg daily nor 4.5 mg twice daily ENTOCORT EC dose levels was statistically different from placebo (Table 4).

Two clinical trials (Studies 4 and 5) compared ENTOCORT EC capsules with oral prednisolone (initial dose 40 mg per day). At baseline, the median CDAI was 277. Equal clinical improvement rates (60%) were seen in the ENTOCORT EC 9 mg daily and the prednisolone groups in Study 4. In Study 5, 13% fewer patients in the ENTOCORT EC group experienced clinical improvement than in the prednisolone group (no statistical difference) (Table 4).

The proportion of patients with normal plasma cortisol values (greater than 150 nmol/L) was significantly higher in the ENTOCORT EC groups in both trials (60 to 66%) than in the prednisolone groups (26 to 28%) at Week 8.

The efficacy and safety of ENTOCORT EC for maintenance of clinical remission were evaluated in four double-blind, placebo-controlled, 12-month trials in which 380 patients were randomized and treated once daily with 3 mg or 6 mg ENTOCORT EC or placebo. Patients ranged in age from 18 to 73 (mean 37) years. Sixty percent of the patients were female and 99% were Caucasian. The mean CDAI at entry was 96. Among the four clinical trials, approximately 75% of the patients enrolled had exclusively ileal disease. Colonoscopy was not performed following treatment. ENTOCORT EC 6 mg per day prolonged the time to relapse, defined as an increase in CDAI of at least 60 units to a total score greater than 150 or withdrawal due to disease deterioration. The median time to relapse in the pooled population of the 4 studies was 154 days for patients taking placebo, and 268 days for patients taking ENTOCORT EC 6 mg per day. ENTOCORT EC 6 mg per day reduced the proportion of patients with loss of symptom control relative to placebo in the pooled population for the 4 studies at 3 months (28% vs. 45% for placebo).

Last reviewed on RxList: 1/10/2012
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

ENTOCORT EC
(EN-toe-cort EE CEE)
(budesonide) Capsules

Read the Patient Information that comes with ENTOCORT EC before you start taking it and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.

What is ENTOCORT EC?

ENTOCORT EC is a prescription glucocorticosteroid medicine used in people with mild to moderate Crohn's disease that affects part of the small intestine (ileum) and part of the large intestine (ascending colon):

  • to treat active Crohn's disease
  • to help keep symptoms from coming back for up to 3 months.

It is not known if ENTOCORT EC is safe and effective in children.

Who should not take ENTOCORT EC?

Do not take ENTOCORT EC if:

  • you are allergic to budesonide or any of the ingredients in ENTOCORT EC. See the end of this leaflet for a complete list of ingredients in ENTOCORT EC.

What should I tell my healthcare provider before taking ENTOCORT EC?

Before you take ENTOCORT EC tell your healthcare provider if you:

  • have liver problems
  • are planning to have surgery
  • have chicken pox or measles or have recently been near anyone with chicken pox or measles
  • have or had a family history of diabetes, cataracts or glaucoma
  • have or had tuberculosis
  • have high blood pressure (hypertension)
  • have decreased bone mineral density (osteoporosis)
  • stomach ulcers
  • any other medical condition
  • are pregnant or plan to become pregnant. It is not known if ENTOCORT EC may harm your unborn baby.
  • are breastfeeding or plan to breastfeed. ENTOCORT EC can pass into breast milk and may harm your baby. You and your healthcare provider should decide if you will take ENTOCORT EC or breastfeed. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. ENTOCORT EC and other medicines may affect each other causing side effects.

Especially tell your healthcare provider if you take:

  • a glucocorticosteroid medicine
  • medicines that suppress your immune system (immunosuppressant)
  • ketoconazale or other medicines that affect how your liver works.

Ask your healthcare provider or pharmacist if you are not sure if your medicine is one listed above.

How should I take ENTOCORT EC?

  • Take ENTOCORT EC exactly as your healthcare provider tells you.
  • Your healthcare provider will tell you how many ENTOCORT EC capsules to take. Your healthcare provider may change your dose if needed.
  • Take ENTOCORT EC in the morning.
  • Take ENTOCORT EC capsules whole. Do not chew or crush ENTOCORT EC capsules before swallowing.

What should I avoid while taking ENTOCORT EC?

  • Do not eat grapefruit or drink grapefruit juice while taking ENTOCORT EC. Eating grapefruit or drinking grapefruit juice can increase the level of ENTOCORT EC in your blood.

What are the possible side effects of ENTOCORT EC?

  • Effects of having too much glucocorticosteroid medicine in your blood (hypercorticism). Long-time use of ENTOCORT EC can cause you to have too much glucocorticosteroid medicine in your blood. Tell your healthcare provider if you have any of the following signs and symptoms of hypercorticism:
    • acne
    • bruise easily
    • rounding of your face (moon face)
    • ankle swelling
    • thicker or more hair on your body and face
    • a fatty pad or hump between your shoulders (buffalo hump)
    • pink or purple stretch marks on the skin of your abdomen, thighs, breasts and arms
  • Adrenal suppression. When ENTOCORT EC is taken for a long period of time (chronic use), adrenal suppression can happen. This is a condition in which the adrenal glands do not make enough steroid hormones. Symptoms of adrenal suppression include: tiredness, weakness, nausea and vomiting and low blood pressure. Tell your healthcare provider if you are under stress or have any symptoms of adrenal suppression during treatment with ENTOCORT EC.
  • Immune system effects and a higher chance of infections.
    ENTOCORT EC weakens your immune system. Taking medicines that weaken your immune system makes you more likely to get infections. Avoid contact with people who have contagious diseases such as chicken pox or measles, while taking ENTOCORT EC.
    Tell your healthcare provider about any signs or symptoms of infection during treatment with ENTOCORT EC, including:

  • fever
  • pain
  • aches
  • chills
  • feeling tired
  • nausea and vomiting

  • Worsening of allergies. If you take certain other glucocorticosteroid medicines to treat allergies, switching to ENTOCORT EC may cause your allergies to come back. These allergies may include eczema (a skin disease) or rhinitis (inflammation inside your nose). Tell your healthcare provider if any of your allergies become worse while taking ENTOCORT EC.

The most common side effects of ENTOCORT EC include:

  • headache
  • infection in your air passages (respiratory infection)
  • back pain
  • upset stomach
  • dizziness
  • abdominal pain
  • excessive stomach or intestinal gas
  • diarrhea
  • sinus infection
  • viral infection
  • joint pain

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of ENTOCORT EC. For more information, ask your healthcare provider or pharmacist.

Call your healthcare provider for medical advice about side effects. You may report side effects to AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

How should I store ENTOCORT EC?

  • Store ENTOCORT EC at 59°F to 86°F (15°C to 30°C).
  • Keep ENTOCORT EC in a tightly closed container.

Keep ENTOCORT EC and all medicines out of reach from children.

General information about ENTOCORT EC.

Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use ENTOCORT EC for a condition for which it was not prescribed. Do not give ENTOCORT EC to other people, even if they have the same symptoms you have. It may harm them.

This Patient Information leaflet summarizes the most important information about ENTOCORT EC. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about ENTOCORT EC that is written for health professionals.

For more information go to.www.ENTOCORTEC.com or call 1-800-236-9933.

What are the ingredients in ENTOCORT EC?

Active ingredient: budesonide

Inactive ingredients: ethylcellulose, acetyltributyl citrate, methacrylic acid copolymer type C, triethyl citrate, antifoam M, polysorbate 80, talc, and sugar spheres.

The capsule shell contains: gelatin, iron oxide, and titanium dioxide.

Last reviewed on RxList: 1/10/2012
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

ENTOCORT EC
(EN-toe-cort EE CEE)
(budesonide) Capsules

Read the Patient Information that comes with ENTOCORT EC before you start taking it and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.

What is ENTOCORT EC?

ENTOCORT EC is a prescription glucocorticosteroid medicine used in people with mild to moderate Crohn's disease that affects part of the small intestine (ileum) and part of the large intestine (ascending colon):

  • to treat active Crohn's disease
  • to help keep symptoms from coming back for up to 3 months.

It is not known if ENTOCORT EC is safe and effective in children.

Who should not take ENTOCORT EC?

Do not take ENTOCORT EC if:

  • you are allergic to budesonide or any of the ingredients in ENTOCORT EC. See the end of this leaflet for a complete list of ingredients in ENTOCORT EC.

What should I tell my healthcare provider before taking ENTOCORT EC?

Before you take ENTOCORT EC tell your healthcare provider if you:

  • have liver problems
  • are planning to have surgery
  • have chicken pox or measles or have recently been near anyone with chicken pox or measles
  • have or had a family history of diabetes, cataracts or glaucoma
  • have or had tuberculosis
  • have high blood pressure (hypertension)
  • have decreased bone mineral density (osteoporosis)
  • stomach ulcers
  • any other medical condition
  • are pregnant or plan to become pregnant. It is not known if ENTOCORT EC may harm your unborn baby.
  • are breastfeeding or plan to breastfeed. ENTOCORT EC can pass into breast milk and may harm your baby. You and your healthcare provider should decide if you will take ENTOCORT EC or breastfeed. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. ENTOCORT EC and other medicines may affect each other causing side effects.

Especially tell your healthcare provider if you take:

  • a glucocorticosteroid medicine
  • medicines that suppress your immune system (immunosuppressant)
  • ketoconazale or other medicines that affect how your liver works.

Ask your healthcare provider or pharmacist if you are not sure if your medicine is one listed above.

How should I take ENTOCORT EC?

  • Take ENTOCORT EC exactly as your healthcare provider tells you.
  • Your healthcare provider will tell you how many ENTOCORT EC capsules to take. Your healthcare provider may change your dose if needed.
  • Take ENTOCORT EC in the morning.
  • Take ENTOCORT EC capsules whole. Do not chew or crush ENTOCORT EC capsules before swallowing.

What should I avoid while taking ENTOCORT EC?

  • Do not eat grapefruit or drink grapefruit juice while taking ENTOCORT EC. Eating grapefruit or drinking grapefruit juice can increase the level of ENTOCORT EC in your blood.

What are the possible side effects of ENTOCORT EC?

  • Effects of having too much glucocorticosteroid medicine in your blood (hypercorticism). Long-time use of ENTOCORT EC can cause you to have too much glucocorticosteroid medicine in your blood. Tell your healthcare provider if you have any of the following signs and symptoms of hypercorticism:
    • acne
    • bruise easily
    • rounding of your face (moon face)
    • ankle swelling
    • thicker or more hair on your body and face
    • a fatty pad or hump between your shoulders (buffalo hump)
    • pink or purple stretch marks on the skin of your abdomen, thighs, breasts and arms
  • Adrenal suppression. When ENTOCORT EC is taken for a long period of time (chronic use), adrenal suppression can happen. This is a condition in which the adrenal glands do not make enough steroid hormones. Symptoms of adrenal suppression include: tiredness, weakness, nausea and vomiting and low blood pressure. Tell your healthcare provider if you are under stress or have any symptoms of adrenal suppression during treatment with ENTOCORT EC.
  • Immune system effects and a higher chance of infections.
    ENTOCORT EC weakens your immune system. Taking medicines that weaken your immune system makes you more likely to get infections. Avoid contact with people who have contagious diseases such as chicken pox or measles, while taking ENTOCORT EC.
    Tell your healthcare provider about any signs or symptoms of infection during treatment with ENTOCORT EC, including:

  • fever
  • pain
  • aches
  • chills
  • feeling tired
  • nausea and vomiting

  • Worsening of allergies. If you take certain other glucocorticosteroid medicines to treat allergies, switching to ENTOCORT EC may cause your allergies to come back. These allergies may include eczema (a skin disease) or rhinitis (inflammation inside your nose). Tell your healthcare provider if any of your allergies become worse while taking ENTOCORT EC.

The most common side effects of ENTOCORT EC include:

  • headache
  • infection in your air passages (respiratory infection)
  • back pain
  • upset stomach
  • dizziness
  • abdominal pain
  • excessive stomach or intestinal gas
  • diarrhea
  • sinus infection
  • viral infection
  • joint pain

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of ENTOCORT EC. For more information, ask your healthcare provider or pharmacist.

Call your healthcare provider for medical advice about side effects. You may report side effects to AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

How should I store ENTOCORT EC?

  • Store ENTOCORT EC at 59°F to 86°F (15°C to 30°C).
  • Keep ENTOCORT EC in a tightly closed container.

Keep ENTOCORT EC and all medicines out of reach from children.

General information about ENTOCORT EC.

Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use ENTOCORT EC for a condition for which it was not prescribed. Do not give ENTOCORT EC to other people, even if they have the same symptoms you have. It may harm them.

This Patient Information leaflet summarizes the most important information about ENTOCORT EC. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about ENTOCORT EC that is written for health professionals.

For more information go to.www.ENTOCORTEC.com or call 1-800-236-9933.

What are the ingredients in ENTOCORT EC?

Active ingredient: budesonide

Inactive ingredients: ethylcellulose, acetyltributyl citrate, methacrylic acid copolymer type C, triethyl citrate, antifoam M, polysorbate 80, talc, and sugar spheres.

The capsule shell contains: gelatin, iron oxide, and titanium dioxide.

Last reviewed on RxList: 1/10/2012
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Entocort EC Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

BUDESONIDE - ORAL

(bue-DES-oh-nide)

COMMON BRAND NAME(S): Entocort EC

USES: This medication is used to treat a flare/attack of a bowel condition called Crohn's disease. While budesonide does not cure this condition, it may decrease symptoms such as pain and diarrhea. Budesonide is an anti-inflammatory drug (corticosteroid hormone). It works by decreasing the body's natural defense response (immune response).

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start using budesonide and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Take this medication by mouth, usually once daily before your morning meal, or as directed by your doctor. Take this medication by mouth with a full glass of water (8 ounces/240 milliliters) unless your doctor directs you otherwise. Swallow the capsules whole. Do not crush or chew the capsules. Doing so can keep the drug from being released properly into the colon and may increase side effects.

The dosage and length of treatment are based on your medical condition and response to treatment.

Avoid eating grapefruit or drinking grapefruit juice while being treated with this medication unless your doctor instructs you otherwise. Grapefruit may increase the amount of certain medications in your body. Consult your doctor or pharmacist for more details.

If you are regularly taking a different corticosteroid by mouth (such as prednisone), you should not stop taking it unless directed by your doctor. Some conditions (such as asthma, allergies) may become worse when the drug is suddenly stopped. You may have withdrawal symptoms if the drug is suddenly stopped. To prevent withdrawal symptoms (such as weakness, weight loss, nausea, muscle pain, headache, tiredness, dizziness), your doctor may direct you to slowly lower the dose of your old medication when you are taking budesonide. Consult your doctor or pharmacist for more details, and report any withdrawal reactions immediately. See also Precautions section.

Use this medication regularly and exactly as prescribed in order to get the most benefit from it. To help you remember, use it at the same time each day. Do not increase your dose, take it more frequently, or use it for a longer time than prescribed because this may increase your risk of serious side effects.

Do not stop taking this medication without consulting your doctor. Some conditions may become worse when this drug is suddenly stopped. Your dose may need to be gradually decreased.

Inform your doctor if your condition persists or worsens.

Disclaimer

Entocort EC Consumer (continued)

SIDE EFFECTS: Budesonide capsules usually have fewer side effects than other corticosteroids because budesonide works in the gut and only small amounts are absorbed into the body. Nausea, heartburn, and headache, may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Because this drug works by weakening the immune system, it may lower your ability to fight infections. This may make you more likely to get a serious (rarely fatal) infection or make any infection you have worse. Tell your doctor immediately if you have any signs of infection (such as cough, sore throat, fever, chills). Use of this medication for prolonged or repeated periods may result in oral thrush or a yeast infection. Contact your doctor if you notice white patches in your mouth or a change in vaginal discharge.

Tell your doctor immediately if any of these rare but serious side effects occur: unusual tiredness, vision problems, easy bruising/bleeding, puffy face, unusual hair growth, mental/mood changes (such as depression, mood swings, agitation), muscle weakness/pain, thinning skin, slow wound healing.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Entocort EC (budesonide) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking budesonide, tell your doctor if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: eye disease (such as cataracts, glaucoma), high blood pressure, liver disease, thyroid problems, diabetes, stomach/intestinal problems (such as diverticulitis, ulcer), brittle bones (osteoporosis), current/past infections (such as tuberculosis, positive tuberculosis test, herpes, fungal), bleeding problems, mental/mood conditions (such as psychosis, anxiety, depression).

Using corticosteroid medications for a long time can make it more difficult for your body to respond to physical stress. Therefore, before having surgery or emergency treatment, or if you get a serious illness/injury, tell your doctor or dentist that you are using this medication or have used this medication within the past 12 months. Tell your doctor immediately if you develop unusual/extreme tiredness or weight loss. If you will be using this medication for a long time, carry a warning card or medical ID bracelet that identifies your use of this medication.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Daily use of alcohol while using this medicine may increase your risk for stomach bleeding. Limit alcoholic beverages. Consult your doctor or pharmacist for more information.

This medication may mask signs of infection. It can make you more likely to get infections or may worsen any current infections. Therefore, wash your hands well to prevent the spread of infection. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles, flu). Consult your doctor if you have been exposed to an infection or for more details.

Budesonide may cause vaccines not to work as well. Therefore, do not have any immunizations/vaccinations while using this medication without the consent of your doctor. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).

This medication may slow down a child's growth if used for a long time. Consult the doctor or pharmacist for more details. See the doctor regularly so your child's height and growth can be checked.

During pregnancy, budesonide should be used only when clearly needed. Discuss the risks and benefits with your doctor. Infants born to mothers who have used corticosteroids for a long time may have hormone problems. Tell your doctor immediately if you notice symptoms such as persistent nausea/vomiting, severe diarrhea, or weakness.

This drug passes into breast milk and may have undesirable effects in a nursing infant. Consult your doctor before breast-feeding.

Disclaimer

Entocort EC Consumer (continued)

DRUG INTERACTIONS: The effects of some drugs can change if you take other drugs or herbal products at the same time. This can increase your risk for serious side effects or may cause your medications not to work correctly. These drug interactions are possible, but do not always occur. Your doctor or pharmacist can often prevent or manage interactions by changing how you use your medications or by close monitoring.

To help your doctor and pharmacist give you the best care, be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products) before starting treatment with this product. While using this product, do not start, stop, or change the dosage of any other medicines you are using without your doctor's approval.

Some products that may interact with this drug include: aldesleukin, other drugs that weaken the immune system (such as azathioprine, cyclosporine, cancer chemotherapy, natalizumab), large doses of aspirin and aspirin-like drugs (salicylates), nonsteroidal anti-inflammatory drugs (NSAIDs such as indomethacin, ibuprofen), mifepristone, quinolone antibiotics (such as ciprofloxacin, levofloxacin), drugs that can cause bleeding/bruising (including "blood thinners" such as warfarin, antiplatelet drugs such as clopidogrel).

If your doctor has directed you to take low-dose aspirin for heart attack or stroke prevention (usually at dosages of 81-325 milligrams a day), you should continue taking it unless your doctor instructs you otherwise. Ask your doctor or pharmacist for more details.

Other medications can affect the removal of budesonide from your body, which may affect how budesonide works. Examples include azole antifungals (such as ketoconazole), macrolide antibiotics (such as erythromycin), rifamycins (such as rifabutin), St. John's wort, drugs used to treat seizures (such as carbamazepine, phenytoin), among others.

This product may interfere with certain lab tests (such as skin tests). Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

If this medication is used for an extended time, laboratory and/or medical tests (such as blood count, bone density tests, eye exams, height/weight measurements) should be performed regularly to check for side effects. Consult your doctor for more details.

This medication may cause bone problems (osteoporosis). Lifestyle changes that may help reduce the risk of bone problems while taking this drug for an extended time include doing weight-bearing exercise, getting enough calcium and vitamin D, stopping smoking, and limiting alcohol. Discuss with your doctor lifestyle changes that might benefit you.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store the US product at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Store the Canadian product at room temperature between 59-86 degrees F (15-30 degrees C).

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised May 2012. Copyright(c) 2012 First Databank, Inc.

Entocort EC Patient Information Including Side Effects

Brand Names: Entocort EC

Generic Name: budesonide (oral) (Pronunciation: bue DES oh nide)

What is budesonide (Entocort EC)?

Budesonide is a steroid. It prevents the release of substances in the body that cause inflammation..

Budesonide is used to treat mild to moderate Crohn's disease.

Budesonide may also be used for other purposes not listed in this medication guide.

Entocort EC 3 mg

gray/pink, imprinted with ENTOCORT 3 mg

What are the possible side effects of budesonide (Entocort EC)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist);
  • increased blood pressure (severe headache, fast or uneven heart rate, blurred vision); or
  • general ill feeling with headache, tiredness, nausea, and vomiting.

Less serious side effects may include:

  • thinning of the skin, easy bruising;
  • headache;
  • runny or stuffy nose, cough, sore throat;
  • muscle pain;
  • mild nausea, stomach pain, indigestion;
  • mild skin rash; or
  • changes in your menstrual periods.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Read the Entocort EC (budesonide) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about budesonide (Entocort EC)?

While taking budesonide, tell your doctor if you have changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist), high blood pressure, (severe headache, fast or uneven heart rate, blurred vision), or a general ill feeling with headache, tiredness, nausea, and vomiting.

Grapefruit and grapefruit juice may interact with budesonide and cause increased levels of the medication in your blood. Discuss the use of grapefruit products with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.

Avoid being near people who are sick or have infections. Call your doctor for preventive treatment if you are exposed to chicken pox or measles. These conditions can be serious or even fatal in people who are using budesonide.

Side Effects Centers

Entocort EC Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking budesonide (Entocort EC)?

You should not take this medication if you are allergic to budesonide, or if you have active tuberculosis or any other type of a serious bacterial, viral, or fungal infection.

Before taking budesonide, tell your doctor if you are allergic to any drugs, or if you have:

  • kidney disease;
  • liver disease (including cirrhosis);
  • stomach ulcer, intestinal bleeding or blockage;
  • measles, scarlet fever, or any other condition with a skin rash;
  • diverticulitis;
  • osteoporosis;
  • high blood pressure;
  • heart disease or coronary artery disease;
  • overactive thyroid;
  • mental illness;
  • a muscle disorder called myasthenia gravis; or
  • a personal or family history of diabetes, glaucoma, or cataract.

FDA Pregnancy Category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

Budesonide can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take budesonide (Entocort EC)?

Take this medication exactly as prescribed by your doctor. Do not take it in larger amounts or for longer than recommended. Follow the directions on your prescription label.

Take this medication with a full glass of water.

Budesonide should be taken before a meal.

Do not crush, chew, break, or open an extended-release capsule. Swallow the pill whole. Breaking or opening the pill may cause too much of the drug to be released at one time.

If you take budesonide long term, your blood may need to be tested on a regular basis. Do not miss any scheduled appointments.

If you need to have any type of surgery, tell the surgeon ahead of time that you are using budesonide. You may need to stop using the medicine for a short time.

Store budesonide at room temperature away from moisture and heat.

Side Effects Centers

Entocort EC Patient Information including If I Miss a Dose

What happens if I miss a dose (Entocort EC)?

Take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Entocort EC)?

Seek emergency medical attention if you think you have used too much of this medicine.

An overdose of budesonide is not expected to produce life-threatening symptoms. However, long-term use of high steroid doses can lead to symptoms such as thinning skin, easy bruising, changes in the shape or location of body fat (especially in your face, neck, back, and waist), increased acne or facial hair, menstrual problems, impotence, or loss of interest in sex.

What should I avoid while taking budesonide (Entocort EC)?

Grapefruit and grapefruit juice may interact with budesonide and cause increased levels of the medication in your blood. Discuss the use of grapefruit products with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.

Avoid being near people who are sick or have infections. Call your doctor for preventive treatment if you are exposed to chicken pox or measles. These conditions can be serious or even fatal in people who are using budesonide.

What other drugs will affect budesonide (Entocort EC)?

Before taking budesonide, tell your doctor if you are also using ketoconazole (Nizoral).

There may be other drugs that can interact with budesonide. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about budesonide.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 2.05. Revision date: 12/15/2010.

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