Entocort EC (budesonide) is a synthetic steroid of the glucocorticoid family used to treat mild-to-moderately-active Crohn's disease involving the ileum (the second half of the small intestine) and/or ascending colon (the beginning of the large intestine). 

It is approved for maintaining remissions for up to three months. Entocort EC also is used for the induction of remission in patients with active, mild to moderate ulcerative colitis (UC).

Common side effects of Entocort EC include

• headache,
• upper respiratory tract infection,
• nausea,
• diarrhea,
• abdominal pain,
• back pain,
• dizziness,
• fatigue,
• indigestion,
• vomiting,
• gas (flatulence),
• acne,
• joint pain,
• constipation,
• abdominal distension,
• urinary tract infections (UTIs),
• viral infections,
• low potassium, and
• fatigue.

Excessive corticosteroid use causes

• easy bruising,
• moon (rounded) face,
• buffalo hump,
• excessive hair growth, and
• swollen ankles.

Serious side effects of Entocort EC include

• adrenal suppression,
• suppression of the immune system,
• infections,
• intracranial hypertension, and
• serious allergic reactions.

Drug interactions of Entocort EC include medicines that block the liver enzymes that break down Entocort EC, because the combination may lead to higher blood concentrations and more side effects of Entocort EC, such as

• ketoconazole,
• fluconazole,
• itraconazole,
• clarithromycin,
• erythromycin,
• verapamil,
• diltiazem,
• ritonavir,
• indinavir, and
• saquinavir.

Grapefruit juice has a similar effect and should not be consumed by patients taking Entocort EC. 

There are no adequate studies of Entocort EC in pregnant women. Entocort EC should only be used in pregnant women if the benefits outweigh the unknown risk. Use of Entocort EC during pregnancy may suppress the adrenal glands of the infant. 

Entocort EC is secreted in human breast milk. Because of the potential for adverse reactions in nursing infants from any corticosteroid, a decision should be made whether to discontinue breastfeeding or discontinue the Entocort EC.

The most common side effects of budesonide are:

• Headache
• Upper respiratory tract infection
• Nausea
• Diarrhea
• Abdominal pain
• Back pain
• Dizziness
• Fatigue
• Indigestion
• Vomiting
• Flatulence (intestinal gas, farting)
• Arthralgia
• Constipation
• Abdominal distension
• Acne
• Urinary tract infections (UTIs)
• Viral infections
• Low potassium
• Fatigue

Excessive corticosteroid use causes:

• Acne
• Easy bruising
• Moon (rounded) face
•  Buffalo hump
• Excessive hair growth
• Swollen ankles

Serious side effects of budesonide include:

• Adrenal suppression
• Suppression of the immune system
• Infections
• Intracranial hypertension
• Serious allergic reactions

The following clinically significant adverse reactions are described elsewhere in labeling:

• Hypercorticism and adrenal axis suppression
• Symptoms of steroid withdrawal in those patients transferred from other systemic corticosteroids
• Increased risk of infection
• Other corticosteroid effects

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.

Adults

• The data described below reflect exposure to Entocort EC in 520 patients with Crohn's disease, including 520 exposed to 9 mg per day (total daily dose) for 8 weeks and 145 exposed to 6 mg per day for one year in placebo controlled clinical trials.
• Of the 520 patients, 38% were males and the age range was 17 to 74 years.

Treatment Of Mild To Moderate Active Crohn's Disease

• The safety of Entocort EC was evaluated in 651 adult patients in five clinical trials of 8 weeks duration in patients with active mild to moderate Crohn's disease.
• The most common adverse reactions, occurring in greater than or equal to 5% of the patients, are listed in Table 1.

Table 1 : Common Adverse Reactions¹ in 8-Week Treatment Clinical Trials

• The incidence of signs and symptoms of hypercorticism reported by active questioning of patients in 4 of the 5 short-term clinical trials are displayed in Table 2.

Table 2: Summary and Incidence of Signs/Symptoms of Hypercorticism in 8-Week Treatment Clinical Trials

Maintenance Of Clinical Remission Of Mild To Moderate Crohn's Disease

The safety of Entocort EC was evaluated in 233 adult patients in four long-term clinical trials (52 weeks) of maintenance of clinical remission in patients with mild to moderate Crohn's disease. A total of 145 patients were treated with Entocort EC 6 mg once daily.

The adverse reaction profile of Entocort EC 6 mg once daily in maintenance of Crohn's disease was similar to that of short-term treatment with Entocort EC 9 mg once daily in active Crohn's disease. In the long-term clinical trials, the following adverse reactions occurred in greater than or equal to 5% and are not listed in Table 1:

• diarrhea (10%);
• sinusitis (8%);
• infection viral (6%); and
• arthralgia (5%).

Signs/symptoms of hypercorticism reported by active questioning of patients in the long-term maintenance clinical trials are displayed in Table 3.

Table 3: Summary and Incidence of Signs/Symptoms of Hypercorticism in Long-Term Clinical Trials

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

Less Common Adverse Reactions In Treatment And Maintenance Clinical Trials

Less common adverse reactions (less than 5%), occurring in adult patients treated with Entocort EC 9 mg (total daily dose) in short-term treatment clinical studies and/or Entocort EC 6 mg (total daily dose) in long-term maintenance clinical trials, with an incidence are listed below by system organ class:

• 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, 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: weight increased
• Metabolism and nutrition disorders: appetite increased
• Musculoskeletal and connective tissue disorders: arthritis, cramps, myalgia
• Nervous system disorders: hyperkinesia, paresthesia, tremor, vertigo, 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: alopecia, dermatitis, eczema, skin disorder, sweating increased, purpura
• Vascular disorders:/b> flushing, hypertension

Bone Mineral Density

• A randomized, open, parallel-group multicenter safety clinical trial 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-naive 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.

Pediatrics—Treatment Of Mild To Moderate Active Crohn's Disease

• Adverse reactions reported in pediatric patients 8 to 17 years of age, who weigh more than 25 kg, were similar to those reactions described above in adult patients.

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

CYP3A4 Inhibitors

• Budesonide is a substrate for CYP3A4. Avoid use with CYP3A4 inhibitors.
• Concomitant oral administration of a strong CYP3A4 inhibitor (ketoconazole) caused an eight-fold increase of the systemic exposure to oral budesonide.
• Inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, and cyclosporine) can increase systemic budesonide concentrations.

Grapefruit Juice

• Avoid ingestion of grapefruit juice with budesonide.
• Intake of grapefruit juice which inhibits CYP3A4 activity with budesonide can increase the systemic exposure for budesonide.