"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"...
The following clinically significant adverse reactions are described elsewhere in labeling:
- Hypercorticism and adrenal axis suppression [see WARNINGS AND PRECAUTIONS]
- Symptoms of steroid withdrawal in those patients transferred from other systemic corticosteroids [see WARNINGS AND PRECAUTIONS]
- Increased risk of infection [see WARNINGS AND PRECAUTIONS]
- Other corticosteroid 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 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
|Adverse Reaction||ENTOCORT EC||Prednisolone2
|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)|
Occurring in greater than or equal to 5% of the patients in any treated group.
2. Prednisolone tapering scheme: either 40 mg in week 1 to 2, thereafter tapering with 5 mg per week; or 40 mg in week 1to 2, 30 mg in week 3 to 4, thereafter tapering with 5 mg per week.
3. This drug is not approved for the treatment of Crohn’s disease in the United States.
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 ClinicalTrials
|Signs/Symptom||ENTOCORT EC 9 mg
|Prednisolone1 40 mg
|Total||145 (34%)||29 (27%)||69 (48%)|
|Acne||63 (15)||14 (13)||33 (23)2|
|Bruising Easily||63 (15)||12 (11)||13 (9)|
|Moon Face||46 (11)||4 (4)||53 (37)2|
|Swollen Ankles||32 (7)||6 (6)||13 (9)|
|Hirsutism3||22 (5)||2 (2)||5 (3)|
|Buffalo Hump||6 (1)||2 (2)||5 (3)|
|Skin Striae||4 (1)||2 (2)||0 (0)|
Prednisolone tapering scheme: either 40 mg in week 1-2, thereafter tapering with 5 mg/week; or 40 mg in week 1 to 2, 30 mg in week 3 to 4, thereafter tapering with 5 mg/week.
2. Statistically significantly different from ENTOCORT EC 9 mg.
3. including hair growth increased, local and hair growth increased, general.
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
|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 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
Investigations: weight increased
Metabolism and nutrition disorders: appetite increased
Psychiatric disorders: agitation, confusion, insomnia, nervousness, sleep disorder
Reproductive system and breast disorders: intermenstrual bleeding, menstrual disorder
Vascular disorders: 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-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.
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.
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
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 [see CLINICAL PHARMACOLOGY].
Avoid ingestion of grapefruit juice with budesonide. Intake of grapefruit juice which inhibits CYP3A4 activity with budesonide can increase the systemic exposure for budesonide [see CLINICAL PHARMACOLOGY].
Read the Entocort EC Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 8/1/2016
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