Side effect of budesonide

Entocort

SIDE EFFECTS

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: 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.

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 entire FDA prescribing information for Entocort (Budesonide)

Uceris (Oral)

Generic Name: budesonide (Oral route)

bue-DES-oh-nide

Medically reviewed by Drugs.com. Last updated on Nov 14, 2018.

  • Overview
  • Side Effects
  • Dosage
  • Professional
  • Interactions
  • More

Commonly used brand name(s)

In the U.S.

  • Entocort EC
  • Uceris

In Canada

  • Pulmicort
  • Pulmicort Spacer

Available Dosage Forms:

  • Tablet, Extended Release
  • Capsule, Delayed Release

Therapeutic Class: Gastrointestinal Agent

Pharmacologic Class: Adrenal Glucocorticoid

Uses for Uceris

Budesonide is used to treat an inflammatory bowel disease called Crohn’s disease. This medicine works inside the intestine (bowel) to reduce inflammation and symptoms of the disease. It also helps keep the symptoms of Crohn’s disease from coming back. Budesonide is a steroid (cortisone-like) medicine.

Budesonide extended-release tablets are used to help get active mild to moderate ulcerative colitis under control (induce remission).

This medicine is available only with your doctor’s prescription.

Before using Uceris

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of budesonide capsules in children 8 years to 17 years of age and weighing more than 25 kilograms (kg). However, safety and efficacy have not been established in children younger than 8 years of age, or in children 8 to 17 years of age and weighs 25 kg or less.

Appropriate studies have not been performed on the relationship of age to the effects of budesonide extended release tablets in the pediatric population. Safety and efficacy have not been established. Because budesonide may cause slowed growth in children, those who will be taking it for a long time should have their weight and growth measured by the doctor regularly.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of budesonide in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving budesonide.

Breastfeeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Desmopressin

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Aceclofenac
  • Acemetacin
  • Amtolmetin Guacil
  • Balofloxacin
  • Bemiparin
  • Besifloxacin
  • Boceprevir
  • Bromfenac
  • Bufexamac
  • Bupropion
  • Celecoxib
  • Ceritinib
  • Choline Salicylate
  • Ciprofloxacin
  • Clonixin
  • Cobicistat
  • Conivaptan
  • Darunavir
  • Dexibuprofen
  • Dexketoprofen
  • Diclofenac
  • Diflunisal
  • Dipyrone
  • Droxicam
  • Duvelisib
  • Enoxacin
  • Etodolac
  • Etofenamate
  • Etoricoxib
  • Felbinac
  • Fenoprofen
  • Fepradinol
  • Feprazone
  • Fleroxacin
  • Floctafenine
  • Flufenamic Acid
  • Flumequine
  • Flurbiprofen
  • Fosnetupitant
  • Gatifloxacin
  • Gemifloxacin
  • Ibuprofen
  • Idelalisib
  • Indomethacin
  • Ivosidenib
  • Ketoprofen
  • Ketorolac
  • Levofloxacin
  • Lomefloxacin
  • Lornoxicam
  • Loxoprofen
  • Lumacaftor
  • Lumiracoxib
  • Macimorelin
  • Meclofenamate
  • Mefenamic Acid
  • Meloxicam
  • Morniflumate
  • Moxifloxacin
  • Nabumetone
  • Nadifloxacin
  • Nadroparin
  • Naproxen
  • Nepafenac
  • Netupitant
  • Niflumic Acid
  • Nimesulide
  • Nimesulide Beta Cyclodextrin
  • Norfloxacin
  • Ofloxacin
  • Oxaprozin
  • Oxyphenbutazone
  • Parecoxib
  • Pazufloxacin
  • Pefloxacin
  • Phenylbutazone
  • Piketoprofen
  • Piroxicam
  • Pranoprofen
  • Proglumetacin
  • Propyphenazone
  • Proquazone
  • Prulifloxacin
  • Ritonavir
  • Rofecoxib
  • Rufloxacin
  • Salicylic Acid
  • Salsalate
  • Sargramostim
  • Sodium Salicylate
  • Sparfloxacin
  • Sulindac
  • Telaprevir
  • Tenoxicam
  • Tiaprofenic Acid
  • Tolfenamic Acid
  • Tolmetin
  • Tosufloxacin
  • Valdecoxib

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Erythromycin
  • Ketoconazole

Interactions with food/tobacco/alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

  • Grapefruit Juice

Other medical problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Cataracts (eye disease), or a family history of or
  • Diabetes, or a family history of or
  • Eczema (skin disease) or
  • Glaucoma, or a family history of or
  • Hypertension (high blood pressure) or
  • Infection (eg, bacteria, virus, fungus) or
  • Osteoporosis (thin bones) or
  • Rhinitis (inflammation inside your nose) or
  • Stomach ulcer, active or history of or
  • Tuberculosis, active or history of or
  • Weakened immune system—Use with caution. May make these conditions worse.
  • Liver disease (including cirrhosis), moderate to severe—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Proper use of budesonide

This section provides information on the proper use of a number of products that contain budesonide. It may not be specific to Uceris. Please read with care.

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. Also, do not stop taking this medicine without first checking with your doctor.

This medicine comes with a patient information insert. Read and follow the instructions carefully. Ask your doctor or pharmacist if you have any questions.

Swallow the capsule and extended-release tablet whole. Do not break, crush, chew, or open it.

Keep using this medicine for the full time of treatment, even if you begin to feel better after a few days. Do not miss any doses.

Grapefruits and grapefruit juice may increase the effects of budesonide by increasing the amount of this medicine in your body. You should not eat grapefruit or drink grapefruit juice while you are taking this medicine.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (capsules):
    • For mild to moderate Crohn’s disease:
      • Adults—9 milligrams (mg) once a day in the morning for up to 8 weeks. Your doctor may adjust your dose as needed.
      • Children 8 to 17 years of age and weighing more than 25 kilograms (kg)—At first, 9 mg once a day in the morning for up to 8 weeks, followed by 6 mg once a day in the morning for 2 weeks.
      • Children 8 to 17 years of age and weighing 25 kg or less—Use and dose must be determined by your doctor.
      • Children younger than 8 years of age—Use and dose must be determined by your doctor.
    • For prevention of symptoms of Crohn’s disease from coming back:
      • Adults—6 milligrams (mg) once a day in the morning for up to 3 months. Your doctor may adjust your dose as needed.
      • Children—Use and dose must be determined by your doctor.
  • For oral dosage form (extended-release tablets):
    • For mild to moderate ulcerative colitis:
      • Adults—9 milligrams (mg) once a day in the morning for up to 8 weeks.
      • Children—Use and dose must be determined by your doctor.

Missed dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions while using Uceris

It is very important that your doctor check your progress at regular visits for any problems or unwanted effects that may be caused by this medicine.

If your condition does not improve or if it become worse, check with your doctor.

This medicine may cause serious allergic reactions, including anaphylaxis. Anaphylaxis requires immediate medical attention. The most serious signs of this reaction are very fast or irregular breathing, gasping for breath, or fainting. Other signs may include changes in color of the skin of the face, very fast but irregular heartbeat or pulse, hive-like swellings on the skin, and puffiness or swellings of the eyelids or around the eyes. If these side effects occur, get emergency help at once.

Using too much of this medicine or using it for a long time may increase your risk of having adrenal gland problems. Talk to your doctor if you have more than one of these symptoms while you are using this medicine: darkening of the skin, diarrhea, dizziness, fainting, loss of appetite, mental depression, nausea, skin rash, unusual tiredness or weakness, or vomiting.

If you are taking another steroid medicine and will switch to Uceris™, check first with your doctor. This may increase your chance of having steroid withdrawal side effects, such as headache, loss of appetite, blurred vision, change in the ability to see colors (especially blue or yellow), or vomiting.

You may get infections more easily while using this medicine. Avoid people who are sick or have infections. Tell your doctor right away if you have been exposed to someone with chickenpox or measles.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine several days before having surgery or medical tests.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter ) medicines and herbal or vitamin supplements.

Uceris side effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

  • Bruising easily
  • chills
  • colds
  • cough or hoarseness
  • fever
  • flu-like symptoms
  • sneezing
  • sore throat

Less common

  • Abdominal or stomach pain
  • bladder pain
  • bleeding after defecation
  • bloody or cloudy urine
  • blurred vision
  • burning while urinating
  • burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
  • chest pain
  • convulsions
  • cough producing mucus
  • decreased urine
  • diarrhea
  • difficult or labored breathing
  • difficult or painful urination
  • dizziness
  • dry mouth
  • eye pain
  • fast, irregular, pounding, or racing heartbeat or pulse
  • feeling of warmth
  • general feeling of discomfort or illness
  • headache
  • heartburn
  • increase in body movements
  • increased thirst
  • increased urge to urinate during the night
  • irregular heartbeat
  • joint pain
  • loss of appetite
  • lower back or side pain
  • mood changes
  • muscle aches and pains
  • nausea or vomiting
  • nervousness
  • numbness or tingling in the hands, feet, or lips
  • pain or discomfort in the chest, upper stomach, or throat
  • pounding in the ears
  • rectal bleeding
  • redness of the face, neck, arms, and occasionally, upper chest
  • runny nose
  • severe constipation
  • shakiness in the legs, arms, hands, or feet
  • shivering
  • slow or fast heartbeat
  • stomach cramps
  • sweating
  • swelling of the legs and feet
  • swelling or puffiness of the face
  • tightness in the chest
  • trouble sleeping
  • uncomfortable swelling around the anus
  • unusual tiredness or weakness
  • upper abdominal or stomach pain
  • waking to urinate at night
  • weight gain
  • weight loss

Incidence not known

  • Bulging soft spot on the head of an infant
  • change in the ability to see colors, especially blue or yellow
  • difficulty with swallowing
  • hives, itching, or skin rash
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  • Acid or sour stomach
  • belching
  • blemishes on the skin
  • heartburn
  • indigestion
  • pain or tenderness around the eyes and cheekbones
  • pimples
  • rounded or moon face
  • stomach discomfort, upset, or pain
  • stuffy nose

Less common

  • Accumulation of pus
  • agitation
  • blistering, crusting, irritation, itching, or reddening of the skin
  • bloated or full feeling
  • change in hearing
  • changes in vision
  • cracked, dry, or scaly skin
  • cracks in the skin at the corners of mouth
  • difficulty having a bowel movement (stool)
  • difficulty with moving
  • dizziness or lightheadedness
  • ear drainage
  • earache or pain in the ear
  • excess air or gas in the stomach or intestines
  • feeling of constant movement of self or surroundings
  • hair loss or thinning of the hair
  • increased appetite
  • increased hair growth, especially on the face
  • lack or loss of strength
  • loss of memory
  • muscle pains or stiffness
  • nervousness
  • pain, swelling, or redness in the joints
  • passing gas
  • pinpoint red or purple spots on the skin
  • pressure in the stomach
  • problems with memory
  • redness, swelling, or soreness of the tongue
  • sensation of spinning
  • skin rash
  • skin rash, encrusted, scaly, and oozing
  • sleepiness or unusual drowsiness
  • soreness or redness around the fingernails and toenails
  • swelling of the abdominal or stomach area
  • swollen joints
  • uterine bleeding between menstrual periods

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 2019 Truven Health Analytics, Inc. All Rights Reserved.

Medical Disclaimer

More about Uceris (budesonide)

  • Side Effects
  • During Pregnancy or Breastfeeding
  • Dosage Information
  • Drug Images
  • Drug Interactions
  • Pricing & Coupons
  • 22 Reviews
  • Generic Availability
  • Drug class: glucocorticoids
  • FDA Approval History

Consumer resources

  • Uceris
  • Uceris (Budesonide Extended-Release Tablets)
  • Uceris (Budesonide Rectal Foam)
  • Uceris Rectal (Advanced Reading)

Other brands: Pulmicort Flexhaler, Pulmicort Turbuhaler, Pulmicort Respules, Entocort EC, Pulmicort Nebuamp

Professional resources

  • Uceris Foam (FDA)
  • … +2 more

Related treatment guides

  • Ulcerative Colitis
  • Ulcerative Colitis, Active

SIDE EFFECTS: This medication usually has 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.

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.

QUESTION

What is Crohn’s disease? See Answer

Treatment Options for Microscopic Colitis

Case Discussion

Oral budesonide has proven to be the most effective treatment for MC, and it is the recommended first-line medical therapy for symptomatic MC in the recently published American Gastroenterological Association (AGA) Institute guidelines for the medical management of MC. Prior Cochrane systematic reviews concluded the same for budesonide in the treatment of collagenous colitis, and probably for lymphocytic colitis as well.

Oral budesonide is a corticosteroid that suppresses inflammation topically in the gastrointestinal tract. Ninety percent of the drug is metabolized by the liver upon absorption, thereby limiting its systemic activity, including potential corticosteroid related adverse effects, such as adrenal suppression and osteoporosis.

Two formulations of oral budesonide are used to treat inflammatory bowel disease in the United States: Entocort® EC (AstraZeneca) and Uceris® (Salix Pharmaceuticals). Entocort EC is designed to release budesonide in the terminal ileum and ascending colon, is approved to treat Crohn disease, and has been the principal formulation of budesonide used in clinical trials and practice to treat MC. Uceris delivers budesonide to the entire colon and is approved to treat ulcerative colitis.

Budesonide was significantly more effective than placebo at inducing short- and long-term clinical response and histologic improvement in a meta-analysis of seven randomized, controlled trials. Budesonide-treated patients were three times more likely to experience short-term clinical improvement than patients who received placebo (risk ratio, 3.07; 95% confidence interval , 2.06-4.57).

The recommended starting dose of budesonide to induce clinical remission of MC is 9 mg/day, with most patients experiencing improvement in their diarrhea in 2-4 weeks. Budesonide induction therapy is typically continued for 4 weeks, and if the patient’s disease is in remission at that time, the medication is tapered down by 3 mg every 2 weeks, and then discontinued. Budesonide induction therapy may be continued for 8-12 weeks if clinical remission is not achieved by 4 weeks.

Patients who are responsive to budesonide are at high risk for relapse when the medications are stopped; disease will remain in remission in only one third of patients. The median time to relapse is 2 weeks after treatment cessation, with patients younger than 60 years at a greater risk for relapse. Patients with relapse may be retreated with either intermittent or low-dose maintenance budesonide therapy.

The AGA guideline recommends maintenance budesonide therapy for patients with recurrent symptoms after discontinuation of induction therapy. Studies have shown that maintenance budesonide therapy at 6 mg/day is three times more effective than placebo at maintaining remission for up to 6 months (RR, 3.22; 95% CI, 1.05-9.89). For budesonide-dependent patients with MC who again achieve remission using budesonide 6 mg/day, Pardi and Kelly recommend reducing the budesonide dosage to 3 mg/day, and to 3 mg every other day if possible, and then attempting discontinuation of maintenance therapy after 6-12 months. If patients experience relapse when off maintenance therapy, budesonide treatment may be resumed and continued indefinitely at the lowest effective dose and frequency.

Budesonide induction and maintenance therapy appear to be safe, given the low systemic activity of the drug; the meta-analysis found no significant difference in adverse effects between budesonide recipients and placebo recipients. However, budesonide-dependent patients should still be monitored for potential corticosteroid-related adverse effects, such as osteoporosis.

According to the AGA guideline, mesalamine may be considered as second-line medical therapy for MC if patients cannot tolerate or afford budesonide. Historically, mesalamine was frequently prescribed for treatment, but it has recently fallen out of favor because studies have failed to show that it effectively treats MC. Specifically, mesalamine (3 g/day) was found to be ineffective or inferior to budesonide (9 mg/day) compared with placebo for the short-term treatment of collagenous colitis in a randomized, double-blind. multicenter trial. Eighty percent of budesonide treated patients (n = 30) achieved clinical remission after 8 weeks of treatment, compared with only 44% of mesalamine-treated patients (n = 25) and 37.8% of placebo recipients (n = 37; budesonide vs placebo, P < .001).

Regarding cholestyramine, the AGA guideline recommends against adding cholestyramine to mesalamine monotherapy and does not discuss cholestyramine monotherapy owing to the lack of clinical trials. It is this author’s opinion that cholestyramine can sometimes be a helpful adjunctive treatment for MC, especially for patients who also have postcholecystectomy diarrhea. Bile acids and bile acid malabsorption have been implicated in the pathogenesis of MC, and cholestyramine has been reported to induce clinical remission in patients with concomitant MC and bile acid malabsorption.

Azathioprine may be considered as a rescue therapy for cases of refractory MC that do not respond to budesonide or second-line therapies once other causes of diarrhea are ruled out, including celiac disease, which is strongly associated with MC. The reported experience of azathioprine therapy for refractory MC is limited to two small case series involving primarily corticosteroid-dependent patients; azathioprine induced a clinical response in 89% (8 of 9) of patients in one of the studies and 41% (19 of 46) of patients in the other study. Azathioprine therapy was complicated in these case series by frequent adverse effects for the majority of patients, including nausea and hepatitis.

Accordingly, given the relative low toxicity of budesonide compared with azathioprine, budesonide is preferred over azathioprine for maintenance therapy of corticosteroid-dependent patients with MC.

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About budesonide

Type of medicine A corticosteroid, also commonly called an oral steroid
Used for Inflammatory bowel disease such as Crohn’s disease or ulcerative colitis; chronic diarrhoea due to collagenous colitis; autoimmune hepatitis
Also called Budenofalk®; Entocort® CR; Cortiment®
Available as Capsules, modified-release capsules, modified-release tablets, and granules

Budesonide works by reducing inflammation, and this eases the symptoms of flare-ups of inflammatory bowel conditions.

Crohn’s disease is a condition which causes inflammation in the gastrointestinal system. Any part of the system can be affected, although the most common site for the disease to start is the lower part of the small intestine, called the ileum. Other parts of the small intestine and the colon are also commonly affected. When the disease flares up, the inflammation causes varying symptoms depending on which part of the gastrointestinal system is affected. Common symptoms are pain, diarrhoea, weight loss and ulcers.

Ulcerative colitis causes inflammation of the large intestine, which leads to problems such as ulceration and bleeding. This causes symptoms such as tummy (abdominal) pain and diarrhoea.

A brand of budesonide called Budenofalk® is used to treat some other conditions associated with inflammation too. It is a treatment for a type of chronic liver inflammation known as autoimmune hepatitis, and it also reduces diarrhoea caused by a chronic inflammatory condition of the large bowel (called collagenous colitis).

There are a number of different budesonide preparations and brands. The way the manufacturers make each of these differs slightly; this allows the different brands to release budesonide in specific areas of the intestine. You will be prescribed the brand that allows budesonide to be released in the part of your intestine which requires it most.

Before taking budesonide

Some medicines are not suitable for people with certain conditions, and sometimes a medicine can only be used if extra care is taken. For these reasons, before you start taking budesonide it is important that your doctor knows:

  • If you are pregnant or breastfeeding (even though budesonide could still be prescribed for you).
  • If you have any kind of infection, or if you have ever had tuberculosis (TB).
  • If you have had a heart attack, or if you have a heart condition.
  • If you have any problems with the way your liver works, or if you have any problems with the way your kidneys work.
  • If you have sugar diabetes, or if you have an eye condition called glaucoma. You should also tell your doctor if a close member of your family has either of these conditions.
  • If you currently have any of the following conditions: high blood pressure, osteoporosis, diverticulitis, an underactive thyroid gland, epilepsy, cataracts, or a condition causing severe muscle weakness (called myasthenia gravis).
  • If you have ever had any of the following: a blood clot in a blood vessel, a stomach ulcer, or a mental health problem such as depression or psychosis.
  • If you are taking any other medicines. This includes any medicines which are available to buy without a prescription, as well as herbal and complementary medicines.
  • If you have ever had an allergic reaction to a medicine, or if you have ever developed muscle pain after taking a steroid medicine.

How to take budesonide

  • Before you start the treatment, read the manufacturer’s printed information leaflet from inside the pack. It will give you more information about budesonide, and will also provide you with a full list of the side-effects which you could experience from taking it.
  • Your doctor will tell you how to take budesonide and this information will also be printed on the label of the pack to remind you about what the doctor said to you. It is important that you take your doses exactly as your doctor tells you to. The following doses are intended as a guide only:
    • If you have been given Budenofalk® capsules, the usual dose is one capsule three times daily, 30-60 minutes before a meal, or alternatively, three capsules taken together in the morning before breakfast.
    • If you have been given Entocort® capsules, the usual dose is three capsules taken together in the morning, preferably before breakfast. Swallow the capsules with a drink of water.
    • Budenofalk® granules are taken as a single dose of one sachet in the morning, 30-60 minutes before breakfast. Place the granules on your tongue and swallow them with a drink of water. Do not chew the granules as you swallow.
    • If you have been given Cortiment® tablets, the usual dose is one tablet in the morning. Swallow the tablet with a drink of water. It can be taken with or without food.
  • Do not take antacids or indigestion remedies during the two hours before and the two hours after you take budesonide. This is because antacids could affect the way the medicine is released and could stop it from getting to the correct part of your bowel.
  • Try to take your doses at the same time(s) of day each day. Doing this will help you to remember to take budesonide regularly. If you do forget to take a dose, take it as soon as you remember (unless it is nearly time for your next dose, in which case leave out the missed dose). Do not take two doses together to make up for a forgotten dose.
  • Continue to take budesonide until your doctor tells you to stop. It is usual to be prescribed a course of treatment that lasts for up to eight weeks. Your doctor may ask you to reduce your dose gradually during the last couple of weeks of the course.

Getting the most from your treatment

  • You will be given a ‘steroid treatment card’ which says that you are on steroids and which contains some important advice for you. It is important that you read this card and carry it with you while you are taking budesonide. It contains details about your dose, how long you have been taking a steroid for, and who prescribed it for you. Please make sure that this information is kept up to date. If you are having an operation or any medical treatment, please tell the person carrying out the treatment that you are taking budesonide and show them your treatment card.
  • Try to keep your regular appointments with your doctor. This is so your doctor can check on your progress. You may need to have some blood tests from time to time.
  • Budesonide can suppress your immune system, so it is important if you become ill that you make an appointment to see your doctor straightaway. Also, if you come into contact with anyone who has measles, shingles or chickenpox (or who suspects they may have one of these viruses), you must see your doctor as soon as possible.
  • It is recommended that you do not drink grapefruit juice while you are on budesonide. This is because a chemical in grapefruit increases the amount of budesonide in your bloodstream. This makes side-effects more likely.
  • If you buy any medicines, check with a pharmacist that they are suitable to take with budesonide.
  • Some vaccines may not be suitable for you while you are being treated with budesonide. If you need any immunisations, make sure you mention that you are taking a steroid medicine.
  • Do not stop taking budesonide without speaking with your doctor first. This is particularly important if you have been taking budesonide for more than three weeks. Your doctor will want you to reduce your dose gradually when this is necessary, as stopping suddenly can lead to problems.

Can budesonide cause problems?

Along with its useful effects, budesonide can cause unwanted side-effects which your doctor will discuss with you. The benefits of taking budesonide usually outweigh the side-effects; however, they can sometimes be troublesome. Although not everyone experiences side-effects, and some will improve as your body adjusts to the new medicine, speak with your doctor or pharmacist if you become concerned about any of the following:

Common budesonide side-effects What can I do if I experience this?
Tummy (abdominal) pain, feeling sick (nausea), indigestion Stick to simple or bland foods – avoid fatty or spicy foods
Changes in behaviour or mood If you become anxious, confused, or start having worrying thoughts about harming yourself, speak with your doctor as soon as possible
Feeling tired If this becomes troublesome, speak with your doctor
Headache Drink plenty of water and ask your pharmacist to recommend a suitable painkiller. If the headaches continue, let your doctor know
Cold or flu-like symptoms, other infections Speak with your doctor about this, especially if you have been in contact with someone with chickenpox, measles or shingles
Blurred eyesight, muscle cramps, itchy skin rash, heavy or irregular periods, the sensation of having a ‘thumping heart’ (palpitations), problems sleeping (insomnia) If any of these become troublesome, speak with your doctor

For more information about side-effects which can develop when steroids are taken longer-term, please see the separate leaflet called Oral Steroids.

If you experience any other symptoms which you think may be due to budesonide, speak with your doctor or pharmacist for further advice.

How to store budesonide

  • Keep all medicines out of the reach and sight of children.
  • Store in a cool, dry place, away from direct heat and light.

Important information about all medicines

Never take more than the prescribed dose. If you suspect that you or someone else might have taken an overdose of this medicine, go to the accident and emergency department of your local hospital at once. Take the container with you, even if it is empty.

This medicine is for you. Never give it to other people even if their condition appears to be the same as yours.

Do not keep out-of-date or unwanted medicines. Take them to your local pharmacy which will dispose of them for you.

If you have any questions about this medicine ask your pharmacist.

Results

PATIENT ENROLMENT

A total of 178 patients were randomised and 177 were treated; 58 patients received budesonide 9 mg once daily, 61 budesonide 4.5 mg twice daily, and 58 received prednisolone. The demography and disease history for all patients treated, recruited at 26 centres, are presented in table 1. The groups were well matched. Out of the 177 patients treated in the study, 36 prematurely discontinued their treatment.

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Table 1

 Demographic characteristics and disease history

The major reason (15%) for treatment withdrawal was disease deterioration or no improvement (therapeutic failure). The frequencies of therapeutic failure observed were comparable in the three groups—that is, 16% in the budesonide once daily group,16% in the budesonide twice daily group, and 12% in the prednisolone group. A χ2 test showed no significant differences between the treatment groups (p=0.78).

CLINICAL EFFICACY

Remission rates

Statistical evaluation of all patients treated showed that after two weeks of treatment the highest remission rate of 48% was observed in the budesonide once daily group, compared with 37% in the prednisolone group, and 27% in the budesonide twice daily group (fig1). These differences in remission rates were not significant (p=0.052). After eight weeks treatment, equal remission rates of 60% were found in the budesonide once daily and prednisolone groups, compared with 42% in the budesonide twice daily group (fig 1). The differences between the three groups were not statistically significant (p=0.062).

Figure 1

: Mean (SE) proportion of patients in remission after two, four, eight, and 12 weeks of treatment with budesonide or prednisolone.

Analyses with respect to prognostic factors

Analyses of remission rates by two-way analysis of variance were also performed with respect to the following prognostic factors:

  • disease activity at inclusion (CDAI ⩾300/CDAI <300)

  • previous bowel resection (yes/no)

  • sex

  • previous steroid treatment during the past year (yes/no).

 After eight weeks of treatment patients admitted to the study with a CDAI <300 showed an overall remission rate significantly higher than patients who entered with a CDAI >300. Of the patients admitted with a CDAI <300, remission was achieved in 31/44 in the budesonide once daily group, in 21/40 in the budesonide twice daily group, and in 22/44 in the prednisolone group. In the group with a CDAI ⩾300, remission was achieved in 4/13, 3/18, and 7/13 in the budesonide once daily, budesonide twice daily, and prednisolone groups, respectively. Disease activity was a prognostic factor which significantly (p=0.0007) influenced the remission rates; however, the difference between treatments did not depend on the disease activity. Furthermore, the absolute decrease in mean CDAI was largest in the budesonide once daily group, irrespective of severity at entry.

There was a statistically significant interaction between treatment and the presence or absence of previous resection (p=0.030); although the remission rate was higher among non-resected patients in both the budesonide once daily group and the prednisolone group, the rate was higher among resected patients in the budesonide twice daily group. Remission rates for male or female patients, or for patients who had or did not have previous steroid treatment, were not significantly different (p=0.80, p=0.15).

CDAI change

The mean initial CDAI score was 277 for the budesonide once daily group, 274 for the budesonide twice daily group, and 279 for the prednisolone group. The most pronounced decrease in CDAI score in all three groups was observed during the first two treatment weeks.

As reflected by remission rates, the mean CDAI scores decreased more in the budesonide once daily group and prednisolone group than in the budesonide twice daily group. The difference between the groups in reduction of CDAI score was statistically significant after two weeks (p=0.050) but not after eight weeks (p=0.093) (fig2).

Figure 2

: Mean (SE) CDAI score at randomisation and after two, four, eight, and 12 weeks of treatment with budesonide or prednisolone.

SAFETY RESULTS

Adverse events

Adverse events (any unfavourable events—such as clinical signs, symptoms, changes in laboratory data—temporarily associated with administration of the study drug) were registered in 78% of patients in the budesonide once daily group, 90% in the budesonide twice daily group, and 90% in the prednisolone group. Most adverse events were related to the gastrointestinal system, probably reflecting the underlying disease. A slightly higher frequency of dyspepsia was observed in the budesonide once daily group, while nausea and epigastric pain were more frequent in the budesonide twice daily group. The highest frequency of patients with Cushingoid features was observed in the prednisolone group. Four patients in the budesonide once daily group reported rashes compared with none in the other groups; the frequency of depression and insomnia, palpitations, and flushing was higher in the prednisolone group. The number of patients with urinary tract infections was higher in the budesonide twice daily group whereas increased frequency of micturition was reported only by prednisolone treated patients.

Eighteen adverse events in 17 patients, of which 10 discontinued study treatment, resulted in hospitalisation and were classified as serious. The majority of admissions were for disease deterioration or complications of Crohn’s disease. A relationship between these serious adverse events and the study drug was judged, by the investigator, to be unlikely.

There was a significant difference between the three groups with respect to change in weight: after eight weeks, mean body weight increased by 1.0 kg in the budesonide once daily group and by 2.1 kg in the prednisolone group, but not at all in the budesonide twice daily group (p<0.0001).

Haematology, clinical chemistry, and inflammatory indicators

Most of the laboratory values found outside normal reference ranges were considered by the investigators to be related to the underlying Crohn’s disease. There were no statistically significant differences between the three groups with respect to changes in the inflammatory indicators (ESR, serum CRP, serum orosomucoid).

Comparison of the mean changes in haematological and clinical chemistry variables from baseline showed a significant difference (p=0.029) at 12 weeks between the groups with respect to leucocyte count. After 12 weeks the mean leucocyte count in the prednisolone group significantly increased by 0.9 × 109/l; it decreased by 0.5 × 109/l in the budesonide once daily group, and very slightly increased by 0.1 × 109/l in the budesonide twice daily group. No other haematological and clinical chemistry variables differed significantly between the groups.

Basal plasma cortisol

The mean plasma cortisol values at randomisation were similar in the groups—that is, 382 nmol/l in the budesonide once daily group, 374 nmol/l in the budesonide twice daily group, and 375 nmol/l in the prednisolone group. There was a decrease in all three groups during the treatment period (fig 3). After eight weeks of treatment the mean plasma cortisol value had decreased by 258 nmol/l in the prednisolone group, by 194 nmol/l in the budesonide once daily group, and by 132 nmol/l in the budesonide twice daily group. The difference between the groups was statistically significant (p=0.0035). There was no significant difference between the two budesonide groups (p=0.096). Mean plasma cortisol values after two, eight, and 12 weeks were always lower in the prednisolone group.

Figure 3

: Mean (SE) morning plasma cortisol at randomisation and after two, four, eight, and 12 weeks of treatment with budesonide or prednisolone.

The proportion of patients with values below the lower plasma cortisol normal reference limit—150 nmol/l—was significantly higher in the prednisolone group compared with both budesonide groups. After eight weeks, 76% of prednisolone treated patients had plasma cortisol values below 150 nmol/l compared with 41% in the budesonide once daily group (p=0.0004) and 36% in the budesonide twice daily group (p<0.0001).

Analysis of adrenal function (short ACTH test) revealed statistically significant differences between the groups at eight weeks (p=0.0023) (table 2). After eight weeks, the proportion of patients with normal adrenal function was reduced in all three groups. The maximum reduction was found in the prednisolone group, the difference versus both budesonide once daily (p=0.013) and budesonide twice daily (p=0.0015) being significant. There was no significant difference between the two budesonide groups in this respect.

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Table 2

 Adrenal function (short ACTH test) before and after treatment

Glucocorticoid associated side effects

The proportion of patients with glucocorticoid associated side effects was not significantly different between the three groups: 50% in the budesonide once daily group, 44% in the budesonide twice daily group, and 59% in the prednisolone group. However, the number of patients with moon faces found in the prednisolone group was approximately three times higher than in the budesonide groups (p=0.0005). The difference between the groups with respect to other GCS associated side effects was also significant (p=0.0098). Table 3 presents a summary of side effects.

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Table 3

 Glucocorticoid associated side effects

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