Corticosteroids (Rectal)

This monograph includes information on the following:

1) Betamethasone *
2) Budesonide *
3) Hydrocortisone
4) Tixocortol *


INN:
Hydrocortisone— Cortisol
{01}
BAN:
Hydrocortisone—Cortisol
{01}

JAN:
Hydrocortisone—Cortisol
{01}
VA CLASSIFICATION
Betamethasone
Primary: RS100

Budesonide
Primary: RS100

Hydrocortisone
Primary: RS100

Tixocortol
Primary: RS100


Commonly used brand name(s): Anu-Med HC3; Anucort-HC3; Anuprep HC3; Anusol-HC3; Anutone-HC3; Anuzone-HC3; Betnesol1; Cort-Dome3; Cortenema3; Cortifoam3; Cortiment-103; Cortiment-403; Entocort2; Hemorrhoidal HC3; Hemril-HC Uniserts3; Hycort3; Proctocort3; Proctosol-HC3; Rectocort3; Rectosol-HC3; Rectovalone4.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.



Category:


Corticosteroid (rectal)—

anti-inflammatory, steroidal (rectal)—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Colitis, ulcerative (treatment)—Rectal corticosteroids are indicated to induce remission in acute exacerbations of mild to moderate ulcerative colitis, {21} {23} {36} especially the distal forms {16} {17} {18} {19} {20} {21} {23} {25} {27} {28} {29} {31} {35} including ulcerative proctitis, {04} {06} {09} {10} {13} {16} {18} {21} {26} {31} {35} {41} ulcerative proctosigmoiditis, {04} {13} {26} and left-sided ulcerative colitis. {07} {21} {25} They also are used as adjuncts to systemic corticosteroids {21} {36} or other pharmacological therapies {35} in severe disease {21} {35} {36} {41} and in mild to moderate disease extending proximal to the reach of topical therapy. {41} Hydrocortisone enema has proven useful in some cases of ulcerative colitis involving the transverse and ascending colons. {07} Systemic effects, such as adrenal suppression, preclude the use of corticosteroids for long-term or maintenance therapy. {21} {23} {25} {27} {32} {35}

Cryptitis (treatment)
Hemorrhoids (treatment) or
Proctitis, factitial (treatment)—Hydrocortisone suppositories are indicated in the treatment of inflammatory rectal disorders including cryptitis, {02} {05} {11} {42} inflamed hemorrhoids, {02} {05} {11} {42} and proctitis caused by radiation (factitial). {02} {05} {09} {11} {35} {42}

Pruritus, anogenital (treatment)—Hydrocortisone rectal dosage forms are indicated for treatment of anogenital pruritus. {02} {05} {11} {42}

[Crohn's disease (treatment)]—Hydrocortisone enema is indicated as an adjunct in the treatment of Crohn's disease (regional enteritis) with left-sided involvement. {09}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Betamethasone sodium phosphate: 516.41 {01}
    Budesonide: 430.54 {01} {14}
    Hydrocortisone: 362.47 {01}
    Hydrocortisone acetate: 404.51 {01}
    Tixocortol pivalate: 462.65 {01}

Solubility
    Hydrocortisone acetate: 1 mg per 100 mL in water. {06}


pH
    Hydrocortisone enema: Between 5.5 and 7. {03}

Mechanism of action/Effect:

Rectal corticosteroids appear to exert a local anti-inflammatory effect on the colonic mucosa. {02} {10} {13} Corticosteroids decrease or prevent tissue responses to inflammatory processes, thereby reducing development of symptoms of inflammation without affecting the underlying cause. {36} Corticosteroids inhibit accumulation of inflammatory cells including macrophages, monocytes, endothelial cells, fibroblasts, and lymphocytes at sites of inflammation, in part by induction of lipocortin, a protein that inhibits phospholipase A 2. {25} {36} As a result, there is a decrease in the production and release of cytokines, {21} {23} {36} an inhibition of the synthesis of arachidonic acid–derived mediators of inflammation (leukotrienes and prostaglandins), {23} {25} {36} and decreased extravasation of leukocytes to areas of injury. {36} An immunosuppressant effect of corticosteroids also may contribute to the anti-inflammatory effect, possibly because both involve inhibition of specific functions of leukocytes. {36}

Absorption:

Betamethasone—There is some systemic absorption following administration of the enema. {08}

Budesonide—Rapid and essentially complete within 3 hours following a 2-mg low viscosity enema in healthy volunteers. {14} {15} {17} Systemic availability is 15 ± 12%. {14} {18} {20} {31} {32}

Hydrocortisone—Partially absorbed following rectal administration. {07} In ulcerative colitis patients, up to 50% may be absorbed. {07}

Hydrocortisone acetate—In normal healthy subjects, approximately 26% of the dose is absorbed following rectal administration of a suppository. {02} {05} {42} However, absorption across abraded or inflamed surfaces may be increased. {02} {05} {35} Systemic absorption may be greater from the foam dosage form than from the enema, because the foam is not expelled. {06} {09}

Tixocortol—Rapidly and well absorbed following rectal administration. {13}

Protein binding:

Budesonide—High (88%); to plasma proteins. {15}

Biotransformation:

Budesonide—Extensive (approximately 90%) {14} {15} first-pass metabolism via oxidative and reductive pathways {15} to major metabolites, 6 beta-hydroxybudesonide and 16 alpha-hydroxyprednisolone. {14} {15} Glucocorticoid activity of metabolites is less than 1% that of budesonide. {14} {15} {16} {20}

Tixocortol—In the blood and liver; transformed into inactive metabolites. {13}

Half-life:

Budesonide—Plasma: 2 to 3 hours. {14} {15}

Time to peak concentration:

Budesonide—1.5 hours. {14} {15}

Tixocortol—20 minutes. {13}

Peak plasma concentration

Budesonide—3 ± 2 nanomoles per L. {14} {15}

Elimination:
    Tixocortol—Urinary and fecal excretion generally are completed within 72 to 96 hours. {13}


Precautions to Consider

Carcinogenicity

Long-term animal studies have not been conducted to determine the carcinogenicity of rectal corticosteroids. {02} {05} {42}

Pregnancy/Reproduction
Fertility—

For betamethasone

Motility and number of spermatozoa may be increased or decreased. {08}


Pregnancy—

For corticosteroids

Appropriate studies have not been done in humans. {02} {05} {07} {08} {10} {11} {13} {42} Corticosteroids should not be used extensively, in large amounts, or for prolonged periods in patients who are pregnant or planning to become pregnant. {02} {05} {06} {09} {42}



For budesonide

Budesonide crosses the placenta. {14} High doses of budesonide administered subcutaneously produced fetal malformations (primarily skeletal defects) in rabbits, rats, and mice. However, the relevance of these findings to humans has not been established. {14}



For hydrocortisone and hydrocortisone acetate

In laboratory animals, low doses administered to gestating females have been associated with an increase in the incidence of fetal abnormalities. {02} {05} {42}

FDA Pregnancy Category C (hydrocortisone acetate). {02} {05} {42}


Breast-feeding

It is not known whether rectal corticosteroids are distributed into breast milk. {02} {05} {13} {14} {42} Systemic corticosteroids are distributed into breast milk {14} and may cause unwanted effects, such as growth suppression, {37} in the infant. Rectal corticosteroids are not recommended for use by breast-feeding mothers. {10}

Pediatrics


For corticosteroids:

Infants born to mothers who received corticosteroids during pregnancy should be monitored closely for signs of hypoadrenalism. {06} {07} {08} {09} {10} {14}

Growth and development should be carefully observed in infants and children. {07} {08} Growth suppression may be a complication of corticosteroid therapy {06} {07} {08} {09} {10} {21} {23} or of ulcerative colitis. {23} Alternate-day therapy may minimize this effect. {21} {23}



For budesonide and tixocortol:

Safety and efficacy have not been established. {13} {14}



Geriatrics


Appropriate studies on the relationship of age to the effects of rectal corticosteroids have not been performed in the geriatric population. However, geriatrics-specific problems that would limit the usefulness of these medications in the elderly are not expected.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Anti-inflammatory drugs, nonsteroidal (NSAIDs){23}{24} or
Aspirin{07}{08}{13}{14}    (potential for gastrointestinal ulceration or hemorrhage {45})

    (caution is recommended when aspirin is used concurrently with corticosteroids in patients with hypoprothrombinemia {07} {08} {13} {14})


Phenytoin{08}    (therapeutic effect of the corticosteroid may be decreased because of increased metabolism and decreased plasma concentration, which may result from phenytoin's induction of hepatic microsomal enzymes; an increase in corticosteroid dosage may be necessary {08})


» Vaccines, live virus, or other immunizations{07}{08}{13}    (immunizations are not recommended because of the increased risk of neurological complications and the possibility of decreased or absent antibody response {07} {08} {13})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test values
Skin tests{07}{08}    (reactions may be suppressed {07} {08})

With physiology/laboratory test values
Calcium, serum{06}{07}{08}{10}    (concentrations may be decreased {06} {07} {08})


Glucose{43}    (because of the intrinsic hyperglycemic activity of corticosteroids, blood and urine concentrations may be increased if significant absorption of the corticosteroid occurs {43})


» Hypothalamic-pituitary-adrenal (HPA) axis function as assessed by:
Adrenocorticotropic hormone (ACTH, corticotropin) or
Cortisol, blood or
Cortisol, urine (24-hour) or
17-hydroxycorticosteroids, urine (24-hour)    (may be decreased {13} {15} {31} {32})

    (because budesonide is almost completely eliminated during first-pass metabolism, {20} it has minimal systemic effect on HPA axis function at a therapeutic dose {14} {15} {18} {20} {31} {32})


Osteocalcin, serum{15}{31}    (may be decreased; serum osteocalcin concentrations are correlated with bone turnover; however, the clinical significance of the effect of rectal corticosteroids on these concentrations is not known {15} {31})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Herpes simplex, ocular{06}{07}{08}{09}{10}{14}    (corneal perforation {07} {08} or ulceration {08} may be more likely to develop with use of corticosteroids)


» Psychosis, acute{06}{07}{08}{09}{10}{14}    (may be aggravated {07} {08})


» Tuberculosis, active, latent, or questionably healed{06}{08}{09}{10}{11}{14}    (may be exacerbated or reactivated; appropriate antitubercular chemotherapy or prophylaxis should be administered concurrently {07} {08})


Risk-benefit should be considered when the following medical problems exist
» Abscess, fecal{06}{07}{08}{09}{10}{13}{14} or
» Anastomoses, intestinal, fresh{06}{07}{08}{09}{10}{13}{14} or
» Diverticulitis{06}{07}{08}{09}{10}{14} or
» Fistulas, intestinal, extensive{06}{07}{09}{10}{13}{14} or
» Obstruction, intestinal{06}{07}{09}{10}{13}{14} or
» Perforation, intestinal{06}{07}{08}{09}{10}{13}{14}{21}{36} or
» Peritonitis{06}{09}{10}{13}{36} or
» Sinus tracts{06}{07}{09}{10}{13}{14}    (rectal corticosteroids should be used with caution {07} to prevent local damage to the mucosa {06} {09} {13} {14})

    (signs and symptoms of perforation and peritonitis may be masked {21} {36})


Cirrhosis{07}{08}{14} or
Hypothyroidism{07}{08}{09}{14}    (effects of corticosteroids may be enhanced {07} {08} {14})


Coronary disease, acute{06}{09}{10}{14} or
Glomerulonephritis, acute{06}{09}{10}{14} or
Hypertension{06}{07}{08}{09}{10}{14} or
Hyperthyroidism{06}{09}{10}{14} or
Limited cardiac reserve{06}{09}{10}{14} or
Myasthenia gravis{06}{07}{08}{09}{10}{14} or
Renal function impairment{07}{08} or
Thrombophlebitis{06}{09}{10}{14}    (corticosteroids should be used with caution {07} {08} {09} {10} {14})


Diabetes mellitus{06}{09}{10}{14}    (loss of control of diabetes may occur {09} {14} due to possible elevations in blood glucose; {38} manifestations of latent diabetes may be precipitated; {08} {09} {14} an increase in the dose of insulin or oral antidiabetic medication may be needed {08})


Glaucoma{14}    (intraocular pressure may be increased {14})


Ileocolostomy, postoperative{06}{07}{09}{10}    (corticosteroids may inhibit wound healing {09})


» Infection, local or systemic{06}{07}{08}{09}{10}{11}{13}{14} or
» Chickenpox{06}{14} or
» Measles{06}{14}    (signs of infection may be masked; new infection may develop; resistance and ability to localize infection may be decreased; {07} {08} {13} {14} if infection occurs during therapy, appropriate antimicrobial therapy should be instituted {07} {08} {13} {42})

    (chickenpox and measles may be more serious or even fatal in nonimmune children and adults using corticosteroids; prophylaxis with varicella zoster immune globulin may be indicated following exposure to chickenpox, and prophylaxis with immune globulin intravenous may be indicated following exposure to measles; if chickenpox develops, treatment with the appropriate antiviral agent should be considered {06} {14})


Osteoporosis{06}{07}{08}{09}{10}{14}    (may be exacerbated)


Peptic ulcer, active{06}{07}{08}{09}{10}{11}{14} or latent{07}{08}{14}    (may cause hyperacidity {08} {09} {14})


Sensitivity to betamethasone, budesonide,{14} hydrocortisone,{02}{05}{10}{42} or tixocortol{13}
» Ulcerative disease, severe{06}{09}{10}{13}{14}    (increased risk of perforation of the bowel wall; {06} {09} {10} {14} when surgery is imminent, it is hazardous to delay surgery while awaiting response to treatment {06} {07} {09} {10} {13})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Adrenal function assessment,{14} may include adrenocorticotropic hormone (ACTH) stimulation test, blood or urine cortisol concentrations, or urine 17-hydroxycorticosteroids concentration    (periodic monitoring may be advisable if therapy is prolonged {14})


Biopsy{07}{41} and
Endoscopy{44}{45} and
Sigmoidoscopy{06}{07}{09}{10}{13}{41} and
Stool examinations{41}    (recommended to confirm the presence of colitis and rule out infectious causes {41} and to determine dosage adjustment, duration of therapy, and rate of improvement {06} {10})

    (endoscopy is recommended to diagnose peptic ulcer when corticosteroid therapy is prolonged and accompanied by epigastric pain, hematemesis, melena, and/or nausea and vomiting {44})


Intraocular pressure{09}{13}    (should be measured when rectal corticosteroids are used in the presence of glaucoma {09} {13})




Side/Adverse Effects

Note: The risk of systemic effects, including adrenal suppression, {06} {07} {09} {10} {28} {32} with the use of rectal corticosteroids, although less than with oral or systemic preparations, {35} generally increases with increasing dosage and duration of therapy. {14} {21} {22} {27}
The risk of systemic effects following the use of conventional corticosteroids, such as betamethasone and hydrocortisone, is greater than the risk with budesonide or tixocortol. {31} {35} Although budesonide and tixocortol are well absorbed, tixocortol is rapidly transformed into an inactive metabolite {13} and budesonide is almost completely eliminated during first-pass metabolism. {14} {15} {20} As a result, the systemic effects of these two agents on adrenal and hypothalamic-pituitary-adrenal (HPA) axis function are minimal at therapeutic doses. {14} {15} {18} {20} {31} {32} However, a decrease in cortisol concentrations has been seen following rectal administration of a high dose (10 mg) of budesonide. {14}
For several months to 1 year after discontinuation of prolonged corticosteroid therapy, acute adrenal insufficiency may be precipitated by periods of unusual stress. {07} {08} {09} {32} {39} The risk of occurrence may be minimized by gradual dosage reduction, but if adrenal insufficiency occurs, it may require reinstatement of corticosteroid therapy or an increase in dosage. {07} {08} {09} {39}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating the need for medical attention
Incidence less frequent or rare
    
Allergic contact dermatitis (burning and itching of skin){02}{05}{42}
    
chills {13}
    
decreased glucose tolerance {06}{07}{08}{09}{10}
    
diarrhea {13}{14}
    
fever {13}
    
folliculitis (painful, red or itchy, pus-containing blisters in hair follicles){02}{05}{42}
    
infection, secondary {02}{05}{42}
    
rectal irritation (rectal bleeding, burning, dryness, itching, or pain not present before therapy){02}{05}{07}{10}{13}{14}{15}{26}{31}{42}
    
neuropathy (sensation of pins and needles; stabbing pain){06}{09}{10}
    
psychic disturbances (depression; false sense of well-being; mood swings; personality changes){06}{08}{09}{10}
    
tenesmus (straining while passing stool)—with tixocortol only{13}



Those occurring principally during prolonged use indicating need for medical attention
    
Acne {06}{09}{10}{13}{15}{18}{31}{40}
    
adrenal suppression {06}{07}{08}{09}{10}{28}{32}
    
cataracts, posterior subcapsular (gradual blurring or loss of vision){06}{07}{08}{09}{10}
    
Cushing's syndrome effects including backache
filling or rounding out of the face
hirsutism or hypertrichosis (unusual increase in hair growth, especially on the face), hunchback
hypertension
impotence (unusual decrease in sexual desire or ability in men), menstrual irregularities
muscle weakness
or striae (reddish purple lines on arms, face, legs, trunk, or groin){06}{07}{08}{09}{10}{13}
    
decreased resistance to infection {06}{08}{09}{10}
    
ecchymosis (nonelevated blue or purplish patch on the skin){06}{07}{08}{09}{10}{13}
    
fluid or sodium retention (rapid weight gain; swelling of feet or lower legs){06}{07}{08}{09}{10}
    
glaucoma with possible damage to optic nerves (blurred vision or other change in vision; eye pain){07}{08}
    
growth suppression —in children{06}{07}{08}{09}{10}{21}{23}
    
hypokalemia (dryness of mouth; increased thirst; irregular heartbeat; mood or mental changes; muscle cramps or pain; nausea or vomiting; unusual tiredness or weakness; weak pulse){06}{07}{08}{09}{10}
    
impaired wound healing {06}{07}{08}{09}{10}
    
increased intracranial pressure (headache; insomnia; unusual tiredness or weakness){06}{07}{08}{09}{10}
    
necrotizing angiitis (chills; coughing; coughing up blood; headache; loss of appetite; pain in joints or muscles; shortness of breath; skin rash; unusual tiredness; unusual weight loss){06}{09}{10}
    
ocular infection, secondary, fungal or viral (blurred vision or other change in vision; eye pain; redness of eye; sensitivity of eye to light; tearing){07}{08}
    
osteopenia, osteoporosis, or bone fractures {06}{07}{08}{09}{10}{44}
    
pancreatitis (abdominal pain; chills; nausea or vomiting){06}{07}{08}{09}{10}{13}
    
peptic ulcer (stomach pain){06}{07}{08}{09}{10}
    
thrombophlebitis {06}{09}{10}(pain or discomfort over vein)



Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent or rare
    
Dry, scaly skin {06}{09}{10}
    
flatulence (passing of gas)—with budesonide only{14}
    
headache {07}{08}{13}
    
hypopigmentation (lightened skin color){02}{05}{06}{07}{10}{42}
    
increased sweating {06}{07}{08}{09}{10}
    
increase in appetite {06}{09}{10}
    
insomnia (trouble in sleeping){13}{14}
    
nausea {13}{14}
    
skin rash {13}{14}
    
thin, fragile skin {07}{08}
    
thinning hair on scalp {06}{09}{10}
    
unusual weight gain {06}{09}{10}{40}
    
vertigo (dizziness; sensation of spinning){07}{08}{13}

Incidence rare
—with tixocortol only    
Anorexia (loss of appetite){13}
    
unusual tiredness or weakness {13}
    
unusual weight loss {13}





Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Chronic
    
Adrenal suppression {14}
    
cataracts, posterior subcapsular {10}
    
Cushing's syndrome {10}{14}
    
glaucoma {10}
    
growth suppression —in children{10}
    
impaired wound healing {10}
    
osteoporosis {10}
    
pancreatitis {10}
    
peptic ulcer {10}
    
psychosis {10}


Treatment of overdose
Since there is no specific antidote available, {02} {05} {09} treatment is symptomatic and supportive, and consists of discontinuing corticosteroid therapy. {02} {05} {14} Acute overdose usually does not require tapering of the dosage. However, corticosteroids should be withdrawn gradually following prolonged use. {10}


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Corticosteroids (Rectal).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to betamethasone, budesonide, hydrocortisone, or tixocortol



Fertility—
Motility and number of spermatozoa may be increased or decreased in men using betamethasone

Pregnancy—High doses and long-term use are not recommended; budesonide crosses the placenta





Breast-feeding—Not recommended for use by breast-feeding mothers





Use in children—Infants born to mothers who received corticosteroids during pregnancy should be monitored for signs of hypoadrenalism; growth suppression also may occur

Other medications, especially live virus vaccines or other immunizations
Other medical problems, especially acute psychosis; chickenpox; diverticulitis; extensive intestinal fistulas; fecal abscess; fresh, intestinal anastamoses; intestinal obstruction or perforation; local or systemic infection; measles; ocular herpes simplex; peritonitis; severe ulcerative disease; sinus tracts; or tuberculosis

Proper use of this medication
» Regular visits to physician to check progress {13}

Proper administration technique; reading patient directions carefully

» Importance of not using more medication than the amount prescribed

» Proper dosing
Missed dose: Using as soon as possible; not using if almost time for next dose

» Proper storage

Precautions while using this medication
» Checking with physician before discontinuing medication; gradual dosage reduction may be necessary

» Checking with physician if symptoms do not improve within 2 or 3 weeks or if condition becomes worse

» Checking with physician immediately if bleeding occurs {05} {06} {07} {09} {10}

Staining of fabric may occur following use of suppositories {05}

» Caution in receiving skin tests

» Caution if any kind of surgery or emergency treatment is required

» Caution if serious infections or injuries occur

» Avoiding exposure to chickenpox or measles (especially for children); telling physician right away if exposure occurs

» Caution in receiving vaccinations or other immunizations

For diabetic patients: May increase blood sugar concentrations


Side/adverse effects
Signs of potential side effects, especially allergic contact dermatitis, chills, decreased glucose tolerance, diarrhea, fever, folliculitis, secondary infection, rectal irritation, neuropathy, psychic disturbances, and tenesmus

Signs of potential side effects occurring principally during prolonged therapy, especially acne; adrenal suppression; posterior subcapsular cataracts; Cushing's syndrome effects; decreased resistance to infection; ecchymosis; fluid or sodium retention; glaucoma with possible damage to optic nerves; growth suppression (in children); hypokalemia; impaired wound healing; increased intracranial pressure; necrotizing angiitis; secondary ocular infection (fungal or viral); osteopenia, osteoporosis, or bone fractures; pancreatitis; peptic ulcer; and thrombophlebitis


General Dosing Information
A complete colorectal examination should be performed before rectal corticosteroid therapy commences {02} {05} {10} {11} {13} {42} to rule out serious pathology and to gauge the extent of the disease process. {10}

If rectal corticosteroid therapy is to be successful in treating the disease, the medication must reach the diseased mucosa. {29} Therefore, the choice of dosage form should be determined by the upper extent of the disease. {23} {41} The spread of the enema dosage form reaches the splenic flexure, {23} {26} {41} whereas the spread of the foam and suppositories dosage forms is restricted to the rectum and sigmoid colon. {26} Many patients prefer the foam to the enema {28} {30} {40} because it allows ambulation immediately after application, {35} interferes less with daily activities, {28} and is easier to retain. {30}

The enema should be retained for at least 1 {07} {09} to 3 {13} hours, but it is preferable to retain it overnight. {07} {09} {13} {15} This may be facilitated by prior sedation and/or antidiarrheal medication, {09} especially early in therapy when the urge to evacuate is the greatest. {07}

Rectal corticosteroids for treatment of ulcerative colitis should be used in conjunction with rational dietary control, sedatives, antidiarrheal agents, antimicrobial therapy, and blood replacement, if necessary. {07} However, anticholinergics, antidiarrheals, and antispasmodics should be used with caution because of the risk of inducing paralytic ileus or toxic megacolon. {23}

The lowest possible dose of rectal corticosteroid should be used to control the condition under treatment. {07} {08} Also, corticosteroid therapy should be withdrawn gradually {08} {10} {35} as soon as possible after a patient reaches remission. At that time, other agents may be used to maintain remission and/or to reduce the likelihood or frequency of relapse. {35}

Satisfactory response to rectal corticosteroid therapy usually occurs within 1 or 2 weeks and is marked by a decrease in symptoms. {06} {07} {08} {09} {10} {15} {32} However, symptomatic improvement (decreased diarrhea and bleeding, weight gain, improved appetite, reduced fever, and decreased leukocytosis) may be misleading and should not be the sole criterion for evaluating efficacy. {06} {07} {10} {13}

If there is no evidence of clinical or colorectal improvement within 2 or 3 weeks, or if the patient's condition worsens, rectal corticosteroid therapy should be discontinued. {06} {07} {09} {10}

In the presence of an infection, appropriate antimicrobial therapy should be instituted. {02} {05} {09} {13} {42} If a favorable response does not occur promptly, the corticosteroid should be discontinued until the infection has been adequately controlled. {02} {05} {42}

BETAMETHASONE

Summary of Differences
Pharmacology/pharmacokinetics: Some systemic absorption.

Precautions: Fertility—May increase or decrease motility and number of spermatozoa.

Side/adverse effects: Risk of systemic effects greater than with budesonide or tixocortol.


Rectal Dosage Forms

BETAMETHASONE SODIUM PHOSPHATE ENEMA

Usual adult dose
Colitis, ulcerative
Rectal, 5 mg as a retention enema every night for two to four weeks. {08}


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


5 mg per 100 mL (Rx) [Betnesol{08}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing.

Auxiliary labeling:
   • For rectal use only.

Note: When dispensing, explain administration technique.



BUDESONIDE

Summary of Differences


Pharmacology/pharmacokinetics:
Biotransformation—Undergoes extensive first-pass metabolism.

Potency ranking—High. {14} {20} {32} {40}



Precautions:
Pregnancy—Crosses the placenta. {14}



Side/adverse effects:
Minimal systemic effect on hypothalamic-pituitary-adrenal axis function at a therapeutic dose.



Rectal Dosage Forms

BUDESONIDE ENEMA

Usual adult dose
Colitis, ulcerative
Rectal, 2 mg as a retention enema every night for four to eight weeks. {14} {15} {16} {31} {32}


Usual pediatric dose
Safety and efficacy have not been established. {14}

Usual geriatric dose
See Usual adult dose .

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


2 mg per 100 mL (Rx) [Entocort (tablet 2.3 mg){14}]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), {14} unless otherwise specified by manufacturer.

Preparation of dosage form:
For each dose, 1 tablet should be added to the enema bottle, then the bottle should be shaken vigorously for 10 seconds or until the tablet dissolves completely. The resulting 115-mL (15 mL is residual volume) suspension will be slightly yellowish in color, and should be used immediately. {14}

Auxiliary labeling:
   • For rectal use only.

Note: When dispensing, explain administration technique.



HYDROCORTISONE

Summary of Differences
Indications: Also indicated in cryptitis, hemorrhoids, factitial proctitis, and anogenital pruritus; and used in left-sided Crohn's disease.

Pharmacology/pharmacokinetics: Potency ranking—Low (acetate and base).

Side/adverse effects: Risk of systemic effects is greater than with budesonide or tixocortol.


Rectal Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

HYDROCORTISONE ENEMA USP

Usual adult dose
Colitis, ulcerative
Rectal, 100 mg as a retention enema at bedtime for two or {09} three weeks or until there is clinical and proctologic remission. {07} Refractory cases may require treatment for up to two to three months. {07}

[Crohn's disease]
Rectal, 100 mg as a retention enema at bedtime for two or three weeks. {09}


Note: If it is necessary to continue therapy beyond three weeks, therapy should be discontinued gradually by reducing administration to every other night for two or three weeks. {07} {09}


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


100 mg per 60 mL (Rx) [Cortenema{07}][Generic]{34}

Canada—


100 mg per 60 mL (Rx) [Cortenema{09}] [Hycort{12}]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), {07} unless otherwise specified by manufacturer. Store in a tight container. {03} Protect from freezing and from light. {12}

Auxiliary labeling:
   • For rectal use only.
   • Shake well before use. {09}

Note: When dispensing, explain administration technique.



HYDROCORTISONE ACETATE FOAM

Note: Each applicatorful delivers approximately 900 mg of foam containing approximately 90 mg of hydrocortisone acetate (80 mg of hydrocortisone base). {10}


Usual adult dose
Colitis, ulcerative
Rectal, 1 applicatorful one or two times a day for two or three weeks, then 1 applicatorful every second day. {06} {10}


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


10% (Rx) [Cortifoam (inert propellants isobutane and propane){06}]

Canada—


10% (Rx) [Cortifoam{10}]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), {06} unless otherwise specified by manufacturer.

Auxiliary labeling:
   • For rectal use only.
   • Shake well before use. {06}

Note: When dispensing, explain administration technique.



HYDROCORTISONE ACETATE SUPPOSITORIES

Usual adult dose
Colitis, ulcerative
Rectal, 25 {02} {05} or 30 {42} mg in the morning and at night for two weeks. {02} {05} {42} In more severe cases, 25 {02} {05} or 30 {42} mg three times a day or 50 {02} {05} or 60 {42} mg two times a day. {02} {05} {42}

Proctitis, factitial
Rectal, 25 {02} {05} or 30 {42} mg in the morning and at night for six to eight weeks, according to response. {02} {05} {42}

Cryptitis or
Hemorrhoids or
Pruritus, anogenital
Rectal, 20 to 30 mg a day for three days; or 40 to 80 mg a day, as needed. {11}


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


25 mg (Rx) [Anucort-HC{34}] [Anu-Med HC{34}] [Anuprep HC{34}] [Anusol-HC{05}] [Anutone-HC{34}] [Anuzone-HC{34}] [Cort-Dome{02}] [Hemril-HC Uniserts{34}] [Hemorrhoidal HC{34}] [Proctosol-HC{34}] [Rectosol-HC{34}][Generic]{34}


30 mg (Rx) [Proctocort{42}]

Canada—


10 mg (Rx) [Cortiment-10{11}]


10 mg (base) (Rx) [Rectocort{33}]


40 mg (Rx) [Cortiment-40{11}]

Packaging and storage:
Store below 30 °C (86 °F), {02} {05} {42} unless otherwise specified by manufacturer. Store in a well-closed container. Protect from freezing. {02} {05}

Auxiliary labeling:
   • For rectal use only.
   • Store in a cool place. {11}
   • May be refrigerated.

Note: When dispensing, explain administration technique.



TIXOCORTOL


Rectal Dosage Forms

TIXOCORTOL PIVALATE ENEMA

Usual adult dose
Colitis, ulcerative
Rectal, 250 mg as a retention enema at bedtime for twenty-one consecutive days. If there is no improvement after twenty-one days, an alternative method of treatment should be considered. {13}


Usual pediatric dose
Safety and efficacy have not been established. {13}

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


250 mg per 100 mL (Rx) [Rectovalone (benzyl alcohol){13}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing.

Auxiliary labeling:
   • For rectal use only.
   • Shake well before use. {13}

Note: When dispensing, explain administration technique.




Revised: 07/29/1998



References
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