Approved for 1 CE unit by the Canadian Council
on Continuing Education in Pharmacy.This lesson is supported by an educational grant by RhoxalPharma

Systemic corticosteroids: Complications of long-term use

Sandra R. Knowles, B.Sc.Phm.


OBJECTIVESUpon successful completion of this lesson, you should:

1. be familiar with long-term adverse effects associated with corticosteroid therapy in adults

2. be able to counsel patients appropriately when they are started on long-term corticosteroid therapy

3. be able to provide information to healthcare professionals and patients on the use of prophylactic medications or tests that will prevent or reduce the risk of long-term corticosteroid adverse effects

Systemic corticosteroids are the most commonly used anti-inflammatory/ immunosuppressive agents, and are prescribed for a wide variety of clinical indications including systemic lupus erythematosus, rheumatoid arthritis and asthma. However, the potential benefits of systemic glucocorticoids must be carefully balanced against the risks associated with these drugs, both in terms of occurrence and degree of harm. Examples of adverse effects include immunosuppression, cataract formation, increased intraocular pressure, osteoporosis and avascular necrosis. Other possible short-term and long-term adverse effects include neuropsychiatric effects (e.g., mood changes, insomnia), dermatologic effects (e.g., acneiform eruptions, striae, atrophy and thin skin), suppression of the hypothalamic-pituitary-adrenal axis and gastrointestinal effects (see Tables 1 and 2).1,2

An in-depth discussion of all side effects of systemic corticosteroids is beyond the scope of this article. Rather, this review will focus on possible long-term complications of systemic corticosteroids in adult patients, and will provide guidance on risk management.

Prior to initiating any therapy, the physician should discuss with the patient the inherent risks of the disease as compared to the possible risks of therapy. The standard of information disclosure consists of side effects (i.e., serious, common and those particularly relevant to the patient), alternatives to the proposed therapy, consequences of refusing treatment, and a discussion of the proposed treatment including expected benefits, the drug regimen, drug monitoring and expected duration of therapy.

The pharmacist is in a unique position to reinforce information that the physician has provided to the patient, especially information on side effects and drug monitoring. In order to develop an appropriate partnership with the patient, some institutions have incorporated the use of a written “Consent to Treatment” form for patients on potentially long-term glucocorticoid therapy. This allows for a standardized dialogue between patient and physician as well as documentation of information in a consistent format.1 Patients on long-term corticosteroid therapy require intensive monitoring (Table 3) and use of prophylactic medications to prevent, or at least minimize, possible adverse effects.


Single-dose therapy administered in the early morning, as compared to treatment with daily divided doses, minimizes suppression of normal diurnal cortisol secretion, while still providing clinical efficacy.2 Except for osteoporosis and posterior subcapsular cataract formation, many of the common side effects associated with corticosteroid therapy are reduced or eliminated with alternate-day therapy.1 Administration of the entire dose in the morning can also help to reduce or eliminate insomnia and unpleasant dreams.3

Whenever possible, locally administered corticosteroid preparations should be used as substitutes for systemic corticosteroids in order to reduce, if not eliminate, some adverse effects. Examples of these include inhaled corticosteroid use in asthma, rectal enema use in inflammatory bowel disease and topical preparations for dermatologic conditions.


It is estimated that skeletal fractures will develop in 11-20 per cent of patients treated for more than one year with a dose of prednisone or equivalent between 7.5 and 10 mg/day; however, this effect plateaus at about 24 months.4 Patient populations considered to be at high risk for the development of corticosteroid-induced osteoporosis include individuals more than 50 or less than 15 years of age, postmenopausal or amenorrheic women with a slim build, and those patients who have already had fractures after minimal trauma.5 Patients with chronic obstructive pulmonary disease or inflammatory bowel disease, those who are immobilized or have undergone organ transplantation, and hypogonadal men, are also considered to be high-risk patients for the development of corticosteroid-induced osteoporosis.6 Other medications that increase the risk of osteoporosis include thyroid hormone replacement, phenytoin and long-term heparin.4

Although the precise pathophysiology of corticosteroid-induced osteoporosis is not fully understood, the main effect of corticosteroids appears to be a long-term suppression of osteoblastic bone formation and increased osteoclastic bone resorption. Trabecular bone is affected to a greater extent than cortical bone. Implications of corticosteroid-induced osteoporosis include a higher risk of hip and vertebral fractures. 7

An intensive preventive program, which includes selecting the lowest possible steroid dose for the least amount of time, should be initiated in patients on long-term corticosteroid therapy (Table 2). “Long-term” corticosteroid treatment is generally considered to be greater than six months,8 although some sources have defined “long-term” as three months or more of treatment.9 Patients should also be encouraged to eliminate other risk factors for the development of osteoporosis, including smoking cessation, limiting alcohol intake and participating in a regular weight-bearing exercise program. Patients initiated on long-term oral corticosteroid treatment should ideally have bone densitometry testing to measure baseline bone mineral density, with repeated measurement once annually.8

Calcium and vitamin D supplements should be encouraged in all patients starting on long-term corticosteroids, if their dietary sources are considered insufficient. In patients who develop hypercalciuria associated with glucocorticoid use, thiazide diuretics in conjunction with sodium restriction are recommended. Hormone replacement therapy should be prescribed to postmenopausal or amenorrheic women, unless contraindicated. Testosterone supplements are also indicated in men with abnormally low serum testosterone levels. Since the publication of guidelines focusing on the prevention of corticosteroid-induced osteoporosis,8,9 a number of studies have shown the effectiveness of bisphosphonates in this patient population.10,11 In patients who are either unable to take hormone replacement therapy, have established osteoporosis, or who continue to show deterioration on bone mineral density despite appropriate preventive therapies, bisphosphonates are indicated4,8,9 (Table 2).


Osteonecrosis (ON) is an unpredictable and severely disabling complication of corticosteroid therapy. It occurs in five to 25 per cent of patients and usually presents after the first six months of treatment.12 Although the risk of ON is greater in patients treated for prolonged periods (i.e., months to years) with high-dose corticosteroid therapy,13 there have been reports of ON in patients on very high short-term corticosteroid doses.14,15 In addition, intra-articular injection16 and topical application17 of corticosteroids have also been associated with the development of ON. The most common site for ON is the femoral head, although it may involve large joints.1 The mechanism of ON is not completely known, but vascular effects (related to accumulation of fat in terminal arterioles of certain sites in bone), are thought to occur.

Patients presenting with ON usually complain of pain or discomfort in the groin; hip-loading activities, such as weight-bearing or stair climbing, may precipitate or exacerbate the symptoms.18 Bone pain almost always precedes radiologic signs of ON by up to six months. In fact, early during the course of ON, standard X-rays may be normal. Magnetic resonance imaging (MRI) may therefore be required, as it is a more specific and sensitive method for diagnosis of ON. Once diagnosed, treatment of early-stage ON usually involves restricted weight bearing, physiotherapy and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Surgical core decompression may decrease the rate of progression to joint destruction.12 Advanced ON usually requires total joint replacement.

Avoidance of other risk factors for ON (e.g., alcohol and/or tobacco use) and prevention of trauma are recommended for all patients on long-term corticosteroid therapy.19 MRI testing may help in the early diagnosis of patients who develop bone pain.



Development of posterior subcapsular cataracts is common, occurring in approximately 40 per cent of patients with rheumatoid arthritis treated with corticosteroids.20 Patients at greater risk include children, and those treated with 10 mg/day or more of prednisone or equivalent for one year or more. Alternate-day schedules do not appear to reduce the risk of cataract development.21 A slit-lamp examination is recommended at baseline, and then every six to 12 months for patients on long-term glucocorticoid therapy.22


Increased intraocular pressure may develop in patients using oral glucocorticoids, especially those patients with a personal or family history of glaucoma, diabetes mellitus or myopia.23 A recent case-control study showed that the use of oral glucocorticoids increased the risk of ocular hypertension or open-angle glaucoma in elderly patients. In addition, a dose-response relation was found in this study.24 The process is reversible in most cases, after discontinuation of corticosteroid therapy.24 Regular (i.e., every six to 12 months) monitoring of intraocular pressure is recommended in patients with pre-existing glaucoma and in patients receiving high doses of oral glucocorticoids.24


Corticocosteroids in high doses impair antibody production and exert a variety of other immunosuppressive effects. Although the use of alternate-day therapy significantly reduces the risk of opportunistic infections, patients on long-term corticosteroid therapy may have an increased susceptibility to many bacterial, fungal, viral and parasitic infections.25 However, studies of large groups of patients receiving low-dose chronic therapy have not demonstrated a significant increased risk.26 As well, the risk of developing active tuberculosis, while receiving glucocorticoids, is less than previously suspected.1 Nevertheless, it is recommended27 that before long-term corticosteroids are started, a chest X-ray and tuberculin test should be done. If active tuberculosis is found, it can be treated in the usual manner, noting a possible drug interaction between rifampin and corticosteroids. Rifampin may enhance the metabolism of corticosteroids, necessitating an increase in corticosteroid dose. Chemoprophylaxis is unnecessary if the patient has inactive disease.

Corticosteroid therapy is not considered to result in significant immunosuppression when it is:

  • short-term (less than two weeks)
  • given in low to moderate dose (¾1 mg/kg/day of prednisone/day or equivalent)
  • prescribed as alternate-day treatment with short-acting preparations
  • used as maintenance therapy with physiologic doses (5-7.5 mg/day)
  • administered topically (including inhaled steroids) or by intra-articular, bursal or tendon injection28

Ideally, all appropriate vaccines/boosters should be administered to immunosuppressed adult patients at least 10-14 days prior to initiation of corticosteroid therapy (Table 4). Alternatively, vaccination should be delayed until at least three months after immunosuppressive drugs have been discontinued or until the therapy is at the minimal dose. There are no contraindications to the use of inactivated vaccines in immunosuppressed patients; however, live vaccines (measles, rubella, mumps, BCG, yellow fever, oral polio and varicella vaccines) are generally contraindicated in most patients. In individuals taking low maintenance doses of immunosuppresive drugs, live vaccines can be administered if the risk of natural infection is significant (e.g., yellow fever vaccination for travel to an area with an epidemic). When healthy household members or other close contacts of immunocompromised patients are immunized against polio, inactivated polio vaccine should be given to avoid spread of live oral polio virus.28,29

Immunosuppressed adult patients should receive routine immunization with tetanus/diphtheria (Td), pneumococcal, and influenza vaccines (see Table 4).29


Early reports indicated that corticosteroids induced peptic ulcer disease.30 However, most of the data suggesting an association was based on uncontrolled studies or anecdotal case reports. Recent studies have found no significant association between systemic corticosteroid use and peptic ulcer disease.31,32 In a meta-analysis of 93 randomized, double-blind controlled trials,31 no difference was found between patients receiving corticosteroids and control patients (0.3% and 0.4%, respectively). The mean daily dose and duration of corticosteroid therapy was 35 mg (in prednisone equivalents) and 64 days, respectively. A case-control study32 showed similar findings; an increased risk of developing peptic ulcer disease was found only in current users of corticosteroids who were also taking NSAIDs.

Although evidence does not support an association between systemic corticosteroid use and the development of peptic ulcer disease, it is recommended that patients on corticosteroid therapy who have two or more risk factors for peptic ulcer disease should be given a prophylactic agent such as an H2-receptor antagonist.33 Specific risk factors include total treatment dose of corticosteroid (over 140 mg dexamethasone or 1000 mg prednisone), previous history of peptic ulcer, and advanced malignant disease. The concomitant use of NSAIDs and corticosteroids is another risk factor; the use of misoprostol should be considered in this group of patients. Further studies are needed to assess the role of H2-receptor antagonists, misoprostol and/or proton pump inhibitors in the prevention of peptic ulcer disease in patients on corticosteroid therapy.


Muscle weakness associated with systemic corticosteroid administration was first described in the 1950s.34 Acute steroid-induced myopathy usually occurs five to seven days after initiation of high-dose steroids, whereas chronic myopathy is associated with long-term treatment. The myopathy involves large proximal muscles and is associated with marked muscle wasting. Nerve function is normal and myopathy spares muscles supplied by cranial nerves as well as sphincters. The myopathy can be severe enough to affect mobility and is easily demonstrated by asking patients to stand up from a sitting position without using their hands.

Although rare, steroid-induced myopathy is most often observed with fluorinated agents such as triamcinolone.35 Improvement in weakness has occurred in as few as three days or as late as five weeks after withdrawal of the steroid, with complete recovery occurring in two months to a year.


Although presentation varies among individuals on corticosteroids, the most common psychiatric side effects include euphoria, depression, and psychotic reactions characterized by delusions, hallucinations, stupor and catatonia.36 Sleep disturbances usually manifest with insomnia and unpleasant dreams.3 These disturbances typically occur within several days of the initiation of treatment and usually resolve within a few weeks of discontinuation. The highest incidence of corticosteroid-induced mental disturbance has been reported among patients with systemic lupus erythematosus.36,37

Using data from the Boston Collaborative Drug Surveillance Program,38 of 676 patients treated with corticosteroids, 3.1 per cent developed acute psychosis or inappropriate euphoria. A significant dose-response relationship was shown: 1.3 per cent of patients receiving <40 mg prednisone daily, 4.6 per cent receiving between 41-80 mg daily and 18.4 per cent of patients receiving >80 mg prednisone daily. Although high doses of corticosteroids increase the risk for developing a psychiatric disturbance, patients with a psychiatric history are not at greater risk.37,38


Adrenal suppression

Suppression of the hypothalamic-pituitary-adrenal (HPA) axis occurs in every patient, although there is considerable variation in the duration of suppression after glucocorticoid therapy is terminated.1 As well, the effect can be minimized by single morning doses, and even more so by using an intermediate-acting steroid (such as prednisone) every other morning. Although the development of adrenal crisis following rapid tapering of glucocorticoid therapy is a potential risk, there have only been a few well-documented cases in the literature.1 It is now recommended that patients who have been on corticosteroids for one month or less be tapered to disease control alone. For patients who require tapering of prednisone, the usual guidelines include a reduction of dose by 20-mg increments at levels above 60 mg/day, 10-mg reductions at levels between 30-60 mg/day, and 5-mg reductions at levels from 30 mg/day to the physiologic dose range.19 The length of the tapering schedule will vary considerably based on the length of time the patient has been on the drug, the indication and the individual’s disease severity.

A “steroid withdrawal syndrome” may occur in patients who are withdrawn after long-term, high-dose corticosteroid therapy. Vulnerability to physiologic stress (e.g., stress or infection) may result in insufficient production of adrenal cortisol for one year or more after long-term therapy. Symptoms such as fatigue, malaise, anorexia, nausea, weight loss, postural hypotension, myalgias and depression can occur. To prevent these symptoms, hydrocortisone should be given prior to stressful situations, such as surgery.19 The dose of hydrocortisone administered varies according to the daily dose of prednisone and the type of surgery. See reference 39 for a detailed review.


Corticosteroids may cause glucose intolerance through mechanisms related both to increased hepatic glucose production and decreased peripheral glucose utilization. A transient glucose intolerance, which reverts to the pretreatment state despite continued therapy, develops in the majority of patients. However, worsening of preexisting or subclinical glucose intolerance can also occur in up to one-fifth of patients on corticosteroids.12 As well, long-term systemic corticosteroid treatment is associated with a greater risk of developing symptomatic de novo diabetes mellitus.19 Patients on oral hypoglycemics or insulin who are initiated on corticosteroid therapy need to have their diabetic medication reassessed, since blood glucose control is likely to deteriorate. Upon discontinuation of the corticosteroid, most patients revert to their prior glucose state.

Weight gain

Weight gain is a common side effect of corticosteroid therapy and is related to increased appetite and fluid retention. Deposits of fat occur most commonly on the face, posterior neck and trunk. Increased facial fat and edema have been estimated to occur in 10 to 15 per cent of patients on therapy for at least two months. Weight gain can be minimized by a proper diet, i.e., a low-calorie, low-fat, low-carbohydrate diet.19


Hyperlipidemia with elevation of both cholesterol and triglyceride levels has been reported.Patients with previous lipid abnormalities are at the highest risk of developing this side effect. Periodic monitoring of lipid levels is recommended (Table 3).


Hypertension is a commonly reported side effect of corticosteroid therapy31 although its incidence, severity, mechanism and relation to dose and duration to therapy are unclear. Patients at greatest risk include those with preexisting hypertension, the elderly, and patients on glucocorticoids with high mineralocorticoid activity (e.g., hydrocortisone). Management of hypertension includes sodium restriction and a thiazide diuretic, if indicated. Blood pressure should be monitored regularly (i.e., at baseline and every one to three months thereafter).

Sodium and water retention may occur during treatment with corticosteroids. The use of a low-salt diet may help to minimize this complication. As well, any potassium losses are usually easily reversible with a diet rich in potassium (e.g., broccoli, carrots, fish, bananas, poultry).


The physician and pharmacist have a shared role in the discussion of drug side effects with patients. This includes all probable or likely risks, all possible but serious risks, and any other issues that could be considered relevant for a particular patient’s situation. For example, a patient who is physically active and is started on long-term corticosteroid therapy needs to be counselled regarding symptoms associated with osteonecrosis, since total joint replacement in these patients is especially devastating. As well, the duration of corticosteroid therapy for a particular patient should influence which side effects are emphasized. For example, a patient who is prescribed a five-day course of prednisone for treatment of an acute dermatitis does not need to be informed of possible long-term effects of corticosteroids such as osteoporosis, but needs to be aware of acute side effects (Table 1).

The monitoring process for detection and possible prevention of side effects requires maximum patient involvement. Patients need to be aware of symptoms that can herald the onset of potentially serious adverse effects. For example, development of pain or discomfort in the groin may suggest the early stages of osteonecrosis.

Patients also require explicit instructions regarding the drug regimen; this is especially important for patients who are being tapered from long-term corticosteroid therapy. In many cases, the pharmacist can provide a calendar that incorporates the withdrawal schedule. The calendar can also serve as a diary to record any potential withdrawal symptoms that the patient may experience.

For patients on long-term corticosteroids, certain laboratory tests are recommended at baseline and at regular intervals during therapy. The patient should be informed of these tests, why they are being done and when they should be done. As well, several preventive measures are needed for patients on long-term corticosteroid therapy. This can include calcium and vitamin D supplementation for prevention of osteoporosis and immunizations to decrease the risk of opportunistic infections.


Corticosteroids are extremely beneficial drugs in a number of disease states. However, there are numerous side effects associated with these groups of drugs that can be severely disabling. The use of prophylactic medications and intensive monitoring may help to reduce the risk of adverse effects associated with long-term corticosteroid therapy.


1. Lester R, Knowles S, Shear N. The risks of systemic corticosteroid use. Dermatol Clin 1998;16:277-88.

2. Baxter J. Minimizing the side effects of glucocorticoid therapy. Adv Intern Med 1990;35:173-94.

3. Turner R, Elson E. Steroids cause sleep disturbance. Br Med J 1993;306:1477-8.

4. Adachi J. Corticosteroid-induced osteoporosis. Am J Med Sci 1997;313:41-9.

5. Jenkinson T, Bhalla A. A re-appraisal of steroid-induced osteoporosis. Br J Hops Med 1993;50:472-6.

6. Picado C, Luengo M. Corticosteroid-induced bone loss: prevention and management. Drug Safety 1996;347-59.

7. Lucas K, Davis S. Calcium in corticosteroid-induced osteoporosis. Ann Pharmacother 1998;32:970-2.

8. American College of Rheumatology Task Force on Osteoporosis Guidelines. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arth Rheum 1996;39:1791-1801.

9. The Scientific Advisory Board, Osteoporosis Society of Canada. Clinical practice guidelines for the diagnosis and management of osteoporosis. CMAJ 1996;155: 1113-29.

10. Saag K, Emkey R, Schnitzer T. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. N Engl J Med 1998;339:292-9.

11. Adachi J, Bensen W, Brown J, et al. Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N Engl J Med 1997;337:382-7.

12. Stanbury R, Graham E. Systemic corticosteroid therapy–side effects and their management. Br J Ophthalmol 1998;82:704-8.

13. Felson D, Anderson J. Across-study evaluation of association between steroid dose and bolus steroids and avascular necrosis of bone. Lancet 1987;I: 902-5.

14. Sambrook P, Hassall J, York J. Osteonecrosis after high dosage, short term corticosteroid therapy. J Rheumatol 1984;11:514-6.

15. Taylor L. Multifocal avascular necrosis after short-term high-dose steroid therapy. J Bone Joint Surg 1984; 66B:431-3.

16. Laroche M, Arlet J, Mazieres B. Osteonecrosis of the femoral and humeral heads after intraarticular corticosteroid injections. J Rheumatol 1990;17:549-51.

17. Tang S, Chan K, Chow S. Osteonecrosis of femoral head after topical steroid therapy. Journal of the Royal College of Surgeons of Edinburgh 1986;31:321-3.

18. Tervonen O, Mueller D, Matteson E, et al. Clinically occult avascular necrosis of the hip: prevalence in an asymptomatic population at risk. Radiology 1992; 182:845-7.

19. Nesbitt L. Minimizing complications from systemic glucocorticosteroid use. Dermatologic Clinics 1995; 13:925-39.

20. Black R, Oglesby R, von Sallman L, et al. Posterior subcapsular cataracts induced by corticosteroids in patients with rheumatoid arthritis. JAMA 1960;174:166-71.

21. Limaye S, Pillai S, Tina L. Relationship of steroid dose to degree of posterior subcapsular cataracts in nephrotic syndrome. Ann Ophthalmol 1988;20:225-7.

22. Wolverton S. Monitoring for adverse effects from systemic drugs used in dermatology. J Am Acad Dermatol 1992;26:661-79.

23. David D, Berkowitz J. Ocular effects of topical and systemic corticosteroids. Lancet 1969;I:149-51.

24. Garbe E, LeLoorier J, Boivin J, et al. Risk of ocular hypertension or open-angle glaucoma in elderly patients on oral glucocorticoids. Lancet 1997;350:979-82.

25. Dale D, Fauci A, Wolff S. Alternate-day prednisone: leukocyte kinetics and susceptibility to infection. N Engl J Med 1974;291:1154-8.

26. Gallant C, Kenny P. Oral glucocorticoids and their complications. J Am Acad Dermatol 1986;14:161-77.

27. Sendorovitz T, Viskum K. Corticosteroid and tuberculosis. Resp Med 1994;88:561-5.

28. National Advisory Committee on Immunization. Canadian immunization guide, 5th ed. Ottawa: MInister of Public Works & Government Services Canada, 1998.

29. American College of Physicians. Guide for adult immunization, 3rd ed. Philadelphia: The College, 1994.

30. Messer J, Reitman D, Sacks H, et al. Association of adrenocorticosteroid therapy and peptic-ulcer disease. N Engl J Med 1983;309:21-4.

31. Conn H, Poynard T. Corticosteroids and peptic ulcer: meta-analysis of adverse events during steroid therapy. J Int Med 1994;236:619-32.

32. Piper J, Raw W, Daugherty J, et al. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med 1991;114:735-40.

33. Ellershaw J, Kelly M. Corticosteroids and peptic ulceration. Palliative Medicine 1994;8:313-9.

34. McEvoy C, Niewoehner D. Adverse effects of corticosteroid therapy for COPD: a critical review. Chest 1997;111:732-43.

35. Nagpal S, Tierney M. Corticosteroid-induced myopathy. Can J Hosp Pharm 1995;48:242-3.

36. Milgrom H, Bender B. Psychologic side effects of therapy with corticosteroids. Am Rev Respir Dis 1993; 147:471-3.

37. Ling M, Perry P, Tsuang M. Side effects of corticosteroid therapy: psychiatric aspects. Arch Gen Psychiatry 1981;38:471-7.

38. Boston Collaborative Drug Surveillance Program. Acute adverse reactions to prednisone in relation to dosage. Clin Pharmacol 1972;13:694-8.

39. Nicholson G, Burrin JM, Hall GM. Peri-operative steroid supplementation. Anaesthesia 1998;53:1091-1104.



Sandra R. Knowles, B.Sc.Phm., is Drug Safety Pharmacist in the Drug Safety Clinic, Sunnybrook & Women’s College Health Sciences Centre (Sunnybrook Site), Toronto, Ont.


All lessons are reviewed by three pharmacists for accuracy, completeness and relevance to current pharmacy practice.


Sandra Knowles, B.Sc.Phm.

Pharmacist, Drug Safety Clinic, Sunnybrook and Women’s College Health Sciences Centre, Toronto, Ont.

Ray Wolanin, B.Sc.Pharm.

Pharmacist, Metro Toronto Hospitals Drug Information Service, North York, Ont.This lesson has been approved for 1 CE unit by the Canadian Council on Continuing Education in Pharmacy. Approved for 1 CEU by l’Ordre des pharmaciens du Québec.This lesson is supported by an unrestricted educational grant by Rhoxalpharma.

TABLE 1: Acute (short-term) side effects of systemic corticosteroids1,2
  • Mood changes, nervousness, insomnia
  • Gastrointestinal intolerance (nausea and/or vomiting)
  • Fluid and/or sodium retention
  • Increased appetite, weight gain
  • Amenorrhea
  • Acneiform eruptions
  • Blood sugar effects
TABLE 2: Monitoring and prophylactic measures for patients on long-term corticosteroid therapy*
Potential side effect Preventive strategies
  • calcium (to achieve a total intake of 1.5 g/day,8 divided in three equal doses)
  • vitamin D (800 IU/day) or calcitriol (0.5 µg/day) (especially in high-risk patients with significant inhibition of calcium absorption, such as the elderly)8
  • mild to moderate exercise
  • hormone replacement therapy (HRT)
    1. postmenopausal women: estrogen +/- progestin replacement therapy
    2. premenopausal women with intact ovarian function: estrogen-containing oral contraceptives (minimum 50 µg of estradiol or equivalent)
    3. men: testosterone, if serum testosterone abnormally low
  • bisphosphonates (e.g., intermittent etidronate 400 mg per day for 14 days, followed by calcium 500 mg daily for 76 days11 or alendronate 5-10 mg daily10) or calcitonin (100 IU/day or every other day, subcutaneously; or 200 IU/day intranasally8), in patients who have contraindications to HRT
  • sodium restriction and thiazide diuretic (e.g., hydrochlorothiazide 25 mg/day) with or without potassium supplementation, in patients with urinary calcium >300 mg/day and not on calcitonin8
  • for patients at high risk, measure bone mineral density at baseline and then once annually4,8
Cataract formation
  • slit-lamp examination at baseline and every 6-12 months thereafter19,22
  • routine (i.e., every 6-12 months) monitoring of intraocular pressure in patients on high-dose, long-term corticosteroid use and in patients with pre-existing glaucoma
  • measure blood pressure at baseline and then every 1-3 months
  • restriction of sodium intake
Weight gain
  • measure weight at baseline and then every 1-3 months
  • management includes low-calorie, low-fat diet and exercise
Peptic ulceration
  • in patients with two or more risk factors (i.e., patients taking other potentially ulcerogenic medications such as nonsteroidal anti-inflammatory medications, patients with a previous history of peptic ulceration, patients with advanced malignant disease and patients with a total treatment dose of corticosteroid over 1000 mg of prednisone or equivalent), prophylaxis may be considered with an H2-antagonist. If a patient is also on concurrent NSAID therapy, then misoprostol should be added.33
Metabolic abnormalities
  • in patients without any risk factors, blood glucose, electrolytes and lipid studies performed at baseline and then once every 6 months
  • in patients with known risk factors (e.g., diabetes), more frequent monitoring is necessary
Sleep disturbances (insomnia)
  • administer as a single morning dose
GI irritation
  • administer medication with food
Suppression of HPA axis
  • use single, early-morning doses, preferably on alternate days
* Adapted from Reference 1.HPA = hypothalamic-pituitary-adrenal axis

NSAID = nonsteroidal anti-inflammatory drug

TABLE 3: Monitoring parameters for adult patients on long-term corticosteroid therapy*,1
Baseline 1 month 3 months 6 months 9 months 1 year
Blood pressure Blood pressure Blood pressure Blood pressure Blood pressure Blood pressure
Blood glucose Blood glucose Blood glucose Blood glucose
Electrolyte and lipid studies Electrolyte and lipid studies Electrolyte and lipid studies Electrolyte and lipid studies
Slit-lamp examination Slit-lamp examination Slit-lamp examination
Intraocular pressure** Intraocular pressure Intraocular pressure Intraocular pressure
Weight Weight Weight Weight Weight Weight
Tuberculin test/ Chest X-ray
Bone mineral density Bone mineral density
Calcium and vitamin D supplementationMild to moderate exercise

Sodium restriction

* For patients with no increased risk for toxicity (e.g., those with no hyperlipidemia, hyperglycemia, hypertension, cataracts, osteoporosis, peptic ulcer disease)**For patients on high-dose corticosteroid therapy
TABLE 4: Immunization guidelines for immunocompromised adults28
Vaccine Routine (not immunocompromised) Severely immunocompromised (non-HIV-related)
Tetanus-diphtheria Recommended Recommended
MMR Use if indicated Contraindicated
Hepatitis B Use if indicated Routine use
influenzae B
Not recommended Routine use
Pneumococcal Recommended if >=65 yrs of age Recommended
Meningococcal Use if indicated Use if indicated
Influenza Recommended if >=65 yrs of age Recommended
Note: Live vaccines are generally contraindicated in immunosuppressed patients.MMR = measles/mumps/rubella