Prednisolone

Prednisolone is the main oral glucocorticoid for inflammatory and immune conditions, given for short bursts or long-term disease suppression. It is cheap, widely available and has a long record of use. Dose, duration and timing decide the benefit and the toxicity: short bursts under 3 weeks need no taper, while longer courses suppress the adrenal axis and cause cumulative harm to bone, glucose, eyes and mood.

Classification. Glucocorticoid. Tablets 1 mg, 5 mg and 25 mg; dispersible and soluble tablets; oral liquid; enteric-coated tablets; eye drops and rectal foam.

Mechanism. Binds the intracellular glucocorticoid receptor, altering gene transcription: reduces cytokine production, suppresses leukocyte migration and lymphocyte function, and increases gluconeogenesis, protein breakdown and lipolysis. It has little mineralocorticoid action.

Pharmacodynamics. Anti-inflammatory potency 4 times hydrocortisone (5 mg equals hydrocortisone 20 mg). Biological effect lasts 12 to 36 hours.

Pharmacokinetics. Oral bioavailability about 80%, peak 1 to 3 hours; 65 to 90% protein bound (concentration dependent); plasma half-life 2 to 4 hours. Metabolised by the liver; excreted in urine.

Acute asthma exacerbation.

• Adults 40 to 50 mg orally once daily for 5 days (up to 7 days), no taper. Children 1 to 2 mg/kg once daily (maximum 40 mg) for 3 to 5 days.

Chronic obstructive pulmonary disease exacerbation. 30 to 40 mg orally once daily for 5 days.

Giant cell arteritis. 40 to 60 mg daily (1 mg/kg, maximum 60 mg) until symptoms resolve and inflammatory markers fall. Then taper by 10 mg every 2 weeks to 20 mg, then 2.5 mg every 2 to 4 weeks to 10 mg, then by 1 mg monthly. Total course 1 to 2 years. With visual loss, give methylprednisolone 500 to 1000 mg intravenously daily for 3 days.

Polymyalgia rheumatica. 15 mg daily, tapering by 2.5 mg every 4 weeks to 10 mg, then by 1 mg every 4 to 8 weeks; course 1 to 2 years.

Rheumatoid arthritis (bridging or flare). 5 to 10 mg daily, or 15 to 20 mg daily for a short flare, tapered to the lowest dose and stopped as disease-modifying therapy takes effect.

Nephrotic syndrome in children (steroid sensitive).

• 60 mg/m2 (about 2 mg/kg, maximum 60 mg) daily for 4 to 6 weeks, then 40 mg/m2 on alternate days for a further 4 to 6 weeks, then taper.
• Relapse: 60 mg/m2 daily until urine protein is negative for 3 days, then alternate days for 4 weeks.
• Directed by a paediatric nephrologist.

Systemic lupus erythematosus and vasculitis. 0.5 to 1 mg/kg daily (maximum 60 mg) for 4 to 8 weeks, tapered to 5 to 7.5 mg daily or lower; severe organ disease starts with methylprednisolone pulses.

Immune thrombocytopenia. 1 mg/kg daily (maximum 80 mg) for 2 to 4 weeks, then taper.

Pneumocystis pneumonia (adjunct in hypoxia). 40 mg twice daily for 5 days, then 40 mg daily for 5 days, then 20 mg daily for 11 days.

Bell's palsy. 50 to 60 mg daily for 10 days (with or without taper) within 72 hours of onset.

Other uses. Tuberculous meningitis and pericarditis (adjunct), sarcoidosis (20 to 40 mg daily), autoimmune hepatitis (30 to 60 mg daily), inflammatory bowel disease flares (40 mg daily, tapered over 8 weeks), allergic and nephrotic conditions.

Taper and adrenal suppression.

• Courses under 3 weeks can stop without a taper if the dose is not very high.
• Longer courses (over 3 weeks), repeated courses, doses over 7.5 mg daily for over 3 months, or evening dosing need a taper. Reduce by 5 to 10 mg every 1 to 2 weeks to 10 mg, then by 1 mg every 2 to 4 weeks, slowing at 5 to 7.5 mg.
• Consider testing the adrenal axis before stopping long courses.

Adjustments.

• Kidney: no change.
• Liver: no change, though prednisolone is preferred to prednisone in liver failure.
• Older adults: use the lowest dose and add bone protection.
• Weight: dose by weight or surface area in children.

Contraindications. Systemic fungal infection; untreated tuberculosis or sepsis (treat the infection alongside); live vaccines at immunosuppressive doses; hypersensitivity.

Serious adverse effects.

• Metabolic: hyperglycaemia, diabetes, weight gain, central obesity, dyslipidaemia, hypokalaemia.
• Bone and muscle: osteoporosis and fractures, avascular necrosis, steroid myopathy.
• Infection: reactivation of tuberculosis and hepatitis B, strongyloides hyperinfection, pneumocystis, candidiasis.
• Neuropsychiatric: insomnia, agitation, mania, depression, psychosis.
• Eye: cataract, raised intraocular pressure.
• Skin: thin skin, bruising, striae, acne.
• Gastric: peptic ulcer risk rises when combined with NSAIDs.
• Hypertension, fluid retention, adrenal suppression and crisis on abrupt stopping.
• Growth suppression in children.

Major interactions.

• Reduced effect: rifampicin, phenytoin, carbamazepine, phenobarbital (increase the dose).
• Increased effect or toxicity: ketoconazole, itraconazole, clarithromycin, ritonavir, oestrogen-containing contraceptives.
• NSAIDs and aspirin: gastrointestinal bleeding.
• Diuretics: hypokalaemia; digoxin toxicity.
• Antidiabetic drugs: glucose rises; raise insulin or other treatment (NPH insulin 0.1 unit/kg for each 10 mg of prednisolone, up to 0.4 unit/kg at 40 mg or more).
• Fluoroquinolones: tendon rupture.
• Warfarin: INR may rise or fall.
• Vaccines: live vaccines are avoided.

Special groups.

• Pregnancy: used when needed; the placenta inactivates most prednisolone. Risk of gestational diabetes, hypertension and, rarely, cleft palate with first-trimester exposure.
• Breastfeeding: compatible; avoid feeding for 4 hours after doses over 20 mg.
• Children: growth suppression; alternate-day dosing reduces this.
• Older adults: bone loss, delirium, infection; use the lowest effective dose.
• Kidney impairment: no change; liver impairment: no change.
• East Africa: tuberculosis, strongyloides, hepatitis B and HIV are common. Screen for latent tuberculosis, and consider a single dose of ivermectin 200 micrograms/kg before prolonged high-dose therapy in patients from areas where strongyloides is common. Many patients get steroids from unlicensed sources or herbal products; ask, and treat adrenal suppression when it follows abrupt stopping.

Formulation and administration. Take as a single morning dose with food to reduce gastric irritation and match cortisol rhythm; split doses for severe disease. Dispersible tablets dissolve in water; enteric-coated tablets are swallowed whole.

Baseline. Blood pressure, weight, glucose or HbA1c, potassium, eye pressure if prolonged use is planned, bone density for courses over 3 months, tuberculosis and hepatitis B screening, and a vaccination review.

Monitoring.

• Blood pressure, weight, glucose and potassium at each visit during long courses.
• Bone density at the start of courses expected to last over 3 months and annually thereafter; consider calcium, vitamin D and a bisphosphonate when doses reach 7.5 mg daily or more for over 3 months.
• Eye pressure and lens annually; growth in children every 3 months.
• Mood and sleep; steroid card for all who take over 3 weeks.

Dose reduction and stopping. Stop short courses (under 3 weeks) without a taper. For longer courses reduce by 5 to 10 mg every 1 to 2 weeks to 10 mg, then by 1 mg every 2 to 4 weeks, slowing at 5 to 7.5 mg. If infection, surgery or trauma occurs during or within 12 months of a long course, give stress-dose cover.

Referral and escalation. Admit suspected adrenal crisis, severe infection, psychosis, or steroid-induced hyperglycaemia with ketosis. Refer for fractures, visual change, resistant disease needing a steroid-sparing agent, or a dose requirement over 10 mg daily at 6 months.