Prednisone

Prednisone is an inactive prodrug of prednisolone, converted by the liver, and is used for the same inflammatory and immune conditions. At equal doses the two give the same effect in people with normal liver function. In practice, prednisolone is preferred in severe liver disease, in neonates and where the liver is immature, and prednisone is the form stocked in some markets.

Classification. Glucocorticoid prodrug. Tablets 1 mg, 2.5 mg, 5 mg, 10 mg, 20 mg and 50 mg; oral solution.

Mechanism. Converted by hepatic 11-beta-hydroxysteroid dehydrogenase type 1 to prednisolone, which binds the glucocorticoid receptor and alters gene transcription: reduced cytokines, suppressed leukocyte migration and lymphocyte function, and increased gluconeogenesis, protein breakdown and lipolysis.

Pharmacodynamics. Equal in effect to prednisolone once converted: 5 mg equals hydrocortisone 20 mg, methylprednisolone 4 mg and dexamethasone 0.75 mg. Biological effect lasts 12 to 36 hours.

Pharmacokinetics. Oral bioavailability about 80%; peak 1 to 2 hours; converted to prednisolone within the first pass; half-life 3 to 4 hours (prednisolone). Metabolised by the liver; excreted in urine.

Prednisone doses equal prednisolone doses mg for mg. The main regimens follow.

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 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 1 mg monthly. Total course 1 to 2 years.

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.

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.

Systemic lupus erythematosus, vasculitis, immune thrombocytopenia, sarcoidosis, autoimmune hepatitis, inflammatory bowel disease. 0.5 to 1 mg/kg daily (maximum 60 mg) for 4 to 8 weeks, tapered to the lowest effective dose.

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.

Taper and adrenal suppression. Courses under 3 weeks can stop without a taper. Longer courses 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.

Adjustments.

• Kidney: no change.
• Liver: switch to prednisolone in severe liver disease and cirrhosis, because conversion is impaired; in mild impairment dose as usual.
• 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.
• Fluoroquinolones: tendon rupture.
• Warfarin: INR may rise or fall.
• Vaccines: live vaccines are avoided.

Special groups.

• Pregnancy: used when needed; the placenta inactivates most of the drug. Risk of gestational diabetes and hypertension.
• Breastfeeding: compatible; avoid feeding for 4 hours after doses over 20 mg.
• Children: growth suppression; alternate-day dosing reduces this.
• Neonates and liver failure: use prednisolone.
• Older adults: bone loss, delirium, infection; use the lowest effective dose.
• Kidney impairment: no change.
• East Africa: screen for tuberculosis, strongyloides, hepatitis B and HIV before prolonged courses. Prednisone is often the stocked or substituted form, so check the label carefully to avoid confusion between the two names.

Formulation and administration. Take as a single morning dose with food; tablets are swallowed whole or crushed for children.

Baseline. Blood pressure, weight, glucose or HbA1c, potassium, 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 and calcium and vitamin D status for courses 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 with hydrocortisone.

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.