Prednisolone is a corticosteroid used to reduce inflammation in many conditions, such as asthma, allergies, rheumatic and bowel diseases. It is taken orally, usually in the morning, and the dose is tapered gradually at the end of treatment.
Increased gastrointestinal bleeding risk when a corticosteroid (Prednisolone) is combined with an NSAID.
NSAIDs such as diclofenac increase the risk of serious gastrointestinal events (bleeding, ulceration and perforation), and the diclofenac label identifies concomitant use of oral corticosteroids as a factor that increases the risk of GI bleeding. Prednisolone, in turn, carries a precaution to use with caution in patients with active or latent peptic ulcer. Together, the risk of ulcer, bleeding and digestive perforation increases additively, especially in the elderly, with a history of ulcer/bleeding or in prolonged treatment. Consider gastroprotection (proton pump inhibitor) in at-risk patients, use the lowest effective dose of each drug and monitor digestive symptoms.
Diclofenac + prednisolone: additive risk of peptic ulcer and gastrointestinal bleeding. Consider gastroprotection in at-risk patients.
Additive gastric mucosal injury (reduced protective prostaglandins).
Watch for dyspepsia and occult blood in stool.
Severe abdominal pain, melaena, haematemesis.
Consider gastric protection (PPIs) if unavoidable; use the lowest effective doses for the shortest time.
DailyMed/FDA (NIH/NLM) — approved Diclofenac label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ddd2278b-70be-41ca-8a84-e3fe0f1a1561 ; approved Prednisolone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52e6e21d-94b8-41a0-8d13-371c0e66bcee
Rifampin lowers Prednisolone levels — reduced anti-inflammatory and immunosuppressive effect.
Prednisolone is metabolised by CYP3A4; rifampicin induces this enzyme and can reduce its concentrations by 30–50%, attenuating the anti-inflammatory/immunosuppressive effect (relevant in autoimmune diseases, transplantation and respiratory diseases). Monitor the clinical response and consider increasing the prednisolone dose during the combination, reducing it after rifampicin discontinuation.
Prednisolone + rifampicin: rifampicin lowers prednisolone levels (CYP3A4 induction), reducing the corticosteroid effect. Consider dose adjustment.
CYP3A4 induction accelerating corticosteroid elimination.
Clinical response; signs of underlying disease flare.
Disease flare (asthma, COPD, autoimmune disease).
Adjust the dose based on response; consider reinforcement during flares.
DailyMed/FDA (NIH/NLM) — approved Rifampin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b ; approved Prednisolone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52e6e21d-94b8-41a0-8d13-371c0e66bcee
Fluconazole may raise prednisolone levels (metabolic inhibition), with a risk of enhanced corticosteroid effects.
Prednisolone is partly metabolised by CYP3A4, and fluconazole is a CYP3A4 inhibitor (in addition to CYP2C9/2C19), which can raise corticosteroid concentrations and their effects. Although the interaction is less documented than with voriconazole, the same pharmacological principle applies: monitor for signs of corticosteroid excess (hyperglycaemia, fluid retention, hypertension, weight gain, Cushing syndrome symptoms) during the combination, especially at high doses or prolonged treatment, and adjust the prednisolone dose if needed.
Fluconazole + prednisolone: the azole can inhibit CYP3A4 and increase corticosteroid exposure. Monitor for signs of corticosteroid excess.
CYP3A4 inhibition by fluconazole reduces prednisolone metabolism.
Blood glucose, blood pressure, signs of iatrogenic Cushing.
Oedema, hyperglycaemia, Cushingoid facies.
Watch for corticosteroid effects (hyperglycaemia, fluid retention); adjust the steroid dose if overdosage symptoms occur.
DailyMed/FDA (NIH/NLM) — approved Fluconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7961c029-746c-48c3-888b-8f8344102873 ; approved Prednisolone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52e6e21d-94b8-41a0-8d13-371c0e66bcee — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Increased gastrointestinal bleeding risk with corticosteroid plus NSAID.
Prednisolone, like systemic corticosteroids, inhibits mucosal repair and can mask signs of perforation; ibuprofen reduces gastroprotective prostaglandins and inhibits platelet aggregation. Together, the risk of ulcer, bleeding and digestive perforation increases, especially in the elderly, at high doses and in prolonged therapy. Whenever possible, use the lowest corticosteroid dose for the shortest time, consider gastroprotection (proton pump inhibitor) in at-risk patients and monitor digestive symptoms and signs of anaemia.
Prednisolone + ibuprofen: additive risk of peptic ulcer and gastrointestinal bleeding. Consider gastroprotection, especially in the elderly.
Additive gastric mucosal injury (reduced protective prostaglandins).
Watch for dyspepsia and occult blood in stool.
Severe abdominal pain, melaena, haematemesis.
Consider gastric protection (PPI) if the combination is unavoidable; use the lowest effective doses.
DailyMed/FDA (NIH/NLM) — approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14515409-736f-4119-b6a0-cb19ee2e948e ; approved Prednisolone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52e6e21d-94b8-41a0-8d13-371c0e66bcee
Corticosteroid + thiazide: additive hypokalaemia and hyperglycaemia.
Hydrochlorothiazide can cause hypokalaemia, and the label explicitly states that hypokalaemia may develop during concomitant use of corticosteroids or ACTH, with intensified electrolyte depletion, particularly potassium. Prednisolone, in turn, causes potassium loss and hypokalaemic alkalosis (listed as fluid and electrolyte disturbances in the label). The combination adds up the risk of hypokalaemia, which can provoke ventricular arrhythmias or sensitise the heart to the toxic effects of digitalis. Monitor serum electrolytes, especially potassium, and consider potassium supplementation.
Hydrochlorothiazide + prednisolone: additive risk of hypokalaemia. Monitor potassium and consider supplementation.
Both promote potassium loss and raised blood glucose.
Potassium, blood glucose and blood pressure.
Weakness, cramps, polyuria, glycaemic decompensation.
Monitor potassium and blood glucose; adjust therapy if needed.
DailyMed (FDA) — approved Prednisolone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52e6e21d-94b8-41a0-8d13-371c0e66bcee ; approved Hydrochlorothiazide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0789baef-3424-43ab-a3fb-4908172da565 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Corticosteroids (such as prednisolone) can raise blood sugar and reduce the effect of metformin. Monitor blood glucose during treatment.
Systemic corticosteroids increase insulin resistance and hepatic glucose production, antagonising the effect of antidiabetics — the Prontuário states explicitly that antidiabetics antagonise the hyperglycaemic effects of corticosteroids and that in diabetics these should only be used when strictly necessary. During prolonged or high-dose corticosteroid therapy, blood glucose must be monitored and antidiabetic therapy adjusted (often the metformin dose must be increased or insulin added).
Glucocorticoids have a hyperglycaemic effect and antagonise antidiabetics; the metformin dose may need adjustment (or insulin added) during corticosteroid therapy, with blood glucose monitoring.
Hyperglycaemic effect of glucocorticoids (increased insulin resistance and gluconeogenesis).
Capillary glucose; symptoms of hyperglycaemia.
Thirst, polyuria, fatigue, blurred vision — decompensated hyperglycaemia.
Monitor blood glucose (and HbA1c on prolonged use) during corticosteroid therapy; adjust the metformin dose as needed and reduce it when the steroid is stopped.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — section 8.2.2 ; DailyMed/FDA (NIH/NLM) — approved Prednisolone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=757b41c4-a0fe-4a09-8816-a4cdb7558f41 ; approved Metformin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=13b1e35f-d047-8ddc-e063-6394a90a24dd
Corticosteroid + anticoagulant: altered INR and bleeding risk.
Prednisolone, like other corticosteroids, can modify the response to warfarin: most reports show an INR decrease (through enzyme induction and fluid retention with haemodilution), but cases of increased effect exist, and the response is unpredictable. The interaction is most relevant in prolonged courses or high doses (e.g. chronic inflammatory diseases, transplantation). The INR should be monitored frequently when starting, adjusting and stopping prednisolone and the warfarin dose adjusted accordingly, with INR re-evaluation after corticosteroid discontinuation.
Corticosteroids can alter the effect of warfarin (usually an INR decrease, but variable). Monitor the INR when starting, adjusting and stopping prednisolone.
Corticosteroids may potentiate or reduce warfarin effect (variable effect on haemostasis and GI mucosa).
Periodic INR and GI symptoms.
Melena, haematemesis, bleeding.
Monitor INR after starting/adjusting corticosteroids; consider gastroprotection.
DailyMed (FDA) — approved Prednisolone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52e6e21d-94b8-41a0-8d13-371c0e66bcee ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Corticosteroid + loop diuretic: additive hypokalaemia risk.
Furosemide causes renal potassium loss and hypochloraemic alkalosis, and corticosteroids such as prednisolone increase potassium excretion (sodium and water retention, potassium loss, hypokalaemic alkalosis — listed as fluid and electrolyte disturbances in the corticosteroid labels). The combination adds up the risk of hypokalaemia, which can precipitate arrhythmias, muscle weakness and worsen heart failure control. Monitor serum electrolytes, especially potassium, and consider potassium supplementation or a potassium-sparing diuretic under guidance.
Furosemide + prednisolone: additive risk of hypokalaemia and hypokalaemic alkalosis. Monitor potassium and consider supplementation.
Both increase renal potassium loss.
Serum potassium and hypokalaemia symptoms.
Weakness, cramps, arrhythmias.
Monitor serum potassium; consider supplementation if needed.
DailyMed (FDA) — approved Prednisolone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52e6e21d-94b8-41a0-8d13-371c0e66bcee ; approved Furosemide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6d9caaab-d874-4cf1-b9fe-408452a18998 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Corticosteroid + NSAID: additive gastrointestinal risk (ulcer/bleeding).
NSAIDs such as naproxen increase the risk of serious gastrointestinal events (bleeding, ulceration and perforation), with a higher risk in the elderly and in patients with a history of peptic ulcer or GI bleeding; concomitant use of oral corticosteroids is a recognised factor increasing the risk of GI bleeding in the NSAID labels. Prednisolone carries a precaution to use with caution in patients with active or latent peptic ulcer. Together, the risk of ulcer, bleeding and digestive perforation increases additively. Consider gastroprotection (proton pump inhibitor) in at-risk patients, use the lowest effective dose of each drug and monitor digestive symptoms.
Naproxen + prednisolone: additive risk of peptic ulcer and gastrointestinal bleeding. Consider gastroprotection in at-risk patients.
Both weaken gastric mucosal protection and increase the risk of GI ulcer and bleeding.
Watch for dyspepsia, abdominal pain and signs of GI bleeding.
Abdominal pain, melena, haematemesis.
Combine only if necessary; consider gastroprotection and the lowest effective dose of both.
DailyMed (FDA) — approved Naproxen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=24d44eb6-921e-4150-a6b2-81f42ced32ab ; approved Prednisolone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52e6e21d-94b8-41a0-8d13-371c0e66bcee — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Voriconazole raises Prednisolone levels (CYP3A4 inhibition), with a risk of enhanced corticosteroid effects.
Voriconazole inhibits CYP3A4, the enzyme that metabolises corticosteroids, and the voriconazole label states that this inhibition can lead to corticosteroid excess and adrenal suppression, with Cushing syndrome (with or without subsequent adrenal insufficiency) reported in patients receiving voriconazole concomitantly with corticosteroids; careful monitoring for adrenal dysfunction during and after voriconazole treatment is recommended, and patients should be instructed to seek immediate medical care if signs of Cushing or adrenal insufficiency appear (fatigue, hypotension, hyperpigmentation, weight loss). Consider reducing the corticosteroid dose and monitor metabolic effects (glycaemia, fluid retention).
Prednisolone + voriconazole: the azole inhibits CYP3A4 and can cause corticosteroid excess, Cushing and adrenal suppression. Monitor closely.
CYP3A4 inhibition by voriconazole reduces prednisolone metabolism.
Blood glucose, blood pressure, signs of iatrogenic Cushing.
Oedema, hyperglycaemia, Cushingoid facies.
Watch for corticosteroid effects; adjust the steroid dose if overdosage signs occur.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Prednisolone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52e6e21d-94b8-41a0-8d13-371c0e66bcee — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Alcohol may increase GI risk.
Limit alcohol during treatment.
EMC-UK (MHRA) — approved Prednisolone SmPC: https://www.medicines.org.uk/emc/product/2427/smpc
Taking with food reduces gastric irritation.
Take with food or milk, preferably in the morning.
EMC-UK (MHRA) — approved Prednisolone SmPC: https://www.medicines.org.uk/emc/product/2427/smpc
Corticosteroids may raise intraocular pressure.
Monitor intraocular pressure on long-term therapy.
EMC-UK (MHRA) — approved Prednisolone SmPC: https://www.medicines.org.uk/emc/product/2427/smpc
Long-term corticosteroids accelerate bone loss.
Use the lowest dose/duration; consider calcium + vitamin D and monitor bone density.
EMC-UK (MHRA) — approved Prednisolone SmPC: https://www.medicines.org.uk/emc/product/2427/smpc
Corticosteroids raise blood glucose.
Monitor blood glucose and adjust antidiabetics during therapy.
EMC-UK (MHRA) — approved Prednisolone SmPC: https://www.medicines.org.uk/emc/product/2427/smpc
Corticosteroids may mask and worsen infections, including severe varicella.
Avoid in active systemic infections without antibiotic cover; keep vaccinations up to date before long-term therapy.
EMC-UK (MHRA) — approved Prednisolone SmPC: https://www.medicines.org.uk/emc/product/2427/smpc
Corticosteroids increase acid and pepsin secretion and, with NSAIDs, the risk of ulcer and GI bleeding.
Use with caution in patients with peptic ulcer; consider gastroprotection and watch for signs of GI bleeding.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — section 8.2.2
Corticosteroids are contraindicated in systemic fungal infections and can worsen infections by several agents (viral, bacterial, fungal, protozoal).
Do not use corticosteroids in systemic fungal infections; during prolonged therapy, watch for the onset or reactivation of infections (including latent tuberculosis).
DailyMed/FDA (NIH/NLM) — approved Prednisolone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=757b41c4-a0fe-4a09-8816-a4cdb7558f41
Corticosteroids can lower the seizure threshold, especially in patients with poorly controlled epilepsy.
Use with caution in patients with epilepsy; watch for seizures during corticosteroid therapy.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — section 8.2.2
Corticosteroids with mineralocorticoid activity cause sodium and water retention, worsening hypertension and potentially precipitating heart failure.
Monitor blood pressure and weight during corticosteroid therapy; adjust antihypertensive therapy if needed.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — section 8.2.2
Corticosteroids cross the placenta; low risk at low doses, but associated with cleft palate (small increase) in the 1st trimester and growth restriction with prolonged use.
Use the lowest effective dose for the shortest duration; monitor fetal growth.
Low doses are compatible with breastfeeding; high doses: wait 3-4 h after dosing.
No routine contraception needed; plan with the doctor, especially long-term therapy.
EMC-UK (MHRA) — approved Prednisolone SmPC: https://www.medicines.org.uk/emc/product/2427/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Synthetic glucocorticoid with predominantly glucocorticoid properties, used mainly for its potent anti-inflammatory and immunosuppressive effects. It promotes gluconeogenesis, increases protein catabolism and lipolysis, inhibits inflammatory processes (oedema, fibrin deposition, capillary dilatation, leucocyte migration and phagocytosis) and suppresses corticotropin production. It has slight mineralocorticoid activity.
Binds to the glucocorticoid receptor, modulating gene transcription; the pharmacological effects result from regulation of the expression of pro- and anti-inflammatory genes.
Well absorbed after oral administration. It is 70 to 90% bound to plasma proteins and the volume of distribution is 0.22 to 0.7 L/kg.
Mainly metabolised in the liver and excreted in urine as sulfate and glucuronide conjugates; reversible interconversion with prednisone occurs.
Prednisolone is eliminated from plasma with a mean half-life of about 2.6 hours (2 to 3.5 hours).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
