Prednisolone

Mechanism

Similar to ASA + methylprednisolone. Prednisolone + antiplatelet – additive risk of GI ulcer and bleeding.

Symptoms

Epigastric pain, nausea, heartburn. With prolonged therapy: peptic ulcer and GI bleeding risk (black stools, vomiting blood). Older patients and prior peptic ulcer disease: higher risk.

Management

Aspirin SmPCs, including those for 100 mg tablets, advise against combining aspirin with systemic glucocorticoids because together they raise the risk of ulcers and gastrointestinal bleeding (aspirin 100 mg and 500 mg SmPCs). If the combination cannot be avoided, use it with caution: tell the patient in advance about the signs of bleeding (black stools, vomiting blood, marked weakness, low blood pressure, cold sweat, abdominal pain, dizziness) and that if they appear, aspirin is stopped and they must see a doctor at once (aspirin SmPCs). The prednisolone SmPC also asks for patient monitoring: prednisolone can speed up salicylate elimination and weaken its effect (prednisolone SmPC). In hypoprothrombinaemia, aspirin is used cautiously with corticosteroids (US prednisolone label).

Mechanism

Prednisolone (a systemic glucocorticoid) modestly lowers the seizure threshold; bupropion also lowers it. The effect is clinically significant during prolonged high-dose prednisolone, especially with prior epilepsy.

Symptoms

Seizures (generalised tonic-clonic or focal). Agitation, anxiety, insomnia from both drugs are possible.

Management

Avoid the combination in patients with prior epilepsy. If unavoidable, do not increase bupropion dose and use prednisolone at the minimum effective dose. Alternative antidepressants without seizure threshold reduction: sertraline, escitalopram.

Mechanism

Additive tendon injury risk. Fluoroquinolones disrupt collagen synthesis in tendon fibres; glucocorticoids suppress repair. FDA carries a boxed warning for tendinitis and Achilles tendon rupture.

Symptoms

Pain and swelling in the Achilles tendon (less often other large tendons). Sudden 'snap' and inability to bear weight indicates rupture. Symptoms typically appear within 1–4 weeks.

Management

Avoid the combination, especially in patients over 60 and athletes. Alternative antibiotics: a cephalosporin or nitrofurantoin (no tendon effect). If ciprofloxacin is needed, limit physical activity for the whole course and 1 month after.

Mechanism

Similar to ibuprofen – additive GI bleeding risk. Diclofenac has a higher ulcerogenic potential among NSAIDs.

Symptoms

Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Risk multiplies in older patients and with prior peptic ulcer disease.

Management

Avoid prolonged combination. If diclofenac is needed, use the minimum effective dose for 5–7 days with mandatory pantoprazole cover. For chronic analgesia: paracetamol or celecoxib.

Mechanism

Two separate risks add up in the same pair. First the mucosa: the corticosteroid slows epithelial turnover and escitalopram depletes platelet serotonin, so gastrointestinal bleeding risk rises. Second the rhythm: escitalopram prolongs the QT interval in a dose-dependent way, and a systemic corticosteroid drives potassium loss. The droperidol and amiodarone labels name glucocorticoids alongside potassium-wasting diuretics as drugs that induce electrolyte imbalance and raise torsade de pointes risk. The escitalopram label contraindicates use with QT-prolonging drugs and asks for hypokalaemia and hypomagnesaemia to be corrected before starting.

Symptoms

On the gastrointestinal side: epigastric pain, black stools, coffee-ground vomit, anaemia with no obvious cause. On the cardiac side: palpitations, dizziness, syncope; on ECG, a prolonged QTc. Muscle weakness and cramps flag the low potassium that precedes the arrhythmia.

Management

Potassium and magnesium before the pair starts and during follow-up, with an ECG and QTc if the corticosteroid runs for weeks or other factors are present: older age, heart disease, another QT-prolonging drug. The escitalopram dose over 65 is capped at 10 mg a day per the label. With a corticosteroid beyond two weeks, a history of ulcer or older age, gastroprotection with a proton pump inhibitor is added. Check whether the corticosteroid is still indicated: the shortest route is stopping what is no longer needed.

Mechanism

Additive gastroesophageal ulcer and bleeding risk. Glucocorticoids reduce GI mucosal repair; NSAIDs block protective prostaglandins.

Symptoms

Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Risk multiplies in older patients and with prior peptic ulcer disease.

Management

Avoid prolonged combination. If ibuprofen is needed for a short course on prednisolone, use the minimum effective dose for 5–7 days with mandatory pantoprazole cover. For chronic analgesia: paracetamol or celecoxib.

Mechanism

Prednisolone (a systemic glucocorticoid) suppresses muscle glucose uptake and stimulates hepatic gluconeogenesis – steroid-induced diabetes develops or existing type 2 diabetes decompensates. Metformin offsets part of the effect but not all.

Symptoms

Hyperglycaemia: thirst, polyuria, fatigue, rising fasting glucose and HbA1c. With high prednisolone doses: decompensation risk with ketoacidosis in type 1 diabetes.

Management

Monitor glucose 4 times daily during the first week of combination, then by self-monitoring. Increase metformin to maximum (2000–2500 mg/day) as needed. If decompensation occurs, add an α-glucosidase inhibitor, a GLP-1 receptor agonist, or temporary insulin.

Mechanism

Prednisolone (a systemic glucocorticoid) raises fibrinogen and clotting factors but can also alter warfarin metabolism through liver enzymes. The effect is unpredictable: INR may either drop or rise.

Symptoms

If INR drops: thromboembolic risk (deep vein thrombosis, stroke in atrial fibrillation). If INR rises: gum bleeding, epistaxis, bruising, GI bleeding (amplified by glucocorticoid-induced gastric mucosa injury).

Management

When prednisolone starts, is escalated, or is withdrawn, check INR at 1 week, then every 2 weeks until stable. Titrate warfarin to INR. PPI cover with pantoprazole is mandatory.

Mechanism

Prednisolone causes sodium and water retention via mineralocorticoid effect, antagonising amlodipine's antihypertensive action.

Symptoms

Gradual blood pressure rise 2–4 weeks after starting the glucocorticoid. In heart failure: oedema, weight gain.

Management

For short prednisolone courses, no adjustment. For prolonged systemic therapy, increase amlodipine or add a diuretic (hydrochlorothiazide, indapamide) with blood pressure monitoring.

Mechanism

Prednisolone causes sodium and water retention via mineralocorticoid effect, reducing bisoprolol's antihypertensive effect.

Symptoms

Gradual blood pressure rise 2–4 weeks after starting the glucocorticoid. In heart failure: oedema, weight gain.

Management

For short prednisolone courses (up to 7 days), no adjustment. For prolonged systemic therapy, increase bisoprolol or add a diuretic with blood pressure monitoring every 2 weeks.

Mechanism

Glucocorticoids retain sodium and water via mineralocorticoid effect, blunting the ACE inhibitor's antihypertensive effect. Both can also cause hyperkalaemia (prednisolone via muscle catabolism, ACE inhibitor via aldosterone suppression).

Symptoms

Return or rise of blood pressure, leg oedema. Hyperkalaemia symptoms in CKD: Weakness, fatigue, paraesthesias, arrhythmia. Symptoms develop at potassium above 5.5 mmol/L; life-threatening above 6.5 mmol/L.

Management

For short prednisolone pulses (3–7 days), no specific adjustment needed. For long-term therapy, check BP weekly in the first month; if it rises, increase enalapril or add a diuretic. Potassium and creatinine every 2 weeks in the first month.

Mechanism

Both cause hypokalaemia: glucocorticoids via mineralocorticoid effect and muscle catabolism; furosemide via direct urinary potassium loss. Additive risk, especially on long-term prednisolone.

Symptoms

Weakness, muscle cramps, fatigue, palpitations, arrhythmia (particularly dangerous with digoxin). Symptoms appear at potassium below 3.5 mmol/L.

Management

For short prednisolone courses (3–7 days), no specific adjustment needed. For long-term therapy, check potassium at 1, 2, and 4 weeks, then monthly. If it falls below 3.5 mmol/L, add potassium supplements (10–20 mmol/day) or a potassium-sparing diuretic. On digoxin, hypokalaemia is dangerous — arrhythmia risk.

Mechanism

Prednisolone retains sodium and water via mineralocorticoid effect, blunting the ARB's antihypertensive effect. Both also contribute to hyperkalaemia in CKD.

Symptoms

Return or rise of blood pressure, leg oedema. Weakness, fatigue, paraesthesias, arrhythmia. Symptoms develop at potassium above 5.5 mmol/L; life-threatening above 6.5 mmol/L.

Management

For short prednisolone courses (3–7 days), no specific adjustment needed. For long-term therapy, check BP weekly in the first month. If BP rises, increase losartan or add a thiazide. Potassium and creatinine every 2 weeks.

Mechanism

Prednisolone is ulcerogenic — suppresses prostaglandin synthesis and gastric mucosal turnover. Sertraline reduces platelet aggregation via serotonin uptake. Additive GI bleeding risk.

Symptoms

Epigastric pain, heartburn, black or tarry stools, blood in vomit, bruising. Higher risk in older patients and prior peptic ulcer disease.

Management

On the combination, in patients over 65, with prior peptic ulcer, or on long-term prednisolone (over 2 weeks), add pantoprazole 20 mg/day. For short courses (3–7 days), additional gastroprotection is not mandatory.