Dexamethasone

Mechanism

Additive ulcerogenic effect. Dexamethasone suppresses GI mucosal repair; aspirin blocks protective prostaglandins.

Symptoms

Epigastric pain, nausea, heartburn. With prolonged therapy: peptic ulcer and GI bleeding risk (black stools, vomiting blood or coffee-ground material). 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). The exception is hydrocortisone used as replacement therapy in Addison's disease. 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). In patients with peptic ulcer disease, give an anti-ulcer drug together with dexamethasone (dexamethasone SmPC). Corticosteroids can increase salicylate clearance, and in hypoprothrombinaemia the patient is monitored for aspirin toxicity on this combination (US dexamethasone label).

Mechanism

The point of contact is potassium, not cytochrome. The amiodarone label asks for caution with drugs that can cause hypokalaemia or hypomagnesaemia and names diuretics alone or in combination, systemic corticosteroids, tetracosactide and intravenous amphotericin B. In the same document: hypokalaemia alters the effects of amiodarone, increases QT prolongation and the risk of torsade de pointes. Dexamethasone is a potent systemic corticosteroid and produces that potassium loss. Its role as a weak CYP3A4 inducer is real but clinically counts for less than the electrolyte imbalance.

Symptoms

Palpitations, dizziness, presyncope and syncope. On ECG, a prolonged QTc and ventricular ectopy; torsade de pointes can degenerate into ventricular fibrillation. Muscle weakness, cramps and fatigue from low potassium usually come before the arrhythmia.

Management

Potassium and magnesium before dexamethasone starts in someone on amiodarone and during the course, correcting them first if already low. ECG with QTc at the start and at any rhythm symptom. The corticosteroid course is kept to the minimum indicated. If a potassium-wasting diuretic joins the pair, monitoring tightens, because the losses accumulate.

Mechanism

Dexamethasone is a CYP3A4 and P-glycoprotein inducer. It reduces apixaban (a substrate of both) levels by 30–50%, raising thrombotic event risk.

Symptoms

The patient feels no symptoms. Stroke risk in atrial fibrillation rises, as do deep vein thrombosis and pulmonary embolism risks.

Management

For prolonged systemic dexamethasone, do not increase apixaban (no titration data); switch to warfarin with INR monitoring instead. For short dexamethasone pulse therapy (1–3 days), no clinically significant effect.

Mechanism

Dexamethasone is a potent CYP3A4 inducer and weak CYP2B6 inducer (which metabolises bupropion). Bupropion levels may fall, giving partial loss of antidepressant effect. The glucocorticoid itself also lowers the seizure threshold.

Symptoms

Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.

Management

For prolonged dexamethasone therapy, bupropion may be increased by 50% with clinical monitoring. For short courses, no adjustment is usually needed. After dexamethasone stops, induction persists for 1–2 weeks.

Mechanism

Fluoroquinolones, including ciprofloxacin, can cause tendinitis and tendon rupture, most often of the Achilles tendon. The risk is higher in older patients, in renal impairment, after solid organ transplantation and in patients who take corticosteroids at the same time (ciprofloxacin SmPC); the dexamethasone SmPC also lists use with fluoroquinolones as a risk factor for tendinitis and tendon rupture (dexamethasone SmPC). The US Food and Drug Administration (FDA) label specifies age over 60 and adds strenuous physical activity and previous tendon disorders as risk factors (ciprofloxacin FDA label). A second mechanism is metabolic: dexamethasone is cleared by the CYP3A4 enzyme (dexamethasone SmPC), and the FDA classes ciprofloxacin as a moderate CYP3A inhibitor (FDA list), so dexamethasone levels may rise.

Symptoms

Pain, swelling and inflammation of the Achilles tendon, less often of tendons in the shoulder, hand or biceps, sometimes on both sides, up to tendon rupture (ciprofloxacin labels). Symptoms can start within 48 hours of starting ciprofloxacin and as late as several months after the course ends (ciprofloxacin SmPC).

Management

The ciprofloxacin SmPC says concomitant use of corticosteroids should be avoided because of the risk of tendinitis and tendon rupture (ciprofloxacin SmPC). The dexamethasone SmPC also advises avoiding CYP3A inhibitors unless the benefit outweighs the higher risk of systemic corticosteroid adverse effects, and monitoring the patient for them if the combination is used (dexamethasone SmPC); the US Food and Drug Administration (FDA) classes ciprofloxacin as a moderate CYP3A inhibitor (FDA list). Ciprofloxacin is generally not given to patients who have had tendon disorders with a quinolone before (ciprofloxacin SmPC). Warn the patient about the symptoms: at the first sign of tendinitis, such as painful swelling or inflammation, stop ciprofloxacin at once and immobilise the affected limb, and do not use corticosteroids if there are signs of tendinopathy (ciprofloxacin SmPC).

Mechanism

Both labels point to the same spot from opposite sides. The dexamethasone label states that non-steroidal anti-inflammatories, for example indometacin and salicylates, increase the risk of ulcer and gastrointestinal bleeding. The diclofenac label notes that concomitant use with other NSAIDs or corticosteroids can increase gastrointestinal adverse effects. The steroid also retains sodium and raises blood glucose, adding to the renal and blood pressure effect of the NSAID.

Symptoms

Epigastric pain, nausea, black stools, coffee-ground vomit. The steroid masks fever and pain, so a perforation may present with few symptoms. Add high blood glucose in diabetics, oedema and rising blood pressure.

Management

Avoid overlapping the two unless clearly indicated, and then for the shortest time. When the combination is necessary, add gastric protection with a proton pump inhibitor and monitor stools, haemoglobin and blood glucose. For background pain, paracetamol allows the NSAID to be reduced or dropped.

Mechanism

Dexamethasone is a weak CYP3A4 inducer. With prolonged therapy, amlodipine plasma levels may modestly fall and the antihypertensive effect weaken.

Symptoms

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

Management

For short dexamethasone courses (up to 7 days), no adjustment. For prolonged systemic therapy, monitor blood pressure every 2 weeks; increase amlodipine if needed.

Mechanism

Dexamethasone induces CYP3A4. With prolonged therapy, atorvastatin plasma levels may fall modestly and lipid-lowering effect weakens.

Symptoms

The patient feels nothing. Laboratory: LDL cholesterol and total cholesterol rise during prolonged systemic glucocorticoid therapy.

Management

For short dexamethasone courses, no adjustment. For prolonged systemic therapy, monitor lipid profile every 2–3 months; increase atorvastatin by 25–50% if needed.

Mechanism

Dexamethasone causes sodium and water retention via mineralocorticoid effect, reducing the antihypertensive effect of the beta-blocker.

Symptoms

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

Management

For short dexamethasone courses (up to 7 days), no adjustment. For prolonged systemic therapy, increase bisoprolol or add a diuretic (hydrochlorothiazide, indapamide) with blood pressure monitoring.

Mechanism

Dexamethasone has minimal mineralocorticoid activity but, at high doses and prolonged use, blunts the ACE inhibitor's antihypertensive effect. The effect is weaker than with prednisolone.

Symptoms

Possible rise in blood pressure with long-term therapy. Weakness, fatigue, paraesthesias, arrhythmia. Symptoms develop at potassium above 5.5 mmol/L; life-threatening above 6.5 mmol/L.

Management

For short dexamethasone courses, no specific adjustment needed. For long-term therapy, check BP every 1–2 weeks. If BP rises, intensify antihypertensive therapy (increase enalapril or add a thiazide). Potassium and creatinine monthly.

Mechanism

Dexamethasone stimulates gluconeogenesis and reduces tissue insulin sensitivity. The glycaemic effect is stronger than with prednisolone due to long half-life and high potency.

Symptoms

Return of thirst and polyuria, rising fasting glucose, fatigue. In type 2 diabetes, possible decompensation with HbA1c rise of 0.5–1.5%.

Management

For short dexamethasone pulses (1–3 days, e.g. cerebral oedema or post-chemotherapy), no metformin adjustment needed — transient hyperglycaemia is tolerated. For long-term therapy, increase metformin or add long-acting insulin. Check glucose twice daily in the first week.

Mechanism

Dexamethasone is a weak CYP3A4 inducer and a potential weak CYP2C9 inhibitor. Effect on INR is unpredictable and usually mild: INR may fall in some patients and rise in others.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, black or tarry stools, haematuria. Higher risk in older patients, prior peptic ulcer disease, and chronic kidney disease.

Management

For short dexamethasone courses (3–5 days), no special monitoring needed. For longer therapy, check INR at one week, then every 2 weeks. Beyond the INR effect, glucocorticoids add gastrointestinal bleeding risk via mucosal ulcerogenic action.