Budesonide

Mechanism

Budesonide is broken down mainly by the CYP3A4 enzyme, and amiodarone and its metabolite inhibit this enzyme (amiodarone SmPC). Budesonide levels may rise, and with them the risk of systemic corticosteroid effects; these effects are less likely with inhaled than with oral budesonide (inhaled budesonide SmPC). A second mechanism involves systemic corticosteroids: they can lower potassium, and low potassium during amiodarone treatment raises the risk of torsades de pointes (amiodarone SmPC). Amiodarone is eliminated slowly, so interactions can occur for several months after it is stopped (amiodarone SmPC).

Symptoms

With long-term treatment: rounded face, weight gain with fat redistribution, thin skin, acne, muscle weakness, mood changes, raised blood glucose. If potassium falls during amiodarone treatment: palpitations, fainting, QT prolongation on the electrocardiogram (ECG) and, in severe cases, torsades de pointes.

Management

Oral budesonide should not be combined with CYP3A4 inhibitors unless the benefit outweighs the higher risk of systemic corticosteroid effects; if the combination is used, monitor the patient for these effects (oral budesonide SmPC). Amiodarone inhibits CYP3A4 (amiodarone SmPC), so this applies to it. The inhaled budesonide SmPC says to avoid strong CYP3A inhibitors and gives itraconazole, ketoconazole, human immunodeficiency virus (HIV) protease inhibitors and cobicistat-containing products as examples; amiodarone is not among them. With a 1–2 week course the interaction with inhaled budesonide is of limited relevance; in long-term treatment take it into account and watch for systemic effects (inhaled budesonide SmPC). Use amiodarone with caution alongside systemic corticosteroids: prevent and correct low potassium, monitor the QT interval, and do not give antiarrhythmic drugs if torsades de pointes occurs (amiodarone SmPC). Interactions with amiodarone can occur for several months after it is stopped (amiodarone SmPC).

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 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).

Symptoms

Pain, swelling and inflammation of the Achilles or other tendons, sometimes on both sides, up to tendon rupture. 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). It does not specify the route; inhaled budesonide can also have systemic effects, especially at high doses and in long-term use (inhaled budesonide SmPC). 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

Clarithromycin blocks CYP3A4 – the main hepatic metabolic route for budesonide. Systemic budesonide exposure (oral or inhaled) rises 4- to 8-fold. Cushing's syndrome and adrenal insufficiency have been reported.

Symptoms

Moon face, central obesity, abdominal striae, hypertension, hyperglycaemia (Cushing's syndrome). With prolonged combination and abrupt withdrawal: risk of adrenal insufficiency with hypotension and weakness.

Management

For short clarithromycin courses (5–7 days), halve budesonide temporarily. For prolonged therapy, switch antibiotics (azithromycin, doxycycline) or replace budesonide with fluticasone/mometasone (less CYP3A4-dependent).

Mechanism

Budesonide is broken down mainly by the CYP3A4 enzyme. Fluvoxamine moderately inhibits this enzyme (fluvoxamine SmPC), so budesonide levels may rise, and with them the risk of systemic corticosteroid effects. These effects are less likely with inhaled than with oral budesonide (inhaled budesonide SmPC), but they are possible: with high-dose inhaled budesonide, itraconazole raised its plasma levels about fourfold on average (inhaled budesonide SmPC).

Symptoms

On long-term therapy: moon face, weight gain with fat redistribution, skin thinning, acne, muscle weakness, mood disturbance, hyperglycaemia.

Management

The fluvoxamine SmPC requires drugs metabolised by the CYP3A4 enzyme to be started or adjusted to the low end of their dose range when given with fluvoxamine, with monitoring of their effects and side effects and dose reduction if needed (fluvoxamine SmPC). Oral budesonide should not be combined with CYP3A4 inhibitors unless the benefit outweighs the higher risk of systemic corticosteroid effects; if the combination is used, monitor the patient for these effects (oral budesonide SmPC). The inhaled budesonide SmPC says to avoid strong CYP3A inhibitors and gives itraconazole, ketoconazole, human immunodeficiency virus (HIV) protease inhibitors and cobicistat-containing products as examples. With a 1–2 week course the interaction with inhaled budesonide is of limited relevance; in long-term treatment take it into account, watch for systemic effects and keep the inhaled corticosteroid at the lowest dose that controls asthma (inhaled budesonide SmPC).

Mechanism

Ketoconazole strongly blocks CYP3A4 – the main budesonide metabolic route. Systemic budesonide exposure (oral or inhaled) rises 6- to 12-fold. High Cushing's syndrome risk with prolonged combination.

Symptoms

Moon face, central obesity, abdominal striae, hypertension, hyperglycaemia. With prolonged combination and abrupt withdrawal: adrenal insufficiency risk.

Management

The combination is not prescribed. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses. Alternative inhaled corticosteroid: fluticasone/mometasone (less CYP3A4-dependent).

Mechanism

Ritonavir is the most potent CYP3A4 inhibitor available. Systemic budesonide exposure (inhaled or oral) rises 8- to 10-fold. High risk of iatrogenic Cushing's syndrome, especially during long-term inhaled therapy for asthma or COPD.

Symptoms

Moon face, central obesity, abdominal striae, hypertension, hyperglycaemia. With prolonged combination and abrupt withdrawal: adrenal insufficiency risk.

Management

Avoid the combination. Alternative inhaled corticosteroid: beclomethasone (less CYP3A4-dependent) or short-acting β2-agonists with inhaled anticholinergics. If replacement is impossible: minimum effective budesonide dose with glucose and blood pressure monitoring.

Mechanism

Additive ulcerogenic effect with oral budesonide (used in inflammatory bowel disease). Inhaled forms have minimal systemic effect.

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

Inhaled budesonide for asthma or COPD requires no special measures. For oral therapy (Crohn's disease, ulcerative colitis): PPI cover with pantoprazole, cardioprotective aspirin no more than 100 mg/day.

Mechanism

Systemic (oral) budesonide causes sodium retention and weakens the antihypertensive effect of the beta-blocker. With inhaled use, systemic effect is minimal, so no clinical impact.

Symptoms

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

Management

Inhaled budesonide for asthma or COPD does not require bisoprolol adjustment. For oral therapy in inflammatory bowel disease, check blood pressure every 2–4 weeks.

Mechanism

Systemic budesonide retains sodium and water via mineralocorticoid effect (weaker than prednisolone), antagonising the ACE inhibitor's antihypertensive effect. Inhaled budesonide does not clinically affect BP.

Symptoms

On long-term therapy: return or rise of blood pressure, leg oedema. Hyperkalaemia possible with reduced renal function.

Management

For short systemic budesonide courses (3–7 days), no specific adjustment needed. For long-term therapy, check BP weekly in the first month. If BP rises, intensify antihypertensives or switch to an oral corticosteroid with less mineralocorticoid activity (methylprednisolone). Inhaled budesonide with captopril is unproblematic.

Mechanism

Systemic budesonide retains sodium and water, blunting the beta-blocker's antihypertensive effect. Inhaled budesonide does not clinically affect BP.

Symptoms

On long-term systemic therapy: return or rise of blood pressure, leg oedema.

Management

For short systemic budesonide courses, no specific adjustment needed. For long-term therapy, check BP weekly in the first month. If BP rises, increase carvedilol or add an ACE inhibitor. Inhaled budesonide with carvedilol is unproblematic.

Mechanism

Glucocorticoid plus NSAID — additive GI ulcer risk with systemic budesonide. Celecoxib (selective COX-2 inhibitor) gives lower gastric risk than non-selective NSAIDs, but the effect persists.

Symptoms

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

Management

On systemic budesonide and celecoxib, in older patients, prior peptic ulcer, or long-term therapy: pantoprazole 20 mg/day. Alternatives in osteoarthritis: topical NSAIDs, paracetamol up to 2 g/day. Inhaled budesonide with celecoxib is safe.

Mechanism

Systemic budesonide retains sodium and water via mineralocorticoid effect, blunting clonidine's antihypertensive effect. Inhaled budesonide does not clinically affect BP.

Symptoms

On long-term systemic therapy: return or rise of blood pressure, leg oedema.

Management

For short systemic budesonide courses, no specific adjustment needed. For long-term therapy, check BP weekly in the first month. If BP rises, increase clonidine or add a diuretic. Inhaled budesonide with clonidine is unproblematic.

Mechanism

Glucocorticoid plus NSAID — additive GI ulcer and bleeding risk with systemic budesonide. Inhaled budesonide does not clinically affect risk.

Symptoms

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

Management

On systemic budesonide, limit diclofenac to short courses (no more than 5–7 days) with pantoprazole 20 mg/day. For long-term analgesia: paracetamol up to 2 g/day or topical NSAIDs. Inhaled budesonide with diclofenac is safe. In older patients and prior peptic ulcer, risk outweighs benefit.

Mechanism

Oestradiol raises corticosteroid-binding globulin, increasing the bound budesonide fraction. The free fraction changes minimally. The interaction is clinically minor.

Symptoms

No specific clinical manifestations. On long-term systemic therapy, both drugs' side effects may appear.

Management

No dose adjustment needed. In women on menopausal hormone therapy and oral budesonide, check BP, weight, and lipid profile every 6 months. With systemic budesonide over 3 months, consider switching to inhaled glucocorticoids.

Mechanism

Oestrogens raise corticosteroid-binding globulin, increasing the bound budesonide fraction, but the effective free fraction changes minimally. The interaction is clinically minor.

Symptoms

No specific clinical manifestations. On systemic long-term therapy, both drugs' side effects may appear.

Management

No dose adjustment needed. In women on combined oral contraceptives and oral budesonide, check BP and weight every 3 months. With significant systemic budesonide side effects, consider switching to inhaled glucocorticoids or mesalazine.

Mechanism

Additive GI ulcer and bleeding risk with systemic budesonide. Inhaled budesonide does not clinically affect risk.

Symptoms

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

Management

On systemic budesonide, limit ibuprofen to short courses (no more than 5–7 days) with pantoprazole 20 mg/day. For long-term analgesia: paracetamol up to 2 g/day. Inhaled budesonide with ibuprofen is safe. In older patients and prior peptic ulcer, risk outweighs benefit — consider paracetamol or topical NSAIDs.

Mechanism

Dual immunomodulation. Isotretinoin is teratogenic and affects liver function and skin barrier. Systemic budesonide suppresses immunity and raises infection risk. No direct pharmacokinetic interaction.

Symptoms

On long-term combination: increased infection susceptibility (bacterial sinusitis, pneumonia, candidiasis). Skin and mucosal dryness intensifies. Cases of intestinal mucosal ulceration on the combination have been reported.

Management

Systemic budesonide and isotretinoin are not co-prescribed without strong indication. In inflammatory bowel disease (Crohn's) with severe acne, options: treat acne topically and with adapalene, or start isotretinoin after inflammation remits and glucocorticoids are stopped. Inhaled budesonide with isotretinoin is safe.

Mechanism

Glucocorticoid plus NSAID — additive risk of GI ulcers and bleeding. Systemic budesonide (Cortiment, Entocort) raises risk; inhaled budesonide does not.

Symptoms

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

Management

Ketorolac is not prescribed with systemic budesonide — risk outweighs benefit. For acute pain: paracetamol up to 3 g/day or metamizole. If NSAIDs are necessary (short course in cancer or postoperative pain), add pantoprazole 20 mg/day and cap ketorolac at 5 days. Inhaled budesonide with NSAIDs is safe.

Mechanism

No clinically significant direct interaction. With long-term oral budesonide, mild additive sodium retention may slightly reduce amlodipine's antihypertensive effect. Inhaled budesonide does not clinically affect BP.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

For short systemic budesonide courses, no adjustment needed. For long-term therapy, check BP monthly. If BP rises, increase amlodipine or add a diuretic.