Amlodipine

Mechanism

At high aspirin doses (above 1 g/day), vasodilator prostaglandins are suppressed, weakening amlodipine's antihypertensive effect. At cardioprotective doses (75–100 mg/day), the effect is minimal.

Symptoms

Gradual blood pressure rise 1–2 weeks after starting the NSAID. In chronic kidney disease: risk of fluid retention and oedema.

Management

Cardioprotective aspirin doses (75–100 mg) are acceptable without adjustment. At anti-inflammatory aspirin doses, monitor blood pressure and increase amlodipine if needed.

Mechanism

Amlodipine weakly inhibits CYP3A4 – a partial atorvastatin metabolic route. Atorvastatin plasma levels rise by about 18%. Clinically significant myopathy is rare.

Symptoms

Usually no additional symptoms. In patients with risk factors (older age, chronic kidney disease, hypothyroidism): muscle pain and weakness are possible.

Management

The combination is acceptable without dose change. Cap atorvastatin at 40 mg/day if needed. Check creatine kinase on muscle symptoms.

Mechanism

Dihydropyridine calcium channel blocker (amlodipine) + cardioselective beta-blocker (bisoprolol) – additive bradycardia and hypotension. In reduced ejection fraction (below 40%), heart failure decompensation risk.

Symptoms

Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk. With additional antihypertensives: bradycardia (pulse below 60/min).

Management

The combination is a standard hypertension and angina treatment. In heart failure with reduced ejection fraction, cap amlodipine at 5 mg/day. Check pulse and blood pressure at 1–2 weeks.

Mechanism

Bupropion blocks CYP2D6. Amlodipine is minorly metabolised via CYP2D6 (main route is CYP3A4). The effect is weak – possible mild amlodipine level rise without clinically significant effect.

Symptoms

Minimal changes. Mild additional hypotension or ankle oedema possible in some patients.

Management

No dose adjustment is usually needed. In older patients and reduced ejection fraction, check blood pressure and pulse 2 weeks after starting bupropion.

Mechanism

Additive hypotension and peripheral oedema. Amlodipine causes ankle oedema; the beta-blocker (carvedilol) may potentiate fluid retention.

Symptoms

Lower-leg and ankle oedema, weight gain. Hypotension and dizziness on standing. Worsening dyspnoea in heart failure patients.

Management

Standard combination in ischaemic heart disease with hypertension. In heart failure with reduced ejection fraction, titrate carefully and monitor weight and dyspnoea. For marked ankle oedema: switch to lercanidipine (less oedema among dihydropyridines).

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

NSAIDs weaken amlodipine's antihypertensive effect via prostaglandin suppression. Diclofenac additionally raises cardiovascular risk.

Symptoms

Gradual blood pressure rise 1–2 weeks after starting the NSAID. In chronic kidney disease: risk of fluid retention and oedema.

Management

Avoid prolonged diclofenac use. For acute pain: short course (5–7 days) with pantoprazole cover. For chronic analgesia: paracetamol, celecoxib, or topical NSAIDs.

Mechanism

Dual calcium channel blockade: amlodipine (dihydropyridine), diltiazem (non-dihydropyridine). Additive vasodilation, oedema. Sometimes used in refractory hypertension under cardiology supervision.

Symptoms

Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.

Management

Avoid in routine practice. Alternative for refractory hypertension: triple therapy amlodipine + ARB + diuretic. If unavoidable: monitor pulse, blood pressure, ECG.

Mechanism

SGLT2 inhibitors (empagliflozin) cause osmotic diuresis and mild hypovolaemia. Combined with amlodipine: risk of hypotension and acute kidney injury in dehydration.

Symptoms

Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.

Management

Standard combination in type 2 diabetes with hypertension. In hypovolaemia (dehydration, vomiting, diarrhoea), temporarily stop empagliflozin. Check blood pressure and creatinine 2 weeks after start.

Mechanism

Fluconazole at high doses (200 mg/day or above) blocks CYP3A4 – the main amlodipine metabolic route. Amlodipine plasma levels may rise. The effect is clinically weak in short courses.

Symptoms

Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.

Management

For short fluconazole courses (up to 7 days), no adjustment is usually needed. For prolonged systemic therapy (>14 days), reduce amlodipine by 25% with blood pressure monitoring.

Mechanism

Fluoxetine and its active metabolite norfluoxetine moderately block CYP3A4 – the main amlodipine metabolic route. Amlodipine plasma levels may rise modestly. In older patients: additive hypotension.

Symptoms

Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.

Management

The combination is acceptable in most patients without dose change. In older patients, monitor blood pressure and hypotension symptoms 2 weeks after start.

Mechanism

Additive hypotension (haloperidol blocks α1-adrenoceptors) and sedation. Haloperidol prolongs QT; amlodipine does not contribute to QT.

Symptoms

Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.

Management

Avoid the combination, especially with parenteral haloperidol. Alternative antipsychotics with minimal α1-blockade: olanzapine or aripiprazole.

Mechanism

NSAIDs weaken amlodipine's antihypertensive effect via renal prostaglandin suppression. Additive acute kidney injury risk in dehydration.

Symptoms

Gradual blood pressure rise 1–2 weeks after starting the NSAID. In chronic kidney disease: risk of fluid retention and oedema.

Management

For short ibuprofen courses (5–7 days), monitor blood pressure. For chronic analgesia: switch to paracetamol, celecoxib (with PPI cover), or topical NSAIDs.

Mechanism

Ketorolac suppresses vasodilator prostaglandins, weakening amlodipine's antihypertensive effect. Plus additive nephrotoxicity.

Symptoms

Gradual blood pressure rise 1–2 weeks after starting the NSAID. In chronic kidney disease: risk of fluid retention and oedema.

Management

Ketorolac courses are limited to 5 days. Monitor blood pressure and creatinine in the first days. In chronic kidney disease or reduced ejection fraction, avoid ketorolac; use paracetamol or a short opioid course for analgesia.

Mechanism

Linezolid is a reversible MAO inhibitor. It can potentiate sympathomimetic effects of tyramine-containing foods, but the effect on amlodipine is weak.

Symptoms

Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.

Management

The combination is acceptable for short linezolid courses with blood pressure monitoring. In hypovolaemia or with the first dose: increased orthostatic hypotension risk. The main linezolid combination risk is serotonin syndrome with SSRI/SNRI (see those pairs).

Mechanism

Synergistic blood pressure reduction – a target hypertension combination. Amlodipine dilates peripheral vessels; losartan (ARB) blocks the renin-angiotensin system.

Symptoms

Older patients may have symptomatic and orthostatic hypotension, dizziness on standing. With the first losartan dose: risk of marked blood pressure drop.

Management

Standard hypertension treatment (fixed-dose product available). Take the first losartan dose in the evening, lying down. Check blood pressure and creatinine 1–2 weeks after start.

Mechanism

NSAIDs antagonise amlodipine's antihypertensive effect via renal prostaglandin-dependent sodium regulation suppression.

Symptoms

Gradual blood pressure rise 1–2 weeks after starting meloxicam. In chronic kidney disease: fluid retention and oedema risk.

Management

For short meloxicam courses (5–7 days), monitor blood pressure. For chronic analgesia: switch to paracetamol or celecoxib (with PPI cover).

Mechanism

Similar to amlodipine + prednisolone. Methylprednisolone causes sodium retention via mineralocorticoid effect, reducing 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 methylprednisolone courses, no adjustment. For prolonged systemic therapy, increase amlodipine or add a diuretic (hydrochlorothiazide, indapamide) with blood pressure monitoring every 2 weeks.

Mechanism

Target combination in angina and hypertension. Amlodipine dilates vessels; metoprolol slows heart rate. The drugs compensate each other's reflex effects.

Symptoms

Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.

Management

Standard combination in ischaemic heart disease with hypertension. Check pulse and blood pressure 1–2 weeks after start. In patients with ejection fraction below 40%, watch for heart failure decompensation.

Mechanism

Additive hypotension and sedation. Morphine reduces sympathetic tone; amlodipine dilates vessels. Older patients: fall risk.

Symptoms

Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.

Management

The combination is acceptable in palliative care and acute coronary syndrome. Titrate morphine from a low dose; monitor pulse, blood pressure, and saturation. Older patients: enhanced fall monitoring.

Mechanism

NSAIDs weaken amlodipine's antihypertensive effect via renal prostaglandin suppression.

Symptoms

Gradual blood pressure rise 1–2 weeks after starting naproxen. In chronic kidney disease: fluid retention and oedema risk.

Management

For short naproxen courses (5–7 days), monitor blood pressure. For chronic analgesia: switch to paracetamol or celecoxib (with PPI cover).

Mechanism

Additive hypotension with sublingual or parenteral nitroglycerin. Both drugs are vasodilators (amlodipine – calcium channel blocker, nitroglycerin – nitrate vasodilator).

Symptoms

Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.

Management

The combination is acceptable in angina. The patient takes the first nitroglycerin dose sitting or lying down. Older patients: fall risk after nitroglycerin. Advise the patient to consult a clinician with frequent episodes.

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

Additive bradycardia and hypotension. Propranolol is non-selective (blocks β1 and β2); risk is higher than with bisoprolol – bronchospasm possible in asthma.

Symptoms

Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.

Management

The combination is acceptable in ischaemic heart disease. In asthma or COPD, a selective beta-blocker (bisoprolol, metoprolol) is preferable. Check pulse and blood pressure 1–2 weeks after start.

Mechanism

Additive hypotension. Quetiapine blocks α1-adrenoceptors; amlodipine dilates vessels.

Symptoms

Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.

Management

The combination is acceptable at low quetiapine doses (≤300 mg/day). Check blood pressure 1–2 weeks after start. In older patients, olanzapine or aripiprazole (less α1-blockade) is preferable.

Mechanism

Ritonavir is the most potent CYP3A4 inhibitor available – the main amlodipine metabolic route. Amlodipine plasma levels rise 2- to 3-fold, with hypotension and peripheral oedema.

Symptoms

Lower blood pressure, postural dizziness, marked lower-leg oedema. Older patients: fall risk.

Management

Halve amlodipine when combined (starting 2.5 mg/day) and monitor blood pressure 1–2 weeks after. Alternative antihypertensive on ritonavir: ACE-I or ARB (no CYP3A4 dependence).

Mechanism

Additive hypotension via different mechanisms – calcium channel blockade (amlodipine) + PDE5 blockade (sildenafil). Clinically significant in patients with prior hypotension.

Symptoms

Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.

Management

The combination is acceptable in stable hypertension. Take the first sildenafil dose lying down; do not exceed 25–50 mg. Warn the patient about orthostatic hypotension.

Mechanism

Tacrolimus and amlodipine are both CYP3A4 substrates competing for the enzyme. Tacrolimus plasma levels may rise.

Symptoms

Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. In transplant patients: accelerated graft decline.

Management

The combination is acceptable in post-transplant patients with hypertension. Check tacrolimus trough (C0) 1 week after starting or changing amlodipine. Alternative: an ARB or α-blocker (no CYP3A4 dependence).