Losartan

Mechanism

Dual RAAS blockade (ACE-I + ARB). Additive hyperkalaemia, hypotension, and acute kidney injury risk without added benefit.

Symptoms

Weakness, postural dizziness, syncope. Reduced urine output, rising creatinine. Weakness and paraesthesia from hyperkalaemia.

Management

The combination is not prescribed. Choose one: ACE-I if tolerated, ARB if there is a dry cough.

Mechanism

Similar to enalapril + celecoxib. NSAIDs reduce renal blood flow; the ARB (losartan) lowers glomerular pressure. The combination causes acute kidney injury.

Symptoms

Reduced urine output, rising creatinine and potassium, oedema. Symptoms appear earlier in older patients and in chronic kidney disease.

Management

For prolonged celecoxib therapy, check creatinine 2–4 weeks after start, then every 3 months. In older patients and chronic kidney disease, paracetamol is preferable.

Mechanism

Trimethoprim blocks sodium channels via an amiloride-like mechanism, additively with an ARB (losartan) causing hyperkalaemia. In older patients, sudden death risk rises.

Symptoms

Muscle weakness, paraesthesia, slowed pulse, arrhythmias. ECG: peaked T waves, widened QRS. Severe cases progress to cardiac arrest.

Management

During co-trimoxazole therapy, check potassium 3 days after start. In older patients and chronic kidney disease, prefer alternative antibiotics (nitrofurantoin, fosfomycin).

Mechanism

Dual RAAS blockade: ACE-I blocks angiotensin II formation, ARB blocks its receptors. Additive risk of hyperkalaemia, hypotension, and acute kidney injury without additional clinical benefit.

Symptoms

Weakness, dizziness on standing, syncope. Reduced urine output, rising serum creatinine. Weakness and paraesthesia from hyperkalaemia. Symptoms typically appear in the first 1–4 weeks.

Management

The combination is not prescribed. Large trials (ONTARGET, ALTITUDE) showed no benefit and more adverse effects. Choose one agent: ACE-I if tolerated, ARB if there is a dry cough or intolerance.

Mechanism

Losartan (ARB) reduces aldosterone synthesis and angiotensin-dependent constriction of glomerular afferent arterioles. In a volume-depleted patient on a loop diuretic, the first losartan dose can sharply lower glomerular blood flow and trigger acute kidney injury.

Symptoms

Sharp blood pressure drop on the first dose: dizziness, syncope. Reduced urine output, rising creatinine. Weakness and paraesthesia from hyperkalaemia.

Management

The combination is standard in hypertension and heart failure. Before starting losartan, confirm there is no dehydration (after intensive diuretic therapy). Take the first dose in the evening, lying down. Check potassium and creatinine at 1 week.

Mechanism

A thiazide diuretic plus an ARB synergistically lower blood pressure: the thiazide reduces circulating volume, losartan vasodilates by suppressing the RAAS. This is a target combination in hypertension and available as a fixed-dose product (losartan + hydrochlorothiazide).

Symptoms

Excessive blood pressure drop during titration: postural dizziness, syncope. Hypokalaemia and hyponatraemia from the thiazide, plus a mild rise in creatinine, can occur in the first weeks.

Management

The combination is a treatment standard. Doses are individualised, usually starting with losartan 50 mg + hydrochlorothiazide 12.5 mg/day. Check potassium, sodium, and creatinine 2–4 weeks after start, then annually.

Mechanism

NSAIDs reduce renal blood flow via prostaglandin blockade. The ARB (losartan) lowers glomerular pressure. The combination causes acute kidney injury, especially in older patients, chronic kidney disease, and dehydration.

Symptoms

Reduced urine output, rising creatinine and potassium, oedema. Symptoms appear earlier in older patients and in chronic kidney disease.

Management

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

Mechanism

Drugs that block the renin-angiotensin system increase steady-state serum lithium concentrations (US lithium label, FDA). Reversible rises in lithium levels and lithium toxicity have been reported with angiotensin-converting enzyme inhibitors and, very rarely, with angiotensin II receptor blockers such as losartan (losartan SmPC). Lithium has a narrow therapeutic range: toxic concentrations are close to therapeutic ones (US lithium label).

Symptoms

Tremor, muscle twitching, nausea, vomiting, diarrhoea, poor coordination and confusion; severe cases progress to seizures and coma. Toxicity is expected at serum lithium concentrations of about 1.5 mmol/L and above, but some patients develop it at lower levels, including within the therapeutic range.

Management

The Spanish losartan SmPC advises combining it with lithium with caution and only if the combination is essential; in that case, monitor lithium levels throughout co-administration (losartan SmPC). When losartan is started, stopped or its dose is changed, measure lithium more often, moving to weekly checks (lithium SmPC), and reduce the lithium dose according to levels and clinical response if needed (US lithium label, FDA). Take the lithium sample 12 hours after the last dose (lithium SmPC). The UK National Institute for Health and Care Excellence (NICE) advises taking any start or change of an angiotensin II receptor blocker into account when reviewing lithium levels and seeking specialist advice if in doubt (NICE NG222). Warn the patient about signs of lithium toxicity: diarrhoea, vomiting, coarse tremor, poor coordination, confusion and seizures (NICE NG222).

Mechanism

Losartan (angiotensin II receptor blocker, ARB) suppresses the renin-angiotensin-aldosterone system and reduces aldosterone release. Spironolactone directly blocks aldosterone receptors. Both retain potassium.

Symptoms

Muscle weakness, paraesthesia in the limbs, slowed pulse, arrhythmias. ECG shows peaked T waves and widened QRS. Severe cases progress to cardiac arrest. Symptoms typically appear within 1–2 weeks of starting the combination.

Management

The combination is appropriate in heart failure. Check potassium and creatinine 1 week after start, then monthly. If potassium exceeds 5.5 mmol/L, reduce the dose of one agent; above 6.0 mmol/L, stop one of them.

Mechanism

At high, anti-inflammatory doses aspirin suppresses renal prostaglandin synthesis. Together with losartan this lowers glomerular filtration, which in older or dehydrated patients can lead to acute kidney failure, and it can raise blood potassium (aspirin 100 mg and losartan SmPCs). Loss of vasodilating prostaglandins also weakens the blood-pressure-lowering effect of losartan. The US label for low-dose aspirin (FDA) describes the same kidney and blood pressure risks.

Symptoms

Blood pressure creeps up. If kidney function worsens, urine output falls, oedema appears, and creatinine and potassium rise on blood tests. The risk is higher in older patients, with dehydration, on diuretics, or with already reduced kidney function.

Management

The Spanish SmPCs describe the interaction mainly for high, anti-inflammatory aspirin doses (losartan and aspirin 100 mg SmPCs). With such doses, keep the patient well hydrated and check kidney function after starting the combination and periodically afterwards, with particular care in older patients (losartan SmPC). The FDA asks for periodic kidney checks even with low-dose aspirin when the patient is elderly, volume-depleted, on diuretics or has reduced kidney function (US aspirin label). Blood pressure is kept under close medical supervision (aspirin 100 mg SmPC), since losartan may work less well (losartan labels).

Mechanism

Additive hypotension. Alprazolam sedation may mask orthostatic symptoms.

Symptoms

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

Management

In older patients, check standing and sitting blood pressure 1–2 weeks after start. Alternative anxiolytic: hydroxyzine or a short lorazepam course.

Mechanism

Additive orthostatic hypotension. Losartan (ARB) dilates vessels; amitriptyline blocks α1-adrenoceptors. Older patients: fall risk.

Symptoms

Postural dizziness, syncope, fatigue. Older patients: fall and fracture risk.

Management

In older patients, check standing and sitting blood pressure 1–2 weeks after starting amitriptyline. For neuropathic pain, alternative: gabapentin or pregabalin.

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

ARBs, like ACE inhibitors, improve tissue insulin sensitivity. In patients on insulin or sulfonylureas with metformin, the glucose-lowering effect may be amplified.

Symptoms

Signs of hypoglycaemia: sweating, tremor, hunger, tachycardia, confusion. Symptoms appear at glucose below 3.9 mmol/L.

Management

On metformin alone, no dose adjustment needed. On insulin or sulfonylureas, intensify glucose self-monitoring for the first 2 weeks after starting losartan. The effect is helpful in type 2 diabetes with arterial hypertension.

Mechanism

Target combination in heart failure and arterial hypertension. Synergistic blood pressure reduction. The ARB does not mask the adrenergic response to hypoglycaemia.

Symptoms

On starting, in older patients: symptomatic hypotension, dizziness. Metoprolol bradycardia is amplified as sympathetic activation drops.

Management

Start both at minimal doses with up-titration every 2 weeks to target. Check standing/sitting BP, heart rate, creatinine and potassium at 2 weeks. In diabetes, monitor for hypoglycaemia: metoprolol is cardioselective and weakly masks adrenergic symptoms.

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

Both lower blood pressure by different routes: losartan blocks the angiotensin II receptor, sildenafil relaxes vascular smooth muscle through the nitric oxide/cGMP pathway. The effect is additive and quantified in the label for a comparable antihypertensive: with amlodipine, sildenafil 100 mg lowered supine systolic pressure by a further 8 mmHg and diastolic by 7 mmHg.

Symptoms

Dizziness on standing, vision darkening for a few seconds, facial flushing, headache, palpitations. In older or dehydrated people the drop can reach syncope. The nitrate combination is contraindicated and should not be confused with this one.

Management

The pair is acceptable with controlled blood pressure. Start at the lowest sildenafil dose, avoid alcohol, and stand up slowly for the first hours. Skip it on the day the antihypertensive dose is adjusted or a diuretic is added, and always check for nitrates, where the combination is no longer possible.

Mechanism

Tadalafil is a phosphodiesterase type 5 (PDE5) inhibitor with vasodilator properties: on its own it causes a slight and transient fall in blood pressure (tadalafil SmPC, EMA). Losartan lowers blood pressure by blocking angiotensin II receptors, and other substances with a hypotensive effect add to its action (losartan SmPC). In studies with angiotensin II receptor blockers tadalafil 20 mg produced a small additional fall in blood pressure without a clinically significant interaction; in people with uncontrolled hypertension the fall was larger, but in most of them without symptoms of hypotension (tadalafil SmPC, EMA). The interaction is pharmacodynamic: two blood-pressure-lowering effects add up (Cialis label, FDA).

Symptoms

Usually none: the fall in blood pressure is small and not clinically relevant (tadalafil SmPC, EMA). Dizziness, weakness or light-headedness on standing can signal a drop in blood pressure; the risk is higher with uncontrolled hypertension and with volume or sodium depletion from diuretics, diarrhoea, vomiting or a salt-restricted diet, when losartan itself can cause symptomatic hypotension (tadalafil and losartan SmPCs).

Management

By the SmPCs the combination is acceptable and no dose change of losartan or tadalafil is needed: no clinically significant interaction with angiotensin II receptor blockers was found (tadalafil SmPC, EMA). The patient is told that blood pressure may fall slightly in addition to antihypertensive treatment (tadalafil SmPC, EMA). Before tadalafil is prescribed, cardiovascular status is assessed, because sexual activity itself carries some cardiac risk (tadalafil SmPC, EMA); with uncontrolled hypertension or blood pressure below 90/50 mm Hg tadalafil is not recommended, and in people with uncontrolled hypertension the fall in pressure was larger (Cialis label, FDA; tadalafil SmPC, EMA). Volume or sodium depletion after diuretics, diarrhoea or vomiting is corrected before losartan starts, or losartan is started at a lower dose (losartan SmPC).