Losartan

Angiotensin II receptor blockers (ARBs)

ATC code: C09CA01 (Losartan)

Mechanism of action

Selective angiotensin II receptor (AT1 subtype) antagonist. Blocks angiotensin II action on vascular and adrenal receptors, causing vasodilation and reducing aldosterone secretion. Unlike ACE inhibitors, does not affect bradykinin degradation, so dry cough is much less common. Additionally has a uricosuric effect, lowering uric acid levels.

Indications

Chronic kidney disease

First line

Losartan slows progression of diabetic nephropathy in type 2 diabetes. The RENAAL trial showed a 25 % reduction in doubling of creatinine and a 28 % reduction in end-stage renal disease. Monitor creatinine and potassium 1–2 weeks after initiation.

Diabetic nephropathy in type 2 diabetes patients.

Heart failure

First line

ARBs are an alternative to ACE inhibitors in HFrEF when ACEi are not tolerated due to cough. Mortality and hospitalization reduction is comparable to ACEi based on CHARM-Alternative (candesartan) and ELITE II (losartan) trials. Titration to maximum tolerated dose is mandatory.

Prescribed when ACE inhibitors are not tolerated (most commonly due to cough).

Hypertension

First line

Losartan is a first-line antihypertensive. Start at 50 mg once daily, maximum 100 mg. Prescribed as an alternative to ACE inhibitors, especially when ACEi-induced cough develops. The LIFE trial showed losartan superior to atenolol for stroke risk reduction in patients with hypertension and LVH.

Practical notes

Timing and administration

Take once daily with or without food. Time of day does not matter, but bedtime dosing may be preferred in nocturnal hypertension. Full antihypertensive effect is reached in 3–6 weeks.

Monitoring

Check potassium and creatinine 1–2 weeks after initiation and each dose increase. A creatinine rise up to 30 % is acceptable. Larger rises warrant investigation for renal artery stenosis, hypovolemia, or concurrent NSAID use.

Safety

Contraindications

Pregnancy (all trimesters)
Severe hyperkalemia
Bilateral renal artery stenosis or stenosis of a single functioning kidney
Concurrent aliskiren in patients with diabetes or CKD

Serious adverse effects

Angioedema (much less common than with ACEi, but possible)
Acute renal failure (in bilateral renal artery stenosis)

Common adverse effects

Dizziness
Hyperkalemia
Hypotension (more common with hypovolemia)
Creatinine elevation

PregnancyFDA D

FDA category D. Drugs acting on the renin-angiotensin system cause fetal renal injury, oligohydramnios, pulmonary and skeletal hypoplasia. Discontinue when pregnancy is planned.

Breastfeeding

No data on excretion in breast milk. Not recommended during breastfeeding. Alternative antihypertensives are chosen if therapy is needed.