Losartan

Key points

• In people with type 2 diabetes and nephropathy, losartan reduces the rate of progression of kidney disease, an effect measured by the doubling of serum creatinine or the need for dialysis or a kidney transplant.
• Losartan’s own terminal half-life is about 2 hours, while its active metabolite lasts longer, with a half-life of about 6 to 9 hours.
• Many patients need more than one medicine to reach their blood pressure goal.

How it works

Angiotensin II is a potent vasoconstrictor and the primary vasoactive hormone of the renin-angiotensin system, and it is an important part of the pathophysiology of hypertension. It also stimulates the adrenal cortex to release aldosterone and, according to the UK SmPC for Cozaar, stimulates smooth muscle cell proliferation. Losartan and its principal active metabolite block angiotensin II’s vasoconstrictor and aldosterone-secreting effects by selectively blocking angiotensin II from binding to the AT1 receptor, found in tissues including vascular smooth muscle and the adrenal gland. There is also an AT2 receptor found in many tissues, but it is not known to be associated with cardiovascular homeostasis. Neither losartan nor its active metabolite acts as a partial agonist at the AT1 receptor, and both bind it with much greater affinity than the AT2 receptor.

Safety specific to Losartan

Losartan carries a boxed warning for fetal toxicity. If pregnancy is detected, losartan should be discontinued as soon as possible: medicines that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. Losartan is contraindicated in the second and third trimester of pregnancy.

Losartan has been linked to angioedema (swelling of the face, lips, throat and/or tongue), and anyone with a past episode of angioedema should be closely monitored while taking it. Reported cases have included swelling of the larynx and glottis, which can obstruct the airway, and swelling of the intestine. Intestinal angioedema has been reported in people treated with angiotensin II receptor antagonists, including losartan.

People who are low on fluid or salt, for example from vigorous diuretic use, a low-salt diet, diarrhoea or vomiting, can develop symptomatic low blood pressure on losartan, particularly when treatment begins or shortly after a dose is increased.

Losartan is not recommended together with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes or other medicines that can raise blood potassium, such as trimethoprim-containing products. Electrolyte imbalances are common in people with renal impairment, with or without diabetes, and should be addressed.

Losartan combined with aliskiren-containing products is contraindicated in people with diabetes mellitus or renal impairment, defined here as a GFR below 60 ml/min per 1.73 square metres of body surface area.

When to seek urgent care

Seek urgent medical care for sudden swelling of the face, lips, tongue or throat, or for difficulty breathing: losartan has been linked to angioedema, which can include swelling of the larynx and glottis severe enough to obstruct the airway. Intestinal angioedema, with abdominal symptoms, has also been reported in people treated with losartan and other angiotensin II receptor antagonists.

Further reading

• COZAAR- losartan potassium tablet, film coated
• COZAAR 12.5 mg Film-Coated Tablets