Losartan

Is losartan safe?

Yes, for most adults who are not pregnant. Losartan, sold as Cozaar since 1995, is an angiotensin II receptor blocker (ARB). In US trials its side effect rate was close to placebo's: 2.3% of people stopped it because of side effects, against 3.7% of those on a dummy pill. We score it 81, slightly above the ACE inhibitor lisinopril because it causes far less cough and angioedema.

What lowers the score is the paperwork, not the pills people take today: a boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary for pregnancy shared with all drugs of its type, and a long run of recalls of generic tablets over impurities between 2018 and 2022.

The US label starts most adults on 50 mg once a day, with a maximum of 100 mg. People who are dehydrated or on diuretics, and those with mild to moderate liver problems, start on 25 mg. Losartan is also used to protect the kidneys in type 2 diabetes and is combined with hydrochlorothiazide as Hyzaar.

What happened with the losartan recalls?

In summer 2018 the FDA reported that some generic ARBs, starting with valsartan, contained nitrosamines, impurities that the agency calls probable or potential human carcinogens. Losartan was drawn in soon after:

Date	Maker	Impurity
November 2018	Sandoz (losartan with hydrochlorothiazide)	NDEA
December 2018 to September 2019	Torrent, in several expanding rounds	NDEA, then NMBA
February to March 2019	Hetero Labs, sold by Camber (87 lots)	NMBA
March 2020	Teva, Avet	NMBA
March to May 2022	Lupin, Macleods, Strides	Azido impurity

The FDA said in March 2019 that the Hetero recall was the first caused by NMBA, the third nitrosamine found in ARBs. Many repackagers then recalled their own stock, which is why the FDA enforcement database lists dozens of losartan recalls.

How big was the risk? The FDA's worst-case estimate, made for valsartan, was that if 8,000 people took the highest dose containing NDMA every day for four years, there might be one extra case of cancer over their lifetimes. It described the risk to individual patients as very low, said most people were exposed to far less, and advised patients to keep taking their medicine until a pharmacist or doctor provided a replacement, because untreated high blood pressure is the bigger danger.

Side effects: better than ACE inhibitors on two counts

Cough is the clearest advantage. In two label trials of people who had coughed on an ACE inhibitor, the cough came back in 17% and 29% on losartan, against 69% and 62% on lisinopril. Rates on losartan were close to those on a diuretic or placebo (25% and 35%), which shows that much of what remained was not caused by the drug.

Angioedema, the sudden swelling of lips, tongue or throat, is rarer too. In the FDA's Mini-Sentinel study of new users, 0.62 per 1,000 people starting an ARB had angioedema within a year, close to the rate on beta-blockers and about a third of the ACE inhibitor rate. It is not zero: the label reports cases with airway swelling, some in people who had reacted to ACE inhibitors before.

The common effects are mild: dizziness (3% against 2% on placebo), and, according to the NHS, tiredness, headache and swollen ankles. Losartan can raise potassium and reduce kidney function, particularly in people with kidney disease, narrowed kidney arteries or severe heart failure, so doctors check blood tests.

Pregnancy and interactions

The boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary is the same as for every ACE inhibitor and ARB. Used in the second and third trimesters, losartan can damage the baby's kidneys and cause low amniotic fluid, skull and lung problems, and death. The label says to stop it as soon as pregnancy is detected, and the NHS says it is not usually used in pregnancy. If you could become pregnant, talk to your doctor about a plan before trying to conceive.

The interactions mirror those of lisinopril:

• Potassium supplements, potassium salt substitutes and potassium-sparing diuretics: risk of high potassium.
• NSAIDs such as ibuprofen and naproxen: possible kidney injury and weaker blood pressure control, most of all in older or dehydrated people on diuretics.
• Lithium: levels can rise to toxic ones.
• ACE inhibitors or aliskiren: more kidney injury and high potassium with no added benefit; aliskiren is contraindicatedContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary in people with diabetes.

Who should be careful

• Anyone pregnant, trying to conceive or breastfeeding.
• People with kidney disease or diabetes, who are more prone to high potassium.
• Older people who are also on a diuretic and take painkillers like ibuprofen.
• People who have had angioedema before.

In an overdose, in the US call Poison Control on 1-800-222-1222; in the UK the NHS says to call 111. If side effects or the recall history worry you, talk to your doctor or pharmacist rather than stopping. Many people take losartan with amlodipine when one medicine is not enough.

How we scored it

Dependence (98), track record (94), overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (85) and serious side effects (84) are strong. Interactions (70) reflect the potassium and NSAID risks. Regulatory warnings (45) is the weakest factor because of the pregnancy boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary and four years of impurity recalls.