Lisinopril

Is lisinopril safe?

For most adults with high blood pressure or heart failure, yes. Lisinopril has been on the US market since 1988, it is cheap, and serious harm is uncommon. We score it 79. The catches are specific and worth knowing: it must not be used in pregnancy, it can rarely cause swelling of the face and throat, and it raises potassium, which matters if you also take potassium supplements, certain diuretics or regular anti-inflammatory painkillers.

Lisinopril is an ACE inhibitor, sold as Zestril and Prinivil, and combined with hydrochlorothiazide as Zestoretic. The US label starts most adults on 10 mg once a day (5 mg if they already take a diuretic). The usual range is 20 mg to 40 mg once a day; doses up to 80 mg have been used but do not seem to add much.

How rare is angioedema?

Angioedema is swelling under the skin, usually of the lips, tongue, face or throat. With ACE inhibitors it can appear on the first day or after years of trouble-free use, which is why it catches people out. If it involves the tongue or larynx it can block the airway, and the label notes that some reactions have been fatal.

The best numbers come from the FDA's Mini-Sentinel programme, which followed 1.8 million people starting an ACE inhibitor between 2001 and 2010. In the first year, 1.79 per 1,000 developed angioedema, against 0.62 per 1,000 on ARBs and 0.58 on beta-blockers. In the OCTAVE trial of 25,302 people, 0.68% of those on enalapril, a close relative of lisinopril, had angioedema within 24 weeks. The risk is higher in Black patients (both the label and the NHS say so), in people with a past episode, and in those also taking mTOR inhibitors such as sirolimus or the heart failure drug sacubitril.

A rarer form affects the gut and shows up as stomach pain with nausea or vomiting, sometimes with no facial swelling at all. It is easy to miss, so mention lisinopril if you go to hospital with unexplained abdominal pain.

The cough and other common effects

The side effect people notice most is a dry, nagging cough. In US hypertension trials, headache was 3.8 percentage points more common than on placebo, dizziness 3.5 points and cough 2.5 points, and 5.7% of people stopped lisinopril because of side effects. The cough is harmless but can last for weeks, and it is a common reason doctors switch to an ARB such as losartan.

Dizziness is most likely in the first few days, and when you are dehydrated from heat, sweating, vomiting or diarrhoea. Lisinopril can also reduce kidney function, mainly in people with narrowed kidney arteries, severe heart failure or dehydration, so doctors check kidney function and potassium with blood tests.

Pregnancy: the boxed warning

All drugs that act on the renin-angiotensin system, ACE inhibitors and ARBs alike, carry the same 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. Used in the second and third trimesters, they reduce the baby's kidney function and can cause low amniotic fluid, underdeveloped lungs and skull, kidney failure and death. The label says to discontinue lisinopril as soon as pregnancy is detected, and the NHS says doctors will recommend a safer alternative. If you could become pregnant, talk to your doctor about contraception and about a plan for switching before trying to conceive.

Interactions that matter

Combined with	Risk	Label advice
Potassium supplements, potassium salt substitutes, spironolactone, amiloride, triamterene	High potassium	Monitor potassium; ask before using salt substitutes
NSAIDs (ibuprofen, naproxen, celecoxib)	Kidney injury, weaker blood pressure control	Monitor kidney function
Other ACE inhibitors, ARBs, aliskiren	High potassium, kidney injury, low blood pressure	Generally avoid; aliskiren 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 diabetes
Sacubitril/valsartan (Entresto)	Angioedema	Do not take within 36 hours of each other
Lithium	Lithium toxicity	Monitor lithium levels
Insulin, diabetes tablets	Low blood sugar, mainly in the first month	Monitor blood sugar

The NSAID combination matters most in everyday life because ibuprofen and naproxen are sold over the counterOver-the-counterA medicine you can buy without a prescription, in a pharmacy or shop, with directions on the pack for safe use without a doctor.More in the glossary. Combined with a diuretic as well, the three together can tip an older or dehydrated person into kidney injury. Our ibuprofen page explains the wider risks.

Who should be careful

• Anyone who is pregnant, trying to conceive or breastfeeding.
• People who have had angioedema before, from any cause.
• People with kidney disease, diabetes or heart failure, who are more prone to high potassium.
• Anyone on dialysis with high-flux membranes or having bee or wasp venom desensitisation, where the label reports serious allergic-type reactions.

In an overdose the main danger is a big drop in blood pressure; in the US call Poison Control on 1-800-222-1222, and in the UK call 111 or go to A&E. Many people take lisinopril alongside a statin such as atorvastatin or diabetes medicines such as metformin. If side effects bother you, talk to your doctor or pharmacist rather than stopping, because uncontrolled blood pressure carries its own risks.

How we scored it

Dependence (98), track record (95) and 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 (88) are strong. Serious side effects (76) reflects rare but potentially fatal angioedema, high potassium and kidney effects. Interactions (65) and 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 (50) are the weakest factors.