Lisinopril interactions to avoid

Key takeaways | Drug interactions | Other interactions | Avoiding interactions | When to see a doctor

Lisinopril is a member of the drug class called angiotensin-converting enzyme inhibitors, or ACE inhibitors. It is approved by the Drug and Food Administration (FDA) to treat hypertension or high blood pressure. Known by the brand names Zestril and Qbrelis, lisinopril can also be used to treat heart failure and improve survival after a myocardial infarction or heart attack. 

Lisinopril is a popularly prescribed drug—as of 2020, it was the fourth most prescribed medication in the U.S., with almost 20 million patients filling about 89 million prescriptions. 

Lisinopril interacts with various drugs, including angiotensin II receptor blockers (ARBs), diuretics, and non-steroidal anti-inflammatory drugs (NSAIDs).

For those who take lisinopril, it’s essential to be aware of interactions that can affect lisinopril’s effectiveness and cause or worsen side effects, including serious side effects such as liver problems or high potassium levels.

Key takeaways:

• Lisinopril is an ACE inhibitor used to treat high blood pressure as well as heart failure and to improve survival after a heart attack.
• Lisinopril has various drug interactions to be aware of, such as diuretics, ARBs, NSAIDs, and others. Interactions can affect how lisinopril works and cause or worsen side effects of lisinopril.
• Always ensure a healthcare provider knows a complete medical history, medication allergies, and all medicines taken, including prescription drugs, OTC medicines, vitamins, and dietary supplements.

Lisinopril drug interactions

Lisinopril interacts with various drugs, including prescription and over-the-counter medications. Continue reading to learn more about lisinopril interactions.

Diuretics 

Sometimes, healthcare providers prescribe lisinopril and a diuretic. For example, the combination medication Hyzaar is one pill containing lisinopril and hydrochlorothiazide (HCTZ), a diuretic. Or, some individuals may take lisinopril along with a separate diuretic pill (as two separate pills). In these cases, additional blood pressure-lowering effects will be needed. 

However, people who already take a diuretic and then start taking lisinopril may have an excess lowering of blood pressure, causing blood pressure to become too low. People who take a specific type of diuretic, called a potassium-sparing diuretic (such as spironolactone), in combination with lisinopril have a higher risk of hyperkalemia (high potassium levels in the blood). Symptoms of hyperkalemia may include tiredness, weakness, nausea, muscle cramps, chest pain, an irregular heartbeat, and trouble breathing—although some individuals have no symptoms. Too much potassium can lead to a heart attack, so if any of these symptoms arise, call 911 for emergency medical help. 

People who take both lisinopril and a diuretic should monitor their potassium levels and blood pressure regularly. 

Insulin and sulfonylureas

People who use insulin for diabetes or take oral diabetes medication in the sulfonylurea drug class should consult their healthcare provider about a potential lisinopril interaction. The combination could cause an increased blood sugar-lowering effect, resulting in hypoglycemia (low blood sugar). Examples of these medications include:

• Insulins such as Novolog, Humalog, Tresiba, or Lantus
• Sulfonylurea diabetes medications such as glipizide, glimepiride, or glyburide

Nonsteroidal anti-inflammatory drugs (NSAIDs) 

NSAIDs are used for fever, pain, and inflammation. They are available in a variety of formulations—both over-the-counter (OTC) and prescription. Certain combination products contain an NSAID, too—such as Excedrin Migraine or Advil Cold and Sinus. 

In older individuals who are volume-depleted (including those who take a diuretic) or who have kidney disease, combining an NSAID with lisinopril can lead to (or worsen) kidney problems, including possible kidney failure. Healthcare providers will weigh the benefits and risks and consider other options that do not contain an NSAID, such as Tylenol (acetaminophen). If the combination of lisinopril and an NSAID is prescribed, the patient will be monitored for kidney function. Some examples of NSAIDs include:

• Advil, Motrin (ibuprofen)
• Aleve (naproxen)
• Aspirin
• Celebrex (celecoxib) 
• Mobic (meloxicam)
• Relafen (nabumetone)
• Voltaren (diclofenac)

Angiotensin receptor blockers (ARBs) and aliskiren

Angiotensin receptor blockers, or ARBs, are similar to ACE inhibitors (like lisinopril) in that they both work on a system called the renin-angiotensin-aldosterone system and lower the effects of a hormone called angiotensin-2 (AT-2). AT-2 narrows blood vessels, causing high blood pressure and potentially kidney damage, as well as worsening heart problems. ACE inhibitors and ARBs work at different parts of the renin-angiotensin-aldosterone system. ACE inhibitors decrease the amount of AT2 your body makes. ARBs work later in the process. Picture a lock and key. AT-2 is the key and needs to fit into the lock (receptor) to raise blood pressure. ARBs block the lock, so AT-2 can’t fit into the lock. By blocking the receptors, AT-2 cannot narrow the blood vessels and increase blood pressure. 

Aliskiren is a renin inhibitor that works on the renin-angiotensin-aldosterone system at an earlier stage than ACE inhibitors. 

Combining an ACE inhibitor with an ARB or aliskiren can increase the risk of hypotension (low blood pressure), high potassium levels, and kidney problems (including kidney failure). In rare cases, the combination may be prescribed with close monitoring of blood pressure, kidney function, and electrolytes. However, in most cases, an ACE inhibitor like lisinopril will not be combined with an ARB or aliskiren. People with diabetes or kidney problems (with a GFR less than 60 mL/minute) should never take lisinopril with aliskiren. 

Examples of ARBs include:

• Avapro (irbesartan)
• Benicar (olmesartan)
• Cozaar (losartan)
• Diovan (valsartan)

This list also includes combination drugs that contain an ARB, such as:

• Avalide (irbesartan/HCTZ)
• Benicar HCT (olmesartan/HCTZ)
• Diovan HCT (valsartan/HCTZ)
• Hyzaar (losartan/HCTZ)

Aliskiren can be found as a generic drug, as well as under the brand name Tekturna.

Entresto

Entresto (sacubitril/valsartan) is a combination drug classified as a neprilysin inhibitor/ARB. It’s used by people with heart failure. 

Individuals who take an ACE inhibitor such as lisinopril should not take Entresto. 

If switching to or from Entresto, at least 36 hours should elapse between taking lisinopril and taking Entresto. The combination of lisinopril and Entresto could increase the risk of angioedema, a type of swelling. In this case, angioedema could involve swelling of the face, lips, tongue, throat, or extremities, which could cause difficulty breathing or swallowing. Some reactions have been life-threatening or fatal. Some individuals have experienced intestinal angioedema.

mTOR inhibitors

A type of drug class called mTOR inhibitors has the same risk as Entresto. mTOR stands for the rapamycin signaling pathway’s mechanistic (formerly mammalian) target. Combining lisinopril with an mTOR inhibitor can increase the risk of angioedema, and the combination should not be given. 

Examples of mTOR inhibitors include:

• Afinitor (everolimus), used to treat certain types of cancers
• Zortress (everolimus), used to prevent kidney or liver transplant rejection
• Rapamune (sirolimus), used to prevent kidney transplant rejection or treat a rare lung condition called lymphangioleiomyomatosis
• Torisel (temsirolimus), used to treat renal cell cancer

Lithium 

Lithium is a mood stabilizer used to treat bipolar disorder. Combining lisinopril with lithium could result in lithium toxicity, which is generally reversible after the combination is stopped. Consult a healthcare provider for medical advice if taking lithium. The provider may want to avoid the combination or prescribe the combination but monitor lithium levels closely. 

Other lisinopril interactions

In addition to drug-drug interactions, there are some other interactions to consider.

Lisinopril and medical conditions

Lisinopril is not safe for everyone. Do not take this medication if:

• Pregnant or breastfeeding
• Allergic to (or have a history of angioedema with) lisinopril, any ACE inhibitor, or any ingredient in the medicine
• Hereditary or idiopathic angioedema is present
• Entresto is being taken
• Aliskiren is being taken in conjunction with diabetes.
• Hyperkalemia is present
• There is a history of kidney problems with previous lisinopril use or certain other kidney problems

Lisinopril and potassium

Because lisinopril can cause hyperkalemia, it’s important to discuss potassium intake with a healthcare provider. Potassium supplements, a high-potassium diet, and salt substitutes that contain potassium can all increase potassium levels. 

Check with a provider about any suggested dietary changes that may help avoid hyperkalemia, such as avoiding a high-potassium diet and salt substitutes that contain potassium. 

How to minimize lisinopril interactions

Although lisinopril has many potential interactions, in many cases, it can still be taken safely with some precautions. 

Always consult a healthcare provider before beginning a new medicine. Before starting lisinopril, make the provider aware of all medical conditions, especially if you are: 

• Are pregnant, trying to become pregnant, or breastfeeding (Individuals who are pregnant or breastfeeding should never take lisinopril)
• Have diabetes
• Have heart disease
• Have blood vessel problems
• Have a history of angioedema (swelling)
• Have kidney problems
• Have low blood pressure
• Have ever had an allergic reaction to an ACE inhibitor

Inform the doctor about any medications, including over-the-counter and prescription medications, vitamins, and supplements. While taking lisinopril, do not start any new medications unless approved by a healthcare professional.

A healthcare provider may need to change a person’s medications or adjust the dose of lisinopril (or another medicine) in case of a possible drug interaction. Always take medication as directed by a healthcare provider. 

While taking lisinopril, be aware of potential warning signs of drug interactions, such as symptoms of high potassium levels described above—or signs of liver problems such as dark urine, clay-colored stools, fatigue, and yellowing of the skin and whites of the eyes. If any questions or concerns about drug interactions arise, always consult a healthcare provider for medical advice. 

When to talk to a healthcare provider about lisinopril interactions

This article reviews various lisinopril interactions but does not list every possible interaction. Tell the healthcare providers about all medicines being taken—including prescription drugs, over-the-counter medicines, vitamins, supplements, and any existing medical conditions. This helps ensure proper management and monitoring of your condition. While taking lisinopril, do not start any new medication unless approved by a healthcare provider.