Lisinopril is a widely prescribed angiotensin-converting enzyme (ACE) inhibitor. It is primarily used to treat high blood pressure, manage heart failure, and improve outcomes following a heart attack. Lisinopril works by blocking the production of Angiotensin II, a hormone that constricts blood vessels, leading to vessel widening and a subsequent reduction in blood pressure.
A drug interaction occurs when a substance, such as a medication, food, or supplement, changes how another drug works in the body. These changes can alter Lisinopril’s absorption, elimination, or effect, potentially leading to reduced effectiveness or increased harmful side effects. Since Lisinopril affects the renin-angiotensin-aldosterone system, patients must discuss potential interactions with their healthcare provider before starting treatment.
Medications That Elevate Potassium Levels
Lisinopril reduces the level of the hormone aldosterone, causing the body to retain potassium. The danger arises when other medications that also increase potassium levels are taken concurrently, leading to hyperkalemia, or dangerously high blood potassium.
Hyperkalemia can disrupt the heart’s electrical signaling, potentially causing life-threatening heart rhythm abnormalities. Common interacting groups include potassium-sparing diuretics (spironolactone, amiloride, and triamterene) and potassium supplements.
Non-prescription products like salt substitutes, which replace sodium chloride with potassium chloride, can also significantly raise potassium levels. Additionally, the antibiotic Trimethoprim (often combined with Sulfamethoxazole in Bactrim) can impair potassium excretion. Symptoms include muscle weakness, tingling or numbness, and an irregular heartbeat.
NSAID Interactions
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), such as ibuprofen (Advil, Motrin) and naproxen (Aleve), are a common and hazardous interaction with Lisinopril. Lisinopril helps maintain kidney blood flow, while NSAIDs cause constriction of the blood vessels leading to the kidney’s filtering units.
When taken together, these opposing actions severely reduce blood flow and pressure within the kidney’s filtration system. This can rapidly lead to acute kidney injury (AKI), a sudden loss of kidney function.
The risk is significantly heightened for older patients, those with pre-existing kidney issues, or those also taking a diuretic—a combination often called the “Triple Whammy.” This three-drug combination drastically restricts the kidney’s ability to filter waste and maintain fluid balance.
Because NSAIDs are readily available over-the-counter, patients may not realize the severity of this interaction. Patients taking Lisinopril should avoid regular use of these pain relievers unless approved by a physician. Acetaminophen (Tylenol) is a safer alternative for minor aches and pains.
Drugs Used for Blood Pressure or Heart Conditions
Combining Lisinopril with other medications intended to lower blood pressure can result in severe hypotension. The most regulated combination involves dual inhibition of the Renin-Angiotensin-Aldosterone System (RAAS), such as pairing Lisinopril with an Angiotensin Receptor Blocker (ARB) like Losartan, or a Direct Renin Inhibitor like Aliskiren.
Although dual RAAS blockade was once studied for greater benefits, clinical trials showed it increases the risk of severe side effects, including hyperkalemia and acute kidney injury. It does not offer additional cardiovascular protection compared to using a single drug. Therefore, this combination is typically avoided unless under highly specialized monitoring.
Combining Lisinopril with other blood pressure medications, such as alpha-blockers or other vasodilators, can also produce an exaggerated effect. This can cause a “first-dose” phenomenon, where the initial dose results in profound hypotension, leading to dizziness or fainting.
Medications that have blood pressure-lowering effects as a side effect, such as some tricyclic antidepressants, can also exacerbate this issue. When starting a new medication in these categories, careful dosage adjustments and close medical supervision are necessary to prevent dangerous drops in blood pressure.
Guidance on Supplements and Other Medications
Lisinopril can interact with medications used for conditions other than the heart or blood pressure, requiring careful monitoring. A notable example is Lithium, used to treat bipolar disorder.
Lisinopril reduces the kidney’s ability to excrete Lithium due to its effect on sodium and fluid balance. This reduced clearance can quickly lead to toxic Lithium levels, causing symptoms like confusion, severe tremors, and muscle twitching.
Patients taking both medications must have their blood Lithium levels monitored frequently, especially when starting or changing the dose of Lisinopril.
Common substances like alcohol can also increase the effects of Lisinopril. Alcohol acts as a vasodilator, widening blood vessels, which compounds Lisinopril’s action. Drinking alcohol can result in exaggerated blood pressure lowering, causing dizziness or fainting.
Finally, many herbal and dietary supplements, such as alfalfa, dandelion, and horsetail, have potassium-elevating properties that pose the same risk as potassium supplements. It is important to maintain a complete list of all prescription drugs, over-the-counter products, and herbal supplements, and to review this list with a physician or pharmacist.