Does Zestril (lisinopril) cause side effects?

Zestril (lisinopril) is an angiotensin converting enzyme (ACE) inhibitor used to treat high blood pressure (hypertension), heart failure and to prevent kidney failure due to high blood pressure and diabetes

ACE is important because it is an enzyme responsible for producing the chemical, angiotensin II. Angiotensin II causes muscles in most arteries, including the arteries of the heart, to contract, thereby narrowing the arteries and elevating blood pressure.

ACE inhibitors such as Zestril lower blood pressure by reducing the production of angiotensin II, thereby relaxing arterial muscle and enlarging arteries. 

When the blood pressure is lower, the heart does not have to work as hard to pump blood. The arteries supplying the heart with blood also enlarge during treatment with ACE inhibitors.

This increases the flow of blood and oxygen to the heart, further improving the ability of the heart to pump blood. The effects of ACE inhibitors are particularly beneficial to people with congestive heart failure

In the kidneys, the narrowing of the arteries by angiotensin II decreases blood flow and damages the kidneys. ACE inhibitors enlarge and reduce the blood pressure in the arteries going to the kidney. This reduces damage to the kidneys caused by the high blood pressure

Common side effects of Zestril include

Serious side effects of Zestril rarely include a decrease in

Zestril should be stopped if there are symptoms or signs of an allergic reaction including

  • feelings of swelling of the face, lips, tongue or throat.

Severe allergic reactions (anaphylaxis) and hives occasionally occur.

Drug interactions of Zestril include potassium supplements or diuretics that conserve potassium, for example, hydrochlorothiazide/triamterene, since blood potassium levels may rise to dangerous levels. 

There have been reports of increased lithium levels when lithium is used in combination with ACE inhibitors. 

There have been reports that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen, indomethacin, and naproxen may reduce the effects of ACE inhibitors. 

Nitritoid reactions (symptoms of facial flushing, nausea, vomiting and hypotension) may occur when injectable gold sodium aurothiomalate used in the treatment of rheumatoid arthritis, is combined with ACE inhibitors, including Zestril.

Zestril should not be taken during pregnancy because fetuses and neonates have died when Zestril was administered during pregnancy. 

It is unknown if Zestril is excreted in breast milk. Consult your doctor before breastfeeding

What are the important side effects of Zestril (lisinopril)?

First doses of lisinopril can cause dizziness due to a drop in blood pressure.

This drug also can cause:

Like all ACE inhibitors, lisinopril may cause a nonproductive cough that resolves when the drug is discontinued.

Lisinopril should be stopped if there are symptoms or signs of an allergic reaction including feelings of swelling of the face, lips, tongue or throat. Severe allergic reactions (anaphylaxis) and hives occasionally occur.

Rarely, lisinopril may cause a decrease in red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia).

Why does lisinpril cause a cough?

Like all ACE inhibitors, lisinopril may cause a nonproductive cough that resolves when the drug is discontinued.

Zestril (lisinopril) side effects list for healthcare professionals

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Hypertension

In clinical trials in patients with hypertension treated with Zestril, 5.7% of patients on Zestril discontinued with adverse reactions.

The following adverse reactions (events 2% greater on Zestril than on placebo) were observed with Zestril alone:

  • headache (by 3.8%),
  • dizziness (by 3.5%),
  • cough (by 2.5%).
Heart Failure

In patients with systolic heart failure treated with Zestril for up to four years, 11% discontinued therapy with adverse reactions. In controlled studies in patients with heart failure, therapy was discontinued in 8.1% of patients treated with Zestril for 12 weeks, compared to 7.7% of patients treated with placebo for 12 weeks.

The following adverse reactions (events 2% greater on Zestril than on placebo) were observed with Zestril:

In the two-dose ATLAS trial in heart failure patients, withdrawals due to adverse reactions were not different between the low and high groups, either in total number of discontinuation (17-18%) or in rare specific reactions ( < 1%). The following adverse reactions, mostly related to ACE inhibition, were reported more commonly in the high dose group:

Table 1 : Dose-related Adverse Drug Reactions : ATLAS trial

High Dose
(n=1568)
Low Dose
(n=1596)
Dizziness19%12%
Hypotension11%7%
Creatinine increased10%7%
Hyperkalemia6%4%
Syncope7%5%

Acute Myocardial Infarction

Patients treated with Zestril had a higher incidence of hypotension (by 5.3%) and renal dysfunction (by 1.3%) compared with patients not taking Zestril.

Other clinical adverse reactions occurring in 1% or higher of patients with hypertension or heart failure treated with Zestril in controlled clinical trials and do not appear in other sections of labeling are listed below:

Body as a whole: Fatigue, asthenia, orthostatic effects.

Digestive: Pancreatitis, constipation, flatulence, dry mouth, diarrhea.

Hematologic: Rare cases of bone marrow depression, hemolytic anemia, leukopenia/neutropenia and thrombocytopenia.

Endocrine: Diabetes mellitus, inappropriate antidiuretic hormone secretion.

Metabolic: Gout.

Skin: Urticaria, alopecia, photosensitivity, erythema, flushing, diaphoresis, cutaneous pseudolymphoma, toxic epidermal necrolysis, Stevens - Johnson syndrome, and pruritus.

Special Senses: Visual loss, diplopia, blurred vision, tinnitus, photophobia, taste disturbances, olfactory disturbance.

Urogenital: Impotence.

Miscellaneous: A symptom complex has been reported which may include a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia, fever, vasculitis, eosinophilia, leukocytosis, paresthesia and vertigo. Rash, photosensitivity or other dermatological manifestations may occur alone or in combination with these symptoms.

Clinical Laboratory Test Findings

Serum Potassium: In clinical trials hyperkalemia (serum potassium greater than 5.7 mEq/L) occurred in 2.2% and 4.8% of Zestril-treated patients with hypertension and heart failure, respectively.

Creatinine, Blood Urea Nitrogen: Minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 2% of patients with hypertension treated with Zestril alone. Increases were more common in patients receiving concomitant diuretics and in patients with renal artery stenosis. Reversible minor increases in blood urea nitrogen and serum creatinine were observed in 11.6% of patients with heart failure on concomitant diuretic therapy. Frequently, these abnormalities resolved when the dosage of the diuretic was decreased.

Patients with acute myocardial infarction in the GISSI-3 trial treated with Zestril had a higher (2.4% versus 1.1% in placebo) incidence of renal dysfunction in-hospital and at six weeks (increasing creatinine concentration to over 3 mg/dL or a doubling or more of the baseline serum creatinine concentration).

Hemoglobin and Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.4 g% and 1.3 vol%, respectively) occurred frequently in patients treated with Zestril but were rarely of clinical importance in patients without some other cause of anemia. In clinical trials, less than 0.1% of patients discontinued therapy due to anemia.

Post-marketing Experience

The following adverse reactions have been identified during post-approval use of Zestril that are not included in other sections of labeling. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Other reactions include:

Metabolism and Nutrition Disorders

Hyponatremia, cases of hypoglycemia in diabetic patients on oral antidiabetic agents or insulin

Nervous System and Psychiatric Disorders

Mood alterations (including depressive symptoms), mental confusion, hallucinations

Skin and Subcutaneous Tissue Disorders

Psoriasis

What drugs interact with Zestril (lisinopril)?

Diuretics

  • Initiation of Zestril in patients on diuretics may result in excessive reduction of blood pressure.
  • The possibility of hypotensive effects with Zestril can be minimized by either decreasing or discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with Zestril. If this is not possible, reduce the starting dose of Zestril.
  • Zestril attenuates potassium loss caused by thiazide-type diuretics. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) can increase the risk of hyperkalemia. Therefore, if concomitant use of such agents is indicated, monitor the patient's serum potassium frequently.

Antidiabetics

  • Concomitant administration of Zestril and antidiabetic medicines (insulins, oral hypoglycemic agents) may cause an increased blood-glucose-lowering effect with risk of hypoglycemia.

Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenas e-2 Inhibitors (COX-2 Inhibitors )

  • In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including lisinopril, may result in deterioration of renal function, including possible acute renal failure.
  • These effects are usually reversible. Monitor renal function periodically in patients receiving lisinopril and NSAID therapy.
  • The antihypertensive effect of ACE inhibitors, including lisinopril, may be attenuated by NSAIDs.

Dual Blockade Of The Renin-Angiotensin System (RAS)

  • Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.
  • The VA NEPHRON trial enrolled 1448 patients with type 2 diabetes, elevated urinary-albumin-tocreatinine ratio, and decreased estimated glomerular filtration rate (GFR 30 to 89.9 ml/min), randomized them to lisinopril or placebo on a background of losartan therapy and followed them for a median of 2.2 years.
  • Patients receiving the combination of losartan and lisinopril did not obtain any additional benefit compared to monotherapy for the combined endpoint of decline in GFR, end state renal disease, or death, but experienced an increased incidence of hyperkalemia and acute kidney injury compared with the monotherapy group.
  • In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on Zestril and other agents that affect the RAS.
  • Do not co-administer aliskiren with Zestril in patients with diabetes. Avoid use of aliskiren with Zestril in patients with renal impairment (GFR < 60 ml/min).

Lithium

  • Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs, which cause elimination of sodium, including ACE inhibitors.
  • Lithium toxicity was usually reversible upon discontinuation of lithium and the ACE inhibitor.
  • Monitor serum lithium levels during concurrent use.

Gold

  • Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including Zestril.

mTOR Inhibitors

  • Patients taking concomitant mTOR inhibitor (e.g. temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema.

Summary

Zestril (lisinopril) is an angiotensin converting enzyme (ACE) inhibitor used to treat high blood pressure (hypertension), heart failure and to prevent kidney failure due to high blood pressure and diabetes. Common side effects of Zestril include dizziness due to a drop in blood pressure, nonproductive cough, nausea, headaches, anxiety, insomnia, drowsiness, nasal congestion, and sexual dysfunction. Zestril should not be taken during pregnancy because fetuses and neonates have died when Zestril was administered during pregnancy. It is unknown if Zestril is excreted in breast milk.

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Medically Reviewed on 9/25/2020
References
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Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.
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