Side Effects of Vaseretic (enalapril/hydrochlorothiazide)

Does Vaseretic (enalapril and hydrochlorothiazide) cause side effects?

Vaseretic (enalapril and hydrochlorothiazide) is a combination of an angiotensin converting enzyme (ACE) inhibitor and a diuretic (water pill) used to treat high blood pressure (hypertension). 

ACE is an enzyme in the body that causes the formation of angiotensin II. Angiotensin II causes the muscles surrounding the arteries in the body to contract, thereby narrowing the arteries and elevating the blood pressure

ACE inhibitors such as enalapril (Vasotec) lower blood pressure by preventing the formation of angiotensin II thereby relaxing the arteries. Hydrochlorothiazide (HCTZ) works by blocking salt and water reabsorption in the kidneys, thus causing increased urine output (diuresis). 

The mechanism of its action in lowering high blood pressure is not well understood. The combination of enalapril and HCTZ reduces blood pressure better than either drug alone.

Common side effects of Vaseretic include

Serious side effects of Vaseretic include

Drug interactions of Vaseretic include diuretics, because the combination with enalapril may cause excessive reduction in blood pressure.

  • Stopping the diuretic or increasing salt intake prior to taking enalapril may prevent excessive blood pressure reduction.
  • Enalapril may increase potassium levels (hyperkalemia) in blood. Therefore, there is an increased risk of hyperkalemia when enalapril is given with potassium supplements or drugs that increase potassium levels (for example, spironolactone).
  • There have been reports of increased lithium levels when lithium is used in combination with ACE inhibitors, which may lead to toxicity from lithium. Hydrochlorothiazide reduces the elimination of lithium by the kidneys and can lead to lithium toxicity.
  • 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.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the blood pressure lowering effects of hydrochlorothiazide.
  • Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and low blood pressure) may occur when injectable gold (sodium aurothiomalate), used in the treatment of rheumatoid arthritis, is combined with ACE inhibitors, including enalapril.
  • Blood sugar levels can be elevated by hydrochlorothiazide, necessitating adjustment in the doses of medications that are used for treating diabetes.
  • Combining hydrochlorothiazide with corticosteroids may increase the risk for low levels of blood potassium and other electrolytes.
  • Low blood potassium (hypokalemia) can increase the toxicity of digoxin.
  • Cholestyramine and colestipol bind to hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by 43% to 85%. 

ACE inhibitors, including enalapril, can be harmful to the fetus and should not be taken by pregnant women. There are no adequate studies of hydrochlorothiazide in pregnant women. Thiazides may increase the risk of fetal or neonatal jaundice, low platelet levels, and possibly other adverse reactions that have occurred in adults. 

ACE inhibitors, including enalapril, should be avoided in nursing mothers. Hydrochlorothiazide is excreted in breast milk. Intense diuresis using hydrochlorothiazide may reduce the production of breast milk. 

What are the important side effects of Vaseretic (enalapril and hydrochlorothiazide)??

The side effects of the Vaseretic are similar to the side effects of the individual component drugs:

  • A dry, persistent cough has been reported commonly with the use of ACE inhibitors. Coughing resolves after discontinuing the medication.

Other side effects include of ACE inhibitors include:

In rare instances

  • liver dysfunction and skin yellowing (jaundice) have been reported with ACE inhibitors.
  • In susceptible individuals ACE inhibitors may reduce kidney function. Enalapril may cause hypersensitivity (allergic) reactions and angioedema (swelling of face, lips, tongue, throat).

Side effects of HCTZ include:

  • weakness,
  • low blood pressure,
  • sunlight sensitivity,
  • impotence,
  • nausea,
  • abdominal pain,
  • electrolyte disturbances,
  • pancreatitis,
  • jaundice,
  • anaphylaxis, and
  • rashes, both mild and severe.

Patients allergic to sulfa may also be allergic to HCTZ because of the similarity in the chemical structure of the medications.

Vaseretic (enalapril and hydrochlorothiazide) side effects list for healthcare professionals

Vaseretic has been evaluated for safety in more than 1500 patients, including over 300 patients treated for one year or more. In clinical trials with Vaseretic no adverse experiences peculiar to this combination drug have been observed.

Adverse experiences that have occurred have been limited to those that have been previously reported with enalapril or hydrochlorothiazide.

The most frequent clinical adverse experiences in controlled trials were:

  • dizziness (8.6 percent),
  • headache (5.5 percent),
  • fatigue (3.9 percent) and
  • cough (3.5 percent).

Generally, adverse experiences were mild and transient in nature. Adverse experiences occurring in greater than two percent of patients treated with Vaseretic in controlled clinical trials are shown below.

Percent of Patients in Controlled Studies
(n=1580) Incidence (discontinuation)
(n=230) Incidence
Dizziness8.6 (0.7)4.3
Headache5.5 (0.4)9.1
Fatigue3.9 (0.8)2.6
Cough3.5 (0.4)0.9
Muscle Cramps2.7 (0.2)0.9
Nausea2.5 (0.4)1.7
Asthenia2.4 (0.3)0.9
Orthostatic Effects2.3 (<0.1)0.0
Impotence2.2 (0.5)0.5
Diarrhea2.1 (<0.1)1.7

Clinical adverse experiences occurring in 0.5 to 2.0 percent of patients in controlled trials included:

  • Body as a Whole: Syncope, chest pain, abdominal pain
  • Cardiovascular: Orthostatic hypotension, palpitation, tachycardia
  • Digestive: Vomiting, dyspepsia, constipation, flatulence, dry mouth
  • Nervous/Psychiatric: Insomnia, nervousness, paresthesia, somnolence, vertigo
  • Skin: Pruritus, rash
  • Other: Dyspnea, gout, back pain, arthralgia, diaphoresis, decreased libido, tinnitus, urinary tract infection
  • Angioedema: Angioedema has been reported in patients receiving Vaseretic, with an incidence higher in black than in non-black patients. Angioedema associated with laryngeal edema may be fatal. If angioedema of the face, extremities, lips, tongue, glottis and/or larynx occurs, treatment with Vaseretic should be discontinued and appropriate therapy instituted immediately.
  • Hypotension: In clinical trials, adverse effects relating to hypotension occurred as follows: hypotension (0.9 percent), orthostatic hypotension (1.5 percent), other orthostatic effects (2.3 percent). In addition syncope occurred in 1.3 percent of patients.
  • Cough: See prescribing information.

Clinical Laboratory Test Findings

  • Serum Electrolytes: See prescribing information.
  • Creatinine, Blood Urea Nitrogen: In controlled clinical trials minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 0.6 percent of patients with essential hypertension treated with Vaseretic. More marked increases have been reported in other enalapril experience. Increases are more likely to occur in patients with renal artery stenosis.
  • Serum Uric Acid, Glucose, Magnesium, and Calcium: See prescribing information.
  • Hemoglobin and Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.3 g percent and 1.0 vol percent, respectively) occur frequently in hypertensive patients treated with Vaseretic but are rarely of clinical importance unless another cause of anemia coexists. In clinical trials, less than 0.1 percent of patients discontinued therapy due to anemia.
  • Liver Function Tests: Rarely, elevations of liver enzymes and/or serum bilirubin have occurred.
  • Other adverse reactions that have been reported with the individual components are listed below and, within each category, are in order of decreasing severity.
Enalapril Maleate

Enalapril has been evaluated for safety in more than 10,000 patients. In clinical trials adverse reactions which occurred with enalapril were also seen with Vaseretic. However, since enalapril has been marketed, the following adverse reactions have been reported:

  • Body as a Whole: Weakness;
  • Digestive: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation, anorexia;
  • Hematologic: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia;
  • Hypersensitivity: Purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions;
  • Musculoskeletal: Muscle spasm;
  • Nervous System/Psychiatric: Restlessness;
  • Renal: Renal failure, renal dysfunction, interstitial nephritis;
  • Skin: Erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis, alopecia;
  • Special Senses: Transient blurred vision, xanthopsia.

Postmarketing Experience

Non-melanoma Skin Cancer
  • Hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer.
  • In a study conducted in the Sentinel System, increased risk was predominantly for squamous cell carcinoma (SCC) and in white patients taking large cumulative doses.
  • The increased risk for SCC in the overall population was approximately 1 additional case per 16,000 patients per year, and for white patients taking a cumulative dose of ≥50,000 mg the risk increase was approximately 1 additional SCC case for every 6,700 patients per year.

To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-3214576 or FDA at 1-800-FDA-1088 or

What drugs interact with Vaseretic (enalapril and hydrochlorothiazide)?

No Information provided


Vaseretic (enalapril and hydrochlorothiazide) is a combination of an angiotensin converting enzyme (ACE) inhibitor and a diuretic (water pill) used to treat high blood pressure (hypertension). Common side effects of Vaseretic include dry and persistent cough, abdominal pain, diarrhea, dizziness, fatigue, headache, loss of appetite, nausea and vomiting, chest pain, fainting, sexual dysfunction, increased potassium levels, numbness or tingling in the hands or feet, mild rash, a sore or swollen throat, weakness, low blood pressure, sunlight sensitivity, impotence, abdominal pain, and electrolyte disturbances. ACE inhibitors, including enalapril, can be harmful to the fetus and should not be taken by pregnant women. ACE inhibitors, including enalapril, should be avoided in nursing mothers.

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