Hydrochlorothiazide / lisinopril Side Effects

Not all side effects for hydrochlorothiazide / lisinopril may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to hydrochlorothiazide / lisinopril: oral tablet

In addition to its needed effects, some unwanted effects may be caused by hydrochlorothiazide / lisinopril. In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking hydrochlorothiazide / lisinopril:

Less common
  • Blurred vision
  • body aches or pain
  • chills
  • confusion
  • cough
  • diarrhea
  • difficulty breathing
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • ear congestion
  • fever
  • headache
  • loss of voice
  • nasal congestion
  • nausea
  • runny nose
  • sneezing
  • sore throat
  • sweating
  • unusual tiredness or weakness
  • vomiting

Some of the side effects that can occur with hydrochlorothiazide / lisinopril may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

Less common
  • Acid or sour stomach
  • belching
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • decreased interest in sexual intercourse
  • heartburn
  • inability to have or keep an erection
  • indigestion
  • lack or loss of strength
  • loss in sexual ability, desire, drive, or performance
  • muscle cramps
  • rash
  • stomach discomfort, upset, or pain

For Healthcare Professionals

Applies to hydrochlorothiazide / lisinopril: oral tablet


Cardiovascular side effects are relatively common. Hypotension and orthostasis have been associated with lisinopril and hydrochlorothiazide (HCTZ) in approximately 1.4% and 3.2% of patients, respectively. In one study, the incidence of hypotension-related undesirable side effects was 4% in patients with congestive heart failure (CHF), compared to 0.6% in patients without CHF. Angina pectoris or palpitations have been reported in approximately 1% of patients. HCTZ-induced hypokalemia can predispose some patients to various cardiac arrhythmias, such as ventricular ectopy and complete AV heart block. Hypokalemia is much less likely with the addition of lisinopril, since ACE inhibitors may decrease serum aldosterone. Angioneurotic edema (0.2% of patients) has been associated with lisinopril therapy.

Hypotension is most likely in patients who are sodium and intravascular volume depleted.

A possible relationship between lisinopril use and a case of penile angioedema has been published. After six days of lisinopril therapy, a 74-year-old patient complained of penile "swelling". Lisinopril was suspected as the cause of the angioedema and was discontinued. The localized angioedema resolved within a few days following discontinuation.


Patients with renal artery stenosis maintain glomerular filtration by efferent arteriolar vasoconstriction, which is blocked by lisinopril.

Although lisinopril may be associated with a rise in serum creatinine and BUN, GFR has been shown to remain unchanged or improve in most patients.

HCTZ has been used to treat nephrogenic diabetes insipidus. However, a case in which the drug was believed to have caused this condition has been reported.

Renal side effects including new or worsened renal insufficiency may develop in up to 10% of patients. This problem may be more likely in patients with preexisting renal insufficiency or who are angiotensin-dependent, such as patients with CHF. Patients with renal artery stenosis should not receive lisinopril or any other ACE inhibitor since it may precipitate acute renal failure. While there is a growing body of literature describing decreased proteinuria in some patients, new onset proteinuria may develop during ACE inhibition. Rare cases of interstitial nephritis have been associated with hydrochlorothiazide.

Nervous system

Nervous system side effects have included dizziness in 8% and headache in 5% of patients. Paresthesias are reported in 2% of patients. Rare cases of cerebrovascular insufficiency have been associated with hydrochlorothiazide-induced plasma volume contraction.


Respiratory side effects, including reversible dry cough, have been reported in up to 4% of patients. Cough appears to be as common in women as men, but in some reviews, women have reported cough more often than men. Rare respiratory system side effects include stridor associated with lisinopril and acute noncardiogenic pulmonary edema associated with hydrochlorothiazide.

A retrospective study has revealed a significantly higher incidence of discontinuation of ACE inhibitor therapy due to cough among black patients compared to non-black patients (9.6% vs. 2.4%).


In at least two cases of lisinopril-associated angioedema of the face and neck, the affected patients did not have a history of reactive airways disease. Patients with intestinal angioedema generally present with abdominal pain (with or without nausea or vomiting) and in some cases there was no prior history of facial angioedema, and C-1 esterase levels were normal. These symptoms resolve after stopping the ACE inhibitor.

A 68-year-old man with a history of hypertension, diabetes mellitus, stroke, and myocardial infarction developed dyspnea, chest tightness, and increased oxygen requirements one week after beginning lisinopril. Associated findings included a truncal rash, arterial acidosis, and vocal cord edema and erythema per bronchoscopy. The patient required artificial airway management and corticosteroid therapy. Lisinopril was not at first suspected, and due to improvement, the patient was extubated. While still receiving lisinopril, stridor and dyspnea persisted, requiring reintubation of the patient. Once suspected, lisinopril was discontinued, and the patient improved without recurrent respiratory complaints.

A 68-year-old man with a history of myocardial infarction (MI) developed dyspnea, chest tightness, a low grade fever, dizziness, sweating, and vomiting associated with cyanosis, a mild leukocytosis, radiographic evidence of pulmonary edema, clinical evidence of hypovolemia, and respiratory acidosis. MI and infection were ruled out. The patient recovered after restoration of his intravascular volume with saline and albumin. The only precipitating factor per history was the ingestion of HCTZ, which the patient had taken without incident for two years. Rechallenge resulted in recurrent acute pulmonary edema. Other signs of hypersensitivity, such as rash and eosinophilia, were absent.

Hypersensitivity reactions to either drug are rare but may be life-threatening. Rash is reported in less than 2% of patients. ACE inhibitor-induced angioedema occurs in approximately 0.2% of patients. Angioedema of the face, extremities, lips, tongue, glottis and/or pharynx have been reported rarely in patients receiving ACE inhibitors. Obstructive laryngeal and glossal angioedema due to lisinopril is a rare, but potentially fatal reaction. In addition, intestinal angioedema has been reported in patients treated with ACE inhibitors. It is recommended that any patient with dyspnea, dysphagia, or significant facial angioedema stop therapy immediately and avoid ACE inhibitor therapy in general.

Hypersensitivity reactions to hydrochlorothiazide may present as nausea, vomiting, diarrhea, or rash. Case reports of acute pulmonary edema, interstitial cystitis, interstitial nephritis, and anaphylaxis have been associated with hydrochlorothiazide.


Metabolic side effects including hypokalemia associated with hydrochlorothiazide is much less likely with the addition of lisinopril because ACE inhibitors may decrease serum aldosterone levels. By the same token, the mild hyperkalemia, although clinically insignificant, that often accompanies the use of lisinopril, is much less likely due to hydrochlorothiazide-induced kaliuresis. Hydrochlorothiazide can induce hypochloremic metabolic alkalosis, hyponatremia, hypomagnesemia, hypercalcemia, hyperglycemia, and elevated serum uric acid levels. It may also increase serum cholesterol. Lisinopril and other ACE inhibitors appear to have a beneficial effect on plasma insulin levels. Cases of hypoglycemia have been reported in diabetic patients receiving ACE inhibitors when concurrently treated with oral antidiabetic agents or insulin.

HCTZ may increase total serum cholesterol by 11%, LDL lipoprotein cholesterol by 12%, and VLDL lipoprotein cholesterol levels by 50%, as well as reduce insulin secretion. It should be used with caution in patients with diabetes or hypercholesterolemia.

Hyperuricemia may be an important consideration in patients with a history of gout. Hypophosphatemia and low serum magnesium concentrations may also occur, but are usually clinically insignificant except in malnourished patients.


A 67-year-old white woman with hypothyroidism, hypercalcemia, depression, and hypertension developed facial erythema, headaches, tremors, confusion, and personality changes associated with a new positive ANA and anti-nRNP, and skin biopsy consistent with lupus erythematosus while taking HCTZ, levothyroxine, and amitriptyline. The eruption resolved upon discontinuation of HCTZ, but she later developed a higher ANA titer associated with symptomatic diffuse interstitial pulmonary infiltrates. She was successfully treated with corticosteroids.

Dermatologic reactions associated with hydrochlorothiazide have included erythema annular centrifugum, acute eczematous dermatitis, and morbilliform or leukocytoclastic vasculitis. Thiazides may induce phototoxic dermatitis. In addition, a rare, distinct entity with clinical and laboratory features indistinguishable from those of subacute cutaneous lupus erythematosus has been associated with hydrochlorothiazide. Rare instances of urticaria, alopecia, herpes zoster, photosensitivity, skin lesions, skin infections, pemphigus, erythema, psoriasis, and rare cases of other severe skin reactions, including toxic epidermal necrolysis and Stevens-Johnson Syndrome, (causal relationship has not been established), have been associated with lisinopril.


Thiazide diuretics may increase serum cholesterol and triglycerides, resulting in an increased risk of cholesterol gallstone formation. Cases of bowel strictures associated with thiazide ingestion have been reported in the 1960's, although these patients were on a combination HCTZ-potassium product.

Gastrointestinal disturbances have included diarrhea (3%), nausea (2%), and vomiting (1%) in patients treated with lisinopril. Taste disturbances and constipation are reported in less than 1% of patients taking lisinopril alone. Rare cases of pancreatitis have been associated with lisinopril and HCTZ. In addition, rare cases of acute cholecystitis have been associated with HCTZ.


Endocrinologic problems associated with thiazide diuretics have included glucose intolerance and a potentially deleterious effect on the lipid profile, either of which may be important in some patients with or who are at risk for diabetes or coronary artery disease.

Case reports have suggested that lisinopril may rarely result in the development of the syndrome of inappropriate secretion of antidiuretic hormone.

A prospective study of 34 patients who received oral thiazide diuretics for 14 years without interruption revealed an increased mean fasting blood glucose level after treatment. Withdrawal of thiazide therapy for seven months in 10 of the patients resulted in mean reductions of 10% in fasting blood glucose and 25% in the 2-hour glucose tolerance test value. A control group was not reported.


A case of a 52-year-old man who developed noninfectious hematuria, proteinuria, and IgA leukocytoclastic vasculitis has been reported. Lisinopril alone was discontinued, and the patient recovered within three months.

There are rare case reports of HCTZ-induced immune hemolytic anemia. The following illustrates a fatal case:

A 53-year-old man with hypertension developed nausea, vomiting, diarrhea, and progressive anorexia and weakness associated with scleral icterus, anemia with spherocytosis, dark red urine with proteinuria, bilirubinuria, hemoglobinuria, and elevated lactic dehydrogenase levels 18 months after beginning HCTZ and methyldopa. Haptoglobin was less than 50 mg/dL. Direct and indirect Coombs tests were positive. The patient died suddenly. Autopsy revealed no obvious cause of death, left ventricular hypertrophy, and mild coronary atherosclerosis.

Hematologic side effects are rare. Neutropenia and bone marrow depression have rarely been associated with lisinopril and other ACE inhibitors. Isolated cases of immune-complex hemolytic anemia, aplastic anemia, and thrombocytopenia have been associated with hydrochlorothiazide. A case of Henoch-Schonlein purpura complicated by polyarthritis has been associated with lisinopril.


Musculoskeletal cramps have been reported in 2% of patients.


Genitourinary complaints are limited to impotence in approximately 1% of male patients treated with hydrochlorothiazide.


Other side effects associated with the lisinopril component have included olfactory disturbance.


Ocular side effects have included idiosyncratic reactions to the hydrochlorothiazide component resulting in acute transient myopia and acute angle-closure glaucoma.

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