Hydrochlorothiazide / quinapril Side Effects

Not all side effects for hydrochlorothiazide / quinapril 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 / quinapril: oral tablet

In addition to its needed effects, some unwanted effects may be caused by hydrochlorothiazide / quinapril. 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 / quinapril:

Less common
  • Cough producing mucus
  • diarrhea
  • difficulty breathing
  • tightness in the chest
  • Blurred vision
  • confusion
  • decreased urination
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • dry mouth
  • increase in heart rate
  • irregular heartbeat
  • muscle cramps or pain
  • numbness, tingling, pain, or weakness in the hands or feet
  • rapid breathing
  • seizures
  • sunken eyes
  • sweating
  • thirst
  • trembling
  • unusual tiredness or weakness
  • weakness and heaviness of the legs
  • wrinkled skin

Some of the side effects that can occur with hydrochlorothiazide / quinapril 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
  • Coughing
  • lack or loss of strength
  • sleepiness or unusual drowsiness
  • Back pain
  • change in vision
  • difficulty having a bowel movement (stool)
  • discouragement
  • feeling sad or empty
  • impaired vision
  • irritability
  • lack of appetite
  • loss of interest or pleasure
  • trouble concentrating
  • trouble sleeping

For Healthcare Professionals

Applies to hydrochlorothiazide / quinapril: oral tablet


Hydrochlorothiazide-quinapril has been evaluated for safety in more than 1,571 patients with hypertension with 153 treated for more than one year prior to its approval by the FDA. Adverse side effects were usually mild and transient, with no relationship to gender, race, age, or total daily dosage. In controlled trials, discontinuation of therapy was reported in 2.1% of patients due to adverse side effects.


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

Respiratory side effects including reversible, dry cough has been reported in 3.2% of patients presumably due to the inhibition of the degradation of endogenous bradykinin. Cough appears to be as common in women as men, but women have, in some reviews, reported cough more often than men. Less frequently reported respiratory side effects include rhinitis (2%), upper respiratory infection (1.3%), bronchitis (1.2%) and pharyngitis (1.1%). These side effects occurred more often with placebo than with HCTZ-quinapril. Rare respiratory system side effects have included pneumonia, asthma, respiratory infiltration, lung disorder, and acute noncardiogenic pulmonary edema.


Patients with renal artery stenosis maintain glomerular filtration rate (GFR) by efferent arteriolar vasoconstriction, which is blocked by quinapril.

Although quinapril 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 especially in patients with preexisting renal insufficiency or in patients who are angiotensin-dependent, such as those with CHF. Patients with renal artery stenosis should not receive quinapril 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 HCTZ.


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

Cardiovascular side effects reported include vasodilatation, vertigo, and chest pain in 1% of patients. Palpitations and tachycardia were reported in less than 1% of patients. Rarely reported side effects include heart failure, myocardial infarction, cerebrovascular accident, hypertensive crisis, orthostatic hypotension, and cardiac rhythm disturbance. Additional postmarketing side effects include bradycardia, cor pulmonale, vasculitis, and deep thrombosis. 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 quinapril, since ACE inhibitors may decrease serum aldosterone.


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..

There have been approximately 34 known cases of thiazide-induced pulmonary edema, encompassing 52 episodes of pulmonary edema, as of 1991 (per a 1996 review). In some cases, doses as small as 12.5 mg were associated with the development of pulmonary edema. The average time to onset of this adverse reaction was 44 minutes, women have a relative risk of 9:1, and the average age was 56 years. The mortality rate was 6%. Some experts consider this side effect grossly underreported.

Hypersensitivity reactions to angiotensin converting enzyme (ACE) inhibitors may be life threatening. Angioedema of the face, extremities, lips, tongue, glottis and/or pharynx have been reported rarely in patients receiving ACE inhibitors. 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 HCTZ have included nausea, vomiting, diarrhea, and rash in less than 1% of patients. Acute pulmonary edema, interstitial cystitis, interstitial nephritis, and anaphylaxis have rarely been associated with the use of HCTZ.

Nervous system

Nervous system side effects have included headache (5.7%), dizziness (4.8%), fatigue (2.9%), insomnia (1.2%), somnolence (1.2%), and asthenia (1.1%). Rare cases of cerebrovascular insufficiency have been associated with HCTZ-induced plasma volume contraction. Postmarketing side effects include paralysis, hemiplegia, speech disorder, abnormal gait, meningism, and amnesia.


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.

Metabolic side effects including hypokalemia associated with HCTZ is much less likely with the addition of quinapril because ACE inhibitors may decrease serum aldosterone levels. By the same token, the mild hyperkalemia, although clinically insignificant, that often accompanies the use of quinapril, is much less likely due to HCTZ-induced kaliuresis. HCTZ can induce metabolic alkalosis, hyponatremia, hypomagnesemia, hypercalcemia, hyperglycemia, and elevated serum uric acid levels. It may also increase serum cholesterol.


Hematologic side effects are rare. Neutropenia and bone marrow depression have rarely been associated with quinapril and other ACE inhibitors. Isolated cases of immune-complex hemolytic anemia, aplastic anemia, and thrombocytopenia have been associated with HCTZ.

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.


Gastrointestinal disturbances have included nausea and vomiting (1.8%), abdominal pain (1.7%), diarrhea (1.4%), and dyspepsia (1.2%). Dry mouth and gastrointestinal hemorrhage have been reported in less than 1% of patients. Rare cases of pancreatitis and acute cholecystitis have been associated with HCTZ.

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


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 HCTZ include 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 HCTZ. Rare instances of pruritus, increased sweating, erythema, alopecia, and pemphigus have been reported in 1% or less of patients. Postmarketing side effects reported include urticaria, maculopapular rash, and petechiae.


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

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.


Musculoskeletal side effects have rarely been reported and include myalgias, chills, myopathy, myositis, muscle spasm, back pain, and arthritis.


Genitourinary complaints are limited to impotence in less than 1% of male patients.


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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