Dutoprol Side Effects

Generic Name: hydrochlorothiazide / metoprolol

Note: This page contains information about the side effects of hydrochlorothiazide / metoprolol. Some of the dosage forms included on this document may not apply to the brand name Dutoprol.

Not all side effects for Dutoprol 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 / metoprolol: oral tablet

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

More common
  • Chest pain or discomfort
  • convulsions
  • decreased urine
  • dry mouth
  • increased thirst
  • lightheadedness, dizziness, or fainting
  • loss of appetite
  • mood changes
  • muscle pain or cramps
  • nausea or vomiting
  • numbness or tingling in the hands, feet, or lips
  • shortness of breath
  • slow or irregular heartbeat
  • unusual tiredness or weakness
Less common
  • Ankle, knee, or great toe joint pain
  • decreased ability to exercise
  • difficult or labored breathing
  • joint stiffness or swelling
  • lower back or side pain
  • swelling of the face, fingers, feet, or lower legs
  • tightness in the chest
  • wheezing

If any of the following symptoms of overdose occur while taking hydrochlorothiazide / metoprolol, get emergency help immediately:

Symptoms of overdose
  • Blurred vision
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • chemical imbalance in the blood
  • cold, clammy skin
  • coma
  • confusion
  • cough
  • difficulty with breathing
  • dilated neck veins
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • drowsiness
  • extreme fatigue
  • fast or pounding heartbeat or pulse
  • frequent urination
  • headache
  • increased volume of pale, dilute urine
  • irregular breathing
  • irritability
  • mood changes
  • noisy breathing
  • not able to pass urine
  • pain or aching in the lower legs
  • pain or weakness in the hands or feet
  • seizures
  • sweating
  • trembling
  • unconsciousness
  • very drowsy or sleepy
  • weak pulse
  • weakness and heaviness of the legs
  • weight gain

Some of the side effects that can occur with hydrochlorothiazide / metoprolol 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:

More common
  • Chills
  • diarrhea
  • feeling of constant movement of self or surroundings
  • fever
  • general feeling of discomfort or illness
  • muscle aches
  • nightmares
  • runny nose
  • sensation of spinning
  • shivering
  • sleepiness
  • sore throat
  • trouble sleeping
  • unusual drowsiness, dullness, or feeling of sluggishness
Less common
  • Continuing ringing or buzzing or other unexplained noise in the ears
  • decreased interest in sexual intercourse
  • difficulty having a bowel movement (stool)
  • earache
  • hearing loss
  • inability to have or keep an erection
  • loss in sexual ability, desire, drive, or performance
  • pinpoint red or purple spots on the skin
  • weight loss

For Healthcare Professionals

Applies to hydrochlorothiazide / metoprolol: oral tablet, oral tablet extended release


Cardiovascular side effects associated with metoprolol reported in 3% of patients have included bradycardia and dyspnea. AV heart block, syncope, chest pain, hypotension, cold extremities, palpitations, peripheral edema, coronary artery spasm, congestive heart failure, and arterial insufficiency (usually of the Raynaud type) have been reported in 1% of patients. Very rarely, gangrene has been reported in patients with severe preexisting peripheral circulatory disorders.

Rarely, HCTZ-induced hypokalemia or hyponatremia have been associated with significant cardiac arrhythmias including ventricular ectopy and complete AV heart block.

A 53-year-old male with hyperlipidemia, hypertension, single-vessel coronary artery disease, and tobacco abuse developed documented right coronary artery spasm inducible by intravenous ergonovine and made more inducible with intravenous metoprolol. The authors believe that, since beta-blockade may result in unopposed alpha stimulation, the use of metoprolol (and other beta-blockers) are controversial in patients with coronary artery spasm (variant angina pectoris).


Metabolic side effects associated with metoprolol have included significant increases in VLDL cholesterol and total serum triglycerides, and significant decreases in HDL cholesterol. A case of hyperkalemia has been reported. Very rarely, weight gain has also been reported.

Metabolic side effects are commonly associated with daily HCTZ doses of 50 mg or more. Mild hypokalemia (decrease of 0.5 mEq/L) have occurred in up to 50% of patients, and have predisposed patients to cardiac arrhythmias. Metabolic alkalosis, hyponatremia, hypomagnesemia, hypercalcemia, hyperglycemia, and elevated serum uric acid levels have been commonly reported.

Severe and symptomatic hyperkalemia associated with metoprolol has been reported in a 45-year-old male with diabetes, hypertension, and dialysis-dependent diabetic nephropathy. Cellular potassium channels are beta-receptor mediated.

Since HCTZ may increase total serum cholesterol by 11%, LDL lipoprotein cholesterol by 12%, and VLDL lipoprotein cholesterol levels by 50%, and may reduce insulin secretion, it should be used with caution in diabetic patients and in those with hypercholesterolemia.

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

Nervous system

Nervous system complaints associated with the use of metoprolol include general fatigue in 1% to 10%, dizziness in 1% to 10%, headache in 0.3% to 4.0%, insomnia in 2%, and nightmares in 1% of patients. Rare cases of cerebrovascular insufficiency have been associated with HCTZ-induced plasma volume contraction.


Endocrinologic changes associated with both drugs may be important in patients with or who are at risk for diabetes or coronary artery disease. Metoprolol or hydrochlorothiazide may significantly increase VLDL cholesterol and total serum triglyceride, and significantly decrease HDL cholesterol. Thiazide diuretics can induce glucose intolerance.

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 72-year-old woman with a history of myocardial infarction, noninsulin-dependent diabetes mellitus, hypertension, chronic renal insufficiency, gout, and ACE inhibitor sensitivity was hospitalized for chest pain accompanied by pulmonary edema. During the first day of hospitalization, while intubated, she developed emergent hypertension, and was given metoprolol 5 mg IV. Within one hour, the patient developed profound tongue and lip swelling. Wheezing was absent. She was successfully treated with methylprednisolone and diphenhydramine. Besides ACE inhibitor sensitivity, there was no personal or family history of allergies, anaphylaxis, or atopic diathesis.

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 are unusual. Pruritus or rash has been reported in 5% of patients. Serious reactions, often presenting as nausea, vomiting, diarrhea, or rash, have been reported in less than 1% of patients. Case reports of acute pulmonary edema, interstitial cystitis, interstitial nephritis, and anaphylaxis have been associated with hydrochlorothiazide use.


Gastrointestinal side effects associated with metoprolol have included diarrhea (5%). Nausea, dry mouth, gastric pain, constipation, flatulence, digestive tract disorders, and heartburn have been reported in 1% of patients. Vomiting has been reported frequently. Retroperitoneal fibrosis has also been reported, although a causal relationship to metoprolol has not been established. Rare cases of pancreatitis and acute cholecystitis have been reported with hydrochlorothiazide use.

Approximately three cases of retroperitoneal fibrosis, presenting as a bowel obstruction in two and ureteral obstruction in one, are associated with metoprolol.

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


Respiratory side effects associated with metoprolol have included wheezing and dyspnea in 1% of patients. Rhinitis has also been reported. Approximately 30 case reports of acute noncardiogenic pulmonary edema have been reported with HCTZ.

Small studies in patients with asthma reveal significant decreases in maximal midexpiratory flow (MMEF), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1) associated with metoprolol relative to placebo.

In one study, metoprolol was associated with an increase in the number of obstructive breathing patterns in 5 of 12 obese male patients with hypertension.


Genitourinary complaints are limited mainly to male patients. Metoprolol may decrease free and total testosterone, although impotence occurs in only 0.2% of patients.


Dermatologic side effects associated with metoprolol very rarely have included worsening of psoriasis. A case of generalized psoriasiform lesions has been reported. Urticaria has also been reported in postmarketing experience.

Erythema annular centrifugum, acute eczematous dermatitis, and morbilliform and leukocytoclastic vasculitis have been associated with HCTZ. Phototoxic dermatitis has been reported. Rarely, a distinct entity with clinical and laboratory features indistinguishable from those of subacute cutaneous lupus erythematosus has been reported.

A 62-year-old man with ischemic heart disease developed a generalized, chronic, nummular, psoriasiform, erythematous rash that disappeared after metoprolol was withheld. Subsequent skin patch testing revealed sensitivity to metoprolol.

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 hydrochlorothiazide, but she later developed a higher ANA titer associated with symptomatic diffuse interstitial pulmonary infiltrates. She was successfully treated with corticosteroids.


Renal side effects including new or worsened renal insufficiency may occur due to hydrochlorothiazide-induced intravascular volume depletion. Rare cases of interstitial nephritis have been associated with hydrochlorothiazide use.

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


There are approximately five case reports of severe myalgias/arthralgias in patients without a history of arthritis. In one, a 60-year-old male with hypertension developed a microcytic anemia, weight loss, myalgias, anorexia, and fatigue within seven years after starting metoprolol and furosemide. The patient's signs and symptoms resolved within two months after discontinuing metoprolol. A review of the literature reveals that the most commonly affected joints are the knees and accompanying complaints may include fever and chills.

Musculoskeletal side effects associated with metoprolol have been reported extremely rarely. Cases of a polymyalgia rheumatica-like syndrome and arthralgia have been reported. Very rarely, arthritis has also been reported.

Myalgias and chills have occasionally been associated with HCTZ-induced diuresis.


Hematologic side effects are rare. Cases of immune-complex hemolytic anemia, aplastic anemia, and thrombocytopenia have been associated with HCTZ use.

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, and hemoglobinuria, and elevated lactic dehydrogenase levels 18 months after beginning HCTZ and methyldopa. Haptoglobin was less than 50 mg per 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.


Psychiatric depression has been reported in 2% to 5% of patients who were taking metoprolol alone.


A 56-year-old female with a history of migraine headaches developed seronegative hepatitis associated with metoprolol. Her signs and symptoms resolved within 48 hours after discontinuing metoprolol, and were reproducible on rechallenge.

Hepatic side effects including a single case of hepatotoxicity has been associated with the use of metoprolol.


Ocular side effects associated with metoprolol have rarely included blurred vision and dry eyes. Very rarely, photosensitivity has also been reported. FDA has received reports of idiosyncratic reactions to the hydrochlorothiazide component resulting in acute transient myopia and acute angle-closure glaucoma.

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