Applies to hydrochlorothiazide: oral capsule, oral tablet

Along with its needed effects, hydrochlorothiazide may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking hydrochlorothiazide:

Incidence not known

• Abdominal or stomach pain
• back, leg, or stomach pains
• black, tarry stools
• bleeding gums
• blistering, peeling, or loosening of the skin
• bloating
• blood in the urine or stools
• bloody urine
• blue lips and fingernails
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain
• chills
• clay-colored stools
• cloudy urine
• cold sweats
• confusion
• constipation
• cough or hoarseness
• coughing that sometimes produces a pink frothy sputum
• coughing up blood
• cracks in the skin
• darkened urine
• decrease in urine output or decrease in urine-concentrating ability
• decreased frequency or amount of urine
• diarrhea
• difficult, fast, or noisy breathing, sometimes with wheezing
• difficulty with breathing
• difficulty with swallowing
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position
• dry mouth
• fast or irregular heartbeat
• fever
• flushed, dry skin
• fruit-like breath odor
• general body swelling
• general feeling of discomfort or illness
• general feeling of tiredness or weakness
• greatly decreased frequency of urination or amount of urine
• headache
• hives
• increased blood pressure
• increased hunger
• increased sweating
• increased thirst
• increased urination
• indigestion
• itching
• joint pain, stiffness, or swelling
• loss of appetite
• loss of heat from the body
• lower back or side pain
• muscle cramps or pain
• nausea or vomiting
• nosebleeds
• numbness, tingling, pain, or weakness in the hands or feet
• pain in the joints or muscles
• painful or difficult urination
• pains in the stomach, side, or abdomen, possibly radiating to the back
• pale skin
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rash
• red, irritated eyes
• red skin lesions, often with a purple center
• red, swollen skin
• redness, soreness, or itching skin
• scaly skin
• seizures
• shortness of breath
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• sores, welting, or blisters
• sugar in the urine
• swelling of the face, fingers, legs, ankles, feet, or lower legs
• swollen or painful glands
• tenderness of salivary glands
• thickening of bronchial secretions
• tightness in the chest
• trembling
• troubled breathing
• unpleasant breath odor
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight loss
• vomiting of blood
• weakness and heaviness of the legs
• weight gain
• wheezing
• yellow eyes or skin

Some side effects of hydrochlorothiazide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Incidence not known

• Cramping
• decreased interest in sexual intercourse
• difficulty having a bowel movement (stool)
• feeling of constant movement of self or surroundings
• hair loss or thinning of the hair
• inability to have or keep an erection
• increased sensitivity of the skin to sunlight
• loss in sexual ability, desire, drive, or performance
• muscle spasm
• pinpoint red or purple spots on the skin
• redness or other discoloration of the skin
• restlessness
• sensation of spinning
• severe sunburn
• weakness

Applies to hydrochlorothiazide: compounding powder, oral capsule, oral solution, oral tablet

Frequency not reported: Electrolyte imbalance, hyperglycemia, glycosuria, hyperuricemia, mild hypokalemia (decrease of 0.5 mEq/L) occurs in up to 50% of patients (and may predispose patients to cardiac arrhythmias), metabolic alkalosis, hyponatremia, hypomagnesemia, hypercalcemia, hyperglycemia, elevated serum uric acid levels, glucose intolerance and a potentially deleterious effect on the lipid profile (i.e., increased serum cholesterol)

Since hydrochlorothiazide 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. True glucose intolerance may develop in approximately 3% of patients. It is typically reversible within six months after discontinuation of therapy.

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

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 is 44 minutes, women carry a relative risk of 9:1, and the average age is 56 years. The mortality rate is 6%. Some experts consider this side effect grossly underreported.

Frequency not reported: Anaphylactic reactions, necrotizing angiitis (vasculitis and cutaneous vasculitis), respiratory distress (including pneumonitis and pulmonary edema), photosensitivity, fever, urticaria, rash, purpura, toxic epidermal necrolysis

A 67-year-old 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 a skin biopsy consistent with lupus erythematosus while taking hydrochlorothiazide (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.

Frequency not reported: Erythema multiforme (including Stevens-Johnson syndrome), exfoliative dermatitis (including toxic epidermal necrolysis), alopecia, erythema annular centrifugum, acute eczematous dermatitis, morbilliform and leukocytoclastic vasculitis, phototoxic dermatitis

Although hydrochlorothiazide 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.

Frequency not reported: Renal insufficiency (manifest as an increase in serum creatinine and BUN may occur due to hydrochlorothiazide-induced intravascular volume depletion), interstitial nephritis, renal failure

Frequency not reported: Hypotension including orthostatic hypotension (may be aggravated by alcohol, barbiturates, narcotics or antihypertensive drugs), cardiac arrhythmias (including ventricular ectopy and complete AV heart block)

The incidence of premature ventricular contractions as measured by 48-hour ambulatory ECG monitoring is the same in both patients with and without left ventricular hypertrophy despite a similar fall in serum potassium concentrations.

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

Frequency not reported: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), diarrhea, vomiting, sialadenitis, cramping, constipation, gastric irritation, nausea, anorexia, acute cholecystitis

Although rare, nearly 40 cases of hydrochlorothiazide-induced noncardiogenic pulmonary edema have been reported including at least two fatalities. Onset of symptoms can occur within minutes (range 10 to 150 minutes) of first exposure to the drug. Associated symptoms include dyspnea, hypoxia, respiratory distress, wheezing, cough, tachypnea, dizziness, nausea, vomiting, diarrhea, and hypotension. Ninety percent of cases have occurred in women at a mean dose of 38.7 mg. Treatment varies, but following discontinuation of hydrochlorothiazide most patients respond, with symptoms resolving in a mean 3.5 days. Rechallenge can result in a more severe reaction, even months to years after the initial exposure. Rechallenge with any thiazide diuretic is not recommended.

Rare (less than 0.1%): Acute noncardiogenic pulmonary edema

There are rare case reports of hydrochlorothiazide-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 hydrochlorothiazide 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.

Rare (less than 0.1%): Allergic vasculitis, hemolytic anemia, development of a rash histologically identical to subacute cutaneous lupus

Frequency not reported: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia

Frequency not reported: Muscle spasm, myalgias

Frequency not reported: Weakness, vertigo, paresthesias, dizziness, headache, restlessness, chills

Frequency not reported: Transient blurred vision, idiosyncratic reactions to hydrochlorothiazide resulting in acute transient myopia and acute angle-closure glaucoma, xanthopsia

Frequency not reported: Impotence