From the FDA Drug Label
ADVERSE REACTIONS The adverse reactions associated with hydrochlorothiazide have been shown to be dose related. In controlled clinical trials, the adverse events reported with doses of 12. 5 mg hydrochlorothiazide once daily were comparable to placebo. The following adverse reactions have been reported for doses of hydrochlorothiazide 25 mg and greater and, within each category, are listed in the order of decreasing severity. Body as a whole: Weakness Cardiovascular: Hypotension including orthostatic hypotension (may be aggravated by alcohol, barbiturates, narcotics or antihypertensive drugs). Digestive: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), diarrhea, vomiting, sialadenitis, cramping, constipation, gastric irritation, nausea, anorexia Hematologic: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia. Hypersensitivity: Anaphylactic reactions, necrotizing angiitis (vasculitis and cutaneous vasculitis), respiratory distress including pneumonitis and pulmonary edema, photosensitivity, fever, urticaria, rash, purpura Metabolic: Electrolyte imbalance (see PRECAUTIONS), hyperglycemia, glycosuria, hyperuricemia. Musculoskeletal: Muscle Spasm. Nervous System/Psychiatric: Vertigo, paresthesia, dizziness, headache, restlessness. Renal: Renal failure, renal dysfunction, interstitial nephritis (see WARNINGS) Skin: Erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis, alopecia. Special Senses: Transient blurred vision, xanthopsia. Urogenital: Impotence. Postmarketing Experience: The following adverse reaction has been identified during post-approval use of hydrochlorothiazide. Because the reaction is reported voluntarily from a population of uncertain size, it is not possible to reliably estimate the frequency or establish a causal relationship to drug exposure 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 adverse effects of hydrochlorothiazide (HCTZ) include:
- Cardiovascular: hypotension, orthostatic hypotension
- Digestive: pancreatitis, jaundice, diarrhea, vomiting
- Hematologic: aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia
- Hypersensitivity: anaphylactic reactions, necrotizing angiitis, respiratory distress, photosensitivity
- Metabolic: electrolyte imbalance, hyperglycemia, glycosuria, hyperuricemia
- Musculoskeletal: muscle spasm
- Nervous System/Psychiatric: vertigo, paresthesia, dizziness, headache, restlessness
- Renal: renal failure, renal dysfunction, interstitial nephritis
- Skin: erythema multiforme, exfoliative dermatitis, alopecia, non-melanoma skin cancer
- Special Senses: transient blurred vision, xanthopsia
- Urogenital: impotence 1
From the Research
Hydrochlorothiazide (HCTZ) can cause several adverse effects, most notably hypokalemia, which affects approximately 12.6% of users, as reported in a recent study published in the Journal of Human Hypertension 2. The most common adverse effects of HCTZ include:
- Electrolyte imbalances, particularly hypokalemia (low potassium), hyponatremia (low sodium), and hypercalcemia (high calcium)
- Increased urination, dizziness, lightheadedness, and orthostatic hypotension, especially when standing up quickly
- Metabolic effects, such as hyperglycemia (elevated blood sugar), hyperuricemia (increased uric acid levels which may trigger gout attacks), and elevated cholesterol and triglyceride levels Some patients may also experience photosensitivity reactions, skin rashes, or allergic reactions. Less common but serious side effects include severe electrolyte disturbances, kidney dysfunction, blood disorders like thrombocytopenia, and rare cases of pancreatitis. According to a study published in the Journal of Human Hypertension, factors associated with hypokalemia in HCTZ users include female sex, non-Hispanic black ethnicity, underweight, and long-term therapy 2. Another study published in the American Journal of Medicine found that thiazide diuretics, including HCTZ, can cause hypokalemia and hypomagnesemia, which can increase the risk of cardiac arrhythmias 3. It is essential to monitor electrolytes, kidney function, and blood glucose regularly during HCTZ treatment and consider potassium supplementation if prescribed by a healthcare provider. Additionally, a study published in Expert Opinion on Pharmacotherapy suggested that HCTZ may not be the best choice for hypertension treatment due to its potential to increase cardiovascular death and coronary artery disease compared to other diuretics 4.