Hydrochlorothiazide

Hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia may occur. Development of electrolyte disturbances can be minimized when used in combination with other electrolyte sparing antihypertensives (eg, ACE inhibitors or angiotensin receptor blockers) (Sica 2011).

In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by hydrochlorothiazide. This risk may be increased with doses ≥25 mg (Gurwitz 1997).

Hypersensitivity reactions may occur with hydrochlorothiazide. Risk is increased in patients with a history of allergy or bronchial asthma.

May cause acute transient myopia and acute angle-closure glaucoma, typically occurring within hours to weeks following initiation. Discontinue therapy immediately in patients with acute decreases in visual acuity or ocular pain; additional treatments may be needed if uncontrolled intraocular pressure persists. Risk factors may include a history of sulfonamide or penicillin allergy.

Photosensitization may occur.

The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes. Disease-related concerns:

Avoid use of diuretics for treatment of elevated blood pressure in patients with primary adrenal insufficiency (Addison disease). Adjustment of glucocorticoid/mineralocorticoid therapy and/or use of other antihypertensive agents is preferred to treat hypertension (Bornstein 2016; Inder 2015).

Use with extreme caution or avoid hydrochlorothiazide in the management of ascites due to cirrhosis; may lead to rapid development of hyponatremia when used in combination with spironolactone and furosemide (AASLD [Runyon 2012]).

Use with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control.

Use with caution in patients with severe hepatic dysfunction; in progressive or severe liver disease, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy/coma.

Thiazide diuretics may decrease renal calcium excretion; consider avoiding use in patients with hypercalcemia.

Use with caution in patients with moderate or high cholesterol concentrations; increased cholesterol and triglyceride levels have been reported.

Use with caution in patients with hypokalemia; correct before initiating therapy.

Thiazide diuretics reduce calcium excretion; pathologic changes in the parathyroid glands with hypercalcemia and hypophosphatemia have been observed with prolonged use; should be discontinued prior to testing for parathyroid function.

Cumulative effects may develop, including azotemia, in patients with impaired renal function. Avoid in severe renal disease (ineffective).

May cause SLE exacerbation or activation. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

If given the morning of surgery, hydrochlorothiazide may render the patient volume depleted and blood pressure may be labile during general anesthesia. Dosage form specific issues:

Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.