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Hydrochlorothiazide: Drug information

Copyright 1978-2005 Lexi-Comp, Inc. All rights reserved.

(For additional information see "Hydrochlorothiazide: Patient drug information"

and see "Hydrochlorothiazide: Pediatric drug information")

U.S. BRAND NAMES – Microzide™

PHARMACOLOGIC CATEGORY
Diuretic, Thiazide

DOSING: ADULTS
Edema (diuresis): Oral: 25-100 mg/day in 1-2 doses; maximum: 200 mg/day

Hypertension: Oral: 12.5-50 mg/day; minimal increase in response and more

electrolyte disturbances are seen with doses >50 mg/day

DOSING: PEDIATRIC – Hypertension, edema (diuretic): Oral (effect of drug may

be decreased when used every day):

(For additional information see "Hydrochlorothiazide: Pediatric drug information")

Children <6 months: 2-3 mg/kg/day in 2 divided doses

Children >6 months: 2 mg/kg/day in 2 divided doses

Note: In pediatric patients, chlorothiazide may be preferred over

hydrochlorothiazide as there are more dosage formulations (eg, suspension)
available.

DOSING: ELDERLY – Oral: 12.5-25 mg once daily; minimal increase in response

and more electrolyte disturbances are seen with doses >50 mg/day (see Special
Geriatric Considerations).

DOSING: RENAL IMPAIRMENT – Clcr<30 mL/minute: Dosing adjustment not

effective, therefore not generally recommended.

DOSAGE FORMS
Capsule (Microzide™): 12.5 mg

Tablet: 25 mg, 50 mg

GENERIC EQUIVALENT AVAILABLE – Yes

ADMINISTRATION – May be taken with food or milk. Take early in day to avoid
nocturia. Take the last dose of multiple doses no later than 6 PM unless instructed
otherwise.
USE – Management of mild to moderate hypertension; treatment of edema in
congestive heart failure and nephrotic syndrome

USE - UNLABELED / INVESTIGATIONAL – Treatment of lithium-induced

diabetes insipidus

ADVERSE REACTIONS SIGNIFICANT

1% to 10%:
Cardiovascular: Orthostatic hypotension, hypotension
Dermatologic: Photosensitivity
Endocrine & metabolic: Hypokalemia
Gastrointestinal: Anorexia, epigastric distress

<1% (Limited to important or life-threatening): Agranulocytosis, allergic

myocarditis, allergic reactions (possibly with life-threatening anaphylactic shock),
alopecia, aplastic anemia, eosinophilic pneumonitis, erythema multiforme,
exfoliative dermatitis, hemolytic anemia, hepatic function impairment,
hypercalcemia, interstitial nephritis, leukopenia, pancreatitis, renal failure,
respiratory distress, Stevens-Johnson syndrome, thrombocytopenia, toxic
epidermal necrolysis

CONTRAINDICATIONS – Hypersensitivity to hydrochlorothiazide or any

component of the formulation, thiazides, or sulfonamide-derived drugs; anuria;
renal decompensation; pregnancy

WARNINGS / PRECAUTIONS – Avoid in severe renal disease (ineffective).

Electrolyte disturbances (hypokalemia, hypochloremic alkalosis, hyponatremia)
can occur. Use with caution in severe hepatic dysfunction; hepatic encephalopathy
can be caused by electrolyte disturbances. Gout can be precipitate in certain
patients with a history of gout, a familial predisposition to gout, or chronic renal
failure. Cautious use in diabetics; may see a change in glucose control.
Hypersensitivity reactions can occur. Can cause SLE exacerbation or activation.
Use with caution in patients with moderate or high cholesterol concentrations.
Photosensitization may occur. Correct hypokalemia before initiating therapy.

Chemical similarities are present among sulfonamides, sulfonylureas, carbonic

anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in
patients with sulfonamide allergy is specifically contraindicated in product labeling,
however, a risk of cross-reaction exists in patients with allergy to any of these
compounds; avoid use when previous reaction has been severe.

DRUG INTERACTIONS
ACE inhibitors: Increased hypotension if aggressively diuresed with a thiazide
diuretic.

Beta-blockers increase hyperglycemic effects in type 2 diabetes mellitus

(noninsulin dependent, NIDDM)

Cholestyramine: Hydrochlorothiazide absorption may be decreased.

Colestipol: Hydrochlorothiazide absorption may be decreased.

Cyclosporine and thiazides can increase the risk of gout or renal toxicity; avoid
concurrent use.

Digoxin toxicity can be exacerbated if a thiazide induces hypokalemia or

hypomagnesemia.

Lithium toxicity can occur by reducing renal excretion of lithium; monitor lithium
concentration and adjust as needed.

Neuromuscular blocking agents can prolong blockade; monitor serum potassium

and neuromuscular status.

NSAIDs can decrease the efficacy of thiazides reducing the diuretic and
antihypertensive effects.

ETHANOL / NUTRITION / HERB INTERACTIONS

Food: Hydrochlorothiazide peak serum levels may be decreased if taken with food.
This product may deplete potassium, sodium, and magnesium.

Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic

activity). Dong quai may also cause photosensitization. Avoid ephedra, ginseng,
yohimbe (may worsen hypertension). Avoid garlic (may have increased
antihypertensive effect).

PREGNANCY RISK FACTOR – B (show table) (manufacturer); D (expert

analysis)

PREGNANCY IMPLICATIONS – Although there are no adequate and well-

controlled studies using hydrochlorothiazide in pregnancy, thiazide diuretics may
cause an increased risk of congenital defects. Hypoglycemia, hypokalemia,
hyponatremia, jaundice, and thrombocytopenia are also reported as possible
complications to the fetus or newborn.

LACTATION – Enters breast milk/use caution (AAP rates "compatible")

PRICING – (data from drugstore.com)

Capsules (Hydrochlorothiazide)
12.5 mg (30): $13.99

Capsules (Microzide)
12.5 mg (30): $28.23

Tablets (Hydrochlorothiazide)
25 mg (100): $8.99
50 mg (100): $8.99

MONITORING PARAMETERS – Assess weight, I & O reports daily to determine

fluid loss; blood pressure, serum electrolytes, BUN, creatinine

TOXICOLOGY / OVERDOSE COMPREHENSIVE – Symptoms include

hypermotility, diuresis, lethargy, confusion, and muscle weakness. Following GI
decontamination, therapy is supportive with I.V. fluids, electrolytes, and I.V.
pressors if needed.
CANADIAN BRAND NAMES – Apo-Hydro®; Novo-Hydrazide

INTERNATIONAL BRAND NAMES – Apo-Hydro® (CA, SG); Aquazide® (IN);

Clorana® (BR); Dehydratin® (BG); Dichlorosal® (IL); Dichlotride® (AU, BE, DK,
HK, LU, TH); Diclotride® (MX); Didralin® (SG); Di-Ertride® (SG); Disalunil® (DE,
PL); Disothiazide® (IL); Diu-Melusin® (DE); Diunorm® (YU); Diural® (AR);
Diuret-P® (TH); Diurex® (AR); Drenol® (BR); Esidrex® (AT, CH, ES, FR, IT, LU,
MT, NL, NO, SE); Esidrix® (DE); HCT 1A Pharma® (DE); HCTad® (DE); HCT-
beta® (DE); HCT Biochemie® (DE); HCT gamma® (DE); HCT Hexal® (DE);
H.C.T. (ID); HCT-Isis® (DE); HCT Muti® (DE); HCT-ratiopharm® (DE); HCT
Sandoz® (DE); HCT von ct® (DE); Hexazide® (ZA); Hidroclorotiazida® (BR, CO,
RO); Hidroclorotiazida Genfar® (CO); Hidroclorotiazida L.CH.® (CL);
Hidroclorotiazida MK® (CO); Hidroclorozil® (BR); Hidroronol® (CL);
Hidrosaluretil® (ES); Hydrex® (FI); Hydrochlorothiazide® (CY);
Hydrochlorothiazid Leciva® (CZ); Hydrochlorothiazidum® (PL); Hydrozide® (HK,
SG, TH); Hypothiazid® (HU, RU); Nefrix® (RO); Newtolide® (JP); Novo-
Hydrazide (CA); Pantemon® (JP); Ridaq® (ZA); Tandiur® (AR)

MECHANISM OF ACTION – Inhibits sodium reabsorption in the distal tubules

causing increased excretion of sodium and water as well as potassium and
hydrogen ions

PHARMACODYNAMICS / KINETICS
Onset of action: Diuresis: ~2 hours
Peak effect: 4-6 hours

Duration: 6-12 hours

Absorption: ~50% to 80%

Distribution: 3.6-7.8 L/kg

Protein binding: 68%

Metabolism: Not metabolized

Bioavailability: 50% to 80%

Half-life elimination: 5.6-14.8 hours

Time to peak: 1-2.5 hours

Excretion: Urine (as unchanged drug)

PATIENT EDUCATION – May be taken with food or milk; take early in day to
avoid nocturia; take the last dose of multiple doses no later than 6 PM unless
instructed otherwise. A few people who take this medication become more
sensitive to sunlight and may experience skin rash, redness, itching, or severe
sunburn, especially if sun block SPF > or =15 is not used on exposed skin areas.
May increase blood glucose levels in diabetics.

(For additional information see "Hydrochlorothiazide: Patient drug information")

 References
1. Chobanian, AV, Bakris, GL, Black, HR, et al. The Seventh Report of the Joint
National Committee on Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure: The JNC 7 Report. JAMA 2003; 289:2560.
2. Consensus Recommendations for the Management of Chronic Heart Failure. On
Behalf of the Membership of the Advisory Council to Improve Outcomes Nationwide
in Heart Failure. Am J Cardiol 1999; 83:1A.
3. Hunt, SA, Baker, DW, Chin, MH, et al. ACC/AHA Guidelines for the Evaluation and
Management of Chronic Heart Failure in the Adult: Executive Summary. A Report of
the American College of Cardiology/American Heart Association Task Force on
Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and
Management of Heart Failure). J Am Coll Cardiol 2001; 38:2101.