Spironolactone / Hydrochlorothiazide

Pronunciation: (SPEER-oh-no-LAK-tone/high-droe-klor-THIGH-uh-zide)
Class: Diuretic combination

Trade Names

Aldactazide
- Tablets 25 mg spironolactone and 25 mg hydrochlorothiazide
- Tablets 50 mg spironolactone and 50 mg hydrochlorothiazide

Aldactazide 25 (Canada)
Aldactazide 50 (Canada)
Novo-Spirozine (Canada)

Pharmacology

Spironolactone

Competitively inhibits aldosterone in distal tubules, resulting in increased excretion of sodium and water and decreased excretion of potassium.

Hydrochlorothiazide

Increases chloride, sodium, and water excretion by interfering with transport of sodium ions across renal tubular epithelium.

Indications and Usage

Edematous conditions for patients with CHF, cirrhosis of the liver accompanied edema or ascites, nephrotic syndrome, or essential hypertension.

Contraindications

Patients with anuria; acute renal insufficiency, significant impairment of renal excretory function; severe hepatic failure; hyperkalemia; hypersensitivity to any component of product or sulfonamide-derived drugs.

Dosage and Administration

Edema (CHF, hepatic cirrhosis, nephrotic syndrome)
Adults

PO Usual maintenance dose is 100 mg each of spironolactone and hydrochlorothiazide daily, administered in a single dose or divided doses, ranging from 25 to 200 mg of each component daily, depending on the response to the initial titration.

Essential Hypertension
Adults

PO Varies depending on titration of individual ingredients; however, many patients have an optimal response to 50 to 100 mg each of spironolactone and hydrochlorothiazide daily, given in a single dose or divided doses.

Storage/Stability

Store tablets at controlled room temperature (59° to 86°F).

Drug Interactions

ACE inhibitors (eg, captopril)

Severe hyperkalemia may occur.

Alcohol, barbiturates, narcotics

Orthostatic hypotension may be potentiated.

Antidiabetic agents (oral and insulin)

May require dosage adjustment of antidiabetic agent.

Corticosteroids, ACTH

Electrolyte depletion, particularly hypokalemia, may occur.

Digoxin

The t½ of digoxin may be prolonged and serum levels may be elevated, increasing the risk of toxicity.

Lithium

Renal clearance of lithium may be decreased, increasing the risk of toxicity.

Nondepolarizing skeletal muscle relaxants (eg, tubocurarine)

Unresponsiveness to muscle relaxant may occur.

NSAIDs (eg, indomethacin)

The diuretic, natriuretic, and antihypertensive effect of hydrochlorothiazide may be reduced.

Pressor amines (eg, norepinephrine)

The vascular response to norepinephrine may be reduced.

Laboratory Test Interactions

Hydrochlorothiazide

May decrease serum protein-bound iodine levels without signs of thyroid disturbances. May cause diagnostic interference of serum electrolyte levels, blood and urine glucose levels, serum bilirubin levels, and serum uric acid levels.

Adverse Reactions

Cardiovascular

Hypotension (including orthostatic).

CNS

Mental confusion; ataxia; headache; drowsiness; lethargy; vertigo; paresthesia; dizziness; restlessness.

Dermatologic

Urticaria; rash; purpura; erythema multiforme; pruritus.

EENT

Transient blurred vision; xanthopsia.

GI

Gastric bleeding; ulceration; gastritis; diarrhea and cramping; nausea; vomiting; sialadenitis; constipation; gastric irritation; anorexia; pancreatitis.

Genitourinary

Gynecomastia; inability to achieve and maintain erection; irregular menses; amenorrhea; postmenopausal bleeding; renal dysfunction; renal failure; interstitial nephritis.

Hematologic

Agranulocytosis; aplastic anemia; leukopenia; hemolytic anemia; thrombocytopenia.

Hepatic

Mixed cholestatic/hepatocellular toxicity; jaundice (intrahepatic cholestatic jaundice).

Metabolic

Electrolyte imbalance; hyperglycemia; glycosuria; hyperuricemia.

Respiratory

Respiratory distress (including pneumonitis and pulmonary edema.)

Miscellaneous

Hypersensitivity (fever, urticaria, maculopapular or erythematous cutaneous eruptions); vasculitis; weakness; anaphylactic reactions; necrotizing angiitis; photosensitivity; fever; muscle spasm.

Precautions

Pregnancy

Category C .

Lactation

Canrenone, a major and active metabolite of spironolactone, is excreted in breast milk.

Children

Safety and efficacy not established.

Special Risk Patients

Use with caution in patients with severe renal disease or impaired hepatic function.

Combination Therapy

Fixed-dose combination therapy is not indicated for initial therapy of edema or hypertension. Therapy should be titrated to the individual. If the fixed combination represents the dosage so determined, its use may be more convenient in patient management.

Electrolyte imbalance and BUN increase

Hyperkalemia (serum potassium greater than 5.5 mEq/L) hyponatremia, hypochloremia, and increases in BUN may occur.

Systemic lupus erythematosus (SLE)

Hydrochlorothiazide may exacerbate or activate SLE.

Overdosage

Symptoms

Drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, diarrhea, hyperkalemia, electrolyte imbalance, hypokalemia and/or hyponatremia, thirst, restlessness, depression, lethargy, fatigue.

Patient Information

Advise patient to take every day or twice daily as prescribed, without regard to meals but to take with food if GI upset occurs.
Inform patient that drug controls, but does not cure, hypertension and to continue taking medication as prescribed even when BP is not elevated.
Caution patient not to change the dose or stop taking unless advised to do so by health care provider.
Instruct patient to continue taking other BP medications as prescribed by health care provider.
Instruct patient in BP and pulse measurement skills.
Advise patient to monitor and record BP and pulse at home and to inform health care provider should abnormal measurements be noted. Also advise patient to take record of BP and pulse to each follow-up visit.
Instruct patient to lie or sit down if experiencing dizziness or lightheadedness when standing.
Caution patient that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to excessive fall in BP resulting in lightheadedness or fainting.
Instruct diabetic patient to monitor blood glucose more frequently when drug is started or dose is changed and to inform health care provider of significant changes in readings.
Caution patient to avoid unnecessary exposure to UV light (sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light to avoid photosensitivity reaction.
Emphasize to hypertensive patient importance of other modalities on BP: weight control, regular exercise, smoking cessation, and moderate intake of alcohol and salt.
Instruct patient to stop taking drug and immediately report any of these symptoms to health care provider: abnormal skin sensations, muscle weakness, or slow pulse.