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Chlorothiazide

Pronunciation: KLOR-oh-THYE-a-zide
Class: Thiazide diuretic

Trade Names

Chlorothiazide
- Tablets 250 mg
- Tablets 500 mg

Diuril
- Oral suspension 250 mg per 5 mL
- Injection, lyophilized powder for solution 500 mg

Pharmacology

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

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Pharmacokinetics

Distribution

Chlorothiazide crosses the placenta but not the blood-brain barrier.

Metabolism

Chlorothiazide is not metabolized.

Elimination

Excreted by the kidney. Plasma t ½ 45 to 120 min. Following IV administration, 96% is excreted unchanged in the urine within 23 h.

Onset

Within 2 h after oral administration; within 15 min after IV administration.

Peak

Approximately 4 h after oral administration; approximately 30 min after IV administration.

Duration

Approximately 6 to 12 h after oral administration.

Indications and Usage

Adjunctive treatment in edema associated with CHF, hepatic cirrhosis, and corticosteroid and estrogen therapy; edema caused by various forms of renal function impairment such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure (oral and IV); management of hypertension (oral).

Unlabeled Uses

Calcium nephrolithiasis; diabetes insipidus; osteoporosis.

Contraindications

Anuria, hypersensitivity to sulfonamide-derived drugs or any component of this product.

Dosage and Administration

Diuresis and Control of Hypertension
Children younger than 6 mo of age (see Precautions)

PO 30 mg/kg in 2 divided doses may be required.

Children 6 mo to 2 yr of age (see Precautions)

PO 10 to 20 mg/kg/day in single or 2 divided doses (max, 375 mg/day).

Children 2 to 12 yr of age (see Precautions)

PO 1 g/day.

Edema
Adults

PO 500 to 1,000 mg once or twice daily. Many patients respond to intermittent therapy (alternate day therapy or administration on 3 to 5 days each wk). IV 500 to 1,000 mg once or twice daily. Should be reserved for patients unable to take oral medication or for emergency situations. Individualize dosage according to patient response, using the smallest dosage necessary.

Hypertension
Adults

PO 500 to 1,000 mg as a single or divided dose. Increase or decrease dose according to BP response. Rarely, some patients may require up to 2 g/day in divided doses.

General Advice

  • Tablets and suspension
  • Administer without regard to meals. Administer with food if GI upset occurs.
  • Shake suspension well before measuring dose. Use dosing syringe, spoon, or cup to measure prescribed dose of suspension.
  • Injection
  • Reconstitute powder for injection following manufacturer's recommendations using sterile water for injection.
  • Do not administer if particulate matter, cloudiness, or discoloration is noted.
  • Administer by slow IV injection or IV infusion as ordered. Take special precautions to avoid extravasation. Do not give subcutaneously or IM.
  • Discard any unused portion of vial. Do not save for future use. For single dose only.

Storage/Stability

Store oral suspension at controlled room temperature (59° to 86°F). Protect from freezing. Store powder for injection between 36° and 77°F. Store tablets at 68° to 77°F. Dispense in light-resistant container.

Drug Interactions

Alcohol, barbiturates, narcotics

May potentiate orthostatic hypotension.

Antihypertensive agents

Coadministration may result in additive antihypertensive effects, or the effects may be potentiated.

Bile acid sequestrants

May reduce thiazide absorption; give thiazide at least 2 h before bile acid sequestrants.

Cisapride

Cisapride is contraindicated in patients who experience rapid reduction in plasma potassium, including patients receiving chlorothiazide.

Corticosteroids

Increased electrolyte depletion, especially hypokalemia.

Diazoxide

May cause hyperglycemia.

Digitalis glycosides

Diuretic-induced hypokalemia and hypomagnesemia may precipitate digitalis-induced arrhythmias.

Dofetilide

Dofetilide is contraindicated in patients receiving chlorothiazide because hypokalemia may occur, increasing the risk of torsades de pointes.

Insulin, sulfonylureas

May decrease hypoglycemic effect of sulfonylureas. Because chlorothiazide may elevate blood glucose levels, may need to increase dosage of sulfonylureas or insulin.

Lithium

May decrease renal excretion of lithium.

Loop diuretics

Synergistic effects may result in profound diuresis and serious electrolyte abnormalities.

Nondepolarizing muscle relaxants (eg, tubocurarine), skeletal muscle relaxants

Response to muscle relaxants may be increased.

NSAIDs

Pharmacologic effects of chlorothiazide may be reduced.

Pressor amines (eg, norepinephrine)

Effect of pressor amines may be reduced.

Laboratory Test Interactions

May produce false-negative results with the phentolamine and tyramine tests; may interfere with the phenolsulfonphthalein test because of decreased excretion; may cause diagnostic interference of serum electrolyte levels, blood and urine glucose levels, and a decrease in serum protein-bound iodine levels without signs of thyroid disturbance.

Adverse Reactions

Cardiovascular

Hypotension; orthostatic hypotension.

CNS

Dizziness; headache; paresthesia; restlessness; vertigo.

Dermatologic

Alopecia; erythema multiforme; exfoliative dermatitis; Stevens-Johnson syndrome; toxic epidermal necrolysis.

EENT

Transient blurred vision; xanthopsia.

GI

Anorexia; constipation; cramping; diarrhea; gastric irritation; nausea; pancreatitis; sialadenitis; vomiting.

Genitourinary

Hematuria (IV use); impotence; interstitial nephritis; renal failure; renal function impairment.

Hematologic-Lymphatic

Agranulocytosis; aplastic anemia; hemolytic anemia; leukemia; thrombocytopenia.

Hepatic

Jaundice (intrahepatic cholestasis).

Hypersensitivity

Anaphylactic reactions; fever; necrotizing angiitis (vasculitis and cutaneous vasculitis); photosensitivity; purpura; rash; respiratory distress, including pneumonitis and pulmonary edema; urticaria.

Metabolic-Nutritional

Electrolyte imbalance; glycosuria; hyperglycemia; hyperuricemia.

Musculoskeletal

Muscle spasm; weakness.

Precautions

Monitor

Blood sugar

Monitor blood sugar in diabetic patients when drug is started or dose is changed. Advise patient to report significant changes to health care provider.

BP/Pulse

Monitor and record BP and pulse. Should hypotension result, advise patient to hold medication and notify health care provider.

Chloride deficit

Generally mild except in certain circumstances (eg, liver or renal disease), which may require treatment including chloride replacement for the treatment of metabolic alkalosis.

Orthostatic hypotension

Take safety precautions if orthostatic hypotension occurs.

Routine tests

Ensure that serum electrolytes, BUN, creatinine, and uric acid are monitored periodically.


Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established. Oral dosing recommendation is supported by empiric use in children and published literature regarding the treatment of hypertension.

Elderly

Use with caution, usually starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Hypersensitivity

May occur in patients with or without history of allergy or bronchial asthma; cross-sensitivity with sulfonamides also may occur.

Renal Function

Drug may precipitate azotemia; use drug with caution.

Hepatic Function

Minor alterations of fluid and electrolyte balance may precipitate hepatic coma; use with caution.

Diabetes mellitus

May become manifest.

Dilutional hyponatremia

May occur in edematous patients in hot weather.

Electrolytes

Increased urinary excretion of sodium, potassium, or magnesium may occur; decreased urinary excretion of calcium may occur.

Hyperuricemia

May occur or frank gout may be precipitated.

Lipids

Increased cholesterol and triglycerides may occur.

Lupus erythematosus

Exacerbation or activation may occur.

Post-sympathectomy patients

Antihypertensive effects may be enhanced.

Overdosage

Symptoms

Electrolyte depletion (hypochloremia, hypokalemia, hyponatremia); dehydration; hypokalemia may accentuate cardiac arrhythmias if digitalis is being administered.

Patient Information

  • Tablets and Suspension
  • Advise patient to take prescribed dose once or twice daily without regard to meals, but to take with food if stomach upset occurs.
  • Advise patient or caregiver using suspension to shake well before measuring dose and to use dosing spoon, syringe, or cup to measure prescribed dose.
  • Advise patient that medication will initially increase urination, but that this should go away after a few weeks of treatment.
  • Advise patient if a dose is missed to skip that dose and take the next dose at the regularly scheduled time. Caution patient not to double the dose to catch up.
  • Inform patient that drug controls but does not cure hypertension and to continue taking medication as prescribed even when BP is not elevated.
  • 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 if 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 light-headedness when standing.
  • Caution patient that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to excessive fall in BP, resulting in light-headedness or fainting.
  • Instruct patients with diabetes 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 (eg, sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light until tolerance is determined.
  • Emphasize to hypertensive patient importance of the following modalities on BP: weight control, regular exercise, smoking cessation, moderate intake of alcohol and salt.
  • Instruct patient to inform health care provider if any of the following occur: abnormal skin sensations; drowsiness; excessive thirst; increased heart rate; muscle pain, weakness, or cramps; persistent nausea or vomiting; unexplained joint pain; unexplained tiredness.
  • Injection
  • Advise patient that medication will be prepared by a health care provider and administered in a health care setting.

Copyright © 2009 Wolters Kluwer Health.

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