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Hydrochlorothiazide


Pronunciation

 (hye droe klor oh THYE a zide)


U.S. Brand Names

 Microzide™


Synonyms

 HCTZ


Generic Available

 Yes


Canadian Brand Names

 Apo-Hydro®; Novo-Hydrazide


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


Pregnancy Risk Factor

 B (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")


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.


Adverse Reactions

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


Overdosage/Toxicology

 Symptoms of overdose include hypermotility, diuresis, lethargy, confusion, and muscle weakness. Treatment is supportive.


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).


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)


Dosage

 Oral (effect of drug may be decreased when used every day):

Children (in pediatric patients, chlorothiazide may be preferred over hydrochlorothiazide as there are more dosage formulations [eg, suspension] available):

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

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

Adults:

Edema: 25-100 mg/day in 1-2 doses; maximum: 200 mg/day

Hypertension: 12.5-50 mg/day; minimal increase in response and more electrolyte disturbances are seen with doses >50 mg/day

Elderly: 12.5-25 mg once daily

Dosing adjustment/comments in renal impairment: Clcr 25-50 mL/minute: Not effective


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.


Monitoring Parameters

 Assess weight, I & O reports daily to determine fluid loss; blood pressure, serum electrolytes, BUN, creatinine


Test Interactions

 Increased creatine phosphokinase [CPK] (S), ammonia (B), amylase (S), calcium (S), chloride (S), cholesterol (S), glucose, increased acid (S), decreased chloride (S), magnesium, potassium (S), sodium (S); Tyramine and phentolamine tests, histamine tests for pheochromocytoma


Patient Education

 Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. This medication does not replace other antihypertensive interventions; follow prescriber's instructions for diet and lifestyle changes. Take as directed, with meals, early in the day to avoid nocturia. Your prescriber may prescribe a potassium supplement or recommend that you eat foods high in potassium (include bananas and/or orange juice in daily diet). Do not change your diet on your own while taking this medication, especially if you are taking potassium supplements or medications to reduce potassium loss; too much potassium can be as harmful as too little. If you have diabetes, monitor serum glucose closely; this medication may increase serum glucose levels. May cause dizziness or postural hypotension (use caution when rising from sitting or lying position, when driving, climbing stairs, or engaging in tasks that require alertness until response to drug is known); nausea or vomiting (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); impotence (reversible); constipation (increased exercise, fluids, fruit, or fiber may help); or photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). Report persistent flu-like symptoms, chest pain, palpitations, muscle cramping, respiratory difficulty, skin rash or itching, unusual bruising or easy bleeding, or excessive fatigue. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Consult prescriber if breast-feeding.


Additional Information

 If given the morning of surgery it may render the patient volume depleted and blood pressure may be labile during general anesthesia. Effect of drug may be decreased when used every day.


Anesthesia and Critical Care Concerns/Other Considerations

 If given the morning of surgery it may render the patient volume depleted and blood pressure may be labile during general anesthesia.

Thiazide diuretics are effective first-line therapeutic agents in the management of hypertension and have proven to be of benefit in terms of cardiovascular outcome. They may act synergistically to lower blood pressure when combined with an ACE inhibitor or beta-blocker.


Cardiovascular Considerations

 Thiazide diuretics are effective first-line therapeutic agents in the management of hypertension and have proven to be of benefit in terms of cardiovascular outcome. They may act synergistically to lower blood pressure when combined with an ACE inhibitor or beta-blocker. The initial concern about thiazide diuretic-induced hypokalemia, glucose intolerance, and lipid profiles does not appear to be of substantial clinical consequence in the treatment of hypertension. The benefits of this class of agents in the treatment of hypertension is established and compares well with other first-line therapeutic agents.

Diuretics are standard therapy for the management of edema in patients with heart failure. However, it is important to ensure that edema is not secondary to pericardial effusion. Marked reduction in intravascular volume with consequent decreased cardiac filling pressures may precipitate significant hypotension in these circumstances.


Dental Health: Effects on Dental Treatment

 Key adverse event(s) related to dental treatment: Orthostatic hypotension and hypotension.


Dental Health: Vasoconstrictor/Local Anesthetic Precautions

 No information available to require special precautions


Mental Health: Effects on Mental Status

 None reported


Mental Health: Effects on Psychiatric Treatment

 Used to treat lithium-induced diabetes insipidus; monitor for hypokalemia; may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels


Dosage Forms

Capsule (Microzide™): 12.5 mg

Tablet: 25 mg, 50 mg


References

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(19):2560-71.

"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(2A):1A-38A.

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(7):2101-13.


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, RO); Hidroclorotiazida L.CH.® (CL); 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)


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