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Medication Safety Issues
Sound-alike/look-alike issues:
Esidrix may be confused with Lasix®
HCTZ is an error-prone abbreviation (mistaken as hydrocortisone)
Hydrochlorothiazide may be confused with hydrocortisone, hydroflumethiazide
Microzide™ may be confused with Maxzide®, Micronase®
International issues:
Microzide™ may be confused with Nitrobide® which is a brand name for isosorbide dinitrate in Japan
Microzide™ may be confused with Mikrozid® which is a brand name for ethanol/propanol combination in Great Britain
Pronunciation
(hye droe klor oh THYE a zide)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
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 Considerations
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
Concerns related to adverse effects:
• Electrolyte disturbances: Hypokalemia, hypochloremic alkalosis, and hyponatremia can occur.
• Photosensitivity: Photosensitization may occur.
• Sulfa allergy: 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. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns:
• Diabetes: Use with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control.
• Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated.
• Hepatic impairment: Use with caution in patients with severe hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy.
• Hypercholesterolemia: Use with caution in patients with moderate or high cholesterol concentrations.
• Hypokalemia: Use with caution in patients with hypokalemia; correct before initiating therapy.
• Renal impairment: Avoid in severe renal disease (ineffective).
• Systemic lupus erythematosus (SLE): Can cause SLE exacerbation or activation.
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
Drug Interactions
ACE Inhibitors: Thiazide Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy
Allopurinol: Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification
Calcitriol: Thiazide Diuretics may enhance the hypercalcemic effect of Calcitriol. Risk C: Monitor therapy
Calcium Salts: Thiazide Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Dofetilide: Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
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): Edema, hypertension:
<6 months: 1-3 mg/kg/day in 2 divided doses
>6 months to 2 years: 1-3 mg/kg/day in 2 divided doses; maximum: 37.5 mg/day
>2-17 years: Initial: 1 mg/kg/day; maximum: 3 mg/kg/day (50 mg/day)
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 <10 mL/minute: Avoid use. Usually ineffective with GFR <30 mL/minute. Effective at lower GFR in combination with a loop diuretic.
Administration: Oral
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
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.
Geriatric Considerations
Hydrochlorothiazide is not effective in patients with a Clcr <30 mL/minute, therefore, it may not be a useful agent in many elderly patients.
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
Hypertension: 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. The ALLHAT study (ALLHAT Collaborative Group, 2002) compared CV outcomes of lisinopril, amlodipine, or chlorthalidone in hypertensive patients having at least one other risk factor for coronary heart disease. Investigators found no difference between the groups on the primary outcome of fatal coronary disease or nonfatal MI. The JNC 7 recommends diuretics for the treatment of hypertension with concurrent heart failure where diuresis is also required (loop diuretics may more frequently be required), high coronary disease risk (as in the ALLHAT trial), diabetes (beneficial in reducing CVD and stroke incidence), and recurrent stroke prevention (in combination with an ACE inhibitor). Thiazides are useful in slowing demineralization in osteoporosis, but need to be used cautiously in gout and in patients with significant history of hyponatremia.
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
Nursing: Physical Assessment/Monitoring
Assess allergy history prior to beginning therapy (sulfonamides). Assess potential for interactions with other pharmacological or herbal products patient may be taking (altered affect of oral hypoglycemics, increased risk of hypotension, or toxicity). Assess results of laboratory tests (electrolytes, BUN, creatinine), therapeutic effectiveness (according to purpose for use), and adverse response (eg, hypotension, hypokalemia, confusion) regularly during therapy. Caution patients with diabetes to monitor glucose levels closely; may alter glucose control. Teach proper use, possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: 12.5 mg
Microzide™: 12.5 mg
Tablet: 25 mg, 50 mg
Pricing: U.S. (www.drugstore.com)
Capsules (Microzide)
12.5 mg (30): $30.99
Tablets (Hydrochlorothiazide)
25 mg (100): $12.99
50 mg (100): $15.99
References
Aronoff GR, Berns JS, Brier ME, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults, 4th ed. Philadelphia, PA: American College of Physicians; 1999.
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, Abraham WT, Chin MH , et al, "ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure)," available at http://www.acc.org/qualityandscience/clinical/guidelines/failure/update/index.pdf.
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents,” Pediatrics, 2004, 114(2 Suppl):555-76.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
Content last modified August 2008
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