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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Medication Safety Issues
Sound-alike/look-alike issues:
Dyazide® may be confused with diazoxide, Dynacin®
Maxzide® may be confused with Maxidex®, Microzide®
Pronunciation
(hye droe klor oh THYE a zide & trye AM ter een)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of hypertension or edema (not recommended for initial treatment) when hypokalemia has developed on hydrochlorothiazide alone or when the development of hypokalemia must be avoided
Pregnancy Risk Factor
C
Pregnancy Considerations
See individual agents.
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
See individual agents.
Contraindications
Hypersensitivity to hydrochlorothiazide, triamterene, any component of the formulation, or sulfonamide-derived drugs; anuria; acute and chronic renal insufficiency or significant renal impairment; patients receiving other potassium-sparing diuretics, potassium-containing salt substitutes, or potassium supplements (except in severe cases of hypokalemia); preexisting hyperkalemia
Warnings/Precautions
Boxed warnings:
• Hyperkalemia: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Electrolyte disturbances: Hypokalemia, hypochloremic alkalosis, and hyponatremia can occur with hydrochlorothiazide.
• Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur with triamterene; patients at risk include those with renal dysfunction, diabetes mellitus, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction. Avoid potassium supplements (except in severe cases of hypokalemia), potassium-containing salt substitutes, a diet rich in potassium, or other drugs that can cause hyperkalemia. Discontinue if hyperkalemia develops.
• 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 alter glycemic control.
• Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by hydrochlorothiazide.
• Hepatic impairment: Use caution in patients with severe hepatic impairment; 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; increased cholesterol and triglyceride levels have been reported with thiazides.
• Kidney stones: Use triamterene with caution in patients with kidney stones.
• Parathyroid disease: With prolonged use, hydrochlorothiazide may produce pathologic changes in the parathyroid gland with hypercalcemia and hypophosphatemia. Thiazides should be discontinued prior to tests for parathyroid function.
• Renal impairment: Avoid hydrochlorothiazide in severe renal disease (ineffective). Triamterene may cause hyperkalemia in patients with renal impairment.
• Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children.
Adverse Reactions
Also see individual agents. Frequency not defined.
Cardiovascular: Angina, arrhythmia, postural hypotension, tachycardia
Central nervous system: Anxiety, dizziness, depression, fatigue, headache, insomnia, restlessness, vertigo
Dermatologic: Photosensitivity, purpura, rash, subacute cutaneous lupus erythematosus-like reactions, urticaria
Endocrine & metabolic: Acidosis, diabetes mellitus, hypercalcemia, hyperglycemia, hyper-/hypokalemia, hyperuricemia, hypochloremia, hypomagnesemia, hyponatremia
Gastrointestinal: Abdominal pain, anorexia, burning of tongue, constipation, diarrhea, loss of appetite, nausea, pancreatitis, sialadenitis, stomach cramps, taste alteration, tongue discoloration (bright orange), upset stomach, vomiting, xerostomia
Genitourinary: Impotence
Hematologic: Aplastic anemia, agranulocytosis, hemolytic anemia, leukopenia, thrombocytopenia, megaloblastic anemia
Hepatic: Jaundice, liver function tests (abnormal)
Neuromuscular & skeletal: Muscle cramping, parasthesia, weakness
Ocular: Blurred vision (transient), xanthopsia
Renal: Acute renal failure, BUN increased, glycosuria, interstitial nephritis, necrotizing vasculitis, renal stone formation, serum creatinine increased, urinary sediment abnormal, urine discoloration
Respiratory: Allergic pneumonitis, dyspnea, pulmonary edema, respiratory distress
Miscellaneous: Anaphylaxis, systemic lupus erythematosus (SLE) exacerbation
Drug Interactions
ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
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
Alcohol (Ethyl): May enhance the orthostatic effect of Thiazide Diuretics. 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
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk D: Consider therapy modification
Analgesics (Opioid): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Antidiabetic Agents: Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Barbiturates: May enhance the orthostatic effect of Thiazide Diuretics. 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
Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. 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 X: Avoid combination
Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. 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
Indomethacin: May enhance the nephrotoxic effect of Triamterene. Risk C: Monitor therapy
Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Mitotane: Potassium-Sparing Diuretics may diminish the therapeutic effect of Mitotane. High dose diuretics (eg, Cushings syndrome) may present significantly higher risk than low doses (eg, CHF). Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Avoid food with high potassium content and potassium-containing salt substitutes.
Storage
Store at 20°C to 25°C (68°F to 77°F). Protect from light.
Mechanism of Action
Based on triamterene component: Interferes with potassium/sodium exchange (active transport) in the distal tubule, cortical collecting tubule and collecting duct by inhibiting sodium, potassium-ATPase; decreases calcium excretion; increases magnesium loss
Based on hydrochlorothiazide component: Inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water as well as potassium and hydrogen ions
Pharmacodynamics/Kinetics
See individual agents.
Dosage
Oral: Adults:
Hydrochlorothiazide 25 mg and triamterene 37.5 mg: 1-2 tablets/capsules once daily
Hydrochlorothiazide 50 mg and triamterene 75 mg: 1/2-1 tablet daily
Monitoring Parameters
Monitor blood pressure, serum electrolytes, BUN, creatinine, liver function tests, signs of hyperkalemia
Dietary Considerations
Should be taken after meals.
Patient Education
See individual agent for Hydrochlorothiazide.
Geriatric Considerations
The efficacy of hydrochlorothiazide is limited in patients with a Clcr <30 mL/minute; monitor serum potassium.
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. 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 combination of hydrochlorothiazide and triamterene may reduce the incidence of hypokalemia.
Diuretics are standard therapy for the management of edema in patients with heart failure.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause lethargy or anorexia
Mental Health: Effects on Psychiatric Treatment
May decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels
Nursing: Physical Assessment/Monitoring
See individual agent for Hydrochlorothiazide.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral: Hydrochlorothiazide 25 mg and triamterene 37.5 mg; hydrochlorothiazide 25 mg and triamterene 50 mg
Dyazide®: Hydrochlorothiazide 25 mg and triamterene 37.5 mg
Tablet: Hydrochlorothiazide 25 mg and triamterene 37.5 mg; hydrochlorothiazide 50 mg and triamterene 75 mg
Maxzide®: Hydrochlorothiazide 50 mg and triamterene 75 mg [scored]
Maxzide®-25: Hydrochlorothiazide 25 mg and triamterene 37.5 mg [scored]
Pricing: U.S. (www.drugstore.com)
Capsules (Dyazide)
37.5-25 mg (30): $43.04
Capsules (Triamterene-HCTZ)
37.5-25 mg (100): $15.99
50-25 mg (100): $49.99
Tablets (Maxzide)
75-50 mg (30): $61.59
Tablets (Maxzide-25)
37.5-25 mg (30): $34.09
Tablets (Triamterene-HCTZ)
37.5-25 mg (100): $29.99
75-50 mg (100): $17.99
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.
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://content.onlinejacc.org/cgi/reprint/46/6/e1.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2009
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