Triamterene/Hydrochlorothiazide

Description

Triamterene and hydrochlorothiazide is a combination of triamterene, a potassium-conserving diuretic, and hydrochlorothiazide, a natriuretic agent. The formulation is available in two tablet strengths: each Triamterene and Hydrochlorothiazide 37.5 mg/25 mg Tablet, USP contains 37.5 mg of triamterene, USP and 25 mg of hydrochlorothiazide, USP, while each Triamterene and Hydrochlorothiazide 75 mg/50 mg Tablet, USP contains 75 mg of triamterene, USP and 50 mg of hydrochlorothiazide, USP.

The tablets are intended for oral administration and include the following inactive ingredients: lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The 37.5 mg/25 mg tablets also contain D&C Yellow No.10 Aluminum Lake and FD&C Blue No.1 Aluminum Lake.

Triamterene is chemically designated as 2,4,7-triamino-6-phenylpteridine. It is characterized by its practical insolubility in water, benzene, chloroform, ether, and dilute alkali hydroxides, while being soluble in formic acid and sparingly soluble in methoxyethanol. It exhibits very slight solubility in acetic acid, alcohol, and dilute mineral acids. Hydrochlorothiazide is identified as 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, with a molecular weight of 297.73. Hydrochlorothiazide is slightly soluble in water and freely soluble in sodium hydroxide solution, n-butylamine, and dimethylformamide, but is sparingly soluble in methanol and insoluble in ether, chloroform, and dilute mineral acids.

Uses and Indications

This fixed combination drug is indicated for the treatment of hypertension or edema in patients who develop hypokalemia while on hydrochlorothiazide alone. It is also indicated for patients who require a thiazide diuretic and in whom the development of hypokalemia cannot be risked, such as those on concomitant digitalis preparations or with a history of cardiac arrhythmias.

This drug is not indicated for the initial therapy of edema or hypertension except in individuals where the risk of developing hypokalemia is unacceptable. Triamterene and hydrochlorothiazide may be used alone or in combination with other antihypertensive agents, including beta-blockers; however, dosage adjustments may be necessary due to potential enhancement of the actions of these drugs.

Limitations of Use The routine use of diuretics in otherwise healthy pregnant women is inappropriate and poses unnecessary risks to both mother and fetus. Diuretics do not prevent the development of toxemia of pregnancy, nor is there satisfactory evidence supporting their efficacy in treating established toxemia.

In cases of edema during pregnancy, thiazides may be indicated when the edema is due to pathological causes. However, dependent edema resulting from the mechanical effects of pregnancy should be managed through non-pharmacological means, such as elevation of the lower extremities and the use of support hose. The hypervolemia associated with normal pregnancy is typically not harmful and is often accompanied by edema. If this edema causes discomfort, increased recumbency may provide relief. In rare instances where extreme discomfort occurs and is not alleviated by rest, a short course of diuretics may be appropriate.

Dosage and Administration

The usual dosage of Triamterene and Hydrochlorothiazide 37.5 mg/25 mg is one or two tablets administered daily as a single dose, with appropriate monitoring of serum potassium levels. For the 75 mg/50 mg formulation, the recommended dosage is one tablet daily, also with serum potassium monitoring.

There is no clinical experience supporting the use of more than one 75 mg/50 mg tablet or more than two 37.5 mg/25 mg tablets in a single day. In patients who require hydrochlorothiazide therapy but cannot tolerate hypokalemia, treatment may be initiated with the 37.5 mg/25 mg formulation of triamterene and hydrochlorothiazide.

If an optimal blood pressure response is not achieved with the 37.5 mg/25 mg dosage, the healthcare provider may consider increasing the dose to either two 37.5 mg/25 mg tablets daily as a single dose or one 75 mg/50 mg tablet daily.

Patients currently receiving 50 mg of hydrochlorothiazide who develop hypokalemia may be transitioned directly to the 75 mg/50 mg formulation. Similarly, patients on 25 mg of hydrochlorothiazide who experience hypokalemia may be switched directly to the 37.5 mg triamterene/25 mg hydrochlorothiazide formulation.

Clinical studies indicate that patients taking less bioavailable formulations of triamterene and hydrochlorothiazide, with daily doses ranging from 25 mg to 50 mg of hydrochlorothiazide and 50 mg to 100 mg of triamterene, can be safely converted to one 37.5 mg/25 mg tablet of triamterene and hydrochlorothiazide daily.

Contraindications

Triamterene and hydrochlorothiazide are contraindicated in the following situations:

Use is contraindicated in patients with elevated serum potassium levels (≥ 5.5 mEq/liter) due to the risk of hyperkalemia. The combination should not be administered to patients receiving other potassium-conserving agents, such as spironolactone or amiloride hydrochloride, as this may further increase serum potassium levels. Additionally, concomitant potassium supplementation, including medications, potassium-containing salt substitutes, or potassium-enriched diets, is contraindicated.

The use of triamterene and hydrochlorothiazide is also contraindicated in patients with anuria, acute or chronic renal insufficiency, or significant renal impairment, as these conditions may exacerbate renal function and increase the risk of adverse effects. Furthermore, the combination should not be used in individuals with a known hypersensitivity to triamterene, hydrochlorothiazide, or other sulfonamide-derived drugs.

In cases of developing hyperkalemia or increasing azotemia, discontinuation of the drug is recommended, and a thiazide alone should be considered as a substitute.

Warnings and Precautions

Patients receiving triamterene and hydrochlorothiazide must be closely monitored for the potential development of hyperkalemia, characterized by serum potassium levels equal to or exceeding 5.5 mEq/liter. This condition is particularly prevalent in individuals with renal impairment, diabetes (even in the absence of renal dysfunction), the elderly, or those who are severely ill. Given the risk of fatal outcomes associated with uncorrected hyperkalemia, it is imperative that serum potassium levels are assessed at frequent intervals, especially during the initiation of therapy, following dosage adjustments, or in the presence of any illness that may affect renal function.

In cases where hyperkalemia is suspected, indicated by symptoms such as paresthesias, muscular weakness, fatigue, flaccid paralysis of the extremities, bradycardia, or shock, an electrocardiogram (ECG) should be performed. It is crucial to note that mild hyperkalemia may not present with ECG changes, thus ongoing monitoring of serum potassium levels is essential.

Should hyperkalemia be confirmed, triamterene and hydrochlorothiazide must be discontinued immediately, and a thiazide diuretic alone should be considered as a substitute. If serum potassium levels exceed 6.5 mEq/liter, more aggressive therapeutic interventions are warranted, which may include intravenous administration of calcium chloride or sodium bicarbonate, and/or the administration of glucose with a rapid-acting insulin preparation. Cationic exchange resins, such as sodium polystyrene sulfonate, may also be utilized either orally or rectally. In cases of persistent hyperkalemia, dialysis may be necessary.

The risk of hyperkalemia is heightened in patients with renal impairment. Therefore, individuals with mild renal functional impairment should not be prescribed this combination without rigorous and continuous monitoring of serum electrolytes, as cumulative drug effects may occur. Additionally, hyperkalemia has been documented in diabetic patients using potassium-sparing agents, even when renal function appears normal. Consequently, triamterene and hydrochlorothiazide should be avoided in diabetic patients unless serum electrolytes can be monitored frequently. Caution is also advised when co-administering these agents with angiotensin-converting enzyme (ACE) inhibitors due to their potassium-sparing effects.

General precautions necessitate careful monitoring for fluid and electrolyte imbalances, including hyponatremia, hypochloremic alkalosis, hypokalemia, and hypomagnesemia. Regular determination of serum electrolytes is recommended, particularly during episodes of vomiting or when patients are receiving parenteral fluids. Triamterene and hydrochlorothiazide may elevate blood urea nitrogen (BUN) and creatinine levels; thus, periodic assessments of these parameters are essential, especially in elderly patients or those with suspected hepatic or renal insufficiencies. If azotemia worsens, discontinuation of the medication is advised.

Caution is warranted in patients with impaired hepatic function or progressive liver disease, as even minor disturbances in fluid and electrolyte balance could precipitate hepatic coma. Additionally, triamterene has been associated with the formation of renal stones, and its use should be approached with caution in individuals with a history of renal lithiasis. As a weak folic acid antagonist, triamterene may contribute to megaloblastosis in patients with diminished folic acid stores; therefore, periodic blood evaluations are recommended in these cases. Furthermore, hyperuricemia and acute gout may be triggered in certain patients undergoing thiazide therapy.

In summary, vigilant monitoring of serum potassium levels, electrolytes, BUN, and creatinine is essential for patients on triamterene and hydrochlorothiazide to mitigate the risks associated with hyperkalemia and other potential complications.

Side Effects

Patients may experience a range of adverse reactions while using this medication, which can be categorized by seriousness and frequency.

Serious adverse reactions include hypersensitivity reactions such as anaphylaxis, photosensitivity, and respiratory distress, including pneumonitis. Hematologic reactions such as agranulocytosis, thrombocytopenia, and aplastic anemia have also been reported. Renal complications, including acute renal failure and acute interstitial nephritis, may occur, alongside the formation of renal stones composed of triamterene. Patients with impaired hepatic function or progressive liver disease should be monitored closely due to the risk of hepatic coma.

Common gastrointestinal adverse reactions include nausea, vomiting, diarrhea, constipation, and appetite disturbance. Patients may also experience jaundice, pancreatitis, gastric irritation, and cramping. Central nervous system effects such as drowsiness, fatigue, insomnia, headache, dizziness, and dry mouth have been noted, along with psychological symptoms including depression, anxiety, and restlessness.

Cardiovascular reactions may manifest as tachycardia, shortness of breath, and chest pain, with orthostatic hypotension potentially exacerbated by alcohol, barbiturates, or narcotics. Renal-related adverse reactions include urine discoloration and the formation of renal stones.

Ophthalmic effects such as xanthopsia and transient blurred vision have been reported. Additionally, patients may experience muscle cramps, weakness, and decreased sexual performance.

Altered laboratory findings are also significant. Patients may present with hyperkalemia, hypokalemia, hyponatremia, hypomagnesemia, and hypochloremia. Reversible elevations in blood urea nitrogen (BUN) and serum creatinine levels have been observed, along with hyperglycemia and glycosuria. Elevated liver enzymes have been reported in patients receiving triamterene and hydrochlorothiazide.

Warnings regarding hyperkalemia are critical, as abnormal elevations in serum potassium levels (≥5.5 mEq/liter) can lead to symptoms such as paresthesias, muscular weakness, and bradycardia. Potassium-conserving therapy should be avoided in severely ill patients at risk for respiratory or metabolic acidosis.

Patients should be monitored for fluid or electrolyte imbalances, including hyponatremia and hypochloremic alkalosis. Hydrochlorothiazide may cause acute myopia and secondary angle-closure glaucoma, presenting with acute onset of decreased visual acuity or ocular pain. Furthermore, triamterene is a weak folic acid antagonist and may contribute to megaloblastosis, while hyperuricemia and acute gout may be precipitated in certain patients receiving thiazide therapy.

Drug Interactions

Thiazide diuretics may enhance the effects of other antihypertensive agents, potentially leading to additive hypotensive effects. Clinicians should monitor blood pressure closely when initiating or adjusting therapy with thiazides in patients already receiving antihypertensive medications.

Thiazides can diminish arterial responsiveness to norepinephrine; however, this effect does not compromise the therapeutic efficacy of norepinephrine as a pressor agent. Additionally, thiazides have been observed to increase responsiveness to neuromuscular blocking agents such as tubocurarine, which may necessitate adjustments in dosing or monitoring of neuromuscular function.

Concomitant use of lithium with diuretics, including thiazides, is generally contraindicated due to the potential for reduced renal clearance of lithium, significantly increasing the risk of lithium toxicity. It is advisable to consult the lithium package insert for specific guidance on managing such interactions.

Caution is warranted when administering non-steroidal anti-inflammatory drugs (NSAIDs) alongside triamterene and hydrochlorothiazide, as acute renal failure has been reported in some patients under such combined therapy. Monitoring of renal function is recommended in these cases.

The combination of potassium-sparing agents with angiotensin-converting enzyme (ACE) inhibitors should be approached with extreme caution due to a markedly increased risk of hyperkalemia. Frequent monitoring of serum potassium levels is essential to mitigate this risk.

Lastly, triamterene and quinidine share similar fluorescence spectra, which may interfere with the accurate measurement of quinidine levels when used concurrently with triamterene and hydrochlorothiazide. Clinicians should consider alternative monitoring strategies to ensure accurate assessment of quinidine concentrations.

Packaging & NDC

The table below lists all NDC Code configurations of Triamterene and Hydrochlorothiazide, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established. Therefore, the use of this medication in children, infants, and adolescents should be approached with caution until further data is available.

Geriatric Use

Elderly patients, particularly those aged 65 and older, are at an increased risk for hyperkalemia, especially if they have underlying renal impairment or diabetes. It is essential to monitor serum potassium levels at frequent intervals in this population, particularly when initiating treatment with triamterene and hydrochlorothiazide, when dosages are adjusted, or during any illness that may affect renal function.

Cumulative drug effects may be more pronounced in elderly patients with impaired renal function. Studies have demonstrated that the renal clearances of hydrochlorothiazide and the pharmacologically active metabolite of triamterene are reduced in this demographic, leading to increased plasma levels following administration.

Additionally, periodic assessments of blood urea nitrogen (BUN) and creatinine levels are recommended, as elevations in these parameters may occur more frequently in elderly patients. Careful monitoring and appropriate dose modifications are advised to ensure the safety and efficacy of treatment in this vulnerable population.

Pregnancy

The use of triamterene and hydrochlorothiazide during pregnancy is classified as Pregnancy Category C. The safety of these medications in pregnant patients has not been established due to the absence of adequate and well-controlled studies in this population. Therefore, triamterene and hydrochlorothiazide should only be administered during pregnancy if the potential benefits to the mother outweigh the risks to the fetus.

It is important to note that both thiazides and triamterene can cross the placental barrier and are detectable in cord blood. Consequently, healthcare professionals must carefully consider the anticipated benefits against the potential hazards to the fetus when prescribing these medications. Known risks associated with their use during pregnancy include fetal or neonatal jaundice, pancreatitis, thrombocytopenia, and possibly other adverse reactions that have been observed in adults.

Given that animal reproduction studies do not always predict human responses, triamterene and hydrochlorothiazide should be used during pregnancy only when clearly necessary.

Lactation

Thiazides and triamterene in combination have not been studied in nursing mothers. However, triamterene has been shown to appear in animal milk, suggesting that it may also be excreted in human breast milk. Additionally, thiazides are known to be excreted in human breast milk.

If the use of the combination drug product is deemed essential, it is recommended that the lactating mother discontinue breastfeeding.

Renal Impairment

Patients with renal impairment are at an increased risk for hyperkalemia, particularly those with diabetes (even in the absence of renal impairment), elderly patients, or those who are severely ill. Serum potassium levels should be monitored at frequent intervals, especially when initiating treatment with triamterene and hydrochlorothiazide, during dosage adjustments, or in the presence of any illness that may affect renal function.

For patients with mild renal functional impairment, the use of this drug is not recommended without ongoing and frequent monitoring of serum electrolytes. Cumulative drug effects may occur in patients with impaired renal function, as evidenced by reduced renal clearances of hydrochlorothiazide and the active metabolite of triamterene, leading to increased plasma levels following administration in elderly patients and those with renal impairment.

In diabetic patients, the use of potassium-conserving agents has been associated with hyperkalemia, even without apparent renal impairment; therefore, triamterene and hydrochlorothiazide should be avoided in this population. If these medications are used in severely ill patients, it is crucial to avoid potassium-conserving therapy, particularly in cases where respiratory or metabolic acidosis may develop, as this condition can lead to rapid increases in serum potassium levels. Frequent evaluations of acid/base balance and serum electrolytes are necessary in these patients.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

In cases of overdosage with triamterene and hydrochlorothiazide, it is important to note that specific data regarding human overdosage are lacking, and no specific antidote is available.

Clinical Manifestations The primary concern in overdosage is the potential for fluid and electrolyte imbalances. Excessive doses of triamterene may lead to hyperkalemia, dehydration, nausea, vomiting, weakness, and possibly hypotension. Conversely, overdosing on hydrochlorothiazide has been associated with hypokalemia, hypochloremia, hyponatremia, dehydration, lethargy (which may progress to coma), and gastrointestinal irritation.

Management Management of overdosage is symptomatic and supportive. It is recommended that therapy with triamterene and hydrochlorothiazide be discontinued immediately. Healthcare professionals should consider inducing emesis or performing gastric lavage to mitigate absorption of the drug. Continuous monitoring of serum electrolyte levels and fluid balance is essential to address any imbalances that may arise.

Supportive measures should be instituted as necessary to maintain hydration, electrolyte balance, and the proper functioning of respiratory, cardiovascular, and renal systems.

Nonclinical Toxicology

Studies evaluating the teratogenic effects of triamterene and hydrochlorothiazide tablets, as well as the triamterene/hydrochlorothiazide combination or triamterene alone, have not been conducted. However, non-teratogenic effects were observed with hydrochlorothiazide, which demonstrated no adverse effects on the fertility of both male and female mice and rats when administered dietary doses of up to 100 mg/kg/day and 4 mg/kg/day, respectively, prior to mating and throughout gestation. These doses correspond to multiples of the Maximum Recommended Human Dose (MRHD) of 100 for mice and 4 for rats based on body weight, and 9.4 for mice and 0.8 for rats based on body surface area.

Long-term studies involving triamterene and hydrochlorothiazide tablets or the triamterene/hydrochlorothiazide combination have not been performed. In studies conducted by the National Toxicology Program, rats were fed diets containing triamterene at concentrations of 0, 150, 300, or 600 ppm, while mice were fed diets with 0, 100, 200, or 400 ppm. Male and female rats at the highest concentration received approximately 25 and 30 mg/kg/day, respectively, while male and female mice received about 45 and 60 mg/kg/day, respectively. An increased incidence of hepatocellular neoplasia, primarily adenomas, was noted in male and female mice at the highest dosage level, which represents 7.5 times and 10 times the MRHD of 300 mg/kg (or 6 mg/kg/day based on a 50 kg patient) for male and female mice, respectively, when calculated based on body weight, and 0.7 times and 0.9 times the MRHD based on body surface area. In contrast, hepatocellular neoplasia in the rat study was limited to males exposed to triamterene, with no dose-dependent relationship and no statistically significant difference from control incidence at any dose level.

Two-year feeding studies in mice and rats, also conducted under the National Toxicology Program, involved doses of hydrochlorothiazide up to 600 mg/kg/day for mice and 100 mg/kg/day for rats. These doses correspond to 600 times (in mice) and 100 times (in rats) the MRHD for hydrochlorothiazide (50 mg/day or 1 mg/kg/day based on a 50 kg patient) when assessed on a body-weight basis, and 56 times (in mice) and 21 times (in rats) based on body surface area. These studies revealed no evidence of carcinogenic potential for hydrochlorothiazide in rats or female mice, although equivocal evidence of hepatocarcinogenicity was observed in male mice.

Studies assessing the mutagenic potential of triamterene and hydrochlorothiazide tablets or the triamterene/hydrochlorothiazide combination have not been performed. Triamterene was found to be non-mutagenic in bacterial strains (S. typhimurium strains TA 98, TA 100, TA 1535, or TA 1537) with or without metabolic activation. It did not induce chromosomal aberrations in Chinese hamster ovary (CHO) cells in vitro, regardless of metabolic activation, but did induce sister chromatid exchanges in CHO cells in vitro with and without metabolic activation. Hydrochlorothiazide was not genotoxic in various in vitro assays, including the Ames test using strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538, the CHO test for chromosomal aberrations, or in vivo assays involving mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. However, positive results were obtained in the in vitro CHO sister chromatid exchange test and in mouse lymphoma cell assays at hydrochlorothiazide concentrations ranging from 43 to 1300 mcg/mL. Additionally, positive results were noted in the Aspergillus nidulans nondisjunction assay using an unspecified concentration of hydrochlorothiazide.

Postmarketing Experience

Postmarketing experience has identified several important considerations regarding the use of triamterene and hydrochlorothiazide.

Hyperkalemia has been reported more frequently in patients with renal impairment, diabetes (even in the absence of renal impairment), elderly patients, and those who are severely ill. Monitoring of serum potassium levels is essential, particularly in patients initiating treatment, those undergoing dosage adjustments, or those experiencing illnesses that may affect renal function. Warning signs of hyperkalemia include paresthesias, muscular weakness, fatigue, flaccid paralysis of the extremities, bradycardia, and shock; an electrocardiogram (ECG) should be performed if hyperkalemia is suspected. In cases of confirmed hyperkalemia, it is recommended to discontinue triamterene and hydrochlorothiazide immediately and consider substituting with a thiazide alone.

The risk of developing hyperkalemia is heightened in patients with renal impairment, and cumulative drug effects may be observed in this population. Patients with mild renal functional impairment should be monitored closely for serum electrolyte levels if prescribed this medication. Additionally, hyperkalemia has been noted in diabetic patients using potassium-sparing agents, even without evident renal impairment.

Hydrochlorothiazide has been associated with acute myopia and secondary angle-closure glaucoma, which may present as an acute onset of decreased visual acuity or ocular pain within hours to weeks of initiation. Untreated acute angle-closure glaucoma can result in permanent vision loss, necessitating the rapid discontinuation of hydrochlorothiazide. Risk factors for this condition may include a history of sulfonamide or penicillin allergy.

Adverse effects linked to the use of triamterene and hydrochlorothiazide include intrahepatic cholestatic jaundice, pancreatitis, gastrointestinal disturbances (nausea, vomiting, diarrhea, constipation), neurological effects (drowsiness, dizziness, headache), and hematological changes (leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia). Other reported side effects encompass respiratory distress, muscle cramps, decreased sexual performance, and various skin reactions.

Moderate to severe adverse reactions warrant a reduction or withdrawal of therapy. Reversible elevations in blood urea nitrogen (BUN) and serum creatinine levels have been observed in hypertensive patients treated with this combination, along with elevated liver enzymes.

Patient Counseling

Patients should be monitored for potential fluid or electrolyte imbalances, including conditions such as hyponatremia, hypochloremic alkalosis, hypokalemia, and hypomagnesemia. Healthcare providers should ensure that serum electrolytes are determined at appropriate intervals, particularly in patients experiencing vomiting or those receiving parenteral fluids.

Patients should be made aware of warning signs or symptoms indicative of fluid and electrolyte imbalance. These may include dryness of the mouth, increased thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.

For patients receiving triamterene and hydrochlorothiazide, it is important to advise them that hypokalemia may develop, particularly in cases of brisk diuresis, severe cirrhosis, or during concomitant use of corticosteroids, ACTH, or amphotericin B. Patients should also be informed that the use of these medications may lead to elevated blood urea nitrogen (BUN) and creatinine levels, which are typically not indicative of renal toxicity but rather a secondary effect of reduced glomerular filtration rate or depletion of intravascular fluid volume. Periodic assessments of BUN and creatinine should be conducted, especially in elderly patients or those with suspected or confirmed hepatic disease or renal insufficiencies.

Patients should be cautioned about the risk of hyperkalemia, particularly in individuals with renal impairment, diabetes, or those who are elderly or severely ill. If hyperkalemia is suspected, patients should be instructed to seek medical attention immediately.

Additionally, patients should be informed that hydrochlorothiazide can cause an idiosyncratic reaction leading to acute transient myopia and acute angle-closure glaucoma, with symptoms that may include an acute onset of decreased visual acuity or ocular pain.

It is essential to communicate to patients that the use of diuretics in otherwise healthy women during pregnancy is inappropriate and poses unnecessary risks to both the mother and fetus. If the use of triamterene and hydrochlorothiazide is considered essential during pregnancy, patients should be advised that the anticipated benefits must be carefully weighed against potential hazards to the fetus.

Nursing mothers should be informed that triamterene may appear in animal milk and could also be present in human milk; therefore, if the combination drug product is deemed necessary, the patient should discontinue nursing. Lastly, patients should be made aware that the safety and effectiveness of this medication in pediatric patients have not been established.

Storage and Handling

The product is supplied in a tight, light-resistant container equipped with a child-resistant closure. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F) in accordance with USP Controlled Room Temperature guidelines. Additionally, it is essential to protect the product from light to maintain its integrity.

Additional Clinical Information

Serum potassium levels must be monitored at frequent intervals, particularly in patients initiating treatment with triamterene and hydrochlorothiazide, during dosage adjustments, or in the presence of any illness that may affect renal function. Clinicians should also perform periodic assessments of serum electrolytes to identify potential imbalances, as well as regular BUN and creatinine tests, especially in elderly patients or those with suspected or confirmed hepatic or renal impairments.

The standard dosing regimen for Triamterene and Hydrochlorothiazide 37.5 mg/25 mg is one or two tablets daily, administered as a single dose, while the 75 mg/50 mg formulation is typically prescribed as one tablet daily, both requiring appropriate monitoring of serum potassium. Patients should be counseled to watch for signs of hyperkalemia, including paresthesias, muscular weakness, fatigue, flaccid paralysis, bradycardia, and shock, and to understand the risks of electrolyte imbalances necessitating regular monitoring.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Triamterene and Hydrochlorothiazide as submitted by Aidarex Pharmaceuticals LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)