TRIAMTERENE AND HYDROCHLOROTHIAZIDE- triamterene and hydrochlorothiazide tablet

United States - English - NLM (National Library of Medicine)

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Active ingredient:
TRIAMTERENE (UNII: WS821Z52LQ) (TRIAMTERENE - UNII:WS821Z52LQ), HYDROCHLOROTHIAZIDE (UNII: 0J48LPH2TH) (HYDROCHLOROTHIAZIDE - UNII:0J48LPH2TH)
Available from:
Bryant Ranch Prepack
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
This fixed combination drug is not indicated for the initial therapy of edema or hypertension except in individuals in whom the development of hypokalemia cannot be risked. - Triamterene and hydrochlorothiazide tablets are indicated for the treatment of hypertension or edema in patients who develop hypokalemia on hydrochlorothiazide alone. - Triamterene and hydrochlorothiazide is also indicated for those patients who require a thiazide diuretic and in whom the development of hypokalemia cannot be risked (e.g., patients on concomitant digitalis preparations, or with a history of cardiac arrhythmias, etc.). Triamterene and hydrochlorothiazide may be used alone or in combination with other antihypertensive drugs such as beta-blockers. Since triamterene and hydrochlorothiazide may enhance the actions of these drugs, dosage adjustments may be necessary. The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent developmen
Product summary:
Product: 63629-8191 NDC: 63629-8191-1 30 TABLET in a BOTTLE
Authorization status:
Abbreviated New Drug Application
Authorization number:
63629-8191-1

TRIAMTERENE AND HYDROCHLOROTHIAZIDE- triamterene and

hydrochlorothiazide tablet

Bryant Ranch Prepack

----------

Triamterene and

Hydrochlorothiazide

Tablets, USP

Revised: November 2014

Rx only

DESCRIPTION:

Triamterene and hydrochlorothiazide tablets, USP, combines triamterene, a potassium-conserving

diuretic, with the natriuretic agent, hydrochlorothiazide. Triamterene and hydrochlorothiazide tablets

are available in two strengths. Each triamterene and hydrochlorothiazide tablet, 75 mg/50 mg, contains

triamterene, USP, 75 mg and hydrochlorothiazide, USP, 50 mg. Each triamterene and

hydrochlorothaizide tablet, 37.5 mg/25 mg, contains triamterene, USP, 37.5 mg and hydrochlorothiazide,

USP, 25 mg.

Both strengths of triamterene and hydrochlorothiazide tablets for oral administration contain the

following inactive ingredients: anhydrous lactose, microcrystalline cellulose, polacrilin potassium,

polyethylene glycol 8000, povidone, and magnesium stearate. Triamterene and hydrochlorothiazide

tablets, 37.5 mg/25 mg also contain FD&C Blue #2.

Triamterene is 2, 4, 7-triamino-6-phenylpteridine. Triamterene is practically insoluble in water,

benzene, chloroform, ether and dilute alkali hydroxides. It is soluble in formic acid and sparingly

soluble in methoxyethanol. Triamterene is very slightly soluble in acetic acid, alcohol and dilute

mineral acids. Its molecular weight is 253.27. Its structural formula is:

Hydrochlorothiazide is 6-chloro-3, 4-dihydro-2H-1, 2, 4-benzothiadiazine-7-sulfonamide 1, 1-dioxide.

Hydrochlorothiazide is slightly soluble in water and freely soluble in sodium hydroxide solution, n-

butylamine and dimethylformamide. It is sparingly soluble in methanol and insoluble in ether,

chloroform and dilute mineral acids. Its molecular weight is 297.73. Its structural formula is:

CLINICAL PHARMACOLOGY:

Triamterene and hydrochlorothiazide is a diuretic, antihypertensive drug product, principally due to its

hydrochlorothiazide component; the triamterene component reduces the excessive potassium loss which

may occur with hydrochlorothiazide use.

Hydrochlorothiazide:

Hydrochlorothiazide is a diuretic and antihypertensive agent. It blocks the renal tubular absorption of

sodium and chloride ions. This natriuresis and diuresis is accompanied by a secondary loss of

potassium and bicarbonate. Onset of hydrochlorothiazide’s diuretic effect occurs within 2 hours and the

peak action takes place in 4 hours. Diuretic activity persists for approximately 6 to 12 hours.

The exact mechanism of hydrochlorothiazide’s antihypertensive action is not known, although it may

relate to the excretion and redistribution of body sodium. Hydrochlorothiazide does not affect normal

blood pressure. Following oral administration, peak hydrochlorothiazide plasma levels are attained in

approximately 2 hours. It is excreted rapidly and unchanged in the urine.

Well-controlled studies have demonstrated that doses of hydrochlorothiazide as low as 25 mg given

once daily are effective in treating hypertension, but the dose-response has not been clearly established.

Triamterene:

Triamterene is a potassium-conserving (antikaliuretic) diuretic with relatively weak natriuretic

properties. It exerts its diuretic effect on the distal renal tubule to inhibit the reabsorption of sodium in

exchange for potassium and hydrogen. With this action, triamterene increases sodium excretion and

reduces the excessive loss of potassium and hydrogen associated with hydrochlorothiazide.

Triamterene is not a competitive antagonist of the mineralocorticoids and its potassium-conserving

effect is observed in patients with Addison’s disease, i.e., without aldosterone. Triamterene’s onset and

duration of activity is similar to hydrochlorothiazide. No predictable antihypertensive effect has been

demonstrated with triamterene.

Triamterene is rapidly absorbed following oral administration. Peak plasma levels are achieved within

one hour after dosing. Triamterene is primarily metabolized to the sulfate conjugate of

hydroxytriamterene. Both the plasma and urine levels of this metabolite greatly exceed triamterene

levels.

The amount of triamterene added to 50 mg of hydrochlorothiazide in triamterene and

hydrochlorothiazide tablets was determined from steady-state dose-response evaluations in which

various doses of liquid preparations of triamterene were administered to hypertensive persons who

developed hypokalemia with hydrochlorothiazide (50 mg given once daily). Single daily doses of 75

mg triamterene resulted in greater increases in serum potassium than lower doses (25 mg and 50 mg),

while doses greater than 75 mg of triamterene resulted in no additional elevations in serum potassium

levels. The amount of triamterene added to the 25 mg of hydrochlorothiazide in triamterene and

hydrochlorothiazide tablets 37.5 mg/25 mg was also determined from steady-state dose-response

evaluations in which various doses of liquid preparations of triamterene were administered to

hypertensive persons who developed hypokalemia with hydrochlorothiazide (25 mg given once daily).

Single daily doses of 37.5 mg triamterene resulted in greater increases in serum potassium than a lower

dose (25 mg), while doses greater than 37.5 mg of triamterene, i.e., 75 mg and 100 mg, resulted in no

additional elevations in serum potassium levels. The dose-response relationship of triamterene was also

evaluated in patients rendered hypokalemic by hydrochlorothiazide given 25 mg twice daily.

Triamterene given twice daily increased serum potassium levels in a dose-related fashion. However,

the combination of triamterene and hydrochlorothiazide given twice daily also appeared to produce an

increased frequency of elevation in serum BUN and creatinine levels. The largest increases in serum

potassium, BUN and creatinine in this study were observed with 50 mg of triamterene given twice daily,

the largest dose tested. Ordinarily, triamterene does not entirely compensate for the kaliuretic effect of

hydrochlorothiazide and some patients may remain hypokalemic while receiving triamterene and

hydrochlorothiazide. In some individuals, however, it may induce hyperkalemia (see WARNINGS).

The triamterene and hydrochlorothiazide components of this product are well absorbed and are

bioequivalent to liquid preparations of the individual components administered orally. Food does not

influence the absorption of triamterene or hydrochlorothiazide from triamterene and

hydrochlorothiazide tablets. The hydrochlorothiazide component of triamterene and

hydrochlorothiazide tablets is bioequivalent to single entity hydrochlorothiazide tablet formulations.

INDICATIONS AND USAGE:

This fixed combination drug is not indicated for the initial therapy of edema or hypertension

except in individuals in whom the development of hypokalemia cannot be risked.

1. Triamterene and hydrochlorothiazide tablets are indicated for the treatment of hypertension or

edema in patients who develop hypokalemia on hydrochlorothiazide alone.

2. Triamterene and hydrochlorothiazide is also indicated for those patients who require a thiazide

diuretic and in whom the development of hypokalemia cannot be risked (e.g., patients on concomitant

digitalis preparations, or with a history of cardiac arrhythmias, etc.).

Triamterene and hydrochlorothiazide may be used alone or in combination with other antihypertensive

drugs such as beta-blockers. Since triamterene and hydrochlorothiazide may enhance the actions of

these drugs, dosage adjustments may be necessary.

Usage in Pregnancy:

The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and

fetus to unnecessary hazard. Diuretics do not prevent development of toxemia in pregnancy, and there is

no satisfactory evidence that they are useful in the treatment of developed toxemia.

Edema during pregnancy may arise from pathological causes or from the physiologic and mechanical

consequences of pregnancy. Thiazides are indicated in pregnancy when edema is due to pathologic

causes, just as they are in the absence of pregnancy. Dependent edema in pregnancy, resulting from

restriction of venous return by the expanded uterus, is properly treated through elevation of the lower

extremities and use of support hose; use of diuretics to lower intravascular volume in this case is

illogical and unnecessary. There is hypervolemia during normal pregnancy which is harmful to neither

the fetus nor the mother (in the absence of cardiovascular disease), but which is associated with edema,

including generalized edema, in the majority of pregnant women. If this edema produces discomfort,

increased recumbency will often provide relief. In rare instances, this edema may cause extreme

discomfort which is not relieved by rest. In these cases, a short course of diuretics may provide relief

and may be appropriate.

CONTRAINDICATIONS:

Hyperkalemia:

Triamterene and hydrochlorothiazide should not be used in the presence of elevated serum potassium

levels (greater than or equal to 5.5 mEq/liter). If hyperkalemia develops, this drug should be

discontinued and a thiazide alone should be substituted.

Antikaliuretic Therapy or Potassium Supplementation:

Triamterene and hydrochlorothiazide should not be given to patients receiving other potassium-

conserving agents such as spironolactone, amiloride hydrochloride or other formulations containing

triamterene. Concomitant potassium supplementation in the form of medication, potassium-containing salt

substitute, or potassium-enriched diets should also not be used.

Impaired Renal Function:

Triamterene and hydrochlorothiazide is contraindicated in patients with anuria, acute and chronic renal

insufficiency or significant renal impairment.

Hypers ens itivity:

Triamterene and hydrochlorothiazide should not be used in patients who are hypersensitive to

triamterene or hydrochlorothiazide or other sulfonamide-derived drugs.

WARNINGS:

Hyperkalemia: Abnormal elevation of serum potassium levels (greater than or equal to 5.5

mEq/liter) can occur with all potassium-conserving diuretic combinations, including triamterene

and hydrochlorothiazide. Hyperkalemia is more likely to occur in patients with renal impairment,

diabetes (even without evidence of renal impairment), or elderly or severely ill patients. Since

uncorrected hyperkalemia may be fatal, serum potassium levels must be monitored at frequent

intervals especially in patients first receiving triamterene and hydrochlorothiazide, when dosages

are changed or with any illness that may influence renal function.

If hyperkalemia is suspected (warning signs include paresthesias, muscular weakness, fatigue, flaccid

paralysis of the extremities, bradycardia and shock), an electrocardiogram (ECG) should be obtained.

However, it is important to monitor serum potassium levels because mild hyperkalemia may not be

associated with ECG changes.

If hyperkalemia is present, triamterene and hydrochlorothiazide should be discontinued immediately and

a thiazide alone should be substituted. If the serum potassium exceeds 6.5 mEq/liter, more vigorous

therapy is required. The clinical situation dictates the procedures to be employed. These include the

intravenous administration of calcium chloride solution, sodium bicarbonate solution and/or the oral or

parenteral administration of glucose with a rapid-acting insulin preparation. Cationic exchange resins

such as sodium polystyrene sulfonate may be orally or rectally administered. Persistent hyperkalemia

may require dialysis.

The development of hyperkalemia associated with potassium-sparing diuretics is accentuated in the

presence of renal impairment (see CONTRAINDICATIONS). Patients with mild renal functional

impairment should not receive this drug without frequent and continuing monitoring of serum

electrolytes. Cumulative drug effects may be observed in patients with impaired renal function. The

renal clearances of hydrochlorothiazide and the pharmacologically active metabolite of triamterene, the

sulfate ester of hydroxytriamterene, have been shown to be reduced and the plasma levels increased

following triamterene and hydrochlorothiazide administration to elderly patients and patients with

impaired renal function.

Hyperkalemia has been reported in diabetic patients with the use of potassium-conserving agents even in

the absence of apparent renal impairment. Accordingly, triamterene and hydrochlorothiazide should be

avoided in diabetic patients. If it is employed, serum electrolytes must be frequently monitored.

Because of the potassium-sparing properties of angiotensin-converting enzyme (ACE) inhibitors,

triamterene and hydrochlorothiazide should be used cautiously, if at all, with these agents (see

PRECAUTIONS: Drug Interactions).

Metabolic or Respiratory Acidosis:

Potassium-conserving therapy should also be avoided in severely ill patients in whom respiratory or

metabolic acidosis may occur. Acidosis may be associated with rapid elevations in serum potassium

levels. If triamterene and hydrochlorothiazide is employed, frequent evaluations of acid/base balance

and serum electrolytes are necessary.

Acute Myopia and Secondary Angle-Closure Glaucoma:

Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient

myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or

ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure

glaucoma can lead to permanent vision loss. The primary treatment is to discontinue

hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be

considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-

closure glaucoma may include a history of sulfonamide or penicillin allergy.

PRECAUTIONS:

General:

Electrolyte Imbalance and BUN Increases:

Patients receiving triamterene and hydrochlorothiazide should be carefully monitored for fluid or

electrolyte imbalances, i.e., hyponatremia, hypochloremic alkalosis, hypokalemia, and hypomagnesemia.

Determination of serum electrolytes to detect possible electrolyte imbalance should be performed at

appropriate intervals. Serum and urine electrolyte determinations are especially important and should be

frequently performed when the patient is vomiting or receiving parenteral fluids. Warning signs or

symptoms of fluid and electrolyte imbalance include: dryness of mouth, thirst, weakness, lethargy,

drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia,

and gastrointestinal disturbances such as nausea and vomiting.

Any chloride deficit during thiazide therapy is generally mild and usually does not require any specific

treatment except under extraordinary circumstances (as in liver disease or renal disease). Dilutional

hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction,

rather than administration of salt, except in rare instances when the hyponatremia is life threatening. In

actual salt depletion, appropriate replacement is the therapy of choice.

Hypokalemia may develop with thiazide therapy, especially with brisk diuresis, when severe cirrhosis

is present, or during concomitant use of corticosteroids, ACTH, amphotericin B, or after prolonged

thiazide therapy. However, hypokalemia of this type is usually prevented by the triamterene component

of triamterene and hydrochlorothiazide tablets.

Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia can

sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased

ventricular irritability).

Triamterene and hydrochlorothiazide may produce an elevated blood urea nitrogen level (BUN),

creatinine level or both. This is probably not the result of renal toxicity but is secondary to a reversible

reduction of the glomerular filtration rate or a depletion of the intravascular fluid volume. Elevations in

BUN and creatinine levels may be more frequent in patients receiving divided dose diuretic therapy.

Periodic BUN and creatinine determinations should be made especially in elderly patients, patients with

suspected or confirmed hepatic disease, or renal insufficiencies. If azotemia increases, triamterene and

hydrochlorothiazide should be discontinued.

Hepatic Coma:

Triamterene and hydrochlorothiazide should be used with caution in patients with impaired hepatic

function or progressive liver disease, since minor alterations of fluid and electrolyte balance may

precipitate hepatic coma.

Renal Stones:

Triamterene has been reported in renal stones in association with other calculus components.

Triamterene and hydrochlorothiazide should be used with caution in patients with histories of renal

lithiasis.

Folic Acid Deficiency:

Triamterene is a weak folic acid antagonist and may contribute to the appearance of megaloblastosis in

instances where folic acid stores are decreased. In such patients, periodic blood evaluations are

recommended.

Hyperuricemia:

Hyperuricemia may occur or acute gout may be precipitated in certain patients receiving thiazide

therapy.

Metabolic and Endocrine Effects:

The thiazides may decrease serum PBI levels without signs of thyroid disturbance.

Calcium excretion is decreased by thiazides. Pathological changes in the parathyroid gland with

hypercalcemia and hypophosphatemia have been observed in a few patients on prolonged thiazide

therapy. The common complications of hyperparathyroidism such as renal lithiasis, bone resorption, and

peptic ulceration have not been seen. Thiazides should be discontinued before carrying out tests for

parathyroid function.

Insulin requirements in diabetic patients may be increased, decreased or unchanged. Diabetes mellitus

which has been latent may become manifest during thiazide administration.

Hypersensitivity:

Sensitivity reactions to thiazides may occur in patients with or without a history of allergy or bronchial

asthma.

Possible exacerbation or activation of systemic lupus erythematosus by thiazides has been reported.

Drug Interactions:

Thiazides may add to or potentiate the action of other antihypertensive drugs.

The thiazides may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient

to preclude effectiveness of the pressor agent for therapeutic use. Thiazides have also been shown to

increase the responsiveness to tubocurarine.

Lithium generally should not be given with diuretics because they reduce its renal clearance and add a

high risk of lithium toxicity. Refer to the package insert on lithium before use of such concomitant

therapy.

Acute renal failure has been reported in a few patients receiving indomethacin and formulations

containing triamterene and hydrochlorothiazide. Caution is therefore advised when administering non-

steroidal anti-inflammatory agents with triamterene and hydrochlorothiazide.

Potassium-sparing agents should be used very cautiously, if at all, in conjunction with angiotensin-

converting enzyme (ACE) inhibitors due to a greatly increased risk of hyperkalemia. Serum potassium

should be monitored frequently.

Drug/Laboratory Test Interactions:

Triamterene and quinidine have similar fluorescence spectra; thus, triamterene and hydrochlorothiazide

may interfere with the measurement of quinidine.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Carcinogenesis: Long-term studies with triamterene/hydrochlorothiazide combination have not been

conducted.

Triamterene: In studies conducted under the auspices of the National Toxicology Program, groups of

rats were fed diets containing 0, 150, 300 or 600 ppm triamterene and groups of mice were fed diets

containing 0, 100, 200 or 400 ppm triamterene. Male and female rats exposed to the highest tested

concentration received triamterene at about 25 and 30 mg/kg/day, respectively. Male and female mice

exposed to the highest tested concentration received triamterene at about 45 and 60 mg/kg/day,

respectively.

There was an increased incidence of hepatocellular neoplasia (primarily adenomas) in male and female

mice at the highest dosage level. These doses represent 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 based on

body-weight and 0.7 times and 0.9 times the MRHD when based on body-surface area. Although

hepatocellular neoplasia (exclusively adenomas) in the rat study was limited to triamterene-exposed

males, incidence was not dose-dependent and there was no statistically significant difference from

control incidence at any dose level.

Hydrochlorothiazide: Two-year feeding studies in mice and rats, conducted under the auspices of the

National Toxicology Program (NTP), treated mice and rats with doses of hydrochlorothiazide up to

600 and 100 mg/kg/day, respectively. On a body-weight basis, these doses are 600 times (in mice) and

100 times (in rats) the Maximum Recommended Human Dose (MRHD) for the hydrochlorothiazide

component of triamterene and hydrochlorothiazide tablets (50 mg/day or 1 mg/kg/day based on a 50 kg

patient). On the basis of body-surface area, these doses are 56 times (in mice) and 21 times (in rats) the

MRHD. These studies uncovered no evidence of carcinogenic potential of hydrochlorothiazide in rats

or female mice, but there was equivocal evidence of hepatocarcinogenicity in male mice.

Mutagenes is :

Studies of the mutagenic potential of the triamterene and hydrochlorothiazide combination have not been

performed.

Triamterene: Triamterene was not mutagenic in bacteria (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 with or without metabolic activation, but it did induce sister

chromatid exchanges in CHO cells in vitro with and without metabolic activation.

Hydrochlorothiazide: Hydrochlorothiazide was not genotoxic in in vitro assays using strains TA 98, TA

100, TA 1535, TA 1537 and TA 1538 of Salmonella typhimurium (the Ames test), in the Chinese hamster

ovary (CHO) test for chromosomal aberrations, or in in vivo assays using mouse germinal cell

chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive

lethal trait gene. Positive test results were obtained in the in vitro CHO sister chromatid exchange

(clastogenicity) test, and in the mouse lymphoma cell (mutagenicity) assays, using concentrations of

hydrochlorothiazide of 43 to 1300 mcg/mL. Positive test results were also obtained in the Aspergillus

nidulans nondisjunction assay using an unspecified concentration of hydrochlorothiazide.

Impairment of Fertility: Studies of the effects of the triamterene/ hydrochlorothiazide combination, or of

triamterene alone on animal reproductive function have not been conducted.

Hydrochlorothiazide: Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of

either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4

mg/kg/day, respectively, prior to mating and throughout gestation. Corresponding multiples of the

MRHD are 100 (mice) and 4 (rats) on the basis of body-weight and 9.4 (mice) and 0.8 (rats) on the basis

of body-surface area.

Pregnancy:

Teratogenic Effects: Category C: Animal reproduction studies to determine the potential for fetal harm

by triamterene and hydrochlorothiazide tablets have not been conducted. Nevertheless, a One

Generation Study in the rat approximated triamterene and hydrochlorothiazide’s composition by using a

1:1 ratio of triamterene to hydrochlorothiazide (30:30 mg/kg/day). There was no evidence of

teratogenicity at those doses that were, on a body-weight basis, 15 and 30 times, respectively, the

MRHD, and, on the basis of body-surface area, 3.1 and 6.2 times, respectively, the MRHD.

The safe use of triamterene and hydrochlorothiazide tablets in pregnancy has not been established since

there are no adequate and well-controlled studies with triamterene and hydrochlorothiazide tablets in

pregnant women. Triamterene and hydrochlorothiazide tablets should be used during pregnancy only if

the potential benefit justifies the risk to the fetus.

Triamterene: Reproduction studies have been performed in rats at doses as high as 20 times the

Maximum Recommended Human Dose (MRHD) on the basis of body-weight, and 6 times the MRHD on

the basis of body-surface area without evidence of harm to the fetus due to triamterene.

Because animal reproduction studies are not always predictive of human response, this drug should be

used during pregnancy only if clearly needed.

Hydrochlorothiazide: Hydrochlorothiazide was orally administered to pregnant mice and rats during

respective periods of major organogenesis at doses up to 3000 and 1000 mg/kg/day, respectively. At

these doses, which are multiples of the MRHD equal to 3000 for mice and 1000 for rats, based on

body-weight, and equal to 282 for mice and 206 for rats, based on body-surface area, there was no

evidence of harm to the fetus. There are, however, no adequate and well-controlled studies in pregnant

women. Because animal reproduction studies are not always predictive of human response, this drug

should be used during pregnancy only if clearly needed.

Nonteratogenic Effects: Thiazides and triamterene have been shown to cross the placental barrier and

appear in cord blood. The use of thiazides and triamterene in pregnant women requires that the

anticipated benefits be weighed against possible hazards to the fetus. These hazards include fetal or

neonatal jaundice, pancreatitis, thrombocytopenia, and possibly other adverse reactions that have

occurred in the adult.

Nursing Mothers:

Thiazides and triamterene in combination have not been studied in nursing mothers. Triamterene appears

in animal milk and this may occur in humans. Thiazides are excreted in human breast milk. If use of the

combination drug product is deemed essential, the patient should stop nursing.

Pediatric Use:

Safety and effectiveness in pediatric patients have not been established.

ADVERSE REACTIONS:

Side effects observed in association with the use of triamterene and hydrochlorothiazide tablets, other

combination products containing triamterene/hydrochlorothiazide, and products containing triamterene

or hydrochlorothiazide include the following:

Gastrointestinal: jaundice (intrahepatic cholestatic jaundice), pancreatitis, nausea, appetite disturbance,

taste alteration, vomiting, diarrhea, constipation, anorexia, gastric irritation, cramping.

Central Nervous System: drowsiness and fatigue, insomnia, headache, dizziness, dry mouth,

depression, anxiety, vertigo, restlessness, paresthesias.

Cardiovascular: tachycardia, shortness of breath and chest pain, orthostatic hypotension (may be

aggravated by alcohol, barbiturates or narcotics).

Renal: acute renal failure, acute interstitial nephritis, renal stones composed of triamterene in

association with other calculus materials, urine discoloration.

Hematologic: leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia and

megaloblastosis.

Ophthalmic: xanthopsia, transient blurred vision.

Hypersensitivity: anaphylaxis, photosensitivity, rash, urticaria, purpura, necrotizing angiitis (vasculitis,

cutaneous vasculitis), fever, respiratory distress including pneumonitis.

Other: muscle cramps and weakness, decreased sexual performance and sialadenitis.

Whenever adverse reactions are moderate to severe, therapy should be reduced or withdrawn.

Altered Laboratory Findings:

Serum Electrolytes: hyperkalemia, hypokalemia, hyponatremia, hypomagnesemia, hypochloremia

(see WARNINGS and PRECAUTIONS).

Creatinine, Blood Urea Nitrogen: Reversible elevations in BUN and serum creatinine have been

observed in hypertensive patients treated with triamterene and hydrochlorothiazide tablets.

Glucose: hyperglycemia, glycosuria and diabetes mellitus (see PRECAUTIONS).

Serum Uric Acid, PBI and Calcium: (see PRECAUTIONS).

Other: Elevated liver enzymes have been reported in patients receiving triamterene and

hydrochlorothiazide tablets.

To report SUSPECTED ADVERSE REACTIONS, contact Actavis at 1-800-272-5525 or FDA at

1-800-FDA-1088 or www.fda.gov/medwatch.

OVERDOSAGE:

No specific data are available regarding triamterene and hydrochlorothiazide overdosage in humans and

no specific antidote is available.

Fluid and electrolyte imbalances are the most important concern. Excessive doses of the triamterene

component may elicit hyperkalemia, dehydration, nausea, vomiting and weakness and possibly

hypotension. Overdosing with hydrochlorothiazide has been associated with hypokalemia,

hypochloremia, hyponatremia, dehydration, lethargy (may progress to coma) and gastrointestinal

irritation. Treatment is symptomatic and supportive. Therapy with triamterene and hydrochlorothiazide

should be discontinued. Induce emesis or institute gastric lavage. Monitor serum electrolyte levels and

fluid balance. Institute supportive measures as required to maintain hydration, electrolyte balance,

respiratory, cardiovascular, and renal function.

DOSAGE AND ADMINISTRATION:

Note: 37.5 mg/25 mg= 37.5 mg triamterene and 25 mg hydrochlorothiazide

75 mg/50 mg= 75 mg triamterene and 50 mg hydrochlorothiazide

The usual dosage of triamterene and hydrochlorothiazide as a tablet is 37.5 mg/25 mg or 75 mg/50 mg

daily, given as a single dose, with appropriate monitoring of serum potassium (see WARNINGS).

There is no experience with the use of more than 75 mg/50 mg daily of triamterene and

hydrochlorothiazide. Clinical experience with the administration of 37.5 mg/25 mg of triamterene and

hydrochlorothiazide twice daily in divided doses (rather than as a single dose) suggests an increased

risk of electrolyte imbalance and renal dysfunction.

Patients receiving 50 mg of hydrochlorothiazide who become hypokalemic may be transferred to this

75 mg/50 mg product directly. Patients receiving 25 mg hydrochlorothiazide who become hypokalemic

may be transferred to a 37.5 mg/25 mg product directly.

In patients requiring hydrochlorothiazide therapy and in whom hypokalemia cannot be risked, therapy

may be initiated with 37.5 mg/25 mg of triamterene and hydrochlorothiazide. If an optimal blood

pressure response is not obtained with 37.5 mg/25 mg triamterene and hydrochlorothiazide, the dose

should be increased to 75 mg/50 mg daily as a single dose. If blood pressure still is not controlled,

another antihypertensive agent may be added (see PRECAUTIONS: Drug Interactions).

Clinical studies have shown that patients taking less bioavailable formulations of triamterene and

hydrochlorothiazide in daily doses of 25 mg to 50 mg hydrochlorothiazide and 50 mg to 100 mg of

triamterene may be safely changed to 37.5 mg/25 mg of triamterene and hydrochlorothiazide daily. All

patients changed from less bioavailable formulations to triamterene and hydrochlorothiazide tablets

should be monitored clinically and for serum potassium after the transfer.

HOW SUPPLIED:

Product: 63629-8191

NDC: 63629-8191-1 30 TABLET in a BOTTLE

TRIAMTERENE/HCTZ 75/50MG TAB

TRIAMTERENE AND HYDROCHLOROTHIAZIDE

triamterene and hydrochlorothiazide tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 36 29 -8 19 1(NDC:0 59 1-0 348 )

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

TRIAMTERENE (UNII: WS8 21Z52LQ) (TRIAMTERENE - UNII:WS8 21Z52LQ)

TRIAMTERENE

75 mg

Bryant Ranch Prepack

HYDRO CHLO RO THIAZIDE (UNII: 0 J48 LPH2TH) (HYDROCHLOROTHIAZIDE -

UNII:0 J48 LPH2TH)

HYDROCHLOROTHIAZIDE 50 mg

Inactive Ingredients

Ingredient Name

Stre ng th

ANHYDRO US LACTO SE (UNII: 3SY5LH9 PMK)

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

PO LACRILIN PO TASSIUM (UNII: 0 BZ5A0 0 FQU)

PO LYETHYLENE GLYCO L 8 0 0 0 (UNII: Q6 6 2QK8 M3B)

PO VIDO NE, UNSPECIFIED (UNII: FZ9 8 9 GH9 4E)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

Product Characteristics

Color

YELLOW

S core

2 pieces

S hap e

ROUND

S iz e

10 mm

Flavor

Imprint Code

WATSON;348

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 36 29 -8 19 1-1

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /0 2/20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 718 51

0 9 /23/19 9 3

Labeler -

Bryant Ranch Prepack (171714327)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Bryant Ranch Prepack

171714327

REPACK(6 36 29 -8 19 1) , RELABEL(6 36 29 -8 19 1)

Revised: 8/2019

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