Hydrochlorothiazide 50 MG / Triamterene 75 MG Oral Tablet

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.

DRUG INTERACTIONS

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.

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.

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 hydrochlorothazide 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-2 H -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: Triamterene Chemical Structure Hydrochlorothiazide Chemical Structure

HOW SUPPLIED

: Triamterene and Hydrochlorothiazide Tablets USP, 75 mg/50 mg, are yellow, round, scored tablets, debossed with Watson 348 and are available in bottles of 50.

Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature].

Protect from light.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Manufactured by: Watson Pharma Private Limited Verna, Salcette Goa 403 722 INDIA Distributed by: Watson Pharma, Inc.

Parsippany, NJ 07054 USA Revised: April 2012 Repackaged by: KAISER FOUNDATION HOSPITALS Livermore, CA 94551

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.

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.

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.

PEDIATRIC USE

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

PREGNANCY

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.

NUSRING MOTHERS

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.

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.