DESCRIPTION
id: 30f779be-c2a2-4bf7-bdfa-87141d2d3b2d
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Each triamterene and hydrochlorothiazide capsule for oral use contains triamterene 37.5 mg and hydrochlorothiazide 25 mg. Hydrochlorothiazide is a diuretic/antihypertensive agent and triamterene is an antikaliuretic agent.
Hydrochlorothiazide is slightly soluble in water. It is soluble in dilute ammonia, dilute aqueous sodium hydroxide, and dimethylformamide. It is sparingly soluble in methanol.
Hydrochlorothiazide is 6-chloro-3,4-dihydro-2H-1, 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide, and its structural formula is:
Molecular Formula: C7H8CIN3O4S2
M.W. 297.74
At 50°C, triamterene is practically insoluble in water (less than 0.1%). It is soluble in formic acid, sparingly soluble in methoxyethanol, and very soluble in alcohol.
Triamterene is 2, 4, 7-triamino-6-phenylpteridine and its structural formula is:
Molecular Formula: C12H11N7
M.W. 253.26
Inactive ingredients consist of lactose monohydrate, pregelatinized starch, sodium starch glycolate, polysorbate 80, citric acid anhydrous, povidone, and magnesium stearate. The capsule shell consists of titanium dioxide and gelatin. The capsule imprinting ink consists of shellac glaze in ethanol, iron oxide black, n-butyl alcohol, propylene glycol, ethanol, methanol, FD&C Blue # 2 Aluminum Lake, FD&C Red # 40 Aluminum Lake, FD&C Blue # 1 Aluminum Lake, and D&C Yellow # 10 Aluminum Lake.
Triamterene and hydrochlorothiazide capsules, USP meet USP Dissolution Test 3 as published in the current USP monograph for triamterene and hydrochlorothiazide capsules.
CLINICAL PHARMACOLOGY
id: adc50d9a-3148-484e-865a-c3a9d60ee015
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1
The triamterene and hydrochlorothiazide capsule is a diuretic/antihypertensive drug product that combines natriuretic and antikaliuretic effects. Each component complements the action of the other. The hydrochlorothiazide component blocks the reabsorption of sodium and chloride ions, and thereby increases the quantity of sodium traversing the distal tubule and the volume of water excreted. A portion of the additional sodium presented to the distal tubule is exchanged there for potassium and hydrogen ions. With continued use of hydrochlorothiazide and depletion of sodium, compensatory mechanisms tend to increase this exchange and may produce excessive loss of potassium, hydrogen, and chloride ions. Hydrochlorothiazide also decreases the excretion of calcium and uric acid, may increase the excretion of iodide, and may reduce glomerular filtration rate. The exact mechanism of the antihypertensive effect of hydrochlorothiazide is not known.
The triamterene component of triamterene and hydrochlorothiazide capsules, USP exerts its diuretic effect on the distal renal tubule to inhibit the reabsorption of sodium in exchange for potassium and hydrogen ions. Its natriuretic activity is limited by the amount of sodium reaching its site of action. Although it blocks the increase in this exchange that is stimulated by mineralocorticoids (chiefly aldosterone), it is not a competitive antagonist of aldosterone and its activity can be demonstrated in adrenalectomized rats and patients with Addison’s disease. As a result, the dose of triamterene required is not proportionally related to the level of mineralocorticoid activity, but is dictated by the response of the individual patients, and the kaliuretic effect of concomitantly administered drugs. By inhibiting the distal tubular exchange mechanism, triamterene maintains or increases the sodium excretion and reduces the excess loss of potassium, hydrogen and chloride ions induced by hydrochlorothiazide. As with hydrochlorothiazide, triamterene may reduce glomerular filtration and renal plasma flow. Via this mechanism it may reduce uric acid excretion although it has no tubular effect on uric acid reabsorption or secretion. Triamterene does not affect calcium excretion. No predictable antihypertensive effect has been demonstrated for triamterene.
Duration of diuretic activity and effective dosage range of the hydrochlorothiazide and triamterene components of triamterene and hydrochlorothiazide capsules, USP are similar. Onset of diuresis with triamterene and hydrochlorothiazide capsules, USP takes place within 1 hour, peaks at 2 to 3 hours and tapers off during the subsequent 7 to 9 hours.
Triamterene and hydrochlorothiazide capsules, USP are well absorbed.
Upon administration of a single oral dose to fasted normal male volunteers, the following mean pharmacokinetic parameters were determined:
|
AUC
(0-48)
ng*hrs/mL
(±SD)
|
C
max
ng/mL
(±SD)
|
Media
n
T
max
Hrs
|
Ae Mg
(±SD)
|
| Triamterene |
148.7 (87.9) |
46.4 (29.4) |
1.1 |
2.7 (1.4) |
| hydroxytriamterene sulfate |
1,865 (471) |
720 (364) |
1.3 |
19.7 (6.1) |
| hydrochlorothiazide |
834 (177) |
135.1 (35.7) |
2.0 |
14.3 (3.8) |
where AUC(0-48), Cmax, Tmax and Ae represent area under the plasma concentration versus time plot, maximum plasma concentration, time to reach Cmax, and amount excreted in urine over 48 hours.
One triamterene and hydrochlorothiazide capsule is bioequivalent to a single-entity 25 mg hydrochlorothiazide tablet and 37.5 mg triamterene capsule used in the double-blind clinical trial below (see Clinical Trials).
In a limited study involving 12 subjects, coadministration of triamterene and hydrochlorothiazide capsules, USP with a high-fat meal resulted in: (1) an increase in the mean bioavailability of triamterene by about 67% (90% confidence interval = 0.99,1.90), p-hydroxytriamterene sulfate by about 50% (90% confidence interval = 1.06, 1.77), hydrochlorothiazide by about 17% (90% confidence interval = 0.90, 1.34); (2) increases in the peak concentrations of triamterene and p-hydroxytriamterene; and (3) a delay of up to 2 hours in the absorption of the active constituents.
INDICATIONS AND USAGE
id: 5d63f2de-0729-4f37-a191-a30c3cf4c37e
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
This fixed combination drug is not indicated for the initial therapy of edema or hyper
tension
except in individuals in whom the developme
nt of hypokalemia cannot be ris
ked.
Triamterene and hydrochlorothiazide capsules, USP are indicated for the treatment of hypertension or edema in patients who develop hypokalemia on hydrochlorothiazide alone.
Triamterene and hydrochlorothiazide capsules, USP are also indicated for those patients who require a thiazide diuretic and in whom the development of hypokalemia cannot be risked.
Triamterene and hydrochlorothiazide capsules, USP may be used alone or as an adjunct to other antihypertensive drugs, such as beta-blockers. Since triamterene and hydrochlorothiazide capsules, USP may enhance the action of these agents, dosage adjustments may be necessary.
Us
age 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 of 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. Diuretics 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
id: 8cb7c1ed-02f1-476c-be6b-ad4d1b245ef2
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
A
ntikaliuretic Therapy and Potass
ium Supplementation: Triamterene and hydrochlorothiazide capsules, USP should not be given to patients receiving other potassium-sparing agents such as spironolactone, amiloride, or other formulations containing triamterene. Concomitant potassium containing salt substitutes should also not be used.
Potassium supplementation should not be used with triamterene and hydrochlorothiazide capsules, USP except in severe cases of hypokalemia. Such concomitant therapy can be associated with rapid increases in serum potassium levels. If potassium supplementation is used, careful monitoring of the serum potassium level is necessary.
Impaired Renal Function: Triamterene and hydrochlorothiazide capsules, USP are contraindicated in patients with anuria, acute and chronic renal insufficiency or significant renal impairment.
Hypersens
itivity: Hypersensitivity to either drug in the preparation or to other sulfonamide-derived drugs is a contraindication.
Hyperkalemia: Triamterene and hydrochlorothiazide capsules, USP should not be used in patients with preexisting elevated serum potassium.
ADVERSE REACTIONS
id: b2b1b129-57b9-49a8-9b3f-abf3836b15a6
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
Adverse effects are listed in decreasing order of severity.
Hypersens
itivity: Anaphylaxis, rash, urticaria, subacute cutaneous lupus erythematosus-like reactions, photosensitivity.
Cardiovas
cular: Arrhythmia, postural hypotension.
Metabolic: Diabetes mellitus, hyperkalemia, hypokalemia, hyponatremia, acidosis, hypercalcemia, hyperglycemia, glycosuria, hyperuricemia, hypochloremia.
Gastrointes
tinal: Jaundice and/or liver enzyme abnormalities, pancreatitis, nausea and vomiting, diarrhea, constipation, abdominal pain.
Renal: Acute renal failure (one case of irreversible renal failure has been reported), interstitial nephritis, renal stones composed primarily of triamterene, elevated BUN, and serum creatinine, abnormal urinary sediment.
Hematologic: Leukopenia, thrombocytopenia and purpura, megaloblastic anemia.
Musculos
keletal: Muscle cramps.
Central Nervous Sys
tem: Weakness, fatigue, dizziness, headache, dry mouth.
Miscellaneous
: Impotence, sialadenitis.
Thiazides alone have been shown to cause the following additional adverse reactions:
Central Nervous Sys
tem: Paresthesias, vertigo.
Ophthalmic: Xanthopsia, transient blurred vision.
Res
piratory: Allergic pneumonitis, pulmonary edema, respiratory distress.
Other: Necrotizing vasculitis, exacerbation of lupus.
Hematologic: Aplastic anemia, agranulocytosis, hemolytic anemia.
Neonate and infancy: Thrombocytopenia and pancreatitis–rarely, in newborns whose mothers have received thiazides during pregnancy.
Skin: Erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis.
OVERDOSAGE
id: 545ba658-38be-47fe-bfcf-9c7e33f59ac4
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
Electrolyte imbalance is the major concern (see WARNINGS section). Symptoms reported include: polyuria, nausea, vomiting, weakness, lassitude, fever, flushed face, and hyperactive deep tendon reflexes. If hypotension occurs, it may be treated with pressor agents such as levarterenol to maintain blood pressure. Carefully evaluate the electrolyte pattern and fluid balance. Induce immediate evacuation of the stomach through emesis or gastric lavage. There is no specific antidote.
Reversible acute renal failure following ingestion of 50 tablets of a product containing a combination of 50 mg triamterene and 25 mg hydrochlorothiazide has been reported.
Although triamterene is largely protein-bound (approximately 67%), there may be some benefit to dialysis in cases of overdosage.
DOSAGE AND ADMINISTRATION
id: ced7444e-b46a-43ba-9293-2ce6a0f48500
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
The usual dos
e of triamtere
ne and hydrochlorothiazide caps
ule
s, USP is one or two capsules
given once daily, with appropriate monitoring of
serum potass
iu
m and of the clinical effect (s
ee
WARNINGS, Hyperkalemia
).
HOW SUPPLIED
id: a358f66a-bff8-4afe-b33d-534da31edf82
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Triamterene and Hydrochlorothiazide Capsules, USP contain 37.5 mg triamterene and 25 mg hydrochlorothiazide, and are available in size # 4 white opaque/white opaque capsules imprinted with Logo “LANNETT” on the cap and “1632” on the body. They are supplied as follows:
Bottles of 100, NDC 10135-0581-01
Bottles of 1000, NDC 10135-0581-10
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light.
Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure.
Distributed by:
Marlex Pharmaceuticals, Inc.
New Castle, DE 19720
Made in the USA
Rev. 10/14LAN
PRINCIPAL DISLPAY PANEL
id: dcf5fe75-cc26-42a2-80d0-37bb3fba4483
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
NDC 10135-0581-01
Marlex
Triamterene and Hydrochlorothiazide Capsules
37.5 mg/25 mg
Rx Only
100 Capsules
