(diuretic – antihypertensive)
CAPSULES
DESCRIPTION
CLINICAL PHARMACOLOGY
INDICATIONS AND USAGE
CONTRAINDICATIONS
WARNINGS
PRECAUTIONS
ADVERSE REACTIONS
DOSAGE AND ADMINISTRATION
OVERDOSAGE
HOW SUPPLIED
Each Dyazide capsule for oral use, with opaque red cap and opaque white body, contains
hydrochlorothiazide 25 mg and triamterene 37.5 mg, and is imprinted with the product name
DYAZIDE and SB. 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 demethylformamide. 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:
At 50°C, triamterene is practically insoluble in water (less than 0.1%). It is soluble in formic acid,
sparingly soluble in methoxyenthanol and very slightly soluble in alcohol.
Triamterene is 2,4,7-triamino-6-phenylpteridine and its structural formula is:
Inactive ingredients consist of benzyl alcohol, cetylpyidinium chloride, D&C; Red No.33, FD&C;
Yellow No. 6, gelatin, glycine, lactose, magnesium sterate, microcrystalline cellulose,
povidone, polysorbate 80, sodium starch glycolate, titanium dioxide and trace amounts of other
inactive ingredients.
Dyazide 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 Dyazide exerts its diuretic effect on the distal renal tubule to
inhibit the reabsorption of sodium in exchange for potassium and hydrogen ions. Its natriuetic
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. Trimterene 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 Dyazide are similar. Onset of diuresis with Dyazide takes place
within 1 hour, peaks at 2 to 3 hours and tapers off during the subsequent 7 to 9 hours.
Dyazide capsule is well absorbed.
Upon administration of a single oral dose to fasted normal make volunteers, the following mean
pharmacokinetic parameters were determined:
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.
Dyazide capsule is bioequivalent to a single-entity 25 mg hydrochlorothiazide tablet and 37.5 mg
trimterene capsule used in the double-blind clinical trial below.(see Clinical Trials.)
In a limited study involving 12 subject, coadministration of Dyazide with a high-fat meal resulted
in: (1) an increase in the mean bioavailability of triamterene by about 67% (90% confidence
interva l= 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.
Clinical Trials
A placebo-controlled, double-blind trial was conducted to evaluate the efficacy of Dyazide
capsules. This trial demonstrated that Dyazide
(25 mg hydrochlorothiazide/37.5 mg trimterene) was effective in controlling blood pressure while
reducing the incidence of hydrochlorothiazide-induced hypokalemia. This trial involved 636
patients with mild to moderate hypertension controlled by hydrochlorothiazide 25 mg daily and
who had hypokalemia (serum potassium < 3.5 mEq/L) secondary to the hydrochlorothiazide.
Patients were randomly assigned to 4 weeks treatment with once-daily regimens of 25 mg
hydrochlorothiazide plus placebo, or 25 mg hydrochlorothiazide combined with one of the
following doses of trimterene: 25 mg, 37.5 mg, 50 mg or 75 mg.
Blood pressure and serum potassium were monitored at baseline and throughout the trial. All
five treatment groups had similar mean blood pressure and serum potassium concentrations at
baseline (mean systolic blood pressure range: 137 (+ or -) 14 mmHg to 140 (+ or -) 16 mmHg; mean diastolic
blood pressure range: 86 (+ or -) 9 mmHg to 88 (+ or -) 8 mmHg: mean serum potassium range: 2.3 to 3.4
mEq/L with the majority of patients having values between 3.1 and 3.4 mEq/L.
While all tramterene regimens reversed hypokalemia, at week 4 the 37.5 mg regimen proved
optimal compared with the other tested regimens. On this regimen, 81% of the patients had a
significant (p < 0.05) reversal of hypokalemia vs. 59% of patients on the
placebo/hydrochlorothiazide regimen. The mean serum potassium concentration on 37.5 mg
triamterene went from 3.2 (+ or -) 0.2 mEq/L at baseline to 3.7 (+ or -) 0.3 m Eq/L at week 4, a significantly
greater (p < 0.05) improvement that that achieved with placebo/hydrochlorothiazide (i.e., 3.2 (+ or -) 0.2
mEq/L at baseline and 3.5 (+ or -) 0.4 mEq/L at week 4) also, 51% of patients in the 37.5 mg trimterene
group had an increase in serum potassium of > or = to 0.5 mEq/L at week 4 vs. 33% in the placebo group.
The 37.5 mg triamterene/25 mg hydrochlorothiazide regimen also maintained control of blood
pressure; mean supine systolic blood pressure at week 4 was 138 (+ or -) 21 mmHg while mean supine
diastolic blood pressure was 87 (+ or -) 13 mmHg.
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.
Dyazide is indicated for the treatment of hypertension or edema in patients who develop
hyokalemia on hydrochlorothiazide alone.
Dyazide is also indicated for those patients who require a thiazide diuretic and in whom the
development of hypokalemia cannot be risked.
Dyazide may be used alone or as an adjunct to other antihypertensive drugs, such as beta-
blockers. Since Dyazide may enhance the action of these agents, 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 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’re 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.
Antikaliuretic Therapy and Potassium
Supplementation
Dyazide 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 Dyazide except in severe cases of
hypokalemia. Such concomitant therapy can be associated with rapid increases in serum
potassium levels. If potassium supplementationis used, careful monitoring of the serum
potassium level is necessary.
Impaired Renal Function
Dyazide is contraindicted in patients with anuria, acute and chronic renal insufficiency or
significant renal impairment.
Hypersensitivity
Hypersensitivity to either drug in the preparation or to other sulfonamide-derived drugs is a
contraindication.
Hyperkalemia
Dyazide should not be used in patients with preexisting elevated serum potassium.
Hyperkalemia
Abnormal elevation of serum potassium levels (greater than or equal to 5.5 mEq/liter) can occur
with all potassium-sparing diuretic combinations, including Dyazide. Hyperkalemia is more likely
to occur in patients with renal impairment and diabetes (even without evidence of renal
impairment), and in the elderly or severely ill. Since uncorrected hyperkalemia may be fatal,
serum potassium levels must be monitored at frequent intervals especially in patients first
receiving Dyazide, when dosages are changed or with any illness that may influence renal
function.
If hyperkalemia is suspected (warning signs include paresthesias, muscular weakness, fatigue,
flacid paralysis of the extremities, bradycardia and shock), an electrocardiogram (ECG) should
be obtained. However, it is important to monitor serum potassium levels because hyperkalemia
may not be associated with ECG changes.
If hyperkalemia is present, Dyazide should be discontinued immediately and 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 parental 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 hypelkalemia associated with potassium-sparing diuretics is accentuated in
the presence of renal impairment (see CONTRAINDICATIONS section). 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 trimterene, the sulfate ester of hydroxytriamterene, have been shown to be
reduced and the plasma levels increased following Dyazide administration to elderly patients and
patients with impaired renal function.
Hyperkalemia has been reported in diabetic patients with the use of potassium-sparing agents
even in the absence of apparent renal impairment. Accordingly, serum electrolytes must be
frequently monitored if Dyazide is used in diabetic patients.
Metabolic or Respiratory Acidosis
Potassium-sparing 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 Dyazide is employed, frequent evaluations of acid/base and serum
electrolytes are necessary.
Impaired Hepatic Function
Thiazides should be used with caution in patients with impaired hepatic function. They can
precipitate hepatic coma in patients with severe liver disease. Potassium depletion induced by
the thiazide may be important in this connection. Administer Dyazide cautiously and be alert for
such early signs of impending coma as confusion, drowsiness and tremor; if mental confusion
increases discontinue Dyazide for a few days. Attention must be given to other factors that may
precipitate hepatic coma, such as blood in the gastrointestinal tract or potassium depletion.
Hypokalemia
Hypokalemia is uncommon with Dyazide, but should it develop, corrective measuers should be
taken such as potassium supplementaion or increased intake of potassium-rich foods. Institute
such measures cautiously with frequent determinations of serum potassium levels, especially in
patients receiving digitailis or with a history of cardiac arrhythmias. If serious hypokalemia
(serum potassium less than 3.0 mEq/L) is demonstrated by repeat serum potassium
determinations, Dyazide should be discontinued and potassium chloride supplementation
initiated. Less serious hypokalemia should be evaluated with regard to other coexisting
conditions and treated accordingly.
Electrolyte Imbalance
Electrolyte imbalance, often encountered in such conditions as heart failure, renal disease or
cirrhosis of the liver, may also be aggravated by diuretics and should be considered during
Dyazide therapy when using high doses for prolonged periods or in patients on a salt-restricted
diet. Serum determinations of electrolytes should be performed, and are particularly important if
the patient is vomiting excessively or receiving fluids parenterally. Possible fluid and electrolyte
imbalance may be indicated by such warning signs as: dry mouth, thirst, weakness, lethargy,
drowsiness, restlessness, muscle pain or cramps, muscular fatigue, hypertension, oliguria,
tachycardia and gastrointestinal systems.
Hypochioremia
Although any chloride deficit is generally mild and usually does not require specific treatment
except under extraordinary circumstances (as in liver disease or renal disease), chloride
replacement may be required in the treatment of metabolic alkalosis. 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.
Renal Stones
Triamterene has been found in renal stones in association with the other usual calculus
components. Dyazide should be used with caution in patients with a history of renal stones.
Laboratory Tests
Serum Potassium: The normal adult range of serum potassium is 3.5 to 5.0 m / per liter with 4.5
mEq often being used for a reference point. If hypokalemia should develop, corrective
measures should be taken such as potassium supplementaion or increased dietary intake of
potassium-rich foods.
Institute such measures cautiously with frequent determinations of serum potassium levels.
Potassium levels persistently above 6 mEq per liter require careful observation and treatment.
Serum potassium levels do not necessarily indicate true body potassium concentration. A rise in
plasma pH may cause a decrease in plasma potassium concentration and an increase in the
intracellular potassium concentration. Discontinue corrective measures for hypokalemia
immediately if laboratory determinations reveal an abnormal elevation of serum potassium.
Discontinue Dyazide and substitute a thiazide diuretic alone until potassium levels return to
normal.
Serum Creatinine and BUN: Dyazide may product an elevated blood urea nitrogen level,
creatinine level or both. This apparently is secondary to a reversible reduction of glomerular
filtration rate or a depletion of intravascular fluid volume (prerenal azotemia) rather than renal
toxcity; levels usually return to normal when Dyazide is discontinued. If azotemia increases,
discontinue Dyazide, periodic BUN or serum creatinine determinations should be made
especially in elderly patients and in patients with suspected or confirmed renal insufficiency.
Serum PBI: Thiazide may decrease serum PBI levels without sign of thyroid disturbance.
Parathyroid Function: Thiazides should be discontinued before carrying out tests for parathyroid
function. Calcium excretion is decreased by thiazides. Pathologic changes in the parathyroid
glands with hypercalemia and hypophosphatemia have been observed in a few patients on
prolonged thiazide therapy. The common complications of hyperparathyroidism such as bone
resorption and peptic ulceration have not been seen.
Drug Interactions
Angiotensin-converting enzyme inhibitors: Potassium sparing agents should be used with
caution in conjunction with angiotensin-converting enzyme(ACE) inhibitors due to an increased
risk of hyperkalemia.
Oral hypoglycemic drugs: Concurrent use with chlorpropamide may increase the risk of severe
hyponatremia.
Nonsterodial anti-inflammatory drugs: A possible interaction resulting in acute renal failure has
been reported in a few patients on Dyazide when treated with indomethacin, a nonsterodial anti-
inflammatory agent. Caution is advised in administering non-steroidal anti-inflammatory agents
with Dyazide.
Lithium: Lithium generally should not be given with diuretics because they reduce its renal
clearance and increase the risk of lithium toxicity. Read circulars for lithium preparations before
use of such concomitant therapy with Dyazide.
Surgical considerations: Thiazides have been shown to decrease arterial responsiveness to
norepinephrine (an effect attributed to loss of sodium.) This diminution is not sufficient to
preclude effectiveness of the pressor agent for therapeutic use. Thiazides have also been
shown to increase the paralyzing effect of nondepolarizing muscle relaxants such as tubocurarine
(an affect attriubuted to potassium loss); consequently caution should be observed in patients
undergoing surgery.
Other Considerations: Concurrent use of hydrochlorothiazide with amphotercin B or
corticosteroids or corticotropin (ACTH) may intensify electrolyte imbalance, particularly
hypokalemia, although the presence of triamterene minimizes the hypokalemic effect.
Thiazides may add to or potentiate the action of other antihypertensive drugs. See
INDICATIONS AND USAGE for concomitant use with other antihypertensive drugs.
The effect of oral anticogulants may be decreased when used concurrently with
hydrochlorothiazide; dosage adjustments may be necessary.
Dyazide may raise the level of blood uric acid; dosage adjustments of antigout medication may
be necessary to control hyperuricemia and gout.
The following agents given together with triamterene may promote serum potassium
accumulation and possibly result in hyperkalemia because of the potassium sparing nature of
triamterene, especially in patients with renal insufficiency: blood from blood bank (may contain
up to 30 mEq of potassium per liter of plasma or up to 65 mEq of potassium per liter of plasma
or up to 65 Eq of potassium per liter of plasma or up to 65 mEq of whole blood when stored for
more than 10 days) low salt milk (may contain up to 60 mEq of potassium per liter); potassium-
containing medications (such as parenteral penicilin G potassium); salt substitutes (most contain
substantial amounts of potassium).
Exchange resins, such as sodium polystyrene sulfonate, whether administered orally or rectally,
reduce serum potassium levels by sodium replacement of the potassium; fluid retention may
occur in some patients because of the increased sodium intake.
Chronic or overuse of laxatives may reduce serum potaassium levels by promoting excessive
potassium loss from the intestinal tract; laxatives may interfere with the potassium-retaining
effects of triamterene.
The effectiveness of methenamine may be decreased when used concurrently with
hydrochlorothiazide be cause of alkalinization of the urine.
Drug/Laboratory Test Interactions
Triamterene and quinidine have similar fluorescence spectra; thus, Dyazide will interfere with the
fluorescent measurement of quinidine.
Carcinogenesis, Mutagenesis, impairment of Fertility
Carcinogenesis
Long-term studies have not been conducted with Dyazide (the triamterene/hydrochlorothiazide
combination), or with triamterene alone.
Hydrochlorothazide: 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 100mg/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 Dyazide at 50 mg/day (or 1.0 mg/kg/day based on 50 kg
individuals.) 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.
Mutagenesis
Studies of the mutagenic potential of Dyazide (the triamterene/hydrochlorothiazide combination),
or of triamterene alone have not been performed.
Hydrochlorothiazide: Hydrochlorothiazide was not genotoxic in in vitro assays using strains TA
98, TA 98, TA 100, TA 1535 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 Dyazide (the triamterene/hydrochlorothiazide combination), or of
triamterene alone of 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 where 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: Category C
Teratogenic Effects
Dyazide: Animal reproduction studies to determine the potential for fetal harm by Dyazide have
not been conducted. However, a One Generation Study in the rat approximated Dyazide
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 which 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 Dyazide in pregnancy has not been established since there are no adequate
and well-controlled studies with Dyazide in pregnant women. Dyazide 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 does as high as 20 times the
MRHD on the basis of body weight, and 6 times the human dose 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 adminisered 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 edequate 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 trimterene 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 benefit be weighed against possible hazards to the fetus. These hazards include
fetal or neonatal jaundice, pancreatitis, thrombocytopenia and possible other adverse reactions
which have occurred in the adult.
Nursing Mothers– Thiazides and triamterene in combination have not been studied in nursing
mothers. Triamterene appears in animal milk; 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 children have not been established.
Adverse effects are listed in decreasing order of frequency; however, the most serious adverse
effects are listed first regardless of frequency. The serious adverse effects associated with
Dyazide have commonly occurred in less than 0.1 % of patients treated with this product.
Hypersensitivity: anaphylaxis, rash, urticaria, photosensitivity.
Cardiovascular:arrhythmia, postural hypotentension.
Metabolic: diabetes, mellitus, hyperuricemia, hyperglycemia, glycosuriam, hyperuricemia,
hypokalemia, hyponatremia, acidosis, hypochloremia.
Gastrointestinal: 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 urinery sediment.
Hematologic: leukopenia, thrombocytopenia and purpura, megaloblasatic anemia.
Musculoskeletal: muscle cramps.
Central Nervous System: weakness, fatigue, dizziness, headache, dry mouth.
Miscellaneous: impotence, sialadentis.
Thiazides alone have been shown to cause the following additional adverse reactions.
Central Nervous System: paresthesias, vertigo.
Ophthalmic: xanthopsia, transient blurred vision.
Respiratory: allergic pneumonitis, pulmonary edema, respiratory distress.
Other: necrotizing vasculitis, exacerbation of lupus.
Hematologic: aplastic anemia, agranulocytosis, hemolyticanemia .
Neonate and infancy: thrombocytopenia and pancreatitis rarely, in newborns whose mothers
have received thiazides during pregnancy.
The usual dose of Dyazide is one or two capsules given once daily, with appropriate monitoring
of serum potassium and of the clinical effect. (See WARNINGS, Hyperkalemia.)
Electrolyte imbalance is the major concern (see WARNINGS selection). Symptoms reported
include: polyuria, nausea, vomiting, weakness, lassitude, fever, flushed faced 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 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.
Capsules containing 25 mg hydrochlorothiazide and 37.5 mg triamterine, in bottles of 1000
capsules; in Single Unit Packages (unit-doses) of 100 (intended for institutional use only); in
Patient-PakTM unit-use-bottles of 100.
They are supplied as follows:
NDC 007-3650-21 single Unit Packages (unit-dose) of 100 (intended for institutional use only).
NDC 0007-3650-22 in Partient Pak unit-of-use bottles of 100.
NDC 0007-3650-30 bottles of 1000.
Store between 15° and 30°C (59° and 86°F). Protect from light. Dispense in a tight, light resistant
container.
DATE OF ISSUANCE MAR.1995
© SmithKline Beecham, 1995
SmithKline Beecham Pharmaceuticals
Philadelpia, PA 19101
DZ:L65A
Printed in U.S.A.