Data from FDA - Curated by EPG Health - Last updated 19 December 2016

Indication(s)

INDICATIONS AND USAGE TEVETEN® HCT is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensives such as calcium channel blockers. This fixed dose combination is not indicated for initial therapy (see DOSAGE AND ADMINISTRATION ).

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Advisory information

contraindications
CONTRAINDICATIONS TEVETEN® HCT is contraindicated in patients who are hypersensitive to this product or any of its components. Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.
Special warnings and precautions

PRECAUTIONS General Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.

Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.

Thiazides may decrease urinary calcium excretion.

Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism.

Marked hypercalcemia may be evidence of hidden hyperparathyroidism.

Thiazides should be discontinued before carrying out tests for parathyroid function.

In diabetic patients, dosage adjustment of insulin or oral hypoglycemic agents may be required.

Hyperglycemia may occur with thiazide diuretics.

Thus, latent diabetes mellitus may become manifest during thiazide therapy.

The antihypertensive effects of hydrochlorothiazide may be enhanced in postsympathectomy patients.

Electrolyte Imbalance Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.

All patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte imbalance: hyponatremia, hypochloremic alkalosis, and hypokalemia.

Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids.

Warning signs or symptoms of fluid and electrolyte imbalance, irrespective of cause, include: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.

Hypokalemia may develop, especially with brisk diuresis, when severe cirrhosis is present, or after prolonged therapy.

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

Hypokalemia may cause cardiac arrhythmia and may also sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability).

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.

Risk of Renal Impairment As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function have been reported in susceptible individuals treated with angiotensin II antagonists; in some patients, these changes in renal function were reversible upon discontinuation of therapy.

In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure), treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death.

TEVETEN® HCT would be expected to behave similarly.

In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or BUN have been reported.

Similar effects have been reported with angiotensin II antagonists; in some patients, these effects were reversible upon discontinuation of therapy.

Thiazides should be used with caution in severe renal disease.

In patients with renal disease, thiazides may precipitate azotemia.

Cumulative effects of the drug may develop in patients with impaired renal function.

If progressive renal impairment becomes evident, consider withholding or discontinuing diuretic therapy.

Information for Patients

Pregnancy: Female patients of childbearing age should be told about the consequences of second - and third-trimester exposure to drugs that act on the renin-angiotensin system, and they should also be told that these consequences do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester.

These patients should be asked to report pregnancies to their physicians as soon as possible so that treatment may be discontinued under medical supervision.

Symptomatic Hypotension: A patient receiving TEVETEN® HCT should be cautioned that lightheadedness can occur, especially during the first days of therapy, and that it should be reported to the prescribing physician.

The patient should be told that if syncope occurs, TEVETEN® HCT should be discontinued until the physician has been consulted.

All patients should be cautioned that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of lightheadedness and possible syncope.

Potassium Supplements: A patient receiving TEVETEN® HCT should be told not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician (see PRECAUTIONS, Drug Interactions, Eprosartan Mesylate).

Drug Interactions Eprosartan Mesylate: Eprosartan has been shown to have no effect on the pharmacokinetics of digoxin and the pharmacodynamics of warfarin and glyburide.

Thus, no dosing adjustments are necessary during concomitant use with these agents.

Because eprosartan is not metabolized by the cytochrome P450 system, inhibitors of CYP450 enzyme would not be expected to affect its metabolism, and ketoconazole and fluconazole, potent inhibitors of CYP3A and 2C9, respectively, have been shown to have no effect on eprosartan pharmacokinetics.

Ranitidine also has no effect on eprosartan pharmacokinetics.

Eprosartan (up to 400 mg b.i.d. or 800 mg q.d.) doses have been safely used concomitantly with a thiazide diuretic (hydrochlorothiazide).

Eprosartan doses of up to 300 mg b.i.d. have been safely used concomitantly with sustained-release calcium channel blockers (sustained-release nifedipine) with no clinically significant adverse interactions.

As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements or salt substitutes containing potassium may lead to increases in serum potassium (see PRECAUTIONS, Information for Patients, Potassium Supplements).

Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including eprosartan, may result in deterioration of renal function, including possible acute renal failure.

These effects are usually reversible.

Monitor renal function periodically in patients receiving eprosartan and NSAID therapy.

The antihypertensive effect of angiotensin II receptor antagonists, including eprosartan may be attenuated by NSAIDs including selective COX-2 inhibitors.

Hydrochlorothiazide: When administered concurrently the following drugs may interact with thiazide diuretics: Alcohol, barbiturates, or narcotics - potentiation of orthostatic hypotension may occur.

Antidiabetic drug (oral agents and insulin) - dosage adjustment of the antidiabetic drug may be required.

Other antihypertensive drugs - additive effect or potentiation.

Cholestyramine and colestipol resins - Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins.

Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85 % and 43 %, respectively.

Corticosteroids, ACTH - intensified electrolyte depletion, particularly hypokalemia.

Pressor amines (e.g., norepinephrine) - possible decreased response to pressor amines but not sufficient to preclude their use.

Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine) - possible increased responsiveness to the muscle relaxant.

Lithium - should not generally be given with diuretics.

Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity.

Refer to the package insert for lithium preparations before use of such preparations with TEVETEN® HCT. Nonsteroidal Anti-Inflammatory Drugs - in some patients, the administration of a nonsteroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics.

Therefore, when TEVETEN® HCT and nonsteroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.

Carcinogenesis, Mutagenesis, Impairment of Fertility No carcinogenicity studies have been conducted with eprosartan mesylate in combination with hydrochlorothiazide.

Eprosartan mesylate was not carcinogenic in dietary restricted rats or ad_libitum fed mice dosed at 600 mg and 2000 mg eprosartan/ kg/day, respectively, for up to 2 years.

In male and female rats, the systemic exposure (AUC) to unbound eprosartan at the dose evaluated was only approximately 25 % of the exposure achieved in humans given TEVETEN® HCT.

In mice, the systemic exposure (AUC) to unbound eprosartan was approximately 35 times the exposure achieved in humans given TEVETEN® HCT.

Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses of up to approximately 100 mg/kg/day).

The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice.

Eprosartan mesylate was not mutagenic in_vitro in mammalian cells (mouse lymphoma assay).

Eprosartan mesylate alone or in combination with hydrochlorothiazide was not mutagenic in_vitro in bacteria (Ames test) and did not cause structural chromosomal damage in_vivo (mouse micronucleus assay).

In human peripheral lymphocytes in_vitro, eprosartan mesylate in combination with hydrochlorothiazide was positive for clastogenicity with and without metabolic activation.

In the same assay, eprosartan mesylate alone was associated with polyploidy but there was only equivocal evidence of structural chromosomal damage.

Hydrochlorothiazide was not genotoxic in_vitro in the Ames test and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in_vivo in 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) and Mouse Lymphoma Cell (mutagenicity) assays and in the Aspergillus nidulans non-disjunction assay.

No fertility studies have been conducted with eprosartan mesylate in combination with hydrochlorothiazide.

Eprosartan mesylate had no adverse effects on the reproductive performance of male or female rats at oral doses up to 1000 mg eprosartan/ kg/day.

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 conception and throughout gestation.

Pregnancy Pregnancy Category C (first trimester) and D (second and third trimesters): See WARNINGS: Fetal/Neonatal Morbidity and Mortality.

Nursing Mothers Eprosartan is excreted in animal milk; it is not known whether eprosartan is excreted in human milk.

Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from eprosartan, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Thiazides appear in human milk.

Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

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

Geriatric Use In the controlled clinical trials where patients received eprosartan/hydrochlorothiazide combination therapy, 15 % to 33 % of the patients were 65 years of age or greater.

There was no difference in the effect of TEVETEN® HCT 600/12.5 mg treatment according to age.

However, following single oral dose administration of eprosartan to healthy elderly men, (aged 68 to 78 years), AUC, Cmax, and Tmax eprosartan values increased, on average, by approximately twofold, compared to healthy young men (aged 20 to 38 years) who received the same dose.

(See Pharmacokinetics, Special Populations).

Adverse reactions

ADVERSE REACTIONS TEVETEN® HCT 600/12.5 mg has been evaluated for safety in 268 patients in double-blind, controlled clinical trials.

Most of these patients were treated with TEVETEN® HCT 600/12.5 mg for 29 to 60 days.

Eprosartan/hydrochlorothiazide combination therapy has been evaluated for safety in 890 patients in open-label, long-term clinical trials.

Approximately 50 % of these patients were treated with eprosartan/hydrochlorothiazide for over 2 years.

Eprosartan/hydrochlorothiazide combination therapy was well tolerated.

Most adverse events were of mild or moderate severity and did not require discontinuation of therapy.

Adverse experiences were similar in patients regardless of age, gender, or race.

In the controlled clinical trials, about 3 % of the 268 patients treated with TEVETEN® HCT 600/12.5 mg discontinued therapy due to clinical adverse experiences.

Adverse Events Occurring at an Incidence of Greater Than 3 % Among TEVETEN® HCT Treated Patients The following table lists adverse events that occurred at an incidence of >3 % among TEVETEN® HCT 600/12.5 mg - or monotherapy-treated patients who participated in the controlled clinical trials.

Of the 268 patients who received TEVETEN® HCT 600/12.5 mg during the double-blind treatment period in the controlled trials, 110 patients were reported to have adverse events.

Table 1 Incidence of Adverse Events >3 % During the Double-Blind Treatment Period by Preferred Term and Treatment Grouping: Controlled Studies Placebo (N=246) Eprosartan 600 mg (N=275) HCTZ 12.5 mg (N=117) HCTZ 25 mg (N=52) Eprosartan 600 mg/HCTZ 12.5 mg (N=268) Preferred Term n (%) n (%) n (%) n (%) n (%) Dizziness 4 (1.6) 5 (1.8) 2 (1.7) 2 (3.8) 11 (4.1) Headache 22 (8.9) 10 (3.6) 4 (3.4) 3 (5.8) 9 (3.4) Back pain 6 (2.4) 7 (2.5) 2 (1.7) 2 (3.8) 7 (2.6) Fatigue 6 (2.4) 5 (1.8) 1 (0.9) 2 (3.8) 5 (1.9) Myalgia 8 (3.3) 2 (0.7) 3 (2.6) 0 (0.0) 1 (0.4) Upper Respiratory Tract

Infection 8 (3.3) 2 (0.7) 0 (0.0) 2 (3.8) 1 (0.4) Sinusitis 4 (1.6) 1 (0.4) 0 (0.0) 2 (3.8) 0 (0.0) Viral Infection 4 (1.6) 0 (0.0) 2 (1.7) 2 (3.8) 0 (0.0) The adverse events reported in over 600 patients that received TEVETEN®/hydrochlorothiazide combination therapy for at least 1 year in the open-label, long-term clinical trials were comparable to those reported in the controlled trials.

Eprosartan Mesylate: In addition to the adverse events above, potentially important adverse events that are included in the current labeling for TEVETEN® monotherapy are listed below.

Most of these adverse events occurred in <1 % of patients, or were as frequent or more frequent in the placebo group.

It is not known if these events were related to eprosartan usage: Body as a Whole: alcohol intolerance, asthenia, substernal chest pain, dependent edema, peripheral edema, facial edema, fatigue, fever, hot flushes, influenza-like symptoms, injury, malaise, pain, rigors, viral infection; Cardiovascular: angina pectoris, bradycardia, abnormal ECG, specific abnormal ECG, extrasystoles, atrial fibrillation, hypotension (including orthostatic hypotension), tachycardia, palpitations; Gastrointestinal: abdominal pain, anorexia, constipation, diarrhea, dry mouth, dyspepsia, esophagitis, flatulence, gastritis, gastroenteritis, gingivitis, nausea, periodontitis, toothache, vomiting; Hematologic: anemia, purpura; Liver and Biliary: increased SGOT, increased SGPT

Metabolic and Nutritional: increased creatine phosphokinase, diabetes mellitus, glycosuria, gout, hypercholesterolemia, hyperglycemia, hyperkalemia, hypokalemia, hyponatremia, hypertriglyceridemia; Musculoskeletal: arthralgia, arthritis, aggravated arthritis, arthrosis, skeletal pain, tendinitis; Nervous System/Psychiatric: anxiety, ataxia, depression, dizziness, insomnia, migraine, neuritis, nervousness, paresthesia, somnolence, tremor, vertigo; Resistance Mechanism: herpes simplex, otitis externa, otitis media, upper respiratory tract infection; Respiratory: asthma, bronchitis, coughing, epistaxis, pharyngitis, rhinitis; Skin and Appendages: eczema, furunculosis, pruritus, rash, maculopapular rash, increased sweating

Special Senses: conjunctivitis, abnormal vision, xerophthalmia, tinnitus; Urinary: albuminuria, cystitis, hematuria, micturition frequency, polyuria, renal calculus, urinary incontinence, urinary tract infection; Vascular: leg cramps, peripheral ischemia.

Hydrochlorothiazide: Other adverse events that have been reported for hydrochlorothiazide, without regard to causality, are listed below: Body as a Whole: weakness; Cardiovascular: hypotension (including orthostatic hypotension); Digestive: pancreatitis, jaundice (intrahepatic cholestatic jaundice), diarrhea, vomiting, sialadenitis, cramping, constipation, gastric irritation, nausea, anorexia; Hematologic: aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia; Hypersensitivity: anaphylactic reactions, necrotizing angiitis (vasculitis and cutaneous vasculitis), respiratory distress including pneumonitis, and pulmonary edema, photosensitivity, fever, urticaria, rash, purpura

Metabolic: electrolyte imbalance including hyponatremia, hypokalemia, and hypochloremic alkalosis, hyperglycemia, glycosuria, hyperuricemia; Musculoskeletal: muscle spasm; Nervous System/Psychiatric: vertigo, paresthesias, restlessness; Renal: renal failure, renal dysfunction, interstitial nephritis, azotemia; Skin: erythema multiform, including Stevens-Johnson syndrome, exfoliative dermatitis, including toxic epidermal necrolysis, alopecia; Special Senses: transient blurred vision, xanthopsia; Urogenital: impotence.

Laboratory Test Findings: In placebo-controlled studies, clinically important changes in standard laboratory parameters were rarely associated with administration of TEVETEN®. Patients were rarely withdrawn from TEVETEN® because of laboratory test results.

Laboratory test findings that have been reported for TEVETEN® are listed below: Creatinine, Blood Urea Nitrogen:

Minor elevations in creatinine and in BUN occurred in 0.6 % and 1.3 %, respectively, of patients taking TEVETEN® and 0.9 % and 0.3 %, respectively, of patients given placebo in controlled clinical trials.

Two patients were withdrawn from clinical trials for elevations in serum creatinine and BUN, and three additional patients were withdrawn for increases in serum creatinine.

Liver Function Tests: Minor elevations of ALAT, ASAT, and alkaline phosphatase occurred for comparable percentages of patients taking TEVETEN® or placebo in controlled clinical trials.

An elevated ALAT of >3.5 x ULN occurred in 0.1 % of patients taking TEVETEN® (one patient) and in no patient given placebo in controlled clinical trials.

Four patients were withdrawn from clinical trials for an elevation in liver function tests.

Hemoglobin: A greater than 20 % decrease in hemoglobin was observed in 0.1 % of patients taking TEVETEN® (one patient) and in no patient given placebo in controlled clinical trials.

Two patients were withdrawn from clinical trials for anemia.

Leukopenia: A WBC count of?3.0 x 103/ mm3 occurred in 0.3 % of patients taking TEVETEN® and in 0.3 % of patients given placebo in controlled clinical trials.

One patient was withdrawn from clinical trials for leukopenia.

Neutropenia: A neutrophil count of?1.5 x 103/ mm3 occurred in 1.3 % of patients taking TEVETEN® and in 1.4 % of patients given placebo in controlled clinical trials.

No patient was withdrawn from any clinical trials for neutropenia.

Thrombocytopenia: A platelet count of?100 x 109/L occurred in 0.3 % of patients taking TEVETEN® (one patient) and in no patient given placebo in controlled clinical trials.

Four patients receiving TEVETEN® in clinical trials were withdrawn for thrombocytopenia.

In one case, thrombocytopenia was present prior to dosing with TEVETEN®. Serum Potassium: A potassium value of?

5.6 mmol/L occurred in 0.9 % of patients taking TEVETEN® and 0.3 % of patients given placebo in controlled clinical trials.

One patient was withdrawn from clinical trials for hyperkalemia and three for hypokalemia.

Additional Information: Among the adverse events reported for patients receiving either TEVETEN® monotherapy or TEVETEN®/hydrochlorothiazide combination therapy in the TEVETEN® HCT clinical trials, some adverse events are not included in the current labeling for either TEVETEN® or hydrochlorothiazide monotherapy.

The adverse events which are not currently included in the labeling for TEVETEN® or hydrochlorothiazide monotherapy include the following: angioedema, bilirubinemia, blood urea nitrogen increased, edema periorbital, eosinophilia, and NPN increased.

The majority of these adverse events were reported in the open-label, long-term trials and were reported in small numbers of patients receiving TEVETEN® alone or TEVETEN® in combination with hydrochlorothiazide.

All of these adverse events were either not reported in patients receiving TEVETEN® monotherapy or combination therapy with hydrochlorothiazide during the double-blind period of the controlled trials, or were reported at an incidence of?1 % or in only one patient per treatment group in the controlled trials.

The overall safety profile of the TEVETEN®/hydrochlorothiazide combination treatment is as expected based on the safety profile of each of the components and what is generally known about the patient population.

OVERDOSAGE Eprosartan Mesylate: Limited data are available regarding overdosage.

Appropriate symptomatic and supportive therapy should be given if overdosage should occur.

There was no mortality in rats and mice receiving oral doses of up to 3000 mg eprosartan/ kg and in dogs receiving oral doses of up to 1000 mg eprosartan/ kg.

Hydrochlorothiazide: The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, and hyponatremia) and dehydration resulting from excessive diuresis.

If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.

The degree to which hydrochlorothiazide is removed by hemodialysis has not been established.

The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in both mice and rats.

Usage information

Dosing and administration

DOSAGE AND ADMINISTRATION The usual recommended starting dose of eprosartan is 600 mg once daily when used as monotherapy in patients who are not volume-depleted (see WARNINGS, Hypotension in Volume - and/or Salt-Depleted Patients).

Eprosartan can be administered once or twice daily and total daily doses ranging from 400 mg to 800 mg.

There is limited experience with doses beyond 800 mg/day.

If the antihypertensive effect measured at trough using once-daily monotherapy dosing is inadequate, a twice-a-day regimen at the same total daily dose or an increase in dose may give a more satisfactory response.

Achievement of maximum blood pressure reduction in most patients may take 2 to 3 weeks.

Hydrochlorothiazide is effective in doses of 12.5 mg to 50 mg once daily.

To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.

The side effects (see WARNINGS) of eprosartan are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent (primarily hypokalemia) and dose-independent (e.g., pancreatitis) phenomena, the former much more common than the latter.

Therapy with any combination of eprosartan and hydrochlorothiazide will be associated with both sets of dose-independent side effects.

Replacement Therapy TEVETEN® HCT may be substituted for the individual components.

The usual recommended dose of TEVETEN® HCT is 600 mg/12.5 mg once daily when used as combination therapy in patients who are not volume-depleted (see WARNINGS, Hypotension in Volume-and/or Salt-Depleted Patients).

If the antihypertensive effect measured at trough using TEVETEN® HCT 600/12.5 mg is inadequate, patients may be titrated to TEVETEN® HCT 600/25 mg once daily.

Higher doses have not been studied in combination.

Achievement of maximum blood pressure reduction in most patients may take 2 to 3 weeks.

If the patient under treatment with TEVETEN® HCT requires additional blood pressure control at trough, or to maintain a twice a day dosing schedule of monotherapy, 300 mg TEVETEN® may be added as evening dose.

TEVETEN® HCT may be used in combination with other antihypertensive agents such as calcium channel blockers if additional blood-pressure-lowering effect is required.

Discontinuation of treatment with eprosartan does not lead to a rapid rebound increase in blood pressure.

Elderly, Hepatically Impaired or Renally Impaired Patients: No initial dosing adjustment is generally necessary for elderly or hepatically impaired patients or those with renal impairment.

No initial dosing adjustment is generally necessary in patients with moderate and severe renal impairment with maximum dose not exceeding 600 mg daily.

TEVETEN® HCT may be taken with or without food.

Pregnancy and lactation

Nursing Mothers Eprosartan is excreted in animal milk; it is not known whether eprosartan is excreted in human milk.

Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from eprosartan, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Thiazides appear in human milk.

Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Interactions

Drug Interactions Eprosartan Mesylate: Eprosartan has been shown to have no effect on the pharmacokinetics of digoxin and the pharmacodynamics of warfarin and glyburide.

Thus, no dosing adjustments are necessary during concomitant use with these agents.

Because eprosartan is not metabolized by the cytochrome P450 system, inhibitors of CYP450 enzyme would not be expected to affect its metabolism, and ketoconazole and fluconazole, potent inhibitors of CYP3A and 2C9, respectively, have been shown to have no effect on eprosartan pharmacokinetics.

Ranitidine also has no effect on eprosartan pharmacokinetics.

Eprosartan (up to 400 mg b.i.d. or 800 mg q.d.) doses have been safely used concomitantly with a thiazide diuretic (hydrochlorothiazide).

Eprosartan doses of up to 300 mg b.i.d. have been safely used concomitantly with sustained-release calcium channel blockers (sustained-release nifedipine) with no clinically significant adverse interactions.

As with other drugs that block angiotensin

II or its effects, concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements or salt substitutes containing potassium may lead to increases in serum potassium (see PRECAUTIONS, Information for Patients, Potassium Supplements).

Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including eprosartan, may result in deterioration of renal function, including possible acute renal failure.

These effects are usually reversible.

Monitor renal function periodically in patients receiving eprosartan and NSAID therapy.

The antihypertensive effect of angiotensin II receptor antagonists, including eprosartan may be attenuated by NSAIDs including selective COX-2 inhibitors.

Hydrochlorothiazide: When administered concurrently the following drugs may interact with thiazide diuretics: Alcohol, barbiturates, or narcotics - potentiation of orthostatic hypotension may occur.

Antidiabetic drug (oral agents and insulin) - dosage adjustment of the antidiabetic drug may be required.

Other antihypertensive drugs - additive effect or potentiation.

Cholestyramine and colestipol resins - Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins.

Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85 % and 43 %, respectively.

Corticosteroids, ACTH - intensified electrolyte depletion, particularly hypokalemia.

Pressor amines (e.g., norepinephrine) - possible decreased response to pressor amines but not sufficient to preclude their use.

Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine) - possible increased responsiveness to the muscle relaxant.

Lithium - should not generally be given with diuretics.

Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity.

Refer to the package insert for lithium preparations before use of such preparations with TEVETEN® HCT. Nonsteroidal Anti-Inflammatory Drugs - in some patients, the administration of a nonsteroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics.

Therefore, when TEVETEN® HCT and nonsteroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.

More information

Category Value
Authorisation number NDA021268
Agency product number 0J48LPH2TH
Orphan designation No
Product NDC 54868-5281
Date Last Revised 03-01-2012
Type HUMAN PRESCRIPTION DRUG
RXCUI 352335
Storage and handling STORAGE Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Abbott Laboratories North Chicago, IL 60064 U.S.A. ©2010 Abbott Laboratories Rev. April, 2011 Relabeling and Repackaging by: Physicians Total Care, Inc. Tulsa, OK 74146
Marketing authorisation holder Physicians Total Care, Inc.
Warnings USE IN PREGNANCY When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pr