Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1937
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Teveten (Tablet)
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dailymed-instance:dosage |
The usual recommended starting
dose of TEVETEN 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). TEVETEN can be administered once or twice daily with 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 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. TEVETEN may be
used in combination with other antihypertensive agents such as thiazide
diuretics or 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.<br/>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 may be taken with or without food.
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dailymed-instance:descripti... |
TEVETEN (eprosartan mesylate) is a non-biphenyl non-tetrazole angiotensin
II receptor (AT) antagonist. A selective non-peptide molecule,
TEVETEN is chemically described as the monomethanesulfonate
of (E )-2-butyl-1-(p-carboxybenzyl)-��-2-thienylmethylimid-azole-5-acrylic
acid. Its empirical
formula is CHNOS���CHOS and molecular weight is 520.625. Its structural
formula is: Eprosartan mesylate
is a white to off-white free-flowing crystalline powder that is insoluble
in water, freely soluble in ethanol, and melts between 248��C
and 250��C. TEVETEN is available as aqueous film-coated tablets containing
eprosartan mesylate equivalent to 400 mg or 600 mg eprosartan zwitterion
(pink, oval, non-scored tablets or white, non-scored, capsule-shaped
tablets, respectively).<br/>Inactive Ingredients: The 400 mg tablet
contains the following: croscarmellose sodium, hypromellose, iron
oxide red, iron oxide yellow, lactose monohydrate, magnesium stearate,
microcrystalline cellulose, polyethylene glycol, polysorbate 80, pregelatinized
starch, and titanium dioxide. The 600 mg tablet contains crospovidone,
hypromellose, lactose monohydrate, magnesium stearate, microcrystalline
cellulose, polyethylene glycol, polysorbate 80, pregelatinized starch,
and titanium dioxide.
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dailymed-instance:clinicalP... |
Mechanism of Action: Angiotensin II (formed
from angiotensin I in a reaction catalyzed by angiotensin-converting
enzyme [kininase II]), a potent vasoconstrictor, is the principal
pressor agent of the renin-angiotensin system. Angiotensin II also
stimulates aldosterone synthesis and secretion by the adrenal cortex,
cardiac contraction, renal resorption of sodium, activity of the sympathetic
nervous system, and smooth muscle cell growth. Eprosartan blocksthe
vasoconstrictor and aldosterone-secreting effects of angiotensin II
by selectively blocking the binding of angiotensin II to the ATreceptor found in many tissues (e.g., vascular smooth muscle,
adrenal gland). There is also an ATreceptor found in
many tissues but it is not known to be associated with cardiovascular
homeostasis. Eprosartan does not exhibit any partial agonist activity
at the ATreceptor. Its affinity for the ATreceptor is 1,000 times greater than for the ATreceptor. In vitro binding studies indicate that
eprosartan is a reversible, competitive inhibitor of the ATreceptor. Blockade
of the ATreceptor removes the negative feedback of angiotensin
II on renin secretion, but the resulting increased plasma renin activity
and circulating angiotensin II do not overcome the effect of eprosartan
on blood pressure. TEVETEN does not inhibit kininase II, the enzyme
that converts angiotensin I to angiotensin II and degrades bradykinin;
whether this has clinical relevance is not known. It does not bind
to or block other hormone receptors or ion channels known to be important
in cardiovascular regulation.<br/>Pharmacokinetics:<br/>General: Absolute
bioavailability following a single 300 mg oral dose of eprosartan
is approximately 13%. Eprosartan plasma concentrations peak at 1 to
2 hours after an oral dose in the fasted state. Administering eprosartan
with food delays absorption, and causes variable changes (<25%)
in Cand AUC values which do not appear clinically important.
Plasma concentrations of eprosartan increase in a slightly less than
dose-proportional manner over the 100 mg to 800 mg dose range. The
mean terminal elimination half-life of eprosartan following multiple
oral doses of 600 mg was approximately 20 hours. Eprosartan does not
significantly accumulate with chronic use.<br/>Metabolism and Excretion: Eprosartan
is eliminated by biliary and renal excretion, primarily as unchanged
compound. Less than 2% of an oral dose is excreted in the urine as
a glucuronide. There are no active metabolites following oral and
intravenous dosing with [C] eprosartan in human subjects.
Eprosartan was the only drug-related compound found in the plasma
and feces. Following intravenous [C] eprosartan, about
61% of the material is recovered in the feces and about 37% in the
urine. Following an oral dose of [C] eprosartan, about
90% is recovered in the feces and about 7% in the urine. Approximately
20% of the radioactivity excreted in the urine was an acyl glucuronide
of eprosartan with the remaining 80% being unchanged eprosartan.<br/>Distribution: Plasma protein
binding of eprosartan is high (approximately 98%) and constant over
the concentration range achieved with therapeutic doses. The pooled population
pharmacokinetic analysis from two Phase 3 trials of 299 men and 172
women with mild to moderate hypertension (aged 20 to 93 years) showed
that eprosartan exhibited a population mean oral clearance (CL/F)
for an average 60-year-old patient of 48.5 L/hr. The population mean
steady-state volume of distribution (Vss/F) was 308 L. Eprosartan
pharmacokinetics were not influenced by weight, race, gender or severity
of hypertension at baseline. Oral clearance was shown to be a linear
function of age with CL/F decreasing 0.62 L/hr for every year increase.<br/>Special Populations:<br/>Pediatric: Eprosartan
pharmacokinetics have not been investigated in patients younger than
18 years of age.<br/>Geriatric: Following
single oral dose administration of eprosartan to healthy elderly men
(aged 68 to 78 years), AUC, C, and Teprosartan
values increased, on average by approximately twofold, compared to
healthy young men (aged 20 to 39 years) who received the same dose.
The extent of plasma protein binding was not influenced by age.<br/>Gender: There was
no difference in the pharmacokinetics and plasma protein binding between
men and women following single oral dose administration of eprosartan.<br/>Race: A pooled
population pharmacokinetic analysis of 442 Caucasian and 29 non-Caucasian
hypertensive patients showed that oral clearance and steady-state
volume of distribution were not influenced by race.<br/>Renal Insufficiency: Following
administration of 600 mg once daily, there was a 70-90% increase in
AUC, and a 30-50% increase in Cin moderate or severe
renal impairment. The unbound eprosartan fractions increased by 35%
and 59% in patients with moderate and severe renal impairment, respectively.
No initial dosing adjustment is generally necessary in patients with
moderate or severe renal impairment, with maximum dose not exceeding
600 mg daily. Eprosartan was poorly removed by hemodialysis (CL<1 L/hr) .<br/>Hepatic Insufficiency: Eprosartan
AUC (but not C) values increased, on average, by approximately
40% in men with decreased hepatic function compared to healthy men
after a single 100 mg oral dose of eprosartan. Hepatic disease was
defined as a documented clinical history of chronic hepatic abnormality
diagnosed by liver biopsy, liver/spleen scan or clinical laboratory
tests. The extent of eprosartan plasma protein binding was not influenced
by hepatic dysfunction. No dosage adjustment is necessary for patients
with hepatic impairment .<br/>Drug Interactions: Concomitant administration
of eprosartan and digoxin had no effect on single oral-dose digoxin
pharmacokinetics. Concomitant administration of eprosartan and warfarin
had no effect on steady-state prothrombin time ratios (INR) in healthy
volunteers. Concomitant administration of eprosartan and glyburide
in diabetic patients did not affect 24-hour plasma glucose profiles.
Eprosartan pharmacokinetics were not affected by concomitant administration
of ranitidine. Eprosartan did not inhibit human cytochrome P450 enzymes
CYP1A, 2A6, 2C9/8, 2C19, 2D6, 2E and 3A in vitro. Eprosartan is not metabolized by the cytochrome
P450 system; eprosartan steady-state concentrations were not affected
by concomitant administration of ketoconazole or fluconazole, potent
inhibitors of CYP3A and 2C9, respectively.<br/>Pharmacodynamics and Clinical Effects: Eprosartan inhibits
the pharmacologic effects of angiotensin II infusions in healthy adult
men. Single oral doses of eprosartan from 10 mg to 400 mg have been
shown to inhibit the vasopressor, renal vasoconstrictive and aldosterone
secretory effects of infused angiotensin II with complete inhibition
evident at doses of 350 mg and above. Eprosartan inhibits the pressor
effects of angiotensin II infusions. A single oral dose of 350 mg
of eprosartan inhibits pressor effects by approximately 100% at peak,
with approximately 30% inhibition persisting for 24 hours. The absence
of angiotensin II ATagonist activity has been demonstrated
in healthy adult men. In hypertensive patients treated chronically
with eprosartan, there was a twofold rise in angiotensin II plasma
concentration and a twofold rise in plasma renin activity, while plasma
aldosterone levels remained unchanged. Serum potassium levels also
remained unchanged in these patients. Achievement of maximal blood pressure response to a given dose in
most patients may take 2 to 3 weeks of treatment. Onset of blood pressure
reduction is seen within 1 to 2 hours of dosing with few instances
of orthostatic hypotension. Blood pressure control is maintained with
once- or twice-daily dosing over a 24-hour period. Discontinuing treatment
with eprosartan does not lead to a rapid rebound increase in blood
pressure. There was no change in mean heart rate in patients treated with eprosartan
in controlled clinical trials. Eprosartan increases mean effective renal plasma flow (ERPF) in salt-replete
and salt-restricted normal subjects. A dose-related increase in ERPF
of 25% to 30% occurred in salt-restricted normal subjects, with the
effect plateauing between the 200 mg and 400 mg doses. There was no
change in ERPF in hypertensive patients and patients with renal insufficiency
on normal salt diets. Eprosartan did not reduce glomerular filtration
rate in patients with renal insufficiency or in patients with hypertension,
after 7 days and 28 days of dosing, respectively. In hypertensive
patients and patients with chronic renal insufficiency, eprosartan
did not change fractional excretion of sodium and potassium. Eprosartan (1200 mg once
daily for 7 days or 300 mg twice daily for 28 days) had no effect
on the excretion of uric acid in healthy men, patients with essential
hypertension or those with varying degrees of renal insufficiency. There were no effects on
mean levels of fasting triglycerides, total cholesterol, HDL cholesterol,
LDL cholesterol or fasting glucose.<br/>Clinical Trials: The safety and efficacy
of TEVETEN have been evaluated in controlled clinical
trials worldwide that enrolled predominantly hypertensive patients
with sitting DBP ranging from 95 mmHg to���115 mmHg. There is also some experience
with use of eprosartan together with other anti-hypertensive drugs
in more severe hypertension. The antihypertensive effects of TEVETEN were demonstrated
principally in five placebo-controlled trials (4 to 13 weeks'
duration) including dosages of 400 mg to 1200 mg given once daily
(two studies), 25 mg to 400 mg twice daily (two studies), and one
study comparing total daily doses of 400 mg to 800 mg given once daily
or twice daily. The five studies included 1,111 patients randomized
to eprosartan and 395 patients randomized to placebo. The studies
showed dose-related antihypertensive responses. At study endpoint, patients treated with TEVETEN at doses of 600 mg to 1200 mg given once daily experienced significant
decreases in sitting systolic and diastolic blood pressure at trough,
with differences from placebo of approximately 5-10/3-6 mmHg. Limited
experience is available with the dose of 1200 mg administered once
daily. In a direct comparisonof 200 mg to 400 mg b.i.d. with 400
mg to 800 mg q.d. of TEVETEN, effects at trough were
similar. Patients treated with TEVETEN at doses of
200 mg to 400 mg given twice daily experienced significant decreases
in sitting systolic and diastolic blood pressure at trough, with differences
from placebo of approximately 7-10/4-6 mmHg. Peak (1 to 3 hours) effects were uniformly, but moderately, larger
than trough effects with b.i.d. dosing, with the trough-to-peak ratio
for diastolic blood pressure 65% to 80%. In the once-daily dose-response
study, trough-to-peak responses of���50% were observed at some
doses (including 1200 mg), suggesting attenuation of effect at the
end of the dosing interval. The antihypertensive effect of TEVETEN was similar
in men and women, but was somewhat smaller in patients over 65. There
were too few black subjects to determine whether their response was
similar to Caucasians. In general, blacks (usually a low renin population)
have had smaller responses to ACE inhibitors and angiotensin II inhibitors
than Caucasian populations. Angiotensin-converting enzyme (ACE) inhibitor-induced cough (a dry,
persistent cough) can lead to discontinuation of ACE inhibitor therapy.
In one study, patients who had previously coughed while taking an
ACE inhibitor were treated with eprosartan, an ACE inhibitor (enalapril)
or placebo for six weeks. The incidence of dry, persistent cough was
2.2% on eprosartan, 4.4% on placebo, and 20.5% on the ACE inhibitor;
p=0.008 for the comparison of eprosartan with enalapril. In a second
study comparing the incidence of cough in 259 patients treated with
eprosartan to 261 patients treated with the ACE inhibitor enalapril,
the incidence of dry, persistent cough in eprosartan-treated patients
(1.5%) was significantly lower (p=0.018) than that observed in patients
treated with the ACE inhibitor (5.4%). In addition, analysis of overall
data from six double-blind clinical trials involving 1,554 patients
showed an incidence of spontaneously reported cough in patients treated
with eprosartan of 3.5%, similar to placebo (2.6%).
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dailymed-instance:activeIng... | |
dailymed-instance:contraind... |
TEVETEN is contraindicated in patients who are hypersensitive to this product
or any of its components.
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dailymed-instance:supply |
TEVETEN is available as aqueous film-coated tablets as follows: 400 mg pink, non-scored, oval
tablets, debossed with���SOLVAY���on one side and���5044���on the other. NDC
0074���3025���11 (bottles of 100) 600 mg white, non-scored, capsule-shaped tablets, debossed with���SOLVAY���on one side and���5046���on the other. NDC 0074���3040���11 (bottles of 100)
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dailymed-instance:boxedWarn... |
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 pregnancy is detected, TEVETEN should be discontinued
as soon as possible. See WARNINGS: Fetal/Neonatal Morbidity and Mortality.
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dailymed-instance:activeMoi... | |
dailymed-instance:inactiveI... |
dailymed-ingredient:croscarmellose_sodium,
dailymed-ingredient:hypromellose,
dailymed-ingredient:iron_oxide_red,
dailymed-ingredient:iron_oxide_yellow,
dailymed-ingredient:lactose_monohydrate,
dailymed-ingredient:magnesium_stearate,
dailymed-ingredient:microcrystalline_cellulose,
dailymed-ingredient:polyethylene_glycol,
dailymed-ingredient:polysorbate_80,
dailymed-ingredient:pregelatinized_starch,
dailymed-ingredient:titanium_dioxide
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dailymed-instance:precautio... |
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 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.<br/>Information for Patients:<br/>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.<br/>Drug Interactions: 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.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: 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 20% of the exposure achieved
in humans given 400 mg b.i.d. In mice, the systemic exposure (AUC)
to unbound eprosartan was approximately 25 times the exposure achieved
in humans given 400 mg b.i.d. Eprosartan mesylate was not mutagenic in vitro in bacteria or mammalian cells (mouse lymphoma
assay). Eprosartan mesylate also did not cause structural chromosomal
damage in vivo (mouse micronucleus
assay). In human peripheral lymphocytes in vitro , eprosartan mesylate was equivocal for clastogenicity
with metabolic activation, and was negative without metabolic activation.
In the same assay, eprosartan mesylate was positive for polyploidy
with metabolic activation and equivocal for polyploidy without metabolic
activation. 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.
This dose provided systemic exposure (AUC) to unbound eprosartan approximately
0.6 times the exposure achieved in humans given 400 mg b.i.d.<br/>Pregnancy: Pregnancy Category C (first trimester) and D (second
and third trimesters): See WARNINGS: Fetal/Neonatal
Morbidity and Mortality.<br/>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.<br/>Pediatric Use: Safety and effectiveness
in pediatric patients have not been established.<br/>Geriatric Use: Of the total number
of patients receiving TEVETEN in clinical studies,
29% (681 of 2,334) were 65 years and over, while 5% (124 of 2,334)
were 75 years and over. Based on the pooled data from randomized trials,
the decrease in diastolic blood pressure and systolic blood pressure
with TEVETEN was slightly less in patients���65
years of age compared to younger patients. In a study of only patients
over the age of 65, TEVETEN at 200 mg twice daily
(and increased optionally up to 300 mg twice daily) decreased diastolic
blood pressure on average by 3 mmHg (placebo corrected). Adverse experienceswere similar in younger and older patients.
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dailymed-instance:overdosag... |
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.
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dailymed-instance:genericMe... |
eprosartan mesylate
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dailymed-instance:fullName |
Teveten (Tablet)
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dailymed-instance:adverseRe... |
TEVETEN has been evaluated for safety in more than 3,300 healthy volunteers
and patients worldwide, including more than 1,460 patients treated
for more than 6 months, and more than 980 patients treated for 1 year
or longer. TEVETEN was well tolerated at doses up
to 1200 mg daily. Most adverse events were of mild or moderate severity
and did not require discontinuation of therapy. The overall incidence
of adverse experiences and the incidences of specific adverse events
reported with eprosartan were similar to placebo. Adverse experiences were similar in patients regardless of age, gender,
or race. Adverse experiences were not dose-related. In placebo-controlled clinical trials, about 4% of 1,202 patients
treated with TEVETEN discontinued therapy due to
clinical adverse experiences, compared to 6.5% of 352 patients given
placebo.<br/>Adverse Events Occurring at an Incidence of 1% or More Among
Eprosartan-treated Patients: The following table
lists adverse events that occurred at an incidence of 1% or more among
eprosartan-treated patients who participated in placebo-controlled
trials of 8 to 13 weeks' duration, using doses of 25 mg to 400
mg twice daily, and 400 mg to 1200 mg once daily. The overall incidence
of adverse events reported with TEVETEN (54.4%) was
similar to placebo (52.8%). The following
adverse events were also reported at a rate of 1% or greater in patients
treated with eprosartan, but were as, or more, frequent in the placebo
group: headache, myalgia, dizziness, sinusitis, diarrhea, bronchitis,
dependent edema, dyspepsia, and chest pain. Facial edema was reported in 5 patients receiving eprosartan. Angioedema
has been reported with other angiotensin II antagonists. Rare cases of rhabdomyolysis
have been reported in patients receiving angiotensin II receptor blockers. In addition to the adverse
events above, potentially important events that occurred in at least
two patients/subjects exposed to eprosartan or other adverse events
that occurred in<1% of patients in clinical studies are listed
below. It cannot be determined whether events were causally related
to eprosartan: Body as a Whole: alcohol intolerance, asthenia, substernal
chest pain, peripheral edema, fatigue, fever, hot flushes, influenza-like
symptoms, malaise, rigors, pain; Cardiovascular: angina pectoris, bradycardia, abnormal
ECG, specific abnormal ECG, extrasystoles, atrial fibrillation, hypotension
(including orthostatic hypotension), tachycardia, palpitations; Gastrointestinal: anorexia, constipation,
dry mouth, 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; Musculoskeletal: arthritis, aggravated
arthritis, arthrosis, skeletal pain, tendinitis, back pain; Nervous System/Psychiatric: anxiety,
ataxia, insomnia, migraine, neuritis, nervousness, paresthesia, somnolence,
tremor, vertigo; Resistance Mechanism: herpes simplex, otitis externa,
otitis media, upper respiratory tract infection; Respiratory: asthma, epistaxis; 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; Vascular: leg cramps, peripheral
ischemia.<br/>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.<br/>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.<br/>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.<br/>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.<br/>Leukopenia: A WBC count
of���3.0 x 10/mmoccurred 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.<br/>Neutropenia: A neutrophil
count of���1.5 x 10/mmoccurred 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 trial for neutropenia.<br/>Thrombocytopenia: A platelet
count of���100 x 10/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.<br/>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.
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dailymed-instance:warning |
Fetal/Neonatal Morbidity and Mortality: Drugs that act directly
on the renin-angiotensin system can cause fetal and neonatal morbidity
and death when administered to pregnant women. Several dozen cases
have been reported in the world literature in patients who were taking
angiotensin-converting enzyme inhibitors. When pregnancy is detected,
TEVETEN should be discontinued as soon as possible. The use of drugs that
act directly on the renin-angiotensin system during the second and
third trimesters of pregnancy has been associated with fetal and neonatal
injury, including hypotension, neonatal skull hypoplasia, anuria,
reversible or irreversible renal failure, and death. Oligohydramnios
has also been reported, presumably resulting from decreased fetal
renal function; oligohydramnios in this setting has been associated
with fetal limb contractures, craniofacial deformation, and hypoplastic
lung development. Prematurity, intrauterine growth retardation, and
patent ductus arteriosus have also been reported, although it is not
clear whether these occurrences were due to exposureto the drug. These adverse effects do
not appear to have resulted from intrauterine drug exposure that has
been limited to the first trimester. Mothers whose embryos and fetuses
are exposed to an angiotensin II receptor antagonist only during the
first trimester should be so informed. Nonetheless, when patients
become pregnant, physicians should advise the patient to discontinue
the use of eprosartan as soon as possible. Rarely (probably less often than once in every thousand pregnancies),
no alternative to a drug acting on the renin-angiotensin system will
be found. In these rare cases, the mothers should be apprised of the
potential hazards to their fetuses, and serial ultrasound examinations
should be performed to assess the intra-amniotic environment. If oligohydramnios is
observed, TEVETEN should be discontinued unless it
is considered life-saving for the mother. Contraction stress testing
(CST), a nonstress test (NST) or biophysical profiling (BPP) may be
appropriate, depending upon the week of pregnancy. Patients and physicians
should be aware, however, that oligohydramnios may not appear until
after the fetus has sustained irreversible injury. Infants with histories of in utero exposure to an angiotensin II receptor antagonist should be closely
observed for hypotension, oliguria, and hyperkalemia. If oliguria
occurs, attention should be directed toward support of blood pressure
and renal perfusion. Exchange transfusion or dialysis may be required
as means of reversing hypotension and/or substituting for disordered
renal function. Eprosartan mesylate has been shown to produce maternal and fetal
toxicities (maternal and fetal mortality, low maternal body weight
and food consumption, resorptions, abortions and litter loss) in pregnant
rabbits given oral doses as low as 10 mg eprosartan/kg/day. No maternal
or fetal adverse effects were observed at 3 mg/kg/day; this oral dose
yielded a systemic exposure (AUC) to unbound eprosartan 0.8 times
that achieved in humans given 400 mg b.i.d. No adverse effects on in utero or postnatal development and
maturation of offspring were observed when eprosartan mesylate was
administered to pregnant rats at oral doses up to 1000 mg eprosartan/kg/day
(the 1000 mg eprosartan/kg/day dose in non-pregnant rats yielded systemic
exposure to unbound eprosartan approximately 0.6 times the exposure
achieved in humans given 400 mg b.i.d.).<br/>Hypotension in Volume- and/or Salt-Depleted Patients: In patients with
an activated renin-angiotensin system, such as volume- and/or salt-depleted
patients (e.g., those being treated with diuretics), symptomatic hypotension
may occur. These conditions should be corrected prior to administration
of TEVETEN, or the treatment should start under close
medical supervision. If hypotension occurs, the patient should be
placed in the supine position and, if necessary, given an intravenous
infusion of normal saline. A transient hypotensive response is not
a contraindication to further treatment, which usually can be continued
without difficulty once the blood pressure has stabilized.
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dailymed-instance:indicatio... |
TEVETEN is indicated for the treatment of hypertension. It may be used alone
or in combination with other antihypertensives such as diuretics and
calcium channel blockers.
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dailymed-instance:represent... | |
dailymed-instance:routeOfAd... | |
dailymed-instance:name |
Teveten
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