A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Teveten Side Effects, and Drug Interactions - Eprosartan Mesylate
Teveten Side Effects, and Drug Interactions - Eprosartan Mesylate
SIDE EFFECTS
TEVETEN® Tablets have 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® Tablets were 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 of patients
treated with TEVETEN® Tablets discontinued therapy due to clinical adverse
experiences, compared to 6.5% of 352 patients given placebo.
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® Tablets (54.4%) was similar to placebo (52.8%).
Table 1. Adverse Events Reported by ³1%
of Patients Receiving TEVETEN® (eprosartan mesylate) Tablets and Were
More Frequent on Eprosartan than Placebo
| Adverse Event |
Incidence
|
|
Eprosartan
(n = 1,202)
%
|
Placebo
(n = 352)
% |
| Body as a Whole |
| Infection viral |
2 |
1 |
| Injury |
2 |
1 |
| Fatigue |
2 |
1 |
| Gastrointestinal |
| Abdominal pain |
2 |
1 |
| Metabolic and Nutritional |
| Hypertriglyceridemia |
1 |
0 |
| Musculoskeletal |
| Arthralgia |
2 |
1 |
| Nervous System |
| Depression |
1 |
0 |
| Respiratory |
| Upper respiratory tract infection |
8 |
5 |
| Rhinitis |
4 |
3 |
| Pharyngitis |
4 |
3 |
| Coughing |
4 |
3 |
| Urogenital |
| Urinary tract infection |
1 |
0 |
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, chest pain.
Facial edema was reported in 5 patients receiving eprosartan. Angioedema
has been reported with other angiotensin II antagonists.
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 aprosartan:
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,
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.
Laboratory Test Findings
In placebo-controlled studies, clinically important changes in standard
laboratory parameters were rarely associated with administration of TEVETEN®
(eprosartan mesylate) Tablets. Patients were rarely withdrawn from TEVETEN®
Tablets because of laboratory test results.
Creatinine, Blood Urea Nitrogen
Minor elevations in creatinine and in BUN occurred in 0.6% and 1.3%,
respectively, of patients taking TEVETEN® Tablets 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® (eprosartan mesylate)
Tablets or placebo in controlled clinical trials. An elevated ALAT of
>3.5 x ULN occurred in 0.1% of patients taking TEVETEN® Tablets (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® Tablets (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® Tablets 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® Tablets 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® Tablets (one patient) and
in no patient given placebo in controlled clinical trials. Four patients
receiving TEVETEN® Tablets in clinical trials were withdrawn for thrombocytopenia.
In one case, thrombocytopenia was present prior to dosing with TEVETEN®
Tablets.
Serum Potassium
A potassium value of ³5.6 mmol/L occurred
in 0.9% of patients taking TEVETEN® Tablets and 0.3% of patients given
placebo in controlled clinical trials. One patient was withdrawn from
clinical trials for hyperkalemia and three for hypokalemia.
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.
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