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
Cozaar Side Effects, and Drug Interactions - Losartan
Cozaar Side Effects, and Drug Interactions - Losartan
SIDE EFFECTS
Losartan potassium
has been evaluated for safety in more than 3300 patients treated
for essential hypertension
and 4058 patients/subjects overall. Over 1200 patients were treated
for over 6 months and more than 800 for over one year. In
general, treatment
with losartan potassium
was well-tolerated. The overall incidence
of adverse experiences reported with losartan potassium was similar
to placebo.
In controlled clinical
trials, discontinuation of therapy due to clinical adverse experiences
was required in 2.3 percent
of patients treated with losartan potassium
and 3.7 percent of patients
given placebo.
The following table of
adverse events is based on four 6-12 week placebo controlled trials
involving over 1000 patients on various doses (10-150 mg) of losartan
and over 300 patients given placebo. All doses of losartan are grouped
because none of the adverse events appeared to have a dose-related
frequency. The table includes
all adverse events, whether or not attributed to the treatment,
occurring in at least 1% of patients treated with losartan and that
were more frequent in losartan than placebo. (TABLE 1)
| TABLE 1 |
| |
Losartan |
Placebo |
| |
Incidence (n=1075) |
Incidence (n=334) |
| Digestive |
|
|
2.4 |
2.1 |
|
|
1.3 |
1.2 |
| Musculoskeletal |
|
|
1.1 |
0.3 |
|
|
1.0 |
0.9 |
|
|
1.8 |
1.2 |
|
|
1.0 |
0.0 |
| Nervous System/Psychiatric |
|
|
3.5 |
2.1 |
|
|
1.4 |
0.6 |
| Respiratory |
|
|
2.0 |
1.2 |
|
|
3.4 |
3.3 |
Infection, upper respiratory
|
7.9 |
6.9 |
|
|
1.5 |
1.2 |
|
|
1.0 |
0.3 |
The following adverse events were also reported at a rate
1% or greater in patients treated with losartan, but were as, or
more frequent, in the placebo group: asthenia/fatigue, edema/swelling,
abdominal pain, chest
pain, nausea, headache, pharyngitis.
Adverse events occurred at about the same rates in men and women,
older and younger patients, and black
and non-black patients.
A patient with known
hypersensitivity to aspirin
and penicillin, when treated with losartan potassium, was withdrawn
from study due to swelling of the lips and eyelids and facial
rash, reported as angioedema, which returned to normal
5 days after therapy was discontinued.
Superficial peeling
of palms and hemolysis
was reported in one subject.
In addition to the
adverse events, above potentially important events that occurred
in at least two patients/subjects exposed to losartan or other adverse
events occurred in <1% of patients in clinical
studies are listed below. It cannot be determined whether these
events were casually related to losartan: Body as a Whole:
facial edema, fever,
orthostatic effects, syncope; Cardiovascular: angina
pectoris, second degree AV block, CVA, hypotension, myocardial
infarction, arrhythmias including atrial fibrillation, palpitation,
sinus bradycardia, tachycardia,
ventricular tachycardia, ventricular
fibrillation; Digestive: anorexia, constipation, dental pain,
dry mouth, flatulence, gastritis, vomiting; Hematologic:
anemia; Metabolic: gout; Musculoskeletal: arm
pain, hip pain, joint swelling,
knee pain, musculoskeletal
pain, shoulder pain,
stiffness, arthralgia, arthritis, fibromyalgia, muscle
weakness;Nervous System/Psychiatric: anxiety, anxiety disorder,
ataxia, confusion, depression, dream
abnormality, hypesthesia, decreased libido, memory impairment, migraine,
nervousness, paresthesia, peripheral
neuropathy, panic disorder,
sleep disorder, somnolence,
tremor, vertigo;Respiratory: dyspnea, bronchitis, pharyngeal
discomfort, epistaxis, rhinitis, respiratory congestion; Skin:
alopecia, dermatitis, dry skin, ecchymosis, erythema, flushing,
photosensitivity, pruritus, rash, sweating, urticaria; Special
Senses: blurred vision, burning/stinging in the eye, conjunctivitis,
taste perversion, tinnitus,
decrease in visual acuity; Urogenital: impotence, nocturia,
urinary frequency, urinary tract infection.
Laboratory Test Findings: In
controlled clinical
trials, clinically important changes in standard
laboratory parameters were rarely associated with administration
of losartan potassium.
Creatinine, Blood Urea Nitrogen: Minor increases
in blood urea nitrogen
(BUN) or serum creatinine
were observed in less than 0.1 percent of patients with essential
hypertension treated
with losartan potassium alone (see PRECAUTIONS,
Impaired Renal Function).
Hemoglobin and Hematocrit: Small decreases in hemoglobin
and hematocrit (mean
decreases of approximately 0.11 grams percent
and 0.09 volume percent,
respectively) occurred frequently in patients treated with losartan
potassium alone, but
were rarely of clinical
importance. No patients were discontinued due to anemia.
Liver Function Tests: Occasional elevations of liver
enzymes and/or other serum
bilirubin have occurred.
In patients with essential
hypertension treated with losartan potassium
alone, one patient (<0.1%)
was discontinued to these laboratory adverse experiences.
DRUG INTERACTIONS
Losartan, administered for 12 days, did not affect
the pharmacokinetics or pharmacodynamics
of a single dose of warfarin.
Losartan did not affect the pharmacokinetics
of oral and intravenous
digoxin. Coadministration of losartan and cimetidine
led to an increase of about 18% in AUC
of losartan but did not affect
the pharmacokinetics
of its active metabolite. Coadministration of losartan and phenobarbital
led to reduction of
about 20% in the AUC of losartan and that of its active metabolite.
There is no pharmacokinetic interaction between losartan and hydrochlorothiazide.
No significant
drug-drug pharmacokinetic interactions have been found in interaction
studies with hydrochlorothiazide, digoxin, warfarin, cimetidine
and phenobarbital. Potent inhibitors of cytochrome
P450 3A4 and 2C9 have not been studied clinically but in vitro
studies wshow significant
inhibition of the formation
of the active metabolite
by inhibitors of P450 3A4 (ketoconazole, troleandomycin, gestodene)
or P450 2C9 (sulfaphenazole) and nearly complete inhibition
by the combination of sulfaphenazole and ketoconazole. The pharmacodynamic
consequences of concomitant
use of losartan and these inhibitors have not been examined.
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.
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