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
Diovan Side Effects, and Drug Interactions - Valsartan
Diovan Side Effects, and Drug Interactions - Valsartan
SIDE EFFECTS
Valsartan has been evaluated for safety in more than 4000 patients,
including over 400 treated for over 6 months, and more than 160
for over 1 year. Adverse experiences have generally been mild and
transient in nature
and have only infrequently required discontinuation of therapy.
The overall incidence of adverse experiences with valsartan was
similar to placebo.
The overall frequency of adverse experiences was neither dose-related
nor related to gender, age, race, or regimen. Discontinuation of
therapy due to side effects
was required in 2.3% of valsartan patients and 2.0% of placebo patients.
The most common reasons for discontinuation of therapy with valsartan
were headache and dizziness.
The adverse experiences that occurred in placebo-controlled clinical
trials in at least 1% of patients treated with valsartan and at
a higher incidence in valsartan (n=2316) than placebo
(n=888) patients included viral
infection (3% vs. 2%), fatigue
(2% vs. 1%), and abdominal
pain (2% vs. 1%).
Headache, dizziness, upper respiratory infection, cough, diarrhea,
rhinitis, sinusitis, nausea, pharyngitis, edema, and arthralgia
occurred at a more than 1% rate
but at about the same incidence
in placebo and valsartan
patients.
In trials in which valsartan was compared to an ACE
inhibitor with or
without placebo, the incidence
of dry cough was significantly
greater in the ACE-inhibitor group
(7.9%) than in the groups who received valsartan (2.6%) or placebo
(1.5%). In a 129-patient
trial limited to patients who had had dry cough
when they had previously received ACE
inhibitors, the incidences of cough
in patients who received valsartan, HCTZ, or lisinopril
were 20%, 19%, and 69% respectively (p<0.001).
Dose-related orthostatic
effects were seen in less than 1% of patients. An increase in the
incidence of dizziness
was observed in patients treated with valsartan 320 mg
(8%) compared to 10 to 160 mg
(2% to 4%).
Valsartan has been used concomitantly with hydrochlorothiazide
without evidence of clinically important adverse interactions.
Other adverse experiences that occurred in controlled clinical
trials of patients treated with valsartan (>0.2% of valsartan
patients) are listed below. It cannot be determined whether these
events were causally related to valsartan.
Body as a Whole: Allergic reaction
and asthenia.
Cardiovascular: Palpitations.
Dermatologic: Pruritus and rash.
Digestive: Constipation, dry mouth, dyspepsia, and
flatulence.
Musculoskeletal: Back pain, muscle
cramps, and myalgia.
Neurologic and Psychiatric: Anxiety, insomnia, paresthesia,
and somnolence.
Respiratory: Dyspnea.
Special Senses: Vertigo.
Urogenital: Impotence.
Other reported events seen less frequently in clinical
trials included chest pain, syncope, anorexia, vomiting, and angioedema.
Clinical Laboratory Test Findings
In controlled clinical
trials, clinically important changes in standard laboratory parameters
were rarely associated with administration
of valsartan.
Creatinine: Minor elevations in creatinine
occurred in 0.8% of patients taking valsartan and 0.6% given placebo
in controlled clinical trials.
Hemoglobin and Hematocrit: Greater than 20% decreases
in hemoglobin and
hematocrit were observed
in 0.4% and 0.8%, respectively, of valsartan patients, compared
with 0.1% and 0.1% in placebo-treated patients. One valsartan patient
discontinued treatment
for microcytic anemia.
Liver function
tests: Occasional elevations (greater than 150%) of liver
chemistries occurred in valsartan-treated patients. Three patients
(< 0.1%) treated with valsartan discontinued treatment
for elevated liver chemistries.
Neutropenia: Neutropenia was observed in 1.9% of
patients treated with valsartan and 0.8% of patients treated with
placebo.
Serum Potassium: Greater than 20% increases in serum
potassium were observed in 4.4% of valsartan-treated patients compared
to 2.9% of placebo-treated patients. No patient
treated with valsartan discontinued therapy for hyperkalemia.
DRUG INTERACTIONS
No clinically significant
pharmacokinetic interactions were observed when valsartan was coadministered
with amlodipine, atenolol, cimetidine, digoxin, furosemide, glyburide,
hydrochlorothiazide, or indomethacin. The valsartan-atenolol combination
was more antihypertensive
than either component, but it did not lower the heart
rate more than atenolol
alone.
Coadministration of valsartan and warfarin did not change the pharmacokinetics
of valsartan or the time-course of the anticoagulant
properties of warfarin.
CYP 450 Interactions: The enzyme(s) responsible for
valsartan metabolism have not been identified but do not seem to
be CYP 450 isozymes. The inhibitory or induction
potential of valsartan
on CYP 450 is also unknown.
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