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
Avalide Side Effects, and Drug Interactions - Irbesartan HCTZ
Avalide Side Effects, and Drug Interactions - Irbesartan HCTZ
SIDE EFFECTS
Irbesartan-hydrochlorothiazide
AVALIDE (irbesartan-hydrochlorothiazide) Tablets has been evaluated
for safety in 898 patients treated for essential hypertension. In clinical trials
with AVALIDE, no adverse experiences peculiar to this combination drug product
have been observed. Adverse experiences have been limited to those that were
reported previously with irbesartan and/or hydrochlorothiazide (HCTZ). The overall
incidence of adverse experiences reported with the combination was comparable
to placebo. In general, treatment with AVALIDE was well tolerated. For the most
part, adverse experiences have been mild and transient in nature and have not
required discontinuation of therapy. In controlled clinical trials, discontinuation
of AVALIDE therapy due to clinical adverse experiences was required in only
3.6%.This incidence was significantly less (p=0.023) than the 6.8% of patients
treated with placebo who discontinued therapy.
In these double-blind controlled clinical trials, the following
adverse experiences reported with AVALIDE occurred in ³1%
of patients, and more often on the irbesartan-hydrochlorothiazide combination
then on placebo, regardless of drug relationship:
| |
Irbesartan/HCTZ
|
Placebo
|
Irbesartan
|
HCTZ
|
| |
(n=898)
|
(n=236)
|
(n=400)
|
(n=380)
|
| |
(%)
|
(%)
|
(%)
|
(%)
|
|
Body as a Whole
|
|
Chest Pain
|
2
|
1
|
2
|
2
|
|
Fatigue
|
7
|
3
|
4
|
3
|
|
Influenza
|
3
|
1
|
2
|
2
|
|
Cardiovascular
|
|
Edema
|
3
|
3
|
2
|
2
|
|
Tachycardia
|
1
|
0
|
1
|
1
|
|
Gastrointestinal
|
|
Abdominal Pain
|
2
|
1
|
2
|
2
|
|
Dyspepsia/heartburn
|
2
|
1
|
0
|
2
|
|
Nausea/vomiting
|
3
|
0
|
2
|
0
|
|
Immunology
|
|
Allergy
|
1
|
0
|
1
|
1
|
|
Musculoskeletal
|
|
Musculoskeletal
|
|
|
|
|
|
Pain
|
7
|
5
|
6
|
10
|
|
Nervous System
|
|
Dizziness
|
8
|
4
|
6
|
5
|
|
Dizziness Orthostatic
|
1
|
0
|
1
|
1
|
|
Renal/Genitourinary
|
|
Abnormality
|
|
|
|
|
|
Urination
|
2
|
1
|
1
|
2
|
The following adverse events were also reported at a rate of
1% or greater, but were as, or more, common in the placebo group: headache,
sinus abnormality, cough, URI, pharyngitis, diarrhea, rhinitis, urinary tract
infection, rash, anxiety/nervousness, and muscle cramp.
Adverse events occurred at about the same rates in men and
women, older and younger patients,and black and non-black patients.
Irbesartan
Other adverse experiences that have been reported with irbesartan,
without regard to causality are listed below:
Body as a Whole: fever, chills, orthostatic effects,
facial edema, upper extremity edema
Cardiovascular: flushing, hypertension, cardiac murmur,
myocardial infarction, angina pectoris, hypotension, syncope, arrhythmic/conduction
disorder, cardio-respiratory arrest, heart failure, hypertensive crisis
Dermatologic: pruritus, dermatitis, ecchymosis, erythema
face, urticaria
Endocrine/Metabolic/Electrolyte Imbalances: sexual dysfunction,
libido change, gout
Gastrointestinal: diarrhea, constipation, gastroenteritis,
flatulence, abdominal distention
Musculoskeletal/Connective Tissue: musculoskeletal trauma,
extremity swelling, muscle cramp, arthritis, muscle ache, musculoskeletal chest
pain, joint stiffness, bursitis, muscle weakness Nervous System: anxiety/nervousness,
sleep disturbance, numbness, somnolence, vertigo, emotional disturbance, depression,
paresthesia, tremor, transient ischemic attack, cerebrovas-cular accident
Renal/Genitourinary: prostate disorder
Respiratory: cough, upper respiratory infection, epistaxis,
tracheobronchitis, congestion, pulmonary congestion, dyspnea, wheezing Special
Senses: vision disturbance, hearing abnormality, ear infection, ear pain,
conjunctivitis
Hydrochlorothiazide
Other adverse experiences that have been reported with hydrochlorothiazide,
without regard to causality, are listed below:
Body As A Whole: weakness
Digestive: pancreatitis, jaundice (intrahepatic cholestatic
jaundice), sialadenitis, cramping, gastric irritation
Hematologic: aplastic anemia, agranulocytosis, leukopenia,
hemolytic anemia, thrombocytopenia
Hypersensitivity: purpura, photosensitivity, urticaria,
necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory
distress including pneumonitis and pulmonary edema, anaphylactic reactions
Metabolic: hyperglycemia, glycosuria, hyperuricemia
Musculoskeletal: muscle spasm
Nervous System/Psychiatric: restlessness
Renal: renal failure, renal dysfunction, interstitial
nephritis
Skin: erythema multiforme including Stevens-Johnson
syndrome, exfoliative dermatitis including toxic epidermal necrolysis
Special Senses: transient blurred vision, xanthopsia
Post-Marketing Experience
The following have been very rarely reported in post-marketing
experience: urticaria; angioedema (involving swelling of the face, lips, pharynx,
and/or tongue). Hyperkalemia has been rarely reported.
Very rare cases of jaundice have been reported with irbesartan.
Laboratory Test Findings
In controlled clinical trials,clinically important changes
in standard laboratory parameters were rarely associated with administration
of AVALIDE (irbesartan-hydrochlorothiazide) Tablets.
Creatinine, Blood Urea Nitrogen: Minor increases in
blood urea nitrogen (BUN) or serum creatinine were observed in 2.3 and 1.1 percent,
respectively, of patients with essential hypertension treated with AVALIDE alone.
No patient discontinued taking AVALIDE due to increased BUN. One patient discontinued
taking AVALIDE due to a minor increase in serum creatinine.
Hemoglobin: Mean decreases of approximately 0.2 g/dL
occurred in patients treated with AVALIDE alone, but were rarely of clinical
importance. This compared to a mean of 0.4 g/dL in patients receiving placebo.
No patients were discontinued due to anemia.
Liver Function Tests: Occasional elevations of liver
enzymes and/or serum bilirubin have occurred. In patients with essential hypertension
treated with AVALIDE alone, one patient was discontinued due to elevated liver
enzymes.
Serum Electrolytes: (See PRECAUTIONS.)
DRUG INTERACTIONS
Irbesartan
No significant drug-drug pharmacokinetic (or pharmacodynamic)
interactions have been found in interaction studies with hydrochlorothiazide,
digoxin, warfarin, and nifedipine.
In vitro studies show significant inhibition of the
formation of oxidized irbesartan metabolites with the known cytochrome CYP 2C9
substrates/inhibitors sulphenazole, tolbutamide and nifedipine. However, in
clinical studies the consequences of concomitant irbesartan on the pharmacodynamics
of warfarin were negligible. Concomitant nifedipine or hydrochlorothiazide had
no effect on irbesartan pharmacokinetics. Based on in vitro data, no
interaction would be expected with drugs whose metabolism is dependent upon
cytochrome P450 isozymes 1A1, 1A2,2A6,2B6,2D6,2E1,or 3A4.
In separate studies of patients receiving maintenance doses
of warfarin, hydrochlorothiazide, or digoxin, irbesartan administration for
7 days had no effect on the pharmacodynamics of warfarin (prothrombin time)
or the pharmacokinetics of digoxin. The pharmacokinetics of irbesartan were
not affected by coadministration of nifedipine or hydrochlorothiazide.
Hydrochlorothiazide
When administered concurrently the following drugs may interact
with thiazide diuretics:
Alcohol, Barbiturates, Or Narcotics — potentiation of
orthostatic hypotension may occur.
Antidiabetic Drugs (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
percent, 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 AVALIDE.
Non-steroidal Anti-inflammatory Drugs — in some patients,
the administration of a non-steroidal anti-inflammatory agent can reduce the
diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing
and thiazide diuretics. Therefore, when AVALIDE Tablets and non-steroidal anti-inflammatory
agents are used concomitantly, the patient should be observed closely to determine
if the desired effect of the diuretic is obtained.
top
