ADVERSE REACTIONS
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 ≥1% of patients, and more often on the irbesartan-hydrochlorothiazide combination than on placebo, regardless of drug relationship:
| | Irbesartan/HCTZ
(n=898)
(%) | Placebo
(n=236)
(%) | Irbesartan
(n=400)
(%) | HCTZ
(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: sexualdysfunction, 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, cerebrovascular 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); and hepatitis. Hyperkalemia has been rarely reported.
Very rare cases of jaundice have been reported with irbesartan.
Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers.
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%, 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.)
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