pms-Irbesartan Adverse Reactions

Clinical Trial Adverse Reactions: Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.
Irbesartan was evaluated for safety in > 4,100 patients with essential hypertension including approximately 1,300 patients treated for > 6 months and 400 patients for ≥ 1 year.
In placebo-controlled clinical trials, therapy was discontinued due to a clinical adverse event (AE) in 3.3% of patients treated with irbesartan, versus 4.5% of patients given placebo.
The following potentially serious adverse reactions have been reported rarely with irbesartan in controlled clinical trials: syncope, hypotension.
AEs occurring in ≥ 1% of the 2,606 hypertensive patients in placebo-controlled clinical trials include the following: See Table 6.

Click on icon to see table/diagram/image

AEs of hypotension or orthostatic hypotension, unrelated to dosage, occurred in 0.4% of irbesartan treated patients and in 0.2% of patients receiving placebo.
In addition, the following potentially important events occurred in < 1% of patients receiving irbesartan, regardless of drug relationship: Body as a Whole: fever.
Cardiovascular: angina pectoris, arrhythmic/conduction disorder, cardio-respiratory arrest, flushing, heart failure, hypertension, hypertensive crisis, myocardial infarction.
Dermatologic: dermatitis, ecchymosis, erythema, photosensitivity, pruritus, urticaria.
Endocrine: gout, libido change, sexual dysfunction.
Gastrointestinal: constipation, distension abdomen, flatulence, gastroenteritis, hepatitis.
Hematologic: anemia, lymphocytopenia, thrombocytopenia.
Investigations: increased creatine phosphokinase (CPK).
Musculoskeletal: arthritis, muscle cramp, muscle weakness, myalgia.
Nervous System: cerebrovascular accident, depression, numbness, paresthesia, sleep disturbance, somnolence, transient ischemic attack, tremor, vertigo.
Renal/Genitourinary: abnormal urination.
Respiratory: dyspnea, epistaxis, pulmonary congestion, tracheobronchitis, wheezing.
Special Senses: conjunctivitis, hearing abnormality, taste disturbance, visual disturbance.
Clinical Studies in Hypertension and Type 2 Diabetic Renal Disease: In clinical studies in patients with hypertension and type 2 diabetic renal disease, the adverse drug experiences were similar to those seen in clinical trials of hypertensive patients with the exception of orthostatic symptoms (dizziness, orthostatic dizziness, and orthostatic hypotension) observed in IDNT (The Irbesartan Diabetic Nephropathy Trial) (proteinuria ≥ 900 mg/day, and serum creatinine from 1.0 - 3.0 mg/dL). In IDNT, orthostatic symptoms occurred more frequently in the irbesartan group (dizziness 10.2%, orthostatic dizziness 5.4%, orthostatic hypotension 5.4%) than in the placebo group (dizziness 6.0%, orthostatic dizziness 2.7%, orthostatic hypotension 3.2%). The rates of discontinuations due to orthostatic symptoms for irbesartan versus placebo were: dizziness 0.3% vs 0.5%; orthostatic dizziness 0.2% vs. 0.0%; and orthostatic hypotension, 0.0% vs 0.0%.
Laboratory Test Findings: In controlled clinical trials of hypertension, clinically important differences in laboratory tests were rarely associated with irbesartan.
Liver Function Tests: In placebo-controlled trials, elevations of AST and ALT ≥ 3X upper limit of normal (ULN) occurred in 0.1% and 0.2%, respectively, of irbesartan treated patients compared to 0.3% and 0.3%, respectively, of patients receiving placebo. In patients treated with irbesartan for a mean duration of over 1 year, the cumulative incidence of AST and/or ALT elevations ≥ 3X ULN was 0.4%.
Hyperkalemia: The laboratory test parameter profile was similar in clinical trials conducted in patients with hypertension, type 2 diabetes and renal disease compared to that of patients with hypertension only, with the exception of hyperkalemia. In a placebo-controlled trial in 590 patients with hypertension, type 2 diabetes, microalbuminuria, and normal renal function (IRMA 2), hyperkalemia ≥ 5.5 mEq/L occurred in 29.4% of the patients in the irbesartan 300 mg group compared to 22% of the patients in the placebo group. Discontinuation for hyperkalemia occurred in 0.5% of the patients in the irbesartan group.
In another placebo-controlled trial in 1,715 patients with hypertension, type 2 diabetes, proteinuria ≥ 900 mg/day, and serum creatinine ranging from 1.0 - 3.0 mg/dl (IDNT), hyperkalemia ≥ 5.5 mEq/L occurred in 46.3% of the patients in the irbesartan group compared to 26.3% of the patients in the placebo group. Discontinuation for hyperkalemia occurred in 2.1% and 0.4% of the patients in the irbesartan and placebo groups, respectively.
Creatinine, Blood Urea Nitrogen: Minor increases in blood urea nitrogen (BUN) or serum creatinine were observed in less than 0.7% of patients with essential hypertension treated with irbesartan alone versus 0.9% on placebo.
Hemoglobin: Mean decreases in hemoglobin of 0.16 g/dL were observed in patients receiving irbesartan. No patients were discontinued due to anemia.
Neutropenia: Neutropenia (< 1,000 cells/mm³) was observed in 0.3% of irbesartan treated patients compared to 0.5% of patients receiving placebo.
Post-Market Adverse Reactions: Ear/Nose/Throat: tinnitus.
Endocrine and Metabolism: hypoglycemia (see Precautions).
General: asthenia, syncope.
Hematologic: thrombocytopenia (including thrombocytopenic purpura), anemia (cases of positive dechallenge and rechallenge have been reported post-market).
Hepatic/Biliary/Pancreatic: elevated liver function tests, jaundice.
Immune: anaphylactic shock, angioedema (involving swelling of the face, lips, and/or tongue) has been reported rarely in post-marketing use. Photosensitivity.
Musculoskeletal: muscle pain, muscle weakness, myositis and rhabdomyolysis have been reported in patients receiving ARBs. Myalgia.
Renal: impaired renal function including cases of renal failure in patients at risk (see Renal under Precautions).
Skin: psoriasis (and psoriasis exacerbation).