pms-Irbesartan Special Precautions

Cardiovascular: Hypotension - Volume-Depleted Patients: Occasionally, symptomatic hypotension has occurred after administration of irbesartan, in some cases after the first dose. It is more likely to occur in patients who are volume-depleted by diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. In these patients, because of the potential fall in BP, therapy should be started under close medical supervision (see Dosage & Administration). Similar considerations apply to patients with ischemic heart or cerebrovascular disease, in whom an excessive fall in BP could result in myocardial infarction or cerebrovascular accident.
Dual Blockade of the Renin-Angiotensin System (RAS): There is evidence that co-administration of angiotensin receptor antagonists (ARBs), such as irbesartan, or of angiotensin converting enzyme (ACE) inhibitors with aliskiren increases the risk of hypotension, syncope, stroke, hyperkalemia and deterioration of renal function, including renal failure, in patients with diabetes mellitus (type 1 or type 2) and/or moderate to severe renal impairment (GFR < 60 ml/min/1.73 m²). Therefore, the use of pms-IRBESARTAN in combination with aliskiren-containing drugs is contraindicated in these patients (see Contraindications).
The use of pms-IRBESARTAN in combination with of ACE inhibitors is contraindicated in patients with diabetic nephropathy (see Contraindications).
Further, co-administration of ARBs, including irbesartan, with other agents blocking the RAS, such as ACE inhibitors or aliskiren-containing drugs, is generally not recommended in other patients, since such treatment has been associated with an increased incidence of severe hypotension, renal failure, and hyperkalemia.
Lithium: Increases in serum lithium concentrations and lithium toxicity (including fatal outcome) have been reported with concomitant use of irbesartan and lithium (see Interactions). Therefore, this combination is not recommended. Serum lithium levels should be monitored carefully in patients receiving irbesartan and lithium if the combination is necessary.
Valvular Stenosis: There is concern on theoretical grounds that patients with aortic stenosis might be at particular risk of decreased coronary perfusion when treated with vasodilators because they do not develop as much afterload reduction.
Endocrine and Metabolism: Irbesartan may induce hypoglycemia, particularly in patients treated for diabetes. Therefore, dose adjustment of antidiabetic treatment such as repaglinide or insulin may be required (see Adverse Reactions).
Renal: Renal Impairment: As a consequence of inhibiting the renin-angiotensin-aldosterone system (RAAS), changes in renal function have been seen in susceptible individuals. In patients whose renal function may depend on the activity of the RAAS, such as patients with bilateral renal artery stenosis, unilateral renal artery stenosis to a solitary kidney, or severe congestive heart failure, treatment with agents that inhibit this system has been associated with oliguria, progressive azotemia, and rarely, acute renal failure and/or death. In susceptible patients, concomitant diuretic use may further increase risk.
The use of ARBs including irbesartan, or of ACE inhibitors, with aliskiren-containing drugs is contraindicated in patients with moderate to severe renal impairment (GFR < 60 ml/min/1.73 m²) (see Contraindications and Interactions).
The use of ARBs including irbesartan in combination with an ACEI is contraindicated in patients with diabetic nephropathy due to risk of hyperkalemia, hypotension and renal impairment (see Contraindications and Interactions).
Use of irbesartan should include appropriate assessment of renal function.
In hypertensive type 2 diabetic patients with proteinuria (≥ 900 mg/day), a population which has a high risk of renal artery stenosis, no patient treated with irbesartan in IDNT had an early acute rise in serum creatinine attributable to renal artery disease (see Pharmacology under Actions).
Skin: The use of pms-IRBESARTAN in patients with psoriasis or a history of psoriasis should be carefully weighed as it may exacerbate psoriasis.
Driving and Operating Machinery: The effect of irbesartan on the ability to drive and use of machinery has not been studied, but based on its pharmacodynamic properties, irbesartan is unlikely to affect this ability. When driving vehicles or operating machinery, it should be taken into account that occasionally, dizziness or weariness may occur during treatment of hypertension.
Use in Pregnancy: Drugs that act directly on the renin-angiotensin-aldosterone system (RAAS) can cause fetal and neonatal morbidity and death when administered to pregnant women. When pregnancy is detected, pms-IRBESARTAN should be discontinued as soon as possible.
The use of ARBs is contraindicated during pregnancy. Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors (another class of therapeutic products interfering with the RAAS) during the first trimester of pregnancy has not been conclusive; however, a small increase in risk cannot be excluded. Given the current evidence available on the risk with ARBs, similar risks may exist for this class of drugs. Patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started.
The use of ARBs during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification, retardation) and neonatal toxicity (renal failure, hypotension, hyperkalemia).
Infants with histories of in utero exposure to an ARB should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of BP and renal perfusion. Exchange transfusion may be required as means of reversing hypotension and/or substituting for impaired renal function; however, limited experience with those procedures has not been associated with significant clinical benefit. Irbesartan is not removed by hemodialysis.
Use in Lactation: It is not known whether irbesartan is excreted in human milk, but significant levels have been found in the milk of lactating rats. Because many drugs are excreted in human milk, and because of their potential for affecting the nursing infant adversely, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Use in Children: Pediatrics (< 18 years of age): The safety and efficacy of irbesartan have not been established in children < 18 years of age. Therefore, pms-IRBESARTAN is not indicated in this patient population.
Use in the Elderly: Geriatrics (> 65 years of age): Of the 4,140 hypertensive patients receiving irbesartan in clinical studies, 793 patients were ≥ 65 years of age. No overall age-related differences were seen in the adverse effect profile but greater sensitivity in some older individuals cannot be ruled out.