Chemical formula: C₂₅H₂₈N₆O Molecular mass: 428.529 g/mol PubChem compound: 3749
Irbesartan interacts in the following cases:
When angiotensin II antagonists are administered simultaneously with non-steroidal anti-inflammatory drugs (i.e. selective COX-2 inhibitors, acetylsalicylic acid (>3 g/day) and non-selective NSAIDs), attenuation of the antihypertensive effect may occur.
As with ACE inhibitors, concomitant use of angiotensin II antagonists and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor pre-existing renal function. The combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.
Based on experience with the use of other medicinal products that affect the renin-angiotensin system, concomitant use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium or other medicinal products that may increase serum potassium levels (e.g. heparin) may lead to increases in serum potassium and is, therefore, not recommended.
Other antihypertensive agents may increase the hypotensive effects of irbesartan; however irbesartan has been safely administered with other antihypertensive agents, such as beta-blockers, long-acting calcium channel blockers, and thiazide diuretics. Prior treatment with high dose diuretics may result in volume depletion and a risk of hypotension when initiating therapy with irbesartan.
Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone system (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent.
Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors. Similar effects have been very rarely reported with irbesartan so far. Therefore, this combination is not recommended. If the combination proves necessary, careful monitoring of serum lithium levels is recommended.
Irbesartan has the potential to inhibit OATP1B1. In a clinical study, it was reported that irbesartan increased the Cmax and AUC of repaglinide (substrate of OATP1B1) by 1.8-fold and 1.3-fold, respectively, when administered 1 hour before repaglinide. In another study, no relevant pharmacokinetic interaction was reported, when the two drugs were co-administered. Therefore, dose adjustment of antidiabetic treatment such as repaglinide may be required.
Patients with primary aldosteronism generally will not respond to antihypertensive medicinal products acting through inhibition of the renin-angiotensin system. Therefore, the use of irbesartan is not recommended.
A lower starting dose (75 mg) of irbesartan should be considered for patients undergoing haemodialysis.
As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral valve stenosis, or obstructive hypertrophic cardiomyopathy.
The use of AIIRAs is not recommended during the first trimester of pregnancy. The use of AIIRAs is contraindicated during the second and third trimesters of pregnancy.
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II Receptor Antagonists (AIIRAs), similar risks may exist for this class of drugs. Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started.
Exposure to AIIRA therapy during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia).
Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken AIIRAs should be closely observed for hypotension.
Because no information is available regarding the use of irbesartan during breast-feeding, irbesartan is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
It is unknown whether irbesartan or its metabolites are excreted in human milk.
Available pharmacodynamic/toxicological data in rats have shown excretion of irbesartan or its metabolites in milk.
Irbesartan had no effect upon fertility of treated rats and their offspring up to the dose levels inducing the first signs of parental toxicity.
Based on its pharmacodynamic properties, irbesartan is unlikely to affect the ability to drive and use machines. When driving vehicles or operating machines, it should be taken into account that dizziness or weariness may occur during treatment.
In placebo-controlled trials in patients with hypertension, the overall incidence of adverse events did not differ between the irbesartan (56.2%) and the placebo groups (56.5%). Discontinuation due to any clinical or laboratory adverse event was less frequent for irbesartan-treated patients (3.3%) than for placebo-treated patients (4.5%). The incidence of adverse events was not related to dose (in the recommended dose range), gender, age, race, or duration of treatment.
In diabetic hypertensive patients with microalbuminuria and normal renal function, orthostatic dizziness and orthostatic hypotension were reported in 0.5% of the patients (i.e. uncommon) but in excess of placebo.
The following table presents the adverse drug reactions that were reported in placebo-controlled trials in which 1,965 hypertensive patients received irbesartan. Terms marked with a star (*) refer to the adverse reactions that were additionally reported in >2% of diabetic hypertensive patients with chronic renal insufficiency and overt proteinuria and in excess of placebo.
The frequency of adverse reactions listed below is defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Adverse reactions additionally reported from post-marketing experience are also listed. These adverse reactions are derived from spontaneous reports.
Not known: anaemia, thrombocytopenia
Not known: hypersensitivity reactions such as angioedema, rash, urticaria, anaphylactic reaction, anaphylactic shock
Not known: hyperkalaemia, hypoglycaemia
Common: dizziness, orthostatic dizziness*
Not known: vertigo, headache
Not known: tinnitus
Uncommon: tachycardia
Common: orthostatic hypotension*
Uncommon: flushing
Uncommon: cough
Common: nausea/vomiting
Uncommon: diarrhoea, dyspepsia/heartburn
Not known: dysgeusia
Uncommon: jaundice
Not known: hepatitis, abnormal liver function
Not known: leukocytoclastic vasculitis
Common: musculoskeletal pain*
Not known: arthralgia, myalgia (in some cases associated with increased plasma creatine kinase levels), muscle cramps
Not known: impaired renal function including cases of renal failure in patients at risk
Uncommon: sexual dysfunction
Common: fatigue
Uncommon: chest pain
Very common: Hyperkalaemia* occurred more often in diabetic patients treated with irbesartan than with placebo. In diabetic hypertensive patients with microalbuminuria and normal renal function, hyperkalaemia (≥5.5 mEq/L) occurred in 29.4% of the patients in the irbesartan 300 mg group and 22% of the patients in the placebo group. In diabetic hypertensive patients with chronic renal insufficiency and overt proteinuria, hyperkalaemia (≥5.5 mEq/L) occurred in 46.3% of the patients in the irbesartan group and 26.3% of the patients in the placebo group.
Common: significant increases in plasma creatine kinase were commonly observed (1.7%) in irbesartan treated subjects. None of these increases were associated with identifiable clinical musculoskeletal events. In 1.7% of hypertensive patients with advanced diabetic renal disease treated with irbesartan, a decrease in haemoglobin*, which was not clinically significant, has been observed.
In a randomised trial of 318 hypertensive children and adolescents aged 6 to 16 years, the following adverse reactions occurred in the 3-week double-blind phase: headache (7.9%), hypotension (2.2%), dizziness (1.9%), cough (0.9%). In the 26-week open-label period of this trial the most frequent laboratory abnormalities observed were creatinine increases (6.5%) and elevated CK values in 2% of child recipients.
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