IRBESARTAN Drug Interactions: What You Need to Know

Drug Interactions Lithium: Increases in serum lithium concentrations and lithium toxicity have been reported with concomitant use of irbesartan or thiazide diuretics. Monitor lithium levels in patients receiving irbesartan and lithium. 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. Based on in vitro data, no interaction would be expected with drugs whose metabolism is dependent upon cytochrome P450 isoenzymes 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 pharmacokinetics of digoxin. The pharmacokinetics of irbesartan were not affected by coadministration of nifedipine or hydrochlorothiazide. Concomitant use of potassium-sparing diuretics, potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium.

7.1 Agents Increas ing Serum Potassium Coadministration of irbesartan with other drugs that raise serum potassium levels may result in hyperkalemia, sometimes severe. Monitor serum potassium in such patients.

7.2 Lithium Increases in serum lithium concentrations and lithium toxicity have been reported with concomitant use of irbesartan and lithium. Monitor lithium levels in patients receiving irbesartan and lithium.

7.3 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs )

Including Selective

Cyclooxygenas e-2 Inhibitors (COX-2 Inhibitors ) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists (including irbesartan) may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving irbesartan and NSAID therapy. The antihypertensive effect of angiotensin II receptor antagonists, including irbesartan, may be attenuated by NSAIDs including selective COX-2 inhibitors.

7.4 Dual Blockade of the Renin-Angiotens in Sys tem (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on irbesartan and other agents that affect the RAS. Do not co-administer aliskiren with irbesartan in patients with diabetes. Avoid use of aliskiren with irbesartan in patients with renal impairment (GFR <60 mL/min).

7.1 Agents Increas ing Serum Potassium Coadministration of irbesartan with other drugs that raise serum potassium levels may result in hyperkalemia, sometimes severe. Monitor serum potassium in such patients.

7.2 Lithium Increases in serum lithium concentrations and lithium toxicity have been reported with concomitant use of irbesartan and lithium. Monitor lithium levels in patients receiving irbesartan and lithium.

7.3 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs )

Including Selective

Cyclooxygenas e-2 Inhibitors (COX-2 Inhibitors ) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists (including irbesartan) may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving irbesartan and NSAID therapy. The antihypertensive effect of angiotensin II receptor antagonists, including irbesartan, may be attenuated by NSAIDs including selective COX-2 inhibitors.

7.4 Dual Blockade of the Renin-Angiotens in Sys tem (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on irbesartan and other agents that affect the RAS. Do not co-administer aliskiren with irbesartan in patients with diabetes. Avoid use of aliskiren with irbesartan in patients with renal impairment (GFR <60 mL/min).

Irbesartan is contraindicated in patients who are hypersensitive to any component of this product. Do not coadministrate aliskiren with irbesartan in patients with diabetes. Irbesartan is contraindicated in patients who are hypersensitive to any component of this product. Do not coadministrate aliskiren with irbesartan in patients with diabetes.

AND PRECAUTIONS

• Hypotension: Correct volume or salt depletion prior to administration. ( 5.2 )
• Monitor renal function and serum potassium. ( 5.3 )

5.1 Fetal Toxicity Irbesartan tablets can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue irbesartan tablets as soon as possible <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.1 )]</span>.

5.2 Hypotension in Volume or Salt-Depleted Patients In patients with an activated renin-angiotensin system, such as volume or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initialization of treatment with irbesartan tablets. Correct volume or salt depletion prior to administration of irbesartan tablets or use a lower starting dose <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.4 )]</span>.

5.3 Impaired Renal Function Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe heart failure, or volume depletion) may be at particular risk of developing acute renal failure or death on irbesartan tablets. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on irbesartan tablets <span class="opacity-50 text-xs">[see Drug Interactions ( 7.3 )]</span>.