Benazepril

7 . DRUG INTERACTIONS Diuretics: Excessive drop in blood pressure ( 7.1 ) Antidiabetics: Increased risk of hypoglycemia ( 7.2 ) NSAIDS: Increased risk of renal impairment and loss of antihypertensive efficacy ( 7.3 ) Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension and hyperkalemia ( 7.4 ) Lithium: Symptoms of lithium toxicity ( 7.6 ) Neprilysin Inhibitor: Increased risk of angioedema ( 7.7 ) Gold: Nitritoid reactions ( 7.8 )

7.1 Diuretics Hypotension Patients on diuretics, especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with Lotensin. The possibility of hypotensive effects with Lotensin can be minimized by either discontinuing or decreasing the dose of diuretic prior to initiation of treatment with Lotensin [see Dosage and Administration (2.1) ]. Hyperkalemia Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) can increase the risk of hyperkalemia. Therefore, if concomitant use of such agents is indicated, monitor the patient’s serum potassium frequently.

Lotensin attenuates potassium loss caused by thiazide-type diuretics.

7.2 Antidiabetics Concomitant administration of Lotensin and antidiabetic medicines (insulins, oral hypoglycemic agents) may increase the risk of hypoglycemia.

7.3 Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including benazepril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving benazepril and NSAID therapy. The antihypertensive effect of ACE inhibitors, including benazepril, may be attenuated by NSAIDs.

7.4 Dual Blockade of the Renin-Angiotensin System (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 Lotensin and other agents that affect the RAS. Do not coadminister aliskiren with Lotensin in patients with diabetes.

Avoid use of aliskiren with Lotensin in patients with renal impairment (GFR < 60 mL/min).

7.5 Mammalian Target of Rapamycin (mTOR) Inhibitors Patients receiving coadministration of ACE inhibitor and mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema. Monitor for signs of angioedema [se e Warnings and Precautions (5.2) ] .

7.6 Lithium Lithium toxicity has been reported in patients receiving lithium concomitantly with Lotensin. Lithium toxicity was usually reversible upon discontinuation of lithium or Lotensin. Monitor serum lithium levels during concurrent use.

7.7 Neprilysin Inhibitor Patients taking concomitant neprilysin inhibitors may be at increased risk for angioedema [see Warnings and Precautions ].

7.8 Gold Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy.

8.1 Pregnancy Risk Summary Lotensin 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. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin­ angiotensin system from other antihypertensive agents. When pregnancy is detected, discontinue Lotensin as soon as possible. The estimated background risk of major birth defects and miscarriage for the indicated population are unknown.

All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the general U.S. population, the estimated background risk of major defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypertension in pregnancy increases the maternal rush for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death.

Pregnant women with hypertension should be carefully monitored and managed accordingly. Fetal/Neonatal Adverse Reactions Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia and skeletal deformations, including skull hypoplasia, hypotension, and death. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus.

Perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Lotensin for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occur in neonates with a history of in utero exposure to Lotensin, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing…