Amtrel Warnings

Anaphylactoid Reactions: ACE inhibitors can affect the metabolism of eicosanoid and polypeptides (including intrinsic bradykinin). When patients receive ACE inhibitor therapy, they might experience mild to severe side effects. These side effects usually occur in the 1st few doses. However, some do not experience side effects until after several months of treatment.
Vascular Edema: ACE inhibitors use might occasionally cause vascular edema, including the face, limbs, lips, tongue, glottis and throat. In a clinical trial performed in the United States, it was found that cases in the placebo control group did not develop symptoms of vascular edema, while 0.5% of patients receiving benazepril experienced vascular edema. Vascular edema related to the larynx can be life-threatening; if laryngeal stridor or vascular edema is observed in the face, tongue or glottis, Amtrel should be stopped and the patient should seek appropriate medical attention. When vascular edema occurs in the tongue, glottis or larynx and causing possible obstruction of the respiratory tract, proper treatment should be given immediately eg, SC epinephrine injection 1:1000 (0.3-0.5 mL) (see Adverse Reactions).
Antiallergy Therapy for Anaphylactoid Reactions: Two (2) patients experienced continuous life-threatening anaphylactoid reactions after receiving ACE inhibitor treatment and received antiallergic therapy involving hymenoptera venom.
Allergic Reaction Associated with Contact with Hemodialysis Membrane: Cases of allergy-like reactions were reported with the use of high-flux membranes in dialysis patients taking ACE inhibitors. Allergy-like reactions had occurred in patients who received low-density lipoprotein plasmapheresis therapy by absorbing dextran sulfate.
Increased Angina and/or Myocardial Infarction (MI): When patients with severe obstructive coronary arterial disease start taking calcium-ion blocker or increased its dosage, the frequency, duration and/or severity of angina and/or MI may increase. However, the incident rate of this is low and its mechanism is unclear.
Hypotension: Amtrel can cause generalized hypotension. Like other ACE inhibitors, benazepril has an extremely low chance of causing generalized hypotension in patients with simple hypertension. Generalized hypotension is more easily developed in patients with long-term diuretic use, patients that control dietary salt-intake, dialysis and who lose salt or body fluid due to diarrhea or vomiting. Before using Amtrel, lost body fluids and salt should be replenished first.
Due to the gradual vasodilating effect of amlodipine, the rate of developing acute hypotension is extremely rare with oral amlodipine use. However, when Amtrel is used concurrently with other peripheral vasodilators special caution should be taken, especially in patients with aortic stenosis.
Regardless of the relation with renal dysfunction, ACE inhibitors treatment in patients with congestive heart failure can cause excessive hypotension and subsequently result in oliguria, azotemia and acute renal failure or death (extremely rare). This type of patients should only receive Amtrel under strict medical monitoring. Careful follow-up should be performed when increasing the dosage of benazepril, or adding or increasing the dosage of diuretics. When hypotension occurs, patient should be recumbent. When necessary, IV transfusion of saline solution can be provided. Once blood pressure and body fluids are restored, Amtrel may be continued.
Neutropenia/Agranulocytopenia: Data have shown that usage of another ACE inhibitor, captopril, may result in agranulocytopenia and bone marrow suppression. The incidence is lower in patients with simple hypertension (<1/10,000), while the incidence is higher in patients with renal dysfunction (>1/10,000), especially in patients with collagen vascular disease eg, systemic lupus erythematosus (SLE) or scleroderma. Clinical trial data involving benazepril are insufficient in demonstrating that it will not cause agranulocytopenia similar to captopril. Thus, in patients with collagen vascular disease, the leukocyte count should be monitored, especially when the disease is related with renal dysfunction.
Fetus/Newborn Disease Incidence and Death Rate: In studies from around the world, many cases have demonstrated that ACE inhibitors use in pregnant women can cause disease or death of the fetus. Hence, when a woman determines to be pregnant, the patient should immediately stop taking Amtrel. ACE inhibitors use in the 2nd or 3rd trimester can result in damage to the fetus or newborn, including hypotension, improper development of the skull, anuria, reversible or irreversible renal failure and death. Also, reduced renal function of the fetus can result in nonproduction of amniotic fluid. Oligohydramnios is related to limb contracture and deformity, facial deformity and improper lung development of a fetus. Delayed uterus growth and permanent arterial fistula have been reported, although it is unclear whether they are caused by ACE inhibitors use.
At the present, there are no clinical trials involving Amtrel in pregnant women.
Liver Failure: Very few liver failures are related with ACE inhibitors. Symptoms can start with cholestic jaundice and worsen to fibrotic liver necrosis and sometimes even death. The mechanism for these symptoms is unclear. When patients receiving ACE inhibitors display jaundice or significant increase in liver enzymes, ACE inhibitors should be stopped and patients should receive appropriate medical care.