Perindopril

Pregnancy Pregnancy: The use of ACE inhibitors is not recommended during the first trimester of pregnancy.‍‍‍‍‍‍​​​‍​​​​​​ The use of ACE inhibitors is contraindicated during the second and third trimesters of pregnancy. Breast-feeding Breast-feeding: Perindopril therapy is not recommended during breast-feeding. Hepatic impairment Hepatic impairment: See ACE inhibitors. Renal impairment Renal impairment: See ACE inhibitors. Driving Driving: Individual reactions related to hypotension may occur in certain patients, particularly at the beginning of treatment or when combined with other antihypertensive medication. Consequently, the ability to drive or operate machinery may be impaired. Stable coronary artery disease: If an episode of unstable angina (major or not) occurs during the first month of treatment with perindopril, a careful benefit/risk assessment should be performed before continuing treatment. Hypotension: ACE inhibitors may cause a fall in blood pressure. Symptomatic hypotension has rarely been observed in patients with uncomplicated hypertension and is more likely to occur in patients who have been volume-depleted, e.g. by diuretic therapy, dietary salt restriction, dialysis, diarrhoea or vomiting, or who have severe renin-dependent hypertension. In patients with symptomatic heart failure, with or without associated renal insufficiency, symptomatic hypotension has been observed. This is most likely to occur in patients with more severe degrees of heart failure, as reflected by the use of high doses of loop diuretics, hyponatraemia, or impaired renal function. In patients at increased risk of symptomatic hypotension, initiation of therapy and dose adjustment should be closely monitored. Similar considerations apply to patients with ischaemic heart disease or cerebrovascular disease, in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident. If hypotension occurs, the patient should be placed in the supine position and, if necessary, should receive an intravenous infusion of 9 mg/ml sodium chloride solution. A transient hypotensive response is not a contraindication to further doses, which can usually be given without difficulty once the blood pressure has increased after volume expansion. In certain patients with congestive heart failure who have normal or low blood pressure, an additional lowering of blood pressure may occur with perindopril. This effect is predictable and usually does not require discontinuation of treatment. If hypotension becomes symptomatic, a reduction in dose or discontinuation of perindopril therapy may be necessary. Aortic and mitral valve stenosis/hypertrophic cardiomyopathy: As with other ACE inhibitors, perindopril should be given with caution to patients with mitral valve stenosis and obstruction in the outflow of the left ventricle, such as aortic stenosis or hypertrophic cardiomyopathy. Renal impairment: In cases of renal impairment (creatinine clearance < 60 ml/min), the initial perindopril dosage should be adjusted according to the patient's creatinine clearance values, and then as a function of the patient's response to treatment. Routine monitoring of potassium and creatinine is part of normal medical practice for these patients. In patients with symptomatic heart failure, hypotension following the initiation of ACE inhibitor therapy may lead to further impairment of renal function. In this situation, acute renal failure, usually reversible, has been reported. In certain patients with bilateral renal artery stenosis or stenosis of the artery to a single kidney who have been treated with ACE inhibitors, increases in blood urea and serum creatinine, usually reversible upon discontinuation of treatment, have been observed. This is especially likely in patients with renal insufficiency. If renovascular hypertension is also present, there is an increased risk of severe hypotension and renal insufficiency. In these patients, treatment should be started under close medical supervision with low doses and careful dose titration. Since treatment with diuretics may be a contributory factor to the above, they should be discontinued and renal function should be monitored during the first weeks of perindopril therapy. Some hypertensive patients with no apparent pre-existing renal vascular disease have developed increases in blood urea and serum creatinine, usually minor and transient, especially when perindopril has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of the diuretic and/or perindopril may be required. Haemodialysis patients: Anaphylactoid reactions have been reported in patients dialysed with high-flux membranes and treated concomitantly with an ACE inhibitor. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent. Renal transplantation: There is no experience regarding the administration of perindopril in patients with a recent kidney transplant. Hypersensitivity/Angioedema: In patients treated with an ACE inhibitor, including perindopril, angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and/or larynx has been rarely reported. This may occur at any time during therapy. In such cases, perindopril should be promptly discontinued and appropriate monitoring should be initiated and sustained until complete resolution of symptoms. In cases where swelling was confined to the face and lips, the condition generally resolved without treatment, although antihistamines have been useful in relieving symptoms. Angioedema associated with laryngeal oedema may be fatal. Where there is involvement of the tongue, glottis or larynx, likely to cause airway obstruction, emergency therapy should be administered promptly. This may include the administration of adrenaline and/or the maintenance of a patent airway. The patient should be kept under close medical supervision until complete and sustained resolution of symptoms. Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema when receiving an ACE inhibitor. Intestinal angioedema has been rarely reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases, there was no prior facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain. Anaphylactoid reactions during low-density lipoprotein (LDL) apheresis: Rarely, patients receiving ACE inhibitors during low-density lipoprotein apheresis with dextran sulphate have experienced life-threatening anaphylactoid reactions. These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each apheresis. Anaphylactoid reactions during desensitisation: Patients receiving ACE inhibitors during desensitisation treatment (such as Hymenoptera venom) have experienced anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld. Hepatic failure: Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not known. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up. Neutropenia/Agranulocytosis/Thrombocytopenia/Anaemia: Neutropenia/agranulocytosis, thrombocytopenia and anaemia have been reported in patients receiving ACE inhibitors. In patients with normal renal function and no other complicating factors, neutropenia occurs rarely. Perindopril should be used with extreme caution in patients with collagen vascular disease, immunosuppressive therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors, especially if there is pre-existing renal impairment. Some of these patients developed serious infections which, in a few cases, did not respond to intensive antibiotic therapy. If perindopril is used in such patients, periodic monitoring of white blood cell counts is advised, and patients should be instructed to report any sign of infection (e.g. sore throat, fever). Ethnicity: ACE inhibitors cause a higher rate of angioedema in Black patients than in non-Black patients. As with other ACE inhibitors, perindopril may be less effective in lowering blood pressure in Black patients than in non-Black patients, possibly because of a higher prevalence of low-renin states in the Black hypertensive population. Cough: Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is non-productive, persistent and resolves after discontinuation of therapy. ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough. Surgery/Anaesthesia: In patients undergoing major surgery or during anaesthesia with agents that produce hypotension, perindopril may block angiotensin II formation secondary to compensatory renin release. Treatment should be discontinued one day before surgery. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion. Hyperkalaemia: Increases in serum potassium have been observed in some patients treated with ACE inhibitors, including perindopril. Risk factors for the development of hyperkalaemia include renal insufficiency, worsening of renal function, age (> 70 years), diabetes mellitus, intercurrent events (in particular dehydration, acute cardiac decompensation, metabolic acidosis), and concomitant use of potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes, or other drugs associated with increases in serum potassium (such as heparin). The use of potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes, particularly in patients with impaired renal function, may lead to a significant increase in serum potassium. Hyperkalaemia can cause serious, sometimes fatal, arrhythmias. If concomitant use of the above-mentioned agents is deemed appropriate, they should be used with caution and with frequent monitoring of serum potassium. Diabetic patients: In diabetic patients treated with oral antidiabetic agents or insulin, glycaemic control should be closely monitored during the first month of treatment with an ACE inhibitor. Lithium: The combination of lithium and perindopril is generally not recommended. Pregnancy: ACE inhibitors should not be initiated during pregnancy. Unless continued ACE inhibitor 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 ACE inhibitors should be stopped immediately and, if appropriate, alternative therapy should be started.