Coveram Special Precautions

Perindopril: Hypotension: ACE inhibitors may cause a fall in blood pressure. Symptomatic hypotension is seen rarely in uncomplicated hypertensive patients and is more likely to occur in patients who have been volume-depleted eg, by diuretic therapy, dietary salt restriction, dialysis, diarrhea or vomiting, or who have severe renin-dependent hypertension (see Interactions and Adverse Reactions). In patients at high risk of symptomatic hypotension, blood pressure, renal function and serum potassium should be monitored closely during treatment with Coveram.
Similar considerations apply to patients with ischemic 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 sodium chloride 9 mg/mL (0.9%) solution. A transient hypotensive response is not a contraindication to further doses, which can be given usually without difficulty once the blood pressure has increased after volume expansion.
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 of <60 mL/min) an individual dose titration with the monocomponents is recommended (see Dosage & Administration).
Routine monitoring of potassium and creatinine are part of normal medical practice for patients with renal impairment (see Adverse Reactions).
In some patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, who have been treated with ACE inhibitors, increases in blood urea and serum creatinine, usually reversible upon discontinuation of therapy, have been seen. 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. 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.
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 understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receiver appropriate medical follow-up (see Adverse Reactions).
Race: 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 people than in non-Blacks, possibly because of a higher prevalence of low-renin states in Black hypertensive population.
Cough: Cough has been reported with 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/Anesthesia: In patients undergoing major surgery or during anesthesia with agents that produce hypotension, Coveram may block angiotensin II formation secondary to compensatory renin release. The treatment should be discontinued one day prior to the surgery. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.
Hyperkalemia: Elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including perindopril. Risk factors for the development of hyperkalemia include those with 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 (eg, spironolactone, eplerenone, triamterene or amiloride), potassium supplements or potassium-containing salt substitutes; or those patients taking other drugs associated with increase in serum potassium (eg, heparin). The use of potassium supplements, potassium-sparing diuretics or potassium-containing substitutes particularly in patients with impaired renal function may lead to a significant increase in serum potassium. Hyperkalemia can cause serious, sometimes fatal arrhythmias. If concomitant use of perindopril and any of the above mentioned agents is deemed appropriate, they should be used with caution and with frequent monitoring of serum potassium (see Interactions).
Diabetic Patients: In diabetic patients treated with oral antidiabetic agents or insulin, glycemic control should be closely monitored during the first month of treatment with an ACE inhibitor (see Interactions).
Amlodipine: Patients with Impaired Hepatic Function: As with all calcium antagonists, amlodipine's half-life is prolonged in patients with impaired liver function. The drug should be administered with caution in these patients and with a close monitoring of the hepatic enzymes.
Patients with Heart Failure: Patients with cardiac failure should be treated with caution. In a long-term, placebo controlled study (PRAISE-2) of amlodipine in patients with NYHA III and IV heart failure of nonischemic etiology, amlodipine was associated with increased reports of pulmonary edema despite no significant difference in the incidence of worsening heart failure as compared to placebo (see Pharmacology under Actions).
Coveram: Excipients: Due to the presence of lactose as an excipient, patients with rare hereditary problems of galactose intolerance, glucose-galactose malabsorption, or the Lapp-lactase deficiency should not take Coveram tablet.
Interactions: The concomitant use of Coveram with lithium, potassium-sparing diuretics or potassium supplements or dantrolene is not recommended (see Interactions).
Effects on the Ability to Drive or Operate Machinery: No studies on the effects of Coveram on the ability to drive and use machines have been performed. When driving vehicles or operating machines it should be taken into account that occasionally dizziness or weariness may occur.
Use in pregnancy: Coveram (Perindopril/Amlodipine): Coveram should not be initiated during pregnancy. Unless continued, Coveram 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 Coveram should be stopped immediately, and, if appropriate, alternative therapy should be started (see Contraindications). Perindopril: The use of perindopril is not recommended during the 1st trimester of pregnancy and contraindicated during the 2nd and 3rd trimesters of pregnancy (see Contraindications).
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the 1st trimester of pregnancy has not been conclusive; however a small increase in the risk cannot be excluded. Unless continued, ACE inhibitors therapy is considered essential, patients planning pregnancy should change to an alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with Coveram should be stopped immediately, and if appropriate, alternative therapy should be started.
ACE inhibitors therapy exposure during the 2nd and 3rd trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalemia) (see Toxicology under Actions).
Should exposure to ACE inhibitors have occurred from the 2nd trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension (see Contraindications, Precautions and Cautions for Usage).
Amlodipine: Data on a limited number of exposed pregnancies indicate no adverse effects of amlodipine and other calcium-receptor antagonists on the health of the fetus. However, there may be a risk of prolonged delivery. Animal studies have not shown teratogenic effect (see Toxicology under Actions).
Consequently, amlodipine is not recommended during the 1st trimester of pregnancy. When a pregnancy is planned or confirmed, the switch to an alternative treatment should be initiated as soon as possible.
Coveram is contraindicated during the 2nd and 3rd trimesters of pregnancy.
Should exposure to Coveram occurred from the 2nd trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants exposed in utero to ACE inhibitors should be closely observed for hypotension, oliguria and hyperkalemia.
Use in lactation: There is no clinical experience of the use of perindopril or amlodipine, alone or in combination, during lactation. Therefore, the use of Coveram is not recommended in women who are breast-feeding.