Prestans pills 5mg + 5mg №30

Pills

Composition

1 pill contains: Perindopril arginine 5 mg, which corresponds to the content of perindopril 3395 mg, which corresponds to the content of Amlodipine 10 mg

Excipients: Microcrystalline cellulose, lactose monohydrate, Magnesium stearate, anhydrous colloidal silicon dioxide

Packing

In a polymer bottle with dispenser 30 tablets. In a cardboard box 1 polymer bottle.

Mechanism of action

Prestans pills - a combined antihypertensive and antianginal drug.

Perindopril Perindopril is an inhibitor of the enzyme that converts angiotensin I to angiotensin II (ACE inhibitor). ACE, or kininase II, is exopeptidase, which carries out both the conversion of angiotensin I into a vasoconstrictor substance angiotensin II, and the destruction of bradykinin, which has a vasodilator, to an inactive heptapeptide. Since ACE inactivates bradykinin, ACE suppression is accompanied by an increase in the activity of both the circulating and tissue kallikrein-kinin system, and the prostaglandin system is also activated. Perindopril has a therapeutic effect due to its active metabolite, perindoprilat.Other metabolites have no inhibitory effect on ACE in vitro.
- Hypertension Perindopril is a drug for the treatment of hypertension of any severity. Against the background of its use, a decrease in both systolic and diastolic blood pressure in the prone and standing position is noted. Perindopril reduces OPSS, which leads to a decrease in elevated blood pressure and improvement of peripheral blood flow without changing heart rate. As a rule, perindopril increases renal blood flow, while the glomerular filtration rate does not change. The antihypertensive effect of the drug reaches a maximum after 4-6 hours after a single dose and remains for 24 hours. The anti-hypertensive effect 24 hours after a single dose is about 87-100% of the maximum antihypertensive effect. Reduced blood pressure is achieved quite quickly. The therapeutic effect occurs less than 1 month from the start of therapy and is not accompanied by tachycardia. Discontinuation of treatment does not cause withdrawal syndrome. Perindopril has a vasodilating effect, helps to restore the elasticity of large arteries and the structure of the vascular wall of small arteries, and also reduces left ventricular hypertrophy. Stable coronary artery disease 4 year study (EUROPA).90% of study participants previously had acute myocardial infarction or coronary revascularization. Therapy with perindopril tertbutylamine at a dose of 8 mg / day (equivalent to 10 mg of perindopril arginine) resulted in a significant reduction in the absolute risk of complications by 1.9%, in patients who had previously suffered a myocardial infarction or coronary revascularization, the absolute risk decreased by 2.2% compared with the placebo group.

- Amlodipine Amlodipine is a blocker of slow Calcium channels, a derivative of the dihydropyridine series. Amlodipine inhibits the transmembrane transition of calcium ions into cardiomyocytes and smooth muscle cells of the vascular wall. The antihypertensive effect of amlodipine is due to a direct effect on the smooth muscle cells of the vascular wall. It is established that amlodipine causes expansion of peripheral arterioles, reducing OPSS (afterload), since the heart rate does not change, and the need of myocardium for oxygen decreases. It causes the expansion of coronary arteries and arterioles in both ischemic and intact areas. In patients with Prinzmetal angina, coronary blood flow is improved. In patients with arterial hypertension, taking amlodipine 1 time per day provides a clinically significant reduction in blood pressure while standing and lying down for 24 hours. The antihypertensive effect develops slowly, and therefore the development of acute arterial hypotension is not typical.In patients with angina, taking amlodipine 1 time / day increases exercise tolerance, delaying the onset of an attack of angina and "ischemic" depression of the ST segment, and also reduces the frequency of strokes and Nitroglycerin (short-acting form). Amlodipine does not affect the lipid profile and does not cause changes in the hypolipidemic parameters of blood plasma. The drug can be used in patients with concomitant bronchial asthma, diabetes mellitus and gout. The efficacy and safety of using amlodipine at a dose of 2.5-10 mg / day, an ACE inhibitor lisinopril at a dose of 10-40 mg / day and thiazide diuretic chlortalidone at a dose of 12.5-25 mg / day as a first-line drug was studied in a 5-year study ALLHAT ( involving 33,357 patients aged 55 years and older) in patients with mild or moderate arterial hypertension and at least one of the additional risk factors for coronary complications, such as myocardial infarction or stroke, more than 6 months before inclusion in the study ment, or other evidence of cardiovascular disease of atherosclerotic; diabetes; HDL cholesterol levels of less than 35 mg / dL; left ventricular hypertrophy according to ECG or echocardiography; smoking. The main criterion for evaluating the effectiveness is a combined indicator of the frequency of deaths from IHD and the frequency of nonfatal myocardial infarction.There were no significant differences between the amlodipine and chlorthalidone groups in the main evaluation criteria. The incidence of heart failure in the amlodipine group was significantly higher than in the chlorthalidone group — 10.2% and 7.7%, respectively; the overall incidence of deaths in the amlodipine and chlorthalidone groups did not differ significantly.

- Perindopril and amlodipine Effectiveness with long-term use of amlodipine in combination with perindopril and Atenolol in combination with bendroflumethiazide in patients aged 40 to 79 years with arterial hypertension and at least 3 of the additional risk factors: left ventricular hypertrophy according to an ECG or echocardiography; type 2 diabetes; atherosclerosis of peripheral arteries; previous stroke or transient ischemic attack; male; age 55 years and older; microalbuminuria or proteinuria; smoking; total cholesterol / HDL cholesterol? 6; The early development of coronary artery disease in next of kin was studied in an ASCOT-BPLA study. The main criterion for evaluating the effectiveness is a combined indicator of the frequency of nonfatal myocardial infarction (including painless) and deaths of IHD. The incidence of complications provided for by the main evaluation criteria in the amlodipine / perindopril group was 10% lower than in the atenolol / bendroflumethiazide group, but this difference was not statistically significant. In the amlodipine / perindopril group, there was a significant decrease in the incidence of complications, provided by additional criteria of effectiveness (except for fatal and nonfatal heart failure).

Indications and usage

Arterial hypertension.
- IHD: stable exertional angina in patients requiring perindopril and amlodipine.

Contraindications

Perindopril:
- Angioedema (angioedema) in history (including against the background of taking other ACE inhibitors).
- Hereditary / idiopathic angioedema.
- Age up to 18 years (efficacy and safety have not been established).
- Hypersensitivity to perindopril or other ACE inhibitors.

Amlodipine:
- Severe arterial hypotension (systolic blood pressure less than 90 mm Hg).
- Obstruction of the output tract of the left ventricle (for example, severe aortic stenosis).
- Unstable stenocardia (with the exception of Prinzmetal stenocardia).
- Age up to 18 years (efficacy and safety have not been established).
- Hypersensitivity to amlodipine or other dihydropyridine derivatives.

Prestanz:
- Renal failure (CC less than 60 ml / min).
- Age up to 18 years (efficacy and safety have not been established).
- Hereditary lactose intolerance , lactase deficiency and glucose / galactose malabsorption syndrome.
- Hypersensitivity to excipients that are part of the drug.

Carefully:

Renal artery stenosis (including bilateral).
- The only functioning kidney.
- Liver failure.
- Renal failure.
- Systemic diseases of the connective tissue (includingsystemic lupus erythematosus, scleroderma).
- Therapy with immunosuppressants, Allopurinol , procainamide (risk of developing neutropenia, agranulocytosis).
- Reduced bcc (diuretic intake, salt-free diet, vomiting, diarrhea).
- Atherosclerosis.
- Cerebrovascular diseases.
- Renovascular hypertension.
- Diabetes.
- Chronic heart failure.
- The use of dantrolene, estramustine, potassium-saving diuretics, potassium preparations, potassium-containing food salt substitutes and lithium preparations.
- Hyperkalemia.
- Surgical intervention / general anesthesia.
- Elderly age.
- Conduct hemodialysis using high-flow membranes (for example, AN69®).
- Desensitization therapy.
- Apheresis LDL.
- Aortic stenosis / mitral stenosis / hypertrophic cardiomyopathy.
- Patients of the Negroid race.Use during pregnancy and lactation

The drug is contraindicated for use in pregnancy.

Except for cases when therapy with Prestans is necessary for health reasons, when planning a pregnancy, the drug should be discontinued and other antihypertensive agents prescribed for pregnancy should be prescribed. If pregnancy occurs, you should immediately discontinue taking Prestans and, if necessary, prescribe another therapy.

It is known that the effect of ACE inhibitors on the fetus in the second and third trimesters of pregnancy can lead to impaired development (decreased kidney function, oligohydramnios, delayed ossification of the skull bones) and the development of complications in the newborn (renal failure,arterial hypotension, hyperkalemia). If the patient received ACE inhibitors in the II or III trimester of pregnancy, it is recommended to conduct an ultrasound examination of the fetus to assess the state of the skull and kidney function.

Newborns whose mothers received ACE inhibitors during pregnancy need careful medical supervision because of the risk of arterial hypotension, oliguria and hyperkalemia. The limited data available on taking amlodipine and other slow calcium channel blockers during pregnancy indicate that the drug does not adversely affect the fetus. However, there is a risk of prolonged delivery.

It is not recommended to take Prestans in the period of lactation due to the lack of appropriate clinical experience in the use of perindopril and amlodipine, both in monotherapy and in combination. If you need to take the drug, you should stop breastfeeding.

The drug is administered orally, 1 pill 1 time / day, preferably in the morning before a meal. The dose of the drug Prestants is selected after a previously performed titration of doses of individual components of the drug: perindopril and amlodipine in patients with arterial hypertension and stable angina pectoris.

When therapeutic, the dose of Prestans can be changed, based on individual selection of doses of individual components: 5 mg of perindopril + 5 mg of amlodipine or 5 mg of perindopril + 10 mg of amlodipine or 10 mg of perindopril + 5 mg of amlodipine or 10 mg of perindopril + 10 mg of amlodipine .

Prestans in doses of 10 mg of perindopril + 10 mg of amlodipine is the maximum daily dose of the drug, which is not recommended to exceed.

The elimination of perindoprilat in elderly patients and patients with renal insufficiency is slow. Therefore, in such patients it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma. Can Prestans be prescribed to patients with QA? 60 ml / min. Prestanc is contraindicated in patients with CC <60 ml / min. Such patients are recommended individual selection of doses of perindopril and amlodipine. Changes in the concentration of amlodipine in the blood plasma do not correlate with the severity of renal failure.

Caution should be exercised in the appointment of the drug Prestan in patients with hepatic insufficiency due to the lack of recommendations on the dosing of the drug in these patients.

Prestanza should not be prescribed to children and adolescents under 18 years of age due to the lack of data on the efficacy and safety of perindopril and amlodipine in these groups of patients, both as monotherapy and as combination therapy.

Application for violations of the liver: Caution should be exercised in the appointment of the drug Prestanza patients with liver failure due to the lack of recommendations on the dosing of the drug in these patients.

Application for violations of renal function: Removal of perindoprilat in patients with renal insufficiency is slow. Therefore, in such patients, it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma.Can Prestans be prescribed to patients with QA? 60 ml / min. Prestanc is contraindicated in patients with CC <60 ml / min. Such patients are recommended individual selection of doses of perindopril and amlodipine. Changes in the concentration of amlodipine in the blood plasma do not correlate with the severity of renal failure.

Precautions related to perindopril and amlodipine are applicable to Prestans.

Perindopril:
- Hypersensitivity / angioedema: When taking ACE inhibitors, incl. and perindopril, in rare cases, angioedema of the face, extremities, lips, mucous membranes, tongue, vocal cords and / or larynx may develop. When symptoms appear, the drug should be immediately discontinued, and the patient should be observed until the signs of edema disappear completely. If the edema affects only the face and lips, then its manifestations usually disappear on their own, although antihistamines may be used to treat the symptoms. Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal cords or larynx can lead to airway obstruction. If these symptoms appear, epinephrine (adrenaline) should be injected subcutaneously and / or ensure airway patency. The patient must be under medical supervision until the symptoms disappear completely and permanently.In patients with a history of angioedema, not associated with the use of ACE inhibitors, the risk of its development may be increased when taking drugs in this group. In rare cases, against the background of therapy with ACE inhibitors, angioedema of the intestines develops. At the same time, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases, without prior angioedema of the face and at a normal level of C1-esterase. The diagnosis is established using computed tomography of the abdominal area, ultrasound, or at the time of surgery. Symptoms disappear after discontinuation of ACE inhibitors. Therefore, in patients with abdominal pain, receiving ACE inhibitors, when conducting a differential diagnosis, it is necessary to take into account the possibility of developing angioedema.

- Anaphylactoid reactions during LDL apheresis: In rare cases, life-threatening anaphylactoid reactions may develop in patients receiving ACE inhibitors during LDL apheresis using dextran. To prevent an anaphylactoid reaction, the ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.

- Anaphylactoid reactions during desensitization: There are separate reports on the development of anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy (for example, venom of hymenoptera).In these same patients, the anaphylactoid reaction was avoided by the temporary discontinuation of ACE inhibitors, and when accidentally taking the drug, the anaphylactoid reaction occurred again.

- Neutropenia, agranulocytosis, thrombocytopenia, anemia: Neutropenia / agranulocytosis, thrombocytopenia and anemia may occur in the face of taking ACE inhibitors. In patients with normal renal function and in the absence of other aggravating factors, neutropenia rarely develops. Patients with diffuse diseases of the connective tissue should be treated with particular caution when taking immunosuppressants, allopurinol or procainamide, especially in patients with impaired renal function. Some patients had severe infectious lesions, in some cases, resistant to intensive antibiotic therapy. When prescribing perindopril, it is recommended that such patients periodically monitor the number of leukocytes in the blood. Patients should inform the doctor about any signs of infectious diseases.

- Hypotension: ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic arterial hypotension rarely develops in patients without comorbidities. The risk of an excessive decrease in blood pressure is increased in patients with reduced BCC, which can be observed during diuretic therapy, with a strict salt-free diet, hemodialysis, diarrhea and vomiting, as well as in patients with severe arterial hypertension with high renin activity.In patients with an increased risk of developing symptomatic arterial hypotension, blood pressure, kidney function and serum potassium should be carefully monitored during treatment with Prestans. A similar approach is used in patients with angina pectoris and cerebrovascular diseases in whom severe hypotension can lead to myocardial infarction or impaired cerebral circulation. If arterial hypotension develops, the patient should be placed in a supine position with the legs elevated. If necessary, the BCC should be replenished with IV injection of a 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle to further administration of the drug. After the restoration of BCC and blood pressure treatment can be continued.

- Mitral stenosis, aortic stenosis, hypertrophic cardiomyopathy: Prestanza, like other ACE inhibitors, should be used with caution in patients with obstruction of the left ventricular output (aortic stenosis, hypertrophic cardiomyopathy), as well as in patients with mitral stenosis.

- Impaired renal function: Patients with renal insufficiency (CC less than 60 ml / min) are recommended to select individual doses of perindopril and amlodipine. Such patients require regular monitoring of the content of potassium and creatinine in the blood serum. In patients with bilateral renal artery stenosis or single kidney artery stenosis during therapy with ACE inhibitors, there may be an increase in serum urea and creatinine, usually occurring when therapy is canceled.More often, this effect is observed in patients with renal insufficiency. The additional presence of renovascular hypertension causes an increased risk of developing severe arterial hypotension and renal failure in these patients. In some patients with arterial hypertension without signs of kidney vascular lesions, an increase in serum urea and creatinine may be increased, especially with co-administration of perindopril with a diuretic, usually minor and transient. Most often, this effect is observed in patients with previous kidney dysfunction.

- Hepatic insufficiency: In rare cases, cholestatic jaundice occurs in patients receiving ACE inhibitors. With the progression of this syndrome fulminant necrosis of the liver develops, sometimes with a fatal outcome. The mechanism for the development of this syndrome is unclear. With the appearance of jaundice or a significant increase in the activity of liver enzymes in the background of taking ACE inhibitors, you should stop taking the drug and consult a doctor.

- Ethnic differences: Patients of the Negroid race are more likely to develop angioedema than patients of other races, while taking ACE inhibitors. Perindopril, like other ACE inhibitors, may have a less pronounced hypotensive effect in patients of the Negroid race compared to other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the Negroid race are more likely to have low renin activity.

- Cough A dry cough may occur during therapy with an ACE inhibitor.Coughing persists while taking this group of drugs and disappears after they are canceled. When a patient has a dry cough, you should be aware of the possible iatrogenic nature of this symptom.

- Surgical intervention / general anesthesia: The use of ACE inhibitors in patients undergoing extensive surgery and / or general anesthesia can lead to a pronounced decrease in blood pressure if agents are used for general anesthesia with hypotensive action. This is due to the blocking of the formation of angiotensin II against the background of a compensatory increase in renin activity. If the development of arterial hypotension is associated with the described mechanism, the volume of circulating plasma should be increased. It is recommended to stop taking the drug 24 hours before surgery.

- Hyperkalemia can develop during treatment with ACE inhibitors, incl. and perindopril. Risk factors for hyperkalemia are renal failure, advanced age (older than 70 years), diabetes mellitus, some concomitant conditions (dehydration, acute decompensation of chronic heart failure, metabolic acidosis), simultaneous use of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amine ), as well as preparations of potassium or potassium-containing substitutes for edible salt, as well as the use of other drugs that contribute to an increase in plasma potassium to Peevi (for example, heparin).The use of potassium preparations, potassium-sparing diuretics, potassium-containing salt substitutes can lead to a significant increase in the level of potassium in the blood, especially in patients with reduced kidney function. Hyperkalemia can lead to serious, sometimes fatal heart rhythm disturbances. If simultaneous administration of perindopril and the above preparations is necessary, treatment should be carried out with caution against the background of regular monitoring of the content of potassium in the blood serum.

- Patients with diabetes mellitus: When prescribing the drug to patients with diabetes mellitus who receive hypoglycemic agents for oral use or insulin , during the first month of therapy, it is necessary to carefully monitor the concentration of glucose in the blood.

Amlodipine:
- Hepatic insufficiency: In patients with impaired liver function, T 1/2 of amlodipine is increased. In appointing the drug in such patients, care should be taken to regularly monitor the activity of liver enzymes.

- Chronic heart failure: Caution should be exercised in prescribing amlodipine in patients with chronic heart failure.

- Prestanza: Due to the presence of lactose in the composition of the drug, it should not be prescribed to patients with hereditary lactose intolerance, lactase deficiency and glucose / galactose malabsorption syndrome.
- Impact on the ability to drive vehicles and control mechanisms: In connection with the possible development of weakness and dizziness, Care should be taken when driving and certain activities that require high concentration of attention and fast motor response.

Perindopril:
- Non-recommended drug combinations: ACE inhibitors reduce potassium loss by the kidneys caused by a diuretic. Potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium preparations and potassium-containing substitutes for edible salt can lead to a significant increase in serum potassium. If combined use of an ACE inhibitor and the above remedies is necessary (in the case of confirmed hypokalemia), care should be taken to regularly monitor the potassium content in the blood plasma and ECG parameters. With the simultaneous use of lithium preparations and ACE inhibitors, there can be a reversible increase in the lithium content in the blood plasma and the associated toxic effects. The simultaneous use of perindopril and lithium preparations is not recommended. If necessary, such therapy requires regular monitoring of the lithium content in the blood plasma. Combined use of Prestanza with estramustine is accompanied by an increased risk of developing angioedema.

The combination of drugs that require special attention: The appointment of NSAIDs , including high doses of Acetylsalicylic acid (more than 3 g / day), can lead to a decrease in diuretic, natriuretic and hypotensive effects.With significant fluid loss, as well as in elderly patients, acute renal failure may develop (due to a decrease in glomerular filtration rate). Patients need to compensate for the loss of fluid and at the beginning of treatment carefully monitor kidney function. ACE inhibitors can enhance the hypoglycemic effect of insulin and sulfonylurea derivatives in patients with diabetes. The development of hypoglycemia is observed very rarely (probably due to an increase in glucose tolerance and a decrease in the need for insulin). A combination of medicines that requires attention: At the beginning of therapy with an ACE inhibitor, a significant decrease in blood pressure can be observed, the risk of which can be reduced by canceling the diuretic, administering an increased amount of liquid and / or sodium chloride, and also prescribing perindop yl low dose with further gradual increase it. Sympathomimetics can weaken the hypotensive effect of ACE inhibitors. When prescribing ACE inhibitors, incl. perindopril, nitrate-like reactions (flushing of the skin of the face, nausea, vomiting, arterial hypotension) were observed in patients receiving injectable preparations of gold (sodium aurothiomalate). Simultaneous use with allopurinol, cytostatic and immunosuppressive agents, corticosteroids (with systemic use) and procainamide with ACE inhibitors may be associated with an increased risk of leukopenia.The combined use of ACE inhibitors and agents for general anesthesia can lead to increased hypotensive effect.

Amlodipine:
- Non-recommended combinations of drugs: In laboratory animals, there were cases of ventricular fibrillation with a lethal outcome on the background of the use of Verapamil and iv injection of dantrolene. Extrapolating the available data, the combined use of dantrolene and amlodipine should be avoided.

- A combination of drugs that require special attention: When used simultaneously with cytochrome CYP3A4 inducers (rifampicin, Hypericum perforatum preparations, anticonvulsants, such as Carbamazepine , phenobarbital, phenytoin, fenfenitoin, primidone), it is possible to decrease the plasma concentration of amlodipine, phenitin, phenytoin, phosphenitoin, primidone), it is possible to reduce the plasma concentration of amlodipine, phenytoin, phenentoin, primidone), or decrease in the concentration of amlodipine due to an increase in the concentration of amlodipine due to enhancement of phenyltoin, phenytointoin, primidone. the liver. Caution should be exercised with the simultaneous use of amlodipine and microsomal oxidation inducers and, if necessary, adjust the dose of amlodipine. With simultaneous use with cytochrome CYP3A4 inhibitors (itraconazole, ketoconazole), plasma concentrations of amlodipine can be increased and the risk of side effects may increase. Caution should be exercised with the simultaneous use of amlodipine and itraconazole or Ketoconazole , and if necessary, adjust the dose of amlodipine.

- The combination of medicines that requires attention: When used simultaneously with beta-blockers,used in chronic heart failure (bisoprolol, Carvedilol , metoprolol), increases the risk of hypotension and the deterioration of chronic heart failure in patients with uncontrolled or latent chronic heart failure (increased negative inotropic effect). Also, beta-blockers can reduce excessive reflex cardiac sympathetic activation against the background of concomitant chronic heart failure.

Other drug combinations: There was a safety of amlodipine when used in combination with thiazide diuretics, beta-blockers, ACE inhibitors, nitrates prolonged dosage forms, nitroglycerine (sublingual), Digoxin , Warfarin , Atorvastatin , Sildenafil , antacids (algeldrat, magnesium hydroxide), simethicone, cimetidine, NSAIDs, antibiotics and hypoglycemic agents for oral administration. In addition, special studies have shown the absence of the interaction of the following drugs with amlodipine:
- With the combined use of amlodipine and cimetidine pharmacokinetic parameters of amlodipine did not change.
- With the joint use of amlodipine and sildenafil there is no marked increase in the hypotensive effect of each of the drugs.
- Grapefruit juice: a study involving 20 healthy volunteers showed that taking 240 ml of grapefruit juice with a single dose of amlodipine (10 mg orally) did not significantly affect the pharmacokinetics of amlodipine.

Amlodipine does not affect the pharmacokinetics of the following drugs:

- Atorvastatin: receiving repeated doses of amlodipine 10 mg in combination with atorvastatin at a dose of 80 mg does not lead to a significant change in the equilibrium pharmacokinetic parameters of atorvastatin.
- Digoxin: co-administration of amlodipine and digoxin is not accompanied by a change in the content of digoxin in the blood serum and the renal clearance of digoxin in healthy volunteers.
- Warfarin: in healthy male volunteers who received warfarin, the addition of amlodipine did not significantly affect the change in the amount of prothrombin time due to warfarin.
- Cyclosporine: amlodipine does not have a significant effect on the pharmacokinetic parameters of cyclosporine.

- The combination of drugs that require special attention: When used simultaneously with Baclofen may increase the antihypertensive effect. Blood pressure and kidney function should be monitored, and, if necessary, the dose of amlodipine should be adjusted.

- A combination of drugs that require attention: Antihypertensive drugs (eg, beta-blockers) and vasodilators may enhance the hypotensive effect of perindopril and amlodipine. Caution must be exercised when administered concurrently with nitroglycerin, other nitrates, or other vasodilators, since this may further decrease blood pressure. Corticosteroids (mineral and glucocorticoids),