Instructions for Perindopril tablets 4 mg No. 30
Composition
active ingredient: perindopril;
1 tablet contains 4 mg of perindopril tert-butylamine, which corresponds to 3.338 mg or 6.676 mg of perindopril;
Excipients: lactose monohydrate; microcrystalline cellulose; colloidal hydrophobic silicon dioxide; magnesium stearate.
Dosage form
Pills.
Basic physical and chemical properties: tablets of white or almost white color, flat-cylindrical shape, with a bevel and a line.
Pharmacotherapeutic group
Angiotensin-converting enzyme (ACE) inhibitors, monocomponent. Perindopril. ATC code C09A A04.
Pharmacological properties
Pharmacodynamics
Perindopril is an inhibitor of the enzyme that converts angiotensin I to angiotensin II (ACE). The converting enzyme, or kinase, is an exopeptidase that enables the conversion of angiotensin I to the vasoconstrictor angiotensin II and also causes the breakdown of the vasodilator bradykinin to an inactive heptapeptide. Inhibition of ACE leads to a decrease in the concentration of angiotensin II in the blood plasma, which increases plasma renin activity (by a feedback mechanism) and reduces aldosterone secretion. Since ACE inactivates bradykinin, ACE inhibition also leads to an increase in the activity of the circulating and local kallikrein-kinin system (and, thus, also leads to the activation of the prostaglandin system). This mechanism of action causes the reduction in blood pressure by ACE inhibitors and is partly responsible for the appearance of some of the side effects (e.g. cough).
Perindopril tert-butylamine acts through its active metabolite, perindoprilat. Other metabolites do not demonstrate activity in inhibiting ACE under experimental conditions.
Arterial hypertension
Perindopril effectively lowers blood pressure in all degrees of arterial hypertension - mild, moderate and severe; a decrease in systolic and diastolic blood pressure is observed in the patient both in the supine and standing positions.
Perindopril reduces peripheral vascular resistance, which leads to a decrease in blood pressure. As a result, peripheral blood flow increases without affecting heart rate.
Renal blood flow usually increases, while glomerular filtration rate (GFR) usually does not change.
The maximum antihypertensive effect develops 4–6 hours after a single dose and persists for at least 24 hours: the T/P ratio (minimum efficacy/maximum efficacy during the day) of perindopril is 87–100%.
Blood pressure decreases rapidly. In patients in whom the drug has been effective, normalization of blood pressure occurs within a month and is maintained without tachyphylaxis.
There is no withdrawal effect when perindopril is discontinued.
Perindopril reduces left ventricular hypertrophy
In clinical trials, perindopril has been shown to have vasodilating properties. It improves the elasticity of large arteries and reduces the ratio of wall thickness to lumen for small arteries.
Combination therapy with a thiazide diuretic shows an additive synergistic effect. The combination of an ACE inhibitor and a thiazide diuretic also reduces the risk of diuretic-induced hypokalemia.
Heart failure
Perindopril tert-butylamine facilitates the work of the heart by reducing pre- and afterload on the heart.
Studies involving patients with heart failure have demonstrated:
reduction of right and left ventricular filling pressure; reduction of systemic peripheral resistance; increase in cardiac index and improvement of cardiac output; increase in regional blood flow in myocardial muscles.
In comparative studies, the initial administration of 2 mg perindopril to patients with mild to moderate heart failure was not associated with any significant reduction in blood pressure compared with placebo.
Pharmacokinetics
Absorption
After oral administration, perindopril is rapidly absorbed, with peak plasma concentrations occurring within 1 hour. The plasma half-life of perindopril is 1 hour.
Perindopril is a prodrug. 27% of the total amount of perindopril taken is determined in the blood as the active metabolite - perindoprilat. In addition to the active metabolite, perindoprilat, the drug forms 5 metabolites that are inactive. The maximum concentration of perindoprilat in the blood plasma is reached 3-4 hours after taking the drug.
Food intake reduces the conversion of perindopril to perindoprilat, thus reducing its bioavailability, therefore the daily dose of perindopril tert-butylamine is recommended to be taken once in the morning before meals.
A linear relationship is observed between the dose of perindopril and its concentration in blood plasma.
Distribution
The volume of distribution of unbound perindoprilat is approximately 0.2 l/kg. The binding of perindoprilat to plasma proteins is 20%, mainly to ACE, but this indicator is dose-dependent.
Perindoprilat is excreted in the urine. The terminal half-life of the unbound fraction is approximately 17 hours. Steady-state plasma concentrations are reached within 4 days of initiation of treatment.
Special patient groups
The elimination of perindoprilat is slowed in elderly patients and in patients with heart or renal failure. It is recommended to select the dose for patients with renal failure, taking into account the degree of insufficiency (creatinine clearance).
Dialysis clearance of perindoprilat is 70 ml/min.
The kinetics of perindopril are altered in patients with cirrhosis: the hepatic clearance of perindopril is halved. However, the amount of perindoprilat formed is not reduced. Therefore, no dose adjustment is required in such patients.
Indication
Arterial hypertension; heart failure; prevention of recurrent stroke in patients with cerebrovascular disease; prevention of cardiovascular complications in patients with documented stable ischemic heart disease.
Long-term treatment reduces the risk of myocardial infarction and heart failure (according to the results of the EUROPA study).
Contraindication
Hypersensitivity to the active substance or to any of the excipients of the medicinal product, or to any other ACE inhibitor; history of angioedema after taking an ACE inhibitor; idiopathic or hereditary angioedema;
simultaneous administration with medicinal products containing the active substance aliskiren to patients with diabetes mellitus or renal insufficiency (GFR < 60 ml/min/1.73 m2) (see sections “Interaction with other medicinal products and other types of interactions” and “Special precautions for use”);
pregnancy or planning to become pregnant (see section "Use during pregnancy or breastfeeding")
concomitant use with sacubitril/valsartan (see sections “Interaction with other medicinal products and other types of interactions” and “Special precautions for use”);
extracorporeal treatments that result in blood coming into contact with negatively charged surfaces (see section “Interaction with other medicinal products and other types of interactions”);
significant bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney (see section "Special warnings and precautions for use").
Interaction with other medicinal products and other types of interactions
Clinical trial data suggest that dual blockade of the renin-angiotensin-aldosterone system (RAAS) through the concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher incidence of adverse reactions, such as hypotension, hyperkalemia and decreased renal function (including acute renal failure), compared with the use of a single drug affecting the RAAS.
Drugs that cause hyperkalemia
Some medicinal products or therapeutic classes of medicinal products may cause hyperkalaemia, such as: aliskiren, potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory drugs (NSAIDs), heparins, immunosuppressants such as ciclosporin or tacrolimus, trimethoprim. Concomitant use of these medicinal products increases the risk of hyperkalaemia.
Contraindicated combinations
The concomitant use of perindopril with aliskiren is contraindicated (see section "Contraindications") in patients with diabetes mellitus or patients with impaired renal function due to the increased risk of hyperkalemia, renal dysfunction, cardiovascular morbidity and mortality and is not recommended for all other patient groups (see section "Special warnings and precautions for use").
In the case of extracorporeal treatments that result in contact of blood with negatively charged surfaces, such as high-flux membranes for dialysis or hemofiltration (e.g. polyacrylic membranes) and for low-density lipoprotein apheresis with dextran sulfate, the risk of severe anaphylactoid reactions is increased (see section 4.3). If such treatment is necessary, the use of a different type of dialysis membrane or the use of a different class of antihypertensive drugs should be considered.
Sacubitril/Valsartan
Concomitant use of perindopril with sacubitril/valsartan is contraindicated, as concomitant use of ACE inhibitors and sacubitril/valsartan increases the risk of angioedema. Sacubitril/valsartan should not be initiated earlier than 36 hours after the last dose of perindopril. Perindopril therapy should not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan (see sections 4.3 and 4.4).
Concomitant use of ACE inhibitors and angiotensin receptor blockers. Published data suggest that in patients with established atherosclerosis, heart failure, or diabetes with target organ damage, concomitant use of ACE inhibitors and angiotensin receptor blockers was associated with an increased incidence of hypotension, syncope, hyperkalemia, and renal dysfunction (including acute renal failure) compared with monotherapy with drugs that affect the RAAS. Dual blockade (i.e., the combination of an ACE inhibitor with angiotensin II receptor antagonists) may be used in individual cases and with careful monitoring of renal function, potassium levels, and blood pressure.
Estramustine: Increased risk of adverse reactions such as angioedema.
Co-trimoxazole (trimethoprim/sulfamethoxazole)
Patients receiving concomitant co-trimoxazole (trimethoprim/sulfamethoxazole) are at increased risk of hyperkalemia (see section 4.4).
Potassium-sparing diuretics (e.g. triamterene, amiloride), potassium salts. Hyperkalemia (including fatal) may occur, especially in patients with renal insufficiency (additive hyperkalemic effect). These drugs are not recommended for simultaneous use with perindopril (see section "Special instructions"). However, if the simultaneous administration of these substances is necessary, they should be used with caution and the level of potassium in the blood plasma should be carefully monitored.
Lithium. When using ACE inhibitors with lithium preparations, a reversible increase in the concentration of lithium in the blood plasma is possible and, accordingly, an increase in the risk of its toxic effects. It is not recommended to use perindopril with lithium preparations. In case of proven need for such an appointment, it is imperative to carefully monitor the level of lithium in the blood plasma (see section "Special instructions").
Concomitant use requiring special attention
Antidiabetic agents (insulin, oral hypoglycemic agents). Epidemiological studies suggest that the concomitant use of ACE inhibitors and hypoglycemic agents (insulin, oral hypoglycemic agents) may lead to an increased hypoglycemic effect with a risk of hypoglycemia. This phenomenon is most likely to occur in the first weeks of combined treatment and in patients with renal insufficiency.
Baclofen. The antihypertensive effect is enhanced. If necessary, blood pressure should be monitored and the dose of antihypertensive drugs should be adapted.
Diuretics. In patients taking diuretics, and especially in those with impaired water and electrolyte metabolism, an excessive decrease in blood pressure may occur after starting treatment with an ACE inhibitor. The likelihood of developing a hypotensive effect is reduced by discontinuing the diuretic, increasing circulating blood volume, or salt intake before starting therapy with perindopril tert-butylamine. Treatment should be initiated at low doses and increased gradually.
In hypertension, when a previously prescribed diuretic may have caused water/electrolyte depletion, it should be discontinued before starting treatment with an ACE inhibitor (in such cases, the diuretic may be resumed over time) or an ACE inhibitor should be prescribed at a low dose with a gradual increase in dose.
In congestive heart failure on diuretic therapy, ACE inhibitor therapy should be initiated at the lowest dose, possibly after reducing the diuretic dose.
In any case, it is necessary to monitor kidney function (creatinine level) during the first weeks of treatment with an ACE inhibitor.
Potassium-sparing diuretics (eplerenone, spironolactone). In the case of simultaneous use of eplerenone or spironolactone in doses from 12.5 mg to 50 mg per day with low doses of an ACE inhibitor, it should be borne in mind that:
If the recommendations for the appointment of this combination are not followed, there is a risk of hyperkalemia (possibly fatal) during the treatment of patients with NYHA class II–IV heart failure and an ejection fraction < 40%, who were previously treated with an ACE inhibitor and a loop diuretic; before prescribing such a combination, it is necessary to ensure the absence of hyperkalemia and renal failure; it is recommended to carefully monitor potassium and creatinine weekly during the first month of treatment and monthly thereafter.
NSAIDs, including acetylsalicylic acid ≥ 3 g/day. A weakening of the antihypertensive effect is possible during the simultaneous use of ACE inhibitors with NSAIDs, such as: acetylsalicylic acid in anti-inflammatory doses, COX-2 inhibitors, non-selective NSAIDs. The simultaneous use of ACE inhibitors and NSAIDs may lead to an increased risk of renal dysfunction, including the likelihood of developing acute renal failure, an increase in plasma potassium levels, especially in patients with a history of impaired renal function. Such a combination should be prescribed with caution, especially in elderly patients. Patients should be provided with an adequate amount of fluid and monitor renal function immediately after the appointment of combination therapy and periodically thereafter.
ACE inhibitors (e.g. perindopril) are known to cause angioedema. This risk is increased when used concomitantly with racecadotril (a medicine used to treat acute diarrhoea).
mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus)
Patients receiving concomitant mTOR inhibitors are at increased risk of developing angioedema (see section 4.4).
Simultaneous use, which requires some attention.
Antihypertensives and vasodilators. Concomitant use of antihypertensives may increase the hypotensive effect of perindopril tert-butylamine. Concomitant use with nitroglycerin and other nitrates, or with other vasodilators may contribute to an additional decrease in blood pressure.
Gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin). Patients receiving a combination of a gliptin and an ACE inhibitor may be at increased risk of angioedema due to the gliptin's inhibition of dipeptidyl peptidase-IV (DPP-IV).
Concomitant use of some anesthetics, tricyclic antidepressants or antipsychotics with ACE inhibitors may lead to a further decrease in blood pressure (see section "Special warnings and precautions for use").
Sympathomimetics may weaken the antihypertensive effect of ACE inhibitors.
Gold preparations: A nitrate-like reaction (symptoms: facial flushing, nausea, vomiting, and hypotension) has been reported rarely in patients receiving concomitant ACE inhibitors, including perindopril, and injectable gold preparations (sodium aurothiomalate).
Application features
Stable ischemic heart disease
If an episode of unstable angina (of any severity) occurs during the first month of treatment with perindopril, the risk/benefit ratio should be carefully weighed before deciding whether to continue therapy.
Arterial hypotension
ACE inhibitors may cause a decrease in blood pressure. Symptomatic hypotension is less common in patients with uncomplicated hypertension and is more likely in patients who are volume-depleted, taking diuretics, on a salt-restricted diet, undergoing dialysis, experiencing diarrhoea or vomiting, or in patients with severe renin-dependent hypertension (see sections 4.5 and 4.8). Symptomatic hypotension is more likely in patients with symptomatic heart failure, with or without concomitant renal insufficiency. Symptomatic hypotension is most likely to occur in patients with more severe heart failure, who are receiving high doses of loop diuretics, have a history of hyponatremia or functional renal failure. To reduce the risk of symptomatic hypotension, patients should be closely monitored during initiation of therapy and during dose titration (see sections 4.2 and 4.8). The same precautions apply to patients with ischemic heart disease or cerebrovascular disease, in whom an excessive decrease in blood pressure may result in myocardial infarction or stroke.
If hypotension occurs, the patient should be placed in the supine position and, if necessary, intravenously administered 0.9% (9 mg/ml) sodium chloride solution. Transient hypotension is not a contraindication to continued use of the drug, which can usually be used without any problems after volume repletion and blood pressure elevation.
In some patients with congestive heart failure with normal or low blood pressure, perindopril tert-butylamine may cause an additional decrease in systemic blood pressure. This effect is expected and usually does not require discontinuation of the drug. If hypotension becomes symptomatic, a dose reduction or discontinuation of the drug may be necessary.
Aortic and mitral valve stenosis/hypertrophic cardiomyopathy
As with other ACE inhibitors, perindopril tert-butylamine should be administered with caution to patients with mitral valve stenosis or left ventricular outflow obstruction (aortic stenosis or hypertrophic cardiomyopathy).
Kidney failure
In case of renal insufficiency (creatinine clearance < 60 ml/min), the initial dose of perindopril should be adjusted according to the patient's creatinine clearance (see section 4.2) and then according to the patient's response to treatment. Monitoring of potassium and creatinine is standard practice in such patients (see section 4.8).
In some patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, increases in blood urea and serum creatinine have been observed when using ACE inhibitors, which usually return to normal after discontinuation of treatment. This is especially true in patients with renal insufficiency. In the presence of concomitant renovascular hypertension, the risk of severe arterial hypotension and renal insufficiency increases. Treatment of such patients should be initiated under close medical supervision, with low doses and with careful dose titration.
Given the above precautions, treatment with diuretics may cause arterial hypotension, so they should be discontinued and renal function monitored during the first weeks of treatment with perindopril tert-butylamine.
In some patients with arterial hypertension, in whom renovascular disease was not detected before the start of treatment, the use of perindopril, especially against the background of diuretics, causes an increase in blood urea and serum creatinine, which is usually insignificant and transient. The likelihood of such adverse reactions is higher in patients with impaired renal function. In such cases, it may be necessary to reduce the dose and/or discontinue the diuretic and/or perindopril tert-butylamine.
Patients on hemodialysis
Anaphylactic-type reactions have been reported in patients receiving hemodialysis with high-flux polyacrylic membranes and concomitant ACE inhibitors. Therefore, a decision should be made to use a different type of dialysis membrane or a different class of antihypertensive drug in these patients.
Patients after kidney transplantation
There is no experience with the administration of perindopril tert-butylamine to patients after a recent kidney transplant.
Renovascular hypertension
Patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are at increased risk of hypotension and renal failure when treated with ACE inhibitors (see section 4.3). Diuretics may be a beneficial factor. The decline in renal function may be accompanied by only minor changes in serum creatinine levels, even in patients with unilateral renal artery stenosis.
Hypersensitivity/angioedema
Rare cases of angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and/or larynx have been reported in patients receiving ACE inhibitors, including perindopril tert-butylamine (see section 4.8). This may occur at any time during treatment. In such cases, the drug should be discontinued immediately and the patient should be monitored until symptoms resolve. In those rare cases where the swelling is limited to the face and lips, the patient usually improves without treatment. Antihistamines may be useful in reducing symptoms.
Angioedema associated with laryngeal oedema can be fatal. In cases where the oedema involves the tongue, glottis or larynx causing airway obstruction, urgent emergency treatment is required, including possible administration of adrenaline and/or airway management. Patients should be closely monitored until symptoms resolve and the condition stabilizes.
Patients with a history of angioedema unrelated to ACE inhibitor therapy are at increased risk of developing angioedema while receiving an ACE inhibitor (see section 4.3).
Rare cases of intestinal angioedema have been 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 previous history of facial angioedema and C-1 esterase levels were normal. The diagnosis of intestinal angioedema was made by abdominal computed tomography or ultrasound, or at the time of surgery. Symptoms of angioedema resolved after discontinuation of the ACE inhibitor. Intestinal angioedema should be considered in the differential diagnosis of patients with abdominal pain receiving ACE inhibitors.
Patients receiving concomitant mTOR inhibitors may be at increased risk of angioedema (including airway or tongue oedema, with or without respiratory compromise) (see section 4.5). Concomitant use of perindopril with sacubitril/valsartan is contraindicated due to the increased risk of angioedema (see section 4.3). Sacubitril/valsartan should not be initiated earlier than 36 hours after the last dose of perindopril. If treatment with sacubitril/valsartan is discontinued, perindopril should not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan (see sections 4.3 and 4.5). Concomitant use of other neutral endopeptidase (NEP) inhibitors, such as racecadotril, and ACE inhibitors may also lead to an increased risk of angioedema (see section 4.5). Therefore, a careful benefit-risk assessment should be performed before initiating treatment with NEP inhibitors, such as racecadotril, in patients taking perindopril.
Anaphylactoid reactions during low-density lipoprotein (LDL) plasmapheresis
Rarely, life-threatening anaphylactoid reactions have occurred in patients receiving ACE inhibitors during LDL plasmapheresis with dextran sulfate. Anaphylactoid reactions can be avoided by temporarily stopping ACE inhibitor therapy before each plasmapheresis.
Anaphylactoid reactions during desensitization therapy
Anaphylactoid reactions may occur in patients taking ACE inhibitors during desensitization treatment with bee venom-containing drugs. These reactions can be avoided by temporarily discontinuing the ACE inhibitor, but the reactions may recur if provocation tests are performed carelessly.
Liver failure
Cases of a syndrome that begins with cholestatic jaundice and progresses to transient hepatic necrosis and sometimes fatal outcome have been reported rarely in patients receiving ACE inhibitors. The mechanism of this syndrome is unknown. Patients who develop jaundice or significant elevations of liver enzymes while taking an ACE inhibitor should discontinue the drug, undergo appropriate medical evaluation, and receive appropriate treatment (see section 4.8).
Neutropenia/agranulocytosis/thrombocytopenia/anemia
Neutropenia/agranulocytosis, thrombocytopenia and anaemia have been reported in patients taking ACE inhibitors. Neutropenia is rare in patients with normal renal function and in the absence of other risk factors. Perindopril should be administered with great caution to patients with collagen vascular disease, immunosuppressants, allopurinol or procainamide or a combination of these aggravating factors, especially in the presence of pre-existing renal impairment. Serious infections may occasionally develop in these patients, which in rare cases may not respond to intensive antibiotic therapy. If perindopril is prescribed to such patients, periodic monitoring of the white blood cell count is recommended; patients should also be advised to report any signs of infection (sore throat, fever) to their doctor.
Racial affiliation
ACE inhibitors cause angioedema more often in black patients than in non-blacks. As with other ACE inhibitors, perindopril is less effective in lowering blood pressure in black patients than in non-blacks, possibly because of the lower renin status of African-American hypertensive patients.
Cough
Cough has been reported with ACE inhibitor therapy.
The cough is typically nonproductive, persistent, and resolves after discontinuation of the drug. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.
Surgery/anesthesia
The drug may block the secondary formation of angiotensin II in response to compensatory renin release in patients undergoing surgery or during anesthesia with drugs that cause hypotension. The drug should be discontinued one day before surgery. In the event of arterial hypotension, if it is believed that it is caused by the specified mechanism, the patient's condition can be normalized by increasing the volume of circulating blood.
Increases in serum potassium have been observed in some patients taking ACE inhibitors, including perindopril. Risk factors for hyperkalemia include renal failure, impaired renal function, age (over 70 years), diabetes mellitus, intercurrent conditions such as dehydration, acute cardiac decompensation, metabolic acidosis, and concomitant use of potassium-sparing diuretics (e.g. spironolactone, eplerenone, triamterene or amiloride), potassium supplements or potassium-containing salt substitutes, or other medicinal products that may increase serum potassium (e.g. heparin). The use of potassium supplements, potassium-sparing diuretics or potassium-containing salt substitutes, especially in patients with impaired renal function, may lead to significant increases in serum potassium. Hyperkalemia may cause serious, sometimes fatal, arrhythmias. If concomitant use of perindopril and any of these substances is considered appropriate, they should be used with caution and with frequent monitoring of serum potassium (see section 4.5).
Patients with diabetes
Diabetic patients taking oral hypoglycemic agents or insulin should have their blood glucose levels closely monitored during the first month of treatment with ACE inhibitors (see section 4.5).
Lithium
The concomitant use of lithium and perindopril is generally not recommended (see section "Interaction with other medicinal products and other types of interactions").
Potassium-sparing medicines, potassium-containing food supplements, or potassium-containing salt substitutes.
The concomitant use of perindopril with potassium-sparing medicinal products or potassium-containing food supplements is not recommended (see section "Interaction with other medicinal products and other types of interactions").
Dual blockade of RAAS
There have been reports of hypotension, syncope, stroke, hyperkalemia and renal dysfunction (including acute renal failure), especially with concomitant use of medicinal products that affect the RAAS. The combination of an ACE inhibitor with an angiotensin II receptor blocker (ARB) or with aliskiren, given the dual blockade of the RAAS, is not recommended.
In patients with diabetes mellitus or renal insufficiency (GFR <60 ml/min/1.73 m2), concomitant use with aliskiren is contraindicated (see sections “Contraindications” and “Interaction with other medicinal products and other types of interactions”).
Primary aldosteronism
Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs that act by inhibiting the renin-angiotensin system. Therefore, the use of this drug in such patients is not recommended.
Pregnancy
ACE inhibitors should not be initiated during pregnancy. If continued antihypertensive therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. If pregnancy is diagnosed during treatment, ACE inhibitors should be stopped immediately and, if appropriate, alternative therapy with an approved pregnancy product should be started (see sections 4.3 and 4.8).
Important information about excipients
This medicinal product contains 59.0/118.0 mg of lactose monohydrate. It should not be administered to patients with rare hereditary problems of galactose intolerance, glucose-galactose malabsorption syndrome, Lapp lactase deficiency. Use with caution in patients with diabetes mellitus.
Ability to influence reaction speed when driving vehicles or other mechanisms
Perindopril tert-butylamine has no direct influence on the ability to drive or use machines. However, some patients may experience individual reactions associated with a decrease in blood pressure, especially at the beginning of treatment or when used simultaneously with other antihypertensive drugs. As a result, the ability to drive or use machines may be impaired.
Use during pregnancy or breastfeeding
Pregnancy. The use of ACE inhibitors is contraindicated during pregnancy (see section "Contraindications"). The drug should not be used in pregnant women or women planning to become pregnant. If pregnancy is confirmed during treatment, the drug should be discontinued immediately and replaced with another drug approved for use in pregnancy.
