Charter-d pills 5mg/25mg №28

Mechanism of action

Antihypertensive drug. The drug has an antihypertensive and diuretic effect. Ramipril and hydrochlorothiazide are used alone or together in the treatment of high blood pressure. The hypertensive effects of both components complement each other, which provides almost antihypertensive effect, and the hypokalemic effect of hydrochlorothiazide is reduced by ramipril.

Ramiprilat, an active metabolite of ramipril, inhibits the enzyme dipeptidylcarboxypeptidase I (synonyms: angiotensin-converting enzyme, kininase II). This enzyme catalyzes the conversion of angiotensin I by tissues into the active vasoconstrictor angiotensin II, as well as the breakdown of the active vasodilator bradykinin. Reducing the amount of angiotensin II and suppressing the breakdown of bradykinin leads to vasodilation.

Since angiotensin II also stimulates the release of aldosterone, ramiprilat leads to a decrease in the release of aldosterone.

The use of ramipril leads to a pronounced decrease in peripheral vascular resistance. Significant changes in renal blood flow and glomerular filtration are not usually observed.

Taking ramipril by patients with arterial hypertension lowers blood pressure while standing and lying down without a compensatory increase in heart rate.In most patients, the antihypertensive effect appears 1-2 hours after a single dose. The severity of the effect reaches a maximum after 3-6 h after administration. As a rule, the antihypertensive effect after a single dose is maintained for 24 hours. With prolonged treatment with ramipril, the maximum antihypertensive effect is usually achieved in 2-4 weeks. It has been shown that with long-term therapy, the antihypertensive effect can be maintained for 2 years. Abrupt cessation of ramipril does not lead to a rapid and excessive increase in blood pressure.

Hydrochlorothiazide - thiazide diuretic. Suppresses the reabsorption of sodium ions and chlorine in the distal nephron. Enhanced renal excretion of these ions is accompanied by increased urination (due to osmotic binding of water). The excretion of potassium and Magnesium ions increases, while uric acid is delayed. High doses lead to increased excretion of bicarbonate, and long-term use delays the excretion of Calcium ions. Possible mechanisms of antihypertensive action include: a change in sodium balance, a decrease in extracellular fluid and plasma, a change in renal vascular resistance, or a decrease in reactions to norepinephrine and angiotensin II.

The removal of electrolytes and water begins approximately 2 hours after ingestion, the maximum effect is achieved within 3-6 hours and lasts for 6-12 hours.Antihypertensive effect is achieved within 3-4 days of treatment and lasts for 1 week after completion of the drug. With long-term treatment, a decrease in blood pressure is achieved by using smaller doses than are necessary for the diuretic effect. Decrease in blood pressure is accompanied by a slight increase in glomerular filtration rate, vascular resistance of the renal bed and renin activity in the blood plasma.

Acceptance of single high doses of hydrochlorothiazide leads to a decrease in plasma volume, glomerular filtration rate, renal blood flow, and mean blood pressure. With long-term intake of small doses, the volume of blood plasma remains reduced, while the minute volume and glomerular filtration rate return to the initial level preceding the start of treatment. Mean blood pressure and systemic vascular resistance remain reduced. Thiazide diuretics may interfere with the production of breast milk.

Pharmacokinetics

Suction

After oral administration, ramipril is rapidly absorbed. Judging by the radioactivity detected in the urine after ingestion of labeled ramipril (kidney excretion is only one of several ways), at least 56% of the drug is absorbed. Simultaneous food intake does not affect absorption.

Ramipril is a prodrug, it is metabolized during the "first pass" through the liver, resulting in the formation (due to hydrolysis, mainly in the liver) of the only active metabolite ramiprilat.In addition to becoming the active metabolite ramiprilat, ramipril is conjugated with glucuronic acid and converted into ramipril diketopiperazine ester. Ramiprilat is also conjugated to glucuronic acid and converted into diketopiperazine ramiprilat (acid). Due to the activation / metabolism of ramipril, bioavailability after oral administration is approximately 20%.

C_max ramipril in blood plasma is achieved within 1 h after ingestion. C_max ramiprilat in blood plasma is achieved within 2-4 hours after ingestion of ramipril.

Distribution

Plasma protein binding is approximately 73% and 56% for ramipril and ramiprilat, respectively.

In experimental studies found that ramipril is excreted in breast milk.

Removal

T_1/2 ramipril is approximately 1 hour. The decrease in plasma concentration of ramiprilat has a multiphase character. The phase of initial distribution and elimination is characterized by T_1/2equal to about 3 hours. Then the intermediate phase follows (T_1/2 about 15 h) and the final phase, during which the concentration of ramiprilat in the blood plasma is very low (T_1/2 - 4-5 days). This final phase is due to the slow dissociation of ramiprilat from strong, but saturated complexes with ACE. Despite the duration of the elimination phase, C_ss ramipril is achieved in about 4 days with a daily intake of 2.5 mg or more of ramipril. Effective T_1/2 (parameter related to the choice of dose) is 13-17 hours after taking several doses.

After ingestion of 10 mg of labeled ramipril, about 40% of the radioactivity is released through the intestines and 60% by the kidneys.Within 24 hours after ingestion of 5 mg of ramipril, patients with a catheter that removes the bile that was formed showed equal amounts of ramipril and its metabolites excretion by the kidneys and bile. Approximately 80-90% of metabolites excreted by the kidneys and bile were represented by ramiprilat and preparations for its further metabolism. The share of glucuronide and diketopiperazine derivative ramipril accounted for approximately 10-20%, and unmetabolized ramipril accounted for approximately 2% of the total number of ramipril.

Pharmacokinetics in special clinical situations

The pharmacokinetics of ramipril and ramiprilat in healthy volunteers depend little on age (no differences were found between young people and those aged 65 to 75 years).

In patients with impaired renal function, renal excretion of ramiprilat is reduced. Renal clearance of ramiprilata is proportional to creatinine clearance and correlates with it. Due to this, the concentration of ramiprilat in plasma is higher, and its excretion is carried out for a longer time than in patients with normal renal function.

If ramipril is administered in high doses (10 mg), an abnormal liver function slows down the activation of ramipril (conversion to ramiprilat) and leads to an increase in its concentration in blood plasma. Removal of ramiprilat slows down.

In adult patients with arterial hypertension and chronic heart failure, there is no significant accumulation of ramipril and ramiprilat after oral administration of ramipril (5 mg 1 time / day for 2 weeks).

Suction

Approximately 70% of hydrochlorothiazide is absorbed after oral administration and its bioavailability is also 70%. After oral administration of hydrochlorothiazide at a dose of 12.5 mg C_max is achieved within 1.5-4 hours and is 70 ng / ml; at a dose of 25 mg C_max is achieved within 2-5 hours and amounts to 142 ng / ml; at a dose of 50 mg C_max is achieved within 2-4 hours and is 260 ng / ml.

Distribution

Approximately 40% of hydrochlorothiazide binds to plasma proteins . Hydrochlorothiazide is excreted in small amounts with breast milk.

Removal

Almost completely (more than 95%) is excreted by the kidneys in unchanged form. Within 24 hours after a single ingestion, 50-70% is eliminated. Hydrochlorothiazide is determined in the urine within 60 minutes after ingestion. T_1/2 hydrochlorothiazide is in the range from 5 to 15 h.

Pharmacokinetics in special clinical situations

In violation of the function of the kidneys excretion decreases and T_1/2 increases. Hydrochlorothiazide renal clearance reveals a high correlation with creatinine clearance. In patients with glomerular filtration rate less than 10 ml / min, only 10% of the dose taken is determined in the urine.

According to recent studies, hydrochlorothiazide is partially excreted in the bile. Significant changes in pharmacokinetics in cirrhosis of the liver is not observed.

In patients with heart failure, pharmacokinetics have not been studied.

The simultaneous intake of ramipril and hydrochlorothiazide does not affect the bioavailability of each of the components. A fixed combination of 5 mg ramipril and 25 mg hydrochlorothiazide can be considered in the form of Hartil tablets^®- D is biologically equivalent to the combined reception of 5 mg of ramipril and 25 mg of hydrochlorothiazide.

Indications for use of the drug HARTIL^®-E

- arterial hypertension (to patients for whom combination therapy is indicated).

Dosing regimen

Tablets should be taken 1 time / day. every morning, drinking plenty of water. The drug can be taken regardless of the meal. Tablets are not intended to be divided into parts.

drug chartil^®- It is recommended to appoint only after individual selection of doses of each of the components. The dose can be increased with an interval of at least 3 weeks. The usual starting dose is 2.5 mg ramipril and 12.5 mg hydrochlorothiazide. The usual maintenance dose is 2.5 mg ramipril and 12.5 mg hydrochlorothiazide or 5 mg ramipril and 25 mg hydrochlorothiazide. The recommended maximum daily dose is 5 mg ramipril and 25 mg hydrochlorothiazide.

For elderly patients and patients with QA from 30 to 60 ml / min individual doses of each of the components (ramipril and hydrochlorothiazide) must be carefully selected before switching to the combined drug Hartil^®-D.

Dose of drug chartil^®-D should be as low as possible. The recommended maximum daily dose is 5 mg ramipril and 25 mg hydrochlorothiazide.

Hartil^®-D is contraindicated in patients with severe impaired renal function (CC <30 ml / min / 1.73 m²).

Before moving to Hartil^®-E in patients with mild or moderate hepatic impairment should pick a dose of ramipril.

Hartil drug is not allowed.^®-E patients with severe impaired liver function and / or cholestasis .

Hartil^®-D not recommended children and teenagers (under the age of 18) due to lack of safety and efficacy data for this age group.

Side effect

A number of adverse reactions have been noted while taking ACE inhibitors, ramipril or hydrochlorothiazide.

Severe arterial hypotension was observed at the beginning of the course of treatment and after increasing the dose. This effect is especially characteristic of some risk groups. Symptoms such as dizziness, general weakness, blurred vision, sometimes combined with loss of consciousness (fainting) may occur. Individual cases of tachycardia, palpitations, arrhythmias, angina pectoris, myocardial infarction, severe arterial hypertension and shock, dynamic cerebral circulation disturbance, cerebral hemorrhage and ischemic stroke were observed while taking ACE inhibitors against arterial hypotension.

The frequency of side effects is determined as follows: often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10 000, <1/1000), very rarely (<1/10 000), including in isolated cases.

From the hemopoietic system: rarely - a decrease in the concentration of hemoglobin and hematocrit, leukopenia, thrombocytopenia; very rarely - agranulocytosis, pancytopenia, eosinophilia, hemolytic anemia in patients with deficiency of glucose-6-phosphate dehydrogenase.

From the laboratory indicators: often - hypokalemia, increased levels of uric acid, urea and creatinine in the blood, hyperglycemia, gout; infrequently - hyperkalemia, hyponatremia, hypomagnesemia, hyperhalemia, hypercalcemia; rarely, water and electrolyte balance disorders (especially in patients with kidney disease), hypochloremia, metabolic alkalosis; very rarely - an increase in the level of trigitseridov in the serum, hypercholesterolemia, increased serum amylase, decompensation of diabetes.

From the side of the central nervous system: often - dizziness, fatigue, headache, weakness; infrequently - apathy, nervousness, drowsiness; rarely - a sense of fear, confusion, sleep disturbances, anxiety, disturbances of smell, imbalance, paresthesia.

On the part of the organ of vision: infrequently - conjunctivitis, blepharitis; rarely - transient myopia, blurred vision.

From the organ of hearing: rarely - ringing in the ears.

From the cardiovascular system: pronounced decrease in blood pressure; infrequently - ankles swelling; rarely - fainting, thromboembolic complications; very rarely - angina pectoris, myocardial infarction, arrhythmias, palpitations, tachycardia, dynamic cerebrovascular accident, cerebral hemorrhage, exacerbation of the course of Raynaud’s disease, vasculitis, venous disease, thrombosis, embolism.

On the part of the respiratory system: dry cough, bronchitis; rarely - shortness of breath, sinusitis, rhinitis, pharyngitis, glossitis, bronchospasm, allergic interstitial pneumonia; very rarely, angioedema with a fatal airway obstruction *, pulmonary edema due to increased sensitivity to hydrochlorothiazide.

From the digestive system: nausea, abdominal pain, vomiting, dyspepsia ; infrequently - spasms in the epigastric region, thirst, constipation, diarrhea, loss of appetite; rarely - dry mouth, vomiting, taste disorders, inflammation of the mucous membranes of the mouth and tongue, sialadenitis, glossitis; very rarely - intestinal obstruction, hemorrhagic pancreatitis.

Liver: rarely, increased liver enzymes and / or bilirubin **; very rarely - cholestatic jaundice **, hepatitis, cholecystitis (with cholelithiasis), liver necrosis.

Dermatological reactions: infrequently - photosensitivity, pruritus, urticaria; rarely - flushing of the skin of the face, increased sweating, peripheral edema; very rarely - erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, skin reactions such as psoriatic or pemphigoid, systemic lupus erythematosus, alopecia, exacerbation of psoriasis, onycholysis.

If skin reactions are pronounced, an urgent consultation with a doctor is necessary. It has been reported that taking this drug can lead to a symptom complex represented by at least one of the following components: fever, vasculitis, myalgia, arthralgia / arthritis, a positive reaction to anti-nuclear antibodies, increased ESR, eosinophilia and leukocytosis, rash, photosensitization (other skin manifestations are also possible).

From the musculoskeletal system: rarely - muscle spasm, myalgia, arthralgia, muscle weakness, arthritis; very rarely - paralysis.

From the urinary system: infrequently - proteinuria; rarely - deterioration of kidney function, increased residual nitrogen and serum creatinine, dehydration; very rarely - acute renal failure, nephrotic syndrome, interstitial nephritis, oliguria.

From the reproductive system: infrequently - decreased libido; rarely - impotence.

Allergic reactions: very rarely - Anaphylactic reactions, angioedema *.

* Angioedema often develops in people of the Negroid race. In a small group of patients, the occurrence of angioedema of the face and oropharyngeal region is associated with the use of ACE inhibitors.

** in the case of jaundice or increased activity of the liver enzymes of the patient must be observed.

Contraindications to the use of the drug HARTIL^®-E

- angioedema in history, including associated with prior therapy with ACE inhibitors;

- hereditary / idiopathic angioedema;

- pronounced impaired renal function (CC less than 30 ml / min / 1.73 m²a) anuria;

- severe liver dysfunction and / or cholestasis;

- primary aldosteronism;

- arterial hypotension;

- hemodialysis;

- condition after kidney transplantation (lack of experience in use);

- galactose intolerance, hereditary lactase deficiency or glucose-galactose absorption disorder syndrome (due to the content of lactose in the preparation);

- pregnancy;

- lactation period (breastfeeding);

- age up to 18 years (efficiency and safety have not been established);

- Hypersensitivity to ramipril and other ACE inhibitors, thiazides or sulfonamide derivatives, as well as to any of the drug's excipients.

WITH caution the drug should be used for severe lesions of the coronary and cerebral arteries (risk of reducing blood flow with an excessive decrease in blood pressure), unstable angina, severe ventricular heart rhythm disturbances, chronic heart failure stage IV, decompensated "pulmonary heart", conditions accompanied by a decrease in BCC (in t. including diarrhea, vomiting), systemic diseases of the connective tissue, diabetes mellitus, inhibition of bone marrow hematopoiesis, elderly patients, aortic and mitral stenosis, ipertrophic obstructive cardiomyopathy, bilateral renal artery stenosis or single kidney artery stenosis, gout, hyperkalemia, hyponatremia (including while taking diuretics and a diet with restricted salt intake), hypokalemia, hypercalcemia, ischemic heart disease, renal and / or liver failure. cirrhosis of the liver.

Use of the drug HARTIL^®-D during pregnancy and breastfeeding

It is not recommended to take Hartil^®-D in the first trimester of pregnancy. In the case of a planned or confirmed pregnancy, it is necessary to switch to another therapy as soon as possible. Controlled studies on the use of ACE inhibitors during pregnancy were not conducted.

Hartil^®- D is contraindicated in the II and III trimesters of pregnancy.Long-term administration in the second and third trimesters may cause signs of intoxication in the fetus (depression of renal function, oligohydramnios, delayed ossification of the skull) and the newborn (renal failure of the newborn, hypotension, hyperkalemia).

Prolonged use of hydrochlorothiazide in the third trimester of pregnancy can cause ischemia of the fetus and placenta, the risk of stunted growth. Moreover, in some cases, admission shortly before birth can cause hypoglycemia and thrombocytopenia in newborns. Hydrochlorothiazide may decrease plasma volume and reduce fetoplacental blood flow.

Women taking Hartil^®-D during pregnancy (starting from the II trimester), it is necessary to undergo an ultrasound examination to check the condition of the kidneys and skull in the fetus.

Hartil^®-D is contraindicated during breastfeeding. Ramipril and hydrochlorothiazide are excreted in breast milk. The decrease and cessation of milk excretion is associated with taking thiazides during breastfeeding. Hypersensitivity reactions to sulfonamide drugs, hyperkalemia and nuclear jaundice may occur. Because of the potential for serious side effects in infants, it is necessary to consider stopping breastfeeding.

Application for violations of the liver

At abnormal liver function the reduced or increased effect of the drug Hartil may equally be observed^®therefore, in the early stages of treatment, this category of patients requires careful medical supervision. The maximum daily dose in such cases should not exceed 2.5 mg.

Application for violations of kidney function

correction of dosing regimen required. At moderate renal impairment (CC from 20 to 50 ml / min per 1.73 m² body surfaces) The initial dose is usually 1.25 mg 1 time / day. (1 tablet 1.25 mg / day.). The maximum daily dose should not exceed 5 mg.

special instructions

Symptoms of arterial hypotension

In patients with uncomplicated arterial hypertension, symptoms of arterial hypotension are rarely observed. In patients with arterial hypertension who take ramipril, the likelihood of arterial hypotension increases with a decrease in BCC (for example, as a result of diuretic treatment, restriction of salt intake with food, dialysis, diarrhea or vomiting), as well as in severe forms of renin-dependent arterial hypertension. Symptoms of arterial hypotension were observed in patients with heart failure, regardless of whether it is combined with renal failure. This is most often observed in patients with more severe heart failure, who are forced to take high doses of "loop" diuretics, in whom hyponatremia or functional renal failure is observed.Patients with an increased risk of arterial hypotension require close observation in the initial period of treatment and in the selection of the dose. This also applies to patients with coronary artery disease or vascular disease of the brain, in which a significant drop in blood pressure can lead to myocardial infarction or cerebral circulation.

In the event of arterial hypotension, the patient should be put on his back, legs raised and, if necessary, IV infusion of sodium chloride solution should be made. Transient hypotensive reaction is not a contraindication for subsequent administration of the drug.

In some heart failure patients with normal or low BP, ramipril may cause an additional decrease in systolic BP. This effect can be foreseen, so it is usually not a reason to stop treatment. If hypotension is manifested by symptoms, it may be necessary to reduce the dose or discontinue treatment.

Aortic and mitral stenosis / hypertrophic cardiomyopathy

Like other ACE inhibitors, ramipril should be used with caution in patients with aortic stenosis or difficulty in ejection from the left ventricle (for example, in aortic stenosis or hypertrophic cardiomyopathy). In some cases, the hemodynamic pattern may make it unacceptable to take a fixed combination of ramipril and hydrochlorothiazide.

Primary aldosteronism (Conn's disease)

The use of fixed combinations of ramipril and hydrochlorothiazide is contraindicated, because patients with primary aldosteronism are not sensitive to antihypertensive agents, which are based on the suppression of the renin-angiotensin system.

Renal dysfunction

Patients with heart failure at the beginning of treatment with ACE inhibitors may experience renal impairment. In such situations, described cases of acute renal failure, usually transient.

In some patients with narrowing of both renal arteries or with stenosis of the artery of a single kidney, ACE inhibitors increase the level of urea in the blood and creatinine in the blood serum; usually, these changes disappear after stopping the medication. The likelihood of this is especially high in renal failure. In the presence of renovascular hypertension, there is a high risk of developing severe arterial hypotension and renal failure. In such patients, treatment should begin under close medical supervision with small doses, which should be carefully selected. Since diuretics can contribute to the clinical dynamics described above, they should be discontinued during the first weeks of ramipril treatment, and renal function needs careful monitoring.

In some patients with arterial hypertension without obvious kidney disease, taking ramipril, especially against the background of diuretics, causes an increase in blood urea and creatinine in serum; these changes are usually minor and transient. The probability of their occurrence is higher in patients already suffering from renal dysfunction. In such cases, it may be necessary to reduce the dose and / or stop taking diuretic and / or ramipril.

Condition after kidney transplantation

Due to the lack of experience with the use of ramipril in patients who have recently undergone kidney transplantation, ramipril is not recommended for such patients.

Hypersensitivity / Angioedema

Angioedema of the face, extremities, lips, tongue, vocal cords and / or larynx rarely develops in patients receiving ACE inhibitors, including ramipril During treatment, angioedema can develop at any time. In this case, the reception of ramipril should be immediately discontinued, appropriate treatment should be carried out and patient monitoring should be established; Before letting go of the patient, make sure that all the symptoms of edema are eliminated. Even in cases where the edema is limited only to the tongue and there are no signs of respiratory failure, patients may need long-term follow-up, since treatment with angistamines and GCS may not be sufficient. In rare cases, death of patients due to angioedema of the larynx or tongue has been recorded.

If the edema spreads to the tongue, vocal cords or larynx, it is very likely that the airways overlap, especially in patients who have previously undergone respiratory surgery.In such cases, it is necessary to take emergency treatment measures (administration of epinephrine / adrenaline / and / or maintenance of the airway). The patient must be under close medical supervision until the symptoms disappear completely and permanently.

In patients with a history of angioedema, not associated with taking an ACE inhibitor, the risk of angioedema may be increased in response to taking an ACE inhibitor.

Anaphylactoid reactions in patients on hemodialysis

There are reports of anaphylactoid reactions in patients on hemodialysis using membranes with high hydraulic permeability (for example, AN69) with simultaneous use of ACE inhibitors. In such cases, the use of another type of membrane or antihypertensive drugs of another class should be considered.

Anaphylactoid reactions in the case of LDL apheresis

In rare cases, patients taking an ACE inhibitor, against the background of apheresis of LDL using dextran sulfate, develop life-threatening anaphylactoid reactions. Such reactions can be avoided by temporarily refraining from taking an ACE inhibitor before each apheresis procedure.

Desensitization

Patients taking ACE inhibitors, on the background of desensitization therapy (for example, hymenoptera), develop long-term anaphylactoid reactions. If such patients refrained from taking ACE inhibitors for the period of desensitization, no reactions were observed, however, the accidental administration of ACE provoked an anaphylactoid reaction.

Liver failure

The development of a rare syndrome, which begins with cholestatic jaundice or hepatitis and is converted into transient necrosis of the liver, is sometimes associated with the use of ACE inhibitors and sometimes transforms into transient necrosis of the liver, sometimes with a fatal outcome. The mechanism for the development of this syndrome is not clear. If patients taking ramipril develop jaundice or significantly increase the activity of hepatic enzymes, the drug should be discontinued, leaving the patient under medical supervision until the symptoms disappear.

Neutropenia / Agranulocytosis

It has been reported that patients taking ACE inhibitors may develop neutropenia / agranulocytosis, thrombocytopenia and anemia. With normal kidney function and in the absence of complications, neutropenia rarely develops. Neutropenia and agranulocytosis are reversible and disappear after discontinuation of the ACE inhibitor. Extreme caution should be exercised when prescribing ramipril to patients suffering from connective tissue diseases with vascular manifestations, undergoing treatment with antidepressants, taking Allopurinol or procainamide, as well as a combination of these factors, especially against the background of renal dysfunction. Some of these patients develop severe infections that are not always susceptible to intensive antibiotic therapy. If ramipril is used in the treatment of such patients, it is recommended to periodically check the number of leukocytes, and patients should be warned to report any signs of infection.

Race

ACE inhibitors more often cause the development of angioedema in patients of the Negroid race compared with patients of a different race.

Like other ACE inhibitors, ramipril may be less effective in lowering blood pressure in black patients than in other races, possibly due to a higher incidence of people with low renin levels in a population of black patients suffering from hypertension.

Cough

It has been reported that taking ACE inhibitors may be accompanied by coughing. Characteristically, the cough is dry and persistent, passes after discontinuation of the drug. The fact that a cough is caused by taking an ACE inhibitor should be considered a differential diagnostic sign.

Surgical intervention / general anesthesia

In patients undergoing surgery or general anesthesia with drugs that reduce blood pressure, ramipril can block the increase in the formation of angiotensin II under the influence of compensatory renin release. If it is assumed that arterial hypotension develops by this mechanism, it can be adjusted by increasing the BCC.

Hyperkalemia

In some patients taking ACE inhibitors, including ramipril, an increase in serum potassium is observed. The risk group for the development of hyperkalemia includes patients with renal insufficiency or diabetes mellitus, who take potassium-saving diuretics, or potassium-containing salt substitutes, as well as those who take other drugs that increase the level of serum potassium (eg, heparin).If taking the drugs listed above against the background of treatment with an ACE inhibitor is deemed necessary, regular monitoring of the level of potassium in the blood serum is recommended.

Patients with diabetes

In patients with diabetes mellitus, taking hypoglycemic agents for oral administration or insulin, it is necessary to carefully monitor the level of glucose in the blood during the first month of treatment with an ACE inhibitor.

Lithium

It is usually not recommended to combine the reception of lithium and ramipril.

Renal dysfunction

In patients with kidney disease, thiazides may cause azotemia. Medication in violation of