active ingredients: ramipril, hydrochlorothiazide;
1 tablet contains ramipril 5 mg hydrochlorothiazide 25 mg ramipril 2.5 mg hydrochlorothiazide 12.5 mg
excipients: lactose, microcrystalline cellulose 102, crospovidone, hypromellose, magnesium stearate.
Combined drugs of angiotensin-converting enzyme (ACE). ATC code A05 C09B
Treatment of essential hypertension in patients who are recommended combination therapy (ramipril and hydrochlorothiazide).
Hypersensitivity to ramipril or other ACE inhibitors, hydrochlorothiazide, other thiazide diuretics, sulfonamides or to any of the auxiliary substances that make up the drug.
A history of angioedema (hereditary, idiopathic or previously moved to the background of the use of ACE inhibitors or receptor antagonists of angiotensin II).
Application of methods of extracorporeal treatment, resulting in contact of blood with negatively charged surfaces (see Section "Interaction with other medicinal products and other forms of interaction").
Bilateral renal artery stenosis or unilateral renal artery stenosis in the presence of a single kidney.
Severe renal impairment (creatinine clearance
Clinically significant electrolyte balance disorders, the course of which may worsen during treatment (see section "peculiarities of application").
Severe impairment of liver function, hepatic encephalopathy, cholestasis.
Method of application and doses
For oral administration.
The drug is recommended to take 1 time per day at the same time, preferably in the morning.
The drug can be taken before, during and after meals, as eating does not affect the bioavailability of the drug (see section "Pharmacokinetics"). The tablets should be swallowed whole with water. They can not be chewed or crushed.
Adults. The dose should be adjusted individually, depending on the severity of hypertension and the presence of other associated risk factors. The use of a fixed combination of ramipril and hydrochlorothiazide, as a rule, is recommended only after titration of doses of each of its individual components.
Begin treatment with the lowest possible dose. If necessary, the dose can be gradually increased to reach the target blood pressure. The maximum allowable dose is 10 mg of ramipril and 50 mg of hydrochlorothiazide per day.
Special groups of patients.
Patients who receive diuretics. It is recommended to exercise caution, as patients receiving diuretics, in the beginning of treatment may experience hypotension. Before starting treatment with the drug, you should reduce the dose of diuretics or stop.
Patients with impaired renal function. Due to the presence of hydrochlorothiazide component, the drug is contraindicated in patients with severe renal insufficiency (creatinine clearance
Patients with impaired liver function. In patients with mild and moderate hepatic impairment treatment should only be started under careful control. The maximum daily dose of such cases is 2.5 mg ramipril and 12.5 mg hydrochlorothiazide. The drug is contraindicated in cases of severe liver dysfunction (see section "Contraindications").
Patients of advanced age. The initial dose should be lower, and further titration dose should be carried out more gradually, given the high probability of adverse reactions.
Safety profile of the drug Ramizes Com contains data on the side effects of hypotension and/or decrease in BCC due to increased diuresis. The active substance ramipril can cause a permanent cough, while the active substance hydrochlorothiazide can disrupt the metabolism of glucose, fats and uric acid. Both substances have an irreversible effect on the level of potassium in the blood plasma. Severe adverse reactions include angioedema or anaphylactoid reactions, impaired liver or kidney function, pancreatitis, severe skin reactions and neutropenia/agranulocytosis.
The frequency of side effects is classified as follows: very often (? 1/10); often (?1/100 to<1/10); infrequently (?1/1 000 to<1/100); rarely (?1/10 000 to<1/1 000) very rarely (<1/10 000) unknown (can not be calculated from the available data). In each group, adverse reactions are presented in order to reduce their severity.
System classes organochlorosilane reconnaissance
From the cardiovascular system myocardial Ischemia, including Steno-cardia; arrhythmia tachycardia; sensation of increased heartbeat; peripheral edema arterial hypotension, ortho-static hypotension, syncopa, hot flashes myocardial infarction thrombosis due to a significant reduction of BCC, vascular stasis, hypoperfusion, Raynaud's syndrome, vasculitis
From the blood and lymphatic system
Reducing the keel-bone of white blood cells, decrease if the bones of erythrocytes, decreased hemoglobin, hemali political anemia, reducing the number of platelets Inhibition of bone marrow function neutropenia including agranulocytosis, pancytopenia, eosinophilia; haemoconcentration in the case of fluid retention
From the nervous system
Paraesthesia, tremor, balance disorder, burning sensation, dysgeusia, ageusia
Cerebral ischemia, including ischemic stroke and transient ischemic attack; disorders of psychomotor functions, parosmia
By the organs of vision
Visual impairment, including blurred vision, conjunctivitis
Xanthopsia, reduction of tearing due to the action of hydro - chlorothiazid
Organs of hearing and balance tinnitus
From the respiratory system
Unproductive irritant cough, bronchitis
Sinusitis, shortness of breath, nasal congestion
Bronchospasm, including exacerbation of Bron-Healey asthma allergic Alva OLITE; necardiogenny-tion pulmonary oedema due to hydrochlorothiazide
From the digestive tract
Inflammation in the gastrointestinal-tract, indigestion, abdominal pain, dyspepsia, gastritis, nausea, constipation, gingivitis due to the action of hydro - chlorothiazid
Vomiting, stomatitis, glossitis, diarrhea, dry mouth
Pancreatitis (in rare case s reported lethal naked-Ki in the application of ACE inhibitors), increased levels of enzymes podslon-quark gland, angioedema of the small intestine,
the sialadenitis due to the action of hydrochlorothiazide
From the kidneys and urinary tract
The impairment of renal function, including acute renal failure increase of urine formation; increased levels of blood urea and creatinine Worsening of proteinuria background,
interstitial nephritis as a result of hydrochlorothiazide
From the skin and its derivatives
Angioedema in very exceptional case-s - a violation of the airway due to anyone-ruchnogo edema which can be fatal. Doc; psoriatic dermatitis hyperhidrosis; rash in particular maculopapular; itching alopecia Stevens-Johnson Syndrome, erythema multiforme, exacerbation of disruption-Yu psoriasis, Expo-liative dermatitis, photosensitivity, onycholysis, pempi-goodna or Lihue-OID rash or enanthema, urticaria, systemic lupus erythematosus due to hydrochlorothiazide
From the side of musculoskeletal system and connective tissue
Arthralgia, muscle spasms, muscular weakness, musculoskeletal stiffness, tetanic convulsions due to the action of hydro - chlorothiazid
Metabolic and alimentary disorders
Decompensation of diabetes, reduced glucose tolerance, increased levels of glucose in the blood, increase in uric acid levels, exacerbation Podaga-ry, increase the level of cholesterol and/or triglyce-redev due to the action of hydrochlorothiazidepurchase, loss of appetite, reduced level of potassium Reduction of sodium levels in plasma,
glucosuria, protein metabolis-personally alkalosis, gipohloremia, gipomagniemia, hypercalcemia, dehydration due to the action of hydro - chlorothiazid
Violation of the General state of fatigue, asthenia
Chest pain, pyrexia
From the immune system
Anaphylactic or anaphylactoid reactions to ramipril or anaphylactic reactions to hydrochlorothiazide, raising the level of antinuclear antibodies
From the liver and biliary tract
Cholestatic or cytolytic hepatitis (in very exceptional cases-fatal), increased levels of liver enzymes and/or bilirubin conjugates,
calcium-flax cholecystitis due to the action of hydrochlorothiazide Acute liver failure, cholestatic jaundice, damage to liver cells
From the reproductive system and mammary glands Transient erectile impotence, decreased libido, gynecomastia
Depressed mood, apathy, anxiety, nervousness, time to sleep, ukljucujuci drowsiness, Confusion, impaired attention
Symptoms of overdose of ACE inhibitors is excessive peripheral vasodilatation (with marked hypotension, shock), bradycardia, electrolyte imbalance, renal failure, cardiac arrhythmia, impairment of consciousness including coma, seizures, paresis and paralytic ileus.
Overdose of hydrochlorothiazide can lead to acute urinary retention in patients prone to this (eg patients with prostatic hyperplasia).
It is necessary to carefully monitor the patient's condition.
Treatment is symptomatic and supportive. Therapeutic measures include primary detoxification (gastric lavage, administration of adsorbents), as well as measures aimed at restoring stable hemodynamics, including the introduction of alpha-1 adrenoreceptor agonists or angiotensin II (angiotensinamide). Ramiprilat, an active metabolite of ramipril, is poorly excreted by hemodialysis. The excretion of thiazide diuretics by dialysis is negligible.
If nevertheless dialysis or hemofiltration is supposed to be carried out, the risk of anaphylactoid reactions in the application of high-flow membranes should be taken into account (see section "application Features").
Application during pregnancy and lactation
Pregnancy. ACE inhibitors can cause disease and death of the fetus and newborn, if given to pregnant women. Several cases in different countries have been described in the literature. When diagnosing pregnancy, the use of Ramizes Com should be stopped as soon as possible.
In rare cases (less than 1 in every thousand pregnancies), when there is no alternative to therapy with ACE inhibitor, the pregnant woman should be informed about the possible harm to the fetus. To assess the development of the fetus, the condition and volume of amniotic fluid, it is necessary to conduct serial ultrasound examination of the pregnant woman.
With detection oligohydramnion should stop the drug Rameses K?, unless it is vital for women. Depending on the period of pregnancy may be useful unrecognized test (BNT) and (or) determine the profile of biophysical parameters (PSP). If safety to the fetus, as before, sarigama, you should consider conducting stress tests on contractions (PDP). And patients and clinicians should be aware that oligohydramnios may remain undiagnosed until until irreversible damage of the fetus.
Strict supervision of children with a history of in utero ACE inhibitors is needed to detect arterial hypotension, oliguria and hyperkalemia. If oliguria develops, you should carefully monitor blood pressure and renal perfusion. It may be necessary to exchange transfusion or dialysis as a means to reduce arterial hypotension and (or) restore impaired renal function. However, the existing little experience in carrying out these procedures was not accompanied by a significant clinical result. It remains unknown whether ramipril and ramiprilat can be removed from the body by hemodialysis.
Since the use of Ramizes Com during pregnancy can cause harm to the fetus, which develops, or even cause its death, it should be advised to women of reproductive age, so that they immediately inform the doctor about the occurrence of pregnancy.
Research data. It is unknown whether exposure refers to the first trimester of pregnancy, affect the result of the development of the fetus. The use of ACE inhibitors during second and third trimester of pregnancy is associated with lesions of the fetus and newborn, including hypotension, skull hypoplasia in the newborn, anuria, back or irreversible renal failure and death. Also was and oligohydramnion, which likely evolved due to the deterioration of renal function fetal oligohydramnios in such cases was accompanied by the development of contractures of the limbs of the fetus, craniofacial deformations and hypoplastic lung. Preterm birth and an open arterial duct were also registered, although it is not known that these phenomena are caused by taking an ACE inhibitor.
Lactation. Ramizes Com is contraindicated during breast-feeding. The amount of ramipril and hydrochlorothiazide that gets into breast milk is such that when applying the therapeutic doses of ramipril and hydrochlorothiazide to a child who is breastfed may have their effects. Since there is no adequate data on the use of ramipril during breastfeeding, it is desirable to give preference to other drugs, the use of which during lactation is safer. Hydrochlorothiazide passes into breast milk. The use of hydrochlorothiazide breastfeeding, accompanied by a decrease or even complete cessation of milk production. There may be increased sensitivity to sulfonamide derivatives, hypokalemia and nuclear jaundice. As a combination of active substances may lead to serious adverse effects in children who are breastfed should take a decision on the termination or breastfeeding, or treatment, depending on the importance of this therapy for the mother.
The drug is not recommended for use in children (under 18 years), because there is not enough evidence to support its effectiveness and safety for these patients.
Special groups of patients
Patients in whom there is a high risk of arterial hypotension.
Patients with increased activity of renin-angiotensin -. In patients with increased activity of renin-angiotensin-there is a risk of sudden significant decrease in blood pressure and deterioration of kidney function due to APF depression. This is especially the case when an ACE inhibitor or concomitant diuretic is prescribed for the first time or for the first time increase the dose. Increased activity of renin-angiotensin-requiring medical monitoring, including continuous blood pressure monitoring, can be expected, for example, in patients:
with severe arterial hypertension;
with congestive heart failure,
with haemodynamically significant obstruction of the pathways of inflow and outflow of blood from the left ventricle (such as aortic stenosis or mitral valve)
with unilateral renal artery stenosis in the presence of a second functioning kidney
with severe or latent lack of fluid or electrolytes (including those patients who receive diuretics);
with liver cirrhosis and/or ascites;
undergoing extensive surgery or during anesthesia with the use of drugs, which can cause arterial hypotension.
Before starting treatment, as a rule, it is recommended to correct dehydration, hypovolemia or lack of electrolytes (however, in patients with heart failure, such corrective measures should be carefully weighed in terms of the risk of overloading the volume).
Surgery. If possible, treatment with ACE inhibitors such as ramipril should be stopped 1 day before surgery.
Patients who are at risk of heart or cerebral ischemia in the case of acute arterial hypotension. In the initial phase of treatment, the patient requires careful medical supervision.
Primary hyperaldosteronism. The combination of ramipril + hydrochlorothiazide is not a drug of choice in the treatment of primary hyperaldosteronism. However, if ramipril + hydrochlorothiazide is used in a patient with primary hyperaldosteronism, it is necessary to carefully monitor the level of potassium in the blood plasma.
Patients of advanced age. Cm. the section "Way of administration and doses".
Patients with liver disease. In patients with liver diseases, electrolyte imbalance disorders resulting from treatment with diuretics of hydrochlorothiazides can lead to the development of hepatic encephalopathy.
In case of hepatic encephalopathy treatment should be immediately canceled.
Control of renal function. Kidney function should be monitored before and during treatment and the dose should be adjusted accordingly, especially in the first weeks of treatment. Patients with impaired renal function (see Section "Method of application and dosage") require particularly careful control. There is a risk of deterioration in kidney function, especially in patients with congestive heart failure or after a kidney transplant.
Patients with impaired renal function. In patients with kidney disease, thiazides can provoke the sudden appearance of uremia. In patients with impaired renal function may experience cumulative effects of active substances. If the progression of renal dysfunction becomes apparent, as indicated by the increase in the amount of residual nitrogen, it should be carefully weighed decision to extend treatment. Consider discontinuation of treatment diuretic (see "Contraindications").
Violation of electrolyte balance. As with all patients receiving treatment with diuretics, it is necessary to regularly measure the level of electrolytes in blood plasma at appropriate intervals. Thiazides, including hydrochlorothiazide, can cause water-electrolyte imbalance (hypokalemia, hyponatremia and hypochloremic alkalosis).
Although the use of thiazide diuretics may develop hypokalemia, the simultaneous use of ramipril can reduce hypokalemia caused by diuretics. The risk of hypokalemia is the highest in patients with liver cirrhosis, patients with increased diuresis, patients receiving insufficient amount of electrolytes, and in patients who simultaneously receive treatment with corticosteroids and ACTH (see Section "Interaction with other medicinal products and other forms of interaction "). During the first week of treatment should determine the initial levels of potassium in blood plasma. If you find low levels of potassium must be corrected.
Can occur dileucine hyponatremia. Low levels of sodium at first can be asymptomatic, so it is very important to regularly determine its amount. In elderly patients and patients with cirrhosis of the liver, such tests should be carried out much more often.
It has been demonstrated that thiazides increase the excretion of magnesium in the urine, which can lead to hypomagnesemia.
Hyperkalemia. Some patients who received ACE inhibitors, was observed the occurrence of hyperkalemia. At risk of hyperkalemia are patients with renal insufficiency, the elderly (over 70 years), patients with untreated or improperly controlled diabetes mellitus or those who take potassium salts, potassium-preserving diuretics, as well as other active substances that increase the potassium content in the blood plasma, or patients with conditions such as dehydration, acute cardiac decompensation or metabolic acidosis. If shown simultaneous use of the above drugs, it is recommended to regularly monitor the level of potassium in blood plasma (see section "Interaction with other drugs and other types of interactions").
Hypercalcemia. Hydrochlorothiazide stimulates reabsorption of calcium in the kidneys, which can lead to hypercalcemia. This may distort the results of tests that are carried out to study the function of the parathyroid glands.
Angioneurotic edema. Patients receiving ACE inhibitors such as ramipril, was observed angioedema (see Section "Adverse reactions"). In case of angioedema treatment Remises Com should be discontinued immediately and begin emergency treatment. The patient should be under medical supervision for at least 12-24 hours and can only be discharged after the symptoms have completely disappeared.
Patients receiving ACE inhibitors, such as Rameses Kom, there have been cases of angioedema of the intestine (see Section "Adverse reactions"). These patients complained of abdominal pain (with or without nausea/vomiting).
Anaphylactic reactions during hyposensitization. When using ACE inhibitors, the probability of occurrence and severity of anaphylactic and anaphylactoid reactions to insect venom and other allergens increases. Before carrying out desensitization to temporarily stop taking the drug Rameses Com.
Neutropenia/agranulocytosis. Cases of neutropenia/agranulocytosis have been observed rarely. It was also reported that the function of the bone marrow was inhibited. In order to detect possible leukopenia, it is recommended to monitor the number of leukocytes in the blood. More frequent monitoring is desirable at the beginning of treatment and patients with impaired renal function, patients with concomitant collagenosis (eg systemic lupus erythematosus or scleroderma) and those who simultaneously take other drugs that can cause changes in the blood picture (see. The section on " interaction with other medicinal products and other forms of interactions "and" Adverse reactions ").
Ethnic difference. ACE inhibitors are much more likely to cause angioedema in patients of the Negroid race than in other races. As with other ACE inhibitors, the hypotensive effect of ramipril may be less pronounced in patients of the Negroid race than in representatives of other races. This may be due to the fact that in black patients with arterial hypertension, arterial hypertension with low renin activity is more common.
Athletes. Hydrochlorothiazide can give a positive result when conducting a doping test.
Metabolic and endocrine effects. Treatment with thiazides can lead to impaired glucose tolerance. In some cases, patients with diabetes mellitus may require dose adjustment of insulin and oral antidiabetic agents. In the treatment of thiazide-latent form of diabetes can develop into manifestou.
Therapy with thiazide diuretics may be accompanied by an increase in cholesterol and triglyceride levels. In some patients, the use of thiazide diuretics can provoke the development of hyperuricemia or acute attack of gout.
Cough. With the use of ACE inhibitors have reported on the occurrence of cough. As a rule, this cough is unproductive, long and disappears after the termination of treatment. In the differential diagnosis of cough should be kept in mind when the possibility of cough caused by ACE inhibitors.
Dr. In patients, regardless history of Allergy or bronchial asthma may experience hypersensitivity reactions. It was reported about the possibility of exacerbation or activation of systemic lupus erythematosus.
Faints. If the patient has a fainting condition, he should stop treatment and consult a doctor.
The ability to influence the reaction rate when driving motor transport or operating other mechanisms
Some side effects (e.g. some symptoms of low blood pressure such as dizziness) may impair the ability of the patient to concentrate and the speed of its response. This is especially true when starting treatment or switching to other drugs.
Within a few hours of taking the first dose or further increasing the dose it is not advisable to drive the vehicle or work with other mechanisms.
Interaction with other medicinal products and other forms of interaction
Combinations are contraindicated.
Methods of extracorporeal treatment, resulting in contact of blood with negatively charged surfaces such as dialysis or hemofiltration with certain membranes with high flow rate (for example, membranes made of polyacrylonitrile) and apheresis of low density lipoproteins using dextran sulfate - given the increased risk of severe anaphylactic reactions (see section "Contraindications"). If such treatment is necessary, consideration should be given to the use of another type of dialysis membrane or the use of another class of antihypertensive agents.
Combinations that require extreme caution.
Potassium salts, heparin, potassium-sparing diuretics and other active substances that increase the level of potassium in the blood plasma (including angiotensin II antagonists, trimethoprim, tacrolimus, cyclosporin). There may be hyperkalemia, so you need to carefully monitor the level of potassium in the blood plasma.
Antihypertensive drugs (e.g. diuretics) and other active substances that may reduce blood pressure (e.g. nitrates, tricyclic antidepressants, anesthetics, alcohol, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin). There may be an increased risk of hypotension (see section "dosage and Administration" for diuretics).
Vasopressor sympathomimetics and other active substances (such as epinephrine) that may reduce the antihypertensive effect of ramipril. It is recommended to monitor blood pressure regularly.
Allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics and other substances that can cause changes in the blood picture. Increased likelihood of haematological reactions (see Section "Peculiarities of use").
Lithium salt. Since ACE inhibitors can reduce lithium excretion, this can lead to an increase in the toxicity of lithium. It is necessary to regularly monitor the level of lithium in the blood plasma. With the simultaneous use of thiazide diuretics may increase the risk of lithium toxicity and increase the already increased risk of lithium toxicity caused by the use of ACE inhibitors. Therefore, it is not recommended to use a combination of ramipril/hydrochlorothiazide and lithium at the same time.
Antidiabetic agents, including insulin. May experience a hypoglycemic reaction. Hydrochlorothiazide can weaken the action of antidiabetic drugs. Therefore, at the beginning of the simultaneous use of these drugs, it is necessary to carefully monitor the level of glucose in the blood.
Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid. Expected reduction of antihypertensive effect of the drug Rameses Com. Moreover, the simultaneous use of ACE inhibitors and NSAIDs may be accompanied by an increased risk of renal impairment and increased levels of potassium in the blood.
Oral anticoagulants . While the use of hydrochlorothiazide anticoagulant effect may be weakened.
Corticosteroids, ACTH, amphotericin b, carbenoxolone, eating large amounts of liquorice, laxatives (long-term use) and the simultaneous appointment of other drugs or active substances that reduce the amount of potassium in the blood plasma. Increased risk of hypokalemia.
Digitalis preparations, active ingredients that can increase the duration of THE Qt interval, antiarrhythmic agents. In the presence of electrolyte imbalance disorders (eg hypokalemia, hypomagnesemia) Proarrhythmic effects may increase, and antiarrhythmic effects - weaken.
Methyldopa. Possible hemodialysis.
Cholesterol or other ion exchange resins, which are taken orally. Violation of the absorption of hydrochlorothiazide. Sulfonamide diuretics should be taken at least 1: 00 before or after 4-6 hours after use of these drugs.
Curated muscle relaxants. May increase and increase duration of action of muscle relaxants.
Calcium salts and drugs that increase the level of calcium in the blood plasma. While the use of hydrochlorothiazide can be expected to increase the concentration of calcium in the blood plasma, so it is necessary to carefully monitor the level of calcium in the plasma.
Carbamazepine. There is a risk of hyponatremia due to increased hydrochlorothiazide effect.
Contrast agents containing iodine. In the case of dehydration caused by the use of diuretics, including hydrochlorothiazide, there is an increased risk of developing acute renal failure, especially in the case when administered a significant dose of contrast material containing iodine.
Penicillin. Excretion of hydrochlorothiazide occurs in the distal tubules of nephron, which is why the excretion of penicillin decreases.
Quinine. Hydrochlorothiazide reduces the excretion of quinine.
Mechanism of action.
Ramipril. Ramiprilat, an active metabolite of prodrug-ramipril, is an enzyme inhibitor of dipeptidylcarboxypeptidase I (also known as ACE, or kinase II). In plasma and tissue this enzyme catalyses the conversion of angiotensin I to angiotensin II, the active vasoconstrictor substance, and the breakdown of bradykinin, which is active vasodilators. The decrease in the formation of angiotensin II and the inhibition of bradykinin breakdown lead to vasodilatation.
Since angiotensin II also stimulates the release of aldosterone, ramiprilat causes a decrease in the secretion of aldosterone. In patients Negroid races (Afro-Caribbean origin) with arterial hypertension (population, which is usually characterized by a low level of renin activity) reaction to monotherapy with ACE inhibitors on average was less pronounced than in patients who are representatives of other races.
Hydrochlorothiazide. Hydrochlorothiazide is a thiazide diuretic. As for thiazide diuretics, the mechanism of their antihypertensive action has not yet been fully clarified. They suppress reabsorption of sodium and chlorine ions in the distal tubules. Enhanced renal excretion of these ions is accompanied by increased urination (due to osmotic binding of water). The excretion of potassium and magnesium also increases, whereas the excretion of uric acid decreases. The possible mechanisms of hypotensive action of hydrochlorothiazide are to change the sodium balance, reduce the volume of extracellular fluid and plasma, change the resistance of renal vessels or reduce reactions to norepinephrine and angiotensin II.
Ramipril. The use of ramipril leads to a significant reduction in peripheral arterial resistance. As a rule, significant changes in the renal plasma flow or glomerular filtration rate do not occur. In patients with hypertension, the administration of ramipril leads to a decrease in blood pressure in both horizontal and vertical positions, is not accompanied by a compensatory increase in heart rate.
In most patients, the antihypertensive effect occurs approximately 1-2 hours after oral administration of a single dose of the drug. The maximum effect after oral administration of a single dose usually occurs after 3-6 hours. The antihypertensive effect after a single dose is usually maintained for 24 hours.
With long - term treatment with ramipril maximum antihypertensive effect develops after 3-4 weeks. It is proved that during long-term therapy, the antihypertensive effect persists for 2 years.
Sudden discontinuation of ramipril does not cause a rapid and excessive increase in blood pressure (ricochet phenomenon).
Hydrochlorothiazide. As for hydrochlorothiazide, the beginning of the diuretic effect occurs approximately after 2:00 and lasts for 6-12 hours, and the maximum effect is achieved after 4:00.
Antihypertensive effect occurs after 3-4 days of treatment and can last for 1 week after treatment.
The antihypertensive effect is accompanied by a slight increase in glomerular filtration rate, renal vascular resistance and plasma renin activity.
Simultaneous use of ramipril and hydrochlorothiazide. The use of this combination leads to a more significant reduction