Composition, form of production and packaging
Tablets are white or almost white in color, flat, oval, with a notch on one side and marked with "12.5".
1 tab.
ramipril 2.5 mg
hydrochlorothiazide 12.5 mg
[PRING] sodium carbonate, lactose monohydrate, croscarmellose sodium, corn pregelatinized starch, sodium stearyl fumarate.
7 pcs. - blisters (2) - packs of cardboard.
7 pcs. - blisters (4) - packs of cardboard.
10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
Tablets white or almost white, flat, oval, with a notch on one side and marking "25".
1 tab.
ramipril 5 mg
hydrochlorothiazide 25 mg
[PRING] sodium carbonate, lactose monohydrate, croscarmellose sodium, corn pregelatinized starch, sodium stearyl fumarate.
7 pcs. - blisters (2) - packs of cardboard.
7 pcs. - blisters (4) - packs of cardboard.
10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
Tablets white or almost white, flat, oval, with a notch on one side and marking "25".
1 tab.
ramipril 5 mg
hydrochlorothiazide 25 mg
[PRING] sodium carbonate, lactose monohydrate, croscarmellose sodium, corn pregelatinized starch, sodium stearyl fumarate.
7 pcs. - blisters (2) - packs of cardboard.
7 pcs. - blisters (4) - packs of cardboard.
10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2008.
PHARMACHOLOGIC EFFECT
Ramipril
The ACE inhibitor, prevents the conversion of angiotensin I into angiotensin II without a compensatory increase in heart rate. Reduces the production of aldosterone, OPSS, pressure in the pulmonary capillaries, resistance in the pulmonary vessels, does not change the rate of glomerular filtration, enhances coronary blood flow.With prolonged use of the drug, myocardial hypertrophy decreases in patients with arterial hypertension, the incidence of arrhythmias decreases with myocardial reperfusion; improves circulation of the ischemic myocardium. Cardioprotective effect is due to the effect on the synthesis of prostaglandins, induction of the formation of nitric oxide in endotheliocytes. The drug reduces the aggregation of platelets. The onset of an antihypertensive effect is 1.5 hours after ingestion, the maximum effect is 5-9 hours, the duration of the action is 24 hours. The drug has no withdrawal syndrome.
Hydrochlorothiazide
A thiazide diuretic whose diuretic effect is associated with a disruption of the reabsorption of sodium, chlorine, potassium, magnesium, water in the distal nephron;delays the excretion of calcium ions, uric acid. Has antihypertensive properties; the hypotensive effect develops due to a decrease in bcc, changes in the reactivity of the vascular wall, a decrease in pressor influence and an increase in the depressor effect on the ganglion. Virtually no effect on normal blood pressure. Diuretic effect occurs in 1-2 hours, reaches a maximum after 4 hours and lasts for 6-12 hours. Antihypertensive effect occurs in 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect.
Ramipril and hydrochlorothiazide have an additive effect. Ramipril reduces the loss of potassium ions caused by the intake of hydrochlorothiazide.
PHARMACOKINETICS
The pharmacokinetics of ramipril and hydrochlorothiazide with simultaneous administration does not differ from that in their separate administration.
The absorption of ramipril averages 50-60%. Food intake does not affect the degree of absorption, but reduces its speed, T max - 2-4 hours.
After oral intake of hydrochlorothiazide is 60-80%. C max hydrochlorothiazide in the blood is achieved 1-5 hours after ingestion. The connection of ramipril with plasma proteins is 73%, ramiprilata - 56%. Binding to plasma proteins hydrochlorothiazide - 64%. T 1/2 for ramipril - 5.1 hours; in the phase of distribution and elimination, a decrease in the concentration of ramiprilata in the serum takes place with T 1/2 - 4-5 days. T 1/2 increases with renal insufficiency. V d of ramipril - 90 liters, ramiprilata - 500 liters. Metabolism of ramipril occurs mainly in the liver with the formation of an active metabolite of ramiprilata, which inhibits ACE in 6 times more active than ramipril and an inactive metabolite of diketopiperazine, which are then glucuronized. The drug is excreted mainly in the form of metabolites, kidneys - 60%, intestines - 40%. Hydrochlorothiazide is not metabolized and is rapidly excreted through the kidneys. T 1/2 is 5 to 15 hours.
INDICATIONS
- Arterial hypertension (patients who are shown combined therapy).
DOSING MODE
Inside. the dose is selected individually. Usual Adult Dose - 1 tab. Ramazid H 2.5 mg / 12.5 mg per day. If necessary, can be increased to 1 tab. Ramazid H 5 mg / 25 mg.
If the kidney function is mild or moderate (QC more than 30 ml / min, serum creatinine about 3 mg / dl or 265 Ојmol / l), the usual dose of the drug is recommended. When creatinine clearance is less than 30 ml / min the drug is not recommended.
SIDE EFFECT
Ramipril
From the cardiovascular system: a decrease in blood pressure, orthostatic hypotension, orthostatic collapse, tachycardia, rarely - arrhythmia, angina pectoris, myocardial infarction. On the part of the genitourinary system: the development or strengthening of symptoms of kidney failure, proteinuria, a decrease in the volume of urine, a decrease in libido.
From the side of the central nervous system: cerebral ischemia, stroke, dizziness, headache, weakness, drowsiness, paresthesia, nervous excitability, anxiety, tremor, muscle spasm, mood disorders, when used in high doses - insomnia, anxiety, depression, confusion, fainting .
From the sense organs: vestibular disorders, taste disorders (eg, metallic taste), smell, hearing and vision, tinnitus.
On the part of the digestive system: nausea, vomiting, diarrhea or constipation, epigastric pain, intestinal obstruction, pancreatitis, hepatitis, cholestatic jaundice, liver dysfunction with hepatic insufficiency, dry mouth, thirst, decreased appetite, stomatitis, glossitis.
On the part of the respiratory system: "dry" cough, bronchospasm, dyspnea, rhinorrhea, rhinitis, sinusitis, bronchitis.
Allergic reactions: skin rash, itching, hives, conjunctivitis, photosensitivity; angioneurotic edema of the face, extremities, lips, tongue, throat and / or larynx, exfoliative dermatitis, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome), pemphigus, serositis, onycholysis, vasculitis, myositis, myalgia, arthralgia, arthritis, eosinophilia.
Other: convulsions, alopecia, hyperthermia, increased sweating.
Laboratory indices: hyperkreatininemia, increased urea nitrogen levels, increased activity of "hepatic" transaminases, hyperbilirubinemia, hyperkalemia, hyponatremia, the appearance of antinuclear antibodies.
Influence on the fetus: impaired fetal function, decreased fetal and newborn infants, impaired renal function, hyperkalemia, skull bones hypoplasia, oligohydramnios, limb contracture, skull bones deformation, lung hypoplasia.
Hydrochlorothiazide
From the side of water-electrolyte and acid-base balance: hypokalemia and hypochloremic alkalosis can develop (dry mouth, thirst, heart rhythm, mood and psyche, convulsions or muscle pain, nausea, vomiting, weakness, hypochloremic alkalosis possible development of hepatic encephalopathy or hepatic coma), hyponatremia (confusion, convulsions, apathy, slowing down the process of thinking, fatigue, irritability), hypomagnesemia (arrhythmias).
On the part of the hematopoiesis system: agranulocytosis, thrombocytopenia, hemolytic and aplastic anemia, leukocytopenia.
From the cardiovascular system: arrhythmia, orthostatic hypotension, tachycardia.
On the part of the digestive system: cholecystitis, pancreatitis, jaundice, diarrhea, sialadenitis, constipation, anorexia, epigastric pain.
From the metabolism: hyperglycemia, glucosuria, hyperuricemia, exacerbation of gout.
Allergic reactions: skin rash, purpura, necrotizing vasculitis, Stevens-Johnson syndrome, respiratory distress (pneumonitis, noncardiogenic pulmonary edema), photosensitization; anaphylactic reactions (up to the life threatening anaphylactic shock).
CONTRAINDICATIONS
Ramipril
- Hypersensitivity to ramipril and any other ingredient of the drug or other ACE inhibitors;
- angioedema in history, including those associated with previous therapy with ACE inhibitors;
- hemodynamically significant bilateral stenosis of the renal arteries;
- stenosis of the artery of a single kidney;
- condition after kidney transplantation;
- hemodialysis;
- renal failure (CC less than 20 ml / min.);
- hemodynamically significant aortic or mitral stenosis (risk of excessive blood pressure lowering with subsequent renal dysfunction);
- hypertrophic obstructive cardiomyopathy;
- primary hyperaldosteronism;
- pregnancy and lactation;
- age under 18 years (efficiency and safety not established).
With caution: severe lesions of the coronary and cerebral arteries (risk of blood flow decrease with excessive decrease of blood pressure), unstable angina, severe ventricular arrhythmias, chronic heart failure of stage IV, decompensated pulmonary heart, renal and / or hepatic insufficiency, hyperkalemia, hyponatremia including diuretics and diets with a restriction of salt intake), conditions accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting), systemic diseases of soy diabetes mellitus, oppression of bone marrow circulation, elderly age.
Hydrochlorothiazide
- hypersensitivity to the drug;
- gout;
- diabetes mellitus (severe forms);
- chronic renal failure (creatinine clearance less than 20-30 ml / min, anuria);
- refractory hypokalemia;
- hypercalcemia;
- hyponatremia;
- pregnancy (1 trimester);
lactation period.
With caution: hypokalemia, hyponatremia, hypercalcemia, ischemic heart disease, liver cirrhosis, elderly age.
PREGNANCY AND LACTATION
The drug is contraindicated during pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
The drug is contraindicated in renal failure (CC less than 20 ml / min.).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Use with caution in liver failure.
APPLICATION FOR CHILDREN
The effectiveness and safety of the use of the drug to 18 years are not established.
APPLICATION IN ELDERLY PATIENTS
With caution apply the drug in the elderly.
SPECIAL INSTRUCTIONS
Ramipril
At the beginning of treatment, it is necessary to evaluate the kidney function. Care should be taken to monitor renal function during treatment with ramipril, especially in patients with impaired renal function, renal vessel damage (eg, clinically insignificant stenosis of the renal arteries or hemodynamically significant stenosis of the artery of a single kidney); heart failure.
The risk of hypersensitivity and allergic-like (anaphylactoid) reactions is increased in patients who simultaneously take ACE inhibitors and undergo hemodialysis procedures using dialysis membranes AN69. Similar reactions have been detected in the apheresis of low density lipoproteins with dextran sulfate, so the use of this method should be avoided when treating ACE inhibitors.
During treatment with ramipril in patients with impaired renal function, especially with simultaneous treatment with diuretics, the level of urea and creatinine in the serum can increase. In this case, treatment should be continued with smaller doses of ramipril or discontinue the drug. In patients with impaired renal function, the risk of hyperkalemia increases.
In patients with impaired hepatic function, the metabolism of ramipril and the formation of an active metabolite may be slowed by a decrease in the activity of "liver" enzymes. In this regard, the treatment of such patients should be started only under strict medical supervision.
Caution should be exercised when prescribing ramipril to patients on a low-salt or salt-free diet (increased risk of developing hypotension). In patients with a reduced volume of circulating blood (as a result of diuretic therapy), during dialysis, with diarrhea and vomiting, symptomatic hypotension may develop.
Transient arterial hypotension is not a contraindication for continuing treatment after stabilizing blood pressure. In the case of repeated occurrence of severe arterial hypotension, the dose should be reduced or the drug should be withdrawn.
In patients undergoing extensive surgery or receiving other arterial hypotension agents during general anesthesia, ramipril may cause blockade of the formation of angiotensin II due to compensatory release of renin. If the doctor connects the development of arterial hypotension with the mechanism mentioned above, arterial hypotension can be corrected by an increase in the volume of blood plasma.
In rare cases, during treatment with ACE inhibitors, agranulocytosis, erythrocytopenia, thrombocytopenia, hemoglobinemia or bone marrow suppression are observed. At the beginning and during treatment it is necessary to control the number of white blood cells to detect possible neutropenia / agranulocytosis. More frequent monitoring is recommended in patients with renal insufficiency, with connective tissue diseases (eg, systemic lupus erythematosus or scleroderma) and in patients taking concomitant medications that affect hematopoiesis. Counting blood cells should also be performed if there are clinical signs of neutropenia / agranulocytosis and increased bleeding.
in patients with arterial hypertension in the treatment of ramipril, there is rarely an increase in the serum potassium level. The risk of hyperkalemia increases with chronic heart failure, simultaneous treatment with potassium-sparing diuretics (spironolactone, amiloride, triamterene) and the administration of potassium preparations.
With the use of ACE inhibitors during desensitizing therapy, anaphylactoid reactions (eg, arterial hypotension, dyspnoea, vomiting, skin rash) can occur to aspen or bee venom, which can be life-threatening. Hypersensitivity reactions can occur with insect bites (eg, bees or wasps). If it is necessary to conduct desensitizing treatment with bee or aspenic poison, ACE inhibitors should be discontinued and continued treatment with suitable drugs from other groups.
During the treatment with Ramazid H, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions (possibly dizziness, especially after the initial dose of an ACE inhibitor in patients taking diuretic medicines).Patients are advised to refrain from driving and working with the mechanisms until the response to treatment is clear.
Hydrochlorothiazide
To prevent deficiency of K + and Mg 2+, prescribe potassium-sparing diuretics, salts of K + and Mg 2+ . Regular monitoring of the potassium, glucose, uric acid, lipid and creatinine levels is necessary.
OVERDOSE
Symptoms : marked decrease in blood pressure, bradycardia, shock, disturbance of water-electrolyte balance, acute renal failure, stupor, dry mouth, weakness, drowsiness.
Treatment : the patient is given a horizontal position with raised legs, in mild cases of overdose - gastric lavage, the introduction of adsorbents and sodium sulfate (it is advisable to conduct activities within the first 30 minutes after taking the drug). With a decrease in blood pressure - IV injection of catecholamines, angiotensin II;with bradycardia - the use of pacemaker. The drug is not excreted during hemodialysis.
DRUG INTERACTION
Ramipril
Strengthens the inhibitory effect of ethanol on the central nervous system. Taking salt with food can reduce the hypotensive effect of ramipril.
With the simultaneous use of ramipril and other agents that reduce blood pressure (eg diuretics, nitrates, tricyclic antidepressants, anesthetics) leads to an increase in the hypotensive effect of ramipril.
The simultaneous administration of ramipril and potassium or potassium-sparing diuretics may cause hyperkalemia.
Vasopressornye sympathomimetics (adrenaline, norepinephrine) can reduce the hypotensive effect of ramipril. In this regard, with simultaneous treatment should carefully monitor blood pressure.
Simultaneous administration of ramipril and allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics increases the likelihood of changes in the peripheral blood picture.
Simultaneous administration of ramipril and lithium preparations leads to a decrease in lithium excretion, it is necessary to control the concentration of lithium in the blood serum - the risk of toxic effects.
ACE inhibitors can enhance the effect of hypoglycemic agents (eg, insulin or sulfonylurea derivatives), which in some cases can cause hypoglycemia. In this regard, the level of sugar in the blood should be carefully monitored, especially at the beginning of the joint application.
The simultaneous use of ramipril and non-steroidal anti-inflammatory drugs (eg, acetylsalicylic acid and indomethacin) can reduce the hypotensive effect of ramipril.In addition, simultaneous use can cause hyperkalemia and increase the risk of impaired renal function.
The simultaneous use of heparin and ramipril can cause hyperkalemia.
Anaphylactic and anaphylactoid reactions to the venom of stinging insects (and possibly other allergens) are more pronounced during treatment with ACE inhibitors.
Hydrochlorothiazide
With simultaneous use of digitalis glycosides with thiazide diuretics increases the probability of toxic effects glycosides (including hyperexcitability ventricles) due to the potential development of hypokalemia and hypomagnesemia.
Medicaments intensively binding proteins (indirect anticoagulants, clofibrate, NSAIDs), increase the diuretic effect of hydrochlorothiazide.
The hypotensive effect of hydrochlorothiazide reinforce vasodilators, beta-blockers, barbiturates, phenothiazines, tricyclic antidepressants, ethanol.Hydrochlorothiazide enhances the neurotoxicity salicylates, reduces the effect of oral hypoglycemic drugs, norepinephrine, epinephrine and protivopodagricakih preparations enhances cardiotoxic and neurotoxic effects of drugs lithium peripheral muscle relaxant effect, reduces the excretion of quinidine. At the same time taking methyldopa may develop hemolysis. Cholestyramine reduces the absorption of hydrochlorothiazide.
Hydrochlorothiazide reduces the effect of oral contraceptives.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
At temperatures above 25 В° C. Keep out of the reach of children!
Shelf life 3 years. The drug should not be used after the expiration date printed on the package.
