Hydrochlorothiazide + Ramipril
Ramipril 2.5 mg; Hydrochlorothiazide 12.5 mg; Excipients: sodium carbonate, lactose monohydrate, croscarmellose sodium, pregelatinized corn starch, sodium fumarate.
Ramipril; an ACE inhibitor, prevents the conversion of angiotensin I to angiotensin II without a compensatory increase in heart rate. Reduces the production of aldosterone, round neck, pressure in the pulmonary capillaries, resistance in the pulmonary vessels, does not change the glomerular filtration rate, increases coronary blood flow. With prolonged use of the drug, myocardial hypertrophy is reduced in patients with arterial hypertension, the frequency of arrhythmias during myocardial reperfusion decreases; improves blood circulation ischemic myocardium. Cardioprotective effect due to the effect on the synthesis of prostaglandins, the induction of the formation of nitric oxide in endothelial cells. The drug reduces platelet aggregation. The onset of hypotensive action is 1.5 hours after ingestion, the maximum effect is 5–9 hours, the duration is 24 hours. The drug does not have withdrawal. potassium, magnesium, water in the distal nephron; delays the excretion of calcium ions, uric acid. It has antihypertensive properties; the hypotensive effect develops by reducing the bcc, changing the reactivity of the vascular wall, reducing the pressure of the influence and increasing the depressant effect on the ganglia. Virtually no effect on normal blood pressure. The diuretic effect occurs after 1-2 hours, reaches a maximum after 4 hours and lasts 6-12 hours. The antihypertensive effect occurs after 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 taking hydrochlorothiazide.
The pharmacokinetics of ramipril and hydrochlorothiazide, when administered concurrently, does not differ from that when administered separately;; ramipril absorption averages 50-60%.Meal does not affect the degree of absorption, but reduces its speed, Tmax - 2-4 hours; After oral administration, the absorption of hydrochlorothiazide is 60-80%. Cmax hydrochlorothiazide in the blood is achieved within 1-5 hours after ingestion. The connection of ramipril with plasma proteins is 73%, ramiprilat - 56%. Binding to plasma proteins hydrochlorothiazide - 64%. T1 / 2 for ramipril - 5.1 h; in the distribution and elimination phase, a decrease in the concentration of ramiprilat in the serum occurs from T1 / 2 - 4-5 days. T1 / 2 increases with renal failure. Vd ramipril - 90 l, ramiprilata - 500 l. Ramipril metabolism occurs mainly in the liver with the formation of the active metabolite of ramiprilat, which inhibits ACE 6 times more active than ramipril and the inactive diketopiperazine metabolite, which are then glucuronicized. The drug is excreted mainly in the form of metabolites, by the kidneys - 60%, by the intestines - 40%. Hydrochlorothiazide is not metabolized and is rapidly excreted through the kidneys. T1 / 2 makes 5 - 15 h.
- arterial hypertension (to patients for whom combination therapy is indicated).
Ramipril; - hypersensitivity to ramipril and any other ingredient of the drug or other ACE inhibitors; - angioedema in history, including associated with previous therapy with ACE inhibitors; - hemodynamically significant bilateral renal artery stenosis; - stenosis of the artery of the only kidney; - condition after kidney transplantation; - hemodialysis; - renal failure (CC less than 20 ml / min.); - hemodynamically significant aortic or mitral stenosis (risk of an excessive decrease in blood pressure, followed by impaired renal function); - hypertrophic obstructive cardiomyopathy; - primary hyper aldosteronism; - pregnancy and lactation; - age up to 18 years (efficacy and safety have not been established). With caution: severe lesions of the coronary and cerebral arteries (danger of reducing blood flow with an excessive decrease in blood pressure), unstable angina, severe ventricular arrhythmias, chronic heart failure stage IV, decompensated "pulmonary heart ", renal and / or liver failure, hyperkalemia, hyponatremia (including on the background of diuretics and diets with restriction of salt intake), conditions accompanied by a decrease in circus volume slaying blood (includingdiarrhea, vomiting), systemic diseases of connective tissue, diabetes mellitus, inhibition of bone marrow circulation, advanced 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, coronary heart disease, cirrhosis of the liver, old age.
Use during pregnancy and lactation
The drug is contraindicated during pregnancy and lactation.
Dosage and administration
Inside dose is selected individually. The usual dose for adults - 1 tab. Ramazid H 2.5 mg / 12.5 mg per day. If necessary, it can be increased to 1 tab. Ramazid H 5 mg / 25 mg. In case of impaired renal function of mild or moderate degree (CC more than 30 ml / min, serum creatinine approximately 3 mg / dL or 265 mcmol / l), the usual dose is recommended. For creatinine clearance less than 30 ml / min, the drug is not recommended.
Ramipril; On the part of the cardiovascular system: reduction of blood pressure, orthostatic hypotension, orthostatic collapse, tachycardia, rarely - arrhythmia, angina, myocardial infarction. On the part of the genitourinary system: the development or strengthening of symptoms of renal failure, proteinuria, decrease in urine volume, decreased libido. muscle spasm, mood disorders, when used in high doses - insomnia, anxiety, depression, confusion, fainting.; From the sense organs: vestibular disorders, taste disturbances (for example, metallic taste), smell hearing, vision, and tinnitus thirst, loss of appetite, stomatitis, glossitis. On the part of the respiratory system: "dry" cough,bronchospasm, dyspnea, rhinorrhea, rhinitis, sinusitis, bronchitis.; Allergic reactions: skin rash, itching, urticaria, conjunctivitis, photosensitization; angioedema of the face, extremities, lips, tongue, pharynx and / or larynx, exfoliative dermatitis, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Layel syndrome), vesicle, serositis, onycholysis, vasculitis, myositis, myalgia, arthralgia, arthritis, eosinophilia.; Others: seizures, alopecia, hyperthermia, increased sweating; Laboratory indices: hypercreatininemia, increased urea nitrogen, increased activity of “liver” transaminases, hyperbilirubinemia, hyperkalemia, hyponatremia, the appearance of antinuclear antibodies.; Effect on the fetus: dysfunction of the fetus, lowering blood pressure of the fetus and newborns, renal dysfunction, hyperkalemia, hypoplasia of the skull bones, oligohydramnios, contracture of the extremities, deformity of the skull bones, hypoplasia of the lungs., Hydrochlorothiazide; electrolyte and acid-base balance: possible development of hypokalemia and hypochloremic alkalosis (dry mouth, increased thirst, heart rhythm disturbances, changes in mood and psyche, cramps or muscle pain, nausea that vomiting, weakness; with hypochloremic alkalosis, it is possible to develop hepatic encephalopathy or hepatic coma), hyponatremia (confusion, convulsions, apathy, slowing down the thinking process, fatigue, irritability), hypomagnesemia (arrhythmias) .; leukocytopenia. On the part of the cardiovascular system: arrhythmia, orthostatic hypotension, tachycardia.; On the part of the digestive system: cholecystitis, pancreatitis, jaundice, diarrhea, sialadenitis, zap p, anorexia, epigastric pain.; On the part of the metabolism: hyperglycemia, glycosuria, hyperuricemia, exacerbation of gout.; Allergic reactions: skin rash, purpura, necrotizing vasculitis, Stevens-Johnson syndrome, respiratory distress (pneumonia, non-cardiogenic edema of the lung, Stegens-Johnson syndrome, respiratory distress (pneumonitis, non-cardiogenic edema of the lung) photosensitization; anaphylactic reactions (up to life threatening anaphylactic shock).
Symptoms: marked reduction in blood pressure, bradycardia, shock, impaired water and electrolyte balance, acute renal failure, stupor, dry mouth, weakness, drowsiness.; Treatment: give the patient a horizontal position with raised legs, in mild cases of overdose - gastric lavage, administration adsorbents and sodium sulfate (it is desirable to hold events during the first 30 minutes after taking the drug). With a decrease in blood pressure - in / in the introduction of catecholamines, angiotensin II; in bradycardia - the use of pacemaker. The drug is not displayed during hemodialysis.
Interaction with other drugs
Ramipril; Strengthens the inhibitory effect of ethanol on the central nervous system. Salt intake with food can reduce the hypotensive effect of ramipril. With the simultaneous use of ramipril and other blood pressure reducing agents (eg, diuretics, nitrates, tricyclic antidepressants, anesthetics) leads to an increase in the hypotensive effect of ramipril. Simultaneous administration of ramipril and potassium or potassium-sparing diuretics can cause hyperkalemia.; Vasopressor sympathomimetics (epinephrine, norepinephrine) can reduce the hypotensive effect of ramipril. In this regard, with simultaneous treatment, blood pressure should be carefully monitored; simultaneous administration of ramipril and allopurinol, immunosuppressants, corticosteroids, procainamide, cytotoxic drugs increases the likelihood of changes in the peripheral blood picture; lithium in the blood serum - the risk of toxic effects.; ACE inhibitors can enhance the effect of hypoglycemic agents (for example, Ulin or sulfonylurea derivatives) that in some cases can cause hypoglycemia. In this regard, blood sugar levels should be carefully controlled, especially at the beginning of the joint use. The simultaneous use of ramipril and nonsteroidal anti-inflammatory drugs (for example, acetylsalicylic acid and indomethacin) can weaken the hypotensive effect of ramipril. Additionally, concurrent use may cause hyperkalemia and increase the risk of impaired renal function.; Simultaneous useheparin 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 the simultaneous use of glycosides of digitalis with thiazide diuretics, the likelihood of toxic effects including increased excitability of the ventricles) due to the likely development of hypokalemia and hypomagnesemia.; Drugs that bind intensively with proteins (indirectly s anticoagulants, clofibrate, NSAIDs), increase the diuretic effect of hydrochlorothiazide;. Antihypertensive effect of hydrochlorothiazide reinforce vasodilators, beta-blockers, barbiturates, phenothiazines, tricyclic antidepressants, ethanol. Hydrochlorothiazide enhances the neurotoxicity of salicylates, weakens the action of oral hypoglycemic drugs, norepinephrine, epinephrine and anti-gout drugs, enhances the cardiotoxic and neurotoxic effects of lithium preparations, the effect of peripheral muscle relaxants, reduces the excretion of quinidine. With the simultaneous use of methyldopa may develop hemolysis. Kolestiramin reduces the absorption of hydrochlorothiazide.; Hydrochlorothiazide reduces the effect of oral contraceptives.
Ramipril; At the beginning of treatment, renal function should be evaluated. Renal function must be carefully monitored during ramipril treatment, especially in patients with impaired renal function, with renal vascular damage (for example, clinically insignificant renal artery stenosis or hemodynamically significant stenosis of a single kidney artery); heart failure.; The risk of hypersensitivity and allergy-like (anaphylactoid) reactions is increased in patients simultaneously taking ACE inhibitors and undergoing hemodialysis procedures using AN69 dialysis membrane. Similar reactions have been identified with low density lipoprotein apheresis using dextran sulfate, so the use of this method should be avoided in the treatment with ACE inhibitors. During treatment with ramipril in patients with impaired renal function, especially with simultaneous treatment with diuretics, urea and creatinine levels may increase serum. In this case, treatment should be continued with lower doses of ramipril or discontinue the drug.In patients with impaired renal function, the risk of hyperkalemia increases. In patients with impaired hepatic function, due to a decrease in the activity of “liver” enzymes, ramipril metabolism and the formation of an active metabolite can be slowed down. In this regard, the treatment of such patients should be started only under strict medical supervision.; Care should be taken when prescribing ramipril to patients on a low-salt or salt-free diet (increased risk of arterial hypotension). In patients with reduced circulating blood volume (as a result of diuretic therapy), during dialysis, with diarrhea and vomiting, symptomatic hypotension may develop. Transient arterial hypotension is not a contraindication to continue treatment after stabilization of blood pressure. In case of recurrence of severe arterial hypotension, the dose should be reduced or discontinued. In patients undergoing extensive surgical interventions or receiving other means causing arterial hypotension while undergoing general anesthesia, ramipril can block the formation of angiotensin II due to compensatory renin release. If the doctor connects the development of arterial hypotension with the mechanism mentioned above, arterial hypotension can be corrected by an increase in plasma volume. In rare cases, during treatment with ACE inhibitors, agranulocytosis, erythrocytopenia, thrombocytopenia, hemoglobinemia or bone marrow 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, diseases of the connective tissue (for example, systemic lupus erythematosus or scleroderma) and in patients who are simultaneously taking drugs that affect blood formation. The counting of blood cells should also be carried out in the event of clinical signs of neutropenia / agranulocytosis and increased bleeding. In patients with arterial hypertension, treatment with ramipril rarely increases the level of potassium in the blood serum.The risk of hyperkalemia increases in chronic heart failure, the simultaneous treatment of potassium-sparing diuretics (spironolactone, amiloride, triamterene) and assigning potassium preparations;. When using ACE inhibitors during desensitizing therapy to a wasp or bee venom may arise anaphylactoid reactions (e.g., hypotension, dyspnea. , vomiting, skin rash), which can be life-threatening. Hypersensitivity reactions may occur when insect bites (eg, bees or wasps). If you need desensitization treatment with bee or wasp venom, you need to cancel ACE inhibitors and continue treatment with suitable drugs from other groups. During treatment with Ramazid H, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and psychomotor reactions. (dizziness is possible, especially after the initial dose of an ACE inhibitor in patients taking diuretic drugs. food). Patients are advised to refrain from driving and working with mechanisms until the answer to treatment is clear.; Hydrochlorothiazide; To prevent K + and Mg2 + deficiency, potassium-sparing diuretics, K + and Mg2 + salts are prescribed. Requires regular monitoring of plasma levels of potassium, glucose, uric acid, lipids and creatinine.