Vazolong® H (Vazolong® N)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceHydrochlorothiazide + RamiprilHydrochlorothiazide + Ramipril
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  • Vazolong® H
    capsules inwards 
    Micro Labs Limited     India
  • Ramazid H
    pills inwards 
    Xanthis Pharma Limited     Cyprus
  • Tritace® plus
    pills inwards 
    Sanofi-Aventis Canada Inc.     Canada
    • Dosage form: & nbspcapsules
    Composition:

    Each capsule contains:

    Active substances: hydrochlorothiazide - 12.5 mg, ramipril - 2.5 mg.

    Excipients: pregelatinized starch - 129.173 mg;

    composition of hard gelatin capsule (body): gelatin - 19.7849 mg, purified water - 3.4800 mg, methyl parahydroxybenzoate 0.11920 mg, propyl parahydroxybenzoate 0.400 mg, sodium lauryl sulfate 0.1920 mg, titanium dioxide 0.4759 mg;

    composition of hard gelatin capsule (cap): gelatin - 12,1939 mg, purified water - 2,1750 mg, methyl parahydroxybenzoate - 0,1200 mg, propyl parahydroxybenzoate - 0,0300 mg, sodium lauryl sulfate - 0.0120 mg, titanium dioxide - 0.4388 mg, dye crimson [Ponso 4R] - 0.0137 mg, a brilliant diamond blue dye - 0.0090 mg, a quinoline yellow colorant - 0.0077 mg;

    ink composition: Ethanol - 19-23%, isopropanol 19-23%, shellac 21-25%, titanium dioxide 32-36%, concentrated ammonium solution 1-3%, polysorbate 80 0.5% 2%.

    Description:

    Hard gelatin capsules, white body, gray lid, size No. 4. The capsules with ink bear the inscription "MICRO/MICRO", black color.Capsule contents - powder white or almost white.

    Pharmacotherapeutic group:Hypotensive drug combined (diuretic + ACE inhibitor)
    ATX: & nbsp

    C.09.B.A.05   Ramipril in combination with diuretics

    Pharmacodynamics:

    Vazolong® H is a combination of an angiotensin-converting enzyme (ACE) inhibitor-ramipril and a thiazide diuretic-hydrochlorothiazide. Ramipril and hydrochlorothiazide are used in monotherapy or simultaneously as an antihypertensive drug. Their combination has an additive antihypertensive effect, reducing blood pressure (BP) to a higher degree than each of these drugs individually.

    Ramipril

    Ramipril and, to a much greater extent, the active metabolite of ramipril-ramiprilat, formed under the action of "hepatic" transaminases, are long-acting ACE inhibitors. In blood plasma and tissues, ACE catalyzes the conversion of angiotensin I into angiotensin II and the breakdown of bradykinin. Therefore, when taking ramipril, the formation of angiotensin II decreases and the accumulation of bradykinin occurs, which leads to vasodilation and a decrease in blood pressure. The increase in the activity of the kalikrein-kinin system in blood and tissues causes the cardioprotective and endothelioprotective action of ramipril due to the activation of the prostaglandin system and,increasing the synthesis of prostaglandins, stimulating the formation of nitric oxide in endotheliocytes. Angiotensin II stimulates the production of aldosterone, therefore, taking ramipril leads to a decrease in the secretion of aldosterone and an increase in the potassium content. With a decrease in the concentration of angiotensin II in the blood, its inhibiting effect on renin secretion by negative feedback is eliminated, which leads to an increase in renin activity of the blood plasma. It is assumed that the development of some undesirable phenomena (in particular, "dry" cough) is also associated with an increase in bradykinin activity.

    In patients with hypertension, taking ramipril causes a decrease in blood pressure in the "lying" and "standing" positions without compensatory increase in the heart rate (heart rate). The use of ramipril leads to a significant reduction in total peripheral vascular resistance (OPSS), usually not causing changes in renal blood flow and glomerular filtration rate.

    Ramipril significantly reduces OPSS, almost without causing changes in the renal blood flow and glomerular filtration rate.

    Antihypertensive effect begins to develop 1-2 hours after ingestion of a single dose of the drug, reaching the highest value after 3-9 hours, and persists for 24 hours.With the course of treatment, the antihypertensive effect can gradually increase, stabilizing usually to 3-4 weeks of regular intake of the drug and then remaining for a long time. Sudden discontinuation of the drug does not lead to a rapid and significant increase in blood pressure (the absence of the "withdrawal" syndrome).

    Ramipril increases the sensitivity of tissues to insulin and has a beneficial effect on carbohydrate metabolism and lipid profile, increases the concentration of fibrinogen, reduces platelet aggregation, stimulates the synthesis of the tissue activator of plasminogen (plasminogen), promoting thrombolysis.

    Hydrochlorothiazide

    Hydrochlorothiazide is a thiazide diuretic, it disrupts the reabsorption of sodium, chlorine, potassium, magnesium ions in the distal nephron, delays the excretion of calcium, uric acid. The increase in renal excretion of these ions is accompanied by an increase in the amount of urine (due to the osmotic binding of water). Hydrochlorothiazide reduces the volume of blood plasma, increases the activity of renin in the blood plasma and the secretion of aldosterone. When taken in high doses hydrochlorothiazide increases the excretion of bicarbonates, with prolonged intake reduces calcium excretion.

    Antihypertensive effect develops due to a decrease in the volume of circulating blood (BCC), changes in the reactivity of the vascular wall, decrease of the pressor influence of vasoconstrictive amines (epinephrine, noradrenaline) and intensification of the depressor effect on the ganglion. Does not affect normal blood pressure.

    Diuretic effect occurs after 1-2 hours, reaches a maximum after 4 hours and lasts for 6-12 hours. Antihypertensive effect occurs in 3-4 days, but 3-4 weeks are necessary to achieve the optimal therapeutic effect.

    Pharmacokinetics:

    Ramipril

    After oral administration ramipril quickly absorbed from the gastrointestinal tract (50-60%), simultaneous intake of food does not affect the degree of absorption, but slows absorption.

    In the liver ramipril metabolized to form an active metabolite of ramiprilate (6 times more active inhibits ACE than ramipril) and inactive diketopiperazine, which are then glucuronized. All metabolites formed, with the exception of ramiprilate, have no pharmacological activity. The half-life (T1/2) of ramipril is approximately 1 hour.

    After taking ramipril inside, the maximum plasma concentrations of ramipril and ramiprilata are reached after 1 and 2-4 hours, respectively.

    Bioavailability for ramipril after oral administration 2.5-5 mg - 15-28%; for ramiprilate - 45%. After a daily intake of 5 mg / day, the steady concentration of ramiprilate in blood plasma is reached by day 4. T1/2 for ramipril - 5.1 hours; in the phase of distribution and elimination, the drop in the concentration of ramiprilata in serum occurs with T1/2 - 3 hours, followed by a transition phase with T1/2 - 15 hours and a long final phase with very low concentrations of ramiprilate in blood plasma and T1/2 - 4-5 days.

    T1/2 increases with chronic renal failure. The volume of distribution of ramipril - 90 liters, ramiprilata - 500 liters.

    The connection with blood plasma proteins for ramipril - 73%, ramiprilata - 56%.

    It is excreted by the kidneys - 60%, through the intestines - 40% (mainly in the form of metabolites).

    If renal function is impaired, excretion of ramipril and its metabolites slows in proportion to a decrease in creatinine clearance (CC). The use of ramipril in high doses (10 mg) in patients with impaired liver function leads to a delay in the conversion of ramipril to active ramiprilate, as well as to slowing the excretion of ramiprilate.

    In patients with hypertension, after a two-week treatment with ramipril in a daily dose of 5 mg, there is no clinically significant accumulation of ramipril and ramiprilate. In patients with heart failure, after a two-week treatment with ramipril in a daily dose of 5 mg, there is a 1.5-1.8 fold increase in plasma concentrations of ramiprilate and the area under the pharmacokinetic curve "concentration-time" (AUC).

    Hydrochlorothiazide

    After ingestion, the absorption and bioavailability of hydrochlorothiazide is about 70%. Connection with blood plasma proteins - 60-80%.

    When ingestion of 12.5 mg of hydrochlorothiazide, the maximum plasma concentration is achieved after 1.5-4 hours and is 70 ng / ml, and when administered 25 mg of hydrochlorothiazide, the maximum plasma concentration is reached in 2-5 hours and is 142 ng / ml.

    In the therapeutic range of doses, the average value AUC increases in direct proportion to the increase in dose, with the appointment of 1 time a day, cumulation is negligible.

    Penetrates through the hematoplacental barrier and into breast milk. T1/2 5-6 hours. Hydrochlorothiazide slightly metabolized in the liver.

    Hydrochlorothiazide is excreted almost completely (more than 95%) by the kidneys in unchanged form.50-70% of the dose taken internally is excreted within 24 hours.

    It is excreted by the kidneys: 95% unchanged and about 4% as hydrolyzate-2-amino-4-chloro-m-benzenedisulfonamide (reduced in alkaline urine) by glomerular filtration and active tubular secretion in the proximal nephron.

    Indications:

    Arterial hypertension (with indications for the use of combined antihypertensive therapy).

    Contraindications:

    - Hypersensitivity to ramipril, other ACE inhibitors, hydrochlorothiazide, other thiazide diuretics, sulfonamide derivative or to any of the excipients of the drug (see section "Composition").

    - Angioedema (hereditary or idiopathic, as well as after taking ACE inhibitors) in the anamnesis.

    - Severe renal insufficiency (CC less than 30 ml / min at 1.73 m2 surface of the body) or hemodialysis.

    - Hemodynamically significant stenosis of the renal arteries (bilateral or unilateral in the case of a single kidney).

    - Clinically significant violations of the water-electrolyte balance, such as hypokalemia, hypomagnesemia or hypercalcemia (the possibility of their aggravation in the treatment with Vazolong® H).

    - Severe liver function abnormalities (more than 9 on the Child-Pugh scale) (lack of clinical experience, it is known that under these conditions, minimal disturbances of the water-electrolyte balance can provoke a hepatic coma).

    - Anuria (due to the presence of hydrochlorothiazide in the formulation).

    - Pregnancy.

    - The period of breastfeeding.

    - Age to 18 years (not enough clinical data on the efficacy and safety of this drug in children).

    - Hemodialysis or hemofiltration using some membranes with a negatively charged surface, such as high-flux membranes from polyacrylonitrile (the risk of developing hypersensitivity reactions, including severe anaphylactoid reactions), and the apheresis of low-density lipoproteins using dextran sulfate (the risk of developing hypersensitivity reactions , including severe anaphylactoid reactions).

    - Severe arterial hypotension.

    - Simultaneous reception with drugs containing aliskiren, in patients with diabetes mellitus or with moderate and severe renal insufficiency (CC less than 60 ml / min).

    - Simultaneous reception with antagonists of receptors for angiotensin II in patients with diabetic nephropathy.

    Carefully:

    - With the simultaneous use of the drug Vazolong® H and preparations containing aliskiren, or angiotensin receptor antagonists II (with a double blockade of RAAS, there is an increased risk of a sharp decline in blood pressure, the development of hyperkalemia and impaired renal function) (see section "Special instructions").

    - In conditions accompanied by increased activity of RAAS, in which, with the inhibition of ACE, there is a risk of a sharp decrease in blood pressure with impaired renal function (see section "Special instructions"):

    • severe and especially malignant hypertension;
    • chronic heart failure, especially severe or about which other drugs with antihypertensive action are taken (see section "Special instructions");
    • hemodynamically significant disturbance of blood outflow from the left ventricle or blood flow to the left ventricle (hemodynamically significant stenosis of the aortic or mitral valve), hypertrophic obstructive cardiomyopathy;
    • Renovascular diseases, including hemodynamically significant unilateral renal artery stenosis (careful monitoring of creatinine concentration in the blood,sections "Special instructions", "Side effect");
    • previous treatment with diuretics;
    • disturbance of water-electrolyte balance as a result of insufficient intake of liquid and / or table salt, diarrhea, vomiting, excessive sweating (with inadequate replenishment of fluid and sodium losses);

    - In conditions in which excessive reduction in blood pressure is particularly dangerous (hemodynamically significant stenosis of the coronary or cerebral arteries, regular monitoring of the patient's condition is required, especially at the beginning of treatment with the drug).

    - In case of violations of the kidney function (KK 60-30ml / min) (increased risk of hyperkalemia and leukopenia, correction of the dosing regimen is required, see section "Method of administration and dose" and regular monitoring of kidney function, especially at the beginning of treatment, see "Special instructions ").

    - In a condition after kidney transplantation (careful monitoring of renal function is required, especially at the beginning of treatment).

    - In case of violations of the liver function (risk of worsening liver function, lack of sufficient clinical experience of the drug, see the sections "Side effect", "Special instructions").

    - In systemic connective tissue diseases, such as red systemic lupus erythematosus or scleroderma (the risk of disturbing immune reactions increases, the risk of a decrease in the number of leukocytes in the peripheral blood).

    - When oppression of bone marrow hemopoiesis, concomitant therapy with corticosteroids (glucocorticosteroids and mineralocorticosteroids), immunomodulators, cytostatics, antimetabolites, allopurinol, procainamide (increases the risk of leukocytopenia in peripheral blood, see the sections "Side effect", "Interaction with other drugs", "Special instructions ").

    - In diabetes (the risk of hyperkalemia, and in the case of hypoglycemic drugs - insulin, hypoglycemic agents for oral administration (derivatives of sulfonylureas) - the risk of hypoglycemic reactions due to the presence of the drug ramipril and the risk of increasing blood glucose levels due to the presence of in the composition of hydrochlorothiazide) (see the sections "Side effect", "Interaction with other drugs").

    - In elderly patients (over 65 years of age) (risk of more severe antihypertensive action,requires more regular monitoring of kidney function).

    Pregnancy and lactation:

    Vazolong® H can not be used during pregnancy. Therefore, before starting the drug in women of childbearing age, pregnancy should be excluded, and during treatment they must use reliable methods of contraception. In case of pregnancy during treatment with the drug, it should be stopped as soon as possible and transferred to the patient to take other hypotensive drugs, in which the risk to the child will be the least.

    Because of the risk of adverse effects of ramipril and hydrochlorothiazide on the fetus, it is advisable to avoid conception in women who can not be transferred to another treatment for hypertension (without ACE inhibitors and diuretics).

    It is not known whether the effect of Vazolong® H in the first trimester of pregnancy can have a negative effect on fetal development. The use of ACE inhibitors in the II and III trimesters of pregnancy is combined with impairments that may occur in the fetus and newborn, including a reduction in blood pressure, hypoplasia of the skull bones, anuria, reversible or irreversible renal failure and death.Also reported on the development of oligohydramnion, apparently due to impaired fetal kidney function; oligohydramnios in such cases was accompanied by the development of contractures of the fetal limbs, craniofacial deformities and lung hypoplasia. Preterm births, intrauterine growth retardation, and non-spreading of the botulinum (arterial) duct were also recorded, although it is not known whether these effects are due to ACE inhibitors.

    It is recommended to carefully monitor newborns who have undergone intrauterine exposure to ACE inhibitors to detect a decrease in blood pressure, oliguria, and hyperkalemia. In oliguria it is necessary to maintain blood pressure and renal perfusion by introducing appropriate fluids and vasoconstrictive drugs. Such neonates have a risk of developing oliguria and neurological disorders because of a possible reduction in renal and cerebral blood flow due to a decrease in blood pressure caused by ACE inhibitors.

    It is assumed that with the use of hydrochlorothiazide in the second trimester of pregnancy, the development of thrombocytopenia in newborns is possible.

    As ramipril and hydrochlorothiazide are allocated with breast milk, then if you need to use the drug Vazolong® H in the lactation period, you should stop breastfeeding the baby.

    Dosing and Administration:

    The drug Vazolong® H not intended for the initial course of treatment of hypertension, since patients who had not previously received antihypertensive medications, who immediately started simultaneous treatment with ramipril and a diuretic, may have an excessive decrease in blood pressure.

    Capsules should be swallowed whole and washed down with a sufficient amount (1/2 cup) of water. The essential effect of simultaneous food intake on the bioavailability of the drug is not expected, so it can be taken before, during or after a meal. It is usually recommended that the daily dose be taken once at the same time of day, preferably in the morning.

    Doses of the drug are selected individually. The choice of doses is performed by a doctor in accordance with the severity of arterial hypertension and the presence of associated risk factors, as well as the tolerability of the drug.

    The dose of Vazolong® H is selected by titration (gradual increase or, if necessary, reduction) of the doses of its individual preparations of ramipril and hydrochlorothiazide.Especially careful titration of doses in patients on hemodialysis should be performed.

    After the patient's doses of ramipril and hydrochlorothiazide are selected, for better comfort for the patients, they can be taken to receive Vazolong® H, the appropriate dosage, to receive these doses of ramipril and hydrochlorothiazide in one capsule.

    The usual initial dose: 2.5 mg of ramipril and 12.5 mg of hydrochlorothiazide (corresponds to one capsule of Vazolong® H 2.5 mg / 12.5 mg), in the morning, once. If necessary, the dose may increase with an interval of 2-3 weeks.

    The maximum daily dose: 2 capsules of the drug Vazolong®.

    In most cases, blood pressure is reduced sufficiently when taking Vazolong® H at doses of 2.5 mg ramipril / 12.5 mg hydrochlorothiazide to 5 mg ramipril / 25 mg hydrochlorothiazide.

    If, during maintenance therapy, a dose adjustment is required, then it is better to do this with the use of separate preparations of ramipril and hydrochlorothiazide.

    Treatment of patients receiving diuretics

    Patients who received previous treatment with diuretics,Before taking Vazolong® H, if possible 2-3 days or more (depending on the duration of the action of diuretics), they should be canceled or at least reduced doses.

    If discontinuation of diuretics is not possible, it is recommended to begin treatment with the lowest doses of ramipril (1.25 mg per day), taking individual preparations of ramipril and hydrochlorothiazide. It is recommended that in future the transfer to the preparation of Vasolong® H is carried out in such a way that the initial daily dose does not exceed 2.5 mg of ramipril and 12.5 mg of hydrochlorothiazide.

    Treatment of patients with impaired renal function

    Treatment begins with ramipril monotherapy at a daily dose of 1.25 mg in patients with QC from 30 to 60 ml / min. After a gradual increase in the dose of ramipril, treatment with the combined drug begins with a dose of 2.5 mg ramipril / 12.5 mg hydrochlorothiazide (corresponding to 1 capsule of the drug Vazolong® H 2.5 mg / 12.5 mg).

    The maximum allowed daily dose for patients with renal insufficiency is 5 mg ramipril / 25 mg hydrochlorothiazide (corresponding to 2 capsules of Vazolong® H 2.5 mg / 12.5 mg).

    Treatment of patients with mild or moderate impairment of liver function (less than 9 on the Child-Pugh scale)

    Treatment with Vazolong® H should begin under close medical supervision and the maximum daily dose of ramipril should be 2.5 mg.

    Treatment of elderly patients

    Treatment should begin with lower doses, and the increase in doses should be gradual (with a smaller step of increasing doses) due to a greater likelihood of developing side effects, especially in weakened elderly patients.

    If you skip the next dose, the missed dose should be taken as soon as possible. However, if it is found very close to the time of taking the next dose, it is necessary to skip the intake of the missed dose and return to the usual dosing regimen, avoiding taking a double dose in a short time.

    Side effects:

    Since Vazolong® H is an antihypertensive drug, many unwanted reactions in its application are secondary to its lowering blood pressure, which leads to reflex activation of the sympathetic nervous system or hypoperfusion of various organs. The number of other adverse effects, such as the effect on the water-electrolyte balance,some anaphylactoid reactions or inflammatory reactions on the mucous membranes are a consequence of inhibition of ACE or other pharmacological effects of ramipril or hydrochlorothiazide.

    The undesirable effects that occur with the use of Vazolong® H, its active substances (ramipril and hydrochlorothiazide), other ACE inhibitors or other diuretics like hydrochlorothiazide, which are given in accordance with the classification of the frequency of their occurrence in accordance with the classification of the World Organization health:

    very often: (≥10%);

    often: (≥ 1% - < 10%);

    infrequently: (≥0.1% - <1%);

    rarely: (0.01% - 0.1%);

    frequency is unknown: according to available data, it is impossible to establish the frequency of occurrence of an undesirable effect.

    Heart Disease

    Infrequently: myocardial ischemia, including angina pectoris development; tachycardia, heart rhythm disturbances, palpitations, peripheral edema.

    Frequency unknown: myocardial infarction.

    Violations of the blood and lymphatic system

    Infrequently: decrease in the number of erythrocytes in peripheral blood,a decrease in the number of leukocytes in the peripheral blood, a decrease in hemoglobin, hemolytic anemia, a decrease in the number of platelets in the peripheral blood.

    Frequency unknown: violation of bone marrow hematopoiesis, including agranulocytosis, pancytopenia, eosinophilia, hemoconcentration due to a decrease in the fluid content in the body and, in particular, in the peripheral blood.

    Disturbances from the nervous system

    Often: headache, dizziness (feeling of "lightness" in the head).

    Infrequently: vertigo, paresthesia, tremor, imbalance, burning sensation of the skin, dysgeusia (a violation of taste sensations), agevzia (loss of taste sensations).

    Frequency unknown: cerebral ischemia, including ischemic stroke and transient impairment of cerebral circulation; violation of psychomotor reactions, parosmia (impaired sense of smell, including a subjective sensation of any odor in its objective absence).

    Disturbances on the part of the organ of sight

    Infrequently: visual impairment, including vagueness of the visible image; conjunctivitis.

    Frequency unknown: xantopsy, reduction of tear fluid (due to the presence of hydrochlorothiazide in the formulation).

    Hearing disorders and labyrinthine disorders

    Infrequently: tinnitus.

    Frequency unknown: hearing loss.

    Disturbances from the respiratory system, organs of the chest and mediastinum

    Often: "dry" cough, bronchitis.

    Infrequently: sinusitis, dyspnea, nasal congestion.

    Frequency unknown: bronchospasm, including increased symptoms of bronchial asthma; allergic alveolitis (pneumonitis); noncardiogenic pulmonary edema (due to the presence of hydrochlorothiazide in the formulation).

    Disorders from the digestive system

    Infrequently: inflammation of the mucous membrane of the gastrointestinal tract, digestive disorders, discomfort in the abdomen, dyspepsia, gastritis, nausea, constipation; Gingivitis (due to the presence of hydrochlorothiazide in the formulation).

    Rarely: vomiting, aphthous stomatitis, glossitis, diarrhea, epigastric pain, dryness of the oral mucosa.

    Frequency unknown: pancreatitis (in exceptional cases, when taking ACE inhibitors, pancreatitis was observed with a fatal outcome), increased activity of "pancreatic" enzymes in the blood,angioedema of the small intestine; sialoadenitis (due to the presence of hydrochlorothiazide in the formulation).

    Disorders from the kidneys and urinary tract

    Infrequently: impaired kidney function, including acute renal failure; an increase in the amount of urine released, an increase in the concentration of urea in the blood, an increase in the concentration of creatinine in the blood (even a slight increase in creatinine concentration with unilateral stenosis of the renal artery may indicate impaired renal function).

    Frequency unknown: an increase in pre-existing proteinuria, interstitial nephritis (due to the presence of hydrochlorothiazide in the formulation).

    Disturbances from the skin and subcutaneous tissues

    Infrequently: angioedema; in exceptional cases, airway obstruction can lead to death; psoriasis-like dermatitis, increased sweating, skin rash, in particular maculopapular rash, itching, baldness.

    Frequency unknown: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, increased symptoms of psoriasis,exfoliative dermatitis, photosensitization reactions, onycholysis, pemphigoid or lichenoidal exanthema or enanthema, urticaria; systemic lupus erythematosus (due to the presence of hydrochlorothiazide in the formulation).

    Disturbances from musculoskeletal and connective tissue

    Infrequently: myalgia.

    Frequency unknown: arthralgia, spastic muscle contractions, muscle weakness, muscle rigidity, tetany (due to the presence of hydrochlorothiazide in the formulation).

    Disorders from the endocrine system

    Frequency unknown: syndrome of inadequate secretion of antidiuretic hormone.

    Disorders from the metabolism and nutrition

    Often: decompensation of diabetes mellitus, decreased glucose tolerance, increased blood glucose levels, increased uric acid concentrations in the blood, increased gout symptoms, increased concentrations of cholesterol and triglycerides in the blood (due to the presence of hydrochlorothiazide in the formulation).

    Infrequently: anorexia, decreased appetite, decreased potassium in the blood, thirst (due to the presence of hydrochlorothiazide in the formulation).

    Rarely: an increase in the potassium content in the blood (due to the presence of ramipril in the formulation).

    Frequency unknown: a decrease in the sodium content in the blood, glucosuria, metabolic alkalosis, hypochloraemia, hypomagnesemia, hypercalcemia, dehydration (due to the presence of hydrochlorothiazide in the formulation).

    Vascular disorders

    Infrequently: excessive reduction in blood pressure, orthostatic hypotension, fainting, "tides" of blood to the skin of the face.

    Frequency unknown: thrombosis in severe fluid loss, stenosis of vessels, the appearance or strengthening of circulatory disorders against the background of stenosing lesions, Raynaud's syndrome, vasculitis.

    General disorders and disorders at the site of administration

    Often: increased fatigue, asthenia.

    Infrequently: pain in the chest, increased body temperature.

    Immune system disorders

    Frequency unknown: anaphylactic or anaphylactoid reactions (with the inhibition of ACE it is possible to intensify severe anaphylactic or anaphylactoid reactions to insect venom) or anaphylactic reactions to hydrochlorothiazide; an increase in the titer of antinuclear antibodies.

    Disturbances from the liver and bile ducts

    Infrequently: Cholestatic or cytolytic hepatitis (in exceptional cases with fatal outcome), increased activity of "hepatic" transaminases in the blood, conjugated bilirubin; Calculous cholecystitis (due to the presence of hydrochlorothiazide in the formulation).

    Frequency unknown: acute liver failure, cholestatic jaundice, hepatocellular lesions.

    Violations of the genitals and mammary gland

    Infrequently: transient erectile dysfunction.

    Frequency unknown: decreased libido, gynecomastia.

    Disorders of the psyche

    Infrequently: depressive mood, apathy, anxiety, nervousness, sleep disturbances, including drowsiness.

    Frequency unknown: confusion, anxiety, attention deficit (trouble concentrating).

    Overdose:

    Symptoms

    In case of an overdose, it is possible to develop a persistent increase in the amount of urine output, symptoms of excessive peripheral vasodilation (with a marked decrease in blood pressure, development of shock), bradycardia, violations of the water electrolyte balance,

    insufficiency, disturbances of a heart rhythm, oppression of consciousness up to development of a coma; cerebral cramps, paresis and paralytic intestinal obstruction.

    In patients with impaired urine outflow (for example, with prostatic hyperplasia) copious diuresis can provoke an acute urinary retention with a bladder overgrowth.

    Treatment

    If possible, during the first 30 minutes, you should wash the stomach, give adsorbents, sodium sulfate. In the case of a persistent decline in blood pressure in addition to therapy aimed at replenishment of bcc and electrolytes, the introduction of alpha agonists1-adrenergic receptors (norepinephrine (norepinephrine), dopamine). In the case of refractory to medical treatment of bradycardia, a temporary artificial pacemaker may be required. In case of overdose, it is necessary to control serum concentrations of creatinine and electrolytes. There is no experience regarding the effectiveness of forced diuresis, changes in urinary pH, hemofiltration or hemodialysis to accelerate the excretion of ramipril and ramiprilate. Hydrochlorothiazide can be excreted by hemodialysis. If hemodialysis or hemofiltration is still expected, the risk of developing anaphylactoid reactions when using high-flow membranes should be taken into account and not used (see section "Special instructions").

    Interaction:

    Contraindicated combinations

    - Extracorporeal types of treatment, such as hemodialysis or hemofiltration with certain high-flow membranes (polyacrylonitrile membranes) and low-density lipoprotein apheresis with dextrin sulfate

    The risk of developing severe anaphylactoid reactions (see the section "Contraindications").

    The simultaneous use of the drug Vazolong® H and preparations containing aliskiren

    The simultaneous use of Vazolong® H and preparations containing aliskiren, in patients with diabetes mellitus or moderate and severe renal failure (CC less than 60 ml / min) is contraindicated and not recommended in other patients (see the sections "Contraindications", "With caution", "Special instructions").

    The simultaneous use of Vasolong® H and angiotensin II receptor antagonists (ARA II)

    The simultaneous use of the drug Vazolong® H and ARA II is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see the sections "Contraindications", "With caution", "Special instructions").

    Unrecommended combinations

    - With potassium salts, potassium-sparing diuretics (for example, spironolactone, eplerenone, amiloride, triamterene), other drugs capable of increasing the serum potassium content (including APA II, tacrolimus, ciclosporin; trimethoprim, sulfamethoxazole, which are part of co-trimoxazole (a combined antibacterial agent containing sulfamethoxazole and trimethoprim))

    Possible to increase the content of potassium in the serum, sometimes significantly expressed (while the application requires careful control of potassium in blood serum).

    Combinations, when using which care should be taken

    - With antihypertensive drugs and other drugs that have antihypertensive action (nitrates, tricyclic antidepressants)

    Potentiation of antihypertensive action is possible.

    - With funds for general anesthesia, barbiturates, ethanol

    Perhaps the development of orthostatic hypotension.

    Ramipril can lead to an increase in the symptoms of vasodilation and, due to this, potentiate this effect of ethanol.

    - With diuretics

    There may be an excessive decrease in blood pressure at the beginning of treatment (for concomitant administration with diuretics, see the section "Dosage and administration", "Special instructions").

    - With vasopressor adrenomimetics (epinephrine (adrenaline), isoproterenol, dobutamine, dopamine)

    Reduction of antihypertensive action of the drug Vazolong® H. It is recommended to carefully monitor blood pressure. In addition, the vasopressor effect of adrenomimetics can be weakened by hydrochlorothiazide.

    - FROM allopurinol, immunosuppressive agents, corticosteroids (glucocorticosteroids and mineralocorticosteroids), procainamide, cytostatics and other agents that can alter the picture of peripheral blood

    The probability of developing blood disorders increases (see the sections "Side effect", "Special instructions").

    - With lithium salts

    It is possible to reduce the excretion of lithium,leading to an increase in serum lithium concentrations and an increase in its toxicity. Therefore, it is necessary to monitor the serum concentrations of lithium.

    - FROM hypoglycemic drugs (insulin, hypoglycemic agents for oral administration (derivatives of sulfonylureas))

    ACE inhibitors can reduce insulin resistance. In some cases, in patients receiving hypoglycemic agents, such a decrease in insulin resistance can lead to the development of hypoglycemia. This effect can develop after a few days or months of treatment. Hydrochlorothiazide is able to reduce the effect of hypoglycemic agents. Therefore, at the initial stage of simultaneous appointment of hypoglycemic agents and Vazolong® H requires particularly regular monitoring of blood glucose.

    - With vildagliptin, other glyptins and estramustine

    Increased incidence of angioedema.

    - With inhibitors mTOR (mammalion Target of Rapamycin - a target of rapamycin in mammalian cells), for example, tessirolimus

    In patients taking both ACE inhibitors and inhibitors mTOR, there was an increase in the incidence of angioedema.

    Combinations, which should be taken into account

    - With non-steroidal anti-inflammatory drugs (indomethacin, acetylsalicylic acid (more than 3 g / day))

    Possible weakening of the drug Vazolong® H, an increased risk of impaired renal function and an increase in potassium in the blood serum. A strict control of serum creatinine and potassium concentrations is recommended.

    - With heparin

    Potential increase in potassium in the blood serum.

    - With corticosteroids (glucocorticosteroids and mineralocorticosteroids), carbenoxolone, preparations containing a large amount of licorice root, laxatives (with prolonged use), and other potassium-ruthenium

    Increased risk of hypokalemia.

    - With cardiac glycosides, drugs capable of lengthening the interval QT, antiarrhythmics

    Potential for the development of hypokalemia or hypomagnesemia (due to the content of hydrochlorothiazide in the formulation), which can lead to potentiation of the pro-rhythmogenic effect of these drugs or to reduce the antiarrhythmic effect of antiarrhythmics.

    - FROM methyldopa

    Hemolysis is possible.

    - With calcium salts and drugs that increase the level of calcium in the blood plasma

    When used simultaneously with hydrochlorothiazide, an increase in the serum calcium content is possible, careful monitoring of the calcium content in the blood serum is required.

    - With Vitamin D

    With simultaneous application with hydrochlorothiazide, an increase in the serum calcium content (due to a delay in the excretion of calcium by the kidneys) is required, careful monitoring of the serum calcium content is required.

    - With carbamazepine

    The risk of hyponatremia due to the potentiating effect of hydrochlorothiazide.

    - With iodine-containing contrast agents

    In the case of development of dehydration caused by diuretics, including hydrochlorothiazide, there is an increased risk of developing acute renal dysfunction, especially when high doses of contrast medium are administered.

    - FROM penicillin

    Hydrochlorothiazide is excreted by the distal renal tubules and therefore reduces the excretion of penicillin.

    - With quinidine

    Hydrochlorothiazide reduces the excretion of quinidine.

    - Ionic exchange resins, such as colestramine and Colestypol

    Reduces the absorption of hydrochlorothiazide.

    - With curare relaxants

    Possible enhancement and prolongation of muscle relaxant action.

    - With table salt

    With a large amount of table salt coming from food, it is possible to attenuate the antihypertensive effect of the drug Vazolong® N.

    - With desensitizing therapy

    The likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom increases with inhibition of ACE. It is assumed that similar reactions are possible for other allergens.

    - With warfarin, acenocoumarol

    At their simultaneous appointment with ramipril, there was no effect on the anticoagulant effect of these drugs.

    Impact on laboratory research

    Research of parathyroid function

    Hydrochlorothiazide stimulates renal reabsorption of calcium and can cause hypercalcemia. This should be taken into account when performing tests to assess the function of parathyroid glands (see section "Special instructions").

    Special instructions:

    Simultaneous use of Vazolong® H with preparations containing aliskiren, or with ARA II, leading to a double blockade of RAAS, is not recommended due to the risk of excessive reduction in blood pressure, the development of hyperkalemia and impaired renal function.

    Simultaneous use of Vazolong® H with preparations containing aliskiren, in patients with diabetes mellitus and / or renal insufficiency with a CK of less than 60 ml / min is contraindicated (see the sections "Contraindications", "Interaction with other drugs").

    Simultaneous use with ARA II in patients with diabetic nephropathy is contraindicated (see the sections "Contraindications", "Interaction with other drugs").

    Angioedema

    In the treatment of ACE inhibitors, mainly after the first dose, cases of angioedema have been observed. With the development of angioedema during therapy with an ACE inhibitor, immediate discontinuation of its use is required. Angioedema with involvement of the larynx can lead to death. In case of edema of the face, extremities, lips, tongue or vocal cords and especially the development of breathless breathing, stop taking Vazolong® H and immediately begin treatment aimed at stopping angioedema.

    In cases where the edema is localized on the face and lips, this condition is usually resolved without treatment, however, antihistamines can be used to relieve symptoms. If swelling to the tongue, vocal cords or throat is spread, airway obstruction may occur, in such cases it is necessary to begin promptly appropriate treatment (including immediate subcutaneous or slow intravenous injection of epinephrine (adrenaline) under ECG and blood pressure control). Recommended hospitalization for at least 12-24 hours and discharge from the hospital only after complete relief of symptoms of angioedema.

    Angioedema of the small intestine

    Patients receiving ACE inhibitors reported the development of angioedema of the small intestine, which manifested itself in abdominal pain (with or without nausea or vomiting), while in some cases angioedema was observed simultaneously. The diagnosis is established using computed tomography of the abdominal cavity, ultrasound, or at the time of surgery. Symptoms of angioedema of the intestine passed after the cessation of the use of an ACE inhibitor.

    Acute myopia and secondary closed angle glaucoma

    Hydrochlorothiazide is a sulfonamide derivative. Sulfonamide and sulfonamide derivatives can cause idiosyncrasy reactions leading to the development of transient myopia and acute closed-angle glaucoma, the symptoms of which are acute reduction in visual acuity or eye pain. They usually occur within a few hours to several weeks after starting the drug. In the absence of treatment, acute closed-angle glaucoma can lead to persistent loss of vision. It is necessary to stop taking the drug as soon as possible. Emergency medical or surgical treatment may be required if the intraocular pressure remains uncontrolled. Risk factors for the development of acute myopia or secondary closed-angle glaucoma are anamnestic indications of allergy to sulfonamide derivatives or penicillins.

    Cough

    When taking Vazolong® H, there may be a "dry" cough that usually disappears after the drug is discontinued. Such a probability must be taken into account when conducting a differential diagnosis of cough.

    Anaphylactoid reactions to ACE inhibitors

    With the use of ACE inhibitors, life-threatening, rapidly developing anaphylactoid reactions have been described, sometimes up to the development of shock during hemodialysis using certain high-flow membranes (for example, polyacrylonitrile membranes) (see also membrane manufacturers instructions). It is necessary to avoid joint use of Vazolong® H and this type of membranes, for example, for urgent hemodialysis or hemofiltration. In this case, it is preferable to use other types of membranes or to exclude the use of ACE inhibitors.

    Similar reactions were observed in the apheresis of low-density lipoproteins using dextran sulfate. These reactions could be avoided with the temporary cessation of therapy with an ACE inhibitor before each next apheresis. Antihistamines are ineffective for the removal of these reactions.

    Separate reports of patients with prolonged life-threatening anaphylactoid reactions arising during desensitizing treatment with bee venoms, wasps, and the like were obtained. In some patients, these reactions were avoided with a preliminary temporary withdrawal of ACE inhibitors for a period of at least 24 hours.

    Reactions of hypersensitivity to hydrochlorothiazide do not depend on the presence in the history of allergy or bronchial asthma.

    Arterial hypotension

    After ramipril, usually after the first or second dose, or after increasing the dose, it is possible to develop arterial hypotension, which is most likely in patients whose bcc has been reduced as a result of diuretic therapy, limited intake of table salt with food, dialysis, diarrhea, vomiting or profuse sweating.

    It is generally recommended that dehydration, hypovolemia and hyponatremia be corrected before starting the use of the drug (however, in patients with heart failure, BCC replacement should be carried out with great caution, since there is a risk of decompensation due to excessive volume loading).

    Transient excessive decrease in blood pressure is not a contraindication for the continuation of therapy after stabilization of blood pressure. In the case of repeated excessive decrease in blood pressure should reduce the dose or cancel the drug.

    Patients with activation of RAAS

    In conditions in which the activation of RAAS takes place and / or the renal function depends on its activity (see Fig."With caution"), with the inhibition of ACE, there is an increased risk of a marked decrease in blood pressure and impaired renal function. Therefore, in such cases, at the beginning of the treatment or at the beginning of the increase in the initial dose, BP control is required before the time when no further BP reduction is expected.

    In patients with severe chronic heart failure (including those accompanied by renal insufficiency), therapy with an ACE inhibitor may cause an excessive decrease in blood pressure and be accompanied by oliguria and / or progressive azotemia with acute renal failure, up to a lethal outcome. In such patients, the initiation of treatment with Vazolong® H or its continuation should be carried out only after taking measures against a sharp decrease in blood pressure and impaired renal function.

    Patients, for which an excessive decrease in blood pressure represents a particular danger

    Particular danger is the excessive reduction in blood pressure for patients with coronary heart disease or with severe atherosclerosis of the cerebral vessels, since in this case, it is possible to develop a myocardial infarction or stroke (see the section "With caution").Such patients are subject to strict observation at the beginning of treatment and with an increase in the dose of the drug.

    Patients with dehydration

    All patients should be warned that dehydration due to increased sweating (including in hot weather or physical exertion), vomiting, diarrhea can lead to excessive blood pressure lowering, and in these cases the question of the applied doses of ramipril and hydrochlorothiazide should be decided by the doctor.

    Alcohol intake during treatment

    During treatment with Vazolong® H, alcohol is not recommended (see section "Interaction with other drugs").

    In case of excessive reduction in blood pressure, it is necessary to put the patient in a horizontal position with raised legs, and, if necessary, start an intravenous infusion of 0.9% sodium chloride to replenish the BCC.

    Surgery and general anesthesia

    Before surgery (including dental), it is necessary to alert the surgeon / anesthesiologist about the use of ACE inhibitors. If arterial hypotension develops during general anesthesia, it can be corrected by replenishing the BCC.

    Thiazides can enhance the effects of tubocurarine.

    It is recommended that treatment with ACE inhibitors, including ramipril, was discontinued (if possible) one day before surgery.

    Primary hyperaldosteronism

    Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs acting through inhibition of RAAS. Therefore, the drug Vazolong® H is not a drug of choice for the treatment of primary hyperaldosteronism.

    Hematological control

    When taking the drug Vazolong® H, it is recommended to control the number of leukocytes to detect possible leukopenia. Regular monitoring is recommended at the beginning of treatment and in patients with impaired renal function, systemic connective tissue diseases (systemic lupus erythematosus, scleroderma) or in patients receiving other drugs capable of altering the picture of peripheral blood (see "Side effect", "Interaction with other drugs "). When symptoms appear due to leukopenia (eg, fever, enlargement of lymph nodes, tonsillitis), urgent monitoring of the picture of peripheral blood is needed.In case of signs of bleeding (the smallest petechiae, red-brown rashes on the skin and mucous membranes), it is also necessary to control platelets in the peripheral blood.

    Control of liver function

    A complete liver function test and other studies should be performed to identify symptoms that are suspicious of the disorder: flu-like symptoms that occur in the first weeks or months of treatment (such as fever, malaise, muscle pain, skin rash, or adenopathy, indicating hypersensitivity reactions ), abdominal pain, nausea or vomiting, loss of appetite, jaundice, pruritus, or other unexplained symptoms. If liver function is confirmed, discontinue taking Vazolong® H and, if necessary, prescribe appropriate treatment.

    In patients with impaired hepatic function or with progressive liver diseases, the use of thiazide diuretics requires caution, since in such patients even minimal disturbances of the water-electrolyte balance can provoke a hepatic coma.

    Controlled clinical trials involving patients with cirrhosis and / or liver dysfunction are not available.With extreme caution should be used preparation Vazolong® H in patients with pre-existing liver disorders, which prior to the use of the drug should determine the status of liver function and strictly monitor it during treatment.

    Control of kidney function

    Due to the suppression of RAAS activity in predisposed patients, renal function may worsen, the risk of which increases with the simultaneous use of diuretics.

    It is recommended to closely monitor kidney function, especially in the first weeks of treatment and in the following patient groups:

    - patients with heart failure;

    - patients with renovascular diseases, including hemodynamically significant unilateral renal artery stenosis (in such patients, even a slight increase in serum creatinine concentrations may be a manifestation of a unilateral reduction in renal function);

    - patients with impaired renal function;

    - patients after kidney transplantation.

    In patients with impaired renal function, special care is required when using the drug Vazolong® H, and in these cases, smaller doses of the drug are used (see section "Method of administration and dose").

    Hydrochlorothiazide can promote or enhance azotemia. Cumulative effects of the drug are possible in patients with impaired renal function. If increasing azotemia and oliguria develop during treatment of a serious progressive kidney disease, diuretic therapy should be discontinued.

    Inadequate experience is accumulated in the use of the drug in patients with severe renal impairment (creatinine clearance less than 30 ml / min) and in patients on hemodialysis.

    Control of laboratory indicators

    When therapy with the drug Vazolong® H, it is necessary to control the content of sodium, potassium, calcium, uric acid in the blood serum and glucose in the blood. Patients with impaired renal function, with violations of the water-electrolyte balance require regular monitoring of potassium in the blood serum.

    Other precautions

    Thiazide diuretics can reduce the concentration in the blood of protein-bound iodine without causing signs of thyroid dysfunction.

    Thiazide diuretics can cause a temporary and small increase in serum calcium in the absence of known calcium metabolism disorders.Expressed hypercalcemia may indicate latent hyperparathyroidism. Before analyzing the function of the parathyroid glands, thiazide diuretics should be discarded.

    Risk factors for the development of hyperkalemia include renal failure, diabetes mellitus, and simultaneous use of drugs for the treatment of hypokalemia or other drugs capable of increasing serum potassium (see "Interactions with Other Drugs"). Patients should be advised not to use salt substitutes containing potassium, without first consulting a physician.

    It should be borne in mind that with the use of hydrochlorothiazide, a positive result is possible with doping control.

    In the event of a syncopal condition, it is necessary to stop taking the medication and inform the doctor about it.

    Effect on the ability to drive transp. cf. and fur:

    Some of the undesirable effects of the drug Vazolong® H (some symptoms of lowering blood pressure, such as dizziness, a sense of "lightness" in the head), as well as disorders of the visual organ and others, can disrupt the ability of patients to concentrate and reduce psychomotor reactions,which implies a risk in situations requiring increased concentration of attention and speed of psychomotor reactions (for example, when driving vehicles, working with mechanisms or engaging in other potentially hazardous activities).

    Form release / dosage:

    Capsules, 2.5 mg + 12.5 mg.

    Packaging:

    10 capsules in an aluminum strip.

    For 1, 3, 5 or 10 strips with instructions for use in a cardboard box.

    Storage conditions:

    In a dry, the dark place at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after the expiration date stated on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:PL-000759
    Date of registration:29.09.2011 / 30.09.2016
    Expiration Date:Unlimited
    The owner of the registration certificate:Micro Labs LimitedMicro Labs Limited India
    Manufacturer: & nbsp
    Representation: & nbspMICRO LABS LIMITED MICRO LABS LIMITED India
    Information update date: & nbsp05.02.2017
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