Active substanceLizinopril + HydrochlorothiazideLizinopril + Hydrochlorothiazide
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  • Dosage form: & nbspPills.
    Composition:

    One tablet contains:

    Active substances: lisinopril 20 mg (in the form of lisinopril dihydrate 21,780 mg) and hydrochlorothiazide 12.5 mg or 25 mg.

    Excipients:

    tablets 20 mg + 12.5 mg: calcium hydrophosphate - 111.420 mg; ferric oxide brown oxide 75 (E172) 0.25 mg; corn starch - 20,15 mg; Pregelatinized starch - 14,60 mg; magnesium stearate - 1.70 mg; mannitol - 36.00 mg; povidone - 6.60 mg.

    tablets 20 mg + 25 mg: calcium hydrophosphate - 98.67 mg; iron dye oxide red 30 (E172) - 0.25 mg; corn starch - 20,15 mg; pregelatinized starch - 14.85 mg; magnesium stearate - 1.70 mg; mannitol-36.00 mg; povidone - 6.60 mg.

    Description:

    Tablets 20 mg + 12.5 mg: Round, biconvex tablets are light purple with a risk on one side.

    Tablets 20 mg + 25 mg: Round, biconvex tablets of light pink color, with a risk on one side.

    Pharmacotherapeutic group:hypotensive combined agent (angiotensin-converting enzyme inhibitor + diuretic).
    ATX: & nbsp

    C.09.B.A.03   Lizinopril in combination with diuretics

    Pharmacodynamics:

    Skopryl plus - a combination of an angiotensin-converting enzyme inhibitor (lisinopril) and a diuretic (hydrochlorothiazide). Has antihypertensive and diuretic effect. Lisinopril and hydrochlorothiazide, with simultaneous use, have an additive antihypertensive effect.

    Lisinopril - Angiotensin-converting enzyme (ACE) inhibitor, reduces the formation of angiotensin II from angiotensin 1. Reducing angiotensin II leads to a direct reduction in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces the overall peripheral vascular resistance, arterial pressure (BP), preload, pressure in the pulmonary capillaries, causes an increase in the minute volume of blood and increased tolerance of the myocardium to loads in patients with chronic heart failure. Expands arteries more than veins. Some effects are explained by the effect on tissue renin-angiotensin systems. With prolonged use, myocardial hypertrophy and the walls of arteries of resistive type decrease.Improves the blood supply of the ischemic myocardium.

    ACE inhibitors prolong life expectancy in patients with chronic heart failure, slow the progression of left ventricular dysfunction in patients who underwent myocardial infarction without clinical manifestations of heart failure. The antihypertensive effect begins in about 6 hours and persists for 24 hours.

    The duration of the effect also depends on the size of the dose. The beginning of the action is after 1 hour. The maximum effect is achieved through 6-7 hours. With arterial hypertension, the effect is observed in the first days after the start of treatment, stable action develops after 1 - 2 months.

    With a sharp withdrawal of the drug, no pronounced increase in blood pressure was observed. In addition to reducing blood pressure lisinopril reduces albuminuria. In patients with hyperglycemia contributes to the normalization of the function of the damaged glomerular endothelium.

    Hydrochlorothiazide - a thiazide diuretic whose diuretic effect is associated with a disruption of the reabsorption of sodium, chlorine, potassium, magnesium, and water ions in the distal nephron; delays the excretion of calcium ions, uric acid.Has antihypertensive properties; the hypotensive effect develops due to the expansion of arterioles. Virtually no effect on normal blood pressure.

    Diuretic effect occurs in 1 to 2 hours, the maximum is reached after 4 hours and continues 6-12 hours. Antihypertensive action occurs through 3-4 day, but it may take up to 4 weeks to achieve the optimal therapeutic effect.

    Pharmacokinetics:

    Lisinopril

    -absorption: slowly and not completely absorbed after ingestion. Eating does not affect absorption. Time to reach the maximum concentration (Cmah) after ingestion is achieved after 6 to 8 hours and persists for 24 hours. With repeated dosing, the half-life of lisinopril is about 12 hours. The volume of suction of lisinopril is about 25%.

    - distribution: does not bind to blood plasma proteins.

    -metabolism and excretion: does not undergo significant metabolism and is excreted in

    mostly through the kidneys in unchanged form.

    Passes through the blood-brain barrier slightly.

    There is no data on the penetration of lisinopril into breast milk.

    Hydrochlorothiazide

    -absorption: absorbed quickly after ingestion.

    -distribution: binds to blood plasma proteins. Penetrates through the placental barrier.

    -metabolism: practically not metabolized.

    -reduction: half-life from 5.6 to 14.8 hours. At least 61% of the internal dose of hydrochlorothiazide is excreted by the kidneys unchanged for 24 hours.

    Indications:Arterial hypertension (patients who are shown combined therapy).
    Contraindications:
    If you have any of these diseases, consult a doctor before taking the drug.

    Hypersensitivity to the drug, other ACE inhibitors and sulfonylamide derivatives, anuria, severe renal failure (creatinine clearance less than 30 ml / min), angioedema, including a history of ACE inhibitors, hereditary or idiopathic angioedema edema, hemodialysis using high-flow membranes, hypercalcemia, porphyria, precoma, hepatic coma, hyperkalemia, diabetes mellitus (severe forms), pregnancy, lactation, age under 18 (efficacy and b zopasnost not installed).
    Pregnancy and lactation:
    It is not recommended to use Skopryl Plus during pregnancy and during breastfeeding, except in selected cases under special medical supervision, when the expected benefit for the mother exceeds the risk to the fetus. When establishing a pregnancy, the drug should be stopped as soon as possible. ACE inhibitors in the II and III trimester of pregnancy has adverse effects on the fetus (expressed may decrease blood pressure, renal failure, hyperkalemia, skull hypoplasia, intrauterine death). Data on the negative effects of the drug on the fetus in case of application during the I trimester are not present. For newborns and infants who have undergone intrauterine exposure to ACE inhibitors, careful monitoring is recommended to timely detect a marked decrease in blood pressure, oliguria, and hyperkalemia.
    Women in childbearing age before the drug should be excluded from pregnancy.
    Lizinopril penetrates the placenta, but there is no evidence of its penetration into breast milk. It is proven that thiazides are excreted in breast milk.
    There is no data on the removal of hydrochlorothiazide from the circulation of the newborn, also passing through the placenta.
    For the period of treatment the drug should be abolished breastfeeding.
    Dosing and Administration:

    Inside, regardless of food intake, once a day.

    Arterial hypertension

    For 1 tablet of Skopryl Plus 20 mg + 12.5 mg once a day. With insufficient antihypertensive effect, the dose can be increased to the maximum daily dose - 1 tablet of Skopryl Plus 20 mg + 25 mg once a day.

    Doses in renal failure

    In patients with KK more than 30 and less than 80 ml / min. the drug can be used only after selecting the dose of individual components of the drug. Use of the drug in patients with SC less than 30 ml / min. contraindicated (see section "Contraindications for use"). The recommended initial dose of lisinopril in uncomplicated renal failure is 5-10 mg.

    Prior therapy with diuretics

    After taking the initial dose of the drug, symptomatic arterial hypotension may occur. Such cases are more common in patients who have had a loss of fluid and electrolytes due to previous treatment with diuretics. Therefore, it is necessary to stop taking diuretics 2-3 days before the treatment with Skopryl Plus (see "Precautions for Use").

    Precautions for use:

    If you have any of these diseases, consult a doctor before taking the drug.

    Aortic stenosis / hypertrophic obstructive cardiomyopathy, bilateral renal artery stenosis or arterial stenosis of a single kidney with progressive azotemia, condition after kidney transplantation, renal failure (QC more than 30 ml / min), primary hyperaldosteronism, hypotension, bone marrow hypoplasia, hyponatremia the development of arterial hypotension in patients on a low-salt or salt-free diet), conditions accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting), connective tissue diseases (including systemic lupus erythematosus, scleroderma), diabetes mellitus, gout, hyperuricemia, ischemic heart disease, cerebrovascular diseases (including cerebral circulatory insufficiency), severe chronic heart failure, hepatic insufficiency, advanced age.

    Arterial hypotension and water-electrolyte disorders

    Most often, a marked decrease in blood pressure occurs with a decrease in the volume of circulating blood(Bcc) caused by prior therapy with diuretics, decreasing the amount of salt in the diet, dialysis, vomiting or diarrhea (see. The sections "Side effect", "Interaction with other drugs"). In patients with chronic heart failure with simultaneous renal failure or without it, a marked decrease in blood pressure is possible. It is often diagnosed in patients with severe chronic heart failure - as a result of application of high doses of diuretics, hyponatremia or impaired renal function. In such patients, treatment with the drug should be started under strict medical supervision and periodically monitor the electrolyte content in the blood serum.

    Such rules must be followed in the appointment of the drug to patients with ischemic heart disease, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to heart attack or stroke.

    Transient arterial hypotension is not a contraindication for taking the next dose of the drug.

    Prior to treatment, if possible, should be to normalize the concentration of sodium ions and / or fill bcc carefully controlled initial dose effect on the patient.

    Aortic stenosis / hypertrophic cardiomyopathy

    ACE inhibitors should be administered with caution to patients with left ventricular outflow obstruction.

    Renal impairment

    In patients with chronic heart failure, a marked decrease in blood pressure after initiation of treatment with ACE inhibitors may lead to a further deterioration in kidney function. Cases of acute renal failure are noted.

    In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney receiving ACE inhibitors, there was an increase in the concentration of urea and serum creatinine, usually reversible after discontinuation of treatment. It was more common in patients with impaired renal function.

    Patients on hemodialysis

    Anaphylactic reactions have been observed in patients undergoing hemodialysis using dialysis membranes with high permeability (for example, AN69), which simultaneously take ACE inhibitors. In such cases, it is necessary to consider the possibility of using another type of membrane for dialysis or another antihypertensive agent.

    Anaphylactoid reactions

    In patients receiving ACE inhibitors, life-threatening anaphylactoid reactions were noted during apheresis of low-density lipoprotein (LDL) using dextran sulfate.The appearance of these reactions is prevented with the temporary cessation of treatment with ACE inhibitors before each session of apheresis. In patients taking ACE inhibitors during desensitization with Hepaticoptera venom (eg, bee or aspen poison), life-threatening anaphylactoid reactions were rarely observed. These reactions can be avoided by temporarily stopping the use of an ACE inhibitor before each desensitization to the hymenoptera.

    Diseases of the liver

    Caution should be used with thiazides in patients with impaired hepatic function or progressive liver disease, since minor changes in the water-electrolyte balance may cause a sudden hepatic coma.

    Surgery / general anesthesia

    With extensive surgical interventions, as well as with the use of other drugs that cause a decrease in blood pressure, lisinopril, blocking the formation of angiotensin II, can cause a pronounced unpredictable decrease in blood pressure. The pronounced decrease in blood pressure, which is considered a consequence of this mechanism, can be eliminated by an increase in BCC.

    Before surgery (including dentistry) it is necessary to warnan anesthesiologist on the use of an ACE inhibitor.

    Hypersensitivity / Angioedema

    Angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx was rarely seen in patients treated with ACE inhibitors, including lisinopril, which can occur during any period of therapy. In this case, treatment with Skopryl Plus should be stopped as soon as possible and monitored until the symptoms regressed completely. In cases where edema is localized only on the face and lips, the general condition often passes without treatment, however, it is possible to prescribe antihistamines.

    Angioedema with edema of the larynx can be fatal. When the tongue, epiglottis or larynx are covered, airway obstruction may occur, therefore, an appropriate therapy (0.3-0.5 ml epinephrine (adrenaline) 1: 1000 subcutaneously) and / or measures to ensure airway patency should be taken immediately.

    Patients who had a history of angioedema, unrelated to previous treatment with ACE inhibitors, may be at increased risk during development with ACE inhibitor therapy (see section "Contraindications for use").

    Cough

    Reported the appearance of cough with the use of ACE inhibitors. The characteristic cough is unproductive, persistent and stops after discontinuation of treatment. In the case of a cough, it is necessary to include cough induced by ACE inhibitors in differential diagnosis.

    Potassium in the serum

    In some cases, hyperkalemia was noted. Risk factors for the development of hyperkalemia include renal failure, diabetes mellitus, administration of potassium drugs or agents that cause an increase in potassium in the blood (eg, heparin), especially in patients with impaired renal function.

    Patients who are at risk for symptomatic arterial hypotension (on a low-salt or salt-free diet) with or without hyponatremia, as well as in patients who received high doses of diuretics, the above conditions before the start of therapy with Skopryl Plus should be compensated (loss of fluid and salts) .

    Metabolic and endocrine effects

    Thiazide diuretics can affect glucose tolerance, so you need to adjust the dose of hypoglycemic agents.

    Thiazide diuretics can reduce the release of calcium ions by the kidneys and cause hypercalcemia. Expressed hypercalcemia may be a symptom of latent hyperparathyroidism. It is recommended to stop therapy with thiazide diuretics before the parathyroid gland function test.

    During the treatment with Skopryl Plus, regular monitoring of the potassium, glucose, urea, creatinine and lipid content is necessary.

    During the treatment with Skopryl Plus, it is not recommended to drink alcoholic beverages, since alcohol increases the antihypertensive effect of the drug. Care should be taken when performing physical exercises, hot weather (the risk of dehydration and excessive blood pressure lowering due to a decrease in BCC).

    Side effects:

    In most patients, side effects were mild and transient. The most common side effects: dizziness, headache. Side effects that were less common:

    From the cardiovascular system: marked reduction of blood pressure, chest pain, rarely - orthostatic hypotension, tachycardia, bradycardia, the emergence of symptoms of heart failure, impaired atrioventricular conduction, myocardial infarction.

    From the digestive system: nausea, vomiting, abdominal pain, dryness of the oral mucosa, diarrhea, dyspepsia, anorexia, changes in taste, hepatitis (hepatocellular and cholestatic), jaundice, pancreatitis, salivary gland inflammation, intestinal angioedema.

    From the central nervous system: lability of mood, violation of concentration, paresthesia, fatigue, drowsiness, convulsive twitching of the muscles of the limbs and lips, rarely - asthenic syndrome, confusion, insomnia, depression.

    From the respiratory system: dyspnea, bronchospasm, apnea, dry cough, rhinitis, sinusitis, respiratory distress syndrome, including pneumonitis and pulmonary edema, allergic alveolar / eosinophilic pneumonia.

    From the skin: urticaria, increased sweating, photosensitivity, skin itch, alopecia, exacerbation of psoriasis, pemphigus.

    Allergic reactions: angioedema, facial edema, extremities, lips, tongue, epiglottis and / or larynx (see "Precautions for Use"), skin rash, itching, Stevens-Johnson syndrome, erythema multiforme,lupus-like syndrome and exacerbation of the systemic lupus erythematosus, a syndrome that includes the acceleration of erythrocyte sedimentation rate. Positive reactions to antinuclear antibodies, eosinophilia.

    On the part of the hematopoiesis system: possible leukopenia, neutropenia, agranulocytosis, thrombocytopenia, hemolytic and aplastic anemia, enlarged lymph nodes and autoimmune disease; purpura. With long-term treatment - a decrease in hemoglobin and hematocrit, erythrocytopenia.

    From the genitourinary system: renal dysfunction, uremia, oliguria / anuria, acute renal failure, decreased potency, interstitial nephritis, glucosuria.

    Laboratory indicators: hyperkalemia and / or hypokalemia, hyponatremia, hypomagnesemia, hypochloraemia, hypercalcemia, hyperuricemia, hyperglycemia, increased urea and creatinine concentrations in the blood plasma, rarely - increased activity of "liver" transaminases, hyperbilirubinemia, hypercholesterolemia, hypertriglyceridemia, decreased glucose tolerance.

    Other: arthralgia / arthritis, myalgia, fever, fetal development disorder, gynecomastia, exacerbation of gout.

    If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, inform the doctor about it.

    Overdose:

    Symptoms of overdose, measures to help with overdose:

    Symptoms: marked decrease in blood pressure, dryness of the oral mucosa, drowsiness, urinary retention, constipation, anxiety, increased irritability.

    Giving help: induce vomiting and / or rinse the stomach, symptomatic therapy, intravenous fluids, blood pressure control, control and normalization of the water-electrolyte balance. Control of urea, creatinine and electrolytes in blood serum, diuresis.

    Features of the drug at the first reception:

    Be especially careful when taking the first dose or increasing the dose of the drug. Tell your doctor as soon as possible if you feel dizzy. After taking the initial dose of the drug, symptomatic arterial hypotension may occur.

    Features of the drug during its cancellation:

    Do not stop taking the pills until your doctor tells you in person about the possibility of stopping the drug.

    Features of the actions of a doctor (paramedic), a patient with a missed intake of one or more doses of the drug:

    Do not take a double dose to refund the missed dose. Continue to receive the prescribed scheme.

    Interaction:Special care is required when using the drug simultaneously with potassium-sparing diuretics (spironolactone, triamterene, amiloride); preparations of potassium; substitutes for salt containing potassium (the risk of hyperkalaemia increases, especially if the renal function is impaired, so they can be jointly administered only on the basis of an individual doctor's decision with regular monitoring of serum potassium and kidney function). Caution can be applied together:
    - with vasodilators, barbiturates, phenothiazines, tricyclic antidepressants, ethanol (strengthening of the hypotensive effect);
    - with non-steroidal anti-inflammatory drugs (indomethacin and etc.);
    - with estrogens (decrease of antihypertensive action of lisinopril);
    - with lithium (liberation of lithium may decrease, resulting in increased cardiotoxic and neurotoxic effects of lithium);
    - with antacids and colestyramine - reduce absorption in the gastrointestinal tract. The drug weakens the effect of hypoglycemic agents for ingestion, norepinephrine, epinephrine and antidotal drugs, increases the neurotoxicity of salicylates, enhances the effects of cardiac glycosides, the action of peripheral muscle relaxants, reduces the excretion of quinidine. The drug reduces the effect of oral contraceptives. With the simultaneous administration of methyldopa, the risk of hemolysis increases.
    Effect on the ability to drive transp. cf. and fur:During the use of the drug should refrain from the management of vehicles and mechanisms, as possible the occurrence of dizziness, especially at the beginning of the course of treatment.
    Form release / dosage:
    Tablets of 20 mg + 12.5 mg and 20 mg + 25 mg.


    Packaging:10 tablets per blister are perforated from aluminum foil and PVC film. 3 blisters (30 tablets) together with instructions for use in a pack of cardboard.
    Storage conditions:At a temperature of no higher than 25 ° C. Keep out of the reach of children!
    Shelf life:3 years. Do not use after expiry date.
    Terms of leave from pharmacies:On prescription
    Registration number:LP-000603
    Date of registration:21.09.2011
    Date of cancellation:2016-09-21
    The owner of the registration certificate:Alkaloid, JSCAlkaloid, JSC Macedonia
    Manufacturer: & nbsp
    Alkaloid AO The Republic of Macedonia
    Representation: & nbspALKALOID, AOALKALOID, AO
    Information update date: & nbsp28.12.2015
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