Zofenopril (Zophenoprilum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

ACE Inhibitors

Included in the formulation
  • Zocardis® 7.5
    pills inwards 
    Berlin-Chemie / Menarini Pharma, GmbH     Germany
    • АТХ:

    C.09.A.A.15   Zofenopril

    Pharmacodynamics:
    Zofenopril is an ACE inhibitor. The mechanism of action is associated with a decrease in the formation of angiotensin II from angiotensin I, a decrease in its content leads to a direct decrease in the release of aldosterone. Reduces the overall peripheral vascular resistance, systolic and diastolic blood pressure, post- and preload on the myocardium. Expands arteries more than veins; with a reflex increase in the heart rate is not noted. Reduces the degradation of bradykinin, increases the synthesis of prostaglandins. The hypotensive effect is more pronounced with a high plasma renin concentration than with a normal or reduced concentration of plasma. Lowering blood pressure within the therapeutic limits does not affect cerebral circulation, blood flow in the vessels of the brain is maintained at a sufficient level and against a background of low blood pressure. Strengthens coronary and renal blood flow.
    With prolonged use reduces hypertrophy of the left ventricle of the myocardium and myocytes of the walls of arteries of resistive type,prevents the progression of heart failure and slows the development of dilatation of the left ventricle. Improves the blood supply of the ischemic myocardium. Reduces the aggregation of platelets.
    Zofenopril calcium is a prodrug, since the active inhibitor is a free sulfhydryl compound - zofenoprilat, formed as a result of thioester hydrolysis.
    The hypotensive effect with ingestion comes in 1 hour, reaches a maximum after 4-6 hours and lasts up to 24 hours. Some patients need therapy for several weeks to achieve the optimal level of blood pressure. With heart failure, a noticeable clinical effect is observed with long-term treatment - 6 months or more.
    Pharmacokinetics:
    Zofenopril calcium is rapidly and completely absorbed in the digestive tract and is almost completely metabolized in the liver with the formation of an active metabolite of zofenoprilat, Cmax which is reached in blood 1.5 hours after taking the drug.
    Approximately 88% of zofenopril calcium binds to plasma proteins.
    The half-life of zofenoprilat is 5.5 hours, its total clearance is 1300 ml / min after oral administration of zofenopril calcium.Zofenoprilat is excreted mainly by the kidneys (69%), through the intestine - 26%.
    Indications:
    Arterial hypertension of mild and moderate severity.
    Acute myocardial infarction with symptoms of heart failure in patients with stable hemodynamic parameters and not receiving thrombolytic therapy.
    ICD-10

    IX.I10-I15.I10   Essential [primary] hypertension

    IX.I10-I15.I15   Secondary Hypertension

    IX.I20-I25.I21.9   Acute myocardial infarction, unspecified

    Contraindications:Hypersensitivity to zofenopril and other ACE inhibitors, history of angioedema, associated with treatment with ACE inhibitors, porphyria, severe liver dysfunction, severe renal failure, pregnancy, breastfeeding, under 18 years of age (efficacy and safety not established).
    Carefully:Primary aldosteronism, bilateral stenosis of the renal arteries, stenosis of the single kidney artery, hyperkalemia, condition after kidney transplantation, aortic stenosis, mitral stenosis (with hemodynamic disorders), idiopathic hypertrophic subaortic stenosis,connective tissue diseases, cerebrovascular diseases, diabetes mellitus, renal failure (proteinuria more than 1 g per day), liver failure, in patients with a salt-restricted or hemodialysis diet, simultaneous use with immunosuppressants and saluretic drugs, in the elderly (over 75) years), psoriasis, in patients with a reduced volume of circulating blood (as a result of diuretic therapy, while limiting consumption of table salt, hemodialysis, diarrhea and vomiting) - increased risk of exposure apnea and a pronounced decrease in blood pressure after applying even the initial dose of an ACE inhibitor.
    Pregnancy and lactation:Contraindicated during pregnancy and during breastfeeding (because zofenopril calcium secreted into breast milk). Do not use women of childbearing age in the absence of effective contraception.
    Dosing and Administration:Inside, regardless of the time of ingestion (before, during or after a meal), with a sufficient amount of liquid.
    Arterial hypertension
    Patients with normal renal and hepatic function. To achieve optimal blood pressure, treatment starts with 2 tablets once a day; when the hypotensive effect is insufficient, the dose is gradually increased with an interval of 4 weeks.
    Usually the effective dose is 4 tablets once a day.
    The maximum daily dose is 8 tablets taken once or in 2 divided doses (4 tablets each).
    Patients with a violation of water-salt balance. Initial therapy with ACE inhibitors requires correction of salt and / or water deficiencies, discontinuation of ongoing diuretic therapy for 2-3 days before the initiation of the ACE inhibitor and begins at a dose of 2 tablets 7.5 mg once daily. If this is not possible, the treatment is started with 1 tablet of 7.5 mg once a day.
    Patients with impaired renal function or who are on hemodialysis. In patients with mild renal impairment (creatinine clearance greater than 45 mL / min), no dose reduction is required. Patients with moderate to severe renal impairment (creatinine clearance less than 45 mL / min) are prescribed 1/2 of the therapeutic dose once a day.
    The initial dose for patients on hemodialysis is 1/4 the dose used for patients with normal renal function.
    Patients with impaired hepatic function. In patients with mild and moderate degree of impaired liver function, the initial dose of the drug is half the dose used in patients with normal liver function.
    Elderly patients. In elderly patients with normal clearance of creatinine, dose adjustment is not required. In elderly patients with a creatinine clearance less than 45 mL / min, a 1/2 day dose is recommended.
    Acute myocardial infarction (as part of combination therapy)
    Treatment begins within 24 hours after the onset of the first symptoms of myocardial infarction and continues for 6 weeks.
    In case of excessive lowering of blood pressure at the beginning of treatment or during the first three days after myocardial infarction, the initial dose does not increase or cancel the drug.
    After 6 weeks of therapy, therapy may be discontinued in patients with no evidence of left ventricular failure or heart failure.
    To correct left ventricular failure or heart failure, as well as hypertension, treatment can be continued for a long time.
    Side effects:
    From the cardiovascular system: excessive lowering of blood pressure, orthostatic collapse; rarely - chest pain, stenocardia, myocardial infarction (usually associated with a marked decrease in blood pressure), arrhythmias (atrial brady or tachycardia, atrial fibrillation), palpitations, thromboembolism of the pulmonary artery branches, pain in the heart, fainting.
    From the side of the central nervous system: dizziness, headache, weakness, insomnia, anxiety, depression, confusion, increased fatigue, drowsiness (2-3%), very rarely with high doses - nervousness, paresthesia.
    From the sense organs: rarely - violations of the vestibular apparatus, hearing and vision impairment, tinnitus.
    From the digestive tract: dry mouth, anorexia, dyspeptic disorders (nausea, diarrhea or constipation, vomiting, abdominal pain); very rarely - intestinal obstruction, pancreatitis, impaired liver function and bile secretion, hepatitis, jaundice.
    From the respiratory system: unproductive dry cough; very rarely - interstitial pneumonitis, bronchospasm, dyspnea, rhinorrhea, pharyngitis.
    From the urinary system: impaired renal function, proteinuria.
    Allergic reactions: rarely - skin rash, angioedema, swelling of the face, extremities, lips, tongue, glottis and / or larynx, dysphonia, polymorphic erythema, exfoliative dermatitis; very rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis, pemphigus, pruritus, urticaria, photosensitivity, serositis, vasculitis, myositis, arthralgia, arthritis, stomatitis, glossitis.
    From the laboratory indicators: hyperkreatininemia, increased urea levels, increased activity of hepatic transaminases, hyperbilirubinemia, hyperkalemia, hyponatremia. In some cases, a decrease in hematocrit and hemoglobin, an increase in the rate of erythrocyte sedimentation, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmune diseases), eosinophilia are noted.
    Overdose:Treatment is symptomatic. There is no specific antidote.
    Interaction:The hypotensive effect of ACE inhibitors can be intensified by other antihypertensive agents, diuretics, general anesthetics, antipyretic and analgesic agents, ethanol.With the simultaneous administration of zofenopril with nonsteroidal anti-inflammatory drugs, hypotensive effect of zofenopril may be reduced, with potassium-sparing diuretics - hyperkalemia, with lithium salts - slowing down of lithium excretion. Immunosuppressants, allopurinol, cytotoxic drugs increase hematotoxicity. With simultaneous administration with hypoglycemic agents, the risk of hypoglycemia increases.
    Special instructions:
    A transient, pronounced lowering of blood pressure is not a contraindication for continuing treatment with the drug after stabilizing blood pressure. In the case of a reiterated decrease in blood pressure, the dose should be reduced or the drug should be withdrawn.
    With the development of excessive lowering of blood pressure, the patient is transferred to a horizontal position with a low headboard, if necessary, 0.9% sodium chloride solution and plasma-substituting drugs are administered.
    The use of high-flow dialysis membranes increases the risk of developing an anaphylactic reaction. Correction of the dosing regimen on days free from dialysis should be carried out depending on the level of arterial pressure.Before and after treatment with ACE inhibitors, control of blood pressure, blood counts (hemoglobin, potassium, creatinine, urea), activity of hepatic enzymes, protein in the urine is necessary.
    It should be carefully monitored for patients with severe heart failure, coronary heart disease and cerebral vascular disease, in which a sharp drop in blood pressure can lead to myocardial infarction, stroke, or renal dysfunction. Sudden withdrawal of treatment does not lead to the syndrome of "withdrawal" (a sharp rise in blood pressure).
    Patients with an indication of angioedema development in the anamnesis have an increased risk of its development with the administration of ACE inhibitors.
    For newborns and infants who have been exposed to the intrauterine effect of ACE inhibitors, careful monitoring is recommended to detect the marked decrease in blood pressure, oliguria, hyperkalemia and neurological disorders that are possible due to a reduction in renal and cerebral blood flow when the arterial pressure caused by ACE inhibitors decreases.In oliguria, maintenance of arterial pressure and renal perfusion is necessary by the introduction of appropriate fluids and vasoconstrictors.
    In patients with a decreased renal function, one dose should be reduced or the intervals between doses should be increased.
    During the selection of the therapeutic dose, it is necessary to refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions, since dizziness is possible, especially after the initial dose of an ACE inhibitor in patients taking diuretics.
    Care should be taken when doing physical exercises in hot weather (the risk of dehydration and excessive lowering of blood pressure due to a decrease in the volume of circulating blood). Before surgery (including dentistry), it is necessary to alert the surgeon / anesthesiologist about the use of ACE inhibitors.
    During treatment, it is not recommended to drink alcoholic beverages, since alcohol enhances the hypotensive effect of the drug.
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