Chinapril is a prodrug that is hydrolysed to the active metabolite - quinaprilat - an ACE-converting enzyme inhibitor that works in plasma and tissues. ACE catalyses the conversion of angiotensin I to angiotensin II, which is a potent vasodilator. ACE inhibition results in a decrease in angiotensin II and a reduction in aldosterone release; the bradykinin metabolism is also likely to be inhibited. Quinapril has no effect on the lipid profile and has no negative effect on Glucose metabolism. Chinapril reduces peripheral and renal resistance. There are no clinically significant changes in renal blood flow and glomerular filtration rate. Chinaprilat causes lowering of blood pressure in supine, sitting and standing position. At the recommended doses, the maximum effect is obtained after 2-4 h. In some patients, achieving the maximum antihypertensive effect may take 2-4 weeks. The bioavailability of the active metabolite - quinaprilat is 30-40% of the administered quinapril oral dose. The maximum concentration in the blood is obtained after about 2 hours after administration. About 97% of the active substance binds to plasma proteins. When using multiple doses of T0,5 is 3 hours. The stationary state is reached within 2-3 days. Quinaprilate is excreted mainly in unchanged form in the urine.
Contraindications:
Hypersensitivity to quinapril, the remaining ingredients of the preparation and to other ACE inhibitors. II and III trimester of pregnancy. History of angioedema associated with prior use of ACE inhibitors. Hereditary or idiopathic angioedema. Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (glomerular filtration rate, GFR <60 ml / min / 1.73 m2).
Precautions:
Caution should be exercised in the case of decreased intravascular volume (eg as a result of diuretics, dietary salt restriction, dialysis, diarrhea or vomiting, and in patients with severe renin-dependent hypertension), in patients with impaired renal function, heart failure, patients with stenosis mitral valve and narrowing the outflow pathway from the left ventricle eg aortic valve stenosis, subvalvular stenosis or hypertrophic cardiomyopathy (in cases when haemodynamically significant stenosis should not be used quinapril), in patients with bilateral renal artery stenosis or renal artery stenosis the only active kidneys, in patients with or without liver disease, in patients with diabetes, patients undergoing major surgery or during anesthesia with hypotensive drugs and patients with history of anesthesia, not associated with the administration of ACE inhibitors. Patients who may be included in the high-risk group and for whom treatment should be started in the hospital include: patients treated with high doses of loop diuretics (eg> 80 mg furosemide) or several diuretics, patients with hypovolaemia, hyponatraemia or systolic blood pressure <90 mmHg, patients treated with high doses of vasodilators with creatinine in the blood> 150 μmol / l or patients> 70 years. Particular care should be exercised when using quinapril in patients with collagenosis treated with immunosuppressants, Allopurinol or procainamide, and in patients with which these factors coexist with each other, especially if you have previously had kidney problems. Due to the risk of hyperkalemia, caution should be used in patients with renal failure, diabetes, treated with potassium-sparing diuretics, taking potassium supplements or potassium-containing potassium substitutes, as well as patients taking other medicines that may cause an increase in potassium in the blood (eg heparin).Patients with primary hyperaldosteronism do not respond to treatment with antihypertensive drugs acting through the renin-angiotensin system - ACE inhibitors are not recommended in these patients. Experience with quinapril in patients with severe renal impairment (creatinine clearance <10 ml / min) and dialysis patients is inadequate. There is no experience with the use of quinapril in patients after a recent kidney transplant surgery - the drug is not recommended in this group of patients. The efficacy and safety of the drug in children and adolescents has not been confirmed - the preparation is not recommended in this group of patients. In patients receiving ACE inhibitors treated with hemodialysis using dialysis membranes with high permeability, anaphylactoid reactions have been observed - consideration should be given to using a different type of dialysis membrane or other group of antihypertensive agents. For patients requiring desensitisation (eg Hymenoptera venom) or for LDL-apheresis treatment with dextran sulphate, it is recommended to temporarily discontinue ACE inhibitors due to the risk of life-threatening anaphylactoid reactions. The concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalaemia and renal dysfunction (including acute renal failure) - therefore, dual blocking of the RAA system is not recommended by concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren. If the use of a dual RAA blockade is absolutely necessary, it should only be carried out under the supervision of a specialist, and the vital parameters of the patient, such as kidney function, electrolyte concentration and blood pressure should be closely monitored. In patients with diabetic nephropathy, ACE inhibitors and angiotensin II receptor antagonists should not be used concurrently.
Pregnancy and lactation:
The preparation should not be used during the first trimester of pregnancy. The drug is contraindicated in the second and third trimester of pregnancy and during breastfeeding. Prolonged exposure to ACE inhibitors in the second and third trimester of pregnancy causes toxic effects on the fetus (renal dysfunction, oligohydramnios, delayed ossification of the skull) and the newborn (renal failure, hypotension, hyperkalemia). The drug is excreted in human milk.
Side effects:
Common (> 1/100): pain and dizziness, fatigue, hypotension, cough, nausea, vomiting, diarrhea. Uncommon (> 1/1000, <1/100): sleep disorders, nervousness; paresthesia, drowsiness; palpitations, cardiac arrest, chest pain, angina pectoris; orthostatic hypotension; neutropenia; sinusitis, pharyngitis, upper respiratory tract infections; indigestion, abdominal pain, dry mouth, bloating; rash, pruritus, urticaria, exfoliative dermatitis, increased sweating, eczema; proteinuria (sometimes with worsening of renal function); impotence; weakness, angioneurotic edema. Rarely (> 1 / 10,000, <1/1000): depression, confusion; balance disorders, neuropathy; blurred vision, amblyopia; Tinnitus; tachycardia, syncope, myocardial infarction, transient ischemic attacks, cerebral haemorrhage; agranulocytosis; bronchospasm, dyspnea, bronchitis, rhinitis, exacerbation of asthma symptoms; taste disorders, constipation, pancreatitis, inflammation of the tongue, intestinal obstruction; liver dysfunction; erythema multiforme, Stevens-Johnson syndrome, epidermal necrolysis, psoriasis-like lesions, alopecia, pemphigus, hypersensitivity to light; joint pain, myalgia, back pain; kidney problems, hyperkalemia. Very rare (<1 / 10,000): allergic alveolitis, anaphylactoid reactions; cholestatic jaundice, hepatitis; kidney failure. There are reports of a syndrome consisting of: fever, polyserositis, vasculitis, myalgia, pain / arthritis, positive ANA titre, accelerated ESR, eosinophilia and leukocytosis. Other gynaecomastia, vasculitis, decreased hemoglobin and hematocrit values have been reported with other ACE inhibitors; it can not be ruled out that these side effects are specific to the whole group of drugs. An increase in creatinine and urea nitrogen in the blood has been observed.
Dosage:
Orally. Adults.Arterial hypertension. monotherapy: the recommended starting dose is 10 mg once a day. Depending on the clinical response, the dose may be gradually increased (doubling the dose every 3-4 weeks) to the maintenance dose of 20-40 mg per day administered in 1-2 doses. Typically, the maximum maintenance dose is 40 mg per day, in some patients doses up to 80 mg per day have been used.Concomitant use of diuretics: if possible, the diuretic should be discontinued 2-3 days before the start of quinapril treatment; the recommended starting dose of quinapril is 2.5 mg / day. Then the dose should be gradually increased (keeping the appropriate intervals between the Next dose increase) until the optimal therapeutic response is obtained.Congestive heart failure: the recommended starting dose is 2.5 mg per day. Then the dose should be gradually increased (every 2-3 weeks) until an effective therapeutic dose (up to 40 mg per day) is given, which is given in 1-2 doses, simultaneously with a diuretic and / or cardiac glycoside. Usually, 10-20 mg doses 1-2 times a day with other medicines are effective in long-term treatment. Do not exceed the maximum dose of 40 mg per day. In patients who are included in high-risk groups, treatment should be started in a hospital.Special groups of patients. In the elderly, the recommended starting dose for the treatment of primary hypertension is 2.5 mg; then the dose is gradually increased until an optimal therapeutic response is obtained. In patients with impaired renal function with a creatinine clearance above 60 ml / min, the recommended starting dose is 10 mg, with a clearance of 30-60 ml / min - 5 mg; at a clearance of 10-30 ml / min - 2.5 mg.
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