Chinapril is converted into the active metabolite - quinaprilat - a long-acting ACE inhibitor (an enzyme that catalyzes the conversion of angiotensin I to vasopressure angiotensin II, as well as the breakdown of bradykinin). Suppression of ACE activity results in a decrease in plasma angiotensin II and a reduction in aldosterone secretion. The maximum antihypertensive effect occurs 2-4 h after a single dose. The availability of quinaprilat accounts for 30-40% of the administered quinapril oral dose. Cmax is achieved after about 2 hours (food does not affect the absorption of quinapril). The drug is approximately 97% bound to plasma proteins. T0,5 quinaprilat is 3 hours. Steady state is achieved after 2-3 days of treatment. Chinaprilat is mainly excreted unchanged form by the kidneys. In patients with renal failure T0,5 quinaprilat is prolonged and the concentration is increased. In patients with severe hepatic impairment, the concentration of quinaprilat is reduced due to inhibition of quinapril hydrolysis.
Contraindications:
Hypersensitivity to quinapril, other ACE inhibitors or other components of the preparation. History of angioneurotic edema associated with previous treatment with ACE inhibitors. Hereditary or idiopathic angioneurotic edema. II and III trimester of pregnancy. Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (glomerular filtration rate, GFR <60 ml / min / 1.73 m2).
Precautions:
Renal function and blood pressure should be monitored during treatment. Particularly cautiously used in patients with highly energized renin-angiotensin-aldosterone system, due to the risk of significant hypotension (closely monitor initiation and dose adjustment) - this applies to patients: with hypovolaemia (as a result of diuretic therapy, dialysis, salt reduction in diet, diarrhea or vomiting); with severe renin-dependent hypertension; with symptomatic heart failure with concomitant or impaired renal function; with renal arterial hypertension (with bilateral renal artery stenosis or stenosis of the artery of the sole kidney). Similar recommendations should be used in patients with ischemic heart disease and cerebrovascular disorders, in which a significant reduction in blood pressure can lead to a heart attack or cerebrovascular accident. Since the use of diuretics may contribute to the occurrence of hypotension, it may be necessary to reduce the dose and / or discontinue diuretic therapy. If hypotension occurs during treatment with quinapril, the patient should be positioned on the back and, if necessary, given a saline infusion of physiological saline. Transient hypotension is not a contraindication to the administration of the Next dose of quinapril, which can usually be administered without difficulty when the blood pressure increases after increasing the volume of fluids. Caution should also be exercised in patients undergoing major surgery or under general anesthesia with hypotensive agents, as quinapril may block the production of angiotensin II, secondary to compensatory renin release; if hypotension occurs and it is suspected that this is due to the above mechanism, it can be corrected by supplementing the volume of fluids. Quinapril should be used with caution in patients with mitral valve stenosis or impaired left ventricular outflow, e.g. aortic valve stenosis and hypertrophic cardiomyopathy. In patients with impaired renal function (creatinine clearance <60 ml / min), potassium and creatinine should be monitored during treatment with quinapril. In patients with bilateral renal artery stenosis or stenosis of the artery supplying blood to a single kidney treated with an ACE inhibitor, an increase in serum urea and creatinine was observed (these changes were generally transient after discontinuation of the drug); this particularly applies to patients with renal failure. There are no data available on the use of quinapril in patients who have recently had a kidney transplant - quinapril is not recommended for these patients.Special care should be taken in patients with vascular collagen, using immunosuppressive drugs, taking Allopurinol or procainamide or in patients who co-exist with these factors, in particular coexistence of renal impairment - monitor the patient for infection and periodically control the number of white blood cells. In diabetic patients treated with oral antidiabetic agents or insulin, blood Glucose monitoring should be closely monitored during the first month of treatment with an ACE inhibitor. Caution is required in patients at risk of hyperkalemia: with renal insufficiency, diabetes mellitus as well as in people taking potassium salts, potassium sparing diuretics and other substances that increase potassium levels - if blood co-infusion is required, regular monitoring of potassium levels should be performed. Co-administration of quinapril and lithium is not recommended. In patients undergoing dialysis with high permeability, there is a high probability of anaphylactic reactions - consideration should be given to using an antihypertensive agent from another group or other type of dialysis membranes. In patients requiring venom desease desensitization or LDL-apheresis treatment with dextran sulphate, it is recommended to temporarily discontinue ACE inhibitors due to the risk of life-threatening anaphylactic reactions. In patients who develop angioneurotic edema of the face, limbs, lips, tongue, mucous membranes, glottis and or larynx, the drug should be immediately discontinued, appropriate therapy should be instituted and the patient monitored until the signs of edema have completely resolved (fatal angioedema has been observed associated with laryngeal or tongue swelling). Angioedema of the gut should be taken into account in the differential diagnosis of abdominal pain in patients treated with ACE inhibitors. The black patients are more likely to have angioedema. In black patients, quinapril may be less effective. In case of jaundice or a significant increase in liver enzymes, quinapril should be discontinued and appropriate treatment should be given. In the differential diagnosis of cough, cough induced by ACE inhibitors should be considered. 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. The use of quinapril in children and adolescents <18 years is not recommended.
Pregnancy and lactation:
The use of quinapril in the first trimester of pregnancy is not recommended (there is a risk of teratogenicity). Use in the second and third trimester of pregnancy is contraindicated. Chinapril used in the second and third trimester of pregnancy is toxic to fetal development (deterioration of renal function, oligohydramnios, delayed ossification of the skull) and newborn (renal failure, hypotension, hyperkalemia) - when exposure to the drug occurred from the second trimester of pregnancy, it is recommended an ultrasound examination of the fetus skull and kidneys; children whose mothers took the drug during pregnancy should be closely monitored for hypotension. The concentration of quinapril in breast milk is very low. Although this concentration does not seem clinically relevant, it is not recommended to use the product during breastfeeding of premature babies and newborns (first few weeks of life), due to potential cardiovascular and kidney effects and insufficient clinical experience. For older infants, the use of quinapril during breastfeeding may be considered if treatment is necessary for the mother and the child is observed for side effects.
Side effects:
Common: dizziness, headache, hypotension, cough, upper respiratory tract infection, dyspnoea, pharyngitis, sinusitis, nausea, vomiting, diarrhea, hyperkalemia, fatigue. Uncommon: neutropenia, sleep disturbances, nervousness, paresthesia, fainting, drowsiness, labyrinthine dizziness, palpitations, chest pain, tachycardia, angina pectoris, cardiac arrest, myocardial infarction, vasodilatation, orthostatic hypotension, indigestion , abdominal pain, dry mouth, stomach inflammation, tongue inflammation, intestinal obstruction, eruptions, pruritus, urticaria, exfoliative dermatitis, rash, urinary tract infections, painful or difficult urination, frequent urination, liver failure, fever, anaphylactoid reactions. Rarely: agranulocytosis, white blood cell disorder, depression, confusion, lethargy, neuropathy, cerebral hemorrhage, transient ischemic attacks, amblyopia, visual disturbances, tinnitus, bronchospasm, asthma severity, rhinitis, eosinophilic inflammation, inflammation bronchitis, dysgeusia, constipation, pancreatitis, alopecia, photosensitivity, pemphigus, psoriasis-like rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, angioneurotic edema, joint pain, muscle pain, back pain, renal dysfunction , impotence, hepatitis. Very rare: liver dysfunction, cholestatic jaundice. Occasional: hemolytic anemia, thrombocytopenia. Not known: balance disorders, angioneurotic edema, swelling. In addition, there was a transient increase in blood creatinine and urea (especially in patients receiving diuretic therapy), decreased platelets and white blood cells, increased liver enzymes and bilirubin in the blood, cases of hemolytic anemia in patients with congenital G-6 deficiency -PDH. There have been reports of rare cases of agranulocytosis, as well as the syndrome which included: fever, serositis, muscle pain, joint pain, arthritis, positive ANA titre, ESR increase, eosinophilia and leukocytosis. When other ACE inhibitors have been used, gynecomastia and vasculitis have been observed, as well as a small reduction in hemoglobin and hematocrit - it can not be ruled out that these side effects are specific for this class of drugs.
Dosage:
Orally.Arterial hypertension. monotherapy: the recommended starting dose is 10 mg once a day. The dose can be increased if the current use does not bring the desired therapeutic effect within 3-4 weeks. The usual maintenance dose is 20-40 mg per day. Quinapril should be given as a single dose or as two divided doses. For most patients, a single dose is appropriate.Combination therapy with diuretics: if possible, diuretic should be discontinued 2-3 days prior to initiating quinapril treatment. If diuretic therapy can not be discontinued, quinapril should be started with a 2.5 mg dose. Renal function and serum potassium should be monitored. The maintenance dose should be adjusted depending on the pressure obtained. If necessary, diuretic therapy may be restarted.Uncompensated heart failure. Where appropriate, quinapril should be used as a supplement to the treatment or in combination with a diuretic and / or digitalis. Treatment can be started on an outpatient basis. However, in patients with severe or unstable heart failure, impaired renal function, reduced circulating blood volume, hyponatremia, or systolic blood pressure <90 mmg Hg, treatment should be started at the hospital. This also applies to combination therapy with other vasodilators and high doses of loop diuretics (> 80 mg furosemide), and patients ≥ 70 years of age. Patients should be carefully monitored during the first 2 weeks of treatment and whenever the dose of quinapril or a diuretic is changed. Initially, a dose of 2.5 mg is administered, after which the patient should be carefully monitored for possible symptomatic hypotension.The quinapril dose can be gradually increased to 40 mg daily administered in 2 divided doses. Appropriate control of symptoms in patients is usually achieved at doses of 10-20 mg per day administered in 2 divided doses. Patients with mild to moderate heart failure who are haemodynamically stable over a period of at least one month receiving a 20 mg daily dose given in 2 divided doses may also receive the medicine once a day.Special groups of patients. In patients with renal impairment, the starting dose of quinapril should be reduced depending on the creatinine clearance:> 60 ml / min - 10 mg / day; 30-60 ml / min - 5 mg / day; 10-30 ml / min - 2.5 mg / day. There are currently no data available on patients with creatinine clearance <10 ml / min, including dialysis patients. Dialysis has no apparent effect on the excretion of quinaprilat. If a sufficient response to treatment is not obtained within 3 months, a change in dose should be considered. Elderly patients are advised to start with 5 mg once a day. The presence of food does not affect the absorption of quinapril. The tablets should be swallowed with a full glass of water.
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