2010/09/17

Accupro



Composition, structure and packing

Tablets, coated in white, oval, biconvex, with the risk and the number "5" on both sides.

1 tab. hinapril (in the form of hydrochloride) 5 mg.

Excipients: magnesium carbonate, gelatin, lactose, krospovidon, magnesium stearate.

The composition of the shell: Opadry White OY-S-7331 (gipromelloza, gidroksipropiltsellyuloza, titanium dioxide, macrogol 400), wax candle.

Tablets, coated in white, triangular, biconvex, with risks on both sides and the number "10" on one side.

1 tab. hinapril (in the form of hydrochloride) 10 mg Excipients: magnesium carbonate, gelatin, lactose, krospovidon, magnesium stearate.

The composition of the shell: Opadry White OY-S-7331 (gipromelloza, gidroksipropiltsellyuloza, titanium dioxide, macrogol 400), wax candle.

Tablets, coated white, round, biconvex, with the number "20" on one side and scored on both sides of the tablets. 1 tab. hinapril (in the form of hydrochloride) 20 mg Excipients: magnesium carbonate, gelatin, lactose, krospovidon, magnesium stearate.

The composition of the shell: Opadry White OY-S-7331 (gipromelloza, gidroksipropiltsellyuloza, titanium dioxide, macrogol 400), wax candle.

Coated tablets red-brown, oval, biconvex, with the number "40" on one side and "PD 535" - on the other. 1 tab. hinapril (in the form of hydrochloride) 40 mg Excipients: magnesium carbonate, gelatin, lactose, krospovidon, magnesium stearate.

The composition of the shell: Opadry brown Y-5-9020G (gipromelloza, gidroksipropiltsellyuloza, titanium dioxide, macrogol 400, iron oxide red), wax candle.

Clinico-pharmacological group: ACE inhibitor.

Pharmacological action

Antihypertensive drugs, ACE inhibitor. Hinaprila hydrochloride is a salt hinaprila - ethyl ether hinaprilata ACE inhibitor without a sulfhydryl group.

Hinapril quickly deesterifitsiruetsya with the formation hinaprilata (hinapril diatsid - the main metabolite), which is a potent inhibitor of ACE. ACE - a peptidildipeptidaza catalyzing the conversion of angiotensin I to angiotensin II, which has a vasoconstrictor action and is involved in controlling vascular tone and function through various mechanisms, including stimulation of the adrenal cortex production of aldosterone. Hinapril inhibits the activity of circulating and tissue ACE and thus reduces the pressor activity and the production of aldosterone. The reduction of angiotensin II on the feedback mechanism leads to increased secretion of renin and its activity in blood plasma.

The principal mechanism of antihypertensive action hinaprila consider the suppression of renin-angiotensin-aldosterone system, but the drug takes effect even in patients with low renin hypertension. ACE is identical in structure kininaze II - an enzyme that causes destruction of bradykinin - peptide with powerful vasodilating properties. It remains unknown whether the value of increased levels of bradykinin to the therapeutic effect hinaprila.

The duration of antihypertensive action hinaprila was higher than the duration of its inhibitory effect on circulating ACE. Revealed a close correlation between the suppression of tissue ACE and the duration of antihypertensive action of the drug. ACE inhibitors, including hinapril can increase sensitivity to insulin.

Application hinaprila 10-40 mg in patients with arterial hypertension of mild to moderate severity leads to a decrease in BP as a seated position and standing, and has minimal effect on heart rate. Antihypertensive effect occurs within 1 h and usually reaches its maximum within 2-4 h after ingestion. In some patients, the maximum antihypertensive effect was observed 2 weeks after starting treatment.

Antihypertensive effects of the drug when used in recommended doses in most patients lasted 24 hours and stored on a background of long-term therapy.

Hemodynamic study in patients with hypertension showed that blood pressure reduction under the influence of hinaprila accompanied by a decrease TPVR and resistance of renal vessels, while the heart rate, cardiac index, renal blood flow, glomerular filtration rate and filtration fraction changed little or not change.

The therapeutic effect of the drug in the same daily doses comparable to the elderly (over 65) and in patients with younger age, the elderly frequency of adverse events is not increased. Application hinaprila in patients with chronic heart failure leads to a decrease TPVR, mean arterial pressure, systolic and diastolic blood pressure, pulmonary capillary wedge pressure and improve cardiac output.

In 149 patients who underwent coronary artery bypass grafting, treatment hinaprilom a dose of 40 mg / day compared with placebo reduced the frequency of postoperative ischemic complications within one year after surgery.

In patients with confirmed coronary atherosclerosis, which do not have hypertension or heart failure, hinapril improves endothelial dysfunction in coronary and brachial arteries. Hinaprila effect on endothelial function is associated with an increase in nitric oxide production. Endothelial dysfunction believed important mechanism for the development of coronary atherosclerosis. The clinical significance of improvement of endothelial function is not installed.

Pharmacokinetics

Absorption, distribution, metabolism

Once inside hinaprila Cmax plasma levels achieved within 1 h. The degree of absorption of the drug is about 60%. Eating does not affect the degree of suction, but the speed and extent of absorption hinaprila somewhat reduced, while receiving fatty foods. Hinapril metabolized to hinaprilata (about 38% accepted oral dose) and the small number of other inactive metabolites. T1 / 2 hinaprila from blood plasma is approximately 1 hour hinaprilata Cmax in plasma achieved after approximately 2 hours after ingestion hinaprila. Approximately 97% hinaprila or hinaprilata circulates in the blood plasma in protein-bound form. Hinapril and its metabolites do not penetrate the BBB.

Withdrawal

Hinapril and hinaprilat derived mainly from urine (61%), as well as with the feces (37%); T1 / 2 is about 3 hours

Pharmacokinetics in special clinical situations

In patients with renal failure c T1 / 2 hinaprilata increases with decreasing spacecraft. Pharmacokinetic studies in patients with c end stage renal failure receiving treatment program hemodialysis or continuous ambulatory peritoneal dialysis, showed that dialysis has little effect on the excretion hinaprila and hinaprilata. Revealed a linear correlation between clearance hinaprilata from the plasma and spacecraft. Putting hinaprilata also decreases in the elderly (≥ 65 years) and correlated with their renal function.

Statement
hypertension (as monotherapy or in combination with thiazide diuretics and beta-blockers);
Chronic heart failure (in combination with diuretics and / or cardiac glycosides).

Dosage regimen

In conducting monotherapy hypertension Akkupro recommended initial dose in patients not receiving diuretics is 10 mg or 20 mg 1 time per day. Depending on the clinical effect of the dose can be increased (doubling) to maintenance dose of 20 mg or 40 mg / day, which is usually administered in a reception or divide into 2 parts. As a rule, change the dose at intervals of 4 weeks. The majority of patients achieve adequate control of blood pressure during long-term treatment can be through the use of the drug 1 time / day. The maximum daily dose - 80 mg.

In patients who continued receiving diuretic therapy, the recommended starting dose is 5 mg Akkupro; continue its increase (as above) until until you reach the optimal effect.

In chronic heart failure using the product is shown as a supplement to therapy with diuretics and / or cardiac glycosides. The recommended starting dose in patients with chronic heart failure is 5 mg of 1 or 2 times / day, after taking the medication the patient should be observed in order to identify symptomatic arterial hypotension. If the initial dose tolerability Akkupro good, it can be raised to an effective dose, which is typically 10-40 mg / day in 2 equal reception in conjunction with concomitant therapy.

In case of violation of renal function the recommended initial dose is 5 mg Akkupro patients with CC more than 30 ml / min and 2.5 mg in patients with CC less than 30 ml / min. If portability is a good initial dose, then the next day you can assign Akkupro 2 times / day.

In the absence of severe arterial hypotension or significant deterioration of renal function dose can be increased to weekly intervals in the light of clinical and hemodynamic effects. Given the clinical and pharmacokinetic data in patients with impaired renal function the initial dose is recommended to select as follows.

The recommended starting dose Akkupro in elderly patients is 10 mg 1 time / day and in its subsequent increase until until you reach the optimal therapeutic effect.

Side effect

Adverse events in the application Akkupro are usually poorly marked and transient. Most often cited headache (7.2%), dizziness (5.5%), cough (3.9%), fatigue (3.5%), rhinitis (3.2%), nausea and / or vomiting (2.8%), myalgia (2.2%) . It should be noted that in the typical case of cough is nonproductive, persistent and goes after the cessation of treatment.

Adverse events observed in 0.5-1% of patients receiving Akkupro (in combination with a diuretic or without) are listed below.

On the part of the hemopoietic system: hemolytic anemia, thrombocytopenia.

Allergic reactions: anaphylactic reaction.

From the central nervous system and peripheral nervous system: depression, irritability, drowsiness, vertigo.

On the part of the organ of vision: the weakening of view.

From the Cardiovascular: angina pectoris, palpitation, tachycardia, postural hypotension, syncope, vasodilatation.

On the part of the digestive system: dry mouth or throat, flatulence, pancreatitis. Dermatological reactions: alopecia, exfoliative dermatitis, increased sweating, pemphigus, photosensitivity, pruritus, rash.

On the part of the musculoskeletal system: arthralgia.

From the urinary system: urinary tract infection. Increased (more than 1.25 times compared with FHG) the level of serum creatinine and blood urea nitrogen were observed respectively in 2% and 2% of patients receiving monotherapy Akkupro. The probability of increase of these parameters in patients while receiving diuretics, higher than the intake of one Akkupro. With continued therapy both indicators often return to normal.

On the part of the reproductive system: reduction of potency. Other: edema peripheral and generalized, hyperkalemia, and in rare cases - agranulocytosis and neutropenia, although their connection with the reception Akkupro remains unclear. Rare: patients receiving hinapril, reported cases of angioedema (0.1%).

When using other ACE inhibitors observed in cases of eosinophilic pneumonitis and hepatitis, which in the treatment hinaprilom rare.

Contraindications
angioedema in history associated with treatment with ACE inhibitors.

Cautions

In the treatment with ACE inhibitors are described cases of angioedema in the head and neck in the treatment of hinaprilom he met at 0.1% of patients. When laryngism or angioedema face, tongue or epiglottis should immediately discontinue treatment hinaprilom; patient should appoint adequate treatment and watch it until edema edema. Swelling of the face and lips usually passes without treatment, to reduce the symptoms can be used antihistamines. Angioedema, a spectacular gorge, can lead to death. If you defeat the language, the epiglottis or larynx likely to develop airway obstruction, required emergency treatment, which includes the n / introduction to the solution of epinephrine (adrenaline) 1:1000 (0.3-0.5 ml), and other measures. In the treatment with ACE inhibitors are also described cases of angioedema of the intestine. The patients noted abdominal pain (with or without nausea and vomiting) in some cases without prior angioedema of face and a normal level of C-1 esterase. The diagnosis is established by computed tomography of the abdominal area, ultrasound examination or during surgical intervention. The symptoms disappeared after discontinuation of ACE inhibitors. Therefore, patients with pain in the abdomen, taking ACE inhibitors during the differential diagnosis must take into account the possibility of angioedema of the intestine. Patients who have a history of angioedema observed is not associated with ACE inhibitor, may be at increased risk of its development in the treatment of drugs in this group. Patients receiving ACE inhibitors during desensitizing treatment with poison Hymenoptera (Hymenoptera: wasps, bees, ants), may develop anaphylactoid reactions, life threatening. In such patients these reactions were avoided by suspending the ACE inhibitors, but they have evolved again after accidentally taking the drugs. Anaphylactoid reactions during treatment with ACE inhibitors have been reported in patients who simultaneously held low density lipoprotein apheresis with dextran-sulfate absorption. In patients treated by hemodialysis using certain vysokoprotochnyh membranes (eg, from poliakrilnitrila), increased risk of anaphylactoid reactions, while treatment with ACE inhibitor. To avoid them, you should use other antihypertensive drugs or other membranes for hemodialysis. Symptomatic hypotension is rarely encountered in patients with uncomplicated hypertension treated with Akkupro, but it is a possible complication of ACE inhibitor therapy in patients with a low content of salts in the body, or hypovolemia, for example, after treatment with diuretics, while limiting salt intake or on the background of dialysis.

If you have symptoms of arterial hypotension should put the patient, and if necessary, start in / infusion of isotonic saline. Transient hypotension is not a contraindication to further treatment, but in such cases it is advisable to discuss the possibility of reducing the dose or to assess the feasibility of simultaneous treatment with diuretics. In patients receiving diuretics, the appointment Akkupro may lead to the development of symptomatic arterial hypotension. If the patient requires diuretic therapy, then it is advisable to suspend the 2-3 days before the start of treatment hinaprilom. If monotherapy hinaprilom not provide sufficient antihypertensive effect, the diuretic therapy should be resumed. If the diuretic can not be canceled, then Akkupro designate a low initial dose. In patients with chronic heart failure who have increased risk of severe arterial hypotension, treatment Akkupro should start with the recommended dose under close medical supervision, patients should be monitored during the first 2 weeks of treatment, as well as in all cases where the dose is increased Akkupro.

Treatment with ACE inhibitors in patients with uncomplicated hypertension, in rare cases accompanied by agranulocytosis and bone marrow suppression, and these adverse events were more frequent in patients with impaired renal function, especially those with connective tissue diseases.

In the treatment Akkupro agranulocytosis occur rarely.

If you use this drug (and other ACE inhibitors) in patients with connective tissue diseases and / or kidney disease should control the number of leukocytes in the blood.

In susceptible patients suppression of the renin-angiotensin-aldosterone system can lead to changes in renal function.

In patients with severe heart failure whose renal function may depend on the renin-angiotensin-aldosterone system, treatment with ACE inhibitors, including hinapril, may be associated with oliguria and / or increasing azotemia and, rarely, acute renal failure and / or In rare cases, death. T1 / 2 hinaprila increases with decreasing spacecraft.

Patients with CC <60 ml / min hinapril should be appointed at a lower initial dose.

In these patients, the dose should be gradually increased in view of the therapeutic effect under the control of renal function, although in clinical studies, there has been a further deterioration of renal function in the treatment of drug.

Some patients with hypertension or heart failure with no apparent signs of initial vascular lesions of the kidneys in the treatment of Akkupro, especially in combination with a diuretic, there was increased levels of urea nitrogen and serum creatinine, which was usually minor and reversible.

The risk of such changes was higher in patients with initial impaired renal function. In such cases, may require dose reduction and / or cancellation of the diuretic and / or hinaprila.

In patients with arterial hypertension with unilateral or bilateral renal artery stenosis, treatment with ACE inhibitors in some cases saw an increase in the level of urea nitrogen in blood and serum creatinine. These changes are almost always reversible and disappeared after discontinuation of ACE inhibitor and / or diuretic. In such cases during the first few weeks of treatment should monitor renal function.

Hinapril in combination with a diuretic should be used with caution in patients with impaired function or progressive liver disease, because small changes in water and electrolyte balance may cause the development of hepatic coma. Metabolism hinaprila to hinaprilata normally occurs under the action of liver esterase. Concentrations hinaprilata reduced in patients with alcoholic cirrhosis due to violations deeterifikatsii hinaprila.

In patients receiving hinapril, like other ACE inhibitors, may increase potassium levels in blood serum. With simultaneous application hinapril can reduce hypokalemia caused by thiazide diuretics. Combined use hinaprila with Potassium-sparing diuretics has not been studied. Given the risk of further increasing the level of potassium in the blood serum, combination therapy with potassium-sparing diuretics should be carefully controlled by the level of potassium in the blood serum. ACE inhibitor therapy is sometimes accompanied by the development of hypoglycemia in diabetic patients receiving insulin or oral hypoglycemic drugs; diabetics may require more careful monitoring and correction doses of hypoglycemic drugs. In the treatment with ACE inhibitors, including hinapril, noted the development of cough. In a typical case, it is counter-productive, persistent and goes after the cessation of therapy.

In the differential diagnosis of cough should take into account its possible relationship with ACE inhibitors. Patients who receive surgery or general anesthesia, ACE inhibitors should be used with caution, as they block the formation of angiotensin II, caused by the compensatory secretion of renin. This may lead to arterial hypotension, which is eliminated by the introduction of plasma substitutes. Patients should be warned that inadequate fluid intake, increased sweating or dehydration can lead to excessive blood pressure decrease by reducing the BCC. Other causes of dehydration, such as vomiting or diarrhea may also lead to a marked reduction in BP. In such cases, patients should seek medical advice. If you have any symptoms of infection (eg, sore throat, fever), patients should consult a doctor immediately, since they may be a manifestation of neutropenia.

Use in Pediatrics

Safety and efficacy hinaprila in children and adolescents under the age of 18 is not installed. Effects on ability to drive motor vehicles and management mechanisms should use extreme caution, especially in the beginning of treatment, involvement in potentially hazardous activities that require attention and quickness of psychomotor reactions.

Overdose

Symptoms characteristic of BP decrease.

Treatment: It is advisable to / in the introduction of liquid; spend symptomatically. Hemodialysis and peritoneal dialysis have little effect on excretion hinaprila and hinaprilata.

Drug Interactions

Tetracycline and other drugs that interact with magnesium

The use of tetracycline with hinaprilom accompanied by a decrease absorption of tetracycline by approximately 28-37% due to the presence of magnesium carbonate as an excipient hinaprila forms for oral administration. At the same time appointing hinaprila and tetracycline should be given to the possibility of such interaction.

Lithium preparations

In patients treated with drugs lithium and ACE inhibitors, saw an increase in the level of lithium in blood serum and signs of lithium toxicity through increased excretion of sodium. To prescribe these drugs at the same time be careful, the treatment shown in the regular determination of the level of lithium in blood serum. Simultaneous diuretic may increase the risk of lithium intoxication.

Diuretki

As in the treatment of other ACE inhibitors, patients receiving diuretics, especially when diuretic therapy was initiated recently, the appointment hinaprila sometimes leads to excessive blood pressure decrease. Arterial hypotension was the first dose using hinaprila can be minimized by suspending diuretic a few days before the start of treatment. If you cancel diuretic is not possible, hinapril should be appointed at a lower initial dose. If the patient continues diuretic, it should be observed for up to 2 h after the first dose hinaprila. If a patient receiving hinapril, Showing Potassium-sparing diuretics (eg spironolactone, triamterene or amiloride), potassium preparations, and salt substitutes containing potassium, then put them should be carefully controlled levels of potassium in the blood serum, because increased risk of hyperkalemia.

Other drugs

No evidence of clinically significant pharmacokinetic interaction hinaprila with propranolol, hydrochlorothiazide, digoxin, or cimetidine was not revealed.

Application hinaprila 2 times / day did not significantly affected the anticoagulant effect of warfarin after a single application of its (estimated on the basis of prothrombin time).

Terms and Conditions of storage

The drug should be stored out of reach of children at or above 30 ° C.

Shelf life - 3 years. -Childhood and adolescence to 18 years.