DIROTON

Active material: Lisinopril
When ATH: C09AA03
CCF: ACE inhibitor
ICD-10 codes (testimony): I10, I21, I50.0, N08.3
When CSF: 01.04.01.02
Manufacturer: GEDEON RICHTER Ltd. (Hungary)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills white or nearly white, flat, disc-shaped, chamfered, labeled “2.5” on one side and with Valium – another.

Excipients: magnesium stearate, talc, mannyt, corn starch, calcium hydrogen phosphate dihydrate.

14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.

Pills white or nearly white, flat, disc-shaped, chamfered, labeled “5” on one side and with Valium – another.

Excipients: magnesium stearate, talc, mannyt, corn starch, calcium hydrogen phosphate dihydrate.

14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.

Pills white or nearly white, quadrangular, lenticular, labeled “10” on one side and with Valium – another.

Excipients: magnesium stearate, talc, mannyt, corn starch, calcium hydrogen phosphate dihydrate.

14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.

Pills white or nearly white, pentagonal, lenticular, labeled “20” on one side and with Valium – another.

Excipients: magnesium stearate, talc, mannyt, corn starch, calcium hydrogen phosphate dihydrate.

14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.

Pharmacological action

ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. Reduction of angiotensin II leads to a direct reduction in aldosterone release. It reduces the degradation of bradykinin, and increases the synthesis of prostaglandins. Reduces PR, FROM, preload, the pressure in the pulmonary capillaries, It causes an increase in cardiac output and increase tolerance to myocardial stress in patients with chronic heart failure. It expands the artery to a greater extent, than veins. Some effects are explained by the influence on the tissue renin-angiotensin system. Prolonged use reduces myocardial hypertrophy and arterial walls resistive type. It improves blood flow to ischemic myocardium.

ACE inhibitors prolong survival in patients with chronic heart failure, slow the progression of left ventricular dysfunction in patients, myocardial infarction without clinical symptoms of heart failure.

The onset of action of the drug – through 1 no, reaches through 6-7 h and maintained for a 24 no. Duration of the effect is also dependent on the size of the dose. When hypertension effect observed in the first days after the start of treatment, stable operation is developed through 1-2 of the month. With a sharp lifting of the drug was not observed pronounced increase in blood pressure.

Diroton^® reduces albuminuria. Patients with hyperglycemia helps normalize the function of the damaged glomerular endothelial. No effect on blood glucose in diabetic patients, and does not lead to increased incidence of hypoglycemia.

Pharmacokinetics

Absorption

After oral lisinopril is absorbed from the gastrointestinal tract. Absorption averages 30%, bioavailability – 29%. C_max achieved through 6 no. After taking the drug at a dose 10 mg / C_max is 32-38 ng / ml. Eating does not affect the absorption of the drug.

Distribution

Lisinopril hardly binds to plasma proteins. The permeability of the BBB and placental barrier is low.

Metabolism

Lisinopril is not biotransformed in the body.

Deduction

Excreted by the kidneys in unchanged form.

T_1/2 is 12.6 no .

Testimony

- Arterial hypertension (as monotherapy or in combination with other antihypertensive drugs);

- Congestive heart failure (in a combination therapy for the treatment of patients, taking drugs digitalis and / or diuretics);

- Acute myocardial infarction (first 24 h with stable hemodynamics to maintain these indicators and the prevention of left ventricular dysfunction and heart failure);

- Diabeticheskaya nephropathy (reducing albuminuria in patients with insulin-dependent diabetes in normal and AD patients with non-insulin dependent diabetes mellitus and hypertension).

Dosage regimen

The drug is taken orally 1 time / day, in the morning, for all indications, before or after meals, It is always approximately the same time of the day.

At essential hypertension sick, not receiving other antihypertensives, appoint 10 mg 1 time / day. The usual daily maintenance dose – 20 mg. The maximum daily dose – 40 mg.

Full effect is usually through 2-4 weeks of treatment, What to consider when increasing the dose. With insufficient clinical effect of the drug can be combined with other antihypertensive agents.

If the patient has received prior treatment with diuretics, the need to stop taking them for 2-3 the day before the application Diroton^®. If you can not cancel diuretics, the initial dose Diroton^® should not exceed 5 mg / day. In this case, after the first dose recommended medical supervision for a few hours (maximum effect is achieved after about 6 no), tk. can develop a pronounced reduction in blood pressure.

At renovascular hypertension or other conditions with increased activity of the renin-angiotensin-aldosterone system It is also advisable to assign a lower starting dose - 2.5-5 mg / day under close medical supervision (BP control, renal function, potassium concentration in blood serum). Maintenance dose should be determined depending on the dynamics of AD.

At renal failure since, that lisinopril excreted by the kidneys, initial dose should be determined according to the creatinine clearance, then in accordance with the reaction should be set in a maintenance dose of frequent monitoring of renal function, sodium and potassium concentration in blood serum.

At chronic heart failure the initial dose – 2.5 mg 1 time / day, which can be increased to usual maintenance daily dose 5-20 mg. The daily dose should not exceed 20 mg.

At acute myocardial infarction (in a combination therapy) the first day is prescribed 5 mg, then – 5 mg a day, 10 mg – two days later, and then 10 mg 1 time / day. In patients with acute myocardial infarction drug should be used for at least 6 weeks. At the beginning of treatment or during the first 3 days after acute myocardial infarction in patients with low systolic blood pressure (≤120 mm Hg) the drug should be administered at a dose of 2.5 mg. In the case of BP reduction (systolic blood pressure ≤100 mmHg) while taking Diroton^® daily dose 5 mg can be temporarily reduced to 2.5 mg. In case of prolonged significant decrease in blood pressure (systolic blood pressure <90 mmHg. more 1 no), Treatment diroton^® discontinue.

At diabetic nephropathy in patients with insulin-dependent diabetes mellitus Diroton^® administered at a dose 10 mg 1 time / day. If necessary, the dose can be increased to 20 mg 1 time / day to achieve diastolic BP values ​​below 75 mmHg. in the sitting position. Patients with non-insulin dependent diabetes drug administered in the same dose, in order to achieve diastolic BP values ​​below 90 mmHg. in the sitting position.

Side effect

CNS: often – dizziness, headache (5-6%), weakness; sometimes – fatigue, drowsiness, jerking of the limbs and lips; rarely – asthenic syndrome, mood lability, confusion, reduced potency.

From the digestive system: diarrhea (3%), nausea, vomiting (1-3%), dry mouth, anorexia, dyspepsia, changes in taste, stomach ache, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis.

Cardio-vascular system: orthostatic hypotension, chest pain (1-3%); sometimes – marked reduction in blood pressure; heartbeat, tachycardia, myocardial infarction, cerebrovascular stroke in patients at risk of disease, due to the significant decrease in blood pressure.

On the part of the immune system: (0.1%) angioedema (face, lips, language, larynx, or epiglottis, upper and lower limbs); rarely – syndrome, including acceleration of ESR, arthralgia and the appearance of antinuclear antibodies.

From the hematopoietic system: sometimes – leukopenia, neutropenia, agranulocytosis, thrombocytopenia, long-term treatment – a slight decrease in hemoglobin concentration and hematocrit, erythropenia.

The respiratory system: dry cough (3%).

From the urinary system: rarely (<1%) – impairment of renal function, oligurija, anurija, acute renal failure, uremia, proteinuria.

Dermatological reactions: skin rash (1-3%); rarely (<1%) – hives, increased perspiration, itching, alopecia.

From the laboratory parameters: sometimes (>1%) – hyperkalemia, azotemia, hyperuricemia, giperʙiliruʙinemija, increase in liver enzymes (particularly those with a history of renal disease, diabetes and hypertension, renovascular).

Other: rarely (<1%) – myalgia, fever, impaired fetal growth.

Contraindications

- A history of angioedema (incl. the application of ACE inhibitors);

- Hereditary angioedema;

- Up to 18 years (efficacy and safety have not been established);

- Hypersensitivity to lizinoprilu or other ACE inhibitors.

FROM caution It should be prescribed the drug for severe impaired renal function, bilateral renal artery stenosis or stenosis of the artery to a solitary kidney with progressive azotemia, condition after kidney transplantation, renal failure, azotemii, hyperkalemia, aortic stenosis, hypertrophic obstructive cardiomyopathy, primary hyperaldosteronism, hypotension, cerebrovascular diseases (incl. cerebrovascular insufficiency), CHD, coronary insufficiency, autoimmune systemic diseases of connective tissue (incl. Scleroderma, systemic lupus erythematosus), suppression of bone marrow hematopoiesis, hypovolemic states (incl. due to diarrhea, vomiting); patients, located on a diet with restriction of sodium, elderly patients.

Pregnancy and lactation

Application Diroton^® contraindicated during pregnancy. Lisinopril crosses the placental barrier. In determining the pregnancy the drug should be discontinued as soon as possible. ACE inhibitors in the II and III trimester of pregnancy has adverse effects on the fetus (may be marked reduction of blood pressure, renal failure, hyperkalemia, skull hypoplasia, fetal death). Data about the negative effects of the drug on the fetus when used in the I trimester there. For newborns and babies, who underwent in utero effects of ACE inhibitors, It is recommended to install close observation for early detection of significant decrease in blood pressure, oligurii, hyperkalemia.

Data on the penetration of lisinopril in breast milk is not. If necessary, the appointment during lactation breastfeeding should be discontinued.

Cautions

Most often, there is a marked reduction in blood pressure while reducing the volume of fluid, caused by diuretic therapy, reduction of the salt content in food, dializom, diarrhea or vomiting. In chronic heart failure with simultaneous renal insufficiency with or without the opportunity to express blood pressure reduction. Most pronounced reduction in blood pressure is detected in patients with severe stage of chronic heart failure, as a consequence of the use of diuretics at higher doses, hyponatremia or impaired renal function. In these patients, treatment diroton^® we should start under close medical supervision (with caution in the selection of dose and diuretics).

Similar rules should be followed in the appointment of Diroton^® CHD patients, cerebrovascular insufficiency, in which the sharp decline in blood pressure can lead to heart attack or stroke.

Transient hypotensive response is not a contraindication to receiving the next dose.

When using Diroton^® in some patients with chronic heart failure, but with normal or low blood pressure, there may be a decrease in blood pressure, which is usually not a cause for discontinuation of treatment.

Prior to treatment diroton^®, possibly, sodium concentration should be normalized and / or fill the volume of fluid lost, carefully monitor the effect of the initial dose Diroton^® in the patient's blood pressure.

In the case of stenosis of the renal artery (especially in bilateral stenosis or artery stenosis sole kidney), and circulatory failure due to lack of sodium and / or liquid, use Diroton^® can lead to renal dysfunction, Acute renal failure, which is usually irreversible after drug withdrawal.

In acute myocardial infarction shows the use of standard therapy (thrombolytics, acetylsalicylic acid, beta-blockers). Perhaps the use of Diroton^® together with the in / or administration using therapeutic transdermal systems nitroglycerin.

With extensive surgery, as well as the application of other medicaments, causing a decrease in blood pressure, Lisinopril, blocking the formation of angiotensin II, can cause unpredictable pronounced reduction in blood pressure.

In elderly patients, the use of the standard dose leads to a higher concentration of drug in the blood, therefore requires special care in determining the dose, despite, that differences in the antihypertensive effect Diroton^® in older and younger patients were found.

Since we can not exclude the potential risk of agranulocytosis, requires periodic monitoring of blood picture.

In applying the drug in a dialysis membrane of polyacrylonitrile may occur anaphylactic shock, it is recommended that a different type of dialysis membrane, or administration of other antihypertensive drugs.

Effects on ability to drive vehicles and management mechanisms

No data on the effect of lisinopril on the ability to drive and use machines, However, it should be taken into account, that may cause vertigo, so be careful.

Overdose

Symptoms: marked reduction in blood pressure.

Treatment: if necessary, symptomatic therapy (in / in a liquid, control and normalization of blood pressure, water and electrolyte balance).

Lisinopril can be removed from the body by dialysis.

Drug Interactions

Precautions should be prescribed Diroton^® concurrently with potassium-sparing diuretics (spironolactone, triamterene, amilorid), potassium, salt substitutes, containing potassium, tk. increased risk of hyperkalemia, especially with impaired renal function. Therefore these combinations should only be based on the individual judgment of the treating physician in regular monitoring of serum potassium and renal function.

While the use of diuretics and other antihypertensive drugs developed an additive antihypertensive effect (the risk of significant decrease in blood pressure).

In an application with NSAIDs (incl. with indomethacin), Estrogen, and adrenostimulyatorov reduced antihypertensive effect of lisinopril.

In an application with lithium, lithium excretion may be reduced, so you should regularly monitor the concentration of lithium in blood serum.

In an application with antacids and kolestiraminom lisinopril reduces the absorption from the gastrointestinal tract.

In an application Diroton^® can enhance the effect of ethanol (alcohol).

While the use of diuretics lisinopril reduces the excretion of potassium.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children at temperature from 15 ° to 30 ° C. Shelf life – 3 year.