CO-RENITEC PILLS 20MG/12.5MG

MERCK SHARP and DOHME (MERCK SHARP and DOHME B.V.)

Dosage form: tab. 20 mg + 12.5 mg: 14, 28 or 56 pcs.

Pills yellow, round, biconvex, with a grooved edge, engraved with "MSD 718" on one side and painted on the other.

Excipients: sodium bicarbonate, lactose monohydrate (aqueous lactose), corn starch, pregelatinized corn starch, iron dye yellow oxide, Magnesium stearate.

7 pieces - blisters (2) - packs cardboard.
7 pieces - blisters (4) - packs cardboard.
56 pcs. - polyethylene bottles (1) - packs cardboard.

Indications: - treatment of arterial hypertension in patients for whom combination therapy is indicated. - treatment of arterial hypertension in patients for whom combination therapy is indicated.
Application:

The drug is prescribed by mouth, regardless of the meal.

At hypertension initial dose - 1 tab. 1 time / day If necessary, the dose can be increased to 2 tab. 1 time / day

Symptomatic arterial hypotension may develop at the beginning of Co-oncology, more often in patients with impaired water-electrolyte balance due to previous treatment with diuretics. Diuretic therapy should be discontinued 2-3 days before the start of the use of co-treatment.

Have patients with impaired renal function thiazides may not be effective enough, and QC ≤ 30 ml / min (i.e., moderate to severe renal failure) are ineffective.

At QC 80-30 ml / min Coenitic should be used only after a preliminary selection of doses of each of the components.

At mild renal failure The recommended dose of Enalapril maleate taken alone is between 5 mg and 10 mg.

Contraindications:

- anuria;

- angioedema in the history of, associated with the appointment of previously ACE inhibitors, as well as hereditary or idiopathic angioedema;

- hypersensitivity to the drug;

- hypersensitivity to other sulfonamide derivatives.

WITH caution the drug should be prescribed for aortic stenosis, cerebrovascular diseases (including cerebrovascular insufficiency), ischemic heart disease, chronic heart failure, severe autoimmune systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), bone marrow inhibition, sugar diabetes, hyperkalemia, bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney, condition after kidney transplantation, renal and / or liver failure, on the background of Ety sodium restriction, for conditions involving reduction bcc (including diarrhea, vomiting), elderly patients.

Side effects:

In clinical studies, side effects were usually mild, transient, and in most cases did not require interruption of treatment.

Cardiovascular: 1-2% - orthostatic effects, including hypotension; rarely - fainting, hypotension, regardless of body position, palpitations, tachycardia, chest pain.

Nervous system: often - dizziness, fatigue (usually took place at a lower dose and rarely required discontinuation of the drug); 1-2% - asthenia, headaches; rarely - insomnia, drowsiness, systemic dizziness, paresthesias, irritability.

Respiratory: 1-2% cough; rarely - shortness of breath.

Gastrointestinal: 1-2% - nausea; rarely - pancreatitis, diarrhea, vomiting, dyspepsia, abdominal pain, flatulence, constipation, dry mouth.

Musculoskeletal system: 1-2% - muscle cramps; rarely - arthralgia.

Allergic reactions: rarely - angioedema of the face, extremities, lips, tongue, glottis and / or larynx. There are rare reports of the development of angioedema of the intestine in connection with taking ACE inhibitors, including enalapril.

Dermatologic: rarely - Stevens-Johnson syndrome, hyperhidrosis, skin rash, itching.

Urogenital: rarely - impaired renal function, renal failure.

From the reproductive system: 1-2% - impotence; rarely - decreased libido.

From the laboratory indicators: hyperglycemia, hyperuricemia, hypo-or hyperkalemia, increased blood levels of urea, serum creatinine, increased liver enzyme activity and / or elevated serum bilirubin are possible (these indicators usually returned to normal after stopping Co-therapy); in some cases - a decrease in hemoglobin and hematocrit.

Other: rarely - tinnitus, gout. Symptom complex is described, the possible manifestations of which are fever, serositis, vasculitis, myalgia, myositis, arthralgia / arthritis, a positive test for antinuclear antibodies, accelerated ESR, eosinophilia and leukocytosis; possible development of photosensitivity.

Overdose:

Symptoms: severe arterial hypotension, starting approximately 6 hours after taking the drug, and stupor. After taking enalapril maleate in doses of 330 mg and 440 mg, the concentration of enalaprilat in the blood plasma was 100 and 200 times higher, respectively, at therapeutic doses.

With an overdose of hydrochlorothiazide, the most common symptoms are caused by hypokalemia, hypochloraemia, hyponatremia and dehydration due to excessive diuresis. If therapy with digitalis has been previously administered, the arrhythmia may be aggravated due to hypokalemia.

Treatment: Co-Renitek should be canceled; requires close medical supervision. A gastric lavage is recommended if the drug has been recently taken; conducting symptomatic and maintenance therapy in order to correct disorders of water and electrolyte balance and arterial hypotension.Data on specific therapy of overdose is not available.

In case of enalapril maleate overdose, IV injection of saline is recommended, and administration of angiotensin II is effective. Enalaprilat can be removed from the systemic circulation by hemodialysis.

Pharmachologic effect:

Combined antihypertensive drug, which consists of an ACE inhibitor (enalapril maleate) and thiazide diuretic (hydrochlorothiazide). It has antihypertensive and diuretic effect.

Enalapril is an ACE inhibitor that catalyzes the conversion of angiotensin I to the pressor substance angiotensin II. After absorption, enalapril is converted by hydrolysis to enalaprilat, which inhibits ACE. Inhibition of ACE leads to a decrease in the concentration of angiotensin II in the blood plasma, which entails an increase in plasma renin activity (due to the elimination of the reverse negative reaction to changes in renin production) and a decrease in aldosterone secretion.

ACE is identical to the enzyme kininase II, so enalapril can also block the destruction of bradykinin, a peptide with a vasodilating action. The significance of this mechanism in the therapeutic action of enalapril requires clarification. Despite the fact that enalapril reduces blood pressure by suppressing the renin-angiotensin-aldosterone system, which plays an important role in regulating blood pressure, the drug lowers blood pressure even in patients with arterial hypertension with a low content of renin.

A decrease in blood pressure is accompanied by a decrease in OPSS, a slight increase in cardiac output and the absence of changes or minor changes in heart rate. As a result of enalapril, the renal blood flow increases, the glomerular filtration rate remains unchanged. However, in patients with initially reduced glomerular filtration, its rate usually increases.

Antihypertensive therapy with enalapril leads to a significant regression of left ventricular hypertrophy and the preservation of the systolic function of the left ventricle.

Enalapril therapy is accompanied by a favorable effect on the ratio of lipoprotein fractions and the absence of influence or a favorable effect on the total cholesterol content.

Taking enalapril in patients with arterial hypertension leads to a decrease in blood pressure in both standing and lying positions without a significant increase in heart rate.

Symptomatic postural hypotension rarely develops. In some patients, achieving an optimal reduction in blood pressure may require several weeks of therapy. Interruption of therapy with enalapril does not cause a sharp rise in blood pressure.

Effective inhibition of ACE activity usually develops 2-4 hours after a single dose of enalapril orally. The onset of the antihypertensive effect begins within 1 hour, the maximum decrease in blood pressure is observed 4-6 hours after taking the drug. The duration of action depends on the dose.However, when used in recommended doses, the antihypertensive effect and hemodynamic effects persist for 24 hours.

Hydrochlorothiazide has a diuretic and antihypertensive effect, increases the activity of renin. Although enalapril itself exhibits an antihypertensive effect even in patients with arterial hypertension against a background of low renin concentrations, the concomitant use of hydrochlorothiazide in these patients leads to a more pronounced decrease in blood pressure.

Enalapril reduces the loss of potassium ions caused by the use of hydrochlorothiazide. Enalapril and hydrochlorothiazide have a similar dosing regimen. Therefore, Co-Renitec is a convenient dosage form for co-administration of enalapril and hydrochlorothiazide.

The use of a combination of enalapril and hydrochlorothiazide leads to a more pronounced decrease in blood pressure compared to monotherapy with each drug separately and allows you to maintain the antihypertensive effect of Co-nitrate drug for at least 24 hours.

Pharmacokinetics:

Suction

After ingestion of enalapril, maleate is rapidly absorbed. Cmax enalapril in serum is observed within 1 h after administration. After ingestion, absorption is approximately 60%.

Eating does not affect the absorption of enalapril. The duration of absorption and hydrolysis of enalapril is similar for the various recommended therapeutic doses.

After absorption, enalapril is rapidly hydrolyzed to form the active substance enalaprilat, a powerful ACE inhibitor. Cmax enalaprilat in serum is observed after 3-4 hours after taking the dose of enalapril inside.

Removal

Enalapril is excreted primarily by the kidneys. The main metabolites detected in urine are enalaprilat, which constitutes approximately 40% of the dose, and unchanged enalapril. Data on other significant metabolic pathways of enalapril, with the exception of hydrolysis to enalaprilat, is not available. The concentration curve of enalaprilat in the blood plasma has a long end phase, apparently due to its binding to ACE. In persons with normal renal function, a stable concentration of enalaprilat is reached on the 4th day from the start of enalapril. T1/2 enalaprilat with oral administration of the drug is 11 hours.

Metabolism and distribution

Not metabolized. Hydrochlorothiazide penetrates the placental barrier, but does not penetrate the BBB.

Removal

T1/2 hydrochlorothiazide from 5.6 to 14.8 h. Quickly excreted by the kidneys. At least 61% of the dose taken by mouth is excreted unchanged within 24 hours.

Regular intake of the combination of enalapril and hydrochlorothiazide does not affect or slightly affect the bioavailability of each component of the drug. The use of the combined tablet of the drug Co-Renitec is bioequivalent to simultaneously taking its ingredients in separate dosage forms.

During pregnancy:

It is not recommended to use the drug Co-renitec during pregnancy.When pregnancy is established, the drug should be immediately discontinued.

Appointment of ACE inhibitors in the II and III trimesters of pregnancy can cause disease or death of the fetus or newborn. The negative effect of ACE inhibitors on the fetus and newborn is manifested by arterial hypotension, renal failure, hyperkalemia and / or cranial hypoplasia. Perhaps the development of oligohydramnios, apparently due to impaired renal function of the fetus. This complication can lead to contracture of the limbs, deformation of the skull, including its facial part, to lung hypoplasia.

The use of diuretics in women during pregnancy is not recommended, since there is a risk of jaundice in the fetus and newborn, thrombocytopenia, and possibly other side effects observed in adult patients.

If Co-Renitek is prescribed during pregnancy, the patient should be warned of the potential risk to the fetus. In those rare cases where the prescription of a drug during pregnancy is considered necessary, periodic ultrasound examinations should be performed to assess the condition of the fetus, as well as the intraamniotic space.

Newborns whose mothers took Coeniticus should be carefully monitored for the development of arterial hypotension, oliguria and hyperkalemia. Enalapril, which penetrates the placental barrier, was removed from the blood circulation of the newborn by peritoneal dialysis with some favorable clinical effect, it can theoretically be removed by exchange transfusion.

Enalapril and thiazides, incl. hydrochlorothiazide, are excreted in breast milk. If necessary, the use of the drug during lactation breastfeeding should be discontinued.

When liver failure: C caution should be prescribed the drug for liver failure.
Storage:

The drug should be stored out of reach of children at a temperature not exceeding 30 ° C. The shelf life for tablets in blisters is 3 years, for tablets in high-density bottles is 2 years.

Special instructions:

Have patients with impaired renal function thiazides may not be effective enough, and CC less than or equal to 30 ml / min (i.e. with severe renal failure) are ineffective.

At QC 80-30 ml / min Coenitic should be used only after a preliminary selection of doses of each of the components.

At moderate renal failure The recommended dose of enalapril maleate taken alone is between 5 mg and 10 mg.

Terms of prescription: The drug is released by prescription.
Latin name: CO-RENITEC