On LORISTA

Active material: Gidroxlorotiazid, Lozartan
When ATH: C09DA01
CCF: Antihypertensive drugs
ICD-10 codes (testimony): I10
When CSF: 01.09.16.05
Manufacturer: KRKA d.d. (Slovenia)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills, Film-coated yellow to yellow with greenish tint, Oval, slightly biconcave.

Excipients: pregelatinized starch, microcrystalline cellulose, lactose monohydrate, magnesium stearate.

The composition of the shell: gipromelloza, macrogol 4000, quinoline yellow dye (E104), Titanium dioxide (E171), talc.

7 PC. – blisters (2) – packs cardboard.
7 PC. – blisters (4) – packs cardboard.
7 PC. – blisters (8) – packs cardboard.
7 PC. – blisters (12) – packs cardboard.
7 PC. – blisters (14) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (6) – packs cardboard.
10 PC. – blisters (9) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.
14 PC. – blisters (4) – packs cardboard.
14 PC. – blisters (6) – packs cardboard.
14 PC. – blisters (7) – packs cardboard.

Pharmacological action

Combined antihypertensive drug.

Lozartan – selective antagonist of angiotensin II receptor type AT₁ non-protein nature.

In vivo and in vitro losartan and its biologically active metabolite carboxy (EXP-3174) block all physiologically significant effects on angiotensin II AT₁-receptors regardless of the route of its synthesis: It leads to an increase in plasma renin activity, It reduces the concentration of aldosterone in blood plasma.

Losartan indirectly causes the activation of AT₂-receptors by increasing the level of angiotensin II. Losartan does not inhibit the activity of kininazy II, enzyme, which is involved in the metabolism of bradykinin.

Reduces PR, the pressure in the pulmonary circulation; reduces afterload, It has a diuretic effect.

It prevents the development of myocardial hypertrophy, improves exercise tolerance in patients with chronic heart failure.

Losartan 1 time / day resulted in a statistically significant reduction in systolic and diastolic blood pressure. During the day losartan uniformly control blood pressure, wherein the antihypertensive effect corresponds to the natural circadian rhythm. The decrease in blood pressure at the end of the action dose was approximately 70-80% the effect on the peak of the drug, through 5-6 h after administration. Withdrawal is not observed; Losartan is also no clinically significant effect on heart rate.

Losartan is effective in men and women, and in elderly (≥65 years) and younger patients (≤65 years).

Gidroxlorotiazid – tiazidnый diuretic, diuretic effect which involves a violation of the reabsorption of sodium ions, Chlorine, Potassium, Magnesium, water in the distal nephron; delays excretion of calcium ions, Uric acid. It has antihypertensive properties; hypotensive action develops due to the expansion of arterioles. Almost no effect on normal blood pressure. The diuretic effect after 1-2 no, reaches through 4 hours and lasts 6-12 no.

The antihypertensive effect occurs within 3-4 day, but in order to achieve optimum therapeutic effect may require 3-4 of the week.

Pharmacokinetics

The pharmacokinetics of losartan and hydrochlorothiazide while the application is no different from that in their separate application.

Lozartan

Absorption

Well absorbed from the gastrointestinal tract. Taking the drug with food has no clinically significant impact on its serum concentrations. C_max losartan in plasma achieved through 1 hours after ingestion, a C_max EXP-3174 is achieved in 3-4 hours.

Distribution

More 99% losartan and EXP-3174 binds to plasma proteins, mostly to albumin. V_d Losartan is 34 l. Almost does not penetrate the blood-brain barrier.

Metabolism

Subject to significant first-pass metabolism through the liver, forming the active metabolite EXP-3174 (14%) and a number of inactive metabolites. Bioavailability is about 33%.

Deduction

The plasma clearance of losartan and EXP-3174 is approximately 10 ml / s (600 ml / min) and 0.83 ml / s (50 ml / min) respectively. Renal clearance of losartan and EXP-3174 is about 1.23 ml / s (74 ml / min) and 0.43 ml / s (26 ml / min), respectively. T_1/2 losartan and EXP-3174 is 2 hours and 6-9 hours, respectively. About 58% the drug is excreted in the bile, 35% - Urine.

Gidroxlorotiazid

Absorption and distribution

Absorbed, mainly, in the duodenum and proximal small intestine. Absorption sostavlyaet 70% and increased by 10% when taken with food. C_max of serum is reached after 1.5 – 5 no.

V_d about 3 l / kg. The binding to plasma proteins – 40%, It accumulates in erythrocytes.

Metabolism and excretion

Do not metabolized in the liver.

About 95% the drug is excreted unchanged in the mainly kidneys. Renal clearance of hydrochlorothiazide in healthy volunteers and in patients with hypertension is approximately 5.58 ml / s (335 ml / min). Hydrochlorothiazide is a biphasic elimination profile. T_1/2 in the initial phase of 2 no, in the final phase (10-12 h after administration) - About 10 no.

Testimony

- Arterial hypertension (patients, which shows the combination therapy);

- Reducing the risk of cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy.

Dosage regimen

The drug is taken orally, regardless of the meal. Lorystu^® LP can be combined with other antihypertensive agents.

At hypertension initial and maintenance dose – 1 tab. (100/25 mg) 1 time / day. Usually, the drug is prescribed in the absence of an adequate therapeutic effect Loristy^® N (50/12.5 mg). The maximum antihypertensive effect is reached within 3 weeks of therapy. The maximum daily dose - 1 tab. Loristы^® In GDP.

In snizhennom OCK (eg, in patients receiving high doses of diuretics) The recommended initial dose of losartan in patients with hypovolemia is 25 mg 1 time / day. In connection with this therapy Loristoy^® ND should be started after the cancellation of diuretics and correction of hypovolemia.

In Elderly patients and patients with renal insufficiency moderately (CC 30-50 ml / min), including dialysis, It does not require correction initial dose.

To reduce the risk of cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy the standard starting dose of losartan 50 mg 1 time / day. Patients, who have failed to reach target blood pressure in patients receiving losartan 50 mg / day, It requires the selection of treatment by a combination of losartan with a low dose of hydrochlorothiazide (12.5 mg), and, in case of need, We need to increase the dose of losartan to 100 mg in combination with hydrochlorothiazide in a dose of 12.5 mg / day, further – increase the dose of hydrochlorothiazide, LP for appointing Loristu 1 tab. / day.

Side effect

From the central and peripheral nervous system: often – headache, systemic and non-systemic dizziness, insomnia, fatiguability; sometimes – migraine.

Cardio-vascular system: often – orthostatic hypotension (dozozavisimaya), palpitations, tachycardia; rarely – vasculitis.

The respiratory system: often – cough, infections of the upper respiratory tract, faringitы, rhinedema.

From the digestive system: often – diarrhea, dyspepsia, nausea, vomiting, abdominal pain; rarely – hepatitis, abnormal liver function; rarely – increase in liver enzymes and bilirubin.

On the part of the musculoskeletal system: often – myalgia, backache; sometimes – artralgii.

From the hematopoietic system: infrequently – anemia, purpura Shenleyna-Genoa.

From the laboratory parameters: often – hyperkalemia, increasing the concentration of hemoglobin and hematocrit (not clinically significant); sometimes – moderate increase in urea and creatinine in the serum.

Allergic reactions: sometimes – hives, itching; rarely – anaphylactic reactions, angioedema (including swelling of the larynx and tongue, causing airway obstruction and / or swelling of the face, lips, throat).

Other: often – asthenia, weakness, peripheral edema, chest pain.

Contraindications

- Anurija;

- Expressed by the human kidney (CC<30 ml / min);

- Hyperkalemia;

- Degidratatsiya (incl. in patients receiving high doses of diuretics);

- Expressed human liver;

- Refractory hypokalaemia;

- Hypotension;

- Lactase deficiency;

- Galactosemia and malabsorption syndrome glucose / galactose;

- Pregnancy;

- Lactation;

- Childhood and adolescence up 18 years (efficacy and safety have not been established);

- Hypersensitivity to losartan and other ingredients;

- Hypersensitivity to sulfonamide derivatives.

FROM caution It should be used for violations of water-electrolyte balance of blood (giponatriemiya, hypochloraemic alkalosis, gipomagniemiya, kaliopenia), bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, diabetes, hypercalcemia, hyperuricemia and / or gout, when allergic history (some patients angioedema previously developed while taking other drugs, incl. ACE inhibitors) and bronchial asthma, systemic blood diseases (incl. SLE), simultaneously with NSAIDs (incl. COX-2 inhibitors).

Pregnancy and lactation

Data on the use of losartan during pregnancy is not. Fetal renal perfusion, which depends on the development of the renin-angiotensin system, begins to function in the III trimester of pregnancy. The risk to the fetus increases if losartan in II and III trimesters, tk. taking medicines, directly acting on the renin-angiotensin, during the II and III trimester of pregnancy can lead to fetal death.

Not recommended diuretics during pregnancy due to the risk of jaundice in the fetus and newborn, thrombocytopenia in mothers. Diuretic therapy does not prevent development of toxemia of pregnancy.

In establishing pregnancy therapy Loristoy^® ND should be stopped immediately.

If necessary, use during lactation should decide the issue of termination of breastfeeding.

Cautions

There is no need for a special selection of the starting dose in elderly patients. The drug can increase the concentration of urea and creatinine in the blood plasma in patients with bilateral renal artery stenosis or renal artery stenosis sole kidney.

Hydrochlorothiazide may enhance hypotension and disturbance of water and electrolyte balance (umenyshenie OCK, giponatriemiю, hypochloraemic alkalosis, hypomagnesemia, hypokalemia), disrupt glucose tolerance, reduce urinary excretion of calcium and cause a transient, a slight increase in calcium concentration in blood plasma, increase the concentration of cholesterol and triglycerides, provoke the emergence of hyperuricemia and / or gout.

Losartan^® LP comprises lactose, and the drug is not indicated for patients with lactase deficiency, galactosemia and malabsorption syndrome glucose / galactose.

Effects on ability to drive vehicles and management mechanisms

Virtually all patients during therapy with Lorista^® ND can perform actions, requiring special attention (eg, driving or dangerous technical facilities). In individuals at the beginning of therapy, the drug can cause hypotension and dizziness, thus, indirectly influence their psychophysical condition. For security reasons before beginning the activity, requiring greater attention, Patients must first assess their response to treatment.

Overdose

Lozartan

Symptoms: marked reduction in blood pressure, tachycardia, bradycardia, due to the parasympathetic (vagal) stimulation.

Treatment: diurez, simptomaticheskaya therapy, hemodialysis nyeeffyektivyen.

Gidroxlorotiazid

Symptoms: The most common symptoms are a consequence of deficiency of electrolytes (kaliopenia, chloropenia, giponatriemiya) and dehydration due to excessive diuresis. At the same time taking cardiac glycosides hypokalemia can exacerbate arrhythmias.

Treatment: symptomatic therapy

Drug Interactions

Lozartan

In clinical studies revealed no clinically significant pharmacokinetic interaction of losartan with hydrochlorothiazide, digoksinom, varfarinom, cimetidine, fenoʙarʙitalom, ketoconazole and erythromycin.

Rifampicin and fluconazole snizhayut uroveny aktivnogo metabolite losartan (clinically this interaction has not been studied).

Concomitant use of losartan with potassium-sparing diuretics (spironolactone, triamterene, amilorid), potassium-containing additives or potassium salts can cause hyperkalemia.

NSAIDs, incl. selective COX-2 inhibitors, may reduce the effectiveness of other diuretics and antihypertensives, including losartan.

In patients with impaired renal function, treated with NSAIDs (including COX-2 inhibitors), therapy is angiotensin II receptor antagonists may result in further deterioration of renal function, including acute renal failure, which is usually reversible.

The hypotensive effect of losartan, as well as other antihypertensives, It can be reduced when receiving indomethacin.

Gidroxlorotiazid

While the use of thiazide diuretics, ethanol, barbiturates and narcotics may potentiate the risk of orthostatic hypotension.

While the use of hypoglycemic agents (for oral and insulin) may require dose adjustment of hypoglycemic agents.

When taken in combination with other antihypertensives marked additive effect.

Cholestyramine and colestipol violate the absorption of hydrochlorothiazide.

At simultaneous application with Valium, ACTH levels observed marked reduction of electrolytes, in particular, kaliopenia.

Hydrochlorothiazide reduces the severity of the response to the reception of pressor amines (eg, epinephrine, norepinephrine).

Hydrochlorothiazide increases the effect of non-depolarizing muscle relaxant action type (eg, tuʙokurarina).

Diuretics reduce the renal clearance of lithium and increase the risk of toxic effects of lithium (concurrent use is not recommended).

NSAIDs (including COX-2 inhibitors) may reduce the diuretic, natriuretic and hypotensive effect of diuretics.

In connection with the effect on calcium metabolism receiving thiazide diuretics may distort the results of the research function of the parathyroid glands.

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 or above 30 ° C. Shelf life – 2 year.