Lorista N 100, 12.5 mg+100 mg, film-coated tablets, 30 pcs., KRKA buy in Moscow at a low price

Lorista N 100, 30 pcs., 12.5 mg+100 mg, film-coated tablets

The pharmacokinetics of losartan and hydrochlorothiazide when used simultaneously does not differ from that when used in monotherapy.

Losartan

Absorption

Losartan is well absorbed from the gastrointestinal tract (GIT) when taken orally. It undergoes significant metabolism during the “primary passage” through the liver, forming a pharmacologically active carboxylated metabolite (E-3174) and inactive metabolites. Bioavailability is approximately 33%. Average maximum concentrations of losartan and its active metabolite are achieved after 1 hour and after 3-4 hours, respectively.

Distribution

Losartan and its active metabolite are more than 99% bound to plasma proteins (mainly albumin). The volume of distribution of losartan is 34 liters. It penetrates the blood-brain barrier very poorly.

Metabolism

Losartan is metabolized to form an active (E-3174) metabolite (14%) and inactive ones, including two major metabolites formed by hydroxylation of the butyl group of the chain and a less significant metabolite, N-2-tetrazole glucuronide.

Removal

Plasma clearance of losartan and its active metabolite is approximately 10 ml/sec (600 ml/min) and 0.83 ml/sec (50 ml/min), respectively. The renal clearance of losartan and its active metabolite is approximately 1.23 ml/sec (74 ml/min.) and 0.43 ml/sec (26 ml/min.). The half-life (T1/2) of losartan and the active metabolite is 2 hours and 6-9 hours, respectively. It is excreted mainly with bile through the intestines - 58%, by the kidneys - 35%. Does not accumulate.

When taken orally in doses up to 200 mg, losartan and its active metabolite have linear pharmacokinetics.

Hydrochlorothiazide

After oral administration, absorption of hydrochlorothiazide is 60-80%. The maximum concentration in blood plasma is achieved 1-5 hours after oral administration. Connection with blood plasma proteins - 64%.

Hydrochlorothiazide is not metabolized and is rapidly excreted through the kidneys. T1/2 is 5-15 hours. At least 61% of the dose taken orally is excreted unchanged within 24 hours.

Penetrates the placental barrier and is excreted in breast milk. Pharmacokinetics in selected patient groups

Losartan + hydrochlorothiazide

Elderly patients

The concentrations of losartan and its active metabolite in the blood plasma and the rate of absorption of hydrochlorothiazide in elderly patients with arterial hypertension do not differ significantly from these indicators in young patients with arterial hypertension.

Losartan

Plasma concentrations of losartan were 2 times higher in women with hypertension compared with men with hypertension. This pharmacokinetic difference is not clinically significant. The concentration of the active metabolite does not differ between men and women.

Liver and kidney dysfunction

When losartan was taken orally by patients with mild and moderate alcoholic cirrhosis, the concentrations of losartan and its active metabolite in the blood plasma were, respectively, 5 - 1.7 times higher than in young male volunteers.

Plasma concentrations of losartan in patients with creatinine clearance (CC) above 10 ml/min did not differ from those in patients with preserved renal function. When comparing the area under the concentration-time curve (AUC) in patients with normal renal function, the AUC of losartan in patients on hemodialysis was approximately 2 times greater. Plasma concentrations of the active metabolite do not change in patients with impaired renal function or patients on hemodialysis. Losartan and its active metabolite cannot be removed by hemodialysis.

Instructions for use of LORISTA® H 100 (LORISTA® H 100)

Losartan

Rifampicin

and
fluconazole
reduce the concentration of the active metabolite. The clinical consequences of this interaction have not been studied.

As with other drugs that block angiotensin II or reduce its effect, concomitant use of potassium-sparing diuretics (spironolactone, triamterene, amiloride)

, as well as
supplements or salt substitutes containing potassium
, may lead to an increase in the concentration of potassium in the blood plasma. The simultaneous use of these drugs is not recommended.

As with other drugs that affect sodium excretion, lithium excretion from the body may be reduced. Therefore, with the simultaneous use of angiotensin II receptor antagonists and lithium salts

the concentration of the latter in the blood plasma should be carefully monitored.

When using angiotensin II receptor antagonists and NSAIDs together (for example, selective COX-2 inhibitors, acetylsalicylic acid in anti-inflammatory doses and non-selective NSAIDs)

a weakening of the hypotensive effect may be observed. Concomitant use of angiotensin II receptor antagonists or diuretics with NSAIDs may increase the risk of renal dysfunction, including acute renal failure, and lead to increased plasma potassium concentrations (especially in patients with chronic renal failure). This combination should be used with caution, especially in the elderly. Patients should receive adequate fluid intake and consideration should be given to monitoring renal function parameters after initiation of concomitant therapy and periodically during treatment.

In some patients with impaired renal function receiving NSAIDs, including COX-2 inhibitors, concomitant use of angiotensin II receptor antagonists may lead to a further deterioration of renal function. However, this effect is usually reversible.

Double blockade of the RAAS

Clinical trial results have shown that dual blockade of the RAAS through the combined use of an ACE inhibitor, an angiotensin II receptor antagonist or aliskiren is associated with a higher incidence of side effects such as hypotension, hyperkalemia and renal dysfunction (including acute renal failure) compared with monotherapy .

Based on the available data, dual RAAS blockade with an ACE inhibitor, angiotensin II receptor antagonist, or aliskiren cannot be recommended in any patient, especially in patients with diabetic nephropathy.

In patients with diabetes mellitus or moderate/severe renal failure (GFR <60 ml/min/1.73 m2), the simultaneous use of aliskiren with an ACE inhibitor or angiotensin II receptor antagonist is contraindicated.

In some cases, when the combined use of an ACE inhibitor or an angiotensin II receptor antagonist is absolutely indicated, careful supervision by a specialist and mandatory monitoring of renal function, water and electrolyte balance, and blood pressure are necessary.

Other drugs that have antihypertensive effects include tricyclic antidepressants, antipsychotics, baclofen and amifostine

. Concomitant use of these drugs increases the risk of hypotension.

Hydrochlorothiazide

Interactions may occur when thiazide diuretics and the following drugs are used together.

Ethanol, barbiturates, narcotics and antidepressants

When used concomitantly with hydrochlorothiazide, aggravation of orthostatic hypotension may occur.

Antidiabetic drugs (oral hypoglycemic drugs and insulin)

The use of thiazide diuretics may affect glucose tolerance, which may require dose adjustment of the antidiabetic drug. Metformin should be used with caution due to the risk of lactic acidosis caused by possible functional renal failure associated with the use of hydrochlorothiazide.

Other antihypertensive drugs

With simultaneous use, an additive effect is possible.

Cholestyramine and colestipol resins

The absorption of hydrochlorothiazide is reduced in the presence of anion exchange resins. A single dose of cholestyramine or colestipol resins binds hydrochlorothiazide, reducing its absorption from the gastrointestinal tract by 85% and 43%, respectively.

Corticosteroids, ACTH

With simultaneous use, a pronounced decrease in the concentration of electrolytes (in particular, hypokalemia) is possible.

Pressor amines (eg adrenaline)

A weakened reaction to pressor amines is possible, which, however, is not sufficient to preclude their use.

Non-depolarizing muscle relaxants (eg, tubocurarine)

With simultaneous use, it is possible to increase susceptibility to muscle relaxants.

Lithium

Diuretics reduce the renal clearance of lithium and increase the risk of lithium toxicity. Combined use is not recommended.

Medicines used to treat gout (probenecid, sulfinpyrazone, and allopurinol)

Dosage adjustment of the drug that promotes the removal of uric acid may be necessary, since the use of hydrochlorothiazide may lead to an increase in the concentration of uric acid in the blood plasma. The dose of probenecid or sulfinpyrazone may need to be increased. Thiazide diuretics may increase the likelihood of hypersensitivity to allopurinol.