Losartan + Hydrochlorothiazide - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Angiotensin II receptor antagonists (AT1 subtype)

Diuretics

Included in the formulation

Vasotens H

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SiNViTi Pharma Co., Ltd. Cyprus

Losartan-N Richter

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GEDEON RICHTER, OJSC Hungary

Losartan-N Richter

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GEDEON RICHTER, OJSC Hungary

АТХ:

C.09.D.A Angiotensin II antagonists in combination with diuretics

C.09.D.A.01 Losartan in combination with diuretics

Pharmacodynamics:

The active substances of the combination of losartan / hydrochlorothiazide have an additive antihypertensive effect, reducing arterial pressure more than each of the components alone. Due to the diuretic effect hydrochlorothiazide increases the activity of renin plasma, stimulates the secretion of aldosterone, increases the concentration of angiotensin II and reduces the potassium content in the blood serum. The administration of losartan blocks all the physiological effects of angiotensin II and, as a result of suppression of aldosterone, contributes to a decrease in potassium loss caused by the intake of a diuretic.

Losartan has a moderate and transient uricosuric effect. Hydrochlorothiazide causes a slight increase in the concentration of uric acid in the blood; The combination of losartan and hydrochlorothiazide helps reduce the severity of hyperuricemia caused by a diuretic.

Pharmacokinetics:

The pharmacokinetics of losartan and hydrochlorothiazide with simultaneous administration does not differ from that in their separate application.

Suction

Losartan. Ingestion losartan is well absorbed from the digestive tract, metabolized by "primary passage" through the liver, resulting in the formation of an active carboxylated metabolite and inactive metabolites. Systemic bioavailability of losartan in the form of tablets is about 33%. C_max in the blood plasma of losartan and its active metabolite are achieved after 1 h and 3-4 h respectively. When losartan was taken during a meal, there was no clinically significant effect on the profile of losartan concentration in the blood plasma.

Hydrochlorothiazide. After ingestion incomplete, but fairly quickly absorbed from the digestive tract. 60-80% of the dose is absorbed from the digestive tract. Time to reach C_max in the blood plasma -1,5-3 h.

Distribution

Losartan. The binding of losartan and its active metabolite to blood plasma proteins (mainly albumin) is more than 99%. V_d - 34 liters. Studies in rats have shown that losartan practically does not penetrate the blood-brain barrier.

Hydrochlorothiazide. It penetrates the hematoplacental barrier, it is excreted into breast milk. Does not penetrate blood-brain barrier.

Metabolism

Losartan. After ingestion and intravenous administration of losartan labeled with 14C isotope, the radioactivity of the circulating blood plasma is associated with the presence of losartan and its active metabolite in it.

Hydrochlorothiazide. It is slightly metabolized in the liver. At least 61% of the ingested dose is excreted unchanged for 24 hours.

Excretion

Losartan. The plasma clearance of losartan and its active metabolite is about 600 ml / min and 50 ml / min, respectively. The renal clearance of losartan and its active metabolite is approximately 74 ml / min and 26 ml / min, respectively. After oral administration losartan is excreted by the kidneys - about 4% unchanged and about 6% of the dose in the form of an active metabolite.

After oral administration, the concentration of losartan and its active metabolite in the blood plasma decreases polyexponentially with a finite half-life of approximately 2 hours and 6-9 hours, respectively. With a single dose of 100 mg losartan, nor its active metabolite significantly accumulate in the blood plasma.

The excretion of losartan and its metabolites occurs through the intestine with bile and kidneys. In healthy volunteers, after ingestion of losartan labeled with isotope 14C, about 35% of the radioactive label is found in urine and 58% in feces.

Hydrochlorothiazide. Quickly excreted by the kidneys. The half-life period varied from 5.6 to 14.8 hours. At least 61% of the dose taken orally was excreted unchanged for 24 hours.

Indications:Arterial hypertension.

ICD-10

IX.I10-I15.I10 Essential [primary] hypertension

IX.I10-I15.I15 Secondary Hypertension

Contraindications:

- Hypersensitivity to any of the components of the drug (as well as increased sensitivity to other drugs that are derivatives of the sulfonamide);

- Pregnancy;

- the period of breastfeeding;

- Anuria, severe renal dysfunction (creatinine clearance less than 30 ml / min), patients on hemodialysis;

- severe violations of the liver (more than 9 points on the scale Child-Pugh);

- cholestasis;

- refractory hypokalemia;

- a symptomatic increase in the concentration of uric acid in the blood plasma;

- dehydration;

- children's age till 18 years;

- primary hyperaldosteronism;

- simultaneous use with potassium preparations, potassium-sparing diuretics;

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Carefully:

Violations of the water-electrolyte balance (decrease in the volume of circulating blood, hyponatremia, hypochloraemic alkalosis, hypomagnesemia, hypokalemia), which can develop against intercurrent diarrhea or vomiting; impaired renal function (creatinine clearance more than 30 ml / min); violations of the liver (less than 9 points on the scale Child-Pugh); cardiac ischemia; cerebrovascular diseases; aortic stenosis; mitral stenosis; hypertrophic obstructive cardiomyopathy; bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney; diabetes; hypercalcemia, hyperuricemia and / or gout; weighed allergic anamnesis (in some patients, angioedema has developed earlier with other medications, including ACE inhibitors); bronchial asthma; systemic connective tissue diseases,including systemic lupus erythematosus; hypovolemia, including against a background of high doses of diuretics; and also with simultaneous administration with non-steroidal anti-inflammatory drugs, including cyclooxygenase-2 inhibitors.

Pregnancy and lactation:

Admission of medicines directly acting on renin-angiotensin-aldosterone system, in the II and III trimester of pregnancy can lead to the death of the fetus. When establishing a pregnancy, you should abort the combination as soon as possible. Concerning healthy pregnant women, the use of diuretics is usually not recommended due to the risk of jaundice in the fetus and the newborn, thrombocytopenia in the mother.

FDA recommendation category D.

Dosing and Administration:

Inside, regardless of food intake, with enough water.

The initial and maintenance dose is 1 tablet of 12.5 mg + 50 mg once a day.

For patients who can not achieve adequate control of blood pressure, the dose may be increased - 1 tablet of 25 mg + 100 mg once a day.

The maximum dose is 1 tablet of 25 mg + 100 mg once a day.

The maximum antihypertensive effect in most cases is achieved within 3-4 weeks from the start of treatment.

Side effects:

In clinical studies with losartan / hydrochlorothiazide, no adverse events specific to this combination drug have been observed.

Undesirable effects were limited to those reported earlier with losartan and / or hydrochlorothiazide alone.

Overdose:

There is no data on the specific treatment of an overdose of losartan / hydrochlorothiazide combination.

Interaction:

The combination of losartan, as well as other means blocking angiotensin II or its effects, with potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium-containing additives or potassium salts, can lead to an increase in the potassium content in the blood serum.

If losartan is used simultaneously with lithium preparations, care should be taken because of a possible decrease in lithium excretion.

Non-steroidal anti-inflammatory drugs, including selective inhibitors of COX-2, can reduce the effect of diuretics and other antihypertensive drugs. Therefore, the antihypertensive effect of angiotensin II receptor antagonists can be mitigated with simultaneous use with non-steroidal anti-inflammatory drugs (including COX-2 inhibitors).

In some patients with impaired renal function (eg, elderly patients or patients with reduced circulating blood volume, including those receiving diuretics) receiving non-steroidal anti-inflammatory drugs (including COX-2 inhibitors), treatment with angiotensin II receptor antagonists or ACE inhibitors may cause further deterioration in kidney function, including acute renal failure, which is usually reversible.

The cases of double blockade renin-angiotensin-aldosterone system (for example, with the concomitant use of an ACE inhibitor and an angiotensin II receptor antagonist), patients with diagnosed atherosclerosis, heart failure, and diabetes mellitus were more often accompanied by a marked decrease in blood pressure, syncope, hyperkalemia, and impaired renal function (including acute renal insufficiency) with the use of one of the drugs affecting renin-angiotensin-aldosterone system.

When used simultaneously with tricyclic antidepressants, haloperidol, chlorpromazine, sulpiride, baclofen, amifostine, the risk of a sharp drop in blood pressure increases.

Special instructions:

The combination of losartan and hydrochlorothiazide 50 mg at a dose of 12.5 mg causes fewer side effects than the use of losartan in a dose of 100 mg.

The combination of losartan and hydrochlorothiazide 50 mg at a dose of 12.5 mg is comparable to the coupling efficiency of enalapril in a dose of 20 mg of nifedipine and 10 mg, a combination of captopril in a dose of 50 mg of hydrochlorothiazide and 25 mg.

The combination of losartan and hydrochlorothiazide 50 mg at a dose of 12.5 mg (100 mg + 25 mg) is superior to monotherapy hydrochlorothiazide, losartan 100 mg, candesartan in a dose of 16 mg nifedipine 30 mg.

Telmisartan 80 mg, a combination of telmisartan 40 mg (80 mg) and hydrochlorothiazide in a dose of 12.5 mg of candesartan in a dose of 16 mg, and hydrochlorothiazide in a dose of 12.5 mg, irbesartan, 150 mg, and hydrochlorothiazide in a dose of 12 5 mg exceed the combination of losartan in a dose of 50 mg and hydrochlorothiazide at a dose of 12.5 mg.

The combination of losartan and 100 mg hydrochlorothiazide 25 mg more effectively reduces pressure than the combination of these same drugs in the ratio of 50 mg / 12.5 mg.

Instructions

Losartan + Hydrochlorothiazide (Losartanum + Hydrochlorothiazidum)