Losap PLUS

Active material: Lozartan, Gidroxlorotiazid
When ATH: C09DA01
CCF: Antihypertensive drugs
ICD-10 codes (testimony): I10
When CSF: 01.09.16.05
Manufacturer: ZENTIVA a.s. (Czech Republic)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills, Film-coated light yellow, oblong, to share the risks on both sides.

Excipients: mannitol, microcrystalline cellulose, sodium croscarmellose, povidone, magnesium stearate, gipromelloza 2910/5, macrogol 6000, talc, Simethicone emulsion, dye Opaspray yellow M-1-22801 (Purified water, Titanium dioxide, denatured ethanol (methylated spirit: ethanol 99% and methanol 1%), gipromelloza, Quinolin Yellow dye (E104), Pounceau 4R (E124)).

10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (9) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.

Pharmacological action

Antihypertensive drugs of the combined structure.

Lozartan – specific angiotensin II receptor antagonist (subtype AT₁). He inhibits kinase II – enzyme, destroys bradykinin. Reduces PR, the blood concentration of epinephrine and aldosterone, FROM, 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.

Gidroxlorotiazid – tiazidnый diuretic. It reduces the reabsorption of sodium ions, increases urinary excretion of potassium ions, and hydrogen phosphate. It lowers blood pressure by reducing the BCC, the reactivity of the vascular wall, reduce the pressor effect of vasoconstrictor substances and strengthen the depressive effect on ganglia.

The maximum antihypertensive effect is reached within 3 weeks after initiation of treatment.

Pharmacokinetics

Absorption

After oral administration, losartan and hydrochlorothiazide are rapidly absorbed from the gastrointestinal tract. The bioavailability of losartan – about 33%. The time to reach C_max Losartan is 1 no, ego aktivnogo metabolite – 3-4 no.

Distribution

Binding of losartan to plasma proteins is 99%.

Metabolism

Losartan undergoes effect “first pass” through the liver, metabolized by carboxylation to form the active metabolite.

Hydrochlorothiazide is not metabolized in the liver.

Deduction

T_1/2 lozartana – 1.5-2 no, and its major metabolite 3-4 no. About 35% the dose is excreted in the urine, about 60% – with feces.

T_1/2 hydrochlorothiazide is 5.8-14.8 no. About 61% excreted in the urine as unchanged.

Pharmacokinetics in special clinical situations

Losartan concentration in blood plasma in patients with liver cirrhosis is significantly increased.

Testimony

- Arterial hypertension (patients, for whom combination therapy is optimal);

- To reduce the risk of cardiovascular diseases (incl. stroke) and mortality in patients with hypertension and left ventricular hypertrophy.

Dosage regimen

The drug is taken orally, regardless of the meal.

When treating hypertension middle initial and maintenance dose is 1 tab. / day. If you are taking the drug at a given dose can not achieve adequate blood pressure control, Dose Lozap Plus can be increased to 2 tab. 1 time / day. The maximum dose is 2 tab. 1 time / day.

No need for special selection of the initial dose at elderly patients.

FROM To reduce the risk of cardiovascular diseases (incl. stroke) and mortality in patients with hypertension and left ventricular hypertrophy administered losartan (Lozap) standard initial dose 50 mg / day. Patients, who have failed to reach target blood pressure in patients receiving losartan 50 mg / day, It requires selection of therapy by the combination of losartan with hydrochlorothiazide in a low dose (12.5 mg), provided that the purpose of Lozap plus. If necessary, the dose can be increased Lozap plus up 2 tab. (100 mg and losartan 25 mg of hydrochlorothiazide) 1 time / day.

Side effect

All adverse reactions are limited to those observed previously in the application of losartan and hydrochlorothiazide.

CNS: often – dizziness.

Allergic reactions: hives, angioedema, including edema of the larynx and / or language (leading to airway obstruction), and / or swelling of the face, lips, throat and / or tongue (seldom celebrate in the losartan); some of these patients had previously arisen angioedema when other drugs, incl. and ACE inhibitors. In some cases, (when losartan) – vasculitis, including Henoch's disease.

Cardio-vascular system: hypotension.

From the digestive system: rarely (<1%) when losartan – diarrhea, hepatitis, increase in liver transaminases.

The respiratory system: when losartan – cough.

From the water-electrolyte the balance: rarely (<1%) – hyperkalemia (serum potassium more 5.5 mmol / l).

Contraindications

- Anurija;

- Severe hypotension;

- Expressed by the human kidney (KK≤30 ml / min);

- Expressed human liver;

- Gipovolemiя (incl. due to high doses of diuretics);

- Pregnancy;

- Lactation;

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

- Hypersensitivity to the drug.

FROM caution prescribed to patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, Patients with diabetes mellitus, hypercalcemia, hyperuricemia and / or gout, in systemic connective tissue diseases (incl. SLE), as well as patients with a history of allergy, asthma.

Pregnancy and lactation

Use of the drug Losap plus during pregnancy and lactation is contraindicated. In the event of pregnancy while taking the drug Losap plus it should cancel.

Supplementation, directly acting on the renin-angiotensin, during the II and III trimester of pregnancy can lead to fetal death.

The use of diuretics in healthy pregnant women is not recommended due to the risk of jaundice in the fetus and newborn, thrombocytopenia in mothers. Diuretic therapy does not prevent development of toxemia of pregnancy.

Cautions

Plus, you can assign Losap with other antihypertensive drugs.

Against the background of Lozap Plus may increase the concentration of urea and creatinine in the blood plasma in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney.

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

Gidroxlorotiazid, in connection with the impact on calcium metabolism, It can affect the results of analysis of the function of parathyroid glands.

Use in Pediatrics

The safety and efficacy of the drug plus Losap children and adolescents under the age of 18 years not set.

Effects on ability to drive vehicles and management mechanisms

There are no data on the impact of the drug on the ability to drive vehicles and management mechanisms.

Overdose

Symptoms: lozartan – marked reduction in blood pressure, tachycardia, bradycardia (resulting from stimulation of the vagal); gidroxlorotiazid – loss of electrolytes (kaliopenia, hyperchloremia, giponatriemiya), and dehydration, arising from excessive diuresis.

Treatment: if the drug has recently adopted, should wash out the stomach; symptomatic and supportive therapy; if necessary – correction fluid and electrolyte disorders. Losartan and its active metabolite are not removed by hemodialysis.

Drug Interactions

Losartan enhances the effect of other antihypertensive drugs.

There was no clinically significant interaction with losartan hydrochlorothiazide, digoksinom, nepryamыmy anticoagulants, cimetidine, fenoʙarʙitalom, ketoconazole, Erythromycin.

Co-administration of losartan (as well as other drugs, blokiruyushtih angiotensin II) and potassium-sparing diuretics (eg, spironolactone, triamteren, amilorida), preparations potassium or potassium-salt substitutes can cause hyperkalemia.

In an application with barbiturates hydrochlorothiazide, opioid analgesics, ethanol can occur potentiation of orthostatic hypotension.

With simultaneous use of hydrochlorothiazide with hypoglycemic agents may require correction of the dose.

When concomitant administration of hydrochlorothiazide with other antihypertensive drugs is possible additive effect.

With simultaneous use of hydrochlorothiazide with corticosteroids, ACTH is enhanced loss of electrolytes, especially potassium.

With simultaneous use of hydrochlorothiazide with vasoconstrictor agents may be a slight decrease in their effect, will not interfere with their use.

With simultaneous use of hydrochlorothiazide with non-depolarizing muscle relaxants (eg, tuʙokurarin) may increase their activities.

In some cases, the simultaneous use of NSAIDs may reduce the diuretic, natriuretic and antihypertensive effects of hydrochlorothiazide.

Cholestyramine reduces absorption of hydrochlorothiazide.

Hydrochlorothiazide decreases the renal clearance of lithium and increase the risk of lithium toxicity, therefore their simultaneous use is not recommended.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored in a dry, inaccessible to children at temperature not exceeding 30 ° C. Shelf life – 3 year.