Expiration date: 03/2025
The composition and form of issue:
Tablets, film-coated 1 tablet contains:
losartan potassium 50 mg
hydrochlorothiazide 12.5 mg
auxiliary substances: starch Pregelatinised microcrystalline lactose monohydrate magnesium stearate
shell: hypromellose macrogol 4000 quinoline yellow dye (E104) titanium dioxide (E171) talc
in blister packs for 7, 10 or 14 PCs the paper cartons 2, 4, 8, 12, or 14 blisters (7 pieces) for 3, 6 or 9 blisters (for 10 PCs) at 1, 2, 4, 6 or 7 blister packs (14 PCs.).
Description pharmaceutical form:
Oval, slightly biconvex tablets, film-coated from yellow to yellow with a greenish tint, scored on one side.
Pharmacokinetics:
The pharmacokinetics of losartan and gidrohlorotiazida while receiving no different from that in their separate appointment.
Losartan. Well absorbed from the gastrointestinal tract. Undergoes significant metabolism when "first pass" through the liver, forming the active metabolite (EXP-3174) carboxylato acid and other inactive metabolites. Bioavailability is approximately 33%. Taking the drug with food has no clinically significant effect on its serum concentration. Tmax — 1 h after ingestion, but its active metabolite (EXP-3174), 3-4 p.m.
More than 99% of losartan and EXP-3174 is associated with blood plasma proteins, mainly to albumin. The volume of distribution of losartan is 34 L. Very poorly crosses the GEB.
Losartan is metabolized to the active (EXP-3174) of metabolite (14%) and the inactive, including 2 major metabolites, formed by hydroxylation of the butyl chain group, and a less significant metabolite — N-2-glucuronide tetrazol.
Plasma clearance of losartan and its active metabolite is approximately 10 ml/s (600 ml/min) and 0.83 ml/s (50 ml/min), respectively. Renal clearance of losartan and its active metabolite is about 1.23 ml/s (74 ml/min) and of 0.43 ml/s (26 ml/min). T1/2 of losartan and the active metabolite is 2 h and 6-9 h respectively. It is excreted mainly in the bile — 58%, renal — 35%.
Hydrochlorothiazide. After oral absorption of hydrochlorothiazide is 60-80%. Cmax of hydrochlorothiazide in the blood is achieved through 1-5 hours after ingestion.
Linking blood plasma proteins of hydrochlorothiazide is 64%.
Hydrochlorothiazide is not metabolized and is rapidly excreted through the kidneys. T1/2 is 5-15 hours
Description pharmacological action:
Lorista H — combination drug has a hypotensive effect.
Losartan. Selective antagonist of the angiotensin II receptor (type AT1) for intake of non-protein nature. In vitro and In vivo losartan and its biologically active carboxyl metabolite (EXP-3174) block all physiologically relevant effects of angiotensin II on AT1-receptors.
Losartan indirectly causes activation of the AT2 receptors by increasing levels of angiotensin II.
Losartan does not inhibit the activity of kininase II, an enzyme involved in the metabolism of bradykinin.
Reduces PR, blood pressure is a "small" circulation reduces afterload, has a diuretic effect.
Prevents the development of myocardial hypertrophy, increases tolerance to physical load in patients with chronic heart failure. Taking losartan once a day results in statistically significant reduction in SBP and DBP. Losartan uniformly controls the pressure throughout the day, while 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% of the effect at the peak of drug action, 5-6 h after administration. The syndrome is not observed also the losartan has no clinically significant effect on heart rate.
Losartan effective in men and women, and the elderly (over 65 years) and younger patients (under 65 years).
Hydrochlorothiazide. Thiazide diuretic, the diuretic effect of which is associated with impaired reabsorption of sodium ions, chlorine, potassium, magnesium, water in the distal nephron retards the excretion of calcium, uric acid. Has antihypertensive properties. Almost no effect on normal blood pressure.
The diuretic effect occurs in 1-2 hours, reaches a maximum after 4 hours and lasts 6-12 h. Antihypertensive activity occurs within 3-4 day, but to achieve optimal therapeutic effect may be required 3-4 weeks.
Indications:
- arterial hypertension (in patients, which shows the combined therapy)
- reducing the risk of cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy.
Contraindications:
Hypersensitivity to losartan, drugs are derivatives of sulfonamides and other components of the drug, anuria, expressed by the human kidney (Cl creatinine <30 ml/min), hyperkalemia, dehydration (including in patients receiving high doses of diuretics), severe violations of the liver, refractory hypokalemia, pregnancy, lactation, hypotension, age less than 18 years (efficacy and safety have not been established), lactase deficiency, galactosemia or malabsorption syndrome glucose/galactose.
Caution: disorders of water and electrolyte balance in the blood (hyponatremia, gipohloremichesky alkaloz, gipomagniemia, hypokalemia), bilateral renal artery stenosis or stenosis of artery only kidneys, diabetes mellitus, hypercalcemia, hyperuricemia and/or gout, allergic history (the development of angioedema previously, when the use of other drugs, including ACE inhibitors) and asthma, systemic blood diseases (including systemic lupus erythematosus), coadministration of NSAIDs, including COX-2 inhibitors.
Application of pregnancy and breast-feeding:
Data on the use of losartan during pregnancy not.
Renal perfusion the fetus, which depends on the development of the renin-angiotensin system, begins to function in the III trimester of pregnancy. Risk to the fetus increases when taking losartan in II and III trimestrah. When pregnancy therapy Aristoi N needs to be terminated immediately.
If necessary, the appointment of the drug during lactation should stop breastfeeding.
Side effects:
The blood and lymphatic system: rare — anemia, a disease Henoch-Schonlein purpura.
The immune system: rarely — anaphylactic reactions, angioedema (including swelling of the larynx and tongue, causing airway obstruction and/or swelling of the face, lips, throat).
CNS and peripheral nervous system: often — headache, systemic and non-systemic dizziness, insomnia, fatigue rarely, migraine.
Of the cardiovascular system: often- orthostatic hypotension (dose related), palpitation, tachycardia, rarely — vasculitis.
The respiratory system: often — cough, infections of the upper respiratory tract, pharyngitis, swelling of the nasal mucosa.
By the blood: often — diarrhea, dyspepsia, nausea, vomiting, abdominal pain.
Hepatobiliary system: rarely — hepatitis, abnormal liver function.
On the part of the skin and subcutaneous fat: often — urticaria, pruritus.
From the side of musculoskeletal system and connective tissue: often — myalgia, back pain rare — arthralgia.
Other: often — asthenia, weakness, peripheral edema, chest pain.
The laboratory parameters: often — hyperkalemia, increasing the concentration of hemoglobin and hematocrit levels (not clinically significant) sometimes — a moderate increase in the level of urea and creatinine in blood serum, very rarely — increased activity of liver enzymes and bilirubin.
Drug interactions:
Losartan
In clinical studies no clinically significant pharmacokinetic drug interactions with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin.
Rifampicin fluconazole and reduce the level of active metabolite (clinically, this interaction has not been studied).
The combination of losartan with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium-sparing supplements or potassium salts can lead to hyperkalemia.
NSAIDs, including selective COX-2 inhibitors can reduce the effect of diuretics and other antihypertensive agents, including losartan.
In patients with impaired renal function treated with therapy, NSAIDs (including COX-2 inhibitors) therapy with antagonists of receptors of angiotensin II may lead to further deterioration of renal function, including acute renal failure, which is usually reversible.
Hypotensive effect of losartan, and other antihypertensive agents may be reduced when taking indomethacin.
Hydrochlorothiazide
In combination with thiazide diuretics such drugs as ethanol, barbiturates and narcotics may potentiate the risk of orthostatic hypotension.
Hypoglycemic agents (oral and insulin) may require dosage adjustment of hypoglycemic agents.
Other antihypertensive drugs — additive effect.
Cholestyramine and colestipol in the presence of anionic exchange resins absorption of hydrochlorothiazide is impaired.
Corticosteroids, ACTH — marked reduction in the level of electrolytes, particularly hypokalemia.
Pressor amines (e.g. epinephrine, norepinephrine) — lower the intensity of the response to Pressor amines.
Muscle relaxants non-depolarizing type of action (e.g. tubokurarin) — strengthening effect of the muscle relaxants.
Lithium — diuretics reduce kidney klirens lithium and increase the risk of developing toxic action of lithium concurrent use is not recommended.
NSAIDs (including COX-2 inhibitors) may reduce the diuretic, natriuretic and antihypertensive effect of diuretics. In connection with the effect on calcium metabolism it may be able to skew the results of research of function of the parathyroid glands.
Method of application and dose:
Inside, regardless of meals.
Lorista H can be combined with other antihypertensive agents.
Hypertension. The initial and maintenance dose — 1 tab. Lorista H (50/12,5 mg) 1 times a day. The maximum antihypertensive effect is achieved within 3 weeks of treatment. To achieve a more pronounced effect can increase the dose to 2 table. Lorista H (50/12,5 mg) 1 times a day. The maximum daily dose — 2 tab. drug Lorista H.
In patients with reduced BCC (for example in patients receiving high doses of diuretics) the recommended initial dose of losartan in patients with hypovolemia is 25 mg 1 times per day. In this regard, therapy Lorista H should start after the cancellation of diuretics and correction of hypovolemia.
Elderly patients and patients with moderate renal insufficiency, including those on dialysis, is not required correction initial dose.
Reducing the risk of cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy. The standard starting dose of losartan is 50 mg 1 time a day.
Patients who have failed to achieve target BP levels in patients receiving losartan 50 mg/day, requires selection of the therapy by combination of losartan with low dose of hydrochlorothiazide (12.5 mg) if necessary, increase dosage of losartan to 100 mg in combination with hydrochlorothiazide dose 12.5 mg/day, in future — up to 2 table. Lorista H 50/12,5 mg (100 mg of losartan and 25 mg hydrochlorothiazide 1 time per day).
Overdose:
Losartan
Symptoms: expressed lower AD, tachycardia, bradycardia due to parasympathetic (vagal) stimulation.
Treatment: forced diuresis, symptomatic therapy, hemodialysis is ineffective.
Hydrochlorothiazide
Symptoms: the most common symptoms are a consequence of the lack of electrolytes (hypokalemia, gipohloremia, hyponatremia) and dehydration due to excessive diuresis. While receiving cardiac glycosides gipokaliemia may worsen arrhythmias.
Treatment: symptomatic.
Special instructions:
Can be administered together with other antihypertensives.
No need for special selection of the initial dose elderly patients. The drug may increase the concentration of urea and creatinine in blood plasma in patients with bilateral renal artery stenosis or renal artery stenosis to a solitary kidney.
Hydrochlorothiazide may increase hypotension and violations vodno-elektrolitnogo balance (reduction of BCC, hyponatremia, gipohloremichesky alkalosis, hypomagnesemia, hypokalemia), break tolerance to glucose, to reduce the excretion of calcium in the urine and cause transient, slight increase in the calcium concentration in the blood plasma increase the concentration of cholesterol and triglycerides, provoke hyperuricemia and/or gout. Welcome BOS, directly influencing the system, the renin-angiotensin during II and III trimesters of pregnancy can lead to fetal death. In the event of pregnancy shows removal of the drug.
Pregnant women the use of diuretics are usually not recommended due to risk of jaundice in the fetus and newborn, thrombocytopenia in the mother. Therapy diuretics does not prevent development of toxemia of pregnancy.
Special warnings regarding excipients Lorista H contains lactose, so may not be imposed under the following conditions: lactase deficiency, galactosemia or malabsorption syndrome glucose/galactose.
Effects on ability to drive and other mechanisms. Almost all patients during therapy Aristoi N can perform tasks that require attention (e.g., driving). In individuals at the beginning of drug therapy can cause decreased blood pressure and dizziness, and thus indirectly affect their emotional state. For security purposes, before beginning activities that require greater attention, patients must first assess their response to treatment.
