Losartan inhibits not kininase II, an enzyme which is involved in the metabolism of bradykinin.
Reduces the total equipoise for horses peripheral vascular resistance (SVR), the pressure in the “small” circle of blood circulation; reduces afterload, it has a diuretic effect.
It prevents the development of myocardial hypertrophy, improves exercise tolerance in patients with chronic heart failure (CHF). Losartan once daily resulted in a statistically significant reduction in systolic and diastolic blood pressure (BP). Losartan uniformly controls the pressure throughout the day, with the antihypertensive effect corresponds to the natural circadian rhythm. Lowering blood pressure (BP) at the end of the action of the drug dose was approximately 70-80% at the peak of the effect of the drug, 5-6 hours after administration. The syndrome of “cancellation” is not observed; as losartan has no clinically significant effects on heart rate (HR). Losartan is effective in men and women, and the elderly (> 65 years) and younger patients (<65 years).
. Hydrochlorothiazide is a thiazide diuretic, diuretic effect which is associated with impaired reabsorption of sodium, chlorine, potassium, magnesium, water in the distal nephron; delayed excretion of calcium, uric acid. It has antihypertensive properties; hypotensive action develops due to the expansion of the arterioles. Almost no effect on normal blood pressure (BP). The diuretic effect occurs within 1-2 hours, reaches a peak after 4 hours and lasts 6-12 hours. The antihypertensive effect occurs within 3-4 days, but may need 3-4 weeks to achieve the optimal therapeutic effect.
The pharmacokinetics of losartan and hydrochlorothiazide while receiving no different from that in their separate appointment.
Losartan is well absorbed from the gastrointestinal tract. Subject to significant metabolism in the “first pass” through the liver to form the active metabolite (EHR- 3174) with a carboxylic acid and other inactive metabolites. The bioavailability is approximately 33%. The drug with food has no clinically significant impact on its serum concentrations. TStah 1 hour after ingestion, and its active metabolite (EXP-3174) – 3.4 hours.
More than 99% and losartan, EXP-3174 binds to plasma proteins, mainly albumin. The volume of distribution of losartan is 34 liters. Very poorly crosses the blood-brain barrier.
Losartan is metabolized to produce an active (EXP-3174), a metabolite (14%) and inactive, including two major metabolite produced by hydroxylation chain butyl group and less significant metabolite, N-2-tetrazol-glucuronide.
Plasma clearance of losartan and its active metabolite is about 10 ml / sec. (600 ml / min.) And 0.83 ml / sec. (50 ml / min.), Respectively. Renal clearance of losartan and its active metabolite is about 1.23 ml / sec. (74 ml / min.) And 0.43 ml / sec. (26 ml / min.). The half-life of the active metabolite of losartan, and is 2 hours or 9.6 hours, respectively. Write mainly in the bile -58%, the kidneys – 35%.
After oral administration absorption of hydrochlorothiazide is 60-80%. The maximum concentration of hydrochlorothiazide in the blood is achieved in 1-5 hours after ingestion.
Communicating with hydrochlorothiazide blood plasma proteins – 64%. Hydrochlorothiazide is not metabolized and is rapidly excreted by the kidneys. The half-life is 5-15 hours.
- Hypertension (in patients who have shown combination therapy).
- Reducing the risk of cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy.
: Hypersensitivity to losartan, to the media, is a derivative of sulfonamides and other components of the drug, anuria, marked renal impairment (creatinine clearance (CC) of less than 30 ml / min.), Hyperkalemia, dehydration (including in patients receiving high doses of diuretics ), expressed human liver, refractory hypokalemia, pregnancy, lactation, hypotension, up to age 18 years (effectiveness and safety have not been established), lactase deficiency, galactosemia or malabsorption syndrome glucose / galactose.
Precautions: violations of water-electrolyte balance of blood (hyponatremia, gipohloremichesky alkalosis, hypomagnesemia, hypokalemia), a bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, diabetes, hypercalcemia, hyperuricemia and / or gout, allergic history (in some patients, angioedema previously developed while taking other drugs, including ACE inhibitors) and asthma, systemic blood diseases (including systemic lupus erythematosus), co-administration of nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-II (COX 2 inhibitors).
Application of pregnancy and lactation
on the use of losartan during pregnancy No Data. Fetal renal perfusion, which is dependent on the development of the renin-angiotensin system, begins to operate in the third trimester of pregnancy. The risk to the fetus increases if losartan in the second and third trimesters. In establishing pregnancy Loristoy H therapy should be discontinued immediately. If necessary, the appointment during lactation should stop breastfeeding.
Dosing and Administration
Inside, regardless of meals. Loristu H can be combined with other antihypertensive agents.
The starting and maintenance dose is 1 tablet Loristy H (50 / 12.5 mg), 1 per day. The maximum antihypertensive effect is reached within three weeks of therapy. To achieve a more pronounced effect may increase the dose to 2 tablets Loristy H (50 / 12.5 mg), 1 per day. The maximum daily dose – 2 tablets of the drug Lorista N.
In patients with a decreased volume of circulating blood (for example, in patients receiving large doses of diuretics), the recommended initial dose of losartan in patients with hypovolemia is 25 mg once daily.In connection with this therapy Loristoy H should begin after the cancellation of diuretics and correction of hypovolemia.
Older patients and patients with mild renal insufficiency, including dialysis, the initial dose is not required correction.
Reducing the risk of cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy
The standard initial dose of losartan is 50 mg 1 time per day. Patients who did not achieve target levels of blood pressure in patients receiving losartan 50 mg / day, requires selection by the combination therapy with low doses of losartan hydrochlorothiazide (12.5 mg), and, if necessary, it is necessary to increase the dose up to 100 mg of losartan in combination with hydrochlorothiazide in a dose of 12.5 mg / day, further – to increase up to 2 tablets Loristy H 50 / 12.5 mg total (100 mg losartan and hydrochlorothiazide 25 mg once a day).
Side effect On the part of the blood and lymphatic system: rare: anemia, Henoch-Schönlein purpura.
Rare: anaphylaxis, angioedema (including swelling of the larynx and tongue,
causing airway obstruction and / or swelling of the face, lips, throat).
From the central and peripheral nervous systems:
common: headache, systemic equipoise for horses and non-systemic dizziness, insomnia, fatigue;
common: orthostatic hypotension (dose-dependent), palpitations, tachycardia;
The respiratory system:
frequent: cough, infections of the upper respiratory tract, pharyngitis, swelling of the nasal mucosa.
From the gastrointestinal tract:
common: diarrhea, dyspepsia, nausea, vomiting, abdominal pain.
On the part of the hepatobiliary system:
rare: hepatitis, abnormal liver function.
For the skin and subcutaneous fat:
Uncommon: rash, pruritus.
On the part of the musculoskeletal system and connective tissue disorders:
common: myalgia, back pain;
Common: asthenia, fatigue, peripheral edema, pain in the chest.
common: hyperkalemia, increasing the concentration of hemoglobin and hematocrit (not clinically significant);
rare: a moderate increase in levels of urea and creatinine in blood serum;
very rare: increase in liver enzymes and bilirubin.
Losartan Symptoms: marked reduction of blood pressure, tachycardia; bradycardia caused by parasympathetic (vagal) stimulation. Treatment: forced diuresis, symptomatic therapy, hemodialysis is ineffective.
Hydrochlorothiazide Symptoms: The most common symptoms are a consequence of electrolyte deficiency (hypokalemia, hyposalemia, hyponatremia) and dehydration due to excessive diuresis. At the same time taking cardiac glycosides may aggravate hypokalemia during arrhythmias. Treatment: symptomatic.
Interactions with other drugs
In clinical studies, pharmacokinetic interactions are not clinically significant drug interactions with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin. Rifampicin and fluconazole reduced the level of the active metabolite (not clinically studied this interaction).
The combination of losartan with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium-sparing additives or salts of potassium can lead to hyperkalemia.
NSAIDs, including selective cyclooxygenase-2 inhibitors can reduce the effects of diuretics and other hypotensive drugs, including losartan. In patients with impaired renal function receiving NSAID therapy (including cyclooxygenase-2 inhibitors), angiotensin II receptor antagonist therapy may result in further deterioration of renal function, including acute renal failure, which is usually reversible.
The hypotensive effect of losartan, like other antihypertensive agents can be reduced when receiving indomethacin.
with thiazide diuretics drugs such as ethanol, barbiturates and narcotics, may potentiate the risk of orthostatic hypotension.
Hypoglycaemic agents (oral and insulin) – may be necessary to adjust the dose of hypoglycemic agents.
Other antihypertensive drugs – additive effect.
Cholestyramine and colestipol – in the presence of anionic exchange resins absorption of hydrochlorothiazide is violated.
Corticosteroids, ACTH (adrenocorticotropic hormone) – marked reduction in the levels of electrolytes, particularly hypokalaemia.
Pressor amines (e.g., epinephrine, norepinephrine) – reduction of expression of pressor response to receiving amines.
Muscle relaxants nondepolarizing type of action (eg, tubocurarine) – strengthening the muscle relaxant effect.
Lithium – diuretics reduce the renal clearance of lithium and increase the risk of toxic action of lithium; concurrent use is not recommended.
NSAIDs (including COX-2 inhibitors) – may reduce the diuretic, natriuretic and antihypertensive effects of diuretics.
In connection with the effect on calcium metabolism taking them may distort the results of the research function of the parathyroid glands.
You can assign along with other antihypertensive agents.
No need for special selection of the initial dose of elderly patients. The drug may increase plasma concentrations of urea and creatinine in patients with bilateral renal artery stenosis or stenosis of the renal artery to a solitary kidney.
Hydrochlorothiazide may enhance hypotension and fluid and electrolyte balance (reduction of circulating blood volume, hyponatremia, gipohloremichesky alkalosis, hypomagnesemia, hypokalemia), disrupt glucose tolerance, reduce calcium excretion in the urine and cause a transient, minor increase in the calcium concentration in blood plasma, to improve the concentration of cholesterol and triglycerides, the occurrence provoke hyperuricaemia and / or gout. Receiving drugs directly acting on the renin-angiotensin system during the II and III trimester of pregnancy can lead to fetal death. In the event of pregnancy shows removal of the drug.
Pregnant women diuretic use is generally 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.
Special warnings regarding the excipients:
Lorista H contains lactose, therefore, can not be appointed under the following conditions: lactase deficiency, equipoise for horses galactosemia or malabsorption syndrome glucose / galactose.
Effects on ability to drive and use other mechanisms
Almost all patients during therapy Loristoy H can perform tasks that require special attention (eg, driving). In individuals at the beginning of drug treatment may cause a decrease in blood pressure and dizziness, thus indirectly affect their psycho-emotional state. For safety reasons, before activities requiring increased attention, patients should first assess their response to treatment. stanazolin 10mg