Universal reference book for medicines
Product name: LORISTA ® H 100 (LORISTA ® H 100)

Active substance: hydrochlorothiazide, losartan

Type: Antihypertensive drug

Manufacturer: KRKA (Slovenia)
Composition, form of production and packaging
The tablets covered with a film shell of
white color, oval, biconcave;
on a cross-section - a white rough mass with a film shell of white color.
1 tab.

Losartan Potassium 100 mg

hydrochlorothiazide 12.5 mg

Excipients: pregelatinized starch - 59.2 mg, microcrystalline cellulose - 137.1 mg, lactose monohydrate - 88.4 mg, magnesium stearate - 2.8 mg.

Composition of the film coat: hypromellose - 8 mg, macrogol 4000 - 0.8 mg, titanium dioxide (E171) - 2.4 mg, talc - 0.8 mg.

10 pieces.
- blisters (3) - packs of cardboard.
10 pieces.
- blisters (9) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2015.

PHARMACHOLOGIC EFFECT

Combined antihypertensive drug.
Losartan and hydrochlorothiazide have an additive antihypertensive effect, reducing blood pressure more than each of the components individually.
Due to the diuretic effect, hydrochlorothiazide increases plasma renin activity, stimulates aldosterone secretion, increases the concentration of angiotensin II, and reduces the concentration of potassium in the blood plasma.
The administration of losartan blocks all the physiological effects of angiotensin II and, due to suppression of aldosterone effects, can help reduce the loss of potassium associated with taking 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.
Losartan

Losartan is a selective antagonist of angiotensin II receptor (type AT 1 ) for oral administration.
In vivo and in vitro, losartan and its pharmacologically active metabolite E-3174 block all physiologically significant effects of angiotensin II on AT 1 -receptors regardless of the route of its synthesis: leads to an increase in renin plasma activity, reduces the concentration of aldosterone in the blood plasma. Losartan indirectly causes the activation of AT 2 -receptors by increasing the concentration of angiotensin II.
Does not inhibit the activity of kininase II, an enzyme that is involved in the metabolism of bradykinin.
Reduces OPSS, pressure in a small circle of blood circulation, reduces afterload on the myocardium, has a diuretic effect. Prevents development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure (CHF). The administration of losartan 1 time / day leads to a statistically significant decrease in systolic and diastolic blood pressure.
Lozartan evenly controls blood pressure during the day, while the antihypertensive effect corresponds to a natural circadian rhythm.
Decrease in blood pressure at the end of the dose was about 70-80% of the maximum effect of losartan, 5-6 hours after ingestion. There is no withdrawal syndrome.
Losartan has no clinically significant effect on heart rate.

Losartan is effective in men and women, as well as in patients older than 65 years and younger patients, younger than 65 years.

Hydrochlorothiazide

A thiazide diuretic whose diuretic effect is associated with a disruption of the reabsorption of sodium, chlorine, potassium, magnesium, water in the distal nephron;delays the excretion of calcium ions, uric acid.
Has an antihypertensive effect, the effect of which is due to the expansion of arterioles. Virtually no effect on normal blood pressure. Diuretic effect occurs in 1-2 hours, reaches a maximum after 4 hours and lasts for 6-12 hours. The maximum antihypertensive effect occurs in 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect.
PHARMACOKINETICS

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

Losartan

Suction

After ingestion losartan is well absorbed from the digestive tract.
It is subject to significant metabolism during the "first passage" through the liver, forming a pharmacologically active carboxylated metabolite (E-3174) and inactive metabolites. Bioavailability is approximately 33%. The average C max of losartan and its active metabolite is reached after 1 hour and 3-4 hours, respectively.
Distribution

Lozartan and its active metabolite bind to plasma proteins (mainly albumins) by more than 99%.
V d of losartan is 34 liters.
Very poorly penetrates the BBB.

Metabolism

Lozartan is metabolized with the formation of active (E-3174) metabolite (14%) and inactive, including the two main metabolites formed by hydroxylation of the butyl group of the chain and a less significant metabolite, N-2-tetrazole glucuronide.

Excretion

The plasma clearance of losartan and its active metabolite is approximately 10 ml / sec (600 ml / min) and 0.83 ml / s (50 ml / min), respectively.
The renal clearance of losartan and its active metabolite is about 1.23 ml / s (74 ml / min) and 0.43 ml / s (26 ml / min). T 1/2 of losartan and the active metabolite is 2 h and 6-9 h ,respectively. Excreted mainly with bile through the intestine - 58% , kidneys - 35% . Do not cumulate.
When administered orally at doses up to 200 mg, losartan and its active metabolite have a linear pharmacokinetics.

Hydrochlorothiazide

Suction

After oral intake of hydrochlorothiazide is 60-80%.
C max in blood plasma is achieved 1-5 hours after ingestion.
Distribution

Binding to blood plasma proteins - 64%.

Penetrates through the placental barrier.
Excreted in breast milk.
Metabolism and excretion

Hydrochlorothiazide is not metabolized and is rapidly excreted by the kidneys.
T 1/2 is 5-15 hours. At least 61% of the ingested dose is excreted unchanged for 24 hours.
Pharmacokinetics in special clinical cases

Losartan + hydrochlorothiazide

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 significantly differ from these indices in patients of young age with arterial hypertension.

Losartan

The concentration of losartan in blood plasma was 2 times higher in women with arterial hypertension compared with men with arterial hypertension.
This pharmacokinetic difference is not clinically significant. The concentration of active metabolite in men and women does not differ.
When losartan was administered orally to patients with mild and moderate alcoholic cirrhosis, the concentrations of losartan and its active metabolite in blood plasma were 5-1.7 times higher, respectively, than in young male volunteers.

Concentrations of losartan in blood plasma in patients with QC above 10 ml / min did not differ from those in patients with preserved renal function.
When comparing the values ​​of AUC in patients with normal renal function, the AUC of losartan in patients on hemodialysis was approximately 2-fold greater. Plasma concentrations of the active metabolite do not change in patients with impaired renal function or patients on hemodialysis. Lozartan and its active metabolite can not be removed by hemodialysis.
INDICATIONS

- arterial hypertension (patients who are shown combined therapy);

- reduced risk of cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy.

DOSING MODE

I take it inside, regardless of the meal.

The drug Lorista ® H 100 can be combined with other antihypertensive drugs.

Arterial hypertension

The recommended dose of Lorist ® N 100 is 1 tablet.
(100 mg / 12.5 mg) 1 time / day. As a rule, the drug is prescribed in the absence of an adequate therapeutic effect of Lorist® H (50 mg / 12.5 mg).
The maximum antihypertensive effect is achieved within 3 weeks of therapy.

In elderly patients, in patients with impaired renal function (CK 30-50 ml / min), including patients on dialysis , correction of the initial dose is not required.

Reducing the risk of cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy

The initial and maintenance dose of losartan is 50 mg 1 time / day.

Patients who failed to achieve the target blood pressure level when using losartan at a dose of 50 mg / day require selection of therapy by a combination of losartan with low doses of hydrochlorothiazide (12.5 mg).
If necessary, it is possible to increase the dose of losartan to 100 mg in combination with hydrochlorothiazide at a dose of 12.5 mg / day.
The recommended dose of Lorist ® N is 100-1 tab.
(100 mg / 12.5 mg) 1 time / day.
The maximum daily dose is 1 tablet.
preparation Lorist ® H 100.
In patients with impaired renal function, dose adjustment is not required.

In elderly patients, dose adjustment is not required.

SIDE EFFECT

Classification of the incidence of adverse events (WHO): very often (? 1/10), often (from? 1/100 to <1/10), infrequently (from? 1/1000 to <1/100), rarely (from? 1/10 000 to <1/1000), very rarely (from <1/10 000, including individual messages), the frequency is unknown (the frequency can not be estimated from the available data).

On the part of the immune system: rarely - anaphylactic reactions, angioedema (including swelling of the larynx and tongue, causing airway obstruction and / or swelling of the face, lips, pharynx), urticaria rash.

On the part of the hematopoiesis system: infrequently - anemia, purpura Shenlaine-Henoch, ecchymosis, hemolysis, agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, thrombocytopenia.

From the nervous system: often - headache, dizziness, insomnia, increased fatigue;
infrequently - migraine, anxiety, confusion, depression, sleep disorders, memory impairment, drowsiness, nervousness, paresthesia, tremor, fainting.
From the cardiovascular system: often - orthostatic hypotension (dose-dependent), palpitations, tachycardia;
infrequently - AV-blockade II degree, chest pain, myocardial infarction, arrhythmia; rarely - vasculitis.
On the part of the respiratory system: often - cough, upper respiratory tract infections, sinusitis, swelling of the nasal mucosa, nasal congestion;
infrequently - pharyngitis, laryngitis, rhinitis, dyspnea, bronchitis, nosebleeds.
On the part of the digestive system: often - diarrhea, dyspepsia, nausea, vomiting, abdominal pain;
rarely - hepatitis, a violation of the liver.
From the urinary system: infrequently - urinary tract infections, frequent urination, nocturia, glucosuria.

On the part of the reproductive system: infrequently - weakening of the libido, a decrease in potency.

From the senses: infrequently - blurred vision, burning sensation in the eyes, conjunctivitis.

From the skin: often - alopecia, dry skin, erythema, photosensitivity, increased sweating;
infrequently - hives, itchy skin.
From the musculoskeletal system: often - myalgia, back pain;
infrequently - arthralgia.
Other: often - asthenia, weakness, peripheral edema;
infrequently - anorexia, exacerbation of gout.
On the part of laboratory indicators: often - hyperkalemia, a slight decrease in the concentration of hemoglobin and hematocrit;
infrequent - a moderate increase in the concentration of urea and creatinine in the blood plasma, hyperglycemia, hyperuricemia, violations of the water-electrolyte balance; rarely - increased ALT activity; very rarely - increased activity of ACT and bilirubin concentration.
CONTRAINDICATIONS

anuria;

- severe renal failure (CK <30 ml / min);

severe hepatic impairment;

- Pregnancy;

- the period of lactation (breastfeeding);

- children and adolescents under 18 years of age (efficacy and safety not established);

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

- hypersensitivity to the components of the drug;

- hypersensitivity to sulfonamide derivatives.

With caution: violations of the water-electrolyte balance of blood (hyponatremia, hypochloraemic alkalosis, hypomagnesemia, hypokalemia), bilateral stenosis of the renal arteries, artery stenosis of the only functioning kidney, condition after kidney transplantation, hypercalcemia, hyperuricemia and / or gout, allergic history, bronchial asthma , systemic connective tissue diseases (including systemic lupus erythematosus), concurrent use of NSAIDs, including COX-2 inhibitors, diabetes mellitus, impaired function
kidney damage (KK from 30-50 ml / min), hypovolemia (including against the background of taking diuretics in high doses), acute attack of closed-angle glaucoma.
PREGNANCY AND LACTATION

The use of Lorist® H 100 is contraindicated in pregnancy.
Means that directly affect RAAS, when used in the second and third trimesters of pregnancy, can cause developmental defects or even fetal death. Therefore, when pregnancy occurs, the drug Lorist® N 100 should be discontinued immediately.
Thiazide diuretics penetrate the placental barrier and are identified in the blood of the umbilical vein.
The use of diuretics in pregnant women is not recommended. this increases the risk of fetal embryonic jaundice and jaundice of newborns, and the mother - thrombocytopenia.
The use of Lorist® H 100 is possible if the benefit to the mother exceeds the potential risk to the fetus / child.

There is no evidence that losartan is excreted in breast milk.

It is known that thiazide diuretics are excreted in breast milk.

If you need to use Lorist ® H 100 during lactation, breastfeeding should be discontinued.

APPLICATION FOR FUNCTIONS OF THE LIVER

Contraindicated in renal failure of severe degree (CK <30 ml / min).

With caution in light and moderate disorders of kidney function (KK from 30-50 ml / min).

APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Contraindicated in severe violations of liver function.

With caution when
light and moderate liver function disorders.
APPLICATION FOR CHILDREN

Contraindicated in children and adolescents under 18 years.

APPLICATION IN ELDERLY PATIENTS

In elderly patients, dose adjustment is not required.

SPECIAL INSTRUCTIONS

Losartan

Renal impairment

Against the background of the use of losartan, reversible renal dysfunction, including renal failure, that occur after the withdrawal of losartan is possible.
Drugs that affect RAAS can lead to an increase in the concentration of urea and creatinine in the blood plasma in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney. These changes in kidney function may be reversible and occur after the withdrawal of therapy.
In patients with impaired renal function receiving NSAID therapy (including COX-2 inhibitors), therapy with angiotensin II receptor antagonists can lead to further impairment of renal dysfunction, including acute kidney failure, which is usually reversible, and also increase potassium concentration in blood plasma in patients with pre-existing renal dysfunction.
This combination is recommended for use with caution, especially in elderly patients. Patients should receive a sufficient amount of fluid, as well as monitor kidney function before and after treatment with Lorist® H 100.
Hydrochlorothiazide

Arterial hypotension and disturbance of water-electrolyte balance

As with any antihypertensive drug, symptomatic hypotension may occur in patients.
Patient status should be monitored in order to timely identify clinical signs of water-electrolyte balance disorders, such as dehydration, hyponatremia, hypochloraemic alkalosis, hypomagnesemia, or hypokalemia, which may develop with concomitant diarrhea or vomiting. Such patients need control of the electrolyte content in the blood plasma.
Metabolic and endocrine effects

Therapy with thiazide diuretics can impair glucose tolerance.
In some cases, dosage adjustment of hypoglycemic agents for ingestion and / or insulin may be required.
Thiazides can reduce the excretion of calcium by the kidneys and cause a short-term and insignificant increase in the concentration of calcium in the blood plasma.Expressed hypercalcemia may indicate latent hyperparathyroidism.

Due to the influence of thiazides on calcium metabolism, their use can distort the results of the study of parathyroid gland function, therefore, before the study of parathyroid function, the thiazide diuretic should be canceled.

Increasing the concentration of cholesterol and triglycerides of blood can also be associated with therapy with thiazide diuretics.

In some patients, the use of thiazide diuretics can lead to hyperuricemia and / or gout development.
Since losartan reduces the concentration of uric acid, its combination with hydrochlorothiazide reduces the severity of hyperuricemia caused by a diuretic.
Acute attack of angle-closure glaucoma

Hydrochlorothiazide is a sulfonamide, which can cause an idiosyncratic reaction leading to the development of an acute attack of closed-angle glaucoma.

Symptoms: sudden reduction in visual acuity or pain in the eyes, which appear, usually within a few hours or weeks of the initiation of hydrochlorothiazide therapy.
In the absence of treatment, an acute attack of angle-closure glaucoma can lead to a permanent loss of vision.
Treatment: stop taking hydrochlorothiazide immediately.
If intraocular pressure remains uncontrolled, immediate medical treatment or surgery may be required. Risk factors for the development of an acute attack of closed-angle glaucoma are the allergic reaction to sulfonamide or benzylpenicillin in the anamnesis.
Other effects

In patients receiving thiazide diuretics, hypersensitivity reactions can be observed even in the absence of an anamnesis indicating the presence of allergic reactions or bronchial asthma.
There are reports of the development of exacerbation or progression of systemic lupus erythematosus against the use of thiazide diuretics.
Excipients

It should be borne in mind that the composition of the auxiliary substances of the drug Lorist ® H 100 includes lactose monohydrate, therefore the drug is contraindicated in patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.

Impact on the ability to drive vehicles and manage mechanisms

Caution should be exercised when driving and operating with other technical devices that require high concentration and psychomotor speed reactions.
OVERDOSE

losartan
Symptoms: marked decrease in blood pressure, tachycardia;
bradycardia caused by parasympathetic (vagal) stimulation.
Treatment: forced diuresis, symptomatic therapy, hemodialysis ineffective.
Hydrochlorothiazide

Symptoms: The most common symptoms are a consequence of violations of water-electrolyte balance (hypokalaemia, chloropenia, hyponatremia) and dehydration due to excessive diuresis. With simultaneous use of cardiac glycosides may exacerbate hypokalemia arrhythmias.
Treatment: symptomatic and supportive. Not assigned to what extent hydrochlorothiazide can be removed from the body by hemodialysis.
Lorista ® N 100
No data on the specific treatment of drug overdose Lorista ® H 100.
Treatment: holding symptomatic and supportive therapy. Application Lorista preparation ®H 100 must be stopped and the patient is subject to monitoring. If the drug Lorista ® N 100 adopted recently recommended provocation vomiting, dehydration and removal (recovery bcc), hepatic coma and pronounced reduction in blood pressure by standard techniques.
DRUG INTERACTION

Losartan
In clinical studies found no clinically significant drug interactions with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, erythromycin and ketoconazole.
Rifampicin Fluconazole and reduce the concentration of the active metabolite (this interaction is not clinically studied).
The simultaneous use of potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride), potassium preparations or potassium-containing salt substitutes and the use of other drugs that increase the concentration of potassium in the blood plasma, increase the risk of hyperkalemia.
NSAIDs, including selective inhibitors of COX-2 may reduce the effects of diuretics and other hypotensive drugs, including losartan.
The antihypertensive effect of losartan, like other antihypertensive agents can be reduced when applying indomethacin.
Dual blockade of the RAAS, ie addition to ACE inhibitor therapy angiotensin II receptor antagonist, is only possible in individual cases under careful control of renal function.
Patients with atherosclerosis, heart failure or diabetes with end-organ damage, dual blockade of the RAAS (while the use of angiotensin II receptor antagonists, ACE inhibitors or aliskiren) is accompanied by an increased incidence of hypotension, syncope, hyperkalemia, and renal dysfunction (including acute renal failure) as compared with the use of the preparation of one of these groups.
May reduce the excretion of lithium ions. Therefore, while the use of angiotensin II receptor antagonists with lithium salts should be carefully monitored serum concentrations of lithium.
Hydrochlorothiazide

While the use of thiazide diuretic drugs such as ethanol, barbiturates, and opioid analgesics may potentiate the risk of development of orthostatic hypotension.
With simultaneous use may increase hypoglycemic action hypoglycemic agents for oral use (sulfonylurea derivatives) and / or insulin in patients with diabetes mellitus; if such combinations may increase glucose tolerance which may require correction doses hypoglycemic agents for oral and / or insulin.
When applied simultaneously with other antihypertensives - additive effect.
Absorption of hydrochlorothiazide is broken in the presence of cholestyramine and colestipol.
While the use of corticosteroids, ACTH observed marked reduction in the content of electrolytes, particularly hypokalemia.
A decrease in expression of the therapeutic effect of hydrochlorothiazide on the background of pressor amines (e.g., epinephrine (adrenaline), norepinephrine (noradrenaline)).
Hydrochlorothiazide enhances the effect of non-depolarizing muscle relaxant action type (e.g., tubocurarine chloride).
Diuretics reduce the renal clearance of lithium and increase the risk of toxic action of lithium. Simultaneous use is not recommended.
While the use of barbiturates, narcotic analgesics, antidepressants, ethanol increases the risk of orthostatic hypotension.
Drugs used for treating gout (probenecid, sulfinpyrazone and allopurinol): hydrochlorothiazide is capable of increasing serum concentrations of uric acid, therefore, may need a dose correction preparations urikozuricheskogo action - increasing the dose of probenecid or sulfinpirazona. The simultaneous use of thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol.
Concomitant use of cyclosporine may increase the risk of hyperuricemia and lead to exacerbation of gout.
Anticholinergics (e.g., atropine, biperiden) increase the bioavailability of thiazide diuretics by decreasing gastrointestinal motility and gastric emptying rate.
Thiazide diuretics may reduce renal excretion of cytotoxic drugs (cyclophosphamide, methotrexate) and enhance their myelosuppressive effects.
In the case of high-dose salicylates hydrochlorothiazide may enhance their toxic effects on the CNS.
There are limited data about the development of hemolytic anemia with concomitant use of hydrochlorothiazide and methyldopa.
Thiazide diuretics induced hypokalemia or hypomagnesemia may lead to fibrillation during treatment with cardiac glycosides.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

TERMS AND CONDITIONS OF STORAGE

The drug should be kept out of the reach of children, protected from moisture in the original packaging, at a temperature not higher than 30 ° C.
Shelf life - 3 years.
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