Lorista N, 100 mg+12, 5 mg 30 pcs

hypotensive combination drug (diuretic + angiotensin II receptor antagonist)

Indications

Active ingredient

Composition

1 film-coated tablet contains:

Core:

Active substances:

Hydrochlorothiazide 12.50 mg

Potassium losartan 100.00 mg

Associates:

Pregelatinized starch, microcrystalline cellulose, lactose monohydrate, magnesium stearate

Shell film:

Hypromellose, macrogol-4000, titanium dioxide (E171), talc

How to take, the dosage

Orally, regardless of the time of meals.

Lorista® N 100 can be used simultaneously with other hypotensive agents.

Arterial hypertension

The recommended dose is 1 tablet (combinations of hydrochlorothiazide 12.5 mg + losartan 100 mg)once daily. Generally, the maintenance dose is 1 tablet (combinations of hydrochlorothiazide 12.5 mg + losartan 50 mg) once daily. The maximum dose is 1 tablet of a combination of hydrochlorothiazide 25 mg + losartan 100 mg once daily. Usually the antihypertensive effect is achieved within 3-4 weeks after the start of therapy. 1 tablet (combinations of hydrochlorothiazide 12.5 mg + losartan 100 mg) once daily is indicated for patients who require additional BP control while taking 100 mg losartan.

Risk reduction in associated cardiovascular morbidity and mortality in patients with AH and left ventricular hypertrophy., demonstrated by cumulative reductions in cardiovascular mortality, stroke and myocardial infarction

1 tablet (combinations of hydrochlorothiazide 12.5 mg + losartan 100 mg) once daily. This dosage form is indicated for patients who do not achieve their target BP values when taking hydrochlorothiazide 12.5 mg and losartan 50 mg once daily.

Special patient groups

Application in patients with impaired renal function and in patients on hemodialysis

The initial dose of the drug does not need to be adjusted in patients with moderate renal dysfunction (CK 30-50 ml/min). The combination of hydrochlorothiazide + losartan is not recommended in patients on hemodialysis. The combination of hydrochlorothiazide + losartan should not be used in patients with severe renal failure (CK values less than 30 ml/min) (see section “Contraindications”).

Application in patients with decreased CPR

The drug Lorista® H 100 should not be used during initial therapy in patients with reduced OBC.

Application in patients with impaired liver function

The use of the drug Lorista® N 100 is contraindicated in patients with severe liver dysfunction (see section “Contraindications”).

Application in elderly patients

Lorista® H 100 should not be used during initial therapy in elderly patients.

Interaction

Hydrochlorothiazide

Unrecommended drug combinations

Lithium preparations

Continuous use of hydrochlorothiazide and lithium preparations decreases renal clearance of lithium which may increase blood plasma lithium concentration and its toxicity. If it is necessary to use hydrochlorothiazide concomitantly, the dose of lithium preparations should be chosen carefully, the concentration of lithium in blood plasma should be controlled regularly, and the dose of the drug should be adjusted accordingly.

Drug combinations that require special attention

Drugs capable of causing polymorphic pirouette-type ventricular tachycardia

Hydrochlorothiazide should be used with extreme caution simultaneously with drugs such as:

– Class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, procainamide);

– antiarrhythmic drugs of class III (dofetilide, ibutilide, bretylium tozilate), sotalol, dronedarone, amiodarone;

– other (non-antiarrhythmic) drugs such as:

– neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpiride, thiapride), butyrophenones (droperidol, haloperidol), pimozide, sertindol;

– antidepressants: tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs) (citalopram, escitalopram);

– antibacterials: fluoroquinolones (levofloxacin, moxifloxacin, sparfloxacin, ciprofloxacin),macrolides (erythromycin intravenously, azithromycin, clarithromycin, roxithromycin, spiramycin), co- trimoxazole;

– antifungal agents: azoles (voriconazole, itraconazole, ketoconazole, fluconazole);

– antimalarials (quinine, chloroquine, mefloquine, halofantrine, lumefantrine);

– antiprotozoal agents (pentamidine in parenteral administration);

– antianginal agents (ranolazine, bepridil);

– antineoplastic agents (vandetanib, arsenic trioxide, oxaliplatin, tacrolimus);

– antiemetics (domperidone,ondansetron);

– agents affecting gastrointestinal motility (cisapride);

– antihistamines (astemizole, terfenadine, misolastin);

– other drugs (anagrelide, vasopressin, difemanil methylsulfate, ketanserin, probucol, propofol, sevoflurane, terlipressin, terodiline, cilostazol).

Due to the increased risk of ventricular arrhythmias, especially pirouette-type polymorphic ventricular tachycardia (hypokalemia is a risk factor), plasma potassium should be determined and, if necessary, corrected before starting combined therapy with hydrochlorothiazide with the above drugs. Monitoring of the patient’s clinical condition, plasma electrolyte content and ECG parameters is necessary. In patients with hypokalemia it is necessary to use agents that do not cause polymorphic ventricular tachycardia of “pirouette” type.

Drugs that can prolong the duration of the interval QT

The concomitant use of hydrochlorothiazide with drugs capable of prolonging QT interval should be based on a careful assessment for each patient of the ratio of expected benefit to potential risk (an increased risk of polymorphic pirouette-type ventricular tachycardia may occur). While using such combinations it is necessary to record ECG regularly (for detection of prolongation of QT interval) as well as to monitor potassium content in blood plasma.

Drugs that can cause hypokalemia: amphotericin B (when administered intravenously), gluco- and mineralocorticosteroids (when administered systemically), tetracosactide (adrenocorticotropic hormone [ACTH]), glycyrrhizic acid (carbenoxolone, preparations containing licorice root), laxatives, stimulating intestinal motility

Increased risk of hypokalemia when concomitantly used with hydrochlorothiazide (additive effect). Regular monitoring of plasma potassium is necessary, and its correction, if necessary. Against the background of hydrochlorothiazide therapy it is recommended to use laxatives which do not stimulate intestinal motility.

Heart glycosides

Hypokalemia and hypomagnesemia caused by thiazide diuretics increase the toxicity of cardiac glycosides. When using hydrochlorothiazide and cardiac glycosides concomitantly, plasma potassium and ECG parameters should be monitored regularly and the therapy should be adjusted if necessary.

Drug combinationsdrug combinations

Other hypotensive drugs

Potentiation of the antihypertensive effect of hydrochlorothiazide (additive effect). It may be necessary to adjust the dose of simultaneously prescribed hypotensive drugs. It is recommended to stop taking hydrochlorothiazide 2-3 days before starting therapy with ACE inhibitors to prevent the development of symptomatic arterial hypotension. If this is not possible, the initial dose of ACE inhibitors should be reduced.

Ethanol, barbiturates, antipsychotics (neuroleptics), antidepressants, anxiolytics, narcotic analgesics and general anesthetic agents

It is possible to enhance the antihypertensive effect of hydrochlorothiazide and potentiate orthostatic hypotension (additive effect).

Nedepolarizing myorelaxants (eg, tubocurarine)

The effect of nondepolarizing myorelaxants may be enhanced.

Adrenomimetics (pressor amines)

Hydrochlorothiazide may decrease the effect of adrenomimetics such as epinephrine (adrenaline) and norepinephrine (noradrenaline).

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors and high doses of acetylsalicylic acid (≥3 g/day)

NSAIDs may decrease the diuretic and antihypertensive effects of hydrochlorothiazide. With concomitant use, there is a risk of acute renal failure due to decreased FFR. Hydrochlorothiazide may increase the toxic effects of high doses of salicylates on the central nervous system.

Hypoglycemic agents for oral administration and insulin

Thiazide diuretics affect glucose tolerance (development of hyperglycemia is possible) and reduce the effectiveness of hypoglycemic agents (correction of the dose of hypoglycemic agents may be required).

We should use hydrochlorothiazide and metformin with caution due to the risk of lactoacidosis due to hydrochlorothiazide-induced renal dysfunction.

Beta-adrenoblockers, diazoxide

Simultaneous use of thiazide diuretics (including hydrochlorothiazide) with beta-adrenal blockers or diazoxide may increase the risk of hyperglycemia.

Drugs used to treat gout (probenecid, sulfinpyrazone, allopurinol)

Dose adjustment of uricosuric drugs may be necessary because hydrochlorothiazide increases serum uric acid concentrations. Thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol.

Amantadine

Thiazide diuretics (including hydrochlorothiazide) may decrease amantadine clearance, lead to higher plasma amantadine concentrations, and increase the risk of adverse effects.

Anticholinergic drugs (choline blockers)

Anticholinergic drugs (e.g., atropine, biperiden) increase bioavailability of thiazide diuretics by reducing gastrointestinal motility and gastric emptying rate.

Cytotoxic (antitumor) drugs

Thiazide diuretics reduce renal excretion of cytotoxic drugs (e.g., cyclophosphamide and methotrexate) and potentiate their myelosuppressive effects.

Methyldopa

Cases of hemolytic anemia have been described when hydrochlorothiazide and methyldopa have been used simultaneously

Antioepileptic drugs (carbamazepine, oxcarbazepine, topiramate)

Risk of symptomatic hyponatremia. When concomitant use of hydrochlorothiazide and carbamazepine, the patient’s condition should be monitored and serum sodium should be controlled. When using hydrochlorothiazide and topiramate concomitantly, the content of topiramate in blood serum should also be monitored; if necessary, potassium preparations should be administered or the dose of topiramate should be adjusted.

SNPS

Concomitant use with thiazide diuretics may potentiate hyponatremia. It is necessary to control the sodium content in plasma.

Cyclosporine

The simultaneous use of thiazide diuretics and cyclosporine increases the risk of hyperuricemia and gout exacerbation.

Oral anticoagulants

Thiazide diuretics may decrease the effect of oral anticoagulants.

Iodine contrast agents

Body dehydration from thiazide diuretics increases the risk of acute renal failure, especially when using high doses of iodine-containing contrast agents. Before the use of iodine-containing contrast agents it is necessary to compensate the fluid loss.

Calcium preparations

When concomitant use is possible, increase of plasma calcium content and development of hypercalcemia due to decrease of calcium ions excretion by kidneys. If simultaneous use of calcium containing medicines is necessary, the calcium content in plasma should be monitored and the dose of calcium preparations should be corrected.

Anionic exchange resins (colestyramine and colestipol)

Anionic exchange resins decrease absorption of hydrochlorothiazide. Single doses of colestiramine and colestipol reduce absorption of hydrochlorothiazide in the GI tract by 85% and 43%, respectively.

Lozartan

In clinical trials, no clinically significant interactions of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole, and erythromycin were found.

Rifampicin and fluconazole reduce the concentration of the active metabolite (this interaction is not clinically studied).

Simultaneous use with kali-saving diuretics (spironolactone, eplerenone, triamterene, amiloride), potassium preparations or potassium-containing table salt substitutes, as well as use of other drugs that increase plasma potassium levels, increases the risk of hyperkalemia.

NSAIDs, including selective COX-2 inhibitors, may reduce the effect of diuretics and other hypotensive agents, including losartan. The antihypertensive effect of losartan, as well as other hypotensive agents, may be reduced by the use of indomethacin. Concomitant use of ARA II or diuretics with NSAIDs may cause an increased risk of impaired renal function, including acute renal failure, and increased plasma potassium, especially in patients with underlying renal impairment. Combined treatment should be administered with caution, especially in elderly patients. Adequate hydration of patients should be provided and renal function should be monitored after the start of combined treatment and periodically during treatment. In some patients with impaired renal function treated with NSAIDs, including selective COX-2 inhibitors, concomitant use of ARA II may aggravate renal impairment. These effects are usually reversible.

Double RAAS blockade

The concomitant use of ARA II with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate to severe renal impairment (FFR less than 60 mL/min/1.73 m2 body surface area) and is not recommended in other patients. Concomitant use of ARA II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Double blockade of the RAAS by simultaneous use of ACP inhibitors, ARA IIor aliskiren has been shown in clinical studies to is associated with a higher incidence of adverse events such as arterial hypotension, hyperkalemia, and decreased renal function (including acute renal failure) compared to RAAS monotherapy.

A decrease in lithium ion excretion is possible. Therefore, when using ARA II concomitantly with lithium salts, serum concentrations of lithium should be monitored carefully.

Other drugs that lower BP, such as tricyclic antidepressants, neuroleptics, baclofen, amifostine: Simultaneous use of losartan with these drugs may increase the risk of arterial hypotension.

Special Instructions

Bilateral renal artery stenosis or stenosis of the artery of a single kidney, hyperkalemia, conditions after kidney transplantation (no experience of use), aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy (HOCMP), CHF with associated severe renal impairment, severe CHF (NYHA functional class IV), CHF with life-threatening arrhythmias, coronary heart disease (CHD), cerebrovascular disease, primary hyperaldosteronism, history of angioedema, arterial hypotension, liver dysfunction, renal dysfunction, water-electrolyte imbalance patients with decreased BOD (e.g., those treated with high doses of diuretics) due to the possibility of symptomatic arterial hypotension, hypokalemia, hyponatremia, hypercalcemia, concomitant use of drugs, concomitant use of drugs that may cause polymorphic ventricular tachycardia of “pirouette” type or increase the QT interval duration on ECG, concomitant use of drugs that may cause hypokalemia, cardiac glycosides, history of allergic reactions to penicillin, hyperparathyroidism, hyperuricemia, gout, history of nonmelanoma skin cancer (NSCLC) (see sect. See section “Special Indications”).

It is contraindicated in persons under 18 years of age (efficacy and safety have not been established).

Application in patients with impaired renal function and in patients on hemodialysis

The initial dose of the drug in patients with moderate renal function impairment (CKD 30-50 ml/min) is not required. The combination of hydrochlorothiazide + losartan is not recommended in patients on hemodialysis. The combination of hydrochlorothiazide + losartan should not be used in patients with severe renal failure (CK values less than 30 ml/min) (see section “Contraindications”).

Application in patients with decreased CPR

The drug Lorista® H 100 should not be used during initial therapy in patients with reduced OBC.

Application in patients with impaired liver function

The use of the drug Lorista® N 100 is contraindicated in patients with severe liver dysfunction (see section “Contraindications”).

Application in elderly patients

Lorista® H 100 should not be used during initial therapy in elderly patients.

The use of Lorista® H 100 in patients with acute myocardial infarction is not recommended due to insufficient experience in clinical use.

Also, Lorista® N 100 should not be used to control hypertensive crisis.

Combination of hydrochlorothiazide + losartan

Children and adolescents

There is no experience with the combination of hydrochlorothiazide + losartan in children and adolescents.

If neonates whose mothers have taken Lorista® N 100 during pregnancy develop oliguria or arterial hypotension, symptomatic therapy to maintain BP and renal perfusion is necessary. Blood transfusion or dialysis may be required to prevent the development of arterial hypotension and/or maintain renal function.

Elderly patients

Clinical studies have not identified any features regarding the safety and efficacy of the combination of hydrochlorothiazide + losartan in elderly patients (over 65 years).

Hydrochlorothiazide

Kidney function disorders

In patients with renal function disorders, hydrochlorothiazide may cause azotemia. In patients with renal insufficiency, hydrochlorothiazide may cumulate.

In patients with decreased renal function, periodic CK monitoring is necessary. In progression of renal function impairment and/or onset of oliguria (anuria), hydrochlorothiazide should be discontinued.

Liver function disorders

When using thiazide diuretics in patients with hepatic dysfunction, hepatic encephalopathy may develop. In patients with severe hepatic insufficiency or hepatic encephalopathy thiazide use is contraindicated. In patients with mild to moderate hepatic insufficiency and/or progressive liver disease hydrochlorothiazide should be used with caution, since even a slight change of electrolyte-water balance and accumulation of ammonium in blood serum may cause hepatic coma. In case of encephalopathy symptoms the use of diuretics should be immediately stopped.

Water-electrolyte balance and metabolic disorders

Synopsis

Oval, biconvex, white film-coated tablets.

Breakage appearance: white rough mass with white film coating.

Contraindications

Hypersensitivity to any of the drug components, hypersensitivity to other sulfonamide derivatives, anuria, severe renal dysfunction (CK less than 30 ml/min), therapy-resistant hypokalemia or hypercalcemia, severe hepatic dysfunction, cholestasis and biliary obstruction, resistant hyponatremia, Symptomatic hyperuricemia/podagra, dehydration, severe arterial hypotension, difficult to control diabetes, Addison’s disease, concomitant use with aliskiren or drugs containing aliskiren in patients with diabetes and/or with moderate to severe renal function impairment (glomerular filtration rate [GFR] less than 60 mL/min/1.73 m

Overdose

Hydrochlorothiazide + losartan

There are no data on the specific treatment of overdose with the combination hydrochlorothiazide + losartan. Treatment is symptomatic and supportive. Administration of Lorista® H 100 should be discontinued and the patient should be monitored. If the drug has been taken recently, provocation of vomiting is recommended, as well as elimination of dehydration, water-electrolyte disturbances, hepatic coma and BP reduction by standard methods.

Hydrochlorothiazide

Symptoms

The most common manifestations of hydrochlorothiazide overdose are increased diuresis accompanied by acute fluid loss (dehydration) and electrolyte disturbances (hypokalemia, hyponatremia, hypochloremia). Overdose with hydrochlorothiazide may manifest as the following symptoms:

– cardiovascular system: tachycardia, BP decrease, shock;

– nervous system: weakness, confusion, dizziness and spasms of the calf muscles, paresthesia, disorders of consciousness, fatigue;

– gastrointestinal tract: nausea, vomiting, thirst;

– Renal and urinary tract: polyuria, oliguria, or anuria (due to hemoconcentration);

– laboratory parameters: hypokalemia, hyponatremia, hypochloremia, alkalosis, increased concentration of residual urea nitrogen in blood plasma (especially in patients with renal failure).

Treatment

In overdose symptomatic and supportive therapy is carried out. If hydrochlorothiazide has been taken recently, induction of vomiting or gastric lavage are indicated for its elimination. Absorption of hydrochlorothiazide may be reduced by ingestion of activated charcoal. In case of BP decrease or shock it is necessary to replenish CIC by administration of plasma exchange fluids and electrolyte deficit (potassium, sodium). In case of respiratory failure, oxygen inhalation or artificial lung ventilation is indicated. Water-electrolyte balance (especially serum potassium content) and renal function should be controlled until their normalization.

no specific antidote. Hydrochlorothiazide is excreted by hemodialysis, but the extent of its excretion has not been established.

Lozartan

Information about overdose is limited.

Symptoms

The most likely manifestation of overdose is a marked decrease in BP and tachycardia; bradycardia may occur due to parasympathetic (vagus) stimulation.

Treatment

Symptomatic therapy. In case of symptomatic arterial hypotension, supportive therapy is indicated.

Losartan and its active metabolite are not excreted by hemodialysis.

Pregnancy use

Pregnancy

Hydrochlorothiazide + losartan

The use of Lorista® N 100 is contraindicated in pregnancy. Drugs that affect the renin-angiotensin-aldosterone system (RAAS) can cause serious damage and fetal death, so the combination of hydrochlorothiazide + losartan should be immediately cancelled if pregnancy is diagnosed.

If oligohydramnios is detected, the hydrochlorothiazide + losartan combination should be discontinued unless it is vital for the mother. Depending on the gestational age, appropriate fetal tests should be performed. Patients and physicians should be aware that oligohydramnion may not be detectable until irreversible fetal damage has occurred. Newborns whose mothers have taken the hydrochlorothiazide + losartan combination during pregnancy should be closely monitored to control arterial hypotension, oliguria, and hyperkalemia.

Hydrochlorothiazide

There is limited experience with hydrochlorothiazide during pregnancy (especially in the first trimester). Preclinical data regarding safety are insufficient.

Hydrochlorothiazide penetrates the placental barrier and is determined in umbilical cord blood. Taking into account the mechanism of the pharmacological action of hydrochlorothiazide its use in the second and third trimesters of pregnancy can disrupt the feto-placental perfusion and lead to the development in the fetus and newborn of such complications as jaundice, electrolyte-water balance disorders and thrombocytopenia. Cases of thrombocytopenia have been described in newborns whose mothers received thiazide diuretics.

The use of hydrochlorothiazide during pregnancy is contraindicated. Hydrochlorothiazide should not be used for the treatment of gestosis in the second half of pregnancy (edema, AH, or preeclampsia), as it increases the risk of decreased blood circulation and placental hypoperfusion, but does not have a beneficial effect on the course of these pregnancy complications. Diuretics do not prevent the development of gestosis.

Lozartan

While there is no experience with the use of losartan in pregnant women, preclinical animal studies have shown that administration of losartan results in the development of serious fetal and neonatal damage and fetal or offspring death. The mechanism of these phenomena is thought to be due to the effect on the RAAS.

Fetal renal perfusion dependent on the development of RAAS appears in the second trimester, so the risk to the fetus increases if the combination of hydrochlorothiazide + losartan is used in the second and third trimesters of pregnancy.

The use of drugs affecting the RAAS in the second and third trimester of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and mortality. The development of oligohydramnios may be associated with fetal lung hypoplasia and skeletal deformity. Possible adverse events in newborns include skull bone hypoplasia, anuria, arterial hypotension, renal failure, and death.

The above adverse outcomes are usually caused by the use of drugs affecting the RAAS in the second and third trimesters of pregnancy. Most epidemiological studies of fetal abnormalities after the use of hypotensive drugs in the first trimester of pregnancy have found no differences between RAAS-acting drugs and other hypotensive agents. When prescribing hypotensive therapy to pregnant women, it is important to optimize the possible outcomes for the mother and the fetus.

If alternative therapy cannot be chosen to replace therapy with drugs acting on the RAAS, the patient should be informed about the possible risk of therapy to the fetus. Periodic ultrasound examinations to evaluate the intraamniotic space should be performed.

Breastfeeding period

Hydrochlorothiazide + losartan

The use of Lorista® N 100 is contraindicated during breastfeeding. Because many drugs are excreted with breast milk and there is a risk of possible adverse effects in a breast-fed baby, it is necessary to decide to stop breast-feeding or to cancel the drug taking into account the necessity of its intake for a mother.

Hydrochlorothiazide

Hydrochlorothiazide penetrates the mother’s milk, due to which its use during breastfeeding is contraindicated. If the use of hydrochlorothiazide during lactation is absolutely necessary, breastfeeding should be stopped.

Lozartan

It is unknown whether losartan is excreted with breast milk.

Similarities