Lorista N, 50 mg+12, 5 mg 90 pcs

hypotensive combined agent (diuretic + angiotensin II receptor antagonist).

Indications

– Arterial hypertension (patients indicated for combination therapy).

– Reduced cardiovascular morbidity and mortality risk in patients with arterial hypertension and left ventricular hypertrophy as manifested by cumulative reductions in cardiovascular mortality, stroke and myocardial infarction rates.

Active ingredient

Composition

1 film-coated tablet contains:

Kernel:

Active substances:

Hydrochlorothiazide 12.50 mg

Potassium losartan 50.00 mg

Auxiliary substances:

Pregelatinized starch, microcrystalline cellulose, lactose monohydrate, magnesium stearate

Shell film:

Hypromellose, macrogol-4000, quinoline yellow dye (E104), titanium dioxide (E171), talc

.

How to take, the dosage

Orally, regardless of the time of meals, with plenty of water, once a day. Lorista® N may be taken simultaneously with other hypotensive drugs.

Arterial hypertension

The starting and maintenance dose is 1 tablet of Lorista® H (hydrochlorothiazide 12.5 mg and losartan 50 mg) once daily. In patients without adequate therapeutic response to administration of 1 tablet of Lorista® N once daily for 2-4 weeks, the drug dose may be increased to 2 tablets of Lorista® N once daily.Maximum daily dose is 2 tablets of the drug Lorista® H once a day. Usually the maximum antihypertensive effect is achieved within 3 weeks after the start of therapy.

Risk reduction in cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy

The standard starting dose of losartan is 50 mg once daily. Patients who have failed to achieve target BP values on losartan 50 mg/day should select therapy by combining losartan with low-dose hydrochlorothiazide (12.5 mg). If necessary, the dose of losartan can be increased to 100 mg/day in combination with hydrochlorothiazide at a dose of 12.5 mg/day and further increased to 2 tablets of Lorista ® N (total 25 mg hydrochlorothiazide and 100 mg losartan)once daily.Other hypotensive drugs should be added if additional BP reduction is necessary.

Special patient groups

Patients with impaired renal function or patients on hemodialysis

In patients with moderate renal impairment (CK 30-50 ml/min), no adjustment of the initial dose of the drug is required. The drug Lorista® H is not recommended in patients on hemodialysis. The drug Lorista® H should not be used in patients with severe renal dysfunction (CK less than 30 ml/min) (see section “Contraindications”).

Patients with decreased CPR

Before starting treatment with Lorista®H, the CBC and/or plasma sodium ion content should be restored.

Patients with impaired liver function

The drug Lorista®H is contraindicated in patients with severe liver function impairment (see section “Contraindications”).

Elderly patients

Dose adjustment of Lorista® H is not required.

Interaction

Hydrochlorothiazide

Unrecommended drug combinations

Lithium drugs

The simultaneous use of hydrochlorothiazide and lithium drugs decreases renal clearance of lithium, which may result in increased plasma lithium concentrations and increased toxicity. If simultaneous use of hydrochlorothiazide is necessary, the dose of lithium preparations should be carefully selected, plasma concentration of lithium should be monitored regularly, and the dose of the drug should be adjusted accordingly.

Drug combinations requiring special attention

Drugs capable of causing pirouette-type polymorphic ventricular tachycardia

Particular caution should be exercised when using hydrochlorothiazide concurrently with such drugs as:

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

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

– other (non-antiarrhythmic) medications such as:

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

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

– antibacterial agents: Fluoroquinolones (levofloxacin, moxifloxacin, sparfloxacin, ciprofloxacin), macrolides (erythromycin in intravenous administration, 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 drugs (ranolazine, bepridil);

anti-tumors (vandetanib, arsenic trioxide, oxaliplatin, tacrolimus);

– antiemetics (domperidone, ondansetron);

– agents affecting the motility of the gastrointestinal tract (cisapride);

– antihistamines (astemizole, terfenadine, misolastin);

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

Due to the increased risk of ventricular arrhythmias, especially pirouette-type polymorphic ventricular tachycardia (risk factor – hypokalemia), plasma potassium should be determined and, if necessary, corrected before the start of hydrochlorothiazide combined therapy 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 drugs that do not cause polymorphic ventricular tachycardia of “pirouette” type.

Drugs that can prolong QT interval duration

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

Drugs that can cause hypokalemia: Amphotericin B (when administered intravenously), gluco- and mineralocorticosteroids (when administered systemically), tetracosactide (ACTH), glycyrrhizic acid(carbenoxolone, drugs containing licorice root), laxatives that stimulate bowel motility. Increased risk of hypokalemia when concomitant use 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 that do not stimulate intestinal motility.

Heart glycosides

Hypokalemia and hypomagnesemia due to thiazide diuretics increase the toxicity of cardiac glycosides. Concomitant use of hydrochlorothiazide and cardiac glycosides should be accompanied by regular monitoring of plasma potassium concentration and ECG indexes and, if necessary, therapy adjustment.

Drug combinations requiring attention

Other hypotensive drugs

Potentiation of the antihypertensive effects 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 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 agents for general anesthesia

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

Nedepolarizing myorelaxants (e.g., tubocurarin)

An effect of nondepolarizing myorelaxants may be enhanced.

Adrenomimetics (pressor amines)

Hydrochlorothiazide may reduce the effects of adrenomimetics such as epinephrine (adrenaline) and norepinephrine (noradrenaline).

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors and high-dose 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 (hyperglycemia may develop) and reduce the effectiveness of hypoglycemic agents (hypoglycemic dose adjustment 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-adrenoblockers or diazoxide may increase the risk of hyperglycemia. Drugs used to treat gout (probenecid, sulfinpyrazone, allopurinol)

Dose adjustment of uricosuric drugs may be required because hydrochlorothiazide increases serum uric acid concentration. 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 its adverse effects.

Anticholinergic drugs (choline blockers)

Anticholinergic drugs (e.g., atropine, biperidene) increase the bioavailability of thiazide diuretics by decreasing GI 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 are 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 concomitant use of hydrochlorothiazide and topiramate, serum levels of topiramate should also be monitored, and if necessary, potassium preparations should be prescribed or the dose of topiramate should be adjusted.

Selective serotonin reuptake inhibitors

When concomitantly used with thiazide diuretics, hyponatremia may be potentiated. It is necessary to control plasma sodium content.

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-containing contrast agents

The dehydration of the body on thiazide diuretics increases the risk of acute renal failure, especially when high doses of iodine-containing contrast agents are used. Before using iodine-containing contrast agents it is necessary to compensate for fluid loss.

Calcium preparations

The simultaneous use can increase the plasma calcium content and develop hypercalcemia due to decrease of calcium ions excretion by kidneys. If there is necessity of concomitant administration of calcium containing drugs, plasma calcium content should be monitored and the dose of calcium preparations should be corrected.

Anionic exchange resins (colestyramine and colestipol)

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

Lozartan

Rifampicin and fluconazole reduced the concentration of the active metabolite. The clinical significance of this interaction has not been studied.

Simultaneous use of losartan, as well as other drugs affecting the RAAS, with potassium-saving diuretics (spironolactone, triamterene, amiloride, eplerenone), potassium preparations or potassium-containing salt substitutes may result in increased serum potassium levels. Simultaneous use is not recommended.

The excretion rate of lithium ions may decrease. Therefore, when using ARA II concomitantly with lithium salts, serum concentrations of lithium should be monitored carefully.

When ARA II is used concomitantly with NSAIDs (e.g., selective cyclooxygenase 2 inhibitors (COX-2)and

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 (HACMI), chronic heart failure (CHF) with associated severe renal impairment, severe heart failure (NYHA functional class IV), CHF with life-threatening arrhythmias, coronary heart disease (CHD), cerebrovascular disease, primary hyperaldosteronism, history of angioneurotic edema, arterial hypotension, liver dysfunction, renal dysfunction water-electrolyte balance disorders, 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 penicillin allergy, hyperparathyroidism, hyperuricemia, gout, history of nonmelanoma skin cancer (NSCLC) (see sect. See section “Special Indications”).

Persons under 18 years of age are contraindicated (efficacy and safety of use have not been established).

Patients with impaired renal function or patients on hemodialysis

In patients with moderate renal impairment (CK 30-50 ml/min), no adjustment of the initial dose of the drug is required. The drug Lorista® H is not recommended in patients on hemodialysis. The drug Lorista® H should not be used in patients with severe renal dysfunction (CK less than 30 ml/min) (see section “Contraindications”).

Patients with decreased CPR

Before starting treatment with Lorista®, the CBC and/or plasma sodium ion content should be restored.

Patients with impaired liver function

The drug Lorista® H is contraindicated in patients with severe liver function impairment (see section “Contraindications”).

Elderly patients

Dose adjustment of Lorista® is not required.

The use of Lorista® H in patients with acute myocardial infarction is not recommended due to insufficient experience in clinical use. Also, it should not be used to relieve hypertensive crisis.

Hydrochlorothiazide

Kidney function disorders

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

In patients with reduced 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

Hepatic encephalopathy may develop when using thiazide diuretics in patients with liver function disorders. In patients with severe hepatic insufficiency or hepatic encephalopathy thiazides 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 ammonium accumulation 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, slightly biconvex, film-coated tablets, yellow to yellow with a greenish tint, with a rib on one side.

Fracture appearance: white, rough mass with a yellow to yellowish with greenish tint film coating.

Contraindications

– Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome, because the drug Lorista® H contains lactose.

– Hypersensitivity to losartan, hydrochlorothiazide and other sulfonamide derivatives and excipients.

– Age under 18 years (effectiveness and safety of use have not been established).

– Pregnancy, breast-feeding.

– Hypokalemia or hypercalcemia resistant to therapy.

– Refractory hyponatremia.

– Anuria, severe renal failure (CK less than 30 ml/min).

– Severe liver failure (more than 9 points by Child-Pugh score), cholestasis and obstructive biliary diseases.

– Concurrent use with aliskiren and drugs containing aliskiren in patients with diabetes and/or moderate to severe renal function impairment (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2 body surface area).

– Concurrent use with ACE inhibitors in patients with diabetic nephropathy.

Overdose

Combination of hydrochlorothiazide + losartan

There is no information on overdose with hydrochlorothiazide + losartan combination.

Treatment:symptomatic and supportive therapy. The drug Lorista® H should be stopped and the patient should be closely monitored. If necessary: cause vomiting (if the patient has recently taken the drug), make up the blood circulation, correct water-electrolyte metabolism disorders and expressed BP decrease.

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, impaired consciousness, fatigue;

– gastrointestinal: nausea, vomiting, thirst;

– renal and urinary tract: polyuria, oliguria or anuria (due to hemoconcentration).

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

Treatment:In case of overdose, symptomatic and supportive therapy is given. If the drug was taken recently, induction of vomiting or gastric lavage are indicated for excretion of hydrochlorothiazide. Absorption of hydrochlorothiazide may be reduced by ingestion of activated charcoal. In case of BP decrease or shock it is necessary to replenish BCC (by administering plasma exchange fluids) and electrolyte deficit (potassium, sodium). In case of respiratory disorders, oxygen inhalation or artificial lung ventilation is indicated. Water-electrolyte balance (especially serum potassium) and renal function should be controlled until their normalization. There is no specific antidote. Hydrochlorothiazide is excreted by hemodialysis; however, the extent of its excretion has not been determined.

Lozartan (data limited)

Symptoms: pronounced BP decrease, tachycardia, possible bradycardia due to parasympathetic (vagus) stimulation.

treatment:symptomatic therapy, hemodialysis ineffective.

Pregnancy use

Pregnancy

Use of Lorista® H is contraindicated in pregnancy. If pregnancy is planned, it is recommended to transfer the patient to an alternative hypotensive therapy taking into account the safety profile. In case of confirmation of pregnancy, Lorista® H should be discontinued and, if necessary, transferred to an alternative hypotensive therapy.

The drug Lorista® H, like other drugs that have a direct effect on the RAAS, may cause adverse events in the fetus (impaired renal function, delayed ossification of fetal skull bones, oligohydramnion) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia). If the preparation Lorista® H was nevertheless used in the II-III trimesters of pregnancy, an ultrasound examination of the fetal kidneys and skull bones should be performed.

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 detected in umbilical cord blood. Taking into account the mechanism of pharmacological action of hydrochlorothiazide, its use in the second and third trimesters of pregnancy may disrupt the feto-placental perfusion and lead to the development in the fetus and the newborn of such complications as jaundice, disorders of water-electrolyte balance 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 to treat gestosis in the second half of pregnancy (edema, arterial hypertension, or preeclampsia) because it increases the risk of decreased BOD 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.

Breastfeeding period

The drug Lorista® H is contraindicated during breastfeeding because there is no experience with it. The use of other hypotensive drugs is recommended taking into account the safety profile.It is unknown whether losartan is excreted with breast milk.

Hydrochlorothiazide penetrates into breast milk, therefore its use during breastfeeding is contraindicated. If the use of hydrochlorothiazide during lactation is absolutely necessary, breastfeeding should be stopped.

Similarities