Pharmacological properties of the drug Lozap
Losartan is a specific antagonist of the receptor (AT1 type) of angiotensin II. Angiotensin II binds to the AT1 receptor, which is found in many tissues (eg vascular smooth muscle, adrenal glands, kidneys and heart). Losartan and its pharmacologically active metabolite carboxylic acid (E-3174) block the effects of angiotensin II. Losartan does not bind or block other hormone receptors and ion channels important for cardiovascular regulation. Losartan does not inhibit ACE, but blocks the response to angiotensin I and II and has no effect on the kinin system or bradykinin levels. Losartan has no effect on autonomic reflexes and the level of norepinephrine in the blood plasma. The drug is equally effective in men, women under 65 years of age and in elderly and senile patients with hypertension (arterial hypertension). With simultaneous use of Lozap with thiazide-type diuretics, the degree of blood pressure reduction increases. After oral administration, losartan is well absorbed and, as a result of metabolism during the initial passage through the liver, an active metabolite of carboxylic acid and inactive metabolites are formed. Systemic bioavailability after oral administration of losartan is about 33%. The average maximum concentration of losartan is achieved within 1 hour, and its active metabolite - within 3-4 hours. When using the drug with a standardized diet, no clinically significant effect on the profile of the concentration of losartan in the blood plasma was noted. Plasma clearance for losartan and its active metabolite is approximately 600 and 50 ml/min, respectively. The renal clearance of losartan and its active metabolite is about 74 and 26 ml/min, respectively. After oral administration, almost 4% of the dose is excreted unchanged in the urine and about 6% of the dose as an active metabolite. With oral administration of losartan potassium in doses up to 200 mg, the pharmacokinetics of the drug and its active metabolite are linear. After oral administration, the concentration of the drug and its active metabolite in the blood plasma decreases polyexponentially with a final half-life of 2 hours for losartan and 6–9 hours for the active metabolite. At a single daily dose of 100 mg, neither losartan nor its active metabolite accumulates in the blood plasma in significant quantities.
Lozap plus, 50 mg+12.5 mg, film-coated tablets, 60 pcs.
Losartan
Cases of decreased concentrations of the active metabolite have been described with the combined use of rifampicin and fluconazole. Clinical evidence for such interactions has not been evaluated.
As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium supplements, or potassium-containing salt substitutes may result in increased plasma potassium concentrations. The combined use of these drugs is not recommended.
As with other drugs that affect sodium excretion, the drug may slow down the excretion of lithium. Therefore, when prescribing lithium salts and ARBs simultaneously, it is necessary to carefully monitor the concentration of lithium salts in the blood plasma.
With the simultaneous use of ARBs and NSAIDs, for example, selective COX-2 inhibitors, acetylsalicylic acid in doses used for anti-inflammatory effect, and non-selective NSAIDs, a weakening of the hypotensive effect of Lozap® plus may be observed.
The simultaneous use of ARBs or diuretics and NSAIDs may cause an increased risk of deterioration of renal function, incl. acute renal failure and increased plasma potassium levels, especially in patients with underlying renal impairment. Combination treatment should be prescribed with caution, especially in elderly patients. Patients should be adequately hydrated and renal function monitored after initiation of combination treatment and periodically during treatment. In some patients with impaired renal function receiving treatment with NSAIDs, incl. selective COX-2 inhibitors, concomitant use of ARBs may worsen renal dysfunction. These effects are usually reversible. Dual blockade (for example, adding an ACE inhibitor or aliskiren to an ARB) should be carried out only in selected cases, constantly monitoring blood pressure, renal function and plasma electrolytes. There is evidence that dual blockade of the RAAS in patients with diagnosed atherosclerosis, heart failure or diabetes mellitus with target organ damage is associated with an increased incidence of arterial hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure), when compared with the use of one a drug that affects the RAAS.
The use of losartan together with aliskiren is contraindicated in patients with diabetes mellitus or impaired renal function (Cl creatinine <60 ml/min).
The drug Lozap® plus, when used simultaneously with other drugs that cause a decrease in blood pressure, such as tricyclic antidepressants, antipsychotic drugs, baclofen, amifostine, may increase the risk of developing arterial hypotension.
Hydrochlorothiazide
When taken concomitantly with thiazide diuretics, interactions with the following substances may occur.
Alcohol, barbiturates, narcotics or antidepressants.
The risk of orthostatic hypotension may increase.
Antidiabetic drugs (insulin and oral drugs).
Treatment with thiazide diuretics may affect glucose tolerance. Dosage adjustment of antidiabetic drugs may be required. Metformin should be used with caution due to the risk of lactic acidosis caused by possible functional renal failure associated with the use of hydrochlorothiazide.
Other antihypertensive drugs.
Additive effect.
Cholestyramine and colestipol
. In the presence of ion exchange resins, the absorption of hydrochlorothiazide is impaired. Taking a single dose of cholestyramine or colestipol leads to the binding of hydrochlorothiazide and a decrease in its absorption from the gastrointestinal tract by 85 and 43%, respectively.
Corticosteroids, adrenocorticotropic hormone (ACTH).
Possible worsening of electrolyte deficiency, especially hypokalemia.
Pressor amines (for example adrenaline).
It is possible that the effect of pressor amines may be reduced, but this does not preclude their use.
Non-depolarizing muscle relaxants (eg tubocurarine chloride).
The effect of muscle relaxants may be enhanced.
Lithium preparations.
Diuretics reduce the renal clearance of lithium and significantly increase the risk of lithium toxicity. It is recommended to avoid the simultaneous use of hydrochlorothiazide with lithium preparations.
Medicines used to treat gout (probenecid, sulfinpyrazone and allopurinol).
Dosage adjustment of anti-gout medications may be required since hydrochlorothiazide can increase plasma uric acid concentrations. Concomitant use with thiazides may increase the incidence of hypersensitivity reactions to allopurinol.
Anticholinergic drugs (eg atropine, biperidine).
It is possible to increase the bioavailability of thiazide diuretics by reducing gastrointestinal motility and the rate of gastric emptying.
Cytotoxic drugs (eg cyclophosphamide, methotrexate).
Thiazide diuretics can inhibit the renal excretion of cytotoxic drugs and enhance their myelosuppressive effect.
Salicylates.
When using high doses of salicylates, hydrochlorothiazide may enhance their toxic effects on the central nervous system.
Methyldopa.
Isolated cases of the development of hemolytic anemia have been described in patients simultaneously receiving hydrochlorothiazide and methyldopa.
Cyclosporine.
Concomitant treatment with cyclosporine may increase the risk of hyperuricemia and complications of gout.
Cardiac glycosides.
Hypokalemia or hypomagnesemia caused by thiazide diuretics may contribute to the development of digitalis-induced arrhythmias.
Medicines whose effect is influenced by changes in the concentration of potassium in the blood plasma.
When prescribing Lozap® plus simultaneously with drugs whose effect is affected by changes in the potassium content in the blood plasma (for example, digitalis glycosides and antiarrhythmic drugs), it is recommended to regularly monitor the concentration of potassium in the blood plasma and ECG monitoring. These measures are also recommended when using the drug Lozap® plus simultaneously with the following drugs that can cause torsade de pointes (ventricular tachycardia) (including antiarrhythmics), since hypokalemia is a factor predisposing to the development of torsade de pointes: class 1A antiarrhythmic drugs (for example quinidine, hydroquinidine, disopyramide); class III antiarrhythmics (eg amiodarone, sotalol, dofetilide, ibutilide); some antipsychotic drugs (eg thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol); others (eg bepridil, cisapride, difemanil, erythromycin IV, halofantrine, mizolastine, pentamidine, terfenadine, vincamycin IV).
Calcium salts.
Thiazide diuretics may increase plasma calcium levels by decreasing calcium excretion. If the patient is taking calcium supplements, it is necessary to monitor the calcium level in the blood plasma and adjust the dosage of calcium supplements accordingly.
Influence on laboratory test results.
Due to their effect on calcium metabolism, thiazides may interfere with test results to assess parathyroid function.
Carbamazepine.
There is a risk of developing symptomatic hyponatremia. Clinical observation and laboratory monitoring of blood sodium levels are necessary in patients taking carbamazepine.
Iodinated contrast agents.
In case of dehydration caused by the use of diuretics, the risk of developing acute renal failure increases, especially when taking high doses of iodine preparations. Patients should be rehydrated before administration.
Amphotericin B (parenteral), corticosteroids, ACTH, stimulant laxatives, or glycyrrhizin (found in licorice).
Hydrochlorothiazide may cause electrolyte deficiency, especially hypokalemia.
Indications for use of the drug Lozap
Lozap : hypertension (arterial hypertension); reducing the risk of cardiovascular complications and mortality in patients with hypertension (arterial hypertension) and left ventricular hypertrophy; protection of kidney function with type II diabetes mellitus with proteinuria in order to slow the progression of kidney disease (preventing the need for dialysis and kidney transplantation), as well as to reduce proteinuria; chronic heart failure, if therapy with ACE inhibitors is inappropriate. Lozap Plus : hypertension (arterial hypertension) (patients for whom combination therapy is indicated); reducing the risk of developing cardiovascular complications and mortality in patients with hypertension (arterial hypertension) and left ventricular hypertrophy.
Lozap indication
The use of Lozap is relevant for the following conditions:
- High blood pressure.
- Chronic course of heart failure.
- Prevention of the development of severe vascular and cardiac diseases among patients with hypertension and left ventricular enlargement.
- Nephropathy and high blood pressure in people with diabetes.
- Contraindications
- Absolute contraindications for use are:
- Increase in potassium levels in the blood.
- Low pressure.
- Individual intolerance to the medicinal components included in the composition.
- The time of bearing a child.
- Breastfeeding.
- Symptoms of dehydration.
- Children under 18 years of age.
Use of the drug Lozap
For hypertension (arterial hypertension), the initial and maintenance dose is 50 mg 1 time per day. The maximum antihypertensive effect is achieved 3–6 weeks after the start of administration. In some cases, to achieve a greater effect, the dose is increased to 100 mg once a day. When prescribing the drug to patients with reduced intravascular volume (for example, receiving diuretics in high doses), a lower initial dose is recommended - 25 mg 1 time per day. No dose adjustment is required in elderly patients or patients with impaired renal function, including patients on dialysis. Patients with impaired liver function should be prescribed Lozap at a lower dose. The starting dose for patients with chronic heart failure is 12.5 mg once daily. In the future, the dose should be titrated, as a rule, gradually increasing it every week by 12.5 mg / day (i.e. 12.5; 25; 50 mg / day), reaching an average maintenance dose of 50 mg 1 time per day, depending on tolerability drug. The titration period is determined taking into account individual tolerability of treatment. The drug is taken regardless of meals; The tablet is swallowed without chewing, washed down with water.
Composition and release form
The drug Lozap is available in the form of small tablets for parenteral administration. They are white, slightly elongated and convex on both sides. They have a soluble thin film shell. Packaged in blisters of 10 pieces. One cardboard package contains 3, 6, 9 blisters and includes instructions for use.
The active substance is potassium losartran.
Auxiliary components: cellulose, povidone, talc, magnesium stearate, macrogol, dyes, mannitol, croscarmellose sodium.
Side effects of the drug Lozap
May occur in the form of anaphylactic reactions, angioedema, including swelling of the larynx and glottis, with the development of airway obstruction and/or swelling of the face, lips, pharynx and/or tongue. In controlled clinical trials, the only side effects were dizziness and hypotension. In some cases, patients receiving losartan experienced hepatitis, diarrhea, impaired liver function, migraine, myalgia, arthralgia, urticaria, and itching. Adverse reactions from the respiratory tract have been described: cough, upper respiratory tract infections. When treated with losartan, a dry cough is detected.
Side effects
As a rule, during the course of therapy, patients experience virtually no side effects. If they appear, they go away on their own and quickly, so there is no need to discontinue the drug. The following side effects are possible when taking Lozap:
- Dizziness, increased fatigue, headache, problems falling asleep. Migraines, anxiety, tremor, and depression are less common.
- Infection of the respiratory system. Signs of rhinitis, bronchitis and respiratory distress may appear.
- Dyspeptic symptoms, rarely gastritis, dry mouth, flatulence.
- Disturbance of the musculoskeletal system. Possible pain in the back and muscles, cramps.
- Signs of cardiac dysfunction are expressed in tachycardia, bradycardia, arrhythmia.
- Rarely, kidney problems, sexual dysfunction and infections of the urinary system appear.
- Allergic reactions, dry dermis, excessive sweating.
Special instructions for the use of the drug Lozap
Therapy with Lozap is not prescribed to patients with a deficiency of intravascular fluid volume (for example, patients receiving diuretics in high doses). If you have a history of liver disease, you should consider using the drug at a lower dose. In the presence of acute or chronic renal failure, the drug may lead to deterioration of renal function with or without hyperkalemia. Lozap should be used with caution in patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney. Clinical studies have not revealed age-related differences regarding the effectiveness or safety of the drug. The use of the drug may negatively affect activities that require a high speed of mental and physical reactions (for example, when driving vehicles, servicing machines and mechanisms, working at heights, etc.).
Drug interactions Lozap
In clinical and pharmacological studies, no clinically significant interactions were observed with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin. Rifampicin and fluconazole reduce the level of the active metabolite of losartan. The clinical consequences of these interactions have not been assessed. Strengthens (mutually) the effect of other antihypertensive drugs (diuretics, β-adrenergic receptor blockers, sympatholytics, other drugs that block ACE). Increases the risk of hyperkalemia when combined with potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride) and drugs containing potassium or its salts. NSAIDs, including selective COX-2 inhibitors, reduce the effect of diuretics and other antihypertensive drugs. Therefore, the antihypertensive effect of ACE II receptor antagonists may be reduced by NSAIDs, including COX-2 inhibitors. The severity of the hypotensive effect of losartan, like other antihypertensive drugs, can be reduced with the help of indomethacin.
Interactions with drugs
Combining the drug with Fluconazole and Rifampicin leads to a decrease in the active substance.
Lozap increases the pharmacological activity of other antihypertensive drugs.
It is not recommended to take the medicine in parallel with non-steroidal anti-inflammatory drugs.
When interacting with potassium and potassium-sparing diuretics, it is important to monitor the level of the element in the blood to prevent the occurrence of hyperkalemia.
Patients with obvious symptoms of dehydration while taking diuretics may experience a rapid decrease in blood pressure when taking an antihypertensive drug.
Lozap overdose, symptoms and treatment
In case of overdose (intoxication) of the drug, symptoms such as hypotension, tachycardia may appear, and sometimes bradycardia may occur due to parasympathetic (vagal) stimulation. If symptomatic hypotension occurs, maintenance therapy is provided. In case of accidental overdose (taking the drug in a high dose), it is necessary to carry out symptomatic and supportive therapy, induce vomiting and gastric lavage. Neither losartan nor its active metabolite can be removed by hemodialysis.
