Lozap® plus
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 serum potassium levels. 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 ARA II simultaneously, it is necessary to carefully monitor the level of lithium salts in the blood serum.
With the simultaneous use of ARA II 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 antihypertensive effect of Lozap® Plus may be observed. Concomitant use of ARB II or diuretics and NSAIDs may cause an increased risk of deterioration of renal function, including acute renal failure and increased serum 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, simultaneous use of angiotensin II receptor antagonists may aggravate renal dysfunction. These effects are usually reversible.
Other drugs that cause hypotension, such as tricyclic antidepressants, antipsychotic drugs, baclofen, amifostine: simultaneous use of Lozap® Plus with these drugs that lower blood pressure may increase the risk of developing arterial hypotension.
Hydrochlorothiazide
When taken simultaneously with thiazide diuretics, interactions with the following substances may occur:
Alcohol, barbiturates, opioid analgesics 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):
aggravation of electrolyte deficiency, especially hypokalemia, is possible.
Pressor amines (for example, adrenaline):
it is possible to reduce the effect of pressor amines, however, this does not exclude their use.
Non-depolarizing muscle relaxants (for example, 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 for the treatment of gout (probenecid, sulfinpyrazone and allopurinol):
Dosage adjustments of antigout medications may be necessary because hydrochlorothiazide may increase serum uric acid levels. 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.
Drugs whose effect is affected by changes in serum potassium levels:
When Lozap® Plus is co-administered with drugs whose effect is affected by changes in potassium levels (for example, digitalis glycosides and antiarrhythmic drugs), it is recommended to regularly monitor serum potassium levels and ECG monitoring. These measures are also recommended when using Lozap® Plus simultaneously with the following drugs that can cause torsades de pointes (including antiarrhythmics), since hypokalemia is a factor predisposing to the development of torsades de pointes: class IA antiarrhythmics (for example , quinidine, hydroquinidine, disopyramide), class III antiarrhythmics (eg, amiodarone, sotalol, dofetilide, ibutilide), some antipsychotics (eg, thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol), others (for example, bepridil, cisapride, difemanil, erythromycin IV, halofantrine, mizolastine, pentamidine, terfenadine, vincamycin IV).
Calcium salts:
Thiazide diuretics may increase serum calcium levels by decreasing calcium excretion. If the patient is taking calcium supplements, it is necessary to monitor the level of calcium in the blood serum and, accordingly, adjust the dosage of calcium supplements.
Impact on laboratory results:
Due to their effect on calcium metabolism, thiazides may distort the results of tests to assess the function of the parathyroid glands.
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 (for parenteral administration), corticosteroids, ACTH, stimulant laxatives or glycyrrhizin (found in licorice):
hydrochlorothiazide may cause electrolyte deficiency, especially hypokalemia.
Lozap plus tablets 50 mg+12.5 mg 30 pcs.
The combined drug has a hypotensive effect. Contains losartan potassium - an angiotensin II receptor blocker (antagonist) (AT1 subtype) (ARB) and hydrochlorothiazide - a thiazide diuretic. Losartan/hydrochlorothiazide. Losartan and hydrochlorothiazide demonstrate a synergistic hypotensive effect, reducing blood pressure (BP) to a greater extent than either component alone. It is assumed that this effect is the result of the additive action of both components. In addition, as a result of the diuretic effect, hydrochlorothiazide increases plasma renin activity, aldosterone secretion, reduces the concentration of potassium in the blood plasma and increases the content of angiotensin-II. The use of losartan blocks all physiologically significant actions of angiotensin-II and reduces potassium losses associated with diuretic use through inhibition of aldosterone. Losartan has a mild and short-term uricosuric effect. Hydrochlorothiazide leads to a moderate increase in plasma uric acid; the combination of losartan and hydrochlorothiazide helps to attenuate diuretic-induced hyperuricemia. The hypotensive effect of losartan/hydrochlorothiazide persists for 24 hours. Despite a significant decrease in blood pressure, taking losartan/hydrochlorothiazide does not have a significant clinical effect on heart rate (HR). In clinical studies, it was shown that after 12 weeks of therapy with losartan 50 mg/hydrochlorothiazide 12.5 mg, minimum diastolic blood pressure (measured in the sitting position) decreased by an average of 13.2 mmHg. Art. Losartan/hydrochlorothiazide effectively reduces blood pressure in men and women, patients of black and other races, in young (< 65 years) and elderly (≥ 65 years) patients, and in all degrees of arterial hypertension. Losartan. Losartan is a synthetic angiotensin II receptor blocker (AT1 type). Angiotensin II, a powerful vasoconstrictor, is the main active hormone of the renin-angiotensin-aldosterone system (RAAS) and a major factor in the pathophysiology of arterial hypertension. Angiotensin II binds to AT1 receptors found in many tissues (vascular smooth muscle, adrenal glands, kidneys and heart) and causes a number of biologically important effects, including vasoconstriction and aldosterone release. Angiotensin II also stimulates the proliferation of smooth muscle cells. Losartan selectively blocks AT1 receptors. Losartan and its pharmacologically active carboxyl metabolite E-3174 block all physiologically significant effects of angiotensin-II in vitro and in vivo, regardless of the source and route of synthesis of the latter. Losartan does not have an agonistic effect and does not block other hormone receptors or ion channels that play an important role in regulating the function of the cardiovascular system. In addition, losartan does not inhibit angiotensin-converting enzyme (ACE) (kininase II), an enzyme that breaks down bradykinin. Therefore, there is no potentiation of undesirable effects mediated by bradykinin. When using losartan, elimination of the negative feedback reaction of angiotensin-II on renin secretion leads to an increase in the activity of the latter in the blood plasma. An increase in renin activity leads to an increase in the concentration of angiotensin-II in the blood plasma. Despite this increase, hypotensive activity and a decrease in plasma aldosterone concentrations persist, indicating effective blockade of angiotensin-II receptors. After stopping the use of losartan, plasma renin activity and angiotensin-II levels return to baseline values within 3 days. Both losartan and its main active metabolite have a greater affinity for AT1 receptors than for AT2 receptors. This metabolite is 10-40 times more active than losartan. The incidence of cough is comparable in patients taking losartan or hydrochlorothiazide and significantly lower than when using an ACE inhibitor. In patients with arterial hypertension, proteinuria without diabetes mellitus and taking losartan, there was a significant decrease in proteinuria, fractional release of proteins and immunoglobulin G. Losartan stabilizes the glomerular filtration rate and reduces the filtration fraction. In general, losartan causes a decrease in serum uric acid levels that persists during long-term therapy. Losartan does not affect autonomic reflexes and does not have a long-term effect on the level of norepinephrine in the blood plasma. In patients with left ventricular failure, 25 mg and 50 mg of losartan have positive hemodynamic and neurohumoral effects, characterized by an increase in cardiac index and a decrease in pulmonary capillary wedge pressure, systemic vascular resistance, mean systemic arterial pressure and heart rate, as well as plasma aldosterone and norepinephrine concentrations blood, respectively. The development of hypotension in these patients with heart failure was dose-dependent. Hydrochlorothiazide is a thiazide diuretic. The mechanism of the antihypertensive effect of this group of drugs is not fully known. Thiazide diuretics affect the renal tubular reabsorption mechanisms of electrolytes, directly increasing the excretion of sodium and chloride in approximately equivalent amounts. The diuretic effect of hydrochlorothiazide reduces plasma volume, increases plasma renin activity and increases aldosterone secretion with a subsequent increase in urinary potassium concentrations and bicarbonate loss and a decrease in plasma potassium concentrations. The coupling of renin to aldosterone is mediated by angiotensin II, and therefore concomitant use of an ARB generally reverses the potassium loss caused by thiazide diuretics. When taken orally, the diuretic effect of hydrochlorothiazide begins after 2 hours, reaches a maximum, on average, after 4 hours and lasts from 6 to 12 hours, the hypotensive effect persists for 24 hours.
