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, 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.
