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.
Lozap Plus, tablets coated. captivity. about. 50 mg+ 12.5 mg, 90 pcs.
Losartan
Angioedema
. Patients with a history of angioedema (swelling of the face, lips, pharynx and/or tongue) should be closely monitored.
Arterial hypotension and decreased blood volume
. In patients with hypovolemia and/or reduced sodium levels in the blood plasma resulting from intensive use of diuretics, restriction of dietary salt intake, diarrhea or vomiting, symptomatic arterial hypotension may develop (especially after taking the first dose). It is necessary to correct such conditions before starting to take losartan.
Water-electrolyte imbalance
. Fluid and electrolyte imbalances often occur in patients with impaired renal function, so plasma potassium and creatinine Cl levels must be carefully monitored, especially in patients with heart failure and creatinine Cl in the range of 30–50 ml/min. The simultaneous use of losartan with potassium-sparing diuretics, potassium supplements and potassium-containing salt substitutes is not recommended.
Liver dysfunction
. Pharmacokinetic data indicate a marked increase in plasma concentrations of losartan in patients with liver cirrhosis. Based on these data, losartan should be used with caution in patients with a history of mild or moderate hepatic impairment. There is no experience with the use of losartan in patients with severely impaired liver function, therefore the drug is contraindicated in patients with severely impaired liver function.
Renal dysfunction
. Impaired renal function has been reported due to inhibition of the RAAS, incl. about renal failure (in particular, in patients whose kidney function depends on the RAAS, for example, with severe heart failure or existing renal impairment). As with the use of other drugs that affect the RAAS, cases of increased concentrations of urea and creatinine in the blood plasma have been described in patients with bilateral renal artery stenosis or with renal artery stenosis of a single kidney. These changes in renal function may be reversible and decrease after treatment is discontinued. Losartan should be used with caution in patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney.
Kidney transplant
. There is no experience with the use of losartan in patients who have recently undergone kidney transplantation.
Primary hyperaldosteronism
. Patients with primary hyperaldosteronism typically do not respond to treatment with antihypertensive drugs that inhibit the RAAS. For this reason, the use of losartan is not recommended.
IHD and cerebrovascular disease
. As with any other antihypertensive drugs, an excessive decrease in blood pressure in patients with coronary artery disease or cerebrovascular disease can lead to the development of myocardial infarction or stroke.
Heart failure
. As with other drugs that act on the RAAS, patients with heart failure (with or without renal impairment) are at risk of developing severe hypotension as well as renal dysfunction (often acute).
Aortic and mitral valve stenosis, hypertrophic obstructive cardiomyopathy
. As with other vasodilators, special caution should be exercised when treating patients with aortic or mitral stenosis or hypertrophic obstructive cardiomyopathy.
Differences due to ethnicity
. By analogy with ACE inhibitors, losartan and other ARBs are noticeably less effective in lowering blood pressure in blacks compared to patients of other races. This may be due to more frequent cases of low renin levels in the black population with hypertension.
Double blockade of the RAAS
. There is evidence that the simultaneous use of ACE inhibitors, ARB II or aliskiren increases the risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure). The use of losartan concomitantly with aliskiren is contraindicated in patients with diabetes mellitus or patients with moderate to severe renal impairment (GFR less than 60 ml/min/1.73 m2) and is not recommended in other patients (see “Contraindications”). The use of losartan in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see "Contraindications").
Hydrochlorothiazide
Arterial hypotension and water-electrolyte imbalance
. As with any other antihypertensive drug, symptomatic hypotension may develop in some patients. Patients should be monitored for clinical signs of fluid and electrolyte imbalance, such as hypovolemia, hyponatremia, hypochloremic alkalosis, hypomagnesemia, or hypokalemia, which may develop with concomitant diarrhea or vomiting. In such patients, it is necessary to periodically (at appropriate intervals) monitor the content of electrolytes in the blood plasma. Hypokalemia may occur when prescribing hydrochlorothiazide, as well as any other strong diuretics, especially with increased diuresis, after long-term therapy or in severe liver cirrhosis. Hypokalemia may exacerbate the toxic effects of digoxin (eg, increased ventricular irritability). The risk of developing hypokalemia is higher in patients with liver cirrhosis, increased diuresis, insufficient dietary potassium intake and in patients receiving concomitant treatment with corticosteroids, mineralocorticosteroids or ACTH.
Patients with edema in hot weather may develop hypervolemic hyponatremia.
Endocrine and metabolic effects
. Treatment with thiazides may lead to impaired glucose tolerance. Dosage adjustment of hypoglycemic agents may be required, incl. insulin. During treatment with thiazides in patients with impaired glucose tolerance, the manifestation of diabetes mellitus is possible.
Thiazides may reduce renal excretion of calcium and cause small intermittent increases in plasma calcium concentrations. Severe hypercalcemia may be a sign of hidden hyperparathyroidism. Before testing the function of the parathyroid glands, treatment with thiazides should be discontinued.
Treatment with thiazide diuretics may be accompanied by an increase in the concentration of cholesterol and triglycerides in the blood plasma.
In some patients, treatment with thiazides may provoke the occurrence of hyperuricemia and/or gout. Because losartan reduces uric acid concentrations, use of losartan in combination with hydrochlorothiazide may slow the development of diuretic-induced hyperuricemia.
Liver dysfunction
. Thiazides should be prescribed with caution to patients with impaired liver function or progressive liver diseases due to the risk of developing intrahepatic cholestasis, as well as due to the fact that minor disturbances in water and electrolyte balance may be a prerequisite for the development of hepatic coma. Hydrochlorothiazide is contraindicated in patients with severe hepatic impairment (see Contraindications).
Photosensitivity
. Photosensitivity reactions have been reported with the use of thiazide diuretics. If such reactions occur when using hydrochlorothiazide, it is recommended to stop taking the drug. If re-treatment with diuretics is unavoidable, it is recommended to protect areas exposed to sunlight or artificial UV radiation.
Anti-doping test
. Hydrochlorothiazide may give a positive result during doping control.
Non-melanoma skin cancer and lip cancer
. Two epidemiological studies based on national cancer registries in Denmark documented an increased risk of developing non-melanoma skin cancer and lip cancer (basal cell and squamous cell carcinoma of the skin) with increasing cumulative dose of hydrochlorothiazide.
Hydrochlorothiazide has a photosensitizing effect, which may cause the development of non-melanoma skin and lip cancer.
Patients taking hydrochlorothiazide as monotherapy or in combination with other drugs should be informed of the risk of developing non-melanoma skin and lip cancer and the need to regularly examine the skin for any new changes, as well as changes in existing ones. If any suspicious skin lesions are detected, the patient should immediately consult a doctor.
Particular attention should be paid to patients who have known risk factors for skin cancer, including skin phototypes I and II (pale and fair skin), a family history of skin cancer, a history of skin damage caused by sun or UV radiation, and radiation therapy, smoking and taking drugs with photosensitizing effects. Patients should be advised to take measures to prevent the development of skin cancer, such as limiting time in the sun and exposure to UV rays, and using appropriate sunscreens during sun exposure. Any suspicious skin lesions should be immediately examined, including histological examination of material obtained by biopsy of tissue at the site of the lesion. It may also be necessary to reconsider the use of hydrochlorothiazide in patients with a history of non-melanoma skin cancer and lip cancer.
Other
. During the use of hydrochlorothiazide, cases of the development of transient myopia and an acute attack of angle-closure glaucoma have been reported. Risk factors for the development of an acute attack of angle-closure glaucoma may include anamnestic data on allergic reactions to sulfonamide and penicillin derivatives. Symptoms: Sudden onset, sudden decrease in visual acuity, or eye pain, usually occurring within a few hours to a week after starting therapy. An uncontrolled attack of angle-closure glaucoma can lead to permanent vision loss. The first step is to stop taking hydrochlorothiazide. If IOP does not decrease after discontinuation of hydrochlorothiazide, medical or surgical treatment may be required.
While taking thiazides, it is possible to develop hypersensitivity reactions in patients with a history of bronchial asthma, as well as with a burdened allergic history. Cases of the occurrence or exacerbation of systemic lupus erythematosus during treatment with thiazides have been described.
Excipient
. The drug contains crimson dye (Ponceau 4R), which can cause allergic reactions.
Impact on the ability to drive vehicles and machinery
. Studies have not been conducted to study the effect of the combination of losartan + hypochlorothiazide on the ability to drive vehicles or operate machinery. However, it must be taken into account that during treatment with antihypertensive drugs, dizziness or drowsiness may occur when driving or operating machinery, especially when starting treatment or increasing the dose of the drug.
