Composition, form of production and packaging
The tablets covered with a film cover of light yellow color, round, biconcave; On a cross-section - white to white with a yellowish shade of color.
Losartan potassium 50 mg *
hydrochlorothiazide 12.5 mg
* contains 45.8 mg of losartan in the form of 45 mg of potassium losartan and 4.24 mg of potassium.
Excipients: lactose monohydrate - 26.9 mg, microcrystalline cellulose - 60 mg, pregelatinized starch - 23.6 mg, magnesium stearate - 1.5 mg, silicon dioxide colloid - 0.5 mg.
The composition of the membrane: hypromellose - 1.925 mg, giprolose - 1.925 mg, iron oxide oxide yellow - 0.02 mg, titanium dioxide - 1.13 mg.
10 pieces. - blisters (3) - packs of cardboard.
The tablets covered with a film cover of light yellow color, round, biconcave; On a cross-section - white to white with a yellowish shade of color.
Losartan potassium 100 mg **
hydrochlorothiazide 25 mg
** contains 91.6 mg of losartan in the form of 100 mg of potassium losartan and 8.48 mg of potassium.
Excipients: lactose monohydrate - 53.8 mg, microcrystalline cellulose - 120 mg, pregelatinized starch - 47.2 mg, magnesium stearate - 3 mg, silicon colloidal dioxide - 1 mg.
The composition of the shell: hypromellose - 3.85 mg, giprolose - 3.85 mg, iron oxide oxide yellow - 0.04 mg, titanium dioxide - 2.26 mg.
10 pieces. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
Lozarel В® Plus is a combination of an angiotensin II receptor antagonist (losartan) and a thiazide diuretic (hydrochlorothiazide). The combination of these components has an additive antihypertensive effect and reduces blood pressure more than each of the components separately.
Losartan is a specific antagonist of angiotensin II receptors (type AT 1 ).
Angiotensin II selectively binds to AT 1 -receptors found in many tissues (in smooth muscle cells of the vessels, adrenal, kidney and heart) and performs several important biological functions, including vasoconstriction and aldosterone release. Angiotensin II also stimulates proliferation of smooth muscle cells.
In vitro and in vivo studies have shown that losartan and its pharmacologically active metabolite (E-3174) block all the physiological effects of angiotensin II, regardless of the source or route of its synthesis. Losartan does not inhibit angiotensin-converting enzyme (ACE) - kininase II, and, accordingly, does not prevent the destruction of bradykinin; therefore, side effects mediated by bradykinin (eg, angioedema) are rare. Losartan and its active metabolite have a greater affinity for angiotensin I receptors than for angiotensin II receptors. The active metabolite is 10-40 times more active than losartan. The concentration of losartan and its active metabolite in the blood plasma, as well as the antihypertensive effect of losartan increase with increasing dose of the drug. Because losartan and its active metabolite are antagonists of angiotensin II receptors, they both contribute to the antihypertensive effect:
Reduces OPSS, concentration in the blood of aldosterone, blood pressure, pressure in a small circle of blood circulation, reduces afterload, has a diuretic effect.Prevents development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure (CHF). Stabilizes the concentration of urea in the blood plasma. Does not affect vegetative reflexes and does not have a long-term effect on the concentration of norepinephrine in blood plasma.
After a single oral intake, the hypotensive effect (systolic and diastolic blood pressure decreases) reaches a maximum after 6 hours, then gradually decreases within 24 hours. The maximum hypotensive effect develops 3-6 weeks after the start of the drug.
When conducting controlled clinical trials involving patients with primary mild and moderate arterial hypertension, a statistically significant decrease in systolic and diastolic blood pressure occurred as a result of losartan intake 1 time / day. Comparison of blood pressure, measured after 5-6 hours and 24 hours after ingestion of the dose, showed that blood pressure remains lowered for 24 hours while maintaining a natural daytime rhythm. The decrease in blood pressure at the end of the dosing period was approximately 70-80% of the effect, observed 5-6 hours after ingestion.
The discontinuation of losartan by patients with hypertension does not lead to a sharp increase in blood pressure (withdrawal syndrome). Despite the pronounced decrease in blood pressure, losartan does not have a clinically significant effect on heart rate.
Losartan is equally effective both in the treatment of men and women, young patients, and elderly patients with hypertension.
Hydrochlorothiazide is a thiazide diuretic, it disrupts the reabsorption of sodium, chlorine, potassium, magnesium ions in the distal nephron, delays the excretion of calcium, uric acid. The increase in renal excretion of these ions is accompanied by an increase in the amount of urine (due to the osmotic binding of water).Hydrochlorothiazide reduces the volume of blood plasma, increases the activity of renin in the blood plasma and the secretion of aldosterone. When taken in high doses of hydrochlorothiazide increases the excretion of bicarbonates, with prolonged intake reduces the excretion of calcium. Antihypertensive effect develops due to a decrease in bcc, changes in the reactivity of the vascular wall, decrease of the pressor effect of vasoconstrictive amines (epinephrine, noradrenaline) and enhancement of the depressor effect on the ganglion. Does not affect normal blood pressure. Diuretic effect occurs after 1-2 hours, reaches a maximum after 4 hours and lasts for 6-12 hours.
Antihypertensive effect occurs in 3-4 days, but to achieve the optimal therapeutic effect, 3-4 weeks is necessary.
When ingested, losartan is well absorbed from the digestive tract, metabolized by "first passing" through the liver by carboxylation with the participation of the cytochrome CYP2C9 isoenzyme with the formation of an active metabolite. Systemic bioavailability of losartan is about 33%. Eating does not affect the bioavailability of losartan. C max losartan and its active metabolite in the blood serum is achieved after 1 hour and 3-4 hours after ingestion, respectively.
More than 99% of losartan and its active metabolite binds to blood plasma proteins, mainly with albumins. V d - 34 liters. Losartan practically does not penetrate the BBB.
When administered in doses up to 200 mg, the pharmacokinetics of losartan and its active metabolite is linear.
When taking the drug inside 1 time / day, there is no significant cumulation in the plasma of either losartan, or its active metabolite. With a single admission of the drug inside at a dose of 100 mg / day, neither losartan nor its active metabolite significantly accumulate in the blood plasma.
About 14% of the dose of losartan after ingestion is converted into its active metabolite. After ingestion of losartan, labeled 14 C, the radioactivity of circulating blood plasma is primarily associated with the presence in it of losartan and its active metabolite. Approximately 1% of patients had a low level of losartan metabolism.
The plasma clearance of losartan and its active metabolite is about 600 ml / min and 50 ml / min, respectively. The renal clearance of losartan and its active metabolite is approximately 74 ml / min and 26 ml / min, respectively. When taking losartan, about 4% of the dose is excreted by the kidneys unchanged, about 6% of the dose - in the form of an active metabolite. After oral administration, the plasma concentrations of losartan and its active metabolite decrease polyexponentially with a finite T1/2 of about 2 hours and 6-9 hours, respectively. The excretion of losartan and its metabolites occurs with bile and kidneys. After ingestion of losartan labeled with 14 C, about 35% of radioactivity is found in urine and 58% in feces. After intravenous administration of losartan, labeled 14 C, approximately 43% of radioactivity is detected in urine and 50% in feces.
Pharmacokinetics in specific patient groups
In patients with alcoholic liver cirrhosis of mild and moderate severity, the concentration of losartan was 5 times, and the active metabolite was 1.7 times higher than in healthy male volunteers.
With CC above 10 ml / min, the concentration of losartan in the blood plasma does not differ from that with normal kidney function. In patients on hemodialysis, the AUC value is approximately 2 times higher than in patients with normal renal function. Neither losartan nor its active metabolite is removed from the body by hemodialysis.
The concentrations of losartan and its active metabolite in blood plasma in elderly patients with arterial hypertension do not differ significantly from the values вЂ‹вЂ‹of these parameters in young patients of men with arterial hypertension. Values вЂ‹вЂ‹of plasma concentrations of losartan in women with arterial hypertension are 2 times higher than the corresponding values вЂ‹вЂ‹in men with arterial hypertension.
The concentrations of the active metabolite in men and women do not differ. This pharmacokinetic difference is not clinically relevant.
Suction and distribution
When ingestion hydrochlorothiazide is rapidly absorbed from the digestive tract (about 80%). Systemic bioavailability is about 70%. C max in the blood plasma is reached after 2-5 h after ingestion. Binding to blood plasma proteins - 64%; V d - 0.5-1.1 l / kg.
Metabolism and excretion
It is not metabolized in the liver. It is excreted by the kidneys, mostly in unchanged form (more than 95%). T 1/2 is about 6-8 hours with normal kidney function.
Pharmacokinetics in specific patient groups
With violations of kidney function, T 1/2 increases and in the case of severe renal failure (CC less than 30 ml / min) reaches 20 hours.
The antihypertensive effect of the combined drug persists for 24 hours, the maximum therapeutic effect is achieved 4 weeks after the start of treatment.
- Arterial hypertension (in patients who are shown combined therapy).
The drug is taken orally, 1 time / day, regardless of food intake.
With arterial hypertension, the usual initial and maintenance dose of the drug is 1 tab. Lozarel В® Plus 12.5 mg + 50 mg / day.
In the absence of an adequate therapeutic effect, for 3-4 weeks the dose of the drug should be increased to 2 tablets Lozarel В® Plus 12.5 mg + 50 mg or 1 tablet Lozarel В® Plus 25 mg + 100 mg (maximum daily dose).
In patients with reduced BCC (for example, with diuretics in high doses), the recommended initial dose of losartan is 25 mg 1 time / day. In this regard, therapy with the drug Lozarel В® Plus should start after the elimination of diuretics and correction of hypovolemia.
In elderly patients and patients with moderate renal failure , including those on dialysis, the initial dose adjustment is not required.
According to the WHO, unwanted reactions are classified according to their frequency of development as follows: very often (? 1/10), often (1? / 100, <1/10), infrequently (? 1/1000, <1/100), rarely (? 1/10 000, <1/1000), very rarely (<1/10 000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence. In clinical studies with losartan-hydrochlorothiazide there were no undesirable reactions specific for this combination drug.
Unwanted reactions were limited to those already reported with losartan and / or hydrochlorothiazide alone. The total incidence of adverse reactions reported with this combination was comparable to that of placebo. The frequency of discontinuation of therapy was also comparable to that of patients taking placebo.
In general, treatment with losartan hydrochlorothiazide was well tolerated. In most cases, adverse reactions were mild, transient, and did not require drug withdrawal.
In controlled clinical trials in the treatment of essential hypertension, dizziness was the only one associated with taking the drug with an undesired response that exceeded the frequency of that with placebo taking more than 1% or more.
As shown in controlled clinical trials, in patients with hypertension and left ventricular hypertrophy, the most frequent adverse reactions were systemic and non-systemic dizziness, weakness / fatigue. In the course of post-marketing use of the drug, clinical trials and / or post-marketing use of individual active components of the drug, the following adverse reactions were reported.
From the nervous system: often - dizziness.
From the liver and biliary tract: rarely - hepatitis.
Laboratory and instrumental data: rarely - hyperkalemia, increased activity of hepatic transaminases.
Common disorders: often - asthenia, fatigue, pain in the chest, peripheral edema; infrequently - swelling of the face, fever; frequency unknown - malaise, flu-like symptoms.
From the cardiovascular system: often - a feeling of palpitations, tachycardia; infrequent, marked decrease in blood pressure, orthostatic hypotension (dose-dependent), epistaxis, arrhythmias (atrial fibrillation, ventricular tachycardia, sinus bradycardia, tachycardia), angina pectoris, vasculitis, myocardial infarction, retrosternal pains, AV blockade II degree, cerebrovascular disorders.
On the part of the digestive system: often - abdominal pain, diarrhea, dyspepsia, nausea; infrequently - anorexia, dryness of the oral mucosa, toothache, vomiting, flatulence, gastritis, constipation, hepatitis, a violation of liver function; frequency unknown - pancreatitis.
From the musculoskeletal system: often - pain in the back, legs, spasms of the calf muscles, myalgia, muscle pains; infrequently - arthralgia, arthritis, pain in the hands, shoulder, knee, hip joint, fibromyalgia, muscle weakness; frequency is unknown - rhabdomyolysis.
From the nervous system: often - dizziness, headache, insomnia; infrequently, restlessness, sleep disorders, drowsiness, memory impairment, peripheral neuropathy, paresthesia, hypesthesia, tremor, ataxia, depression, anxiety, panic conditions, confusion, vertigo, faint, ringing in the ears, taste disorder, blurred vision, conjunctivitis, migraine.
On the part of the respiratory system: often - cough, nasal congestion, sinusitis, infections of the upper respiratory tract; infrequently - laryngitis, dyspnoea, rhinitis, pharyngitis, bronchitis.
From the skin and subcutaneous tissues: infrequently - dry skin, erythema, ecchymosis, photosensitization, increased sweating, alopecia, dermatitis.
On the part of the immune system: infrequent exacerbation of the gout, urticaria, skin rash, itching, hypersensitivity reactions (anaphylactic reactions, angioedema, swelling of the larynx and tongue causing airway obstruction and / or swelling of the face, lips, pharynx). In some of these patients angioedema appeared earlier with the use of other drugs, including. ACE inhibitors.
On the part of the blood and lymphatic system: infrequently anemia (a slight decrease in hemoglobin and hematocrit, an average of 0.11 g% and 0.09% v / v, respectively, rarely having clinical significance), thrombocytopenia, eosinophilia, purpura Shenlen-Henoch, hemolysis.
On the part of the genitourinary system: infrequent - imperative urges for urination, nocturia, urinary tract infections, renal dysfunction, kidney failure, decreased libido, impotence.
Laboratory and instrumental data: often - hyperkalemia (the content of potassium in the blood plasma is more than 5.5 mmol / l), hypoglycemia; infrequently - increased concentrations of urea and residual nitrogen and creatinine in the blood serum; very rarely - a moderate increase in hepatic transaminase activity (ACT and ALT), hyperbilirubinemia; frequency is unknown - hyponatremia.
From the side of metabolism and nutrition: infrequently - hyperglycemia, glucosuria, hypokalemia, hyponatremia, hyperuricemia with development of gout attack, hypomagnesemia, hypercalcemia and hypochloraemic alkalosis (dryness of oral mucosa, thirst, irregular heart rhythm, changes in mood or psyche, seizures and pain in the muscles, nausea, vomiting, unusual fatigue or weakness Hypochloremic alkalosis can cause hepatic encephalopathy or hepatic coma); hyponatremia (confusion, convulsions, lethargy, slowing down the thinking process, increased fatigue, excitability, muscle cramps). Treatment with thiazides can disrupt glucose tolerance, latent diabetes mellitus can manifest. When using high doses, lipid concentrations in the serum can increase.
On the part of the digestive system: infrequently - intrahepatic cholestasis, cholecystitis or pancreatitis, cholestatic jaundice, diarrhea, nausea, vomiting, spasms, sialadenitis, constipation, anorexia, irritation of the gastric mucosa.
From the cardiovascular system: infrequently - arrhythmias, orthostatic hypotension, vasculitis.
From the nervous system: often - headache; infrequently - paresthesia, dizziness, insomnia.
From the side of the organ of vision: infrequently - temporarily blurred vision, xantopsy; frequency unknown - acute angle-closure glaucoma.
From the blood and lymphatic system: infrequently - leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia.
On the part of the immune system: infrequently - hives, purpura, necrotizing vasculitis, Stephens-Johnson syndrome, respiratory distress syndrome (including pneumonitis and noncardiogenic pulmonary edema); rarely anaphylactic reactions up to shock.
From the skin and subcutaneous tissue: infrequently - photosensitivity, toxic epidermal necrolysis; frequency unknown - lupus erythematosus.
From the urinary system: infrequently - impaired renal function, renal failure, interstitial nephritis.
Other: infrequent - decreased potency, muscle twitching.
- hypersensitivity to the components of the drug;
- Increased sensitivity to drugs that are derivatives of the sulfonamide;
- severe hepatic insufficiency (more than 9 points on a scale Child-Pugh);
- severe renal impairment (creatinine clearance less than 30 mL / min);
- lactase deficiency, lactose intolerance and malabsorption syndrome;
- lactation period;
- age under 18 years (effectiveness and safety not established);
- refractory hypokalemia and hyperkalemia, hypercalcemia, hyponatremia, refractory;
- symptomatic hyperuricaemia and / or gout;
- dehydration, including in patients receiving high doses of diuretics;
- severe hypotension;
- unmanageable diabetes;
- Addison's disease;
- simultaneous application of aliskiren and aliskirensoderzhaschimi drugs in patients with diabetes mellitus and / or impaired renal function (GFR <60 mL / min / 1.73 m 2 ).
With cautionIt should be prescribed for violations of water-electrolyte balance of the blood, e.g., against diarrhea or vomiting (hyponatremia hypochloraemic alkalosis, hypomagnesaemia); patients with renal failure (creatinine clearance of 30-50 ml / min); with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney; condition after kidney transplantation (application no experience); diabetes; progressive liver and human liver (less than 9 points on the Child-Pugh); allergic history and asthma; systemic connective tissue diseases (including systemic lupus erythematosus), heart failure, life-threatening arrhythmias; coronary artery disease; aortic stenosis or mitral valve; hypertrophic obstructive cardiomyopathy; cerebrovascular insufficiency; primary hyperaldosteronism;acute myopia and secondary angle-closure glaucoma (preparation comprises hydrochlorothiazide); simultaneously with the NSAID (including inhibitors of cyclooxygenase-2 (COX-2)); patients blacks.
PREGNANCY AND LACTATION
Use of the drug Lozarel В® Plus during pregnancy and lactation is contraindicated.
The use of drugs that have a direct impact on the RAAS, in the II and III trimester of pregnancy can harm the developing fetus and even cause his death. Immediately after pregnancy is installed, the drug Lozarel В® Plus should be discontinued.
Controlled epidemiological studies on the risk of application of angiotensin II receptor antagonists has been conducted, similar risks may exist for this class of drugs. Unless continued therapy of angiotensin II receptor antagonists is not considered vital, patients planning to become pregnant, you should switch to alternative antihypertensive drugs with established safety profile, allowing them to use during pregnancy.
Thiazides cross the placental barrier and are determined in the blood of the umbilical cord. The use of diuretics in pregnancy is not recommended, because This increases the risk of the fetus such adverse events, such as jaundice, fetal and neonatal jaundice, and his mother - thrombocytopenia.
There is no evidence that losartan is excreted in breast milk. However, it is known that thiazides are excreted in breast milk. Due to the risk of adverse events in infants in all cases should be made an informed decision about taking the drug during breastfeeding, taking into account the importance of therapy for the mother.
In that case, if it is decided that taking the drug Lozarel В® Plus is necessary, breast-feeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER
In patients with mild renal insufficiency, including dialysis, is required initial dose adjustment.
The caution in patients with renal failure (creatinine clearance of 30-50 ml / min).
Is contraindicated in severe renal failure (creatinine clearance less than 30 mL / min);
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With care in progressive liver and human liver (less than 9 points on the Child-Pugh).
Contraindicated in severe hepatic insufficiency (more than 9 points on a scale Child-Pugh);
APPLICATION FOR CHILDREN
Contraindications - up to age 18 years (effectiveness and safety have been established);
APPLICATION IN ELDERLY PATIENTS
Elderly patients do not require an initial dose adjustment.
Safety and effectiveness of the drug in children are not established.
Drugs that affect the RAAS may increase the concentration of urea in the blood and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. Similar effects were observed in patients receiving losartan; these changes were reversible renal function and disappeared after discontinuation. There are reports that in some patients taking the drug, due to the suppression of RAAS function observed change in kidney function, including kidney failure; These changes were reversible and disappeared after discontinuation of therapy.
As with other antihypertensives, excessive lowering of blood pressure in patients with ischemic cardiovascular and cerebrovascular diseases can lead to myocardial infarction and stroke.
In patients with heart failure with impaired renal function or without it can reduce the risk of blood pressure and acute renal failure.
Losartan as other angiotensin II receptor antagonists are less effective in patients blacks due to the prevalence of hypertensive patients with low activity of renin.
There is no experience with the drug in patients after kidney transplantation.
As in the case of receiving any antihypertensive agents, symptomatic hypotension may occur in some patients. Patients requires supervision for timely detection of clinical signs of violations of water-electrolyte balance, e.g., dehydration, hyponatremia, hypochloremic alkalosis, hypokalemia, hypomagnesemia, or that may develop on the background of intercurrent diarrhea or vomiting. These patients should be monitored in serum electrolytes.
Thiazide therapy can lead to impaired glucose tolerance. In some cases, it may require a dosage adjustment hypoglycemic agents (including insulin).
Thiazides may reduce calcium excretion by the kidneys and cause occasional and slight increase of calcium in blood serum. Marked hypercalcemia may be evidence of hidden hyperparathyroidism.
In connection with the effect of thiazide on calcium metabolism, taking them can distort the results of the research function of the parathyroid glands, so research before parathyroid function thiazide diuretic should be discontinued.
Increasing the concentration of cholesterol and triglycerides it may also be associated with thiazide diuretic therapy.
In some patients receiving thiazide diuretics can cause hyperuricemia and / or exacerbation of gout. These states are contraindication to the use of preparations containing hydrochlorothiazide. But as losartan reduces the concentration of uric acid, its combination with hydrochlorothiazide reduces the severity of hyperuricemia caused a diuretic.
In patients receiving thiazides, hypersensitivity reactions may occur even if there is no indication of the presence of allergy or bronchial asthma in history. There are reports of the development of exacerbation or progression of SLE in patients receiving thiazide diuretics.
In patients with impaired liver function or liver disease may cause progressive intrahepatic cholestasis, minor changes in water-electrolyte balance can cause hepatic coma. In these patients, the drug is recommended to be used with caution.
Hydrochlorothiazide may cause an idiosyncratic reaction, resulting in the development of acute transient myopia and acute angle-closure glaucoma. Symptoms include sudden blurred vision or eye pain, and occur within a few hours to weeks of starting therapy. The lack of treatment of acute angle-closure glaucoma can lead to complete loss of vision. You need to stop taking the drug as soon as possible. If the intraocular pressure remains uncontrolled, you may need urgent medical treatment or surgery. Risk factors for developing acute angle-closure glaucoma include allergic reactions to sulfonamides or penicillin in history.
Patients with primary hyperaldosteronism generally do not respond to antihypertensive agents, acting via inhibition of the RAAS. Therefore it is not recommended to apply the preparation Lozarel В® Plus for treating such patients.
Impact on the ability to drive vehicles and manage mechanisms
During treatment with Lozarel В® Plus (especially early in the course of therapy, and at higher doses) should be careful when driving and busy with other potentially hazardous activities that require high concentration and speed of psychomotor reactions, because of the risk of drowsiness and dizziness .
Symptoms: losartan - marked reduction of blood pressure, tachycardia, bradycardia (a result of vagal stimulation). Hydrochlorothiazide - loss of electrolytes (hypokalemia, hyperchloremia, hyponatremia), as well as dehydration that occurs due to excessive diuresis while receiving cardiac glycosides hypokalemia may exacerbate arrhythmias.
Treatment: symptomatic and supportive therapy. If the drug has recently adopted, it should wash out the stomach; if necessary, a correction fluid and electrolyte disturbances. Losartan and its active metabolite are not removed by hemodialysis.
There was no pharmacokinetic interaction of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin .
According to rifampicin and fluconazole reduces the concentration of the active metabolite in the blood plasma. The clinical significance of this interaction is still unknown. It is shown that in patients without metabolizing losartan's active metabolite, there is very rare and specific defect P450 2C9 isoenzyme.
The combination of losartan, like other means, which are angiotensin II receptor antagonists, or its effects, with potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium-containing additives or potassium salts can lead to an increase in the potassium content in the blood serum.
NSAIDs, including selective cyclooxygenase-2 (COX-2) and aspirin at a dose higher than 3 g / day, may reduce the effectiveness of angiotensin II receptor antagonists and ACE inhibitors.
The combined use of angiotensin II receptor antagonists, NSAIDs, including selective COX-2 inhibitors, especially in the presence of decreased renal function, may lead to renal dysfunction, including acute renal failure and increase of potassium in the blood plasma. This effect is usually reversible. Simultaneous treatment with these drugs should be used with caution in patients with impaired renal function.
When the joint application of angiotensin II receptor antagonists and lithium may increase the concentration of lithium in the blood plasma. Given this, it is necessary to weigh the benefits and risks of combined use of losartan with lithium salts. If necessary to use in conjunction preparations should regularly monitor the concentration of lithium in the blood plasma.
The combined use of losartan with a diuretic has an additive effect. (Mutually) the effect of other antihypertensive agents (diuretics, beta-blockers, simpatolitikov).
In the literature, there are reports thatdual blockade of the RAAS in patients with an established diagnosis of atherosclerosis, heart failure or diabetes with target organ lesion is associated with a higher incidence of arterial hypotension, syncope, hyperkalemia, and renal function (including the development of acute renal failure) as compared with the use of a single component of the RAAS blockade. The question of applying dual blockade of the RAAS (e.g., by combining the ACE inhibitor with an angiotensin II receptor antagonist) should be decided in each case individually and regular monitoring of renal function.
While the use of drugs that cause a decrease in blood pressure(Tricyclic antidepressants, antipsychotics, baclofen, amifostine), possible risk of hypotension.
With simultaneous use of thiazide diuretics with barbiturates, narcotic analgesics, ethanol may increase the risk of orthostatic hypotension.
Diuretics reduce renal clearance of lithium and increase the risk of its toxic action; the combined use of diuretics and drugs lithium is not recommended. Prior to his appointment lithium preparations should refer to instructions for use.
While the use of pressor amines (norepinephrine, epinephrine), a slight decrease in the effect of pressor amines without interfering their destination, with the non-depolarizing muscle relaxants (tubocurarine) - amplification of action.
In applyingSCS, ACTH may increase electrolyte loss, aggravation of hypokalemia.
Thiazides may decrease renal excretion of cytotoxic agents and enhance their myelosuppressive effects.
Hypoglycemic agents (for oral and insulin) - may require a dosage adjustment hypoglycemic agents. Metformin should be used with caution because of the risk of lactic acidosis induced by possible renal failure associated with hydrochlorothiazide.
Other antihypertensive drugs - additive effect; cholestyramine and colestipol - anion exchange resin in the presence of absorption of hydrochlorothiazide is broken, cholestyramine and colestipol bind a single dose hydrochlorothiazide and
reduce its absorption in the gastrointestinal tract by 85% and 43% respectively.
While the use of glycyrrhizic acid (found in licorice root), amphotericin B (w / w), laxatives possible risk of developing hypokalemia.