Composition, form of production and packaging
The tablets covered with a film cover of yellow color, round, biconcave; on a cross section - almost white.
1 tab.
Losartan potassium 50 mg
hydrochlorothiazide 12.5 mg
Excipients: corn starch - 30 mg, croscarmellose sodium - 6.8 mg, mannitol - 36 mg, magnesium stearate - 1.2 mg, povidone - 4 mg, microcrystalline cellulose - 29.5 mg.
The composition of the film shell: opadray yellow - 5 mg (hypromellose (hydroxypropylmethylcellulose) - 1.7 mg, giprolose (hydroxypropylcellulose) 1.75 mg, titanium dioxide 1.342, iron oxide yellow 0.207 mg, aluminum dye-based dye sunset yellow 0.001 mg) .
7 pcs. - packings of cellular contour (1) - packs cardboard.
7 pcs. - packings cellular planimetric (2) - packs cardboard.
10 pieces. - packings of cellular contour (1) - packs cardboard.
10 pieces. - packings cellular planimetric (2) - packs cardboard.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
10 pieces. - packings cellular planimetric (9) - packs cardboard.
28 pcs. - packings of cellular contour (1) - packs cardboard.
28 pcs. - packings cellular planimetric (2) - packs cardboard.
30 pcs. - packings of cellular contour (1) - packs cardboard.
30 pcs. - packings cellular planimetric (3) - packs cardboard.
The tablets covered with a film cover of yellow color, round, biconcave; on a cross section - almost white.
1 tab.
Losartan Potassium 100 mg
hydrochlorothiazide 25 mg
Excipients: corn starch - 60 mg, croscarmellose sodium - 13.6 mg, mannitol - 72 mg, magnesium stearate - 2.4 mg, povidone - 8 mg, microcrystalline cellulose - 59 mg.
The composition of the film shell: opadray yellow - 10 mg (hypromellose (hydroxypropylmethylcellulose) - 3.4 mg, giprolose (hydroxypropyl cellulose) - 3.5 mg, titanium dioxide - 2.685, iron oxide yellow - 0.413 mg, aluminum varnish based on the dye sunset yellow - 0.002 mg) .
7 pcs. - packings of cellular contour (1) - packs cardboard.
7 pcs. - packings cellular planimetric (2) - packs cardboard.
10 pieces. - packings of cellular contour (1) - packs cardboard.
10 pieces. - packings cellular planimetric (2) - packs cardboard.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
10 pieces. - packings cellular planimetric (6) - packs cardboard.
14 pcs. - packings of cellular contour (1) - packs cardboard.
14 pcs. - packings cellular planimetric (2) - packs cardboard.
15 pcs. - packings cellular planimetric (2) - packs cardboard.
15 pcs. - packings cellular planimetric (4) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
Losartan-N Canon is a combined drug that has antihypertensive effect.
Losartan is a highly effective, selective angiotensin II receptor antagonist (type AT 1 ) when administered. Angiotensin II is a potent vasoconstrictor, the main active hormone of RAAS, and the decisive pathophysiological link in the development of hypertension. Angiotensin II selectively binds to AT 1 -receptors found in many tissues (in the smooth muscle cells of the vessels, in the adrenal, kidney and heart) and performs several important biological functions, including vasoconstrictor function and aldosterone release. In addition, angiotensin II stimulates the proliferation of smooth muscle cells.
Losartan and its pharmacologically active metabolite (E-3174) both in vitro and in vivo block all the physiological effects of angiotensin II, regardless of the source or route of synthesis. Unlike some peptide angiotensin II receptor antagonists, losartan does not have the effects of an agonist. Losartan selectively binds to AT 1 -receptors, does not bind or block receptors of other hormones and ion channels, which play an important role in regulating the function of the cardiovascular system.In addition, losartan does not inhibit ACE, which is responsible for the destruction of bradykinin. Therefore, effects not directly related to AT 1 -receptor blockade, including bradykinin mediated effects, and development of peripheral edema (losartan 1.7%, placebo 1.9%), are not relevant to the action of losartan.
Reduces OPSS, blood pressure, the concentration in the blood of norepinephrine and aldosterone, 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). When taking losartan, the plasma activity of renin (PAR) increases, which leads to an increase in angiotensin II in the blood plasma.
After a single dose of antihypertensive effect (decreases systolic and diastolic blood pressure) reaches a maximum after 6 hours, then within 24 hours gradually decreases. In the course of treatment, antihypertensive activity and decrease in plasma aldosterone concentration were manifested after 2 and 6 weeks of therapy, which indicates effective blockade of angiotensin II receptors. However, after the abolition of losartan, the plasma renin activity and angiotensin II level decreased to the baseline values ​​observed 3 days prior to taking the drug.
Both losartan and its active metabolite have a higher affinity for AT 1 receptors than for AT 2 receptors. The active metabolite is 10-40 times more active than losartan.
Hydrochlorothiazide is a thiazide diuretic whose diuretic effect is associated with a disruption of the reabsorption of sodium, chlorine, potassium, magnesium, water in the distal nephron; delays the excretion of calcium ions, uric acid. Has antihypertensive effect, which develops due to the expansion of arterioles. Virtually no effect on normal blood pressure.
Diuretic effect occurs in 1-2 hours, reaches a maximum after 4 hours and lasts for 6-12 hours. Antihypertensive effect occurs in 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect.
PHARMACOKINETICS
The pharmacokinetics of losartan and hydrochlorothiazide with simultaneous administration does not differ from that in their separate application.
Losartan
Suction
When ingested, losartan is well absorbed from the digestive tract and at the same time it undergoes metabolism at the "first passage" through the liver by carboxylation with the participation of the CYP2C9 isoenzyme with the formation of an active metabolite. Systemic bioavailability of losartan is approximately 33%.C max losartan and its active metabolite is reached in the blood serum approximately after 1 hour and 3-4 hours after ingestion, respectively. Eating does not affect the bioavailability of losartan.
Distribution
Lozartan and its active metabolite bind to plasma proteins (mainly albumins) by more than 99%. V d of losartan is 34 liters. Losartan practically does not penetrate the BBB.
Losartan and its active metabolite demonstrate linear pharmacokinetics when administered in doses up to 200 mg. When the dosage regimen is 100 mg 1 time / day, there is no significant cumulation in the plasma of either losartan or its active metabolite.
Metabolism
Approximately 14% of the dose of losartan administered intravenously or inward is converted to its active metabolite. After oral or intravenous administration of radiolabeled 14 C labeled losartan, the radioactivity of the circulating blood plasma is due to the presence of losartan and its active metabolite. In addition to the active metabolite, biologically inactive metabolites are formed, incl. two basic, resulting from the hydroxylation of the butyl side chain, and one secondary is N-2-tetrazole-glucuronide.
Excretion
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 unchanged by the kidneys and about 6% of the dose is excreted by the kidneys as an active metabolite.
After oral administration, plasma concentrations of losartan and its active metabolite decrease polyexponentially with a finite T 1/2 of about 2 and 6-9 hours, respectively. The excretion of losartan and its metabolites occurs through the intestine with bile and kidneys. After ingestion of radiolabeled 14 C of losartan, about 35% of radioactivity is found in urine and 58% in feces. After intravenous administration of radiolabeled 14 C losartan, approximately 43% of radioactivity is detected in urine and 50% in feces.
Pharmacokinetics in specific patient groups
The concentrations of losartan and its active metabolite in blood plasma in elderly male patients with arterial hypertension do not differ significantly from the values ​​of these parameters in male patients of younger age with arterial hypertension.
Values ​​of plasma concentrations of losartan in women with arterial hypertension were 2 times higher than the corresponding values ​​in men with arterial hypertension.The concentrations of active metabolite in men and women did not differ. This apparent pharmacokinetic difference, however, has no clinical significance.
When losartan was administered orally to patients with alcoholic liver cirrhosis of mild and moderate severity, the concentration of losartan and its active metabolite in the blood plasma was, respectively, 5 and 1.7 times higher than in young healthy male volunteers.
Plasma concentrations of losartan in patients with QC above 10 ml / min did not differ from those in patients with unchanged renal function. When comparing AUC in patients with normal renal function, the AUC of losartan in patients on hemodialysis was approximately 2-fold greater. Plasma concentrations of the active metabolite did not change in patients with impaired renal function or on hemodialysis. Lozartan and its active metabolite are not excreted by hemodialysis.
Hydrochlorothiazide
Suction and distribution
After oral administration, the absorption and bioavailability of hydrochlorothiazide is about 70%. When administered hydrochlorothiazide at a dose of 12.5 mg C max is achieved in 1.5-4 hours and is 70 ng / ml, and when administered at a dose of 25 mg, the maximum C max is reached after 2-5 hours and is 142 ng / ml.
Binding to blood plasma proteins - 60-80%. In the therapeutic range of doses, the average value of AUC increases in direct proportion to the increase in dose, with the appointment of 1 time / day, cumulation is negligible. It penetrates through GEB and into breast milk.
Metabolism and excretion
Hydrochlorothiazide is slightly metabolized in the liver. T 1/2 is 5-15 hours. It is excreted almost completely (more than 95%) by the kidneys in unchanged form. 50-70% of the ingested dose is excreted within 24 hours.
INDICATIONS
- arterial hypertension (patients who are shown combined therapy);
- reduction in the risk of developing cardiovascular disease and mortality in patients with hypertension and left ventricular hypertrophy.
DOSING MODE
The drug is taken orally, regardless of food intake. Tablets are swallowed, not liquid, squeezed with water.
The drug Losartan-N Canon can be combined with other antihypertensive agents.
Arterial hypertension
The initial and maintenance dose is 1 tab. (12.5 / 50 mg) 1 time / day. In the absence of an adequate therapeutic effect, the dose of Lozartan-N canon is increased to 25/100 mg. The maximum antihypertensive effect is achieved within 3 weeks of therapy. The maximum daily dose is 1 tablet. (25/100 mg).
In elderly patients and patients with moderate renal insufficiency (CK 30-50 ml / min) , correction of the initial dose is not required.
Reduction of the risk of cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy
The standard initial dose of losartan is 50 mg 1 time / day. Patients who failed to achieve target BP levels when using losartan at a dose of 50 mg / day require a combination of losartan and hydrochlorothiazide at a low dose (12.5 mg); if necessary, increase the dose of losartan to 100 mg in combination with hydrochlorothiazide at a dose of 12.5 mg / day, then 100 mg losartan and 25 mg hydrochlorothiazide 1 time / day (1 table 25/100 mg).
SIDE EFFECT
Classification of WHO frequency of development of side effects: very often -? 1/10 appointments (> 10%); often - from? 1/100 to <1/10 of appointments (> 1% and <10%); infrequently - from? 1/1000 to <1/100 of prescriptions (> 0.1% and <1%); rarely - from? 1/10 000 to <1/1000 appointments (> 0.01% and <0.1%); very rarely - <1/10 000 prescriptions (<0.01%); the frequency is unknown - it is not possible to establish the frequency of occurrence from the available data.
Losartan
On the part of the hematopoiesis system: infrequently - thrombocytopenia, anemia.
Allergic reactions: infrequently - itching, rash, hives, vasculitis, including purple Shenlaine-Genocha; rarely - anaphylactic reactions, angioedema, including edema of the larynx and vocal cords with the development of airway obstruction and / or swelling of the face, lips, pharynx and / or tongue. Some of these patients had angioedema earlier with other medications, including ACE inhibitors.
From the nervous system: often - sleep disturbance, insomnia, headache, dizziness; infrequently - anxiety, drowsiness, memory disorders, peripheral neuropathy, paresthesia, hypesthesia, tremor, migraine, ataxia, depression, panic conditions, anxiety, loss of consciousness, acute impairment of cerebral circulation.
From the side of the organ of vision: infrequently - a violation of visual acuity, conjunctivitis.
From the side of the organ of hearing: infrequent - ringing in the ears.
From the cardiovascular system: infrequent bradycardia, atrial fibrillation, atrial fibrillation and ventricles, tachycardia, ventricular tachycardia, angina pectoris, myocardial infarction, orthostatic hypotension, cerebrovascular disorders, fainting.
From the respiratory system: often - nasal congestion, sinusitis, sinusitis, cough; infrequently - infections of the upper respiratory tract, rhinitis, pharyngitis, laryngitis, dyspnoea, bronchitis, nosebleeds.
On the part of the digestive system: often - diarrhea, indigestion, spasms, abdominal pain, nausea; infrequent - a violation of taste, dry mouth, constipation, flatulence, gastritis, vomiting, anorexia, a violation of liver function; rarely - hepatitis.
From the skin and subcutaneous tissues: infrequently - alopecia, dermatitis, dry skin, skin hyperemia, photosensitization, increased sweating.
From the musculoskeletal system: often - cramps in the muscles of the lower extremities, myalgia, back pain, chest pain, leg pain; infrequently - arthralgia, arthritis, pain in the hands, pain in the knee, shoulder pain, hip pain, rigidity of the muscles, fibromyalgia, rhabdomyolysis.
From the urinary system: infrequent - imperative urination, urinary tract infections, renal dysfunction, acute renal failure.
From the genitals and the breast: infrequently - decreased libido, impotence.
From laboratory indicators: often - hyperkalemia; infrequent - moderate increase in the concentration of urea and serum creatinine, hypoglycemia, hyponatremia, hyperuricemia; very rarely - increased activity of hepatic enzymes, hyperbilirubinemia.
Other: often - asthenia, increased fatigue.
Hydrochlorothiazide
From the hemopoietic system: infrequently - thrombocytopenia, aplastic anemia, hemolytic anemia, leukopenia, agranulocytosis.
Allergic reactions: infrequently - itching, rashes, hives; rarely anaphylactic reactions.
From the nervous system: often - headache, dizziness; infrequently - sleep disturbance, paresthesia, depression.
From the side of the organ of vision: infrequently - a violation of visual acuity, conjunctivitis, xantopsy.
From the cardiovascular system: infrequently - pain behind the breastbone, bradycardia, AV-blockade II degree, angina, orthostatic hypotension, vasculitis.
On the part of the respiratory system: infrequently - respiratory distress syndrome (including pneumonitis and pulmonary edema).
On the part of the digestive system: infrequently - constipation, diarrhea, pancreatitis, inflammation of the salivary glands, decreased appetite, anorexia, intrahepatic cholestasis; rarely - hepatitis.
From the skin and subcutaneous tissues: infrequently - alopecia, skin hyperemia, photosensitization, increased sweating.
From the musculoskeletal system: infrequently - cramps in the muscles of the lower extremities, muscle weakness, arthralgia.
From the urinary system: infrequently - nocturia, interstitial nephritis.
From the genitals and the breast: infrequently - impotence.
From laboratory indicators: often - hyperkalemia; infrequently - hypokalemia, hypomagnesemia, hypercalcemia, hypochloraemic alkalosis, moderate increase in the concentration of urea and creatinine in the blood serum, hyponatremia, hyperuricemia, glucosuria; very rarely - increased activity of hepatic enzymes, hyperbilirubinemia.
Other: infrequently, fever.
The combination of hydrochlorothiazide / losartan
From the nervous system: often - dizziness.
From the digestive system: rarely - hepatitis.
On the part of laboratory indicators: rarely - hyperglycemia, increased activity of hepatic enzymes.
CONTRAINDICATIONS
- arterial hypotension;
anuria;
- severe renal dysfunction (CC less than 30 ml / min);
- Hyperkalemia;
- refractory hypokalemia;
- Dehydration (including against the background of the use of diuretics in high doses);
- severe violations of the liver (more than 9 points on the scale Child-Pugh);
- Addison's disease;
- simultaneous use with aliskiren in patients with diabetes mellitus and patients with renal failure (CC less than 60 ml / min);
- Pregnancy;
- the period of breastfeeding;
- age under 18 years (effectiveness and safety not established);
- Hypersensitivity to the components of the drug and to other derivatives of the sulfonamide.
Carefully
- Violations of the water-electrolyte balance (hyponatremia, hypochloraemic alkalosis, hypomagnesemia, hypokalemia, hyperkalemia, hypercalcemia);
- reduced BCC (including against the background of the use of diuretics in high doses);
- Liver failure (less than 9 on the Child-Pugh scale);
- impaired renal function (QC more than 30 ml / min);
- condition after kidney transplantation (no experience of application);
- bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney;
- IHD;
- aortic and mitral stenosis;
- hypertrophic obstructive cardiomyopathy;
- heart failure with concomitant renal insufficiency of a serious degree;
- chronic heart failure of severe degree (IV functional class according to the NYHA classification);
- heart failure with life-threatening arrhythmias;
- cerebrovascular diseases;
- diabetes;
- symptomatic hyperuricemia and / or exacerbation of gout;
- weighed allergic anamnesis (in some patients angioedema was developed earlier with the use of other drugs, including ACE inhibitors);
- bronchial asthma;
- systemic diseases of connective tissue (including systemic lupus erythematosus);
- acute myopia;
- secondary closed angle glaucoma;
- simultaneous use of NSAIDs, incl. inhibitors of COX-2;
- simultaneous use of cardiac glycosides;
- elderly age.
PREGNANCY AND LACTATION
The drug Losartan-N Canon is contraindicated in pregnancy. At the same time, the risk for the fetus in the first trimester is lower than in the II and III trimesters, since renal perfusion in the fetus, depending on RAAS, appears in the II trimester.
In the first trimester, the drug Losantan-N Canon is not recommended. However, in those extremely rare cases (less than one in a thousand women), when the use of all other antihypertensive drugs is impossible, the administration of the drug under the close supervision of the doctor, including a weekly ultrasound of the fetus is allowed. In case of signs of oligohydramnion, treatment with an angiotensin II receptor antagonist should be discontinued.
Use of an angiotensin II receptor antagonist in the II or III trimester of pregnancy has toxic effects on the fetus (decreased renal function, oligohydramnios development retardation skull ossification) and newborn (renal failure, hypotension, hyperkalaemia).
As the drugs acting on the RAAS in the II and III trimester of gestation may lead to disruption of the development and / or fetal death, should be stopped immediately when detecting that the drug Losartan pregnancy-H Canon.
For newborns and infants who were exposed in utero angiotensin II receptor antagonist, should be closely monitored for timely detection of lowering blood pressure, oliguria and hyperkalemia.
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 adverse events such as jaundice, fetal and neonatal jaundice, and his mother - thrombocytopenia.
It is not known whether losartan is excreted in breast milk, but it is known that thiazides are excreted in breast milk. Due to the risk of adverse events in infants drug Losartan-H Canon is contraindicated during lactation. If necessary, the drug should stop breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Precautions should be prescribed to patients with impaired renal function (creatinine clearance of more than 30 ml / min).
Do not use this drug in patients with severe renal impairment (creatinine clearance less than 30 mL / min) condition after kidney transplantation (offline experience application), bilateral renal artery stenosis or artery stenosis only kidneys.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Precautions should be prescribed to patients with hepatic failure (less than 9 points on the Child-Pugh).
Do not use this drug in patients with severe hepatic impairment (more than 9 points on the Child-Pugh).
APPLICATION FOR CHILDREN
Use of the drug in children and adolescents under the age of 18 years is contraindicated (efficacy and safety have not been established).
APPLICATION IN ELDERLY PATIENTS
With care should be prescribed to elderly patients.
SPECIAL INSTRUCTIONS
Losartan
In patients with reduced BCC (e.g., receiving diuretics in high doses) may be symptomatic hypotension, however before the treatment needs to be filled or bcc begin treatment with losartan Canon-H at a lower dose.
During treatment should regularly monitor the content of potassium in the blood plasma and spacecraft, especially in elderly patients and patients with impaired renal function. Drugs that affect the RAAS may increase the concentration of urea and serum creatinine in patients with bilateral renal stenosis or stenosis of the artery to a solitary kidney.
Caution must be exercised when administering the drug Losartan-H Canon patients with allergic history (including patients who have previously developed angioedema the use of other drugs, including ACE inhibitors), as well as patients with bronchial asthma .
In patients with liver cirrhosis the concentration of losartan in plasma is significantly increased, and therefore the presence of liver diseases in history preparation should be administered at lower doses.
No need for special selection of the initial dose of elderly patients.
The drug may increase the plasma concentrations of urea and creatinine in patients with bilateral renal artery stenosis or stenosis of the renal artery to a solitary kidney.
Experience in the application of losartan in patients after kidney transplantation there.
As with all drugs with vasodilating action, drug-H Canon Losartan should be used with caution in patients with aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy.
In patients with severe chronic heart failure, the use of drugs that affect the RAAS can cause severe hypotension and acute renal failure. There are some reports about the development of oliguria and / or progressive azotemia and acute renal failure, including fatal.
There is not enough experience with losartan in patients with heart failure with concomitant severe renal impairment, in patients with severe chronic heart failure (IV functional class NYHA classification) in heart failure patients with life-threatening arrhythmias. In these groups should be used with caution drug Losartan-H Canon with beta-blockers.
In patients with ischemic cerebrovascular disease character of an excessive fall in blood pressure can lead to stroke. Recommended medical supervision during dose titration.
Patients with primary hyperaldosteronism generally do not respond to therapy with antihypertensive agents, acting via inhibition of the RAAS. Therefore it is not recommended to apply the preparation Losartan-H Canon for treating such patients.
Hydrochlorothiazide
Hydrochlorothiazide may enhance hypotension and disturbance of water-electrolyte balance (decrease BCC, hyponatremia, hypochloraemic alkalosis, hypomagnesemia, hypokalemia), disrupt glucose tolerance, reduce urinary calcium excretion and cause transient, a slight excess of calcium concentration in plasma. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. In connection with the effect of thiazide on calcium metabolism, their use could distort the results of the research function of the parathyroid glands, so to study the functions of the parathyroid glands thiazide diuretic should be discontinued.
Increasing the concentration of cholesterol and triglycerides it may also be associated with thiazide diuretic therapy.
In some patients, the use of thiazide diuretics can cause hyperuricemia and / or aggravate gout.
Hydrochlorothiazide can cause an idiosyncratic reaction, resulting in the development of acute transient myopia and acute angle-closure glaucoma attack. Symptoms include: sudden blurred vision or eye pain, which usually appear within a few hours or weeks of therapy with hydrochlorothiazide. If untreated, acute attack angle-closure glaucoma can lead to permanent vision loss. It is necessary both to stop taking hydrochlorothiazide quickly as possible. If the intraocular pressure remains uncontrolled, may require urgent medical treatment or surgery. Risk factors for acute angle-closure glaucoma attacks are allergic to penicillins and sulphonamide derivatives history.
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 systemic lupus erythematosus during treatment with thiazide diuretics.
Impact on the ability to drive vehicles and manage mechanisms
Studies of the effect on the ability to drive vehicles and use machinery have not been conducted. However, care must be taken while driving or using machinery.
OVERDOSE
Losartan
Symptoms: excessive lowering of blood pressure, tachycardia. Bradycardia can occur due to parasympathetic (vagal) stimulation.
Treatment: forced diuresis, symptomatic therapy. Hemodialysis is not effective.
Hydrochlorothiazide
Symptoms: The most common symptoms are a consequence of electrolyte deficiency (hypokalemia, chloropenia, hyponatremia) and dehydration due to excessive diuresis. With simultaneous use of cardiac glycosides may exacerbate hypokalemia arrhythmias.
Treatment: symptomatic therapy.
DRUG INTERACTION
Losartan
can be used concomitantly with other antihypertensive agents.
There was no any clinically significant drug 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.
As with other means of blocking the formation of angiotensin II and its effects, concomitant administration of potassium-sparing diuretics (spironolactone and eplerenone, triamterene, amiloride), potassium supplements and salts containing potassium, may increase the content of potassium ions in serum.
Antihypertensives may enhance the hypotensive effect of losartan.
Hypotensive effect of losartan can also enhance tricyclic antidepressants, antipsychotics, baclofen, amifostine, which lower blood pressure in a main or side effect and increase the risk of hypotension.
With simultaneous use of the angiotensin II receptor antagonists and NSAIDs (including selective COX-2 inhibitors, acetylsalicylic acid as an anti-inflammatory agent) can be reduced hypotensive effect of losartan. Patients with impaired simultaneous use receptor antagonists of angiotensin II in renal function or diuretics and NSAIDs can cause further deterioration of renal function, including acute renal failure and increase in potassium in serum. This combination should be used with caution, especially in elderly patients.
With simultaneous use of drugs lithium reversible increases lithium concentrations have been reported with ACE inhibitors in serum and the development of toxicity; In very rare cases, this occurred when using angiotensin II receptor antagonists. With simultaneous use of drugs lithium losartan with caution. If the combination is necessary, it is recommended to monitor the concentration of lithium in blood serum.
Mutually reinforces the effect of beta-blockers and sympatholytic; the combined use of losartan with a diuretic causes an additive effect.
Dual blockade of the RAAS (e.g., by combining an angiotensin II receptor antagonist with an ACE inhibitor or aliskiren) in patients with an established diagnosis of atherosclerosis, heart failure or diabetes with lesions target organs associated with a higher incidence of arterial hypotension, syncope, hyperkalemia, and renal dysfunction (including the development of acute renal failure) as compared to using a single-component blockade of the RAAS. The question of the application of double RAAS blockade should be addressed in each case individually and with careful monitoring of blood pressure, fluid and electrolyte balance of the blood and kidney function.
Hydrochlorothiazide
While the use of thiazide diuretic drugs such as ethanol, barbiturates, and drugs, can potentiate the risk of development of orthostatic hypotension.
When applied simultaneously with hydrochlorothiazide hypoglycemic agents (for oral and insulin) may require correction of the last dose. Metformin should be used with caution because of the risk of lactic acidosis due to possible renal failure associated with taking hydrochlorothiazide.
When applied with other antihypertensives possible additive effect.
Corticosteroids, ACTH while the use of hydrochlorothiazide can cause excessive reduction of electrolytes, particularly hypokalemia.
In an application with hydrochlorothiazide may reduce the severity of the response to the reception of pressor amines (e.g., epinephrine, norepinephrine).
Hydrochlorothiazide potentiates the effect of non-depolarizing muscle relaxant action type (e.g., tubocurarine).
Diuretics reduce the renal clearance of lithium and increase the risk of toxic action of lithium; concurrent use is not recommended.
NSAIDs (including COX-2 inhibitors) may reduce the diuretic, natriuretic and antihypertensive effect of diuretics.
The combined use of medicines for the treatment of gout (probenecid, sulfinpyrazone, allopurinol) may require dose adjustments of these medications, as hydrochlorothiazide can increase the concentration of uric acid in the blood serum may be necessary to increase the dose of probenecid or sulfinpirazona. Co-administration of thiazide diuret
