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Lozap represents antihypertensive drug, intended to reduce, maintain and control blood pressure levels within normal or acceptable limits. The drug reduces both blood pressure and pressure in the pulmonary circulation, reduces the load on the heart and causes a moderate diuretic effect. In addition, Lozap prevents myocardial hypertrophy and increases tolerance to physical or emotional stress. The drug is used in the treatment of arterial hypertension and heart failure.
On pharmaceutical market there are two varieties medicinal product– these are Lozap and Lozap plus. These varieties differ in that Lozap contains only one active component, and Lozap Plus - two. Moreover, the main active component in Lozap and Lozap plus is the same, and the second substance in Lozap plus is additional, enhancing the effect of the first. In this article we will consider both types of the drug, since they have almost the same effect, are indicated for use for the same conditions, etc. Both Lozap and Lozap plus are available in a single dosage form- This tablets for oral administration. Lozap contains as an active ingredient losartan, and Lozap plus – losartan and hydrochlorothiazide. The substance losartan is an angiotensin-converting enzyme (ACE) inhibitor, and hydrochlorothiazide is a diuretic. Accordingly, losartan lowers blood pressure and reduces the load on the heart, and hydrochlorothiazide removes excess fluid from the body, increasing hypotensive effect first substance. Therefore, Lozap plus has a stronger hypotensive effect compared to Lozap, since it contains a combination active ingredients, and not just one substance.
In principle, Lozap plus was created for ease of use, since to enhance the effect with ACE inhibitors Diuretics are often used. Manufacturers simply combined these components in one drug, which is very convenient for a person who needs to take only one tablet, and not two, three, etc.
Lozap is available in three dosages - 12.5 mg, 50 mg and 100 mg losartan per tablet. Lozap plus is available in a single dosage - 50 mg losartan + 12.5 mg hydrochlorothiazide. Lozap 12.5 mg tablets have an oblong, biconvex shape, are colored white or almost white and are available in packs of 30, 60 and 90 pieces. Lozap tablets 50 mg and 100 mg have an oblong biconvex shape, are colored white or almost white, are scored on both sides and are available in packs of 30, 60 and 90 pieces. Lozap plus tablets are oblong in shape, light yellow in color, scored on both sides and are available in packs of 10, 20, 30 and 90 pieces.
The therapeutic effect of Lozap is to lower blood pressure and reduce the load on the heart. This effect The drug is provided due to its ability to suppress the activity of angiotensin-converting enzyme (ACE), which ensures the conversion of angiotensin I to angiotensin II. It is precisely because Lozap suppresses the enzyme that it is classified as an ACE inhibitor. Due to the action of Lozap, the human body does not produce angiotensin II, a substance that constricts blood vessels and, accordingly, helps to increase blood pressure. If the formation of angiotensin II is blocked, then the vessels do not narrow, and blood pressure decreases or remains within normal limits. With regular use of Lozap, blood pressure decreases and is kept within the limits normal values. Moreover, the first hypotensive effect is observed within 1 - 1.5 hours after taking the drug and persists for 24 hours, but for a persistent decrease in blood pressure you need to take the medicine for at least 4 - 5 weeks. Lozap for lowering blood pressure is very effective in elderly and young patients suffering from malignant arterial hypertension.
By dilating blood vessels, Lozap reduces the load on the heart, which makes it easier to push blood through them. By facilitating the work of the heart, the drug increases the tolerance of physical and emotional stress in people suffering from chronic heart disease.
Lozap also improves blood supply to the heart and the intensity of renal blood flow, therefore it is successfully used in the treatment of chronic heart failure and diabetic nephropathy.
Lozap combines well with other antihypertensive drugs and has a moderate diuretic effect, due to which fluid is not retained in the body and edema does not form.
Lozap plus has a more pronounced hypotensive effect compared to Lozap, since the diuretic hydrochlorothiazide included in its composition enhances the effect of the ACE inhibitor.
Separately, it should be noted that Lozap increases the excretion of uric acid and, accordingly, reduces its concentration in the blood.
When you stop taking Lozap and Lozap plus, withdrawal syndrome does not develop.
Lozap - indications for use. 
A Lozap tablet of any dosage can be taken regardless of food, swallowing it whole, without chewing or crushing in any other way, but with a small amount of still water (half a glass is enough). Since the drug has long-term action, then everything you need daily dosage They are taken once, that is, the tablets are taken once a day. It is optimal to take the drug every day at the same time, preferably in the evening. Lozap dosages are determined by the disease for which the drug is taken. The course of therapy is usually long - from several months to several years. The duration of use of the drug is determined individually, based on the effectiveness/side effects ratio.
If a person has hypertrophic obstructive cardiomyopathy or aortic or aortic stenosis mitral valve, or heart failure is combined with arrhythmias or severe renal failure, then he should take Lozap or Lozap plus with caution and only under the supervision of doctors.
It is not recommended to take Lozap in combination with other ACE inhibitors (for example, Captopril, Enalapril, etc.) as this increases the risk of side effects, renal problems and hyperkalemia ( increased level potassium in the blood).
If a person is on hemodialysis, then the dosage of Lozap should be reduced by half from that recommended for the condition for which the drug is being taken.
Lozap plus can provoke an exacerbation of systemic lupus erythematosus and visual impairment due to the development of an attack of myopia or angle-closure glaucoma. If such complications develop, you should stop taking the drug and consult a doctor.
Simultaneous use of Lozap plus with the following drugs can provoke arrhythmia, including the deadly “pirouette” type:
Lozap plus in combination with Carbamazepine can provoke hyponatremia (decreased sodium concentration in the blood).
Iodine-containing contrast agents used in combination with Lozap plus, against the background of dehydration, increase the risk of developing acute renal failure. Therefore, before using such contrast agents, it is necessary to normalize water-electrolyte balance and the amount of fluid in the tissues.
Lozap and Lozap plus may provoke the development of the following side effects from various organs and systems: 1. Blood system:
Lozap and Lozap plus have two types of analogues on the pharmaceutical market of the CIS countries - these are synonyms and, in fact, analogues. Synonyms include drugs that contain exactly the same active substances as Lozap and Lozap plus. Analogues include drugs that contain other active substances, but have the most similar therapeutic effect to Lozap and Lozap plus. In principle, analogues of Lozapa are drugs belonging to the group of ACE inhibitors, and Lozapa plus are ACE inhibitors in combination with diuretics. Synonyms Lozap and Lozap plus are reflected in the table.
| Synonyms Lozap | Synonyms Lozap plus |
| Blocktran tablets | Blocktran GT tablets |
| Brozaar tablets | Vasotens N tablets |
| Vasotens tablets | Gizaar and Gizaar forte tablets |
| Zisacar tablets | Gisortan tablets |
| Cardomin-Sanovel tablets | Hydrochlorothiazide+Losartan-TAD tablets |
| Carzartan tablets | Cardomin plus-Sanovel tablets |
| Cozaar tablets | Losartan-N Richter tablets |
| Lakea tablets | |
| Losarel tablets | Lakea N tablets |
| Losartan tablets | Losartan/Hydrochlorothiazide-Teva tablets |
| Losartan-Richter, Losartan-Teva, Losartan-TAD and Losartan McLeods tablets | Losarel Plus tablets |
| Lorista tablets | Presartan N tablets |
| Losakor tablets | Simartan-N tablets |
| Lotor tablets | |
| Presartan tablets | |
| Renicard tablets |
Analogues of Lozap and Lozap plus are also reflected in the table.
| Analogues of Lozap | Analogues of Lozap plus |
| Aprovel tablets | Atacand Plus tablets |
| Atacand tablets | Valz N tablets |
| Angiacand tablets | Valsacor N80, Valsacor N160, Valsacor N320 tablets |
| Artinova tablets | Valsacor ND160 tablets |
| Valz tablets | Vanatex Combi tablets |
| Valsafors tablets | Ibertan Plus tablets |
| Valsacor tablets | Cardosal Plus tablets |
| Valsartan capsules and tablets | Co-Diovan tablets |
| Valaar tablets | Coaprovel tablets |
| Hyposart tablets | |
| Diovan tablets | Candecor ND 32 tablets |
| Ibertan tablets | Micardis Plus tablets |
| Irbesartan tablets | Ordiss N tablets |
| Irsar tablets | Teveten plus tablets |
| Candecor tablets | Edarbi Clo tablets |
| Cardosal 10, Cardosal 20 and Cardosal 40 tablets | |
| Cardosten tablets | |
| Kandesar tablets | |
| Micardis tablets | |
| Naviten tablets | |
| Nortivan tablets | |
| Ordiss tablets | |
| Olimestra tablets | |
| Prytor tablets | |
| Tantordio tablets | |
| Tareg tablets | |
| Teveten tablets | |
| Telmisartan Richter tablets | |
| Firmasta tablets | |
| Edarbi tablets |
| For Lozap | For Lozap plus | |
| Synonyms | Blocktran tablets | Blocktran GT tablets |
| Brozaar tablets | Lorista N, Lorista N 100 and Lorista ND tablets | |
| Losartan tablets | ||
| Lorista tablets | ||
| Valsafors tablets | Candecor N 8, Candecor N 16 and Candecor N 32 tablets | |
| Valaar tablets | Candecor ND 32 tablets | |
| Irsar tablets | ||
| Candecor tablets | ||
| Cardosten tablets | ||
| Kandesar tablets | ||
| Tareg tablets |
Lozap (active ingredient - losartan) is an antihypertensive drug that is a specific antagonist (blocker) of angiotensin II receptors. This drug is produced by the Slovak pharmaceutical company Zentiva and is the first European generic of losartan.
According to modern ideas, a truly effective antihypertensive drug must meet a wider range of criteria than previously thought, including, in addition to reliable control over blood pressure, a minimum number of negative adverse reactions, duration of action, there is also such a qualification requirement as prevention of target organ damage. Thus, one of the key advantages of such an ideal drug is the ability to prevent or reduce the severity of left ventricular hypertrophy, which develops in 70% of hypertensive patients over 45 years of age and significantly worsens the prognosis for arterial hypertension. In the development of this pathology, the renin-angiotensin-aldosterone system (abbreviated as RAAS) plays an important (if not the main) role. Its main regulatory instrument, the hormone angiotensin II, controls the synthesis of collagen by myocardial connective tissue cells and promotes the development of left ventricular fibrosis. Drugs from the group of angiotensin II blockers (ARBs) prevent the effects of this hormone at the receptor level, regardless of the route of its formation, which, in fact, is the key difference between their mechanism of action and that of angiotensin-converting enzyme inhibitors (ACEIs). Today, ARBs are considered as the drugs of choice in patients with arterial hypertension and left ventricular hypertrophy. Losartan (lozap) was the first ARB to be proven to be more effective high efficiency in terms of increasing the survival rate of such patients.
The proven cardioprotective effect is not the only advantage of lozap. In addition, the drug has cerebro- and nephroprotective effects, which greatly expands the range of its use. Thus, the nephroprotective effect of lozap helps reduce the incidence of cardiovascular events and patient mortality. As for the cerebroprotective effect of the drug, it reduces the likelihood of cerebral strokes and their disabling consequences. Lozap is also used in the treatment of arrhythmias, reducing the risk of developing the most dangerous disorders heart rate. The drug is characterized by uniformity of action, which is important in preventing the so-called. cardiovascular accidents, which usually occur in the morning, when the effect of a previously taken antihypertensive drug wears off. One more undeniable dignity Lozapa is the absence of the so-called. withdrawal syndrome when the drug course is interrupted.
Lozap is available in tablet form. For arterial hypertension, the drug is taken 50 mg 1 time per day; maximum daily dose- 100 mg. Patients with heart failure begin taking lozap with a dose of 12.5 mg once a day. Subsequently, every week (but not more often), the dose can be increased stepwise until the 50-mg daily “ceiling” is reached. Elderly patients take the drug on a general basis, dose adjustments vary in this case not required. Another thing is for patients with impaired liver function: for them, the dose of Lozap should be lower than the standard recommended.
Antihypertensive drug. Specific antagonist of angiotensin II receptors (subtype AT 1). Does not inhibit kininase II, an enzyme that catalyzes the conversion of angiotensin I to angiotensin II. Reduces peripheral vascular resistance, blood concentrations of adrenaline and aldosterone, blood pressure, pressure in the pulmonary circulation; reduces afterload and has a diuretic effect. Prevents the development of myocardial hypertrophy, increases tolerance to physical activity in patients with chronic heart failure. Losartan does not inhibit ACE kininase II and, accordingly, does not prevent the destruction of bradykinin, so side effects indirectly related to bradykinin (for example, angioedema) occur quite rarely.
In patients with arterial hypertension without concomitant diabetes mellitus with proteinuria (more than 2 g/day), the use of the drug significantly reduces proteinuria, albumin and immunoglobulin G excretion.
Stabilizes the level of urea in blood plasma. Does not affect autonomic reflexes and does not have long-term exposure on the concentration of norepinephrine in blood plasma. Losartan at a dose of up to 150 mg/day does not affect the levels of triglycerides, total cholesterol and HDL cholesterol in the blood serum in patients with arterial hypertension. At the same dose, losartan does not affect fasting blood glucose levels.
After a single oral dose, the hypotensive effect (systolic and diastolic blood pressure decreases) reaches a maximum after 6 hours, then gradually decreases over 24 hours.
The maximum hypotensive effect develops 3-6 weeks after starting the drug.
Suction
When taken orally, losartan is well absorbed and undergoes first-pass metabolism through the liver by carboxylation with the participation of the cytochrome CYP2C9 isoenzyme to form an active metabolite. Systemic bioavailability of losartan is about 33%. Cmax of losartan and its active metabolite is achieved in the blood serum approximately 1 hour and 3-4 hours after oral administration, respectively. Food intake does not affect the bioavailability of losartan.
Distribution
More than 99% of losartan and its active metabolite are bound to plasma proteins, mainly albumin. V d of losartan - 34 l. Losartan practically does not penetrate the BBB.
Metabolism
Approximately 14% of losartan administered to a patient intravenously or taken orally is converted into an active metabolite.
Removal
Plasma clearance of losartan is 600 ml/min, and the active metabolite is 50 ml/min. The renal clearance of losartan and its active metabolite is 74 ml/min and 26 ml/min, respectively. When taken orally, approximately 4% of the dose taken is excreted unchanged by the kidneys and about 6% is excreted by the kidneys in the form of an active metabolite. Losartan and its active metabolite exhibit linear pharmacokinetics when administered orally in doses up to 200 mg.
After oral administration, plasma concentrations of losartan and its active metabolite decrease polyexponentially with a final T1/2 of losartan of about 2 hours, and of the active metabolite - about 6-9 hours. When taking the drug at a dose of 100 mg/day, neither losartan nor the active metabolite significantly accumulate in blood plasma. Losartan and its metabolites are excreted from the body through the intestines and kidneys. In healthy volunteers, after oral administration of losartan labeled with the 14 C isotope, about 35% of the radioactive label is found in the urine and 58% in the feces.
Pharmacokinetics in special clinical situations
In patients with mild to moderate alcoholic cirrhosis, the concentration of losartan was 5 times higher, and the active metabolite was 1.7 times higher than in healthy male volunteers.
When CC >10 ml/min, the concentration of losartan in the blood plasma does not differ from that with normal renal function. In patients who require hemodialysis, the AUC is approximately 2 times higher than in patients with normal function kidney
Neither losartan nor its active metabolite is removed from the body by hemodialysis.
Plasma concentrations of losartan and its active metabolite in elderly men with arterial hypertension do not differ significantly from the values of these parameters in young men with arterial hypertension.
Plasma concentrations of losartan in women with arterial hypertension are 2 times higher than the corresponding values in men with arterial hypertension. Concentrations of the active metabolite do not differ between men and women. This pharmacokinetic difference is not clinically significant.
White or almost white, film-coated tablets, oblong, biconvex.
Excipients: microcrystalline cellulose, mannitol, crospovidone, colloidal anhydrous silicon dioxide, talc, magnesium stearate.
Film shell composition: sepifilm 752 white (hypromellose, microcrystalline cellulose, macrogol 2000 stearate, titanium dioxide), macrogol 6000.
10 pcs. - blisters (3) - cardboard packs.
10 pcs. - blisters (6) - cardboard packs.
10 pcs. - blisters (9) - cardboard packs.
The drug is taken orally, regardless of food intake. Frequency of application - 1 time/day.
For arterial hypertension, the average daily dose is 50 mg. In some cases, to achieve a greater therapeutic effect, the daily dose can be increased to 100 mg in 2 or 1 dose.
The initial dose for patients with chronic heart failure is 12.5 mg 1 time / day. As a rule, the dose is increased at weekly intervals (i.e., 12.5 mg/day, 25 mg/day, 50 mg/day) to an average maintenance dose of 50 mg 1 time/day, depending on tolerability of the drug.
When prescribing the drug to patients receiving diuretics in high doses, the initial dose of Lozap ® should be reduced to 25 mg 1 time / day.
For elderly patients there is no need for dose adjustment.
When prescribing the drug to reduce the risk of cardiovascular diseases (including stroke) and mortality in patients with arterial hypertension and left ventricular hypertrophy, the initial dose is 50 mg/day. In the future, hydrochlorothiazide may be added at a low dose and/or the dose of Lozap ® may be increased to 100 mg/day in 1-2 doses.
For patients with concomitant type 2 diabetes mellitus with proteinuria, the initial dose of the drug is 50 mg 1 time / day, then the dose is increased to 100 mg / day (taking into account the degree of blood pressure reduction) in 1-2 doses.
For patients with a history of liver disease, dehydration, during hemodialysis, as well as patients over 75 years of age, a lower initial dose of the drug is recommended - 25 mg (1/2 tablet of 50 mg) 1 time / day.
Symptoms: marked decrease in blood pressure, tachycardia; Bradycardia may occur due to parasympathetic (vagal) stimulation.
Treatment: forced diuresis, symptomatic therapy; hemodialysis is not effective.
The drug can be prescribed with other antihypertensive drugs. There is a mutual enhancement of the effects of beta-blockers and sympatholytics. When losartan is used together with diuretics, an additive effect is observed.
There was no pharmacokinetic interaction of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin.
Rifampicin and fluconazole have been reported to reduce plasma concentrations of the active metabolite losartan. Clinical significance this interaction is not yet known.
As with other drugs that inhibit angiotensin II or its action, concomitant use of losartan with potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium supplements and potassium-containing salts increases the risk of hyperkalemia.
NSAIDs, including selective inhibitors COX-2 may reduce the effect of diuretics and other antihypertensive drugs.
With the combined use of angiotensin II receptor antagonists and lithium, an increase in the concentration of lithium in the blood plasma is possible. Considering this, it is necessary to weigh the benefits and risks of combined use of losartan with lithium salts. If combined use is necessary, the concentration of lithium in the blood plasma should be regularly monitored.
When using losartan for the treatment of essential hypertension in controlled studies, among all side effects, only the incidence of dizziness differed from placebo by more than 1% (4.1% versus 2.4%).
A dose-dependent orthostatic effect, characteristic of antihypertensive drugs, was observed in less than 1% of patients when using losartan.
Determination of the frequency of side effects: very often (≥ 1/10); often (≥ 1/100, ≤ 1/10); sometimes (≥ 1/1000, ≤ 1/100); rare (≥ 1/10,000, ≤ 1/1000); very rare (≤ 1/10,000, including isolated reports).
Side effects occurring with a frequency greater than 1%
| Side effects | Losartan (n=2085) | Placebo (n=535) |
| General reactions | ||
| Asthenia, fatigue | 3.8 | 3.9 |
| Chest pain | 1.1 | 2.6 |
| Peripheral edema | 1.7 | 1.9 |
| From the outside cardiovascular system | ||
| Heartbeat | 1.0 | 0.4 |
| Tachycardia | 1.0 | 1.7 |
| From the outside digestive system | ||
| Abdominal pain | 1.7 | 1.7 |
| Diarrhea | 1.9 | 1.9 |
| Dyspeptic phenomena | 1.1 | 1.5 |
| Nausea | 1.8 | 2.8 |
| From the musculoskeletal system | ||
| Pain in back, legs | 1.6 | 1.1 |
| Calf muscle cramps | 1.0 | 1.1 |
| From the side of the central nervous system | ||
| Dizziness | 4.1 | 2.4 |
| Headache | 14.1 | 17.2 |
| Insomnia | 1.1 | 0.7 |
| From the respiratory system | ||
| Cough, bronchitis | 3.1 | 2.6 |
| Nasal congestion | 1.3 | 1.1 |
| Pharyngitis | 1.5 | 2.6 |
| Sinusitis | 1.0 | 1.3 |
| Infections of the upper respiratory tract | 6.5 | 5.6 |
Side effects of losartan are usually transient and do not require discontinuation of the drug.
Side effects occurring with an incidence of less than 1%
From the cardiovascular system: orthostatic hypotension (dose-dependent), epistaxis, bradycardia, arrhythmias, angina pectoris, vasculitis, myocardial infarction.
From the digestive system: anorexia, dry oral mucosa, toothache, vomiting, flatulence, gastritis, constipation, hepatitis, liver dysfunction; very rarely - moderate increase in AST and ALT activity, hyperbilirubinemia.
Dermatological reactions: dry skin, erythema, ecchymosis, photosensitivity, increased sweating, alopecia.
Allergic reactions: urticaria, skin rash, itching, angioedema (including swelling of the larynx and tongue, causing airway obstruction and/or swelling of the face, lips, pharynx).
From the hematopoietic system: sometimes - anemia (slight decrease in the concentration of hemoglobin and hematocrit, on average by 0.11 g% and 0.09 volume%, respectively, rarely - of clinical significance), thrombocytopenia, eosinophilia, Henoch-Schönlein purpura.
From the musculoskeletal system: arthralgia, arthritis, shoulder pain, knee pain, fibromyalgia.
From the central nervous system and peripheral nervous system: anxiety, sleep disturbance, drowsiness, memory disorders, peripheral neuropathy, paresthesia, hypoesthesia, tremor, ataxia, depression, fainting, migraine.
From the senses: ringing in the ears, taste disturbances, visual disturbances, conjunctivitis.
From the urinary system: imperative urge to urinate, urinary tract infections, impaired renal function; sometimes - an increase in the level of urea and residual nitrogen or creatinine in the blood serum.
From the reproductive system: decreased libido, impotence.
From the side of metabolism: often - hyperkalemia (potassium level in blood plasma more than 5.5 mmol/l); gout.
The drug should be used with caution when arterial hypotension, decreased blood volume, water-electrolyte imbalance, bilateral renal artery stenosis or stenosis of the artery of a single kidney, with renal/liver failure.
There are no data on the use of Lozap ® during pregnancy. However, it is known that drugs acting directly on the RAAS, when used in II and III trimesters pregnancies can cause developmental defects or even death of the developing fetus. Therefore, if pregnancy occurs, the use of Lozap ® should be stopped immediately.
If it is necessary to use Lozap during lactation, a decision should be made to either stop breastfeeding, or to stop treatment with the drug.
In patients with impaired renal function, including patients on dialysis, there is no need to adjust the initial dose.
During treatment, the concentration of potassium in the blood should be regularly monitored in case of impaired renal function.
It is necessary to correct dehydration before prescribing the drug Lozap ® or begin treatment with the use of the drug at a lower dose.
Drugs that affect the RAAS may increase blood urea and serum creatinine levels in patients with bilateral renal artery stenosis or solitary renal artery stenosis.
In patients with liver cirrhosis, the concentration of losartan in the blood plasma increases significantly, and therefore, in the presence of a history of liver disease, it should be prescribed in lower doses.
During the treatment period, the concentration of potassium in the blood should be regularly monitored, especially in elderly patients with impaired renal function.
Use in pediatrics
The safety and effectiveness of the drug Lozap ® in children and adolescents under 18 years of age have not been established.
Impact on the ability to drive vehicles and operate machinery
Lozap ® does not affect the ability to drive vehicles or operate machinery.
In this article you can read the instructions for use of the drug Lozap. Feedback from site visitors - consumers - is presented of this medicine, as well as the opinions of specialist doctors on the use of Lozap in their practice. We kindly ask you to actively add your reviews about the drug: whether the medicine helped or did not help get rid of the disease, what complications and side effects were observed, perhaps not stated by the manufacturer in the annotation. Analogues of Lozap in the presence of existing structural analogues. Use for the treatment of high blood pressure and its reduction in adults, children, as well as during pregnancy and lactation.
Lozap- antihypertensive drug. Specific angiotensin 2 receptor antagonist (AT1 subtype). Does not suppress kininase 2, an enzyme that catalyzes the reaction of converting angiotensin 1 into angiotensin 2. Reduces peripheral vascular resistance, blood concentrations of adrenaline and aldosterone, blood pressure, pressure in the pulmonary circulation; reduces afterload and has a diuretic effect. Prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure. Losartan (the active ingredient of the drug Lozap) does not inhibit ACE kininase 2 and, accordingly, does not prevent the destruction of bradykinin, therefore side effects indirectly associated with bradykinin (for example, angioedema) occur quite rarely.
In patients with arterial hypertension without concomitant diabetes mellitus with proteinuria (more than 2 g per day), the use of the drug significantly reduces proteinuria, albumin and immunoglobulin G excretion.
Stabilizes the level of urea in blood plasma. Does not affect autonomic reflexes and does not have a long-term effect on the concentration of norepinephrine in the blood plasma. Losartan at a dose of up to 150 mg per day does not affect the levels of triglycerides, total cholesterol and HDL cholesterol in the blood serum in patients with arterial hypertension. At the same dose, losartan does not affect fasting blood glucose levels.
After a single oral dose, the hypotensive effect (systolic and diastolic blood pressure decreases) reaches a maximum after 6 hours, then gradually decreases over 24 hours.
The maximum hypotensive effect develops 3-6 weeks after starting the drug.
The combined drug Lozap plus additionally contains hydrochlorothiazide, a thiazide diuretic. Reduces the reabsorption of sodium ions, increases the excretion of potassium, bicarbonate and phosphate ions in the urine. Lowers blood pressure by reducing blood volume, changing the reactivity of the vascular wall, reducing the pressor effect of vasoconstrictors and increasing the depressor effect on the ganglia.
The maximum antihypertensive effect is achieved within 3 weeks after the start of treatment.
Pharmacokinetics
When taken orally, Lozap is well absorbed. Food intake does not affect the bioavailability of losartan. Approximately 14% of losartan administered to a patient intravenously or taken orally is converted into an active metabolite. When taken orally, approximately 4% of the dose taken is excreted unchanged by the kidneys and about 6% is excreted by the kidneys in the form of an active metabolite.
Neither losartan nor its active metabolite is removed from the body by hemodialysis.
Plasma concentrations of losartan and its active metabolite in elderly men with arterial hypertension do not differ significantly from the values of these parameters in young men with arterial hypertension.
Plasma concentrations of losartan in women with arterial hypertension are 2 times higher than the corresponding values in men with arterial hypertension. Concentrations of the active metabolite do not differ between men and women. This pharmacokinetic difference is not clinically significant.
Indications
Release forms
Film-coated tablets 12.5 mg, 50 mg and 100 mg.
Lozap plus tablets (in combination with the diuretic hydrochlorothiazide to enhance the effect).
Instructions for use and dosage
The drug is taken orally, regardless of food intake. The frequency of administration is 1 time per day.
For arterial hypertension, the average daily dose is 50 mg. In some cases, to achieve a greater therapeutic effect, the daily dose can be increased to 100 mg in 2 or 1 dose.
The initial dose for patients with chronic heart failure is 12.5 mg 1 time per day. Typically, the dose is increased at weekly intervals (i.e., 12.5 mg per day, 25 mg per day, 50 mg per day) to a mean maintenance dose of 50 mg once daily, depending on drug tolerability.
When prescribing the drug to patients receiving diuretics in high doses, the initial dose of Lozap should be reduced to 25 mg 1 time per day.
For elderly patients there is no need for dose adjustment.
When prescribing the drug to reduce the risk of cardiovascular diseases (including stroke) and mortality in patients with arterial hypertension and left ventricular hypertrophy, the initial dose is 50 mg per day. In the future, hydrochlorothiazide may be added at a low dose and/or the dose of Lozap may be increased to 100 mg per day in 1-2 doses.
For patients with concomitant type 2 diabetes mellitus with proteinuria, the initial dose of the drug is 50 mg 1 time per day, then the dose is increased to 100 mg per day (taking into account the degree of blood pressure reduction) in 1-2 doses.
For patients with a history of liver disease, dehydration, during hemodialysis, as well as patients over 75 years of age, a lower initial dose of the drug is recommended - 25 mg (1/2 tablet of 50 mg) once a day.
Side effect
Contraindications
Use during pregnancy and breastfeeding
There are no data on the use of Lozap during pregnancy. However, it is known that drugs that directly affect the RAAS, when used in the 2nd and 3rd trimesters of pregnancy, can cause developmental defects or even death of the developing fetus. Therefore, if pregnancy occurs, taking Lozap should be stopped immediately.
If it is necessary to use Lozap during lactation, a decision should be made either to stop breastfeeding, or to stop breastfeeding, or to stop treatment with the drug.
Special instructions
It is necessary to correct dehydration before prescribing Lozap or begin treatment with the drug at a lower dose.
Drugs that affect the RAAS may increase blood urea and serum creatinine levels in patients with bilateral renal artery stenosis or solitary renal artery stenosis.
In patients with liver cirrhosis, the concentration of losartan in the blood plasma increases significantly, and therefore, in the presence of a history of liver disease, it should be prescribed in lower doses.
Taking alcohol together also increases the concentration of Lozap in the body.
During the treatment period, the concentration of potassium in the blood should be regularly monitored, especially in elderly patients with impaired renal function.
Use in pediatrics
The safety and effectiveness of Lozap in children and adolescents under 18 years of age have not been established.
Impact on the ability to drive vehicles and operate machinery
Lozap does not affect the ability to drive vehicles or operate machinery.
Drug interactions
The drug can be prescribed with other antihypertensive drugs. There is a mutual enhancement of the effects of beta-blockers and sympatholytics. When losartan is used together with diuretics, an additive effect is observed.
There was no pharmacokinetic interaction of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin.
Rifampicin and fluconazole have been reported to reduce plasma concentrations of the active metabolite losartan. The clinical significance of this interaction is not yet known.
As with other drugs that inhibit angiotensin 2 or its action, concomitant use of losartan with potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium supplements and potassium-containing salts increases the risk of hyperkalemia.
NSAIDs, including selective COX-2 inhibitors, may reduce the effect of diuretics and other antihypertensive agents.
With the combined use of angiotensin 2 receptor antagonists and lithium, an increase in the concentration of lithium in the blood plasma is possible. Taking this into account, it is necessary to weigh the benefits and risks of combined use of losartan with lithium salts. If combined use is necessary, the concentration of lithium in the blood plasma should be regularly monitored.
Analogues of the drug Lozap
Structural analogues of the active substance:
If there are no analogues of the drug for the active substance, you can follow the links below to the diseases for which the corresponding drug helps, and look at the available analogues for the therapeutic effect.
The combined antihypertensive drug Lozap plus is considered by world medicine to be a successful solution. Actively use the medicine positive results from application explain this popularity. What is interesting about Lozap plus, what is special about the drug, is reflected not only in the instructions for its use.
Many patients of cardiologists use the medicine; patient reviews confirm the effectiveness and efficiency of the drug Lozap Plus.
No wonder it is so in demand in the pharmaceutical market. The consumer is not even bothered by the price (lozap plus has cheap analogues, but they are not competitors).
Lozap plus is an improved form of combined antihypertensive drugs. Approved and put into production by pharmaceutical companies in many countries.
The medicine includes substances of two groups: calcium channel blockers () and thiazide diuretics (hydrochlorothiazide). The focus of both is antihypertensive.
INN: Losartan + Hydrochlorothiazide.
The group that includes losartan is also called sartans or calcium antagonists. – diuretic, thiazide diuretic. The drug is mild, but works well in pairs; it is included in many combined antihypertensive drugs.
Coated tablets. The shell is filmy, soluble, white. Compound medicine lozap plus: active substances: calcium antagonist losartan, diuretic hydrochlorothiazide and additives - various excipients. 
The active ingredients are evenly distributed in the supplementary auxiliaries. These are pharmaceutical additives common to drugs:
Each of the additional substances helps preserve the main active substances before entering the body and subsequent correct transformation and therapeutic work after ingestion.
One of the sartans is included in the drug - losartan in combination with the popular diuretic hydrochlorothiazide. Sartans, aka:
The main purpose of losartan is to block slow calcium channels. The result of this blocking: relief of excess tension smooth muscles tissues of organs and blood vessels, provoked by an excess of calcium. The passage of calcium is partially blocked, the disturbed calcium metabolism is normalized.
The contraction-relaxation cycle is restored. The myocardium can function normally and receive full nutrition from the rhythmically pulsating vessels supplying it with blood.
Hydrochlorothiazide fulfills its purpose: it removes excess fluid from the bloodstream, relieves stress on the walls of the coronary and peripheral vessels. Without chemically interfering with losartan, hydrochlorothiazide helps it normalize blood pressure. 
The human body is a grandiose chemical laboratory in which synthetic components skillfully created by scientists can navigate well.
Lozap plus prevents the occurrence of vascular accidents, practically saving lives.
Sartans perform a strictly targeted function. They (losartan too) block part of the calcium channels called “slow”. Along these pathways (L-pathway), excess calcium rushes into the cells from the intercellular space. The reasons for this excess of calcium may vary.
Crash metabolic processes, unhealthy diet, systemic diseases, pathology of the parathyroid glands. Many factors influence the behavior of calcium. But when a lot of it penetrates the cell, it works. And its main job is stimulation contractility muscles. This is how nature programmed it. 
Muscles contract, this is vital. But life processes are debugged only when they are cyclical. After contraction comes relaxation. The massive presence of calcium in tissues blocks the possibility of a normal act of relaxation.
The walls of blood vessels, no matter how thin they may seem, also consist of muscle tissue. “Calcium overstrain” also affects blood vessels. They are compressed, spasmed, and have difficulty letting blood pass through them. Blood pressure grows, the blood supply to the body is disrupted.
All organs suffer. First of all, the command post is the brain and the engine of life processes is the heart.
The excess must be brought to normal; this is the task of losartan.
Hydrochlorothiazide has its own function. By enhancing the excretion of fluid, the medicine controls its condition directly in the kidneys. Prevents reverse absorption (reabsorption) into the blood from the urinary contents of the trace element sodium. It must be removed so that the pressure decreases. Hydrochlorothiazide helps reduce sodium return by inhibiting its reabsorption.Sodium is known to be hydrophilic; it retains fluid in the body, attracting it. At high blood pressure Excess sodium should be eliminated. So that the volume of liquid does not increase. That’s why the diet for hypertensive patients includes limited quantity salt, which contains this trace element. Let's remember: the formula of NaCl salt is sodium and chlorine. Chlorine is also hydrophilic.
But the phenomenon of reabsorption itself is an adaptive reaction, and in some cases the body needs it. In some diseases, calcium is returned through this route—canalicular reabsorption—and other elements if homeostasis (equilibrium, constancy of substance content) is pathologically disturbed.
Reabsorption of almost excreted sodium from primary urine should not be allowed. At the same time, the drug promotes the removal of salts: phosphates, potassium, bicarbonates. Not all of them are superfluous; the conclusion should be moderate. Periodic monitoring of the percentage presence of elements in the blood plasma is required.
Pharmacokinetics
While losartan is in the tablet, it is not a medicine. Predecessor active substance, prodrug. There it is contained in the form of a potassium salt: losartan potassium. Only in the body is it metabolized by the liver into losartan itself, the active ingredient. Adsorption of losartan is rapid.
The peculiarity of losartan when it enters the body’s filter is the liver: it is susceptible to the first pass effect. This effect is called protective function body, filtering by the liver of everything it detects. The liver is a barrier to foreign substances accidentally or intentionally introduced into the body. A huge burden falls on her, but without this security work, not a single drug will receive a “pass” into the body.
Often this is an obstacle to medications; the liver metabolizes them, breaks them down, transforms them, preventing unchanged substances from being absorbed into the gastrointestinal tract and metabolized afterwards. In the case of Lozap Plus, this point is positive.
The merit of the pharmacists: they synthesized the drug so that the liver produces metabolites that are already active and ready for action. Therapeutic effect is not suppressed by it, but prepared.
Immediately after the passage of the protective liver filter provided by nature, the metabolite losartan is sent for its intended purpose: to reduce:
As a result, by 95% connecting with blood elements, it reduces lozap plus, already one integral part(not counting the second one for now - hydrochlorothiazide):
- Blood pressure;
- Load on the heart;
- Excessive vascular tone - peripheral and coronary.
It does not affect any other processes, the amount and synthesis of bradycardin does not affect it, just as lozap plus itself does not affect other metabolic reactions. Its mood is strictly selective: calcium channel receptors. Not all, only the “slow” ones, without medicinal assistance unable to cope with the onslaught of calcium.
Scientists in the pharmaceutical industry have to work hard on the composition of starting substances. All reactions possible upon contact with the liver are taken into account. The output should be a converted, but medicinally active component (or components) of the drug. With Lozap Plus a successful solution was found.
The second element of the drug lozap plus, a diuretic, hydrochlorothiazide, the ratio of both is indicated in the instructions for use. It looks like this: losartan potassium is four times more than hydrochlorothiazide (respectively: 50 and 12.5 mg).
Hydrochlorothiazide passes through the liver successfully, unchanged. It is not metabolized there. It is quickly absorbed into the gastrointestinal tract and begins to work. More than 60% is excreted in the same, unchanged form - by the kidneys.
Tablet form. Oblong tablets are produced in a coating. This usually promotes a slow release of the drug. Lozap plus is a long-acting drug that works 24 hours before next appointment. But there is no prohibition on dividing the tablet; this is evidenced by the risk of breaking. Sometimes you need to take half a tablet, not a whole one, this is not forbidden.
The active ingredients coexist well and combine well. Once in the body, each performs its own work. Both help lower blood pressure. Losartan – blocking slow calcium channels, hydrochlorothiazide - gently removing excess fluid through the kidneys. The blood volume in the vascular bed (BCV) decreases somewhat, and the pressure also decreases.
The parallel operation of two substances more reliably ensures the result: maintaining blood pressure at an optimal functional level.
Lozap plus controls the condition of cardiac vessels and peripheral vascular system also keeps it under control. In the latter, it reduces peripheral resistance, which also contributes to the effect of lowering blood pressure.The maximum therapeutic effect of a single dose occurs, according to the instructions for use, in the sixth hour from taking the medication Lozap Plus. Slowly reducing effect, combined antihypertensive drug works 24 hours - until the next appointment, with some overlap in time.
Conclusions about effectiveness are made after a few (3 – 6) weeks.
Method of administration, dosage
Take Lozap plus once a day, without making adjustments for age, gender, or nationality. There is only one exception: people of the Black race may require a higher dose. Or you need to select a different drug. Their body produces less renin, lozap plus the usual dosage may have insufficient effect.
The dosage of the drug lozap plus is 50 mg (one tablet). If uncompensated CHF is present, the initial dose can be reduced to half a tablet - 12.5 mg. Further - depending on the circumstances. If tolerated, carefully increase once a week to reach the recommended 50 mg.
For some patients, this dose is not sufficient to achieve the desired effect. Then it is increased in the same gradual way to the maximum possible daily dose - 100 mg. Monitor tolerance. If the body accepts 75 mg adequately, and a dose of 100 mg provokes deterioration and the appearance of side effects, leave 75 mg.
What is important is the actual benefit, and not the dose fixed by the instruction template. In case of high doses, take it once a day, even if it is two tablets at once.
The dose for the elderly is not adjusted. Age and even pathological condition kidneys do not mutually affect the functioning of the drug and the effect of lozap plus on the body.
If the patient takes a significant amount of diuretics, the doctor reduces the dose of lozap plus by half. It is necessary to exclude the total effect of diuretics.
Contraindications
Prescription with caution
Representatives of calcium antagonists, a group that includes losartan, are prescribed under supervision to patients:
Side effects
The drug lozan plus, like any substance synthesized for treatment, may have side effects. They will not appear in everyone and not necessarily. But during tests, with different frequencies of occurrence, these effects were noted - they were. Reviews from doctors who practice treatment with Lozap Plus about its side effects are restrained. If the patient is not allergic, serious problems usually do not occur.
During treatment you may encounter:
When the question arises: which medicine is better, just Lozap or the combined Lozap plus, the decision is made individually each time. It’s different for each patient. Not shown to everyone. Those who cannot have them will choose the lozap.
Most people tolerate it better and get a greater effect from the combination of the two. active ingredients. The result is faster and more reliable. Then - lozap plus.
What makes Lozap Plus different is that it contains not only losartan; unlike Lozap, it is also supplemented with the diuretic hydrochlorothiazide. This is the main difference.
Overdose
Losartan directly affects blood pressure and heart function, so an overdose is fraught with:
Persistent drop in blood pressure:
Hydrochlorothiazide enhances fluid excretion; in case of an overdose, loss of necessary organisms electrolytes. There is a shortage:
- Potassium – hypokalemia;
- Sodium – hyponatremia;
- Chlorine – hypochloremia.
An overdose of the diuretic drug hydrochlorothiazide and dehydration of the entire body - dehydration - is dangerous.
Overdose is determined primarily by symptoms:
The entire complex is not necessary, but partial manifestation of symptoms is a reason to be wary.
Help: symptomatic treatment. Relieving symptoms and supporting the heart, restoring water and electrolyte balance. If the symptoms are present, the drug has been taken for a long time, gastric lavage will not help. Losartan is firmly retained by the protein part of the blood plasma and cannot be removed by hemodialysis.
It is necessary to support the body with drip administration of drugs constantly, until Lozap Plus reduces the effect. It is worth considering: an increased dose (overdose) may last longer.
Medical supervision is required.
Drug interactions
Losartan. In combination with antihypertensive drugs, losartan creates a stacking effect. Enhances blood pressure lowering effect.
Losartan has good compatibility with the following drugs:
Hydrochlorothiazide. Treatment with the drug may increase blood glucose levels in diabetics. The endocrinologist will adjust the doses of glucose-lowering substances - he should be notified about treatment with the thiazide diuretic hydrochlorothiazide.
The medicine will give an additive (total) effect with any antihypertensive drugs.
Orthostatic hypotension is possible when taken with drugs:
The cholesterol-lowering drug cholestyramine interferes with the absorption of hydrochlorothiazide.
Corticosteroid hormones lead to hypokalemia, and other electrolytes in this combination are also greatly lost by the body.
Lithium preparations tend to accumulate in the presence of thiazides and create a toxic effect.Myocardial stimulants, pressor amines, helping with acute form heart failure (norepinephrine, dopamine), partially lose effectiveness.
NSAIDs – anti-inflammatory non-steroidal drugs may reduce the effectiveness of the hydrochlorothiazide included in Losap Plus.
Diuresis, sodium excretion and the effect of the drug on blood pressure are reduced. and I.
Special instructions
Sometimes taking the medicine causes dizziness. Some patients feel drowsy. The ability to drive cars and other vehicles may be impaired. There are no strict restrictions: this reaction may appear at the beginning of treatment and then disappear. But it is necessary to control this.
If diabetes is revealed during treatment with Lozap Plus, this is usually not classified as side effects. This is how a latent (hidden) form of an existing, but previously undetected, asymptomatic diabetes may manifest itself. Potentiates the manifestation of the disease - hydrochlorothiazide.
The situation is similar with latent hyperparathyroidism. When there is too much calcium in the blood (hypercalcemia), it is dangerous to ignore this fact. It is necessary to interrupt treatment with Lozap Plus, pause (several days) and examine parathyroid glands. There is a high probability that their work, or one of several, is disrupted. This fact requires immediate correction.
Analogues
Any medicine has analogues, lozap plus too. Drugs of the same composition from different pharmaceutical companies may differ in production technology and, for this reason, in price. Czech lozap plus has a price in Moscow for 30 tablets per package - 365 rubles.
You can also buy it more profitably - a package with 90 tablets, paying 760 rubles. Price of one lozap tablets plus, when purchasing a larger quantity of medicine, it will decrease from 12.2 to 8.4 rubles. In cities, the price for lozap plus is approximately the same: in St. Petersburg you can get it for 377 rubles and more (not much).
Russian cheap analogue the same medicine lozap plus:
The following similar medicinal combination substances are known:
Hypotensive combination drug(angiotensin II receptor antagonist + diuretic)
Active ingredients
Release form, composition and packaging
Film-coated tablets light yellow in color, oblong, with a halving mark on both sides.
Excipients: mannitol - 89 mg, microcrystalline cellulose - 210 mg, croscarmellose sodium - 18 mg, povidone - 7 mg, magnesium stearate - 3.5 mg.
Film shell composition: hypromellose 2910/5 - 6.8597 mg, macrogol 6000 - 1.9 mg, talc - 0.8 mg, simethicone emulsion - 0.3 mg, titanium dioxide - 0.1288 mg, quinoline yellow dye (Quinolin Yellow) (E104) - 0.011 mg, crimson dye [Ponceau 4R ] (Pounceau 4R) (E124) - 0.0005 mg.
10 pcs. - blisters (1) - cardboard packs.
10 pcs. - blisters (3) - cardboard packs.
10 pcs. - blisters (6) - cardboard packs.
10 pcs. - blisters (9) - cardboard packs.
14 pcs. - blisters (2) - cardboard packs.
15 pcs. - blisters (2) - cardboard packs.
15 pcs. - blisters (4) - cardboard packs.
15 pcs. - blisters (6) - cardboard packs.Pharmacological action
The combined drug has a hypotensive effect. Contains losartan potassium - an angiotensin II receptor antagonist (AT subtype 1) and a diuretic.
Losartan/hydrochlorothiazide
Losartan and hydrochlorothiazide demonstrate a synergistic hypotensive effect, reducing blood pressure to a greater extent than either component alone. It is assumed that this effect is the result of the additive action of both components. In addition, as a result of the diuretic effect, hydrochlorothiazide increases the activity of renin in the blood plasma, the secretion of aldosterone, reduces the concentration of potassium in the blood plasma and increases the content of angiotensin II. The use of losartan blocks everything physiologically meaningful actions angiotensin II and reduces potassium losses associated with diuretic use by inhibiting aldosterone.
Losartan has a mild and short-term uricosuric effect. Hydrochlorothiazide leads to a moderate increase in plasma uric acid; the combination of losartan and hydrochlorothiazide helps to attenuate diuretic-induced hyperuricemia.
The hypotensive effect of the losartan/hydrochlorothiazide combination persists for 24 hours. Despite the significant reduction in blood pressure, taking the losartan/hydrochlorothiazide combination does not have a significant clinical effect on heart rate. IN clinical studies it was shown that after 12 weeks of therapy with the combination losartan 50 mg/hydrochlorothiazide 12.5 mg, minimum diastolic blood pressure (measured in the sitting position) decreased by an average of 13.2 mm Hg.
Losartan/hydrochlorothiazide effectively reduces blood pressure in men and women, patients of black and other races, and young people (<65 лет) и пожилых (≥65 лет) пациентов и при любой степени артериальной гипертензии.
Losartan
Losartan is a synthetic angiotensin II receptor blocker (type AT 1). Angiotensin II, a powerful vasoconstrictor. is the main active hormone of the RAAS and the most important factor in the pathophysiology of arterial hypertension. Angiotensin II binds to AT 1 receptors found in many tissues (vascular smooth muscle, adrenal glands, kidneys and heart) and causes a number of biologically important effects, including vasoconstriction and aldosterone release. Angiotensin II also stimulates the proliferation of smooth muscle cells. Losartan selectively blocks AT 1 receptors. Losartan and its pharmacologically active carboxyl metabolite E-3174 block all physiologically significant effects of angiotensin II in vitro and in vivo, regardless of the source and route of synthesis of the latter. Losartan does not have an agonistic effect and does not block other hormone receptors or ion channels that play an important role in regulating the function of the cardiovascular system. In addition, losartan does not inhibit ACE (kininase II), an enzyme that breaks down bradykinin. Therefore, there is no potentiation of undesirable effects mediated by bradykinin.
When using losartan, elimination of the negative feedback reaction of angiotensin II on renin secretion leads to an increase in the activity of the latter in the blood plasma. An increase in renin activity leads to an increase in the concentration of angiotensin II in the blood plasma. Despite this increase, the antihypertensive effect and decrease in plasma aldosterone concentrations are maintained, indicating effective blockade of angiotensin II receptors. After stopping the use of losartan, plasma renin activity and angiotensin II levels return to their original values within 3 days.
Both losartan and its main active metabolite have a greater affinity for AT 1 receptors than for AT 2 receptors. This metabolite is 10-40 times more active than losartan.
The incidence of cough is comparable in patients taking losartan or hydrochlorothiazide, and is significantly lower than when using ACE inhibitors.
In patients with arterial hypertension, proteinuria without diabetes mellitus and taking losartan, there was a significant decrease in proteinuria, fractional release of proteins and immunoglobulin G. Losartan stabilizes the glomerular filtration rate and reduces the filtration fraction. In general, losartan causes a decrease in serum uric acid levels that persists during long-term therapy.
Losartan does not affect autonomic reflexes and does not have a long-term effect on the level of norepinephrine in the blood plasma. In patients with left ventricular failure, losartan at a dose of 25 mg and 50 mg has a positive hemodynamic and neurohumoral effect, characterized by an increase in cardiac index and a decrease in pulmonary capillary wedge pressure, systemic vascular resistance, systemic blood pressure and heart rate, as well as plasma aldosterone and norepinephrine concentrations, respectively. . The development of hypotension in such patients with heart failure was dose-dependent.
Hydrochlorothiazide
Hydrochlorothiazide is a thiazide diuretic. The mechanism of the antihypertensive effect of this group of drugs is not fully known. Thiazide diuretics affect the renal tubular reabsorption mechanisms of electrolytes, directly increasing the excretion of sodium and chloride in approximately equivalent amounts. The diuretic effect of hydrochlorothiazide reduces blood plasma volume, increases plasma renin activity and increases the secretion of aldosterone with a subsequent increase in the concentration of potassium in the urine, loss of bicarbonates and a decrease in the concentration of potassium in the blood plasma. The coupling of renin to aldosterone is mediated by angiotensin II, and therefore concomitant use of angiotensin II receptor antagonists generally reverses the potassium loss caused by thiazide diuretics.
When taken orally, the diuretic effect of hydrochlorothiazide begins after 2 hours, reaches a maximum after an average of 4 hours and lasts from 6 to 12 hours, the hypotensive effect persists for 24 hours.
Pharmacokinetics
Losartan
Suction
Losartan is well absorbed after oral administration and undergoes first-pass metabolism to form an active carboxylic acid metabolite, as well as other inactive metabolites. The systemic bioavailability of losartan in tablet form is approximately 33%. The average Cmax of losartan and its active metabolite is reached after 1 and 3-4 hours, respectively. When losartan was administered concomitantly with a standardized meal, no clinically significant effect on the drug plasma concentration profile was observed.
Distribution
Both losartan and its active metabolite are more than 99% bound to plasma proteins, mainly albumin. V d of losartan is 34 l. Studies have shown that losartan penetrates poorly or does not penetrate the BBB.
When used in a dose of 100 mg 1 time / day, losartan and its active metabolite do not accumulate significantly in the blood plasma. The pharmacokinetics of losartan and its active metabolite are linear when losartan is taken orally in doses up to 200 mg/day.
Metabolism
About 14% of a dose of losartan administered intravenously or orally is converted into its active metabolite. After intravenous administration and oral administration of 14 C-labeled losartan potassium, the radioactivity of circulating blood plasma is mainly due to losartan and its active metabolite. Minimal conversion of losartan to its active metabolite was observed in approximately 1% of study participants. In addition to the active metabolite, inactive metabolites are formed, including 2 major metabolites, which are formed by hydroxylation of the butyl side chain, and a non-major metabolite, N-2-tetrazole glucuronide.
Removal
Plasma clearance of losartan and its active metabolite is approximately 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 taken orally, about 4% of the dose of losartan is excreted unchanged by the kidneys and about 6% of the dose is excreted by the kidneys in the form of an active metabolite.
After oral administration, the concentrations of losartan and its active metabolite in the blood plasma decrease polyexponentially with a final half-life of about 2 and 6-9 hours, respectively. Losartan and its active metabolite are excreted through the intestines and kidneys. After oral administration of 14 C-labeled losartan, approximately 35% of the radioactivity is excreted by the kidneys and 58% through the intestines.
In patients with alcoholic cirrhosis of the liver, mild and medium degree severity when taken orally, the concentrations of losartan and its active metabolite in the blood plasma were 5 and 1.7 times higher, respectively, than in young healthy male volunteers.
Losartan and its active metabolite are not excreted during hemodialysis.
Hydrochlorothiazide
Suction and distribution
Hydrochlorothiazide is rapidly absorbed from the gastrointestinal tract.
Penetrates through the placenta, but does not cross the blood-brain barrier and is not excreted in breast milk.
Metabolism and excretion
Hydrochlorothiazide is not metabolized and is rapidly excreted by the kidneys. About 61% of the drug is excreted unchanged. According to a 24-hour determination of the concentration of hydrochlorothiazide in blood plasma, its T1/2 is 5.8-14.8 hours.
Losartan/hydrochlorothiazide
Pharmacokinetics in special clinical situations
The concentrations of losartan and its active metabolite in the blood plasma, as well as the absorption of hydrochlorothiazide in elderly patients with arterial hypertension do not differ significantly from the indicators observed in young patients with arterial hypertension.
Indications
- arterial hypertension (in patients for whom combination therapy is optimal);
- reduction in the risk of developing cardiovascular diseases and mortality in patients with arterial hypertension and left ventricular hypertrophy, manifested by a cumulative reduction in the incidence of cardiovascular mortality, the incidence of stroke and myocardial infarction.
Contraindications
- refractory hypokalemia or hypercalcemia;
- severe liver dysfunction (>9 points on the Child-Pugh scale);
— obstructive diseases of the biliary tract;
- cholestasis;
- refractory hyponatremia;
- symptomatic hyperuricemia and/or gout;
- severe renal dysfunction (creatinine clearance less than 30 ml/min);
- anuria;
- simultaneous use with drugs containing aliskiren in patients with diabetes mellitus and patients with moderate and severe renal failure (GFR less than 60 ml/min/1.73 m2 body surface area);
- simultaneous use with ACE inhibitors in patients with diabetic nephropathy;
- pregnancy;
- period of breastfeeding;
- age under 18 years (efficacy and safety have not been established);
- hypersensitivity to any of the components of the drug or to other drugs that are sulfonamide derivatives.
With caution prescribed to patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney, hypovolemic conditions (including diarrhea, vomiting), hyponatremia ( increased risk the development of arterial hypotension in patients on a low-salt or salt-free diet), hypochloremic alkalosis, hypomagnesemia, connective tissue diseases (including SLE), patients with impaired liver function or progressive liver diseases, diabetes mellitus, bronchial asthma(including a history), burdened with an allergic history, simultaneously with NSAIDs, incl. COX-2 inhibitors, patients with heart failure with concomitant severe renal failure, severe chronic heart failure class IV according to the NYHA classification, heart failure accompanied life-threatening arrhythmias, ischemic heart disease, hypertrophic obstructive cardiomyopathy, cerebrovascular diseases, hyperkalemia, condition after kidney transplantation (no experience with use), with aortic and mitral stenosis, primary hyperaldosteronism, acute attack myopia and/or angle-closure glaucoma, as well as representatives of the Negroid race and patients over the age of 75 years.
Dosage
The drug is taken orally, regardless of food intake.
Arterial hypertension
Lozap Plus is intended for the treatment of patients who cannot achieve adequate blood pressure control when using losartan or hydrochlorothiazide alone as monotherapy.
Initial dose of the drug: 50 mg+12.5 mg (1 tablet)/day.
For patients who cannot achieve adequate blood pressure control, the dose of the drug can be increased to 100 mg + 25 mg (2 tablets) 1 time / day.
Maximum dose: 100 mg+25 mg (2 tablets) 1 time/day.
The maximum hypotensive effect is achieved within 3-4 weeks after the start of treatment.
Reducing the risk of cardiovascular disease and mortality in patients with arterial hypertension and left ventricular hypertrophy
Initial dose of Lozap Plus: 50 mg+12.5 mg (1 tablet)/day.
If necessary, you need to increase the dose to 100 mg + 25 mg (2 tablets) 1 time / day.
At moderate renal failure (creatinine clearance 30-50 ml/min) no adjustment of the initial dose is required. At severe renal failure (creatinine clearance less than 30 ml/min)
U patients with reduced blood volume it is necessary to correct the blood volume and/or sodium content in the blood plasma before starting to use the drug.
U patients with liver dysfunction the use of the drug is contraindicated.
Elderly patients (over 65 years old) no dose adjustment is required.
The use of the drug is contraindicated in children and adolescents under 18 years of age(no safety or efficacy data available).
Side effects
Frequency of occurrence adverse reactions determined according to the WHO classification: very often (≥1/10); often (≥1/100 and up to<1/10); нечасто (≥1/1000 и до <1/100); редко (≥1/10 000 и до <1/1000); очень редко (<1/10 000), частота неизвестна (не может быть подсчитана на основании имеющихся данных).
In clinical studies with losartan/hydrochlorothiazide, no adverse reactions associated with the drug combination were observed. Adverse reactions are limited to those previously observed with the use of losartan and/or hydrochlorothiazide alone.
In controlled clinical trials for the treatment of essential hypertension in patients receiving losartan and hydrochlorothiazide, the only adverse reaction occurring at an incidence of 1% or more compared with placebo was dizziness.
In addition, there are other adverse reactions that have been reported with the use of the losartan/hydrochlorothiazide combination.
The following are all adverse reactions reported with the combination of losartan and hydrochlorothiazide 1 , losartan monotherapy 2 or hydrochlorothiazide monotherapy 3 .
From the hematopoietic system: uncommon - anemia 2, Henoch-Schönlein disease 2, ecchymosis 2, hemolysis 2, agranulocytosis 3, aplastic anemia 3, hemolytic anemia 3, leukopenia 3, purpura 3, thrombocytopenia 3; frequency unknown - thrombocytopenia 2.
From the immune system: rarely - hypersensitivity reactions 2.3 (anaphylactic reactions, angioedema, including swelling of the larynx and vocal folds with the development of airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue); Some of these patients had a history of angioedema due to the use of other drugs, including ACE inhibitors.
Metabolism and nutrition: uncommon - anorexia 2.3, gout 2, hyperglycemia 3, hyperuricemia 3, hypokalemia 3, hyponatremia 3.
Mental disorders: often - insomnia 2; uncommon - anxiety 2, anxiety disorder 2, panic disorder 2, confusion 2, depression 2, unusual dreams 2, sleep disturbance 2, drowsiness 2, memory impairment 2, insomnia 3.
From the nervous system: often - headache 2.3, dizziness 2; uncommon - increased excitability 2, paresthesia 2, peripheral neuropathy 2, tremor 2, migraine 2, fainting 2; frequency unknown - dysgeusia 2.
From the side of the organ of vision: uncommon - blurred vision 2, burning sensation in the eyes 2, conjunctivitis 2, decreased visual acuity 2, incl. temporary 3, xanthopsia 3; frequency unknown - secondary acute angle-closure glaucoma 3 and/or acute myopia 3.
Hearing and labyrinth disorders: infrequently - vertigo 2, ringing in the ears 2.
From the cardiovascular system: infrequently - pronounced decrease in blood pressure 2, orthostatic hypotension 2, pain in the sternum 2, angina pectoris 2, AV block of the second degree 2, cerebrovascular accident 2, myocardial infarction 2, palpitations 2, arrhythmias 2 (atrial fibrillation, sinus bradycardia, tachycardia , ventricular tachycardia, ventricular fibrillation) 2, vasculitis 2, necrotizing vasculitis 3, cutaneous vasculitis 3; frequency unknown - dose-dependent orthostatic effect 2.
From the respiratory system: often - cough 2, upper respiratory tract infections 2, nasal congestion 2, sinusitis 2, sinus disorders 2; uncommon - discomfort in the throat 2, pharyngitis 2, laryngitis 2, dyspnea 2, bronchitis 2, nosebleeds 2, rhinitis 2, airway congestion 2, respiratory distress syndrome, including pneumonitis and non-cardiogenic pulmonary edema 3.
From the gastrointestinal tract: often - abdominal pain 2, nausea 2, diarrhea 2, dyspepsia 2; uncommon - constipation 2 (including persistent constipation), toothache 2, dry mouth 2, flatulence 2, gastritis 2, vomiting 2; uncommon - sialadenitis 3, spasm 3, gastritis 3, nausea 3, vomiting 3, diarrhea 3, constipation 3, pancreatitis 3; frequency unknown - pancreatitis 2.
From the liver and biliary tract: rarely - hepatitis 1, infrequently - cholestatic jaundice 3; frequency unknown - liver dysfunction 2.
For the skin and subcutaneous tissues: uncommon - alopecia 2, dermatitis 2, dry skin 2, erythema 2, hyperemia 2, photosensitivity 2.3, pruritus 2, urticaria 2.3, skin rash 2, increased sweating 2, toxic epidermal necrolysis 3; frequency unknown - cutaneous form of systemic lupus erythematosus 3.
From the musculoskeletal system: often - muscle cramps 2, back pain 2, pain in the lower extremities 2, myalgia; uncommon - pain in the upper extremities 2, swelling of the joints 2, pain in the knee joints 2, pain in the shoulder joints 2, muscle and bone pain 2, joint stiffness 2, arthralgia 2, arthritis 2, hip pain 2, fibromyalgia 2, muscle weakness 2, muscle cramps 3; frequency unknown - rhabdomyolysis 2.
From the urinary system: often - impaired renal function 2, renal failure 2; uncommon - nocturia, frequent urination 2, urinary tract infections 2, glycosuria 3, interstitial nephritis 3, impaired renal function 3, renal failure 3.
From the genital organs and breast: uncommon - decreased libido 2, erectile dysfunction 2.
General disorders and disorders at the injection site: often - asthenia 2, increased fatigue 2, chest pain 2; infrequently - swelling of the face 2, peripheral edema 2, fever 2.3, dizziness 3; frequency unknown - flu-like symptoms 2, weakness 2.
Laboratory and instrumental data: often - hyperkalemia 2, decreased hematocrit and hemoglobin 2, hypoglycemia 2; infrequently - increased concentrations of urea and creatinine in blood plasma 2; rarely - hyperkalemia 1, increased activity of alanine aminotransferase 1; very rarely - increased activity of liver transaminases and bilirubin concentration in blood plasma 2; frequency unknown - hyponatremia 2.
Overdose
There are no data on specific treatment for overdose of the losartan/hydrochlorothiazide combination. The drug should be discontinued and the patient monitored. In case of overdose, symptomatic therapy is indicated: gastric lavage if the drug has been taken recently, as well as eliminating dehydration, electrolyte disturbances and lowering blood pressure using standard methods (restoring blood volume and water-electrolyte balance).
Losartan
Most common symptoms overdose is a pronounced decrease in blood pressure and tachycardia; bradycardia may be a consequence of parasympathetic (vagal) stimulation.
In case of symptomatic arterial hypotension, maintenance fluid therapy is indicated. Losartan and its active metabolite are not eliminated by hemodialysis.
Hydrochlorothiazide
Most often symptoms overdoses are a consequence of electrolyte deficiency (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excessive diuresis. When taking cardiac glycosides simultaneously, hypokalemia may aggravate the course of arrhythmias.
There is no specific antidote for hydrochlorothiazide overdose. It has not been established to what extent hydrochlorothiazide can be removed from the body by hemodialysis.
Drug interactions
Losartan
Cases of decreased concentrations of the active metabolite have been described with simultaneous use of rifampicin and fluconazole. Clinical evidence for this interaction 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 levels. The simultaneous use of these drugs is not recommended.
As with other drugs that affect the excretion of lithium, the drug may slow down the elimination of lithium. Therefore, when prescribing lithium salts and ARA II simultaneously, it is necessary to carefully monitor the concentration of lithium salts in the blood plasma.
With the simultaneous use of angiotensin II receptor antagonists and NSAIDs, for example, selective COX-2 inhibitors, in doses used for anti-inflammatory effect, and non-selective NSAIDs, a weakening of the antihypertensive effect of losartan may be observed. Concomitant use of angiotensin II receptor antagonists or diuretics and NSAIDs may cause an increased risk of deterioration of renal function, incl. acute renal failure, and increased potassium levels in the blood plasma, 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.
There is evidence that concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure) compared with the use of drugs affecting the RAAS as monotherapy.
The use of losartan concomitantly with aliskiren is contraindicated in patients with diabetes mellitus or in patients with moderate to severe renal impairment (GFR less than 60 ml/min/1.73 m 2 body surface area) and is not recommended in other patients.
The use of losartan in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended for other patients.
Concomitant use of losartan with other drugs that lower blood pressure, such as tricyclic antidepressants, antipsychotics, baclofen, amifostine, may increase the risk of developing arterial hypotension.
Hydrochlorothiazide
When used simultaneously with thiazide diuretics, interactions with the following substances may occur:
Ethanol, 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.
Others: 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, ACTH: aggravation of electrolyte deficiency, especially hypokalemia, is possible.
Pressor amines (for example, adrenaline): it is possible to reduce the effect of pressor amines, but 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 adjustment of anti-gout 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 arrhythmias induced by cardiac glycosides.
Medicines whose effect is affected by changes in potassium levels in the blood plasma: When concomitantly prescribing hydrochlorothiazide with drugs whose effect is affected by changes in the potassium content in the blood plasma (for example, cardiac glycosides and antiarrhythmic drugs), it is recommended to regularly monitor the potassium content in the blood plasma and ECG monitoring. These measures are also recommended when using hydrochlorothiazide simultaneously with the following drugs that can cause torsades de pointes (including antiarrhythmics), since hypokalemia is a factor predisposing to the development of torsade de pointes:
Class IA antiarrhythmics (eg, quinidine, hydroquinidine, disopyramide);
Class III antiarrhythmics (eg, amiodarone, dofetilide, ibutilide), sotalol;
Certain antipsychotics (eg, thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpride, 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 reducing renal excretion of calcium. If the patient is taking calcium supplements, it is necessary to monitor the calcium level in the blood plasma and, accordingly, adjust the dose 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 plasma sodium levels are necessary in patients taking carbamazepine.
(for parenteral administration), corticosteroids, ACTH, stimulant laxatives, or glycyrrhizin (found in licorice): hydrochlorothiazide may cause electrolyte deficiency, especially hypokalemia.
Special instructions
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 resulting from intensive use of diuretics, dietary salt restriction, 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
Water-electrolyte imbalances often occur in patients with impaired renal function, so the potassium content in the blood plasma and creatinine clearance must be carefully monitored, especially in patients with heart failure and creatinine clearance of 30-50 ml/min. The combined 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 severe hepatic impairment, therefore the drug is contraindicated in patients with severe hepatic impairment.
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 serum urea and creatinine concentrations 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 generally 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 impairment (often acute).
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy
As with other vasodilators, special caution should be exercised when treating patients with aortic or mitral stenosis or obstructive hypertrophic cardiomyopathy.
Differences due to ethnicity
By analogy with other ACE inhibitors, losartan and other angiotensin II receptor antagonists are markedly less effective in reducing 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 arterial hypertension.
Double blockade of the RAAS
There is evidence that concomitant use of ACE inhibitors, angiotensin II receptor antagonists 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 m 2 body surface area).
The use of losartan in combination with an ACE inhibitor is contraindicated in patients with diabetic nephropathy.
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 serum electrolyte levels.
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 hypokalemia is higher in patients with cirrhosis, in patients with increased diuresis, in those with insufficient dietary potassium intake, and in patients receiving concomitant treatment with glucocorticoids, mineralocorticoids, 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 antidiabetic drugs 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 serum 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 disease 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.
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 ultraviolet radiation.
Anti-doping test
Hydrochlorothiazide may give a positive result during doping control.
Other
Cases of transient myopia and acute attacks of angle-closure glaucoma have been reported with the use of hydrochlorothiazide. 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 intraocular pressure does not decrease after discontinuation of hydrochlorothiazide, medical or surgical treatment may be required.
While taking thiazides, hypersensitivity reactions may develop in patients with a history of bronchial asthma, as well as in patients 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 operate machinery
Studies have not been conducted to study the effect of the combination of losartan/hydrochlorothiazide on the ability to drive vehicles or operate machines. 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 when increasing the dosage of the drug.
Pregnancy and lactation
Use during pregnancy
The use of angiotensin II receptor antagonists during pregnancy is contraindicated.
Patients planning pregnancy should switch to alternative antihypertensive therapy options with an established safety profile. If pregnancy is diagnosed during treatment with angiotensin II receptor antagonists, therapy should be discontinued immediately and alternative treatment initiated.
It is known that treatment with angiotensin II receptor antagonists in the second and third trimesters leads to fetotoxic effects (decreased renal function, oligohydramnios, delayed ossification of the skull), as well as toxicity to the newborn (renal failure, arterial hypotension, hyperkalemia).
In the case of using angiotensin II receptor antagonists in the second and third trimesters of pregnancy, ultrasound of the fetal kidneys and skull is recommended.
Children whose mothers took angiotensin II receptor antagonists during pregnancy should be closely monitored for the development of arterial hypotension.
Hydrochlorothiazide
Experience with the use of hydrochlorothiazide during pregnancy, especially in the first trimester, is limited. Animal studies are insufficient. Hydrochlorothiazide penetrates the placental barrier and is detected in the umbilical cord blood. Based on the pharmacological mechanism of action of hydrochlorothiazide, its use during pregnancy may impair fetoplacental blood flow and lead to fetal and neonatal disorders such as jaundice, electrolyte imbalance and thrombocytopenia.
The use of hydrochlorothiazide is contraindicated during pregnancy.
Use during breastfeeding
Angiotensin II receptor antagonists
Due to the lack of information on the use of angiotensin II receptor antagonists during breastfeeding, the use of the drug during this period is contraindicated. During breastfeeding, preference is given to alternative treatments with a better studied safety profile.
Hydrochlorothiazide
Hydrochlorothiazide is excreted in breast milk. Thiazides can cause intense diuresis and may inhibit milk production. Therefore, the use of hydrochlorothiazide during breastfeeding is contraindicated.
Use in childhood
The drug is contraindicated in children and adolescents under 18 years of age (efficacy and safety have not been established).
For impaired renal function
In case of moderate renal failure (creatinine clearance 30-50 ml/min), no initial dose adjustment is required. In case of severe renal failure (creatinine clearance less than 30 ml/min), the use of the drug is contraindicated.
With caution
Storage conditions and periods
The drug should be stored out of the reach of children at a temperature not exceeding 30°C. Shelf life - 3 years. Do not use after the expiration date stated on the package.
