Release form of the drug Losartan
The drug Losartan is available in the form of tablets with different contents of the active substance. The tablets are white, round in shape. When cut, the contents are also white. A slight color deviation towards a yellow tint is acceptable.
The main active ingredient is losartan potassium. Additional components include:
- lactose monohydrate;
- pregelatinized starch;
- microcrystalline cellulose;
- Magnesium stearate.
Tablets are produced with different contents of active substance per unit of drug:
- 25mg;
- 50mg;
- 100 mg.
The difference in the concentration of the substance is needed to accurately select the dosage necessary to achieve a therapeutic effect in each specific case.
Losartan: what is it taken for?
Indications for the use of Losartan are:
- Nephropathy of the diabetic type, including damage to the tubules and glomeruli of the kidneys, as well as arterioles and arteries, developing due to disruption of metabolic processes in the renal tissue.
- Presence of a tendency to develop disorders of the cardiovascular system, including strokes.
- Arterial hypertension, in which the indicator exceeds 140 mm Hg. Art.
- Chronic heart failure, in which the circulatory system does not properly supply the body with oxygen either at rest or after exercise.
After entering the gastrointestinal tract, the drug is actively absorbed. As a result of filtration by the liver, a metabolite is formed that is many times more active than Losartan in its original form. The maximum concentration of Losartan in the blood is observed after 1 hour, and the metabolite - after 3-4 hours. About 98% of the drug actively binds to plasma proteins.
The half-life of Losartan is 2-2.5 hours, and the active metabolite is up to 9 hours, depending on the speed of metabolic processes in the body. The drug and its derivatives are excreted unchanged in feces, urine and bile. Most of the medicine comes out through the rectum.
Losartan-N Canon tablets 50+12.5 mg 30 pcs. in Moscow
The use of the drug in patients with acute myocardial infarction is not recommended due to insufficient experience in clinical use. It should also not be used to relieve a hypertensive crisis.
Hydrochlorothiazide
Renal dysfunction
In patients with impaired renal function, hydrochlorothiazide may cause azotemia. In case of renal failure, accumulation of hydrochlorothiazide is possible.
In patients with reduced renal function, periodic monitoring of CK is necessary. If renal dysfunction progresses and/or oliguria (anuria) occurs, hydrochlorothiazide should be discontinued.
Liver dysfunction
When using thiazide diuretics in patients with impaired liver function, hepatic encephalopathy may develop. In patients with severe liver failure or hepatic encephalopathy, the use of thiazides is contraindicated. In patients with mild to moderate hepatic impairment and/or progressive liver disease, hydrochlorothiazide should be used with caution, since even slight changes in fluid and electrolyte balance and serum ammonium accumulation can cause hepatic coma. If symptoms of encephalopathy occur, diuretics should be discontinued immediately.
Water-electrolyte balance and metabolic disorders
Thiazide diuretics (including hydrochlorothiazide) can cause a decrease in blood volume (hypovolemia) and disturbances in water and electrolyte balance (including hypokalemia, hyponatremia, hypochloremic alkalosis). Clinical symptoms of water-electrolyte balance disorders are dryness of the oral mucosa, thirst, weakness, lethargy, fatigue, drowsiness, anxiety, muscle pain or cramps, muscle weakness, marked decrease in blood pressure, oliguria, tachycardia, arrhythmia and gastrointestinal disorders (such such as nausea and vomiting). In patients receiving hydrochlorothiazide therapy (especially with long-term course treatment), clinical symptoms of water-electrolyte imbalance should be identified and the content of electrolytes in the blood plasma should be regularly monitored.
Sodium
All diuretics can cause hyponatremia, sometimes leading to severe complications. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension. A concomitant decrease in chlorine ions can lead to secondary compensatory metabolic alkalosis, but the frequency and severity of this effect are insignificant. It is recommended to determine the content of sodium ions in the blood plasma before starting treatment and regularly monitor this indicator while taking hydrochlorothiazide.
Potassium
When using thiazide and thiazide-like diuretics, there is a risk of a sharp decrease in the potassium content in the blood plasma and the development of hypokalemia (potassium content in the blood plasma less than 3.4 mmol/l). Hypokalemia increases the risk of developing heart rhythm disturbances (including severe arrhythmias) and enhances the toxic effect of cardiac glycosides. In addition, hypokalemia (as well as bradycardia) is a condition that contributes to the development of polymorphic ventricular tachycardia of the “pirouette” type, which can be fatal.
Hypokalemia poses the greatest danger to the following groups of patients: elderly people, patients simultaneously receiving therapy with antiarrhythmic and non-antiarrhythmic drugs that can cause polymorphic ventricular tachycardia of the “pirouette” type or increase the duration of the QT interval on the ECG, patients with impaired liver function, coronary artery disease, CHF . In addition, patients with an increased QT interval are at increased risk. It does not matter whether this increase is caused by congenital causes or the effect of drugs.
In all the cases described above, it is necessary to avoid the risk of developing hypokalemia and regularly monitor the potassium content in the blood plasma. The first measurement of the content of potassium ions in the blood plasma should be carried out within the first week from the start of treatment. If hypokalemia occurs, appropriate treatment should be prescribed. Hypokalemia can be corrected by using potassium-containing medications or eating foods rich in potassium (dried fruits, fruits, vegetables).
Calcium
Thiazide diuretics may reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in plasma calcium levels. In some patients, with long-term use of thiazide diuretics, pathological changes in the parathyroid glands were observed with hypercalcemia and hyperphosphatemia, but without the typical complications of hyperparathyroidism (nephrolithiasis, decreased bone mineral density, peptic ulcer). Severe hypercalcemia may be a manifestation of previously undiagnosed hyperparathyroidism.
Because of their effect on calcium metabolism, thiazides may interfere with laboratory parameters of parathyroid function. Thiazide diuretics (including hydrochlorothiazide) should be discontinued before testing parathyroid function.
Magnesium
Thiazides have been found to increase renal excretion of magnesium, which can lead to hypomagnesemia. The clinical significance of hypomagnesemia remains unclear.
Glucose
Treatment with thiazide diuretics may impair glucose tolerance. When using hydrochlorothiazide in patients with manifest or latent diabetes mellitus, it is necessary to regularly monitor the concentration of glucose in the blood plasma. Dosage adjustment of hypoglycemic medications may be required.
Uric acid
In patients with gout, the frequency of attacks may increase or the course of gout may worsen. Careful monitoring of patients with gout and impaired uric acid metabolism (hyperuricemia) is necessary.
Lipids
When using hydrochlorothiazide, the concentration of both cholesterol and triglycerides in the blood plasma may increase.
Acute myopia/secondary angle-closure glaucoma
Hydrochlorothiazide can cause an idiosyncratic reaction, leading to the development of acute myopia and an acute attack of secondary angle-closure glaucoma. Symptoms include: sudden loss of visual acuity or eye pain, usually occurring within hours to weeks of starting hydrochlorothiazide therapy. If left untreated, acute angle-closure glaucoma can lead to irreversible vision loss. If symptoms appear, you should stop taking hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, emergency medical treatment or surgery may be required. Risk factors for the development of acute angle-closure glaucoma include a history of an allergic reaction to sulfonamides or penicillin. Immune system disorders
There are reports that thiazide diuretics (including hydrochlorothiazide) may cause exacerbation or progression of systemic lupus erythematosus, as well as lupus-like reactions.
In patients receiving thiazide diuretics, hypersensitivity reactions may occur even in the absence of a history of allergic reactions or bronchial asthma.
Photosensitivity
There is information about cases of the development of photosensitivity reactions when taking thiazide diuretics. If photosensitivity occurs while taking hydrochlorothiazide, treatment should be discontinued. If continued use of a diuretic is necessary, the skin should be protected from exposure to sunlight or artificial ultraviolet rays (UV rays).
Non-melanoma skin cancer (NMSC)
Two pharmacoepidemiological studies using data from the Danish National Cancer Registry demonstrated an association between hydrochlorothiazide use and an increased risk of NMSC—basal cell carcinoma and squamous cell carcinoma. The risk of developing NMSC increased with increasing total (cumulative) dose of hydrochlorothiazide. A possible mechanism for the development of NMSC is the photosensitizing effect of hydrochlorothiazide. Patients taking hydrochlorothiazide as monotherapy or in combination with other drugs should be aware of the risk of developing NMSC. It is recommended that such patients undergo regular skin examination to identify any new suspicious lesions as well as changes in existing skin lesions.
Any suspicious skin changes should be reported to your doctor immediately. Suspicious areas of skin should be examined by a specialist. To clarify the diagnosis, histological examination of skin biopsies may be required.
To minimize the risk of developing NMSC, patients should be advised to follow preventive measures, such as limiting exposure to sunlight and UV rays, and using appropriate protective equipment.
In patients with a history of NMSC, it is recommended to reconsider the use of hydrochlorothiazide.
Athletes
Hydrochlorothiazide may give a positive result during doping control in athletes.
Other
In patients with severe atherosclerosis of the cerebral and coronary arteries, hydrochlorothiazide should be used with extreme caution.
Thiazide diuretics can reduce the amount of iodine bound to plasma proteins without causing signs of thyroid dysfunction.
Losartan
Angioedema
Patients with a history of angioedema (of the face, lips, pharynx and/or larynx) should be closely monitored.
Arterial hypotension and hypovolemia (dehydration)
In patients with hypovolemia (dehydration) and/or reduced sodium content in the blood plasma, against the background of diuretic therapy, limited salt intake, diarrhea or vomiting, symptomatic arterial hypotension may develop, especially after taking the first dose of Lorista® N. Before using the drug, you should restore the blood volume and/or sodium content in the blood plasma.
Water-electrolyte imbalance
Fluid and electrolyte imbalances are common in patients with impaired renal function, especially in the setting of diabetes mellitus. In this regard, it is necessary to carefully monitor the potassium content in the blood plasma and CC, especially in patients with heart failure and CC 30-50 ml/min.
Concomitant use of ARA II with aliskiren and drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients . Concomitant use of ARB II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.
Concomitant use with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other drugs that can increase the level of potassium in the blood plasma (for example, heparin) is not recommended.
Liver dysfunction
The concentration of losartan in the blood plasma increases significantly in patients with liver cirrhosis, so Lorista® N should be used with caution in patients with mild or moderate liver dysfunction.
Renal dysfunction
Impaired renal function, including renal failure, may occur due to inhibition of the RAAS (especially in patients whose renal function is dependent on the RAAS, such as those with severe heart failure or a history of renal dysfunction).
Renal artery stenosis
In patients with bilateral renal artery stenosis, as well as stenosis of the artery of the only functioning kidney, drugs affecting the RAAS, including ARA II, can reversibly increase the concentrations of urea and creatinine in the blood plasma.
Losartan should be used with caution in patients with bilateral renal artery stenosis or arterial stenosis of a solitary kidney.
Kidney transplant
There is no experience with the use of Lorista® N in patients who have recently undergone kidney transplantation.
Primary hyperaldosteronism
Patients with primary hyperaldosteronism are resistant to antihypertensive drugs that affect the RAAS, therefore the use of Lorista® N is not recommended for such patients.
IHD and cerebrovascular diseases
As with the treatment of any antihypertensive drugs, a pronounced decrease in blood pressure in patients with coronary artery disease or cerebrovascular diseases can lead to the development of myocardial infarction or stroke.
Heart failure
In patients whose renal function depends on the state of the RAAS (for example, with CHF III-IV functional class according to the NYHA classification, accompanied or not accompanied by impaired renal function), therapy with drugs affecting the RAAS may be accompanied by severe arterial hypotension, oliguria and/or progressive azotemia, in rare cases - acute renal failure. It is impossible to exclude the development of these disorders due to suppression of RAAS activity while taking ARA II.
Stenosis of the aortic and/or mitral valves, HOCM
Lorista® N, like other vasodilators, should be used with caution in patients with hemodynamically significant stenosis of the aortic and/or mitral valves or with HOCM.
Ethnic characteristics
Losartan (like other drugs that affect the RAAS) has a less pronounced antihypertensive effect in patients of the Black race compared to representatives of other races, possibly due to the higher incidence of hyporeninemia in these patients with arterial hypertension.
Special information on excipients
The drug Lorista® N contains lactose, therefore the drug is contraindicated in patients with lactase deficiency, lactose intolerance, and glucose-galactose malabsorption syndrome.
Impact on driving vehicles and machinery
At the beginning of therapy, Lorista® N may cause a decrease in blood pressure, dizziness or drowsiness, thus indirectly affecting the psycho-emotional state. For safety reasons, patients should first assess their response to treatment before engaging in activities requiring increased alertness.
Losartan: instructions for use
Eating does not affect the absorption and activity of the drug. The drug is swallowed whole with a sufficient amount of water. Depending on the diagnosis, a different therapeutic dose may be prescribed:
- Arterial hypertension is treated with a single dose of 50 mg of Losartan. If there is no desired effect, the single dose can be increased to 100 mg per day.
- For chronic heart failure, treatment begins with a single dose of half a tablet containing 25 mg of the active substance. After a week, the daily dose is gradually increased.
- The risk of developing problems in the functioning of the cardiovascular system is reduced by a single dose of 50 mg of Losartan or a two-time dose of 25 mg.
- Liver failure becomes a reason to prescribe 25 mg of the active substance.
Throughout the course of treatment, regardless of the diagnosis, it is necessary to monitor the patient’s blood pressure daily. If the patient takes the course at home, he must keep a diary of tonometer readings after each measurement.
If an excessive decrease in blood pressure is noted, the doctor is required to adjust the daily dose. In addition, the patient must comply with the time of taking the drug. In order to reduce the risk of overdose, the tablet is taken strictly at the same time. If one dose is missed, the next dose is taken at the allotted hour.
Concomitant use with other drugs
Concomitant use with ACE inhibitors leads to the development of such a dangerous condition as hyperkalemia, in which the level of potassium in the blood increases. In addition, this combination increases the risk of kidney failure and life-threatening low blood pressure.
In combination with diuretics, the risk of hypotension is also high. This is due to the fact that taking diuretics itself leads to a decrease in blood pressure, which enhances the effect of Losartan.
It is not recommended to drink Losartan with lithium-containing drugs, so as not to provoke an excess of lithium in the blood, since the combination of drugs disrupts natural metabolic processes.
Uricosuric activity of losartan: clinical implications
Rice. 1. Excretion of uric acid (mg/g creatinine) after taking losartan. *—P
Rice. 2. Plasma uric acid levels after taking losartan. *—P
Rice.
3. Dynamics of urine pH after taking losartan Safety and tolerability
The moderate uricosuric activity of losartan was studied by analyzing data from double-blind and open studies on the safety of losartan in patients with hypertension. These studies showed that long-term treatment with losartan resulted in a very small reduction in serum uric acid levels of 0.2–0.4 mg/dL (i.e., 3–6%) [11]. A safety study (S. Shahinfar et al.) was performed in hypertensive patients with asymptomatic hyperuricemia treated with hydrochlorothiazide (HCTZ). The results did not reveal an increase in dihydrourate (the primary risk factor for crystal formation) when treated with losartan alone or in combination with HCTZ [12]. This study showed that an increase in uric acid excretion was associated with an increase in urine pH. The authors propose this fact as an explanation for reducing dihydrourate and the risk of crystal formation.
Losartan and hydrochlorothiazide
In the United States, approximately 20–30% of patients with hypertension are treated with HCTZ, which in moderate doses can lead to hyperuricemia. Therefore, the combination of losartan with diuretics seems interesting for clinical practice. In a multicenter study, patients in whom HCTZ at a dose of 25 mg for 4 weeks did not lead to adequate control of blood pressure (BP) were additionally prescribed, in a double-blind manner, losartan at a dose of 25, 50 or 100 mg, or placebo once a day for for 12 weeks [13]. The reduction in diastolic blood pressure in all groups receiving losartan was greater than in the placebo group. In addition, the decrease in serum potassium usually associated with HCTZ was reversed. In patients receiving losartan, there was a moderate but statistically significant increase, while in the HCTZ group there was an increase. Thus, the uricosuric effect of losartan can completely neutralize the diuretic-induced increase in serum uric acid levels.
Conclusion
Hyperuricemia occurs in 25–50% of patients with untreated hypertension. This risk factor is independently and significantly associated with the development of hypertension [14–17], coronary heart disease and myocardial infarction [18,19], impaired glucose tolerance [20], dyslipidaemias and all-cause mortality. Although the Coronary Drug Project's conclusion [22] states that cause-and-effect relationships cannot be established due to the association of hyperuricemia with several other risk factors for cardiovascular events, hyperuricemia may be a reflection of hypertensive vascular damage and early renal vascular involvement [ 2]. In general, the role of uric acid as a risk factor for cardiovascular diseases is beyond doubt. Whether lowering blood uric acid levels has a beneficial effect on cardiovascular morbidity and mortality remains to be determined. However, the data discussed suggest that an antihypertensive drug with a mild uricosuric effect may provide additional beneficial effects in hypertension.
Losartan is the only angiotensin II antagonist with moderate uricosuric activity. This fact would be of particular significance if uric acid really serves as an independent risk factor for cardiovascular diseases, but for now this remains a hypothesis. From a clinical point of view, the uricosuric activity of losartan is important because it corrects a pathological condition that is common among hypertensive patients and helps to avoid the development of gout. In addition, some benefit from this action of losartan can be expected in patients who are receiving hydrochlorothiazide and therefore may have hyperuricemia. Finally, the uricosuric activity of losartan may make it an attractive treatment for congestive heart failure, often associated with increased blood uric acid levels.
The list of references can be found on the website https://www.rmj.ru
Prepared by Ph.D. A.N. Nikolaev
based on materials from Arthur B. Ribeiro, MD, Ph.D.
Uricosuric Activity of Losartan: What is the Clinical Benefit? // Receptors in cardiovascular disease, vol. 5: No. 3. References:
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