Lozap AM tabs 5mg + 100mg #30

Instruction for Lozap AM

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Lozap AM is a combined antihypertensive drug.

Release form and composition

The drug is produced in the form of film-coated tablets: biconvex, oblong; dosage 5 mg + 50 mg - almost white or white, on one side with an engraving "AT1"; dosage 5 mg + 100 mg - pink or pale pink, on one side with engraving "AT2" (10 pcs. in a blister, 300 pcs. in a polyethylene bottle; in a cardboard box 1 or 3 blisters, or 1 bottle and instructions for use Lozap AM).
1 tablet contains:
    active ingredients: amlodipine camsylate - 7.84 mg (which is equivalent to 5 mg amlodipine), potassium losartan - 50 mg or 100 mg;
    additional components: sodium carboxymethyl starch, butylhydroxytoluene, microcrystalline cellulose, K30 povidone, mannitol, magnesium stearate, crospovidone;
    film shell: hyprolose, talc, hypromellose, titanium dioxide; additionally for a dosage of 5 mg + 100 mg - dyes iron oxide yellow and iron oxide red.

Pharmacodynamics

Lozap AM is an antihypertensive combination drug that includes a slow calcium channel blocker (BMCC) and an angiotensin II receptor antagonist (ARA II). According to the results of studies in which healthy volunteers took part, Lozap AM in dosages of 5 mg + 50 mg and 5 mg + 100 mg is bioequivalent to the combined use of the corresponding doses of amlodipine kamzilate and losartan potassium in the form of separate preparations.
It was also found that Lozap AM tablets, in which amlodipine camsylate is contained in a dose of 5 mg, are bioequivalent to amlodipine besylate tablets in the same dose.

The mechanism of action of the drug Lozap AM

The active components of Lozap AM, amlodipine (CCB) and losartan (ARA II), have a complementary mechanism of action aimed at enhancing blood pressure (BP) control in patients with arterial hypertension (AH). Losartan inhibits the vasoconstrictor effect of angiotensin II and the latter-induced release of aldosterone by selectively inhibiting the binding of angiotensin II to AT1 receptors. Amlodipine belongs to peripheral arterial vasodilators and acts directly on the smooth muscles of the vascular walls, which causes a weakening of their peripheral resistance and a decrease in blood pressure.
Angiotensin II exhibits a powerful vasoconstrictor (vasoconstrictor) effect, and is the main active hormone of the renin-angiotensin-aldosterone system (RAAS) and an important pathophysiological factor of hypertension. By binding to AT1 receptors localized in the tissues of vascular smooth muscles, kidneys, adrenal glands and heart, angiotensin II provides vasoconstriction and release of aldosterone into the bloodstream. Also, this hormone causes the proliferation of smooth muscle cells.
Losartan, a member of the group of selective ARA II (AT1 receptor) antagonists, demonstrates high efficacy when taken orally. This substance and its active carboxylated metabolite (E-3174) in vitro and in vivo suppress all significant effects of angiotensin II, regardless of the pathway or source of its synthesis. Losartan selectively binds to AT1 receptors, while it does not bind or inhibit the receptors of other hormones and ion channels that regulate the activity of the cardiovascular system (CVS). Also, the active component does not affect the function of the angiotensin-converting enzyme (ACE) - kininase II, which inactivates bradykinin. Thus, the action of losartan is not related to the effects directly caused by the blockade of AT1 receptors (including the appearance of edema).
Amlodipine is a dihydropyridine derivative, an antagonist of calcium ions or BMCC, which prevents the transmembrane entry of calcium ions into cardiomyocytes and vascular smooth muscle cells. It can be assumed on the basis of experimental data that this substance is able to bind on the receptors of slow calcium channels with dihydropyridine and non-dihydropyridine binding regions. Amlodipine selectively inhibits the flow of calcium through membranes, to a greater extent, affecting vascular smooth muscle cells than myocardial cells. The substance does not affect serum blood calcium levels.
Losartan, like amlodipine, lowers blood pressure as a result of weakening peripheral resistance. Inhibition of calcium penetration into the cell and reduction of the vasoconstrictor effect caused by the activity of angiotensin II are complementary mechanisms.

Losartan (additional pharmacological effects)

Losartan inhibits an increase in systolic (SBP) and diastolic (DBP) blood pressure due to infusion of angiotensin II. When the maximum plasma concentration (Cmax) of losartan is reached after taking a dose of 100 mg, the above effect of angiotensin II is suppressed by about 85%, and after 24 hours - by 26–39%, respectively, after a single or multiple doses.
Blocking of renin production by angiotensin II (negative feedback), eliminated by losartan, causes an increase in plasma renin activity (ARP) of the blood, which leads to an increase in the level of angiotensin II in plasma. During a 6-week intake of losartan in a daily dose of 100 mg by patients with hypertension, at the moment the substance reached Cmax, an increase in the plasma concentration of angiotensin II was observed by 2–3 times, and in some cases even higher, mainly with a course of therapy of 14 days. However, an antihypertensive effect and a decrease in plasma aldosterone levels were observed after 2 and 6 weeks of treatment, which indicated an effective blockade of angiotensin II receptors. After stopping the course of losartan administration, the concentration of angiotensin II and ARP decreased over 3 days to the initial values.
When comparing the action of losartan in doses of 20 and 100 mg with the effect of an ACE inhibitor, it was found that losartan, due to a specific mechanism of action, blocked the effects of angiotensin I and II, without affecting bradykinin. The ACE inhibitor suppressed responses to angiotensin I and increased the severity of the effects caused by the activity of bradykinin, without changing the severity of the response to angiotensin II, which confirms the pharmacodynamic difference between ACE inhibitors and losartan.
The antihypertensive effect of losartan, its level and its active metabolite in plasma increase with increasing dose of the drug. Both losartan and its active metabolite have a hypotensive effect.
According to the available data of studies in which healthy men took part, when taking losartan at a dose of 100 mg orally against the background of a high- and low-salt diet, the substance did not affect the glomerular filtration rate (GFR), filtration fraction and effective renal plasma flow. Losartan showed a natriuretic effect, most significant with a low-salt diet, and also led to a transient increase in renal excretion of uric acid.
In the presence of proteinuria (at least 2 g / 24 hours) in patients with hypertension, without diabetes mellitus, receiving losartan at a dose of 50 mg for 8 weeks with a gradual increase in the daily dose to 100 mg, a decrease in proteinuria (by 42%) was recorded, and also fractional excretion of albumin and immunoglobulin G (IgG). In patients of this group, the filtration fraction also decreased and GFR stabilized.
In postmenopausal patients with hypertension, who took losartan 50 mg per day for 4 weeks, no effect of the drug on the systemic and renal level of prostaglandins (PG) was revealed.
The drug, taken before meals (on an empty stomach), in daily doses up to 150 mg did not cause clinically significant changes in the concentration of triglycerides, total cholesterol (CS) and high density lipoprotein cholesterol (HDL), and also did not affect blood glucose levels. The action of the agent provided a decrease in the serum level of uric acid in the blood (usually less than 0.4 mg / dL), which was maintained during long-term therapy.
In a 12-week parallel study in patients with NYHA functional class II – IV left ventricular failure receiving diuretics and / or cardiac glycosides, losartan was compared at daily doses of 2.5; 10, 25 and 50 mg with placebo effect. The drug in doses of 25 and 50 mg demonstrated positive neurohormonal and hemodynamic activity throughout the study. Losartan contributed to an increase in the cardiac index and a decrease in the wedge pressure in the pulmonary capillaries, as well as a weakening of the total peripheral vascular resistance (OPSR), a decrease in the mean systemic blood pressure and heart rate (HR). In these patients, the incidence of arterial hypotension was dose-dependent. The neurohormonal effects consisted of a decrease in the level of norepinephrine and aldosterone in the blood.

Amlodipine (additional pharmacological effects)

The use of amlodipine in therapeutic doses in patients with hypertension leads to vasodilation, and as a consequence to a decrease in blood pressure in the supine and standing positions. This hypotensive effect of the active substance is not accompanied by significant changes in heart rate or plasma catecholamine levels during long-term treatment. Although with a single intravenous (iv) administration of amlodipine during the studies, a decrease in blood pressure and an increase in heart rate were observed, repeated oral administration of the drug did not cause significant changes in heart rate or blood pressure in patients with normal blood pressure and with angina pectoris.
Against the background of long-term oral administration of amlodipine 1 time per day, its antihypertensive effect is observed for at least 24 hours. The plasma level of the active substance in the blood correlates with the hypotensive effect in both young and elderly patients. Indicators of a decrease in blood pressure when using amlodipine are also interrelated with the severity of its increase observed before the start of treatment. In patients with DBP 105-114 mm Hg. Art. (AH of moderate severity) there was an antihypertensive effect approximately 50% greater than that in patients with DBP 90–104 mm Hg. Art. (AH of mild severity). In the presence of normal blood pressure in patients, its clinically significant change was not recorded.
In patients with hypertension against the background of normal renal activity, the administration of amlodipine at therapeutic doses led to a weakening of renal vascular resistance, an increase in effective renal plasma flow and an increase in GFR, without changing the filtration fraction or proteinuria.
In patients taking amlodipine, with normal ventricular function, the hemodynamic parameters of the heart at rest and during exercise showed a generally insignificant increase in the cardiac index without a significant change in the rate of pressure increase at the beginning of the phase of blood expulsion in the left ventricular cavity, or in the volume of the left ventricle / final DBP. According to the assessment of hemodynamic parameters, the active substance in therapeutic doses did not show a negative inotropic effect in healthy volunteers, even when combined with β-blockers. At the same time, similar results were observed in patients with heart failure in the compensation phase or in healthy patients when using drugs that exhibit a pronounced negative inotropic effect.
Atrioventricular conduction (AV conduction) or sinoatrial node function in healthy volunteers was not affected by amlodipine. The intravenous administration of the agent at a dose of 10 mg for chronic stable angina pectoris did not significantly affect the A-H and H-V conductivity and the recovery period of the sinus node after pacing. Similar results were observed in patients taking amlodipine in combination with β-blockers. In the course of studies in patients with hypertension or angina pectoris with combined administration of amlodipine with β-blockers, an undesirable effect on the parameters of the electrocardiogram (ECG) was not observed. In patients with angina pectoris, the use of amlodipine did not affect the ECG intervals and did not cause a greater degree of AV block.

Pharmacokinetics

Losartan

After oral administration, it is well absorbed and undergoes the effect of the first passage through the liver with the formation of one active carboxylated metabolite and other inactive metabolites. For losartan in tablet form, a systemic bioavailability of about 33% is characteristic. Losartan and its active metabolite reach average Cmax values ​​1 and 3-4 hours after administration, respectively. Food intake does not have a clinically significant effect on the plasma concentration profile of a substance.
Losartan and its active metabolite bind to plasma proteins (mostly albumin) by at least 99%. The volume of distribution (Vd) of losartan is 34 liters. According to animal studies, the substance practically does not pass through the blood-brain barrier (BBB). There is no pronounced accumulation in plasma of losartan and its main metabolite when using the drug at a dose of 100 mg 1 time per day. Due to oral administration of losartan in doses up to 200 mg, the substance and its active metabolite demonstrate linear pharmacokinetics.
When losartan is used intravenously or orally, about 14% of its dose is biotransformed into an active metabolite. After oral administration or intravenous administration of 14C losartan (labeled with radioactive carbon), the radioactivity of blood plasma is primarily caused by the presence of losartan and an active product of its metabolism in it. On average, 1% of the subjects studied had an insignificant efficiency in the conversion of losartan into an active metabolite. In addition to the formation of the latter, during the metabolic transformation of losartan, two main biologically inactive metabolites are formed due to hydroxylation of the butyl side chain, and one minor, N-2-tetrazole glucuronide.
Plasma clearance of losartan and its active metabolite is approximately 600 and 50 ml / min, and renal clearance is about 74 and 26 ml / min, respectively. When taken orally, losartan is excreted by the kidneys unchanged about 4% of the dose and in the form of an active metabolite - about 6% of the dose. Plasma concentrations of losartan and its active metabolite decrease polyexponentially with a terminal half-life (T1 / 2) of approximately 2 and 6-9 hours, respectively. Losartan and its metabolite are excreted by the kidneys and through the intestines with bile. After oral administration of 14C losartan in men, on average, 35% of radioactivity is detected in urine and 58% in feces, after intravenous administration, approximately 43% of radioactivity is in urine and 50% in feces.
In hypertension in women, the plasma concentration of losartan was 2 times higher than that in men. The blood level of the active metabolite in men and women was the same. However, this pharmacokinetic difference is not clinically relevant.

Amlodipine

With oral administration of amlodipine in therapeutic doses, its Cmax is noted after 6-12 hours. Absolute bioavailability is 64–90% of the oral dose. The bioavailability of amlodipine does not depend on the simultaneous intake of food.
During the research period, it was found that in patients with hypertension, approximately 93% of circulating amlodipine binds to blood plasma proteins. With daily intake, the steady-state concentration (Css) of amlodipine in plasma is observed after 7-8 days.
Approximately 90% of amlodipine is metabolized in the liver into inactive metabolites, about 10% of the dose taken is excreted by the kidneys unchanged, and 60% in the form of metabolites.
Amlodipine is eliminated from plasma in two phases, the final T1 / 2 phase can vary from 30 to 50 hours.

Indications for use

Lozap AM is recommended for the treatment of hypertension when combined therapy is indicated for patients.

Contraindications

Absolute:
    age under 18;
    pregnancy and lactation;
    severe liver failure (more than 9 points on the Child-Pugh scale);
    shock (including cardiogenic);
    severe arterial hypotension (SBP less than 90 mm Hg);
    hemodynamically unstable heart failure after acute myocardial infarction;
    obstruction of the outflow tract of the left ventricle (including severe aortic stenosis);
    impaired renal function, with creatinine clearance (CC) below 20 ml / min, or the need for hemodialysis treatment;
    combined use with aliskiren, or aliskiren-containing agents, in patients with diabetes mellitus and / or impaired renal function (GFR below 60 ml / min / 1.73 m2);
    hypersensitivity to any of the constituents of the drug.
Relative (use Lozap AM tablets is required with extreme caution):
    hypertrophic obstructive cardiomyopathy;
    heart failure with concomitant severe renal impairment or life-threatening arrhythmias (due to the lack of sufficient experience with losartan);
    ischemic heart disease (IHD), cerebrovascular diseases (since a significant decrease in blood pressure can cause the development of myocardial infarction or stroke);
    unstable angina or myocardial infarction;
    severe heart failure (NYHA functional class III – IV);
    arterial hypotension;
    sick sinus syndrome (SSS);
    aortic / mitral stenosis;
    stenosis of an artery of a single kidney or bilateral stenosis of the renal arteries (losartan can lead to an increase in blood urea and serum creatinine concentration);
    renal failure;
    condition after kidney transplantation (due to lack of experience of use);
    hyperkalemia;
    liver failure (below 9 points on the Child-Pugh scale);
    a history of indications of angioedema;
    primary hyperaldosteronism (if antihypertensive drugs acting by suppressing the RAAS do not cause a positive response to treatment);
    violations of water and electrolyte balance;
    combined use with inducers and inhibitors of the CYP3A4 isoenzyme;
    the presence of a reduced volume of circulating blood (BCC), for example, during therapy with high doses of diuretics (the risk of developing symptomatic arterial hypotension is aggravated).

Lozap AM, instructions for use: method and dosage

Lozap AM tablets are taken orally, regardless of the time of the meal, with a sufficient amount of water. The drug can be used in combination with other antihypertensive drugs.
Patients who have failed to achieve adequate blood pressure control when using losartan or amlodipine as monotherapy drugs can switch to the combination treatment Lozap AM. The drug should be taken once a day, 1 tablet, the maximum dose is 5 + 100 mg 1 time in 24 hours.
Lozap AM 5 + 50 mg is recommended for patients who have not achieved adequate blood pressure control when using amlodipine at a dose of 5 mg or losartan at a dose of 50 mg as monotherapy.
Lozap AM 5 + 100 mg is recommended for patients who have not achieved adequate blood pressure control when using losartan at a dose of 100 mg or Lozap AM 5 + 50 mg. Patients taking amlodipine and losartan as separate medications can switch to Lozap AM (containing the same doses of amlodipine and losartan) to increase treatment adherence.
If Lozap AM is necessary for patients with reduced BCC, with impaired liver function or elderly patients, then before starting treatment with a combined drug with fixed doses of amlodipine and losartan, an individual selection of doses of these active substances should be carried out.
Patients with reduced BCC (including those receiving treatment with diuretics in high doses) are recommended to take losartan at an initial dose of 25 mg once a day as a monotherapy drug, since Lozap AM does not have a dosage that includes losartan 25 mg.

Side effects

In the course of clinical studies against the background of treatment with Lozap AM, the following violations were recorded:
    CVS: infrequently - flushing of the face, palpitations, orthostatic hypotension;
    nervous system: often - headache, dizziness; infrequently - drowsiness;
    gastrointestinal tract (GIT): infrequently - nausea, dyspepsia, abdominal discomfort, reflux esophagitis;
    respiratory system, chest and mediastinal organs: infrequently - shortness of breath;
    skin and subcutaneous tissue: infrequently - urticaria (generalized), pruritus (generalized);
    kidneys and urinary tract: infrequently - pollakiuria;
    labyrinth disorders, organ of hearing: infrequently - vertigo;
    general disorders: infrequently - weakness, a feeling of rapid satiety, discomfort in the chest area, peripheral edema, chest pain.
The adverse events observed in the course of studies in patients with hypertension using losartan as a monotherapy drug included the following reactions (in most cases, they were of a mild transient nature and did not require discontinuation of treatment):
    digestive system: nausea, dyspepsia, diarrhea;
    CVS: palpitations, tachycardia;
    nervous system: insomnia, headache, dizziness;
    musculoskeletal system: back pain, muscle spasms;
    respiratory system: cough, pharyngitis, swelling of the nasal mucosa, sinusitis, upper respiratory tract infections;
    general disorders: fatigue, weakness, chest pain, pain in the stomach, peripheral edema.
In controlled clinical trials in patients with hypertension, the only side effect associated with losartan therapy and observed more often than in the placebo group was dizziness. Less than 1% of study participants also had dose-dependent orthostatic reactions. In the presence of hypertension and left ventricular hypertrophy, weakness, asthenia, systemic / non-systemic dizziness were most often observed.
The adverse reactions of losartan recorded in clinical practice in the post-registration period include the following effects:
    hematopoietic system: thrombocytopenia (rare), anemia;
    digestive system: vomiting, abnormal liver function, hepatitis (rare);
    nervous system: dysgeusia, migraine;
    musculoskeletal system: arthralgia, myalgia;
    respiratory system: cough;
    genitals and mammary gland: erectile dysfunction / impotence;
    skin: skin redness, itching, urticaria, photosensitivity;
    general disorders: feeling of general discomfort;
    hypersensitivity reactions: rarely - anaphylactic reactions and angioedema, spreading to the larynx and pharynx, leading to obstruction of the airways, and / or angioedema of the lips, face, pharynx and / or tongue (some patients had a history of the development of angioedema during therapy with others drugs, including ACE inhibitors); vasculitis, including Shenlein's purpura - Genoch.
The most frequent undesirable effects observed in studies in patients on the background of monotherapy with amlodipine besylate at a dosage of less than 10 mg 1 time per day were headache and edema. Also, in placebo-controlled studies, more than 1% of patients developed increased fatigue, nausea, abdominal pain and drowsiness, which had no pronounced relationship with the dose.
Side effects observed in the course of studies or in the post-registration period of the use of amlodipine besylate (causal relationship is unknown) were the following reactions:
    central and peripheral nervous system: tremor, vertigo, paresthesia, hypesthesia, peripheral neuropathy;
    CVS: chest pain, postural dizziness, ischemic lesions of peripheral vessels, marked decrease in blood pressure, postural hypotension, syncope, tachycardia, bradycardia, arrhythmia (including ventricular tachycardia and atrial fibrillation), vasculitis;
    mental disorders: hyperexcitability, insomnia, sexual dysfunction (in men and women), anxiety, unusual dreams, depression, depersonalization;
    autonomic nervous system: dry mouth, increased sweating;
    sensory organs: ringing in the ears, eye pain, visual impairment, diplopia, conjunctivitis;
    respiratory system: nosebleeds, shortness of breath;
    hematopoietic organs: purpura, leukopenia, thrombocytopenia;
    digestive system: gingival hyperplasia, flatulence, vomiting, constipation, diarrhea, anorexia, dysphagia, dyspepsia, pancreatitis;
    musculoskeletal system: muscle cramps, arthralgia, myalgia, arthrosis;
    urinary system: frequent urination, nocturia, urinary disorders;
    skin: pruritus, rash, angioedema, maculopapular rash, erythematous rash, erythema multiforme;
    metabolism and nutritional disorders: thirst, hyperglycemia;
    general disorders: flushing of the skin of the face, increase / decrease in body weight, rigidity, back pain, malaise, pain, asthenia, allergic reaction.
The following side effects were extremely rare: moisture in the skin and a decrease in temperature, dryness / depigmentation of the skin, dermatitis, alopecia, urticaria, ataxia, muscle twitching, muscle weakness, migraine, increased blood pressure, agitation, apathy, amnesia, cough, rhinitis, parosmia, polyuria, dysuria, increased appetite, taste disturbance, frequent loose stools, gastritis, accommodation disturbance, xerophthalmia, rhythm disturbances, heart failure, extrasystole. Also, during the treatment of amlodipine besylate in the post-registration period, the appearance of jaundice and an increase in the activity of liver enzymes (mainly caused by cholestasis or hepatitis), in some cases quite severe and requiring hospitalization, were noted.

Overdose

There is no information on an overdose of Lozap AM.
Information about an overdose of losartan is limited, most likely in this condition, tachycardia and a pronounced decrease in blood pressure may be noted, the occurrence of bradycardia is possible as a result of parasympathetic stimulation. Therapy is prescribed symptomatic, hemodialysis is ineffective.
Symptoms of an overdose of amlodipine may be excessive peripheral vasodilation with a significant decrease in blood pressure and the possible appearance of reflex tachycardia. There are reports of prolonged and pronounced systemic hypotensive effects, including fatal shock. In case of an overdose, if necessary, prescribe gastric lavage and the intake of activated carbon. If an excessively high dose of the drug is introduced, it is required to monitor the parameters of respiration and the state of hemodynamics, and often measure blood pressure. Against the background of the appearance of arterial hypotension, it is necessary to ensure adequate administration of fluids, to give the patient's limbs an elevated position and to carry out other standard measures to maintain hemodynamics. If the conservative measures carried out are ineffective, the introduction of phenylephrine or other vasoconstrictors may be prescribed, depending on the urine output and the BCC.
The blockade of calcium channels is eliminated by intravenous infusion of calcium gluconate. The hemodialysis procedure is ineffective, since amlodipine has a high degree of binding to plasma proteins.

Special instructions

Since losartan in patients with type 2 diabetes mellitus with proteinuria may increase the risk of hyperkalemia, during the period of therapy, do not take medications and salt substitutes containing potassium without first consulting a doctor.
In CHF III – IV functional class according to NYHA classification of non-ischemic genesis during treatment with amlodipine there was an increase in the incidence of pulmonary edema, including in the absence of symptoms of worsening heart failure.
There are no data confirming the safety and efficacy of Lozap AM in hypertensive crisis.
After the start of the course of treatment with amlodipine or with an increase in its dose, the threat of developing unstable angina pectoris and acute myocardial infarction increases, especially in the presence of severe hypertrophic obstructive cardiomyopathy.
During the period of therapy with amlodipine, it is necessary to maintain oral hygiene and regular visits to the dentist in order to prevent bleeding, soreness and gingival hyperplasia.

Influence on the ability to drive vehicles and complex mechanisms

The study of the influence of Lozap AM on the ability to drive motor transport and other complex mechanisms has not been carried out. However, it should be borne in mind that during the period of therapy, some undesirable effects may appear that can negatively affect the speed of psychomotor reactions and concentration.

Application during pregnancy and lactation

Lozap AM is contraindicated during pregnancy and lactation. Drugs that directly affect the RAAS can lead to serious damage and death of the developing fetus. When pregnancy is diagnosed, the drug must be canceled immediately. If necessary, switch to alternative antihypertensive therapy with a drug that has an approved safety profile for use during pregnancy.
Despite the fact that there is no experience of taking Lozap AM in pregnant women, in the course of preclinical studies on animals it was found that losartan can cause serious embryonic and neonatal injuries and fetal death. It is assumed that the mechanism of these phenomena is associated with the impact on the RAAS.
The use of losartan in the II and III trimesters of pregnancy impairs the activity of the kidneys and increases the incidence of morbidity and mortality in the fetus and newborn. The occurrence of oligohydramnios may be associated with hypoplasia of the fetal lungs and deformities of its skeleton. Adverse reactions due to the intake of losartan in newborns may include arterial hypotension, hypoplasia of the skull bones, anuria, renal failure and death. If treatment with drugs affecting the RAAS in the II and III trimesters of pregnancy cannot be replaced with alternative therapy, the patient should be informed about the potential risk of taking these drugs to the fetus.
Well-controlled and adequate studies of the use of amlodipine in pregnant women have not been conducted.
It is not known whether losartan and amlodipine penetrate into breast milk. If you need to take Lozap AM during lactation, you should stop breastfeeding.
There is no information on the effect of losartan on fertility. There have been reports of cases of reversible biochemical changes in the sperm head observed in some patients treated with BMCC. The clinical data required to assess the potential effects of amlodipine on fertility are insufficient.

Childhood use

The use of Lozap AM in children and adolescents is contraindicated, since in patients under the age of 18 years, the safety and efficacy of drug therapy have not been established.
Newborns whose mothers took ARA II (including losartan) during pregnancy should be closely monitored to control hyperkalemia, oliguria, and arterial hypotension. If the above complications are detected in such children, symptomatic therapy is prescribed, aimed at maintaining renal perfusion and blood pressure. Blood transfusion or dialysis may be required to prevent hypotension and / or to normalize kidney function.

With impaired renal function

In the presence of severe renal impairment (CC below 20 ml / min) or the need for hemodialysis treatment, Lozap AM is contraindicated. Treatment with the drug is not recommended for patients with moderate renal impairment. With caution, it is required to take the remedy for stenosis of an artery of a single kidney or bilateral stenosis of the renal arteries, renal failure, condition after kidney transplantation. It is not required to adjust the dose for patients with functional impairment of renal function with CC - 20-50 ml / min.

For violations of liver function

In case of severe liver failure (more than 9 points on the Child-Pugh scale) - Lozap AM is contraindicated to take, patients with mild and moderate hepatic impairment (less than 9 points on the Child-Pugh scale) should use an antihypertensive agent with caution.
According to pharmacokinetic data demonstrating a significant increase in the plasma level of losartan in patients with liver cirrhosis, Lozap AM is not recommended for patients with a history of cirrhosis or severe liver dysfunction. They require the appointment of losartan in low doses (25 mg 1 time per day) in monotherapy.
Due to the fact that amlodipine is mainly metabolized in the liver, in patients with disorders of its activity T1 / 2 is equal to 56 hours. If it is necessary to use amlodipine in patients with severe hepatic insufficiency, titration of its dose is recommended gradually.

Use in the elderly

When carrying out clinical studies in patients over 65 years old, no features were found regarding the efficacy and safety of treatment with losartan. Since in elderly patients, due to the reduced clearance of amlodipine, the area under the concentration-time curve (AUC) is increased by approximately 40-60%, it is usually recommended to start taking it with a daily dose of 2.5 mg, but since. Lozap AM contains 5 mg of amlodipine, such patients should take amlodipine as a monotherapy drug.

Drug interactions

The study of the interaction of Lozap AM with other drugs has not been conducted.
Possible reactions of interaction of losartan with simultaneous use with other medicinal substances / agents:
    digoxin, hydrochlorothiazide, cimetidine, warfarin, phenobarbital: no clinically significant interactions were detected;
    rifampicin: the level of losartan in the blood decreases;
    erythromycin: there is no clinically significant effect on the pharmacokinetics of losartan when taken orally;
    ketoconazole: there is no effect on the metabolism of losartan after its intravenous administration before the formation of an active metabolite;
    fluconazole (an inhibitor of the isoenzyme CYP2C9): the concentration of the active metabolite of losartan decreases; the pharmacodynamic significance of the combined administration of losartan and inhibitors of the isoenzyme CYP2C9 has not been studied;
    triamterene, spironolactone, amiloride and other potassium-sparing diuretics; potassium supplements or potassium salts: there may be an increase in serum potassium concentration;
    lithium preparations: it is possible to reduce the excretion of lithium; careful monitoring of the level of lithium in the blood is necessary;
    non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2): possibly weakening of the antihypertensive effect of losartan; in elderly patients or patients with dehydration, including those receiving diuretics, with this combination, a reversible deterioration in renal function is possible, including the occurrence of acute renal failure; the combination of drugs requires special care;
    double blockade of RAAS (simultaneous use of ARA II and ACE inhibitors or a renin inhibitor - aliskiren): the risk of arterial hypotension, hyperkalemia, fainting and renal impairment (including acute renal failure) is aggravated when compared with monotherapy; regular monitoring of kidney function, blood pressure and electrolyte concentration in the blood is necessary.
Possible reactions of interaction of amlodipine with simultaneous use with other drugs / agents:
    digoxin, phenytoin, warfarin, indomethacin: there is no effect on the binding of these drugs to blood plasma proteins according to in vitro studies;
    cimetidine; antacids containing magnesium or aluminum hydroxide; grapefruit juice (240 ml): there is no significant effect on the pharmacokinetics of amlodipine when using a single dose of the latter;
    atorvastatin (at a dose of 80 mg): there are no significant changes in the equilibrium pharmacokinetic parameters of atorvastatin with multiple combined administration of amlodipine at a dose of 10 mg;
    sildenafil (single dose of 100 mg): amlodipine pharmacokinetics are not affected against the background of hypertension; with a given combination, each of these substances independently exhibits an antihypertensive effect;
    tacrolimus: the risk of an increase in its plasma concentration increases; the level of this substance in plasma should be monitored;
    simvastatin (at a dose of 80 mg): when taken together with amlodipine at a dose of 10 mg, the exposure of simvastatin increases by 77%; the daily dose of simvastatin in this combination should not be higher than 20 mg;
    dantrolene (intravenous injection): the risk of arrhythmia, collapse, hyperkalemia and a decrease in the force of heart contractions increases;
    cyclosporine: an increase in its concentration is possible; in patients after kidney transplantation, there was an increase in plasma cyclosporine Cmin by about 40%; when combined with Lozap AM, it is required to monitor Cmin of cyclosporine;
    warfarin: there is no increase in prothrombin time;
    ethanol: no significant effect on its pharmacokinetics was detected;
    itraconazole, ketoconazole, ritonavir (strong inhibitors of the CYP3A4 isoenzyme): the plasma concentration of amlodipine may increase; requires regular monitoring of symptoms of arterial hypotension and edema;
    diltiazem (at a dose of 180 mg), erythromycin (inhibitors of the isoenzyme CYP3A4): when diltiazem is combined with amlodipine at a dose of 5 mg, an increase in the AUC of the latter by 1.6 times is detected when this combination is prescribed to elderly patients with hypertension; when combined with erythromycin in healthy volunteers, there is no significant effect on the AUC of amlodipine, however, in the elderly, a significant change in its exposure may be recorded;
    clarithromycin (an inhibitor of the isoenzyme CYP3A4): the threat of lowering blood pressure increases, careful medical supervision is required;
    rifampicin, St. John's wort (inducers of the isoenzyme CYP3A4): no significant effect on the pharmacokinetic characteristics of amlodipine was recorded; it is recommended to regularly monitor blood pressure.

Terms and conditions of storage

Keep out of reach of children, at a temperature not exceeding 30 ° C.
Shelf life is 2 years.

Reviews about Lozap AM

Reviews of Lozap AM are mostly positive. Patients note the high effectiveness of the drug when compared with Lozap, since Lozap AM contains two active substances, it is prescribed for admission with more severe hypertension or with the development of addiction to Lozap. The drug, according to reviews, has a positive effect on the CVS and allows you to adequately control blood pressure.

Terms of sell

You can buy Lozap AM without a doctor's prescription.