Cases of overdose Ashara unknown.
The data on overdose of amlodipine and losartan taken separately are given below.
Amlodipine
Symptoms: An overdose of amlodipine can lead to excessive peripheral vasodilation and possibly reflex tachycardia. In the described cases, there was a long-term pronounced hypotensive effect, up to shock and death.
Treatment: administration of activated charcoal to healthy volunteers directly or within 2 hours after oral administration of 10 mg of amlodipine significantly reduces the absorption of the latter. If necessary, gastric lavage is indicated. Clinically significant hypotension in Amzaar overdose requires a set of measures to normalize the CCC: it is necessary to lift the patient's legs, to constantly monitor the functional parameters of the heart and respiratory system, BCC and the volume of diuresis. To restore vascular tone and blood pressure, the administration of vasoconstrictors may be required, provided that there are no contraindications to their use. To eliminate the blockage of the calcium channels, the intravenous administration of calcium gluconate is effective. Elimination of amlodipine by hemodialysis is unlikely
Losartan
Symptoms: There are limited data on drug overdose in humans. The most characteristic symptoms are: hypotension and tachycardia, possible development of bradycardia due to parasympathetic (vagal) stimulation.
Treatment: If symptomatic hypotension occurs, maintenance therapy should be prescribed. Neither losartan nor its active metabolite can be removed from the body by hemodialysis.
hypersensitivity to the active components and / or auxiliary components of the drug,
pregnancy and lactation (see " Use during pregnancy and lactation»),
severe liver failure (more than 9 points on the Child-Pugh scale),
hemodynamically pronounced stenosis of the aortic mouth,
shock,
age under 18 (efficacy and safety not established),
severe arterial hypotension.
With caution:
The antihypertensive effect of Amzaar may be enhanced when used simultaneously with other antihypertensive agents, so the simultaneous administration of various antihypertensive agents should be justified.
Amlodipine
It can be safely used for the treatment of arterial hypertension together with thiazide diuretics, alpha-blockers or ACE inhibitors. Unlike other BCCs, clinically significant interactions of amlodipine (III generation of BCCs) were not detected when co-administered with NSAIDs, including indomethacin. It is possible to increase the hypotensive effect of BCC when used together with thiazide and loop diuretics, ACE inhibitors and nitrates, as well as to increase their hypotensive effect when used together with α1- adrenoblockers, neuroleptics.
The combined use of amlodipine with CYP3A4 inhibitors requires careful monitoring of the symptoms of hypotension and peripheral edema. With the simultaneous administration of diltiazem at a dose of 180 mg per day and amlodipine at a dose of 5 mg per day to elderly patients, the systemic exposure of amlodipine increases by 60%. Erythromycin when used together increases Cmax amlodipine in young patients by 22%, and in the elderly-by 50%. At the same time, strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) can increase the concentration of amlodipine in the plasma to an even greater extent.
Despite the fact that accurate quantitative assessment of the interaction of amlodipine and CYP3A4 inducers (e.g. rifampicin, Hypericum perforatum) is not obtained, against their common use, it is recommended constant monitoring of blood pressure. β-blockers in concurrent use with amlodipine can cause exacerbation of heart failure.
Although the study of amlodipine negative inotropic effect is usually not observed, nevertheless, some BCC may increase the severity of the negative inotropic effect of antiarrhythmic agents that cause prolongation of the QT interval (for example, amiodarone and quinidine).
A single dose of 100 mg of sildenafil in patients with arterial hypertension does not affect the pharmacokinetic parameters of amlodipine.
Repeated use of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.
Ethanol (beverages containing alcohol): amlodipine with a single and repeated use at a dose of 10 mg does not affect the pharmacokinetics of ethanol.
Neuroleptics and isoflurane: increased hypotensive effect of dihydropyridine derivatives.
With intravenous administration of dantrolene against the background of treatment with amlodipine, collapse, arrhythmias, a decrease in the strength of heart contractions and hyperkalemia are possible.
Calcium supplements can reduce the effect of BCC.
With the combined use of amlodipine with lithium preparations, it is possible to increase the manifestations of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).
Amlodipine does not alter the pharmacokinetics of cyclosporine.
It does not affect the concentration of digoxin in the blood serum and its renal clearance.
It does not significantly affect the effect of warfarin (PV).
Cimetidine does not affect the pharmacokinetics of amlodipine.
In research in vitro amlodipine does not affect the binding to plasma proteins of digoxin, phenytoin, warfarin and indomethacin.
Grapefruit juice: simultaneous single intake of 240 mg of grapefruit juice and 10 mg of amlodipine orally is not accompanied by a significant change in the pharmacokinetics of amlodipine.
Aluminum-or magnesium-containing antacids: their single administration does not significantly affect the pharmacokinetics of amlodipine.
Losartan
As with other agents that block the formation of angiotensin II and its effects, concomitant administration of potassium-sparing diuretics (e.g. spironolactone, triamterene, amiloride), potassium supplements, and potassium-containing salt substitutes may lead to an increase in the potassium content in the blood serum. In some patients with impaired renal function who have been treated with NSAIDs, including selective COX-2 inhibitors, concomitant administration of ACE inhibitors and / or ARA drugs, including losartan, may cause further deterioration of renal function until the development of acute renal failure. Usually this effect is reversible. NSAIDs, including selective COX-2 inhibitors, may reduce the effect of angiotensin II receptor blockers, including losartan. Therefore, the antihypertensive effect of angiotensin II receptor antagonists can be weakened with the simultaneous use of NSAIDs, in particular selective COX-2 inhibitors. Therefore, concurrent use of NSAIDs with Ashara must be made with caution in patients with impaired renal function
Double blockade of the RAAS: it was found that in patients with atherosclerosis, heart failure or diabetes with target organ damage, double blockade of RAAS (simultaneous use of ACE inhibitors and ARA drugs) is associated with more frequent complications of therapy in the form of arterial hypotension, syncope( syncope), hyperkalemia and impaired renal function (including acute renal failure) compared to monotherapy with each drug. In this regard, combined treatment with ACE inhibitors and ARA drugs requires an individualized approach and constant monitoring of the functional activity of the kidneys.
There were no pharmacokinetically significant interactions of the drug with such drugs as hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital.
Taking rifampin, an inducer of drug metabolism, reduces the concentration of losartan and its active metabolite.
In humans, 2 inhibitors of the CYP3A4 isoenzyme were studied. Ketoconazole does not affect the biotransformation of losartan administered intravenously to the active metabolite, and erythromycin does not have a clinically significant effect on the pharmacokinetics of losartan when taken orally.
Fluconazole, an inhibitor of the CYP2C9 isoenzyme, reduces the concentration of the active metabolite and increases the concentration of losartan in blood plasma, but the pharmacodynamic significance of the combined use of losartan and inhibitors of the CYP2C9 isoenzyme has not been established. It has been shown that individuals whose bodies do not convert losartan to the active metabolite have a very rare and specific defect of the CYP2C9 isoenzyme. These data suggest that the biotransformation of losartan to the active metabolite is mediated primarily by the isoenzyme CYP2C9, rather than CYP3A4.
Tablets 5 mg 50 mg: white or almost white, oblong, biconvex, covered with a film shell, with the inscription "AT1" on one side.
Tablets 5 mg 100 mg: pink or light pink, oblong, biconvex, covered with a film shell, with the inscription "AT2" on one side.
Side effects (PE) observed in studies of Amzaar are presented in accordance with the WHO classification by frequency of occurrence: very common (more than 1/10), common (more than 1/100, less than 1/10), infrequent (more than 1/1000, less than 1/100), rare (more than 1/10000, less than 1/1000) and very rare (less than 1/10000), including individual reports, the frequency is unknown (it is impossible to estimate the frequency from available data).
From the nervous system: often-dizziness, headache, infrequently-drowsiness.
General disorders and disorders at the injection site: infrequently-asthenia, discomfort or pain in the chest, a feeling of overflow in the abdomen, peripheral edema.
From the gastrointestinal tract: infrequently-constipation, abdominal discomfort, dyspepsia, vomiting, esophageal reflux.
From the skin and subcutaneous tissues: infrequently-skin itching, urticaria.
From the CCC side: infrequently-a feeling of palpitation, flushes of blood to the skin of the face, orthostatic hypotension.
From the respiratory system, chest and mediastinal organs: infrequently-shortness of breath.
On the part of the organ of hearing and labyrinth disorders: infrequently-systemic vertigo.
From the kidneys and urinary tract: infrequently-increased frequency of urination.
The PE observed when taking the components of Amzaar (amlodipine and losartan) can also serve as its potential PE, despite the fact that these PE were not observed in clinical studies and in the post-registration period of Amzaar use.
Amlodipine
From the central nervous system: often-headache (especially at the beginning of treatment), dizziness, increased fatigue, drowsiness, infrequently-general malaise, hyperesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, unusual dreams, increased excitability, anxiety, very rarely-migraine, apathy, agitation, ataxia, amnesia, asthenia, increased sweating.
From the side of the psyche: rarely, mood lability, and depression.
From the digestive system: often-nausea, abdominal pain, infrequently-vomiting, constipation or diarrhea, flatulence, dyspepsia, anorexia, dryness of the oral mucosa, thirst, rarely-gum hyperplasia, increased appetite, very rarely-pancreatitis, gastritis, jaundice (due to cholestasis), hyperbilirubinemia, increased activity of hepatic transaminases, hepatitis.
From the CCC side: often-a feeling of palpitation, infrequently-an excessive decrease in blood pressure, very rarely-fainting, shortness of breath, vasculitis, orthostatic hypotension, the development or aggravation of the course of chronic heart failure, cardiac arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain, pulmonary edema, edema of the lower extremities.
From the hematopoietic and lymphatic systems: very rarely — thrombocytopenic purpura, leukopenia, thrombocytopenia.
From the urinary system: infrequently-frequent urination, painful urination, nocturia, very rarely-dysuria, polyuria.
From the genitals and breast: infrequently-gynecomastia, impotence.
From the respiratory system: infrequently-shortness of breath, rhinitis, very rarely — cough.
From the musculoskeletal system: infrequently-muscle cramps, myalgia, arthralgia, back pain, arthrosis, rarely-myasthenia gravis.
From the skin: often-flushes of blood to the skin of the face, rarely-exfoliative dermatitis, Stevens-Johnson syndrome, very rarely-alopecia, xeroderma, cold sweat, violation of skin pigmentation.
Allergic reactions: very rarely-skin itching, rash (including erythematous, maculopapular, urticaria), Quincke's edema, erythema multiforme, photosensitivity reactions.
On the part of the senses: infrequently-tinnitus, diplopia, accommodation disorders, xerophthalmia, conjunctivitis, eye pain, very rarely — parosmia.
From the side of metabolism: very rarely — hyperglycemia.
Other: infrequently-weight loss, weight gain, nasal bleeding.
Losartan
From the central nervous system: often-dizziness, asthenia, headache, fatigue, increased weakness, insomnia, infrequently-impaired cerebral circulation, sleep disorders, drowsiness, memory disorder, peripheral neuropathy, paresthesia, hyperesthesia, tremor, ataxia, systemic dizziness, memory impairment, migraine, nervousness.
General disorders and disorders at the injection site: swelling of the face, fever, asthenia, increased weakness.
From the gastrointestinal tract: often-nausea, diarrhea, dyspepsia, abdominal pain, infrequently-anorexia, taste disorders, constipation, toothache, dry mouth, flatulence, gastritis, hepatitis, liver dysfunction, pancreatitis.
From the skin and subcutaneous tissues: infrequently — alopecia, dry skin, skin rash, redness of the skin, Schenlein-Henoch purpura, photosensitization, itching, increased sweating.
Allergic reactions: infrequently-urticaria, angioedema.
From the CCC side: infrequently — myocardial infarction, angina, cardiac arrhythmias (atrial fibrillation, sinus bradycardia, tachycardia, ventricular tachycardia, ventricular fibrillation), palpitations, orthostatic hypotension, syncope (syncope), hypotension, vasculitis.
From the blood and lymphatic system: infrequently-anemia, rarely-thrombocytopenia.
From the respiratory system, chest and mediastinal organs: often-shortness of breath, bronchitis, dry cough, discomfort in the pharynx, nosebleeds, rhinitis, laryngitis, chest pain.
On the part of the organ of hearing and labyrinth disorders: infrequently-ringing in the ears.
From the kidneys and urinary tract: infrequently-violation of the frequency of urination, nocturia, urinary tract infection, very rarely-kidney failure.
Mental disorders: infrequently-anxiety, anxiety disorder, confusion, depression, unusual dreams, panic disorder.
On the part of the visual organ: infrequently - blurred vision, burning / pricking sensation in the eye, conjunctivitis, decreased visual acuity.
From the genitals and breast: infrequently-decreased libido, impotence.
From the side of metabolism and nutrition: infrequently-gout.
Musculoskeletal and connective tissue disorders: often-convulsions, musculoskeletal pain, joint swelling, joint rigidity, infrequently-arthralgia, arthritis, fibromyalgia, rarely-rhabdomyolysis.
According to the recipe.
Patients with reduced BCC
Patients with reduced BCC (for example, when taking high doses of diuretics, severe diarrhea, vomiting, and other conditions leading to hypovolemia) may develop symptomatic hypotension at the beginning of Amzaar therapy. Before assigning Ashara deficit BCC should be eliminated. For patients whose daily dose of losartan is 25 mg, the use of Amzaar is not recommended (see "Method of administration and doses").
Special instructions and precautions related to amlodipine
Thanks to the long T1/2 in the blood plasma, vasodilation, developed as a result of taking amlodipine, may persist after its withdrawal. Thus, the appointment of another vasodilator after the withdrawal of amlodipine should be carried out with caution, with individual assessment of the dose, the dosage interval and active monitoring of the patient's condition.
During the treatment period, it is necessary to control body weight and salt intake, and to prescribe an appropriate diet. It is necessary to maintain dental hygiene and frequent visits to the dentist (to prevent soreness, bleeding and hyperplasia of the gums).
Special instructions and precautions related to losartan
Hyperkalemia (plasma potassium content >5.5 mmol / L) was observed in 1.5% of patients taking losartan as monotherapy. In none of these cases was the withdrawal of the drug required. Concomitant administration of potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium preparations, potassium-containing salt substitutes, as well as drugs that may lead to an increase in the concentration of potassium in the plasma (for example, heparin), should be justified (especially in elderly patients with impaired renal function), and the content of potassium in the plasma should be controlled.
Taking losartan can lead to transient arterial hypotension, accompanied by shock, fainting and shortness of breath.
Asaar the drug should be administered with caution to patients:
- with a reduced BCC,
- who are on a diet with a restriction of table salt,
- with renal insufficiency (creatinine Cl less than 20 ml / min) or on hemodialysis.
Patients with hepatic insufficiency
According to pharmacokinetic studies, patients with cirrhosis of the liver have significantly increased the concentration of losartan in the plasma. The use of losartan is not recommended in patients with severe hepatic insufficiency (more than 9 points on the Child-Pugh scale), as well as in patients with hepatic insufficiency (less than 9 points on the Child-Pugh scale), who are recommended to reduce the dose of losartan to 25 mg/day.
Patients with renal insufficiency
Due to the suppression of RAAS in some patients who took losartan, there were reversible changes in renal function when the drug was discontinued.
In patients whose renal function may depend on the activity of the RAAS (for example, in chronic heart failure of functional class III–IV according to the NYHA classification), the use of ACE inhibitors was accompanied by oliguria and / or increasing azotemia and, occasionally, acute renal failure and / or death. A similar pattern was observed with the use of losartan in such patients. In clinical studies, the use of ACE inhibitors in patients with single or bilateral renal artery stenosis led to an increase in the concentration of creatinine and urea nitrogen in plasma. A similar effect was observed when taking losartan in this group, it was reversible when the drug was discontinued
Influence on the ability to drive a car and work with mechanisms. Caution should be exercised when driving vehicles and other mechanisms when taking the drug Amzaar, given the risk of developing dizziness.
Arterial hypertension in patients who are indicated for combination therapy.
Amzaar is a combination of 2 active components with a complementary antihypertensive effect: amlodipine (belongs to the class of BCC, dihydropyridine derivatives) and losartan (belongs to the class of angiotensin II-ARA receptor antagonists).
The active components of the drug have a different mechanism of hypotensive action: amlodipine-due to vasodilation reduces the OPSS, losartan-due to the effect on the RAAS (inhibits the effects of angiotensin II), which leads to a more pronounced decrease in blood pressure compared to that on the background of monotherapy with each drug.
Amlodipine
Dihydropyridine derivative, which is an optically inactive mixture of optically active isomers. Amlodipine blocks calcium channels, thereby inhibiting the transmembrane transfer of calcium into myocardial cells and vascular smooth muscle cells. Reduces blood pressure by direct relaxing effect on the smooth muscles of the arterial vessels. In preclinical studies, amlodipine had a more pronounced effect on smooth muscle cells compared to cardiomyocytes. Amlodipine has no negative effect on either AV conduction or myocardial contractility. The drug reduces the resistance of the kidney vessels and increases renal blood flow
Studies of amlodipine in patients with chronic heart failure (CHF) of functional classes II–IV according to the NYHA classification (classification of the New York Heart Association) have shown that amlodipine does not have a negative effect on exercise tolerance, ejection fraction or any clinical parameters, as well as metabolism, in particular on the concentration of lipids and glucose in blood plasma. With a single oral administration, the effect of amlodipine begins after 2-4 hours and persists for 24 hours.
The maximum hypotensive effect is achieved no earlier than 4 weeks from the start of taking the drug. Amlodipine reduces blood pressure in patients who are in a lying and sitting position, as well as during physical exertion. Since the pharmacodynamic effect of the drug develops gradually, amlodipine does not cause a sharp decrease in blood pressure or reflex tachycardia.
Amlodipine reduces the severity of left ventricular hypertrophy. The hemodynamic effects of the drug remain unchanged with long-term use.
Amlodipine camsilate is chemically similar to the more common amlodipine bezilate in clinical practice, but has better photostability compared to it. According to preclinical studies, as caselet and besilat have the same rates of pharmacodynamics and pharmacokinetics. In toxicological studies of amlodipine camzilate in animals, no additional toxic effects or genotoxic potential were found relative to amlodipine bezilate.
The pharmacodynamic effect of amlodipine camzilate and amlodipine bezilate was comparable with a single dose of 5 mg in healthy male volunteers. In particular, both amlodipine salts had a comparable effect on sAD and dBP, as well as an increase in heart rate, with a maximum development of the hypotensive effect in the range of 6.7-11.9 hours after administration and a maximum increase in heart rate for 19 hours after administration. Reduction of sBP and dBP by approximately 13 and 15 mmHg. st. accordingly, it was observed in both cases, with a return of blood pressure to the initial values after 24 hours from the moment of administration, which corresponds to the known pharmacokinetic and hemodynamic profile of amlodipine bezilate
Losartan
Losartan is a synthetic antagonist of the angiotensin II receptor (type AT1) for oral administration. Angiotensin II, a potent vasoconstrictor, is the main hormone of the RAAS and an important determinant of the pathophysiology of hypertension. Angiotensin II binds to AT receptors1 It is found in many tissues of the body (vascular smooth muscle, adrenal glands, kidneys, and heart) and mediates important effects such as vasoconstriction and aldosterone release. Angiotensin II also stimulates the proliferation of vascular smooth muscle cells.
Losartan selectively blocks AT1- receptors. How in vitro, and in vivo losartan and its pharmacologically active carboxylated metabolite, E-3174, block all physiologically related actions of angiotensin II, regardless of the source or pathway of its synthesis in the body.
Losartan does not have an agonistic effect and does not block the receptors of other hormones or ion channels involved in the regulation of cardiovascular activity. In addition, losartan does not inhibit ACE, which breaks down bradykinin. Accordingly, when taking losartan, there is no potentiation of bradykinin-mediated undesirable effects. When taking losartan, the elimination of the negative feedback of angiotensin II and renin secretion leads to an increase in plasma renin activity (ARP), which in turn increases the concentration of angiotensin in the blood plasma. Despite these changes, the hypotensive effect and the decrease in the concentration of aldosterone in the blood plasma remain, indicating an effective blockade of AT1- receptors. After 3 days after discontinuation of losartan, ARP and the concentration of angiotensin in the blood plasma decrease to the initial values.
Amlodipine besilat
Suction. When taken in therapeutic doses, amlodipine is well absorbed, and Cmax in blood plasma, it is observed after 6-12 hours. Absolute bioavailability is estimated in the range from 64 to 80%. Food intake does not affect the absorption of amlodipine.
Distribution. T1/2 is 30-40 h, Css it is achieved after 7-8 days of administration. Vd it is about 21 l/kg. Binding to plasma proteins-98%.
Metabolism. The plasma clearance is 7 ml / min / kg. Amlodipine is largely metabolized in the liver to inactive metabolites.
Output. 10% of amlodipine and 60% of the metabolites are excreted by the kidneys.
Patients with hepatic insufficiency. T1/2 amlodipine is increased in patients with hepatic insufficiency.
Amlodipine camsilate
A comparative study of the pharmacokinetics of amlodipine camzilate and the reference drug amlodipine bezilate at a single dose of 5 mg showed similar absorption profiles. Cmax blood plasma concentrations averaged 3.6 ng / ml for amlodipine bezilate and 3.7 ng / ml for amlodipine camzilate, and Tmax - 6.9 and 7.3 hours, respectively, T1/2 - 42.2 hours and 39.3 hours, respectively. The obtained data correspond to the instructions for use and the literature data for amlodipine of besilate. Thus, the bioequivalence of amlodipine camzilate at a dose of 5 mg to the original amlodipine bezilate at the same dose was shown.
Losartan
Suction. When taken orally, losartan is well absorbed. The systemic bioavailability of losartan tablets is about 33%. Cmax losartan and its active metabolite in plasma are observed after 1 and 3-4 hours, respectively.
Distribution. Both losartan and its active metabolite bind to plasma proteins by more than 99%, mainly albumin. Vd losartan is 34 l.
Metabolism. Losartan undergoes the metabolism of the primary passage through the liver to form an active carboxylated metabolite, as well as other, inactive metabolites. About 14% of the intravenous or oral dose of losartan is converted to its active metabolite. For intravenous or oral administration14C-labeled losartan potassium, most of the radioactive label in the bloodstream corresponded to losartan and its active metabolite. The minimum level of losartan biotransformation to the active metabolite observed in clinical studies was 1%.
Output. The clearance of losartan and its active metabolite is 60 and 50 ml / min, respectively. Renal clearance — 74 and 26 ml / min, respectively. When taken orally, about 4% of the dose is excreted by the kidneys in unchanged form and 6% - in the form of an active metabolite. The pharmacokinetics of losartan and its active metabolite are linear when taken orally at doses up to 200 mg.
When ingested, the concentration of losartan and its active metabolite decreases polyexponentially, with a final T1/2 about 2 and 6-9 hours, respectively. At a dose of 100 mg, taken once a day, neither losartan nor its active metabolite accumulate in the plasma.
Losartan and its metabolites are excreted by the kidneys and through the intestine with bile. For oral administration and intravenous administration 14C-labeled losartan in humans, respectively, 35 and 43% of the radioactivity of losartan and its active metabolite is found in the urine, 58 and 50% — in the feces.
Pharmacokinetics in different groups of patients
In elderly patients with elevated blood pressure, the concentration of losartan and its active metabolite in plasma differs slightly from those in young patients.
In women with elevated blood pressure, the concentration of losartan in the plasma is 2 times higher than in men, while the concentration of its active metabolite does not differ in men and women.
In patients with moderate to moderate alcoholic cirrhosis of the liver, the concentrations of losartan and its active metabolite in the plasma when ingested increased by 5 and 1.7 times, respectively, compared to those in young male volunteers.
The plasma concentration of losartan does not change in patients with creatinine Cl above 10 ml/min. Compared to patients with normal renal function, the AUC of losartan is 2 times higher than in patients on hemodialysis. The concentrations of its active metabolite in plasma do not change in patients with renal insufficiency and patients on hemodialysis. Neither losartan nor its active metabolite can be removed by hemodialysis.
The combination of amlodipine, losartan
In comparative clinical studies of the combined use of amlodipine camzilate and losartan and the use of a combination of amlodipine camzilate with losartan at doses of 5 mg 50 mg and 5 mg 100 mg, the pharmacokinetic parameters in both cases were the same for both amlodipine and losartan and its active metabolite E-3174. The bioequivalence between the combination and the co-administration of C values was shownmax, AUC for camsilate amlodipine, losartan and E-3174 in both doses, with the exception of the Cmax losartan in a combination of 5 mg and 50 mg. Since the therapeutic activity of losartan is largely due to its active metabolite, it was concluded that the combination of 5/50 mg is therapeutically equivalent to the co-administered amlodipine at a dose of 5 mg and losartan at a dose of 50 mg.
At a temperature not exceeding 30 °C.
Keep out of reach of children.
The shelf life of the drug Asaarfilm-coated tablets 5 mg 50 mg 5 mg 50 — 2 years.
film-coated tablets 5 mg 100 mg 5 mg 100 — 2 years.
Do not use after the expiration date indicated on the package.
| Film-coated tablets | 1 table. |
| active ingredients: | |
| amlodipine camsilate | 7.84 mg |
| (in terms of amlodipine-5 mg) | |
| losartan potassium | 50 mg |
| excipients: butylhydroxytoluene-0.1 mg, sodium carboxymethyl starch-17 mg, MCC-265.1 mg, mannitol-40 mg, povidone K30-5 mg, crospovidone-12 mg, magnesium stearate-3 mg | |
| the shell film: hypromellose-2910-8 mg, hyprolose-2 mg, titanium dioxide-1.8 mg, talc-0.2 mg |
| Film-coated tablets | 1 table. |
| active ingredients: | |
| amlodipine camsilate | 7.84 mg |
| (in terms of amlodipine-5 mg) | |
| losartan potassium | 100 mg |
| excipients: butylhydroxytoluene-0.1 mg, sodium carboxymethyl starch-17 mg, MCC-407.1 mg, mannitol-40 mg, povidone K30-5 mg, crospovidone-18 mg, magnesium stearate-5 mg | |
| the shell film: hypromellose-2910-12 mg, hyprolose-3 mg, titanium dioxide-2.7 mg, talc-0.3 mg, iron oxide yellow dye-0.045 mg, iron oxide red dye-0.045 mg |
Film-coated tablets, 5 mg 50 mg, 5 mg 100 mg. According to 10 tables. in contour cell packages (blisters) made of aluminum foil, on the one hand laminated with oriented polyamide film, on the other hand — PVC film, sealed with aluminum foil, or 300 tablets each. in vials made of high-density white PE with screw-on lids made of white polypropylene containing a desiccant (granular silica gel) under a PE membrane and equipped with a first-opening control ring.
1 or 3 blisters or 1 bottle in a cardboard pack.
Asaar contraindicated in pregnancy and its reception should be stopped immediately in establishing pregnancy.
Toxic and lethal effects on the body of the fetus and newborn
Amlodipine
Drugs that directly affect the RAAS can cause damage and death of the fetus and newborn when prescribed to pregnant women. Isolated cases of the use of ACE inhibitors in pregnancy are described.
The use of drugs that directly affect the RAAS in the second and third trimesters of pregnancy is associated with such injuries of the fetus and newborn as arterial hypotension, neonatal hypoplasia of the skull bones, anuria, reversible and irreversible renal failure, death. There have also been cases of oligohydramnion, presumably developed as a result of reduced renal function in the fetus. In these cases, oligohydramnion was associated with limb contractures, craniofacial deformities, and fetal lung hypoplasia. In addition, there were cases of preterm birth, intrauterine development delay and non-infection of the ductus arteriosus, but no connection with the effect of the drug was found in these cases. The listed side effects, apparently, are not a consequence of the use of the drug in the first trimester of pregnancy. However, pregnant women who took ARA drugs in the first trimester should be informed about the consequences of taking these drugs in the SECOND-third trimesters
Depending on the duration of pregnancy, you can use a stress test for uterine contractions, a stress-free test, or an assessment of the biophysical profile of the fetus. At the same time, both the doctor and the patient should be aware that oligohydramnion can manifest itself after the development of irreversible fetal damage. Children with a history of exposure in utero Patients who are exposed to ARA drugs should be under medical supervision due to the increased likelihood of hypotension, oliguria and hyperkalemia. In the case of oliguria, first of all, correction of blood pressure and renal perfusion is necessary. Exchange hemotransfusion or hemodialysis is necessary for the correction of arterial hypotension and / or as a replacement for kidney function.
Losartan
The use of drugs acting on RAAS in the second and third trimesters of pregnancy can cause serious damage or even death of the developing fetus, so when pregnancy is established, losartan should be stopped immediately. Since renal perfusion of the fetus, depending on the RAAS, develops from the second trimester of pregnancy, the risk to the fetus increases when taking losartan in the second or third trimesters.
It is not known whether amlodipine and/or losartan are excreted in breast milk, but preclinical studies in animals have reported significant concentrations of amlodipine and/or the active metabolite of losartan in breast milk. Asaar not recommended for use in breastfeeding.
Inside, regardless of the meal, with a small amount of water once a day. Start treatment with Amzaar is necessary in the case of pre-titration of doses of amlodipine and losartan, respectively, 1 Table. Amzaara 5 mg 50 mg or 5 mg 100 mg. If necessary, direct the transition from monotherapy with amlodipine or losartan therapy drug Asar. Amzaar can be prescribed to patients whose blood pressure is insufficiently controlled by amlodipine or losartan in the same doses that are present in combination (5/50 mg or 5/100 mg).
Patients simultaneously receiving losartan and amlodipine, can be translated into Asaar with the same doses of these drugs.
Use in renal insufficiency
With a creatinine Cl of 50 to 20 ml/min, no dose adjustment is required.
Amzaar is not recommended for use in patients with a creatinine Cl of less than 20 ml / min and patients on hemodialysis, because it may be necessary to adjust the dose of the drug components.
Use in patients with reduced BCC
It is not recommended to use Amzaar in patients with reduced BCC (for example, when taking high doses of diuretics).
At the same time, in the case of replenishment of the BCC, taking the drug Amzaar is possible, if a lower dose of losartan — 25 mg is not recommended.
Use in hepatic insufficiency
The use of Amzaar is possible in patients with hepatic insufficiency (less than 9 points on the Child-Pugh scale), who, according to the doctor's decision, can be prescribed losartan at a dose of 50 mg.
Use in the elderly
The drug Amzaar may be used in patients over 65 years of age with a tolerable dose of losartan 50 mg.
Use in children and adolescents
Amzaar is not recommended for use in patients under 18 years of age due to insufficient data on the effectiveness and safety of use in this group (see "Contraindications").
C09DB Angiotensin II antagonists in combination with BCC
