Components:
Method of action:
Medically reviewed by Oliinyk Elizabeth Ivanovna, PharmD. Last updated on 27.03.2022
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Amtas-LP
Amlodipine, Lisinopril
Essential hypertension (patients who are indicated for combination therapy).
Essential hypertension (patients who are indicated for combination therapy).
Inside, regardless of the meal. The recommended dose is 1 tablet of the drug Equator® every day. The maximum daily dose is one tablet of the drug Equator®.
Patients with renal insufficiency. To determine the optimal initial and maintenance dose for patients with renal insufficiency, the dose should be titrated and determined individually, using lisinopril and amlodipine separately. Equator® it is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 20 and 5 mg (or 5 and 10 mg, or 20 and 10 mg), respectively. During treatment with the drug the Equator® it is necessary to monitor the function of the kidneys, the content of potassium and sodium in the blood serum. In case of deterioration of kidney function, taking the drug Equator® it is necessary to cancel and replace it with lisinopril and amlodipine in adequate doses.
Patients with hepatic insufficiency. The elimination of amlodipine may be delayed in patients with impaired liver function. Clear recommendations on the dosage regimen in such cases are not established, so the drug Equator® it should be administered with caution in patients with hepatic insufficiency.
Elderly patients (over 65 years of age). No age-related changes in the efficacy or safety profile of amlodipine and lisinopril were found in clinical studies. To determine the optimal maintenance dose, it is necessary to determine the dosage regimen individually, using lisinopril and amlodipine separately. Equator® it is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 20 and 5 mg (or 5 and 10 mg, or 20 and 10 mg), respectively.
Inside, regardless of the meal. The recommended dose is 1 tablet of Amtas-LP® every day. The maximum daily dose is one tablet of Amtas-LP®.
Patients with renal insufficiency. To determine the optimal initial and maintenance dose for patients with renal insufficiency, the dose should be titrated and determined individually, using lisinopril and amlodipine separately. Amtas-LP® it is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 20 and 5 mg (or 5 and 10 mg, or 20 and 10 mg), respectively. During treatment with Amtas-LP® it is necessary to monitor the function of the kidneys, the content of potassium and sodium in the blood serum. In case of deterioration of renal function, taking the drug Amtas-LP® it is necessary to cancel and replace it with lisinopril and amlodipine in adequate doses.
Patients with hepatic insufficiency. The elimination of amlodipine may be delayed in patients with impaired liver function. Clear recommendations on the dosage regimen in such cases are not established, so the drug Amtas-LP® it should be administered with caution in patients with hepatic insufficiency.
Elderly patients (over 65 years of age). No age-related changes in the efficacy or safety profile of amlodipine and lisinopril were found in clinical studies. To determine the optimal maintenance dose, it is necessary to determine the dosage regimen individually, using lisinopril and amlodipine separately. Amtas-LP® it is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 20 and 5 mg (or 5 and 10 mg, or 20 and 10 mg), respectively.
hypersensitivity to lisinopril or other ACE inhibitors,
hypersensitivity to amlodipine or other dihydropyridine derivatives,
hypersensitivity to other components of the drug,
Quincke's edema in the anamnesis, including against the background of the use of ACE inhibitors,
hereditary or idiopathic angioedema,
hemodynamically significant aortic or mitral valve stenosis or hypertrophic cardiomyopathy,
severe arterial hypotension (sBP less than 90 mmHg).),
cardiogenic shock,
unstable angina (with the exception of Prinzmetal angina),
heart failure after acute myocardial infarction (within the first 28 days),
pregnancy,
breastfeeding period,
age up to 18 years (due to the lack of data on the effectiveness and safety of the drug in this age group).
With caution: severe renal impairment, bilateral renal artery stenosis or single kidney artery stenosis with progressive azotemia, condition after kidney transplantation, azotemia, hyperkalemia, primary hyperaldosteronism, liver function disorders, arterial hypotension, cerebrovascular diseases (in t.tsch. cerebral circulatory insufficiency), ischemic heart disease, coronary insufficiency, sinus node weakness syndrome (pronounced bradycardia, tachycardia), chronic heart failure of non-ischemic etiology of NYHA functional class III–IV, aortic stenosis, mitral stenosis, acute myocardial infarction (and within 1 month after myocardial infarction), autoimmune systemic connective tissue diseases (in t.tsch. scleroderma, systemic lupus erythematosus), suppression of bone marrow hematopoiesis, diabetes mellitus, diet with salt restriction, hypovolemic conditions (in t.tsch. as a result of diarrhea, vomiting), old age, hemodialysis using high-flow dialysis membranes with high permeability (AN69®).
The frequency of adverse reactions in patients receiving the combined drug was not higher than in patients receiving one of the active substances. Adverse reactions were consistent with previous data on amlodipine and / or lisinopril. Adverse reactions were mild, transient, and rarely required discontinuation of treatment.
The most common side effects when taking the combination of drugs were headache (8%), cough (5%), dizziness (3%). The frequency of adverse reactions is given separately for lisinopril and amlodipine.
Data are presented by system-organ classes according to the MedDRA classification and with the following frequency: very common (≥1/10), common (≥1/100 to <1/10), infrequent (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very rare (<1/10000), frequency unknown (cannot be determined based on available data).
Table
| MedDRA Organ System Class | Frequency | Undesirable effects of lisinopril | Adverse effects of amlodipine |
| From the hematopoietic and lymphatic system | Very rare | Inhibition of bone marrow hematopoiesis, agranulocytosis, leukopenia, neutropenia, thrombocytopenia, hemolytic anemia, anemia, lymphadenopathy | Thrombocytopenia |
| On the part of the immune system | Very rare | Vasculitis, a positive test for antinuclear antibodies | Hypersensitivity |
| From the side of metabolism and nutrition | Very rare | Hypoglycemia | Hyperglycemia |
| Mental disorders | Infrequently | Mood changes, sleep disorders | Insomnia, unusual dreams, mood changes, increased excitability, depression, anxiety |
| Rarely | Mental disorders | Apathy, agitation | |
| From the nervous system | Often | Dizziness, headache, drowsiness | Drowsiness, dizziness, headache |
| Infrequently | Systemic dizziness, paresthesia, dysgeusia, convulsive twitching of the muscles of the limbs and lips | Syncope, tremor, dysgeusia, hypesthesia, paresthesia | |
| Rarely | Confusion of consciousness | Migraine | |
| Very rare | — | Peripheral neuropathy, ataxia, amnesia, parosmia | |
| On the part of the visual organ | Infrequently | — | Visually impaired (double vision, disturbance of accommodation), xerophthalmia, conjunctivitis, eye pain |
| On the part of the organ of hearing and the labyrinth | Infrequently | — | Tinnitus |
| From the heart | Often | — | Rapid heartbeat |
| Infrequently | Myocardial infarction, AV conduction disorder, bradycardia, tachycardia, rapid heartbeat, worsening of CHF, chest pain | — | |
| Rarely | — | Aggravation of the course of CHF | |
| Very rare | — | Myocardial infarction, ventricular tachycardia, atrial fibrillation, arrhythmia | |
| From the vascular system | Often | Pronounced decrease in blood pressure, orthostatic hypotension | Hyperemia of the skin |
| Infrequently | Violation of cerebral circulation, Raynaud's syndrome | Pronounced decrease in blood pressure, orthostatic hypotension | |
| Very rare | — | Vasculitis | |
| From the respiratory system, chest and mediastinal organs | Often | Dry cough | — |
| Infrequently | Rhinitis | Dyspnea, rhinitis, nosebleeds | |
| Rarely | Shortness of breath | — | |
| Very rare | Bronchospasm, allergic alveolitis, eosinophilic pneumonia, sinusitis | Cough | |
| From the digestive system | Often | Diarrhea, vomiting | Abdominal pain, nausea |
| Infrequently | Abdominal pain, nausea, indigestion | Vomiting, dyspepsia, constipation or diarrhea, dry mouth, anorexia, thirst | |
| Rarely | Dry mouth | Increased appetite | |
| Very rare | Pancreatitis, intestinal angioedema | Pancreatitis, gastritis, gingival hyperplasia | |
| From the liver and biliary tract | Very rare | Liver failure, hepatitis, cholestatic jaundice | Hepatitis, jaundice, cholestasis |
| From the skin and subcutaneous fat | Infrequently | Allergic reactions, angioedema of the face, limbs, lips, tongue, vocal folds and / or larynx, skin rash, itching, photosensitization | Skin rash, purpura, pruritus, xeroderma. |
| Rarely | Psoriasis, urticaria rash, alopecia | Dermatitis | |
| Very rare | Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, vulgar pemphigus, increased sweating, pseudolymphoma of the skin* | Erythema multiforme, angioedema, urticaria rash, increased sweating, cold sweat, alopecia, skin discoloration | |
| From the musculoskeletal system and connective tissue | Infrequently | — | Arthralgia, myalgia, muscle cramps, back pain, arthrosis |
| Rarely | Arthralgia, myalgia, arthritis | Myasthenia gravis | |
| From the kidneys and urinary tract | Often | Impaired renal function | — |
| Infrequently | — | Urination disorder, nocturia, increased frequency of urination | |
| Rarely | Acute renal failure, uremia | — | |
| Very rare | Oliguria, anuria | — | |
| On the part of the reproductive system and mammary glands | Infrequently | Impotence | Impotence, gynecomastia |
| Rarely | Gynecomastia | — | |
| General (systemic) and local reactions | Often | — | Peripheral edema, increased fatigue |
| Infrequently | Increased fatigue, asthenia | Chest pain, pain, malaise, asthenia | |
| Laboratory parameters | Infrequently | Increased concentration of urea and creatinine in the blood serum, hyperkalemia, increased activity of liver enzymes | The increase in body mass, reduction of body weight |
| Rarely | Decreased hemoglobin and hematocrit, erythropenia, hyperbilirubinemia, hyponatremia | — | |
| Very rare | — | Increased activity of liver enzymes |
* A complex symptom complex has been reported, which may include all or some of the following symptoms: fever, vasculitis, myalgia, arthralgia/arthritis, positive antinuclear antibody test, increased ESR, eosinophilia and leukocytosis, rash, photosensitization, or other skin changes.
Lisinopril
Symptoms: pronounced decrease in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, increased irritability.
Treatment: gastric lavage, administration of activated charcoal, giving the patient a horizontal position with raised legs, replenishment of BCC-IV administration of plasma-substituting solutions, symptomatic therapy, monitoring of the functions of the CCC and respiratory system, BCC, urea, creatinine and electrolytes in the blood serum, as well as diuresis. Lisinopril can be removed from the body by hemodialysis.
Amlodipine
Symptoms: a marked decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (the risk of developing severe and persistent arterial hypotension, including with the development of shock and death).
Treatment: gastric lavage, administration of activated charcoal, maintenance of CCC function, control of CCC and respiratory system functions, giving the patient a horizontal position with raised legs, control of BCC and diuresis. To restore vascular tone — the appointment of vasoconstrictors (in the absence of contraindications to their use), in order to eliminate the consequences of the blockade of calcium channels-intravenous administration of calcium gluconate. Hemodialysis is ineffective.
A combined preparation containing the active ingredients lisinopril and amlodipine.
Lisinopril - ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. A decrease in the content of angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of PG. Reduces heart rate, blood pressure, preload, pressure in the pulmonary capillaries, causes an increase in minute blood volume and increased myocardial tolerance to stress in patients with chronic heart failure. Dilates the arteries to a greater extent than the veins. Some effects are attributed to exposure to tissue RAAS. With prolonged use, the hypertrophy of the myocardium and the walls of the arteries of the resistive type decreases. Improves blood supply to the ischemic myocardium
ACE inhibitors prolong life expectancy in patients with chronic heart failure( CHF), slow the progression of left ventricular dysfunction in patients who have suffered a myocardial infarction without clinical manifestations of heart failure.
The onset of action is 1 hour after oral administration. The maximum antihypertensive effect is determined after 6 hours and persists for 24 hours. With arterial hypertension, the effect is noted in the first days after the start of treatment, a stable effect develops after 1-2 months. With a sharp withdrawal of the drug, there was no pronounced increase in blood pressure. Despite the primary effect, which is manifested in the effect on the RAAS, it is also effective in arterial hypertension with low renin activity. In addition to reducing blood pressure, lisinopril reduces albuminuria. Lisinopril does not affect the concentration of glucose in the blood in patients with diabetes mellitus and does not lead to an increase in cases of hypoglycemia.
Amlodipine — dihydropyridine derivative, BCC, has antianginal and antihypertensive effects. It blocks calcium channels, reduces the transmembrane transfer of calcium ions into the cell (to a greater extent - into vascular smooth muscle cells than into cardiomyocytes).
The antianginal effect is due to the expansion of the coronary and peripheral arteries and arterioles: in angina, it reduces the severity of myocardial ischemia, expanding the peripheral arterioles, reduces the OPSS, reduces the post-load on the heart, reduces the need for oxygen in the myocardium. Expanding the coronary arteries and arterioles in the unchanged and ischemic areas of the myocardium, increases the flow of oxygen to the myocardium (especially in vasospastic angina), prevents spasm of the coronary arteries (in t.tsch. caused by smoking). In patients with stable angina, a single daily dose increases exercise tolerance, slows the development of angina and ST-segment ischemic depression, reduces the frequency of angina attacks and the consumption of nitroglycerin and other nitrates
It has a long-term dose-dependent antihypertensive effect. The antihypertensive effect is due to the direct vasodilating effect on the vascular smooth muscles. In arterial hypertension, a single dose provides a clinically significant reduction in blood pressure for 24 hours (in the patient's lying and standing position ). Orthostatic hypotension in the appointment of amlodipine is quite rare. Does not cause a decrease in exercise tolerance, left ventricular ejection fraction. Reduces the degree of left ventricular myocardial hypertrophy. It does not affect the contractility and conduction of the myocardium, does not cause a reflex increase in heart rate, inhibits platelet aggregation, increases the glomerular filtration rate, has a weak natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria. It does not have any adverse effect on the metabolism and concentration of plasma lipids and can be used in the treatment of patients with bronchial asthma, diabetes mellitus and gout. A significant decrease in blood pressure is observed after 6-10 hours, the duration of the effect is 24 hours
Amlodipine lisinopril. The combination of lisinopril with amlodipine in one drug allows you to prevent the development of possible undesirable effects caused by one of the active substances. Thus, BCC, by directly expanding the arterioles, can lead to sodium and fluid retention in the body, and therefore can activate the RAAS. An ACE inhibitor blocks this process.
Lisinopril
Suction. After oral administration, lisinopril is absorbed from the gastrointestinal tract, its absorption can vary from 6 to 60%. Bioavailability is 29%. Food intake does not affect the absorption of lisinopril.
Distribution. Almost does not bind to plasma proteins. Cmax in blood plasma-90 ng / ml, it is reached after 6-7 hours. The permeability through the BBB and placental barrier is low.
Metabolism. Lisinopril is not biotransformed in the body.
Output. It is excreted by the kidneys in an unchanged form. T1/2 it is 12.6 hours.
Pharmacokinetics in selected groups of patients
Old age. The concentration of lisinopril in the blood plasma and AUC is 2 times higher than in young patients.
In patients with chronic heart failure the absorption and clearance of lisinopril are reduced.
In patients with renal insufficiency the concentration of lisinopril is several times higher than the concentration in the blood plasma in healthy volunteers, and there is an increase in Tmax in blood plasma and T1/2.
Lisinopril is eliminated from the body by hemodialysis.
Amlodipine
Suction. After oral administration, amlodipine is slowly and almost completely (90%) absorbed from the gastrointestinal tract. The bioavailability of amlodipine is 64-80%. Food intake does not affect the absorption of amlodipine.
Distribution. Most of the amlodipine found in the blood (95-98%) binds to plasma proteins. Cmax in the blood serum, it is observed after 6-10 h. Css it is achieved after 7-8 days of therapy. Medium Vd It is 20 l / kg, which indicates that most of the amlodipine is in the tissues, and a smaller part is in the blood.
Metabolism. Amlodipine undergoes a slow but active metabolism in the liver in the absence of a significant first-pass effect. The metabolites do not have significant pharmacological activity.
Output. It consists of two phases, T1/2 the final phase — 30-50 hours. About 60% of the oral dose is excreted by the kidneys mainly in the form of metabolites, 10% - in unchanged form, and 20-25% - in the form of metabolites through the intestine with bile. The total clearance of amlodipine is 0.116 ml / s / kg (7 ml / min / kg, 0.42 l / h / kg).
Pharmacokinetics in selected groups of patients
In elderly patients (over 65 years of age) amlodipine excretion is delayed (T1/2 - 65 h) compared to young patients, but this difference is not clinically significant.
In patients with hepatic insufficiency the increase of T1/2 assumes that with prolonged use, the accumulation of amlodipine in the body will be higher (T1/2 - up to 60 hours).
Kidney failure it does not significantly affect the kinetics of amlodipine. Amlodipine penetrates through the BBB. It is not removed during hemodialysis.
Amlodipine lisinopril
Interaction between the active substances that are part of the drug Equator®, unlikely. AUC, Tmax and Cmax, T1/2 they do not change in comparison with the indicators of each individual active substance. Food intake does not affect the absorption of active substances.
Lisinopril
Suction. After oral administration, lisinopril is absorbed from the gastrointestinal tract, its absorption can vary from 6 to 60%. Bioavailability is 29%. Food intake does not affect the absorption of lisinopril.
Distribution. Almost does not bind to plasma proteins. Cmax in blood plasma-90 ng / ml, it is reached after 6-7 hours. The permeability through the BBB and placental barrier is low.
Metabolism. Lisinopril is not biotransformed in the body.
Output. It is excreted by the kidneys in an unchanged form. T1/2 it is 12.6 hours.
Pharmacokinetics in selected groups of patients
Old age. The concentration of lisinopril in the blood plasma and AUC is 2 times higher than in young patients.
In patients with chronic heart failure the absorption and clearance of lisinopril are reduced.
In patients with renal insufficiency the concentration of lisinopril is several times higher than the concentration in the blood plasma in healthy volunteers, and there is an increase in Tmax in blood plasma and T1/2.
Lisinopril is eliminated from the body by hemodialysis.
Amlodipine
Suction. After oral administration, amlodipine is slowly and almost completely (90%) absorbed from the gastrointestinal tract. The bioavailability of amlodipine is 64-80%. Food intake does not affect the absorption of amlodipine.
Distribution. Most of the amlodipine found in the blood (95-98%) binds to plasma proteins. Cmax in the blood serum, it is observed after 6-10 h. Css it is achieved after 7-8 days of therapy. Medium Vd It is 20 l / kg, which indicates that most of the amlodipine is in the tissues, and a smaller part is in the blood.
Metabolism. Amlodipine undergoes a slow but active metabolism in the liver in the absence of a significant first-pass effect. The metabolites do not have significant pharmacological activity.
Output. It consists of two phases, T1/2 the final phase — 30-50 hours. About 60% of the oral dose is excreted by the kidneys mainly in the form of metabolites, 10% - in unchanged form, and 20-25% - in the form of metabolites through the intestine with bile. The total clearance of amlodipine is 0.116 ml / s / kg (7 ml / min / kg, 0.42 l / h / kg).
Pharmacokinetics in selected groups of patients
In elderly patients (over 65 years of age) amlodipine excretion is delayed (T1/2 - 65 h) compared to young patients, but this difference is not clinically significant.
In patients with hepatic insufficiency the increase of T1/2 assumes that with prolonged use, the accumulation of amlodipine in the body will be higher (T1/2 - up to 60 hours).
Kidney failure it does not significantly affect the kinetics of amlodipine. Amlodipine penetrates through the BBB. It is not removed during hemodialysis.
Amlodipine lisinopril
Interaction between the active substances that are part of the drug Amtas-LP®, unlikely. AUC, Tmax and Cmax, T1/2 they do not change in comparison with the indicators of each individual active substance. Food intake does not affect the absorption of active substances.
- Antihypertensive agent combined (angiotensin converting enzyme inhibitor blocker of "slow" calcium channels) [ACE inhibitors in combinations]
- Antihypertensive agent combined (angiotensin converting enzyme inhibitor blocker of "slow" calcium channels) [Calcium channel blockers in combinations]
Lisinopril
Substances that affect the potassium content- potassium-sparing diuretics (for example, spironolactone, amiloride, and triamterene), potassium-containing dietary supplements, potassium-containing salt substitutes, and any other medications that lead to an increase in serum potassium (for example, heparin) - may lead to hyperkalemia when combined with ACE inhibitors, especially in patients with a history of renal failure and other kidney diseases. When prescribing a drug that affects the potassium content, simultaneously with lisinopril, the content of potassium in the blood serum should be monitored. Therefore, simultaneous administration should be carefully justified and carried out with extreme caution and regular monitoring of both the potassium content in the blood serum and kidney function. Potassium-sparing diuretics can be taken in conjunction with the drug Equator® only under the condition of careful medical supervision.
Diuretics. If a diuretic is prescribed to a patient receiving Equator®, the antihypertensive effect is usually enhanced. Simultaneous use should be carried out with caution. Lisinopril calibrations softens the effect of diuretics.
Other antihypertensive drugs. Concomitant use of these drugs may increase the antihypertensive effect of the drug Equator®. Concomitant use with nitroglycerin, other nitrates, or vasodilators may lead to a marked decrease in blood pressure.
Tricyclic antidepressants, antipsychotics, general anaesthetics, narcotic analgesics. Concomitant administration with ACE inhibitors may lead to a marked decrease in blood pressure.
Ethanol increases the antihypertensive effect.
Allopurinol, procainamide, cytostatic agents, or immunosuppressants (corticosteroids system) may lead to an increased risk of developing leukopenia when used concomitantly with ACE inhibitors.
Antacids and colestyramine when taken concomitantly with ACE inhibitors, the bioavailability of the latter is reduced.
Sympathomimetics They can reduce the antihypertensive effect of ACE inhibitors, it is necessary to carefully monitor the achievement of the desired effect.
Hypoglycemic drugs. Concomitant use of ACE inhibitors and hypoglycemic drugs (insulin and hypoglycemic agents for oral administration) may increase the likelihood of a decrease in blood glucose concentration and the risk of hypoglycemia. This phenomenon is most often observed during the 1st week of combined treatment and in patients with renal insufficiency.
NSAIDs (including selective COX-2 inhibitors). Long-term use of NSAIDs, including high doses of acetylsalicylic acid more than 3 g / day, may reduce the antihypertensive effect of ACE inhibitors. The additive effect of taking NSAIDs and ACE inhibitors is manifested in an increase in the content of potassium in the blood serum and can lead to deterioration of kidney function. These effects are usually reversible. It is very rare to develop acute renal failure, especially in elderly and dehydrated patients.
Lithium preparations. Lithium excretion may be slowed down during concomitant administration with ACE inhibitors, and therefore serum lithium concentrations should be monitored during this period. When used together with lithium preparations, it is possible to increase the manifestations of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).
Preparations of gold. With the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) in/in, a symptom complex is described, including facial hyperemia, nausea, vomiting and arterial hypotension.
Amlodipine
Inhibitors of the CYP3A4 isoenzyme. Studies in elderly patients have shown that diltiazem inhibits the metabolism of amlodipine, probably through the CYP3A4 isoenzyme (plasma/serum concentration increases by almost 50%, and the effect of amlodipine increases). It is not impossible to exclude the possibility that more powerful inhibitors of the CYP3A4 isoenzyme (for example, ketoconazole, itraconazole, ritonavir) may increase the concentration of amlodipine in the serum to a greater extent than diltiazem. Simultaneous use should be carried out with caution.
Inducers of the CYP3A4 isoenzyme. Concomitant use with antiepileptic drugs (for example, carbamazepine, phenobarbital, phenytoin, phosphenytoin, primidone), rifampicin, herbal preparations containing St. John's wort may lead to a decrease in the concentration of amlodipine in the blood plasma. Control with possible dose adjustment of amlodipine during treatment with inducers of the CYP3A4 isoenzyme and after their withdrawal is indicated. Simultaneous use should be carried out with caution.
As monotherapy, amlodipine is well combined with thiazide and loop diuretics, general anesthesia agents, beta-blockers, ACE inhibitors, long-acting nitrates, nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, antacids (aluminum hydroxide, magnesium hydroxide), simetikon, cimetidine, NSAIDs, antibiotics, etc.hypoglycemic agents for oral administration.
It is possible to increase the antianginal and antihypertensive effect of BCC when used together with thiazide and loop diuretics, verapamil, ACE inhibitors, beta-blockers and nitrates, as well as to increase their antihypertensive effect when used together with alpha-blockers, neuroleptics.
A single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the pharmacokinetics 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.
Antiviral agents (ritonavir) increase the plasma concentrations of BCC, including amlodipine.
Neuroleptics and isoflurane - increased antihypertensive effect of dihydropyridine derivatives.
Amlodipine has no significant effect on the pharmacokinetics of ethanol.
Calcium preparations may 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 cause significant changes in the pharmacokinetics of cyclosporine.
Amlodipine does not affect the serum concentration of digoxin and its renal clearance.
Amlodipine does not significantly affect the effect of warfarin (PV).
Cimetidine it does not affect the pharmacokinetics of amlodipine.
It is possible to reduce the antihypertensive effect of the drug Equator® when used simultaneously with estrogens, sympathomimetics.
Procainamide, quinidine, and other drugs that prolong the QT interval, they can contribute to its significant lengthening.
In research in vitro amlodipine does not affect the binding of digoxin, phenytoin, warfarin and indomethacin to blood proteins.
Taking amlodipine with grapefruit juice is not recommended, as in some patients this may lead to an increase in the bioavailability of amlodipine, which increases its antihypertensive effect.
Lisinopril
Substances that affect the potassium content- potassium-sparing diuretics (for example, spironolactone, amiloride, and triamterene), potassium-containing dietary supplements, potassium-containing salt substitutes, and any other medications that lead to an increase in serum potassium (for example, heparin) - may lead to hyperkalemia when combined with ACE inhibitors, especially in patients with a history of renal failure and other kidney diseases. When prescribing a drug that affects the potassium content, simultaneously with lisinopril, the content of potassium in the blood serum should be monitored. Therefore, simultaneous administration should be carefully justified and carried out with extreme caution and regular monitoring of both the potassium content in the blood serum and kidney function. Potassium-sparing diuretics can be taken in conjunction with Amtas-LP® only under the condition of careful medical supervision.
Diuretics. If a diuretic is prescribed to a patient receiving Amtas-LP®, the antihypertensive effect is usually enhanced. Simultaneous use should be carried out with caution. Lisinopril calibrations softens the effect of diuretics.
Other antihypertensive drugs. Concomitant use of these drugs may increase the antihypertensive effect of Amtas-LP®. Concomitant use with nitroglycerin, other nitrates, or vasodilators may lead to a marked decrease in blood pressure.
Tricyclic antidepressants, antipsychotics, general anaesthetics, narcotic analgesics. Concomitant administration with ACE inhibitors may lead to a marked decrease in blood pressure.
Ethanol increases the antihypertensive effect.
Allopurinol, procainamide, cytostatic agents, or immunosuppressants (corticosteroids system) may lead to an increased risk of developing leukopenia when used concomitantly with ACE inhibitors.
Antacids and colestyramine when taken concomitantly with ACE inhibitors, the bioavailability of the latter is reduced.
Sympathomimetics They can reduce the antihypertensive effect of ACE inhibitors, it is necessary to carefully monitor the achievement of the desired effect.
Hypoglycemic drugs. Concomitant use of ACE inhibitors and hypoglycemic drugs (insulin and hypoglycemic agents for oral administration) may increase the likelihood of a decrease in blood glucose concentration and the risk of hypoglycemia. This phenomenon is most often observed during the 1st week of combined treatment and in patients with renal insufficiency.
NSAIDs (including selective COX-2 inhibitors). Long-term use of NSAIDs, including high doses of acetylsalicylic acid more than 3 g / day, may reduce the antihypertensive effect of ACE inhibitors. The additive effect of taking NSAIDs and ACE inhibitors is manifested in an increase in the content of potassium in the blood serum and can lead to deterioration of kidney function. These effects are usually reversible. Very rarely, the development of acute renal failure is possible, especially in elderly and dehydrated patients.
Lithium preparations. The excretion of lithium may be slowed down during concomitant administration with ACE inhibitors, and therefore the concentration of lithium in the blood serum should be monitored during this period. When combined with lithium preparations, it is possible to increase the manifestations of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).
Preparations of gold. With the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) in/in, a symptom complex is described, including facial hyperemia, nausea, vomiting and arterial hypotension.
Amlodipine
Inhibitors of the CYP3A4 isoenzyme. Studies in elderly patients have shown that diltiazem inhibits the metabolism of amlodipine, probably through the CYP3A4 isoenzyme (plasma/serum concentration increases by almost 50%, and the effect of amlodipine increases). It is not impossible to exclude the possibility that more powerful inhibitors of the CYP3A4 isoenzyme (for example, ketoconazole, itraconazole, ritonavir) may increase the concentration of amlodipine in the serum to a greater extent than diltiazem. Simultaneous use should be carried out with caution.
Inducers of the CYP3A4 isoenzyme. Concomitant use with antiepileptic drugs (for example, carbamazepine, phenobarbital, phenytoin, phosphenytoin, primidone), rifampicin, herbal preparations containing St. John's wort may lead to a decrease in the concentration of amlodipine in the blood plasma. Control with possible dose adjustment of amlodipine during treatment with inducers of the CYP3A4 isoenzyme and after their withdrawal is indicated. Simultaneous use should be carried out with caution.
As monotherapy, amlodipine is well combined with thiazide and loop diuretics, general anesthesia agents, beta-blockers, ACE inhibitors, long-acting nitrates, nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, antacids (aluminum hydroxide, magnesium hydroxide), simetikon, cimetidine, NSAIDs, antibiotics, etc.hypoglycemic agents for oral administration.
It is possible to increase the antianginal and antihypertensive effects of BCC when used together with thiazide and loop diuretics, verapamil, ACE inhibitors, beta-blockers and nitrates, as well as to increase their antihypertensive effect when used together with alpha-blockers, neuroleptics.
A single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the pharmacokinetics 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.
Antiviral agents (ritonavir) increase the plasma concentrations of BCC, including amlodipine.
Neuroleptics and isoflurane - increased antihypertensive effect of dihydropyridine derivatives.
Amlodipine has no significant effect on the pharmacokinetics of ethanol.
Calcium preparations may 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 cause significant changes in the pharmacokinetics of cyclosporine.
Amlodipine does not affect the serum concentration of digoxin and its renal clearance.
Amlodipine does not significantly affect the effect of warfarin (PV).
Cimetidine it does not affect the pharmacokinetics of amlodipine.
It is possible to reduce the antihypertensive effect of the drug Amtas-LP® when used simultaneously with estrogens, sympathomimetics.
Procainamide, quinidine, and other drugs that prolong the QT interval, they can contribute to its significant lengthening.
In research in vitro amlodipine does not affect the binding of digoxin, phenytoin, warfarin and indomethacin to blood proteins.
Taking amlodipine with grapefruit juice is not recommended, as in some patients this may lead to an increase in the bioavailability of amlodipine, which increases its antihypertensive effect.
