Composition, form of production and packaging
Tablets, film-coated 1 tab.
aliskiren 150 mg
amlodipine 5 mg
14 pcs. - blisters (1) made of PVC / PTFE and PA / Al / PVC - cardboard packs.
14 pcs. - blisters (2) made of PVC / PTFE and PA / Al / PVC - cardboard packs.
14 pcs. - blisters (4) made of PVC / PTFE and PA / Al / PVC - cardboard packs.
14 pcs. - blisters (7) of PVC / PTFE and PA / Al / PVC - packs of cardboard.
Tablets, film-coated 1 tab.
aliskiren 150 mg
amlodipine 10 mg
14 pcs. - blisters (1) made of PVC / PTFE and PA / Al / PVC - cardboard packs.
14 pcs. - blisters (2) made of PVC / PTFE and PA / Al / PVC - cardboard packs.
14 pcs. - blisters (4) made of PVC / PTFE and PA / Al / PVC - cardboard packs.
14 pcs. - blisters (7) of PVC / PTFE and PA / Al / PVC - packs of cardboard.
Tablets, film-coated 1 tab.
aliskiren 300 mg
amlodipine 5 mg
14 pcs. - blisters (1) made of PVC / PTFE and PA / Al / PVC - cardboard packs.
14 pcs. - blisters (2) made of PVC / PTFE and PA / Al / PVC - cardboard packs.
14 pcs. - blisters (4) made of PVC / PTFE and PA / Al / PVC - cardboard packs.
14 pcs. - blisters (7) of PVC / PTFE and PA / Al / PVC - packs of cardboard.
Tablets, film-coated 1 tab.
aliskiren 300 mg
amlodipine 10 mg
14 pcs. - blisters (1) made of PVC / PTFE and PA / Al / PVC - cardboard packs.
14 pcs. - blisters (2) made of PVC / PTFE and PA / Al / PVC - cardboard packs.
14 pcs. - blisters (4) made of PVC / PTFE and PA / Al / PVC - cardboard packs.
14 pcs. - blisters (7) of PVC / PTFE and PA / Al / PVC - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
Combined therapy with aliskiren and amlodipine is based on a complementary effect on different systems involved in the regulation of blood pressure (BP).Amlodipine, being a blocker of "slow" calcium channels, blocks the flow of calcium ions into the smooth muscle cells of the vascular wall, preventing the contraction of smooth muscles and narrowing of the vessels. The renin inhibitor aliskiren suppresses the enzymatic activity of renin, thus blocking the transfer of angiotensinogen to angiotensin I (AT I) and the formation of angiotensin II (AT II), the main effector molecule of the renin-angiotensin-aldosterone system (RAAS). AT II causes vasoconstriction
(vasoconstriction), enhances the reabsorption of sodium and water. Thus, amlodipine prevents vasoconstriction and
reduces overall peripheral vascular resistance (OPSS) by acting directly, aliskiren is capable of
to prevent vasoconstriction indirectly (by suppressing the formation of AT II).
Aliskiren also affects the balance of fluid and sodium ions, which also contributes to the normalization of blood pressure. The combined action of aliskiren and amlodipine on these two factors, which play a key role in the regulation of blood pressure (vasoconstriction and RAAS-mediated hypertensive effects), leads to an increase in the antihypertensive effect of combined therapy in comparison with the effect of each drug in monotherapy.
Aliskiren
In patients with arterial hypertension (AH), when aliskiren is used at a dose of 150 and 300 mg once a day, a dose-dependent prolonged decrease in both systolic and diastolic blood pressure is observed within 24 hours, including the early morning hours. When taking aliskiren 300 mg / day the ratio of the residual effect of the drug to the maximum or target for diastolic blood pressure is 98%.
After 2 weeks of taking the medication, the blood pressure decreases by 85-90% of the maximum, the antihypertensive effect remains at the reached level during the long-term use (within 1 year of therapy with aliskiren, there was no decrease in the antihypertensive effect).
After the cessation of aliskiren treatment, a gradual return of blood pressure to the baseline level is observed for several weeks, without the development of the "withdrawal" syndrome and increased renin activity of the blood plasma. After 4 weeks from the withdrawal of aliskiren, the level of blood pressure remains significantly lower in comparison with placebo. When using the drug, there is no pronounced decrease in blood pressure in response to taking the first dose of the drug (the effect of the "first dose") and the reflex increase in the heart rate (heart rate) in response to vasodilation.
When using aliskiren in monotherapy and in combination with other antihypertensive agents, the incidence of severe BP decrease is 0.1% and <1%, respectively.
Combined therapy with aliskiren with diuretics and blockers of "slow" calcium channels (BCCI) is good
is tolerated by patients and allows to achieve an additional reduction in blood pressure.
The severity of the antihypertensive effect of the drug does not depend on age, sex, race and body mass index.
Amlodipine
Amlodipine, which is part of the preparation Racilam, inhibits transmembrannoe intake of calcium ions in cardiomyocytes and smooth muscle cells of blood vessels.The mechanism of antihypertensive action of amlodipine is associated with direct
a relaxing effect on smooth muscle vessels, causing a decrease in OPSS and a decrease in blood pressure.
After taking in therapeutic doses in patients with arterial hypertension, amlodipine causes vasodilation,
leading to a decrease in blood pressure. Reduction of blood pressure is not accompanied by a significant change in the heart rate (heart rate) and the level of catecholamines for prolonged use.
Concentrations of the drug in the blood plasma correlate with the therapeutic response, both in young and elderly patients.
With arterial hypertension in patients with normal renal function, amlodipine in therapeutic doses leads to a decrease in renal vascular resistance, an increase in glomerular filtration rate and an effective renal
Plasma current without changing the filtration fraction and the level of proteinuria.
As well as with the use of other BCCI, amlodipine treatment in patients with normal left ventricular (LV) function was accompanied by a change in hemodynamic parameters of evaluation of heart function at rest and under physical
load: a slight increase in the cardiac index, without significantly affecting the maximum rate of increase in pressure in the left ventricle (dP / dt), the end diastolic pressure and the end diastolic volume of the LV.
Hemodynamic studies in healthy volunteers have shown that the use of amlodipine in a range of therapeutic doses is not accompanied by a negative inotropic effect even when used simultaneously with beta-blockers.
Amlodipine does not change the function of the sinoatrial node and does not affect atrioventricular conduction in healthy volunteers. The use of amlodipine in combination with beta-blockers both in patients with arterial hypertension and in patients with angina pectoris was not accompanied by undesirable changes in electrocardiographic parameters.
The clinical efficacy of amlodipine in patients with chronic stable angina, vasospastic angina and angiographically confirmed coronary artery disease was demonstrated.
PHARMACOKINETICS
Racilam (aliskiren + amlodipine)
Eating high-fat food reduces the rate and rate of absorption of aliskiren in the composition of the drug Rasilam (300 mg + 10 mg) in approximately the same way as in the case of using aliskiren as a monotherapy, however, it is clinically insignificant. The pharmacokinetics of amlodipine, taken as a combination of Racilam, as a monotherapy, does not affect food intake.
Aliskiren
Absorption
After taking the drug inside, the time to reach the maximum concentration in the blood plasma (T max ) of aliskiren is 1-3 hours, the absolute bioavailability is 2.6%.Simultaneous food intake reduces the maximum concentration in the blood plasma (C max ) and the area under the concentration-time curve (AUC) of aliskiren, but this does not have a significant effect on the pharmacodynamics of aliskiren. Therefore, aliskiren can be used regardless of time food intake. The increase in C max and AUC of aliskiren has a linear dose dependence in the range of 75 to 600 mg. The equilibrium concentration of aliskiren in blood plasma is attained between 5 and 7 in the afternoon with daily application once a day. The concentration of aliskiren in blood plasma in the equilibrium state is 2 times greater than that after the application of the first dose.
Distribution
Once ingested, aliskiren is evenly distributed in the body. After intravenous administration, the mean
the volume of distribution after reaching the equilibrium concentration is about 135 liters, which indicates
significant extravascular distribution of aliskiren. Aliskiren moderately binds to blood plasma proteins (47-51%), regardless of concentration.
Metabolism and excretion
The average half-life (T 1/2 ) of aliskiren is 40 hours (varies from 34 to 41 hours). Aliskiren is excreted mainly unchanged through the intestine (78%). About 1.4% of the ingested dose is metabolized with the participation of the CYP 3A4 isoenzyme. After oral administration, about 0.6% of aliskiren is excreted by the kidneys. After intravenous administration, the average plasma clearance is about 9 l / h.
Amlodipine
Suction
After ingestion of amlodipine in therapeutic doses, Cmax in blood plasma is achieved in 6-12 hours. Absolute bioavailability averages 64-80%. Eating food does not affect the bioavailability of amlodipine.
Distribution
The distribution volume is approximately 21 l / kg. In studies with amlodipine in vitro, it was shown that in patients with arterial hypertension, approximately 97.5% of the circulating drug binds to blood plasma proteins.
Metabolism
Amlodipine is intensively (approximately 90%) metabolized in the liver with the formation of inactive metabolites.
Excretion
Excretion from the blood plasma is biphasic with T 1/2 , approximately 30 to 50 hours. Equilibrium concentrations in the blood plasma are achieved after application within 7-8 days. 10% of the unchanged drug and 60% in the form of metabolites is excreted by the kidneys.
Pharmacokinetics in special cases
Dysfunction of the liver
In patients with mild and moderate impairment of liver function, the pharmacokinetics of aliskiren does not change significantly, dose adjustment is not required.
Since patients with impaired hepatic function have reduced clearance of amlodipine, which leads to an increase
AUC approximately 40-60%, Racilam should be used with caution.
Renal impairment
The pharmacokinetics of aliskiren has been studied in patients with varying degrees of severity of renal dysfunction. The increase in AUC and C max was found to be 0.8-2 times as compared with healthy volunteers. These changes did not correlate with the severity of renal pathology. In this regard, to start treatment does not require dose adjustment, but patients with severe renal dysfunction of aliskiren is contraindicated.
The pharmacokinetic parameters of amlodipine in patients with impaired renal function do not change significantly.
Patients aged <18 years
The pharmacokinetics of the drug Racilam in patients under the age of 18 years has not been studied.
Patients aged> 65 years
It is not necessary to adjust the initial dose of aliskiren in elderly patients.
T max of amlodipine in plasma in young and elderly patients is the same. However, in elderly patients, clearance of amlodipine tends to decrease, which leads to an increase in AUC and T 1/2 .
INDICATIONS
- Arterial hypertension (in patients in whom monotherapy with aliskiren or amlodipine is ineffective).
DOSING MODE
The preparation of Racilam is recommended to use one tablet per day, regardless of the time of ingestion.
Before prescribing the drug, patients with hypovolemia and / or hyponatremia should be corrected for these disorders and treated under the supervision of a physician.
Regardless of the dose in which the patient received one of the components of the drug in monotherapy, the transfer of the patient to combination therapy with Racilam increases the antihypertensive effect.
Initiation of treatment in patients with moderate and severe arterial hypertension (systolic blood pressure of 160 mm Hg and / or diastolic blood pressure of ≥ 100 mm Hg)
The recommended initial dose is usually 150 mg + 5 mg 1 time per day. The pronounced antihypertensive effect usually develops within 1 week, and the maximum effect is achieved in about 2 weeks. If after 2-4 weeks after starting treatment the blood pressure does not reach the target level, the dose of the drug can be gradually increased to the maximum (300 mg of aliskiren and 10 mg of amlodipine (300 mg + 10 mg) once a day). The dose should be selected individually and adjusted depending on the clinical effect.
With insufficient control of BP against the background of monotherapy with aliskiren or amlodipine
Patients in whom BP is not adequately controlled by aliskiren in monotherapy or amlodipine in monotherapy can be switched to combination therapy with Racilam.The recommended initial dose is usually 150 mg + 5 mg 1 time per day.
Patients who, when using any of the components in monotherapy, develop a dose-limiting toxic effect (development of adverse events), to achieve the same antihypertensive effect, can be transferred to receive Racilam in the same doses in which the component is included in more low dose.
Use in patients who have already received aliskiren together with amlodipine in individual tablets in the same doses
Patients already receiving aliskiren and amlodipine separately can be transferred to the preparation of Racilam in the same doses in terms of aliskiren and amlodipine.
Patients aged? 65 years
Correction of the dose of the drug at the initial stage of treatment in this population of patients is not required.
Patients with impaired renal function
For patients with mild and moderate renal impairment (GFR> 30 mL / min / 1.73 m 2 but <90 mL / min / 1.73 m 2 ), an initial dose adjustment is not required.
Patients with impaired renal function of severe degree (GFR <30 ml / min / 1.73 m 2 ) the drug is contraindicated.
Patients with impaired hepatic function
Since patients with impaired hepatic function have reduced clearance of amlodipine, which increases the AUC by approximately 40-60%, Racilam should be used with caution in this category of patients.
SIDE EFFECT
Racilam (aliskiren + amlodipine)
The total incidence of adverse events (AEs) with Racilam in doses up to 300 mg + 10 mg was similar to that of the use of each component in monotherapy and placebo. The frequency of AE was not related to gender, age, body mass index or race. New AEs, specific for the preparation of Racilam and not established earlier in the case of using each of the components in monotherapy, were not identified. BUT, basically, they were easy and transitory. It is known that against the background of the use of amlodipine (but not aliskiren) peripheral edema can develop, the frequency and degree of which depends on the dose of the drug. The incidence of swelling with Racilam was lower or equal to that of amlodipine in the appropriate doses.
If there are various manifestations of allergic reactions (especially difficulty breathing or swallowing, swelling of the face, extremities, eyelids, lips and tongue), treatment should be stopped and immediately consult a doctor.
AEs arising from the use of each component in monotherapy
AEs noted against the background of the use of each of the components in monotherapy can occur with the administration of the drug Racilam, even if the AE data were not observed in the clinical trials of the drug.
Aniseren
When the drug was administered in a dose up to 300 mg, the total frequency of AE was similar to that of the drug in the context of placebo. NEAs are mild and transient and only occasionally require withdrawal of therapy. The most frequent AE was diarrhea. Among the other AEs observed against the background of aliskiren were skin rash and angioedema, which occurred rarely and with the same frequency as with placebo or hydrochlorothiazide.
The incidence of cough with the placebo and aliskiren was not different.
To assess the incidence of AE, the following criteria were used (according to the WHO classification): very often (? 1/10 appointments); often (? 1/100, <1/10);infrequently (? 1/1000, <1/100); rarely (? 1/10000, <1/1000); very rarely (<1/10000), the frequency is unknown (insufficient data to estimate the frequency of development).
AEs observed with aliskiren during clinical trials:
Disorders from the digestive system: often - diarrhea.
Violation of the skin and subcutaneous tissues: infrequent - skin rash.
Laboratory and instrumental data: often - hyperkalemia.
Hemoglobin and hematocrit: against the background of monotherapy with aliskiren, there was a slight decrease in hemoglobin and hematocrit (an average of 0.05 mmol / L and 0.16% by volume, respectively), not requiring withdrawal of the drug. Reduction of hemoglobin and hematocrit are also observed when using other agents that affect RAAS, in particular, ACE inhibitors and ARA II.
The content of potassium in the blood plasma: on a background of monotherapy with aliskirenom in patients with arterial hypertension, in rare cases there was a slight increase in the potassium content in the blood serum. In patients with diabetes mellitus when using aliskiren together with ACE inhibitors, serum potassium concentration increased more often (5.5%).
AEs observed with aliskiren in clinical practice, including spontaneous reports and cases described in the literature.
Since spontaneous reports of AEs are voluntary from the population of an undetermined sample, it is not possible to estimate the frequency of these AEs (the frequency is unknown):
Disturbance of the skin and subcutaneous tissue: severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, skin itching, reddening of the skin.
Disorders of immune system: hypersensitivity reactions, anaphylactic reactions, urticaria.
Disorders of the nervous system: dizziness.
Violations by the kidneys and urinary tract: light and moderate renal impairment, pronounced renal dysfunction.
Violations of the vessels a marked decrease in blood pressure, peripheral edema.
Disorders of the liver and biliary tract: hepatic failure.
Laboratory and instrumental data: increase of creatinine concentration in serum, increased activity of "liver" enzymes. amlodipine
Blood disorders and lymphatic system: very rarely - leukopenia, thrombocytopenia.
Disorders of immune system: very rarely - hypersensitivity reactions.
Violations by the Metabolism and nutrition: very rarely - hyperglycemia.
Mental disorders: uncommon insomnia / sleep disorders, mood lability.
Disorders of the nervous system: often - dizziness, headache, drowsiness; infrequently - taste disturbances, paresthesia, hypoesthesia, syncope, tremor; very seldom - muscular hypertonicity, neuropathy.
Violations by the organ of vision: rarely - diplopia, visual disturbances.
Violations by the organ of hearing and labyrinth disorders:infrequently - tinnitus.
Violations of the heart: often - a sense of palpitations; very rare - arrhythmia (including bradycardia, ventricular tachycardia, atrial fibrillation), heart attack.
Violations by vessels: often - "tides" of blood to the face; infrequently - a pronounced decrease in blood pressure; very rarely - vasculitis.
Violations of the respiratory system, organs, thoracic and mediastinal disorders; rarely - dyspnea, rhinitis; very rarely - cough.
Disorders of the digestive system: often - abdominal discomfort, pain in the upper abdomen, nausea: infrequently - change in frequency of bowel movements, diarrhea, dryness of the oral mucosa, dyspepsia, vomiting; very rarely - gastritis, gingival hyperplasia, pancreatitis.
Violations of the liver and biliary tract: very rarely - hepatitis, jaundice.
Violations of the skin and subcutaneous tissue disorders: rare - alopecia, rash, sweating,
itching, skin rash, purpura, skin discoloration, photosensitivity; rarely -angionevrotichesky edema, erythema multiforme, rash, Stevens - Johnson.
Violations by musculoskeletal and connective tissue disorders: rarely - arthralgia, back pain, muscle cramps, myalgia.
Violations by the kidneys and urinary tract: rarely - a violation of urination, nocturia, pollakiuria.
Violations by Popov organs and breast cancer:infrequently - erectile dysfunction, gynecomastia.
General disorders and the site of injection: often - fatigue, edema; rarely - fatigue, malaise, weakness, pain in the chest, pain of various localization.
Laboratory and instrumental data: rarely - increase or decrease in body weight; very rarely - increased activity of "liver" enzymes, increased bilirubin concentration in blood plasma.
If any of these instructions side effects occur, compounded, or if you notice any other side effects not mentioned in the instructions, tell your doctor.
CONTRAINDICATIONS
- increased sensitivity to aliskiren (including angioneurotic edema with aliskiren therapy history), amlodipine, increased susceptibility to other
dihydropyridine derivatives or any other component of
the formulation;
- hereditary angioedema, or swelling of the patients on the background of previous treatment with ACE inhibitors or angiotensin II;
- simultaneous with the application of the preparation of ACE inhibitors and
receptor antagonists of angiotensin II (ARA II) patients with type 2 diabetes or impaired renal function (glomerular filtration rate of less than 60 ml / min / 1.73 m 2 );
- anuria, severe renal dysfunction (concentration
blood creatinine> 150 umol / L for men and> 177 umol / L for men and / or estimated glomerular filtration rate (GFR) <30 ml / min / 1.73 m 2 );
- simultaneous with potent inhibitors of P-glycoprotein - cyclosporin, itraconazole;
- severe hypotension (systolic blood pressure less than 90 mm Hg);
- clinically significant aortic stenosis;
- circulatory insufficiency with unstable hemodynamics after acute myocardial infarction;
- shock;
- pregnancy and pregnancy planning, the period of breast
-feeding;
- age of the patients up to 18 years (since safety and
efficacy Rasil drug in children and adolescents under 18 years old are not currently installed).
Carefully
If you have one of these conditions before taking this medication, you should consult with your doctor. Caution must be exercised when using the drug in patients with a reduced volume of circulating blood (BCC), and / or hyponatremia (against application of diuretics in high doses) in patients with nephrotic syndrome or renovascular hypertension, with unilateral or bilateral renal artery stenosis or stenosis of the artery only kidney
(sufficient information for the application is absent), with impaired liver function from mild (5-6 points on the scale
Child-Pugh) to severe (more than 9 points on the Child-Pugh) degree with mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy, chronic heart failure (III-IV functional class classification Heart Association (NYHA)), in patients with hyperkalemia in elderly patients.
PREGNANCY AND LACTATION
Pregnancy
Before the appointment of drugs that affect the RAAS, the physician should inform patients of childbearing age about the possibility of a potential risk to the fetus when using these drugs during pregnancy.
Data on the use of the drug Rasil as a combination of aliskiren, amlodipine, limited in pregnant women.
Given that as the drug enters Rasil aliskiren belonging to Groups RAAS blockers, use is contraindicated in pregnancy drug.
It is known that the use of ACE inhibitors that affect the RAAS in pregnant during trimesters II and III, leading to damage or destruction of the developing fetus. According to a retrospective analysis of ACE inhibitors during I trimester led to the development of the fetus and newborn pathology. Accidental reception ARA II in pregnant described cases of spontaneous abortion, oligohydramnios and renal impairment in the neonate.
Pregnant women and women planning pregnancy, Rasil drug should not be used. If pregnancy is diagnosed during treatment with the drug, treatment should be discontinued immediately.
Breastfeeding
It was found that aliskiren is released into the milk of lactating rats. Data on the allocation of aliskiren and / or amlodipine with breast milk in humans are not available, so the breastfeeding should be discontinued if necessary application Rasil drug.
Fertility
In reproductive toxicity studies in rats showed no undesirable effects of aliskiren and / or amlodipine on fertility. There are no data on the effects of aliskiren and / or amlodipine on fertility in humans.
APPLICATION FOR FUNCTIONS OF THE LIVER
For patients with impaired function of mild and moderate renal (GFR> 30 ml / min / 1.73 m 2 , but <90 mL / min / 1.73 m 2 ) initial correction dose is not required.
Patients with severe impairment of renal function (GFR <30 mL / min / 1.73 m 2 ) drug contraindicated.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Because patients with impaired liver function amlodipine have reduced clearance, which leads to an increase in AUC of about 40-60%, the drug Rasil should be used with caution in these patients.
APPLICATION FOR CHILDREN
Contraindicated in patients under the age of 18 years (since safety and efficacy Rasil drug in children and adolescents under 18 years old are not currently installed).
APPLICATION IN ELDERLY PATIENTS
Correction of the dose in the initial phase of treatment in this patient population is not required.
SPECIAL INSTRUCTIONS
Not simultaneous application of the drug is recommended with ACE inhibitors, ARA II in patients with diabetes or renal function (glomerular filtration rate of less than 60 ml / min / 1.73 m 2 ).
The drug may be used when there is insufficient control of blood pressure monotherapy aliskiren or amlodipine (or other BCCI class of dihydropyridines) for ease of application in patients who have already received aliskiren together with amlodipine single pill at the same doses and for initial treatment of patients with arterial patients hypertension, moderate and severe (systolic blood pressure? 160 mm Hg. Art., and / or diastolic blood pressure ≥ 100 mm Hg. Art.)
In patients with diabetes mellitus periodic monitoring of renal function and blood electrolytes necessary to carry out (in particular, regularly determine the potassium content in blood plasma).
Dual blockade of the RAAS
simultaneous use of aliskiren with other drugs affecting RAAS including ACE ARA and II inhibitors, leads to an increase in the incidence of cases of significant decrease in blood pressure, hyperkalemia, disorders of renal function (including acute renal failure). It is necessary to control blood pressure, kidney function, as well as the content of blood plasma electrolytes Rasil when administering the drug with other drugs that affect the RAAS.
The risk of symptomatic arterial hypotension
After the beginning of therapy with Rasil may occur symptomatic hypotension in patients with
severe hypovolemia and / or reduction of blood electrolytes (diuretics, salt restriction Prema with food, diarrhea or vomiting), and the application Rasil preparation in combination with other drugs, affecting RAAS. It is recommended prior to initiating therapy to correct the above-mentioned conditions, and after the start of therapy with Rasil data patsinetam need additional medical supervision. For patients with uncomplicated hypertension symptomatic hypotension after initiation of drug therapy Rasil occurs in 0.2% of cases, according to clinical trials.
Renal dysfunction
Clinical studies on the use Rasil drug in hypertensive patients with severe renal impairment (creatinine level? 150 mmol / l for women and? 177 mmol / l for men and / or GFR <30 ml / min), hemodialysis history, nephrotic syndrome or renovascular hypertension have been conducted.
Use of the drug Rasil in monotherapy in patients with impaired renal function (GFR of less than 30 ml / min / 1.73 m 2 ), and in combination with other drugs that affect the RAAS in patients with impaired renal function (GFR of less than 60 ml / INN / 1 73 m 2 ) is contraindicated.
In applying the drug Rasil, as well as other means of influencing the RAAS, care must be taken in the case of patients predisposing to disruption of renal function, such as hypovolemia (e.g., due to acute blood loss, severe or prolonged diarrhea and / or vomiting ), heart disease, liver disease or kidney disease. In the event of any signs of renal failure, the drug should be withdrawn.
Renal artery stenosis
in patients with renal artery stenosis (unilateral or bilateral) when using the drug Rasil, as well as other agents affecting the RAAS, there is a risk of impaired renal function, including acute
renal failure; when applying Rasil drug in these patients requires special care.
With the development of impaired renal function, drug treatment should be discontinued.
Patients with mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy
should be particularly careful in the application of amlodipine (and other vasodilating agents) in patients with mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy.
Heart failure
It is recommended to be used with caution blockers "slow" calcium channels (including amlodipine) in patients with chronic heart failure III-IV functional class on classification NYHA.
Angina and acute myocardial infarction
after starting treatment or increasing the dose of amlodipine may develop angina attack or acute myocardial infarction, particularly in patients with severe coronary artery disease.
Patients aged ≥65 years of age
should use caution when using the drug in patients aged? 65 years.
Anaphylactic reactions and angioedema
have been reported cases of anaphylactic reactions and angioedema during therapy
preparations containing aliskiren. In controlled clinical trials, angioedema on
background therapy aliskiren rarely developed at a frequency comparable to placebo or hydrochlorothiazide.
Anaphylactic reactions were detected when using the drug in clinical practice, the frequency of occurrence
is unknown. In the case of any symptoms suggestive of hypersensitivity reaction (eg, difficulty breathing or swallowing, swelling of the face, eyes, lips and / or tongue, limbs) patients should discontinue treatment with the drug and consult a doctor. It is necessary to take appropriate therapeutic measures and to monitor the patient's condition. The risk of hypersensitivity reactions is increased in patients with a history of allergy or bronchial asthma history. Patsieptov should be warned of the need to inform the doctor of any instances of allergic reactions.
Effects on ability to drive and use machinery
When you receive Rasil drug, as well as other antihypertensive agents, caution should be exercised when driving and operating machinery (risk of dizziness).
OVERDOSE
Data on cases of overdose Rasil no drug.
The symptoms
most likely clinical manifestation of overdose is marked decrease in blood pressure caused by antihypertensive action of Aliskiren and Amlodipine.
Amlodipine overdose can cause peripheral vasodilatation and reflex tachycardia. Against the background of amlodipine also been cases of significant decrease in blood pressure (sometimes longer), until the development of fatal shock.
Treatment
In case of clinical manifestations of significant decrease in blood pressure, is a symptomatic and supportive therapy, including monitoring of heart and lung function, giving the patient a horizontal position with the raised feet, control BCC and diuresis in / introduction dopamine, phenylephrine (Mezaton). Amlodipine absorption in the gastrointestinal grakte (F
