Equamer capsules 5mg + 10mg + 10mg №30

Indications and usage

Equamer^® shown as replacement therapy in adult patients, whose condition is adequately controlled by the use of Amlodipine, lisinopril and Rosuvastatin in the same doses as in the preparation of Equmeamer^®in the treatment of hypertension and concomitant dyslipidemia:

- primary hypercholesterolemia (type IIa according to Fredrickson's classification, with the exception of familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb according to Fredrickson's classification) when diet and other non-drug methods (for example, exercise, weight loss) are insufficient;

- familial homozygous hypercholesterolemia, when a diet or other lipid-lowering therapy (for example, LDL-apheresis) is not effective enough;

- hypertriglyceridemia (type IV according to Fredrickson's classification).

The drug is taken orally, regardless of the time of meals.

As a rule, the fixed-dose combination drug is not suitable for initial therapy.

Equamer^® used as a replacement therapy for adults patients who already receive amlodipine, lisinopril, and rosuvastatin in the same doses as in this preparation, and in which the titrated optimal maintenance doses are:

The recommended dose of the drug is 1 caps / day. The maximum daily dose is 1 caps.

If a dose adjustment is necessary, dose titration should be carried out using amlodipine, lisinopril and rosuvastatin separately.

Have patients with renal failure during drug therapy equamer^® should monitor kidney function, the content of potassium and sodium in the blood plasma. In case of deterioration in renal function, the drug should be discontinued. Such patients are recommended individual selection of doses of individual active ingredients. Use of the drug in patients with severe renal failure contraindicated.

The drug is contraindicated patients with liver disease in the active phase and patients with severely impaired liver function (more than 9 points on the Child-Pugh scale).

Safety and efficacy of the drug in children and teenagers not installed.

Have elderly patients the drug should be used with caution. In clinical studies, no data were obtained on the change in the efficacy or safety profile of amlodipine, lisinopril or rosuvastatin, depending on age.

When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different races, there was an increase in the systemic concentration of rosuvastatin in the blood plasma among patients of the Mongoloid race. This fact should be taken into account when prescribing the drug Equamer^® this group of patients. When prescribing rosuvastatin in a dose of 10 mg and 20 mg, the recommended initial dose of rosuvastatin for patients of the Mongoloid race should be 5 mg.

In carriers of the SLCO1B1 genotypes (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA, there was an increase in exposure (AUC) of rosuvastatin compared to the carriers of the SLC01B1 c.521TT and ABCG2 genotypes c.421CC. For patients with genotypes c.521CC and c.421AA, the recommended maximum dose of rosuvastatin is 20 mg / day.

Rosuvastatin binds to various transport proteins (in particular, c OATP1B1 and BCRP). When rosuvastatin is used together with medications (such as cyclosporine, some HIV protease inhibitors (including a combination of ritonavir with atazanavir, lopinavir, and / or tipranavir), the concentration of rosuvastatin in the blood plasma may increase due to interaction with transport proteins, myopathy may increase (including rhabdomyolysis In such cases, you should evaluate the possibility of prescribing alternative therapy or the temporary cessation of taking rosuvastatin. If necessary, the ratio of benefits and risks of concomitant therapy with rosuvastatin should be evaluated and the possibility of reducing its dose should be considered.

Adverse reactions

Adverse adverse reactions are presented according to system-organ classes according to the MedDRA classification and with the frequency of occurrence: very often - 1/10 of appointments (≥10%); often 1/100 of appointments (≥1%, but <10%); infrequently - 1/1000 of appointments (≥0.1%, but <1%); rarely, 1/10 000 appointments (≥0.01%, but <0.1%); very rarely - less than 1/10 000 appointments (<0.01%); frequency unknown - insufficient data to estimate development frequency.

Within each group, adverse reactions are distributed in order of decreasing importance.

With separate treatment with amlodipine, lisinopril and rosuvastatin, the following undesirable adverse reactions were reported.

Amlodipine

Hemic and lymphatic: very rarely - thrombocytopenic purpura, leukopenia, thrombocytopenia.

Allergic reactions: infrequently - pruritus, rash (including erythematous and maculo-papular rash, urticaria); very rarely - angioedema, erythema multiforme.

Metabolism and nutrition: very rarely - hyperglycemia.

Psychological: infrequently - mood lability, unusual dreams, anxiety, depression, anxiety; very rarely - apathy, agitation, amnesia.

Nervous system: often - headache, dizziness, fatigue, drowsiness; infrequently - asthenia, malaise, hypesthesia, paresthesia, peripheral neuropathy, tremor, muscle rigidity, insomnia, taste perversion; rarely seizures; very rarely - migraine, increased sweating, ataxia, parosmia.

Special senses: infrequently - diplopia, disturbance of accommodation, xerophthalmia, conjunctivitis, eye pain, blurred vision.

From the organ of hearing: infrequently - tinnitus.

Cardiovascular: often - increased heartbeat, peripheral edema (ankles and feet), "hot flashes"; infrequently - pronounced decrease in blood pressure; very rarely - the development or aggravation of chronic heart failure, cardiac arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain, syncope, vasculitis, orthostatic hypotension.

Respiratory: infrequently - shortness of breath, rhinitis, nosebleeds; very rarely - cough.

Gastrointestinal: often - nausea, abdominal pain; infrequently - vomiting, constipation, diarrhea, flatulence, dyspepsia, anorexia, dryness of the oral mucosa, thirst; rarely - gingival hyperplasia, increased appetite; very rarely - pancreatitis, gastritis, jaundice (usually cholestatic), hyperbilirubinemia, increased activity of hepatic transaminases, hepatitis.

Urogenital: infrequently - frequent urination, painful urination, nocturia; very rarely - dysuria, polyuria.

From the genital and breast organs: infrequently - erectile dysfunction, gynecomastia.

Skin and Subcutaneous Tissues: rarely - dermatitis; very rarely - alopecia, xerodermia, "cold" sweat, violation of skin pigmentation.

Musculoskeletal system: infrequently - arthralgia, muscle cramps, myalgia, back pain, arthrosis; rarely - myasthenia.

Other: infrequently - pain of unspecified location, increase / decrease in body weight.

Lisinopril

Hemic and lymphatic: rarely, hemoglobin and hematocrit decrease; very rarely, bone marrow suppression, lymphadenopathy, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, hemolytic anemia, anemia; frequency is unknown - erythropenia.

Allergic reactions: infrequently - skin rash, itching; rarely, urticaria, angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx; very rarely - angioedema of the intestine, autoimmune diseases, Stevens-Johnson syndrome, toxic epidermal necrolysis, exudative erythema multiforme.

On the part of the endocrine system: unknown frequency - syndrome of inadequate secretion of antidiuretic hormone.

Metabolism and nutrition: very rarely - hypoglycemia.

Psychological: often - sleep disturbance; infrequently - mood lability; rarely - confusion; frequency unknown - confusion, depression.

Nervous system: often - dizziness, headache; infrequently - paresthesia, drowsiness; rarely, asthenic syndrome; frequency unknown - syncope, convulsive twitching of the muscles of the face and limbs.

Cardiovascular: often - excessive decrease in blood pressure; infrequently - chest pain,myocardial infarction (due to pronounced decrease in blood pressure in high-risk patient groups), impaired cerebral circulation (due to pronounced decrease in blood pressure in high-risk patient groups), Raynaud's syndrome; rarely - tachycardia, bradycardia, worsening of the course of chronic heart failure, impaired AV conduction, rapid heartbeat, orthostatic hypotension; frequency is unknown - vasculitis.

Respiratory: often - dry cough, sinusitis, allergic alveolitis / eosinophilic pneumonia; infrequently - rhinitis; very rarely - bronchospasm; frequency unknown - shortness of breath.

Gastrointestinal: often - liver failure; infrequently - dyspepsia, taste perversion, abdominal pain; rarely, dryness of the oral mucosa; very rarely - pancreatitis, hepatocellular and cholestatic jaundice, hepatitis; frequency unknown - anorexia.

Urogenital: often - impaired renal function; rarely, acute renal failure, uremia; very rarely - oliguria, anuria; frequency is unknown - proteinuria.

From the genital and breast organs: infrequently - reduction of potency; rarely - gynecomastia.

Skin and Subcutaneous Tissues: rarely - alopecia, psoriasis, photosensitivity; very rarely - increased sweating, pemphigus, skin pseudolymphoma.

Musculoskeletal system: frequency unknown - myalgia, arthralgia / arthritis.

From the laboratory and instrumental studies: infrequently - hyperkalemia, hyponatremia, increased concentration of urea and creatinine in the blood serum; rarely, increased liver enzyme activity, hyperbilirubinemia; very rarely - increased ESR, increased titer of antinuclear antibodies; frequency is unknown - eosinophilia, leukocytosis.

Other: frequency is unknown - fever (there are reports of lupus-like syndrome, which may include fever, myalgia, arthralgia / arthritis, an increase in antinuclear antibody titer, an increase in ESR, eosinophilia, leukocytosis, may also develop rashes, photosensitivity reactions or other skin manifestations).

With the simultaneous use of ACE inhibitors and gold preparations for intravenous injection (sodium aurothiomalate), a symptom complex is described, including facial flushing, nausea, vomiting, and a decrease in blood pressure.

Rosuvastatin

The side effects observed with rosuvastatin are usually mild and do not go away on their own. As with the use of other inhibitors of HMG-CoA reductase, the frequency of side effects is mainly dose-dependent.

Hemic and lymphatic: the frequency is unknown - thrombocytopenia.

Allergic reactions: infrequently - pruritus, rash, urticaria; rarely, hypersensitivity reactions, including angioedema; frequency is unknown - Stevens-Johnson syndrome.

On the part of the endocrine system: often - type 2 diabetes (frequency will depend on the presence or absence of risk factors (fasting glucose concentration ≥5.6 mmol / l, BMI> 30 kg / m², an increased concentration of triglycerides, a history of arterial hypertension)); frequency is unknown - dysfunction of the thyroid gland.

Psychological: frequency unknown - depression.

Nervous system: often - headache, dizziness; very rarely, polyneuropathy, memory loss or loss; frequency is unknown - peripheral neuropathy, sleep disorders (including insomnia and nightmares).

Respiratory: frequency is unknown - cough, shortness of breath.

Gastrointestinal: often - constipation, nausea, abdominal pain; rarely - pancreatitis, increased activity of hepatic transaminases; very rarely - jaundice, hepatitis; frequency is unknown - diarrhea.

Urogenital: hematuria is very rare; frequency is unknown - proteinuria.

From the genital and breast organs: frequency unknown - gynecomastia.

Musculoskeletal system: often myalgia; rarely, myopathy (including myositis), rhabdomyolysis with or without the development of acute renal failure; very rarely - arthralgia; unknown frequency - immune-mediated necrotizing myopathy, tendon diseases, in some cases complicated by rupture, temporary increase in CPK activity. In the case of increased activity of CPK (more than 5 times compared with VGN) therapy should be discontinued.

From the laboratory and instrumental studies: unknown frequency - increase in the concentration of bilirubin, blood glucose, increase in the concentration of glycosylated hemoglobin, activity of GGT, alkaline phosphatase.

Other: often - asthenia; frequency unknown - peripheral edema.

The following side effects have been reported with the use of some HMG-CoA reductase inhibitors:

- sexual dysfunction;

- in extremely rare cases, interstitial lung disease, especially with prolonged therapy.

If any of the side effects indicated in the instructions are aggravated or any other side effects that are not indicated in the instructions are noted, the patient should be informed about this by the attending physician.

- angioedema in history, including when using ACE inhibitors;

- hereditary or idiopathic angioedema;

- severe hypotension (systolic blood pressure less than 90 mm Hg. Art.);

- obstruction of the excretory tract of the left ventricle (including severe aortic stenosis);

- hemodynamically unstable heart failure after acute myocardial infarction;

- liver disease in the active phase, including a persistent increase in the activity of transaminases in the serum, as well as any increase in the activity of transaminases (more than 3 times as compared with VGN);

- severe renal dysfunction (CC less than 30 ml / min);

- myopathy;

- predisposition to the development of myotoxic complications;

- simultaneous use with aliskiren-containing drugs in patients with diabetes or renal failure (GFR less than 60 ml / min / 1.73 m²);

- simultaneous use of cyclosporine;

- pregnancy;

- lactation period (breastfeeding);

- use in women who do not use adequate methods of contraception;

- children's and teenage age up to 18 years (efficiency and safety are not established);

- lactose intolerance, lactase deficiency or glucose / galactose malabsorption syndrome;

- Hypersensitivity to amlodipine or other dihydropyridine derivatives;

- Hypersensitivity to lisinopril or other ACE inhibitors;

- Hypersensitivity to rosuvastatin;

- Hypersensitivity to any of the auxiliary components of the drug.

Experience with rosuvastatin in patients with a score above 9 on the Child-Pugh scale is absent.

WITH caution the drug should be prescribed for aortic stenosis; mitral stenosis; hypertrophic obstructive cardiomyopathy; hypotension; cerebrovascular diseases (including cerebrovascular insufficiency); CHD; coronary insufficiency; CHF of non-ischemic etiology of III-IV functional class according to NYHA classification; acute myocardial infarction (and for 1 month after it); unstable angina; SSS (severe tachycardia or bradycardia); severe autoimmune systemic diseases of the connective tissue (including systemic lupus erythematosus, scleroderma); oppression of bone marrow hematopoiesis; diabetes; hyperkalemia; bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney;condition after kidney transplantation; renal failure mild and moderate severity (CC 30-80 ml / min); azotemia; primary aldosteronism; dietary salt control; conditions accompanied by a decrease in BCC (including vomiting, diarrhea); mild hepatic insufficiency (5-6 points on the Child-Pugh scale) and moderate severity (7-9 points on the Child-Pugh scale); hypothyroidism; indication in a personal or family history of hereditary muscular diseases and muscular toxicity in history with the use of other HMG-CoA reductase inhibitors or fibrates; with the simultaneous use of fibrates; a history of liver disease; sepsis; extensive surgical interventions; injuries; severe metabolic, endocrine, or water-electrolyte disturbances or uncontrolled convulsive seizures; conditions in which there is an increase in the plasma concentration of rosuvastatin; alcohol abuse; in patients of the Mongoloid race; elderly patients.

Pregnancy

Use of the drug Equamer^® contraindicated in pregnancy.

Adequate strictly controlled clinical studies on the action of the drug Equamer^® during pregnancy was not carried out.

The use of ACE inhibitors in the II and III trimesters of pregnancy can cause death of the fetus and newborn.Perhaps the development of low water during pregnancy, as well as hypoplasia of the skull bones, deformation of the bones of the skull and face, lung hypoplasia and impaired kidney development in the newborn.

Since cholesterol and other cholesterol biosynthesis products are important for fetal development, the potential risk of inhibition of HMG-CoA reductase exceeds the benefits of rosuvastatin in pregnancy.

Women of reproductive age should use adequate methods of contraception. If pregnancy occurs during therapy, the drug should be immediately discontinued and, if necessary, alternative treatment should be prescribed.

Do not start therapy with Equamer^® during pregnancy. When planning pregnancy, it is necessary to switch to alternative therapy with a proven safety profile during pregnancy.

Lactation period

Use of the drug Equamer^® contraindicated during breastfeeding. It is not known whether the active ingredients are excreted in breast milk. It is known that they penetrate the milk of lactating rats. If necessary, the use of the drug during lactation breastfeeding should be stopped.

Fertility

Adequate strictly controlled clinical studies on the action of the drug Equamer^® fertility was not carried out.

The drug is contraindicated in patients with liver disease in the active phase and in patients with severely impaired liver function (more than 9 points on the Child-Pugh scale).

Precautions should be prescribed the drug for hepatic insufficiency of mild severity (5-6 points on the Child-Pugh scale) and moderate severity (7-9 points on the Child-Pugh scale).

With caution should be prescribed the drug in case of renal failure of mild and moderate severity (CC 30-80 ml / min).

The use of the drug in patients with severe renal failure (CC less than 30 ml / min) is contraindicated.

The drug is contraindicated in children and adolescents under 18 years of age (efficacy and safety have not been established).

Have elderly patients the drug should be used with caution.

special instructions

If a patient is hospitalized in a hospital, he must inform the doctor that he is taking the drug Equamer.^®.

If the patient forgot to take a capsule of the drug Equamer^®The following capsule should be taken at the usual time. You should not take a double dose to make up the missed dose.

When using the drug Equamer^® recommendations for the use of individual components of the drug, described in detail below, should be considered.

Amlodipine

It is necessary to maintain dental hygiene and observation at the dentist (to prevent pain, bleeding and gum hyperplasia).

Elderly patients may increase T_1/2 and decrease clearance of amlodipine.Changing doses is not required, but more careful monitoring of patients in this category is needed.

The efficacy and safety of the use of amlodipine in hypertensive crisis has not been established.

Despite the absence of withdrawal syndrome in BMCC, it is advisable to stop the treatment with amlodipine, gradually reducing the dose of the drug.

Against the background of the use of amlodipine in patients with CHF of non-ischemic genesis of functional class III and IV, according to the NYHA classification, there was an increase in the incidence of pulmonary edema, despite the absence of signs of worsening heart failure.

Lisinopril

Symptomatic arterial hypotension

Most often, an excessive decrease in blood pressure occurs with a decrease in BCC, caused by diuretic therapy, a decrease in table salt in food, dialysis, diarrhea and vomiting. In patients with CHF, as in the presence of concomitant renal failure, and in its absence, the development of symptomatic arterial hypotension is possible. Hypotension was more frequently detected in patients with severe heart failure as a result of the use of diuretic in high doses, hyponatremia or impaired renal function. In such patients, therapy should begin under the strict supervision of a physician (with caution, select the dose of lisinopril and diuretics). Similar rules should be followed when prescribing lisinopril to patients with coronary artery disease, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to myocardial infarction or stroke.

In the event of an excessive decrease in the patient's blood pressure, the patient should be laid down and, if necessary, compensated for the loss of fluid (IV infusion of 0.9% sodium chloride solution). The transient hypotensive reaction is not a contraindication for taking the next dose of lisinopril.

When lisinopril is used in some patients with CHF, but with normal or decreased blood pressure, there may be a decrease in blood pressure, which is usually not a reason to discontinue therapy. If arterial hypotension becomes symptomatic, it is necessary to reduce the dose or discontinue therapy with lisinopril.

Patients who are at risk of developing symptomatic hypotension (who are on a diet with salt restriction or salt-free diet) with or without hyponatremia, as well as in patients who received diuretics in high doses, must compensate for the loss of fluids and salts before starting treatment.

It is necessary to control the antihypertensive effect of the initial dose of lisinopril.

Aortic and mitral valve stenosis / hypertrophic obstructive cardiomyopathy

As in the case of other ACE inhibitors, lisinopril should be used with caution in patients with mitral valve stenosis and obstruction of the left ventricular excretory tract (aortic stenosis or hypertrophic obstructive cardiomyopathy).

Acute myocardial infarction

The use of standard therapy (thrombolytic agents, Acetylsalicylic acid as an antiplatelet agent, beta-blockers) is shown.

Lisinopril can be used in conjunction with the on / in the introduction of Nitroglycerin or with the use of nitroglycerin in the form of a transdermal system.

Lysinopril therapy should not be initiated in patients with acute myocardial infarction, who are at risk of further serious hemodynamic deterioration after the use of vasodilators (patients with systolic BP 100 mmHg or less, patients with cardiogenic shock). During the first 3 days after myocardial infarction, the dose of lisinopril should be reduced if systolic BP is 120 mmHg. st. or lower. Maintenance doses of lisinopril should be reduced to 5 mg or temporarily to 2.5 mg if systolic blood pressure is 100 mmHg. st. or lower. If arterial hypotension persists (systolic blood pressure less than 90 mmHg for more than 1 hour), lisinopril should not be continued.

Renal dysfunction

In patients with CHF, an excessive decrease in blood pressure after the start of treatment with ACE inhibitors can lead to a further deterioration in renal function. Cases of acute renal failure.

In patients with bilateral renal artery stenosis or arterial stenosis of a single kidney who received ACE inhibitors, there was an increase in serum urea and creatinine, usually reversible after stopping treatment and more common in patients with renal insufficiency.

Lisinoporil is not used for acute myocardial infarction in patients with severe impaired renal function, established when the serum creatinine concentration exceeds 177 µmol / L and / or proteinuria exceeds 500 mg / day.If renal dysfunction develops during lisinopril therapy (serum creatinine concentration in excess of 265 µmol / L, or doubling the value compared to the value before treatment), the need for further use of lisinopril should be evaluated.

Hypersensitivity / Angioedema

Angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx, which can occur during any period of therapy, has been rarely seen in patients treated with an ACE inhibitor, including lisinopril. In this case, therapy with lisinopril should be stopped as soon as possible and the patient should be monitored until symptoms are fully regressed. In cases when edema occurs only on the face and lips, this condition most often disappears without treatment, however, it is possible to use antihistamines.

Angioedema with laryngeal edema can be fatal. Swelling of the tongue, epiglottis, or larynx can cause airway obstruction, therefore, it is necessary to immediately conduct appropriate therapy (0.3-0.5 ml of 1: 1000 solution of epinephrine (adrenaline) s / c) and / or take measures to ensure the airway is permeable. It was noted that patients of the Negroid race taking ACE inhibitors developed angioedema more often than patients of other races.

In patients taking ACE inhibitors, angioedema was rarely observed.These patients complained of abdominal pain (with or without nausea and vomiting); in some cases, no previous angioedema of the face was observed, and C-1 esterase activity was within the normal range. Angioedema of the intestine was diagnosed according to computed tomography of the gastrointestinal tract or ultrasound, or during surgery; symptoms disappeared after discontinuation of the ACE inhibitor. The differential diagnosis of abdominal pain in patients taking ACE inhibitors should take into account the development of angioedema.

In patients with a history of angioedema, not associated with previous treatment with ACE inhibitors, the risk of its development during treatment with an ACE inhibitor may be increased.

Anaphylactic reactions during the desensitization procedure

Patients receiving ACE inhibitors during a course of desensitization (for example, hymenoptera poison), in very rare cases, may develop life-threatening Anaphylactic reactions . This can be avoided if you temporarily cancel the ACE inhibitor before each desensitization procedure begins.

Liver dysfunction

The use of ACE inhibitors can lead to the development of cholestatic jaundice with a progression up to fulminant necrosis of the liver, so it is necessary to stop taking lisinopril with increased activity of hepatic transaminases and the appearance of cholestasis symptoms.

Hemodialysis patients

Anaphylactic reactions are also observed in patients on hemodialysis using high-flow membranes (for example, AN69^®) and taking simultaneously ACE inhibitors. If hemodialysis is needed, it is necessary to use another type of membrane or another antihypertensive.