Amlodipine + Lysinopril - instructions for use, dose, side effects, contraindications

The combination of lisinopril with amlodipine in a single medicine can prevent the development of possible undesirable effects caused by one of the active substances. So, the calcium channel blocker, directly expanding the arterioles, can lead to a delay in sodium and fluid in the body, and, therefore, can activate RAAS. The ACE inhibitor blocks this process.

Pharmacokinetics:

Lisinopril

After oral administration lisinopril absorbed from the digestive tract, its absorption can vary from 6 to 60%. Bioavailability - 29%. Eating does not affect the absorption of lisinopril. C_maxin plasma is achieved in 6 hours.

Almost does not bind to blood plasma proteins. Permeability through the BBB and the placental barrier is low.

Lizinopril is not metabolized in the body.

It is excreted unchanged in the urine, T_1/2 - 12.6 h.

Pharmacokinetics in special clinical cases

In elderly patients, the concentration of lisinopril in blood plasma and AUC is 2 times greater 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, with an increase in the time to reach C_maxin blood plasma and an increase in T_1/2.

Lizinopril is excreted from the body by hemodialysis.

Amlodipine

After oral administration amlodipine slowly and almost completely (90%) is absorbed from the digestive tract. The bioavailability of amlodipine is 64% -80%. C_maxin the serum is observed after 6-10 hours. The intake of food does not affect the absorption of amlodipine.

Most of the amlodipine, which is in the blood (95% -98%), binds to blood plasma proteins. C_ss are achieved after 7-8 days of therapy. Average V_dis 20 l / kg body weight, indicating that most of the amlodipine is in the tissues, and the smaller - in the blood. Amlodipine penetrates through the BBB.

Amlodipine undergoes a slow but active metabolism in the liver in the absence of a significant "first pass" effect. Metabolites do not have significant pharmacological activity.

10% of amlodipine is excreted unchanged in urine, 60% in the form of metabolites; 20-25% - in the form of metabolites with bile through the intestine. Excretion has a two-phase character. T_1/2the final phase is 30-50 h.

Pharmacokinetics in special clinical cases

In elderly patients (over 65 years of age) the excretion of amlodipine is slowed (T_{1/2 -} 65 h) compared with young patients, but this difference has no clinical significance.

In patients with hepatic insufficiency, the T_1/2suggests that with prolonged use, cumulation of amlodipine in the body will be higher (T_1/2 - up to 60 hours).

Renal failure does not significantly affect the kinetics of amlodipine. When hemodialysis is not removed.

Amlodipine and lisinopril

Interaction between the active substances that make up the drug is unlikely. AUC, time of achievement and C value_maxin blood plasma, T_1/2 Do not undergo changes in comparison with the indices of each individual active substance. Eating does not affect the absorption of active substances.

Indications:

Essential arterial hypertension (patients who are shown combined therapy).

ICD-10

IX.I10-I15.I10 Essential [primary] hypertension

Contraindications:

Quincke's edema in the anamnesis, incl. on the background of the use of ACE inhibitors; hereditary or idiopathic angioedema; hemodynamically significant stenosis of the aorta or mitral valve; hypertrophic obstructive cardiomyopathy; severe arterial hypotension (systolic blood pressure less than 90 mm Hg); cardiogenic shock; unstable angina (with the exception of Prinzmetal's stenocardia); heart failure after acute myocardial infarction (within the first 28 days); pregnancy; lactation period; children and adolescents under 18 years of age (efficacy and safety not established in this age group);hypersensitivity to the components of the drug; increased sensitivity to lisinopril and other ACE inhibitors; hypersensitivity to other dihydropyridine derivatives.

With caution should be used in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney with progressive azotemia, with azotemia, primary hyperaldosteronism, with severe renal dysfunction, kidney transplantation, hyperkalemia, liver function abnormalities, arterial hypotension, cerebrovascular diseases including cerebral circulatory insufficiency), coronary artery disease, coronary insufficiency, SSSU (pronounced bradycardia, tachycardia), chronic cardiac insufficiency of non-ischemic etiology of III-IV functional class according to NYHA classification, with aortic stenosis, mitral stenosis, acute myocardial infarction (and within 1 month after myocardial infarction), autoimmune systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus ), with oppression of bone marrow hematopoiesis, diabetes mellitus, diet with restriction of table salt, with hypovolemic conditions (incl.as a result of diarrhea, vomiting), in elderly patients, in hemodialysis using high-permeability dialysis membranes with high permeability.

Carefully:

Pregnancy and lactation:

The drug is contraindicated for use in pregnancy.

When diagnosing pregnancy, the drug should be stopped immediately.

Lizinopril can be excreted in breast milk. There is no evidence that amlodipine is excreted in breast milk. However, it is known that other calcium channel blockers of dihydropyridine derivatives are excreted in breast milk. The use of the drug during lactation is not recommended. If you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

The drug is taken orally 1 time / day, regardless of food intake, with a sufficient amount of liquid.

The recommended dose is 1 tab. 1 time / day. To determine the optimal initial and maintenance dose for patients with renal insufficiency dose should be titrated and determined individually, applying separately lisinopril and amlodipine. The drug at a dose of 10 mg / 5 mg is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 10 mg and 5 mg, respectively. 20 mg / 5 mg is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 20 mg and 5 mg, respectively. Dosage of 20 mg / 10 mg is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 20 mg and 10 mg, respectively. During treatment with the drug it is necessary to monitor the kidney function, the content of potassium and sodium in the blood serum. If the kidney function worsens, the drug should be discontinued and replaced with lisinopril and amlodipine in adequate doses.

Excretion of amlodipine may be delayed in patients with impaired hepatic function. Clear recommendations on the dosage regimen in such cases are not established, so the drug should be administered with caution to patients with hepatic impairment.

In clinical studies, age-related changes in efficacy or safety profile for amlodipine and lisinopril have not been observed.Dosage of 10 mg / 5 mg is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 10 mg and 5 mg, respectively.

Side effects:

Lisinopril

From the hemopoietic system: very rarely - oppression of bone marrow circulation, agranulocytosis, leukopenia, neutropenia, thrombocytopenia, hemolytic anemia, anemia, lymphadenopathy.

From the immune system: very rarely - vasculitis, a positive test for antinuclear antibodies.

From the side of metabolism and nutrition: very rarely - hypoglycemia.

Mental disorders: infrequent - mood changes, sleep disturbances; rarely - a violation of the psyche.

From the nervous system: often - dizziness, headache, drowsiness; infrequently - systemic dizziness, paresthesia, dysgeusia, convulsive twitching of the muscles of the extremities and lips; rarely confusion.

From the side of the cardiovascular system: often - a marked decrease in blood pressure, orthostatic hypotension; infrequently, myocardial infarction, AV conduction disorder, bradycardia, tachycardia, palpitations, worsening of the course of chronic heart failure, chest pain, cerebrovascular accident, Raynaud's syndrome.

From the respiratory system: often - dry cough; infrequently - rhinitis; rarely shortness of breath; very rarely - bronchospasm, allergic alveolitis / eosinophilic pneumonia, sinusitis.

From the digestive tract: often - diarrhea, vomiting; infrequently - abdominal pain, nausea, indigestion; rarely dry mouth; very rarely - pancreatitis, intestinal angioedema.

From the liver and bile ducts: very rarely - liver failure, cholestatic jaundice, hepatitis.

Allergic reactions: infrequently - allergic reactions / angioedema, swelling of the face, limbs, lips, tongue, vocal cords and / or larynx, skin rash, skin itch, photosensitivity; rarely - psoriasis, urticaria rash, alopecia; very rarely - toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, vulgar pemphigus, increased sweating, pseudolymphoma of the skin.

From the musculoskeletal system: rarely - arthralgia, myalgia, arthritis.

From the side of the kidneys and urinary tract: often - a violation of kidney function; rarely acute renal failure, uremia; very rarely - oliguria / anuria.

On the part of the reproductive system and mammary glands: infrequently - impotence; rarely - gynecomastia.

Common reactions: infrequent - increased fatigue, asthenia.

On the part of laboratory indicators: infrequently - increased concentration of urea and creatinine in the blood serum, hyperkalemia, increased activity of hepatic enzymes; rarely - reduction of hemoglobin and hemato crit, erythropenia, hyperbilirubinemia, hyponatremia.

Amlodipine

From the hemopoietic system: very rarely - thrombocytopenia.

From the immune system: very rarely - hypersensitivity.

From the side of metabolism and nutrition: very rarely - hyperglycemia.

Mental disorders: infrequent - insomnia, unusual dreams, mood changes, increased excitability, depression, anxiety; rarely - apathy, agitation.

From the nervous system: often - drowsiness, dizziness, headache; infrequently - syncope, tremor, paresthesia, dysgeusia, hypoesthesia; rarely migraine; very rarely - peripheral neuropathy, ataxia, amnesia, parosmia.

From the side of the organ of vision: infrequently - a vision disorder (diplopia, a violation of accommodation), xerophthalmia, conjunctivitis, pain in the eyes.

From the side of the organ of hearing: infrequently - noise in the ears.

From the cardiovascular system: often - heart palpitations, skin hyperemia; infrequent - marked decrease in blood pressure, orthostatic hypotension; rarely - exacerbation of chronic heart failure; very rarely - myocardial infarction, ventricular tachycardia, atrial fibrillation, arrhythmia, vasculitis.

From the respiratory system: infrequently - dyspnoea, rhinitis, nosebleeds; very rarely - cough.

From the side of the digestive tract: often - pain in the abdomen, nausea; infrequently - vomiting, indigestion, constipation or diarrhea, dry mouth, anorexia, thirst; rarely - increased appetite; very rarely - pancreatitis, gastritis, gingival hyperplasia.

From the liver and biliary tract: very rarely - cholestasis, jaundice, hepatitis.

Allergic reactions: infrequently - skin rash, skin itch, purpura, xeroderma; rarely - dermatitis; very rarely - angioedema, urticaria rash, erythema multiforme, increased sweating, cold sweat, alopecia, skin discoloration.

From the side of the kidneys and urinary tract: infrequent - urination disorder, nocturia, increased frequency of urination.

From the musculoskeletal system: infrequently - arthralgia, myalgia, muscle cramps, back pain, arthrosis; rarely - myasthenia gravis.

On the part of the reproductive system and mammary glands: infrequently - impotence, gynecomastia.

General reactions: often - peripheral edema, increased fatigue; infrequently - chest pain, pain, malaise, asthenia.

From the side of laboratory indicators: infrequently - increase or decrease in body weight; very rarely - increased activity of hepatic enzymes.

Overdose:

Amlodipine

Symptoms: marked decrease in blood pressure with possible development of reflex tachycardia and excessive peripheral vasodilation (risk of development of severe and persistent arterial hypotension, including with the development of shock and death).

Treatment: gastric lavage, the appointment of activated charcoal, maintenance of cardiovascular function, control of the functions of the cardiovascular and respiratory systems, giving the patient a horizontal position with raised legs, control of bcc and diuresis. To restore the vascular tone - the use of vasoconstrictor (in the absence of contraindications to their use); with the purpose of elimination of consequences of blockade of calcium channels - in / in the introduction of calcium gluconate. Hemodialysis is ineffective.

Lisinopril

Symptoms: marked decrease in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, increased irritability.

Treatment: gastric lavage, taking activated charcoal, giving the patient a horizontal position with raised legs, replenishment of BCC - IV injection of plasma-substituting solutions, symptomatic therapy, monitoring of cardiovascular and respiratory systems, bcc, urea, creatinine and electrolytes in blood serum, as well as diuresis. Lisinopril can be removed from the body by hemodialysis.

Interaction:

Lisinopril

Potassium-sparing diuretics (for example, spironolactone, amiloride and triamterene), nutritional supplements with potassium, potassium-containing salt substitutes and other medications that can raise serum potassium levels (eg, heparin) can lead to hyperkalemia when combined with ACE inhibitors, especially in patients with renal insufficiency and other kidney disease in the anamnesis. When assigning a drug that affects the concentration of potassium, together with lisinopril should monitor the concentration of potassium in blood serum.Therefore, co-administration should be carefully justified and carried out with extreme caution and regular monitoring as the level of potassium in the blood serum and renal function. Potassium-sparing diuretics can be taken together with the drug only under the condition of medical control.

In the case of the appointment of a diuretic to a patient receiving a hypotensive effect, as a rule, it increases. Therefore, it must be taken with extreme caution in combination with diuretics. Lisinopril softens the potassium -uretic effect of diuretics.

With the simultaneous use of other antihypertensive drugs may increase the antihypertensive effect of the drug.

With simultaneous administration with nitroglycerin, other nitrates or vasodilators, a more pronounced decrease in blood pressure is possible.

With simultaneous use with ACE inhibitors, tricyclic antidepressants / antipsychotics, agents for general anesthesia, opioid analgesics, a more pronounced decrease in blood pressure is possible.

Ethanol enhances the hypotensive effect of the drug.

Allopurinol, procainamide, cytostatics or immunosuppressants (systemic SCS) may increase the risk of developing leukopenia when used concomitantly with ACE inhibitors.

Antacids and colestramine with simultaneous administration with ACE inhibitors reduce the bioavailability of the latter.

Sympathomimetics can reduce the hypotensive effect of ACE inhibitors; it is necessary to carefully monitor the achievement of the desired effect.

With the simultaneous administration of ACE inhibitors and hypoglycemic drugs (insulin and hypoglycemic agents for oral administration), it is possible to increase the likelihood of lowering blood glucose and the risk of hypoglycemia. This phenomenon is most often observed during the first week of combined treatment and in patients with renal insufficiency.

With prolonged use of NSAIDs, including acetylsalicylic acid in high doses, a decrease in the effectiveness of ACE inhibitors is possible. The additive effect of taking NSAIDs and ACE inhibitors is manifested by increased potassium levels in the blood serum and can lead to impaired renal function. These effects are usually reversible. It is very rare to develop acute renal failure, especially in elderly patients and patients in a state of dehydration.

The excretion of lithium can be delayed during simultaneous administration with ACE inhibitors and therefore, the concentration of lithium in serum should be monitored during this period. When combined with lithium preparations, it is possible to intensify the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

With simultaneous use of ACE inhibitors and preparations of gold (sodium aurotomy malate) IV, a symptom complex including facial flushing, nausea, vomiting and arterial hypotension is described.

Amlodipine

Studies among elderly patients have shown that diltiazem suppresses the metabolism of amlodipine, probably due to inhibition of the isoenzyme CYP3A4 (plasma concentration increases by almost 50% and the effect of amlodipine increases). It is impossible to exclude the possibility that stronger inhibitors of the isoenzyme CYP3A4 (i.e. ketoconazole, itraconazole, ritonavir) are able to increase the concentration of amlodipine in the blood plasma to a greater extent than diltiazem. Simultaneous use should be carried out with caution.

When used simultaneously with inducers of the isoenzyme CYP3A4 - with antiepileptic drugs (for example, carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidon), rifampicin,vegetative preparations containing St. John's wort perforated - it is possible to reduce the concentration of amlodipine in the blood plasma. Clinical control is shown with the possible correction of amlodipine dose during treatment with CYP3A4 isoenzyme inducers and after their cancellation. Simultaneous use should be carried out with caution.

As a monotherapy amlodipine was combined with thiazide and loop diuretics, agents for general anesthesia, beta-blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, antacid preparations (aluminum hydroxide, magnesium hydroxide), simethicone, cimetidine , NSAIDs, antibiotics and oral hypoglycemic drugs.

It is possible to intensify the antianginal and antihypertensive action of slow calcium channel blockers when combined with thiazide and loop diuretics, verapamil, ACE inhibitors, beta-blockers and nitrates, as well as enhance their antihypertensive action when combined with alpha-blockers, antipsychotics.

A single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the pharmacokinetics of amlodipine.

The repeated use of amlodipine in 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 drugs (ritonavir) increase plasma concentrations of blockers of slow calcium channels, incl. amlodipine.

Neuroleptics and isoflurane increase the antihypertensive effect of dihydropyridine derivatives.

Amlodipine does not significantly affect the pharmacokinetics of ethanol.

Calcium preparations can reduce the effect of blockers of slow calcium channels.

When amlodipine is used together with lithium preparations, it is possible to intensify manifestations of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus). Amlodipine does not cause significant changes in the pharmacokinetics of cyclosporine.

Does not affect the concentration of serum digoxin and its renal clearance.

Has no significant effect on the effect of warfarin (prothrombin time).

Cimetidine does not affect the pharmacokinetics of amlodipine.

It is possible to reduce the antihypertensive effect of the drug with simultaneous use with estrogens, sympathomimetics.

Procainamide, quinidine and other drugs extending the QT interval may contribute to its significant elongation.

In vitro studies amlodipine does not affect the binding to blood proteins of digoxin, phenytoin, warfarin and indomethacin.

Reception amlodipine with grapefruit juice is not recommended, as in some patients this can lead to an increase in the bioavailability of amlodipine, resulting in increased its antihypertensive effect.

Special instructions:

Arterial hypotension

A marked decrease in blood pressure with the development of clinical symptoms can be observed in patients with reduced BCC and / or sodium content due to diuretics, fluid loss or other reasons, for example, with profuse perspiration, prolonged vomiting and / or diarrhea. In case of arterial hypotension, the patient should be laid and compensated for fluid loss (intravenous infusion of 0.9% sodium chloride solution) if necessary.Preferably, the restoration of loss of fluid and / or sodium is performed prior to initiation of therapy. It is necessary to monitor BP after taking the initial dose. This is especially true for patients with IHD or cerebrovascular disease, when a pronounced decrease in blood pressure can lead to myocardial infarction or stroke.

Aortic and mitral stenosis

Like all vasodilator drugs, caution should be given to patients with obstruction of the outflow tract of the left ventricle and stenosis of the mitral valve.

Impaired renal function

In some patients with arterial hypertension without pronounced manifestations of renovascular diseases, an increase in creatinine and urea in the blood serum was observed, in most cases minimal or transitory, more pronounced with concurrent administration of ACE inhibitors and a diuretic. This is most typical for patients with a history of kidney disease.

To determine the optimal maintenance dose, the dosage regimen must be determined individually, using separately lisinopril and amlodipine, with simultaneous monitoring of kidney function.In case of a decrease in kidney function, the drug should be stopped and replaced by motor therapy with drugs in adequate doses. In addition, a dose reduction or elimination of diuretics may be required.

Angioedema

Angioedema, swelling of the face, extremities, lips, tongue, vocal folds and / or larynx was recorded in patients taking an ACE inhibitor, including lisinopril. In these cases, the medication should be immediately discontinued and the patient should be carefully monitored until the symptoms disappear completely.

Edema of the face, lips and extremities usually pass independently, however, to reduce the severity of symptoms should use antihistamines.

Angioedema, accompanied by swelling of the larynx, can lead to death. If you detect edema of the tongue, pharynx or larynx, which are the cause of airway obstruction, emergency measures should be urgently started. The proper measures include: s / c administration of 0.3-0.5 mg or slow iv injection of 0.1 mg 0.1% solution of epinephrine (adrenaline), followed by intravenous administration of GCS and antihistamines and simultaneous monitoring of vital functions.

In patients who took ACE inhibitors, rarely intestinal angioedema edema of the intestine. These patients complained of abdominal pain (with or without nausea and vomiting); in some cases, the previous edema was not observed, and the activity of C-1 esterase was within normal limits. Intestinal angioedema of the intestine is diagnosed by computed tomography of the gastrointestinal tract, or after an ultrasound examination, or during surgery, the symptoms disappeared after discontinuation of the ACE inhibitor. When performing differential diagnosis of abdominal pain in patients taking ACE inhibitors, you should also consider intestinal angioedema of the intestine.

Anaphylactic reactions in patients on hemodialysis

In patients who underwent hemodialysis through polyacrylonitrile membranes (for example, AN69) and who simultaneously received ACE inhibitors, cases of anaphylactic shock have been recorded, so this combination should be avoided. Patients are recommended to use either another type of dialysis membrane, or an antihypertensive drug of another pharmacotherapeutic group.

Anaphylactic reactions in patients during apheresis of LDL

Rarely in patients who received ACE inhibitors during the apheresis of LDL with dextran sulfate, life-threatening anaphylactic reactions developed. Such reactions were prevented by abolishing the administration of ACE inhibitors prior to each apheresis procedure.

Desensitization by aspen or bee venom

Sometimes anaphylactic reactions developed in patients taking ACE inhibitors when desiccating the venom of Hymenoptera (eg, wasps or bees). Such life-threatening situations can be avoided with timely withdrawal of ACE inhibitors.

Hepatotoxicity

In rare cases, the administration of ACE inhibitors was accompanied by a syndrome that began with cholestatic jaundice or hepatitis and developed into fulminant liver necrosis and in several cases resulted in death. The mechanism of this syndrome is unclear. In patients receiving the drug, with the development of jaundice or increased activity of liver enzymes, it is necessary to cancel the drug with subsequent monitoring of their condition.

Liver failure

In patients with impaired liver function T_1/2amlodipine is elongated. At the moment, recommendations for the dosing regimen have not been developed, so it should be administered with caution, having previously estimated the expected benefit and the potential risk of treatment.

Hematological toxicity

In rare cases, neutropenia, agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. In patients with normal renal function and in the absence of other aggravating factors, neutropenia is rare. Neutropenia and agranulocytosis are reversible and disappear after the withdrawal of the ACE inhibitor. should be used with extreme caution in patients with vascular collagen, during immunosuppressive therapy, during treatment with allopurinol or procainamide, or in a combination of these aggravating factors, especially in the presence of a previous impairment of kidney function. Some of these patients developed serious infectious diseases, which in a few cases did not undergo correction with antibiotic therapy. During treatment with the drug, it is recommended to periodically monitor the level of leukocytes in such patients, and also to warn them about the need to report the appearance of the first signs of an infectious disease.

Cough

Cough was often recorded during the use of ACE inhibitors.As a rule, cough is unproductive, persistent and stopped after the drug was discontinued. With a differential diagnosis of cough, one should also consider a cough caused by the use of ACE inhibitors.

Surgery / general anesthesia

In patients who undergo extensive surgery or during general anesthesia with drugs leading to hypotension, lisinopril can block the formation of angiotensin II after compensatory release of renin. If arterial hypotension develops, probably as a result of the above mechanism, it is possible to correct the increase in BCC.

Elderly patients

Patients of the elderly with a violation of the kidney function should be corrected dose of the drug.

Hyperkalemia

In some patients who received ACE inhibitors, an increase in the serum potassium level was observed. Risk groups for the development of hyperkalemia are patients with renal insufficiency, diabetes mellitus, acute heart failure, dehydration, metabolic acidosis or with the simultaneous intake of potassium-sparing diuretics, dietary supplements with potassium,potassium-containing salt substitutes or any other medications that lead to an increase in the serum potassium level (eg, heparin). If you need a simultaneous intake with the above drugs should monitor the concentration of potassium in the blood serum.

Patients with reduced body weight, low growth patients and patients with severe liver dysfunction may need a dose reduction.

Does not have any adverse effect on the metabolism and lipids of blood plasma and can be used in the treatment of patients with bronchial asthma, diabetes and gout.

During treatment, it is necessary to control body weight and monitor the dentist (to prevent soreness, bleeding and gingival hyperplasia).

Use the drug with caution (the risk of a pronounced decrease in blood pressure and dizziness). Therefore, at the beginning of treatment, it is recommended to avoid driving vehicles, working with mechanisms and performing other work requiring increased concentration of attention.

Instructions

Amlodipine + Lysinopril (Amlodipinum + Lisinoprilum)