Parnavel Amlo - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate (milk sugar) - 71.56 mg, microcrystalline cellulose - 10.0 mg, povidone-K25-2.5 mg, sodium carboxymethyl starch - 4,0 mg, magnesium stearate 1.0 mg

1 tablet 10 mg + 8 mg

Active substances: Amlodipine besylate - 13.88 mg in terms of amlodipine base - 10.0 mg and perindopril erbumine 8.0 mg

Excipients: lactose monohydrate (sugar milk) - 143.12 mg, microcrystalline cellulose - 20.0 mg, povidone-K25 - 5.0 mg, sodium carboxymethyl starch - 8.0 mg, magnesium stearate - 2.0 mg

1 tablet 10 mg + 4 mg

Active substances: Amlodipine besylate - 13.88 mg in terms of amlodipine base - 10.0 mg and perindopril erbumine 4.0 mg

Excipients: lactose monohydrate (sugar milk) - 147.12 mg, microcrystalline cellulose - 20.0 mg, povidone-K25 - 5.0 mg, sodium carboxymethyl starch - 8.0 mg, magnesium stearate - 2.0 mg

1 tablet 5 mg + 8 mg

Active substances: Amlodipine besylate - 6.94 mg in terms of amlodipine base - 5,0mg and perindopril erbumine - 8.0 mg

Excipients: lactose monohydrate (sugar milk) - 150.06 mg, sodium - 8.0 mg, magnesium stearate - 2.0 mg.

Description:

Dosage of 5 mg + 4 mg: round flat tablets of white or almost white color, with a risk of one and chamfers from both sides.

Dosage of 10 mg + 8 mg: round flat tablets of white or almost white color, with a risk of one and chamfers from both sides.

Dosage of 10 mg + 4 mg: round biconvex tablets white or almost white, with a risk on one side.

Dosage of 5 mg + 8 mg: round flat tablets white or almost white, with a cross-shaped risk on one side and chamfers on both sides.

Pharmacotherapeutic group:hypotensive combined agent (angiotensin-converting enzyme (ACE) inhibitor + "slow" calcium channel blocker (BCCC)).

ATX: & nbsp

C.09.A.A.04 Perindopril

C.08.C.A.01 Amlodipine

Pharmacodynamics:

Perindopril

Perindopril is an inhibitor of the enzyme converting angiotensin I to angiotensin II (an ACE inhibitor). An angiotensin-converting enzyme, or kininase II, is an exopeptidase that performs both the conversion of angiotensin I into a vasoconstrictor substance, angiotensin II, and the destruction of bradykinin, which has a vasodilating effect, to an inactive heptapeptide.

Since ACE inactivates bradykinin, ACE inhibition is accompanied by an increase in the activity of both the circulating and tissue kallikrein-kinin system, and the system of prostaglandins is also activated.

Perindopril has a therapeutic effect due to the active metabolite, perindoprilat. Other metabolites have no inhibitory effect on ACE.

Arterial hypertension

Perindopril is a drug for the treatment of arterial hypertension of any severity. Against the background of its use, there is a decrease in both systolic and diastolic arterial pressure (BP) in the "lying" and "standing" positions. Perindopril reduces overall peripheral vascular resistance, which leads to a decrease in elevated blood pressure and an improvement in peripheral blood flow without alteration heart rate (heart rate).

As a rule, the intake of perindopril increases the renal blood flow, the rate of glomerular The filtering does not change in this case.

Antihypertensive effect of the drug reaches a maximum in 4-6 hours after a single oral intake and is maintained for 24 hours.

Antihypertensive action 24 hours after a single oral intake is about 87-100% of the maximum antihypertensive effect. Decrease in blood pressure is achieved quickly enough.

The therapeutic effect occurs less than 1 month after the start of therapy and is not accompanied by tachycardia. Termination of treatment does not cause withdrawal syndrome. Perindopril has a vasodilating effect, helps restore the elasticity of large arteries and the structure of the vascular wall of small arteries, and also reduces left ventricular hypertrophy.

Stable ischemic heart disease (CHD)

The efficacy of perindopril in patients with stable coronary artery disease without clinical symptoms of chronic heart failure led to a significant reduction in the absolute risk of complications in patients who had had previous myocardial infarction or a revascularization procedure.

Amlodipine

Amlodipine is a blocker of "slow" calcium channels (BCCC), a dihydropyridine derivative. Amlodipine inhibits the transmembrane transition of calcium ions to cardiomyocytes and smooth muscle cells of the vascular wall.

The antihypertensive effect of amlodipine is due to direct action on the smooth muscle cells of the vascular wall. It was found that amlodipine:

- causes the peripheral arterioles to expand, decreasing the total peripheral resistance of the vessels (afterload), since the heart rate does not change at the same time, and myocardial oxygen demand decreases.

- causes the expansion of the coronary arteries and arterioles both in the ischemic and intact zones. In patients with Prinzmetal angina, coronary blood flow is improved.

In patients with arterial hypertension (AH), amlodipine once a day provides a clinically significant decrease in blood pressure in the "standing" and "lying" for 24 hours. Antihypertensive effect develops slowly, and therefore, the development of acute arterial hypotension is uncharacteristic.

In patients with angina, receiving amlodipine once a day increases tolerance to physical activity, delays the onset of an attack of angina and "ischemic" depression segment ST, and also reduces the incidence of angina attacks and consumption nitroglycerin (short-acting forms).

Amlodipine has no effect on the lipid profile and does not cause changes in lipid-lowering plasma parameters. The drug can be used in patients with concomitant bronchial asthma, diabetes and gout.

Cardiac ischemia

The results of the efficacy evaluation suggest that amlodipine intake is characterized by fewer hospitalizations for angina and revascularization procedures in patients with ischemic heart disease.

Amlodipine + Perindopril

The main criterion for evaluating the effectiveness of long-term use of amlodipine in combination with perindopril is a combined indicator of the incidence of non-fatal myocardial infarction (including painless) and lethal outcome of IHD. The incidence of complications decreases with the use of amlodipine in combination with perindopril.

Pharmacokinetics:

The amount of absorption of perindopril and amlodipine with Parnavel Amlodoes not differ from that in the application of monopreparations.

Perindopril

Ingestion perindopril quickly absorbed, the maximum concentration in the blood plasma is reached within 1 hour. The half-life (T1 / 2) from the blood plasma is 1 hour. Perindopril does not possess pharmacological activity. Approximately 27% of the total amount of perindopril ingested enters the bloodstream as an active metabolite of perindoprilate. In addition to perindoprilata, another 5 metabolites are formed, not possessing pharmacological activity. The maximum concentration of perindoprilat in Plasma blood is reached after 3 to 4 hours after ingestion. Eating slows the conversion of perindopril to perindoprilat, thus affecting bioavailability. Therefore, the drug should be taken 1 time per day, in the morning, before eating.

There is a linear dependence of the concentration of perindopril in the blood plasma from its dose. The volume of distribution of free perindoprilata is approximately 0.2 l / kg. The association of perindoprilata with plasma proteins, mainly with ACE, is about 20% and is dose-dependent.

Perindoprilat is excreted from the body by the kidneys. The final half-life (T1 / 2) of the free fraction is about 17 hours, so the equilibrium state is reached within 4 days. The excretion of perindoprilat is delayed in old age, as well as in patients with cardiac and renal insufficiency. Therefore, these groups of patients should regularly monitor the concentration of creatinine and potassium in the blood plasma. The dialytic clearance of perindoprilat is 70 ml / min.

The pharmacokinetics of perindopril is disrupted in patients with cirrhosis of the liver: its hepatic clearance is reduced by a factor of 2. Nevertheless, the amount of perindoprilat formed does not decrease, which does not require dose adjustment (see the sections "Dosage and Administration" and "Special instructions").

Amlodipine

After oral administration amlodipine slowly absorbed from the gastrointestinal tract (GIT). The maximum concentration of amlodipine in the blood plasma is reached 6-12 hours after ingestion. Absolute bioavailability is about 64-80%, the volume of distribution is about 21 l / kg. Eating food does not affect the bioavailability of amlodipine. 97.5% of circulating amlodipine is associated with plasma proteins.The final half-life (T1 / 2 amlodipine from the blood plasma is 35-50 h, which allows taking the drug 1 time per day.

Amlodipine is metabolized in the liver with the formation of inactive metabolites, with 10% of the accepted dose of amlodipine excreted unchanged and 60% of the kidneys - in the form of metabolites. Amlodipine is not excreted from the body by dialysis.

The time from taking the drug to reaching the maximum concentration of amlodipine does not differ in elderly patients and younger age. Older patients have a slower clearance of amlodipine, which leads to an increase in the area under the concentration-time curve (AUC).

The increase in AUC and T1 / 2 in patients with chronic heart failure (CHF) corresponds to the estimated value for this age group. In patients with impaired renal function, changes in amlodipine concentration in the blood plasma do not correlate with the degree of renal failure. Perhaps a slight increase in T1 / 2.

Data on the use of amlodipine in patients with hepatic impairment are limited. In patients with hepatic insufficiency, amlodipine clearance decreases, which leads to an increase in T1 / 2 and the AUC is approximately 40-60%.

Indications:

Arterial hypertension and / or ischemic heart disease (IHD): stable angina in patients requiring perindopril and amlodipine therapy.

Contraindications:

Perindopril

- Hypersensitivity to perindopril or other ACE inhibitors;

- Angioedema (Quincke's edema) in the anamnesis (including against the background of taking other ACE inhibitors);

- Hereditary / idiopathic angioedema;

-Year up to 18 years of age (efficiency and safety not established).

- The simultaneous use of perindopril and preparations containing aliskiren in patients with renal insufficiency (KC less than 60 ml / min) and patients with diabetes mellitus.

Amlodipine

- Increased sensitivity to amlodipine or other dihydropyridine derivatives;

-Heart arterial hypotension (systolic blood pressure (BP) less than 90 mmHg);

-Struction of the left ventricular outflow tract (eg, severe aortic stenosis); -Instable angina (with the exception of Prinzmetal's stenocardia);

-Year up to 18 years of age (efficiency and safety not established).

-Shock (including cardiogenic).

-Hemodynamically unstable heart failure after acute myocardial infarction.

Amlodipine + Perindopril

- Hypersensitivity to the excipients included in the preparation;

- Renal insufficiency (creatinine clearance (CK) less than 60 ml / min);

- Age under 18 years (efficiency and safety not established);

- Hereditary lactose intolerance, lactase deficiency and glucosogalactose malabsorption.

Carefully:

Stenosis of the renal artery (including bilateral), the only functioning kidney, liver failure, renal failure, systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), immunosuppressant therapy, allopurinol, procainamide (risk of developing neutropenia, agranulocytosis) , decreased circulating blood volume (bcc) (diuretic intake, salt-free diet, vomiting, diarrhea), atherosclerosis, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, chronic kai heart failure, the simultaneous use of dantrolene, estramustine, potassium-sparing diuretics, potassium preparationspotassium-containing substitutes for dietary salt and lithium preparations, hyperkalemia, surgical intervention / general anesthesia, advanced age, hemodialysis using high-flow membranes (for example, AN69®), desensitizing therapy, low-density lipoprotein apheresis (LDL), aortic stenosis / mitral stenosis / hypertrophic obstructive cardiomyopathy, use in patients of the Negroid race, CHF of non-ischemic etiology III-IV functional class by classification NYHA.

Pregnancy and lactation:

Pregnancy

The drug is contraindicated for use in pregnancy. Except in cases when Parnavel Amlo therapy is necessary for life reasons, when planning pregnancy, it is necessary to cancel the drug and prescribe other hypotensive drugs that are allowed for use in pregnancy. When diagnosing pregnancy, immediately stop taking Parnavel Amlo and, if necessary, prescribe another antihypertensive therapy. It is known that the effect of ACE inhibitors on the fetus in the II and III trimesters of pregnancy can lead to a disruption of its development (decreased kidney function,oligohydramnion, slowing ossification of the skull bones) and development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).

If the patient has received an ACE inhibitor during II or III trimester of pregnancy, it is recommended to conduct ultrasound newborn to assess the status of the skull and renal function.

Newborns whose mothers received ACE inhibitors during pregnancy should be under careful medical supervision because of the risk of developing arterial hypotension, oliguria, and hyperkalemia (see "Contraindications" and "Special instructions").

The limited information available on the use of amlodipine and other BCC in pregnancy indicates that the drug does not adversely affect the fetus. However, there is a risk of lengthening labor.

Amlodipine

In experimental studies fetotoxic and embryotoxic effects of the drug have not been established, but use in pregnancy is possible only if the benefit to the mother exceeds the potential risk to the fetus. In some patients treated with blockers of "slow" calcium channels, a reversible decrease in sperm motility was noted.Clinical data concerning the potential effect of amlodipine on reproductive function is not enough.

The period of breastfeeding.

Amlodipine

There is no evidence of excretion of amlodipine in breast milk. However, it is known that other BCCC - dihydropyridine derivatives are excreted in breast milk. In this connection, when it is necessary to prescribe the drug amlodipine During the lactation period, the issue of stopping breastfeeding should be addressed.

Perindopril

Due to the lack of information regarding the use of perindopril during breastfeeding, the use of perindopril is not recommended, it is preferable to follow an alternative treatment with a more studied safety profile during breastfeeding.

Amlodipine + Perindopril

It is not recommended to use the drug Parnavel Amlo during lactation due to the lack of appropriate clinical experience with perindopril and amlodipine both in monotherapy and in combination therapy. If you need to take the drug during lactation, you should stop breastfeeding.

Dosing and Administration:

Inside, 1 tablet 1 time per day, preferably in the morning before eating. Dose Parnavel Amlo selected after a previous dose titration of the individual components of the preparation: perindopril and amlodipine in patients with hypertension and / or coronary heart disease.

When the therapeutic necessity dose Parnavel Amlo preparation may be varied or pre-selection of individual doses of individual components can be carried out: 4 mg perindopril + 5 mg amlodipine or 8 mg of perindopril + 5 mg amlodipine or 4 mg of perindopril + 10 mg of amlodipine or 8 mg of perindopril + 10 mg of amlodipine.

Parnavel Amlo at doses of 4 mg perindopril + 10 mg amlodipine and 8 mg perindopril + 10 mg amlodipine is the maximum daily dose ofwhich should not be exceeded.

Special patient groups

Elderly patients and patients with renal insufficiency (see the sections "Pharmacokinetics" and "Special instructions")

The excretion of perindoprilat in elderly patients and patients with renal insufficiency is slowed. Therefore, in such patients it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma. Parnavel Amlo can be given to patients with QC equal to or greater than 60 ml / min.Parnavel Amlo is contraindicated in patients with SC less than 60 ml / min (see section "Contraindications"). Such patients are recommended individual selection of doses of perindopril and amlodipine.

Amlodipine, used in equivalent doses, is equally well tolerated by patients, both elderly and younger patients. It is not necessary to change the dosage regimen in elderly patients, but the dose increase should be carried out with caution, which is associated with age-related changes and an increase in T1 / 2. The change in the concentration of amlodipine in the blood plasma does not correlate with the degree of renal insufficiency. Amlodipine is not excreted from the body by dialysis.

Patients with hepatic insufficiency.

For patients with mild or moderate hepatic insufficiency, dose selection should be performed with caution. It is recommended to start taking the drug from low doses (see section "Special instructions"). The search for an optimal initial and maintenance dose for patients with hepatic insufficiency should be carried out individually, using amlodipine and perindopril preparations in monotherapy.The pharmacokinetics of amlodipine in patients with severe hepatic insufficiency has not been studied. For such patients, amlodipine should be taken at the lowest dose and increased gradually.

Children and teens

Parnavel Amlo should not be prescribed to children and adolescents under 18 years of age because of the lack of data on the efficacy and safety of perindopril and amlodipine in these patient groups, both in monotherapy and in combination therapy.

Side effects:

The frequency of adverse reactions that were noted in monotherapy with perindopril and amlodipine is given in the following gradation: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000), including individual messages; frequency (frequency can not be calculated from available data).

From the blood and lymphatic system:

Rarely: leukopenia / neutropenia, agranulocytosis, pancytopenia, thrombocytopenia, hemolytic anemia in patients with congenital deficiency of glucose-6-phosphate dehydrogenase, a decrease in hemoglobin and hematocrit.

From the immune system:

Infrequently: allergic reactions.

Metabolic disorders:

Rarely: hyperglycemia.

Unspecified frequency: hypoglycemia.

From the central nervous system:

Often: drowsiness (especially at the beginning of therapy), dizziness (especially at the beginning of therapy), headache, paresthesia, vertigo;

Infrequently: insomnia, mood lability (including anxiety), sleep disorders, tremor, hypoesthesia, depression, fainting;

Rarely: confusion of consciousness;

Rarely: peripheral neuropathy, hypertonia.

From the side of the organ of vision:

Often: visual impairment (including diplopia).

From the organ of hearing:

Often: noise in ears.

From the cardiovascular system:

Often: a feeling of palpitation, "hot flashes" of blood to the skin of the face, a pronounced decrease in blood pressure;

Rarely: angina pectoris, myocardial infarction, possibly due to excess BP reduction in patients at high risk (see section "Special instructions"), arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), stroke, possibly due to excessive reduction BP in patients from the high-risk group (see section "Special instructions"), vasculitis.

From the respiratory system:

Often: shortness of breath, cough;

Infrequently: rhinitis, bronchospasm;

Rarely: eosinophilic pneumonia.

From the digestive system:

Often: abdominal pain, nausea, vomiting, indigestion, diarrhea, constipation;

Infrequently: a violation of taste perception, a change in the rhythm of defecation, dryness of the oral mucosa;

Rarely: pancreatitis, gingival hyperplasia, gastritis.

From the liver and bile ducts:

Rarely: hepatitis, jaundice, increased activity of "hepatic" transaminases (most often in combination with cholestasis), cytolytic or cholestatic hepatitis (see section "Special instructions").

From the skin and subcutaneous fat:

Often: pruritus, rash, exanthema;

Infrequently: angioedema, swelling of the face, extremities, lips, mucous membranes, tongue, vocal cords and / or larynx (see section "Special instructions"), alopecia, hemorrhagic rash, skin discoloration, increased sweating, urticaria; Rarely: Quincke's edema, erythema multiforme; syndrome. Stevens-Johnson, exfoliative dermatitis, photosensitivity.

From the osteomuscular system and connective tissue:

Often: muscle spasms, swelling of the legs;

Infrequently: arthralgia, myalgia, back pain.

From the side of the kidneys and urinary tract:

Infrequently: violation of urination, nocturia, frequent urination, renal failure;

Rarely: acute renal failure.

From the reproductive system and the mammary glands:

Infrequently: impotence, gynecomastia.

General disorders and symptoms:

Often: peripheral edema, asthenia, increased fatigue;

Infrequently: pain in the chest, malaise, pain.

Laboratory indicators:

Infrequently: weight gain, weight loss;

Rarely: increased bilirubin concentration.

Unspecified frequency: increase in the concentration of urea and creatinine in the blood serum, hyperkalemia (see section "Special instructions").

Individual cases of extrapyramidal syndrome have been reported with the admission of blockers of "slow" calcium channels.

Overdose:

Amlodipine

Information about an overdose of amlodipine is limited.

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 (sorbents) in 2 hours after an overdose), maintaining the function of cardiovascular and respiratory system, elevated limb position, control of bcc and diuresis, symptomatic and maintenance therapy, intravenous calcium intake gluconate and dopamine. Hemodialysis is ineffective. With a significant decrease in blood pressure Patient follow-up should be monitored in a cardiac department intensive care. In the absence of contraindications to restore the tone vessels and blood pressure can be used vasoconstrictors.

Perindopril

Data on perindopril overdose are limited.

Symptoms: a significant reduction in blood pressure, shock, water-electrolyte disorders, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and cough.

Treated: with a significant decrease in blood pressure, the patient should be transferred to the "lying" position on the back with raised legs, if necessary, correction of hypovolemia (for example, intravenous infusion of 0.9% sodium chloride solution). Intravenous administration of catecholamines is also possible.

With the help of hemodialysis can be removed perindopril from the systemic blood flow (see section "Special instructions"). With a bradycardia resistant to therapy, it may be necessary to install an artificial pacemaker. Dynamic control of the physical state, concentration of creatinine and electrolytes of blood plasma is necessary.

Emergency measures are reduced to removing the drug from the body: gastric lavage and / or the appointment of activated carbon, followed by the restoration of the water-electrolyte balance.

Interaction:

Perindopril

Not recommended combination of drugs

Potassium-sparing diuretics, potassium preparations and potassium-containing substitutes for edible salt: Despite the fact that the potassium content in the blood serum remains within the normal range, in some patients, peripodopril may exhibit hyperkalemia. Potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride, eplerenone), potassium preparations and potassium-containing substitutes for edible salt can lead to a significant increase in the potassium content in the blood serum. Therefore, simultaneous use of an ACE inhibitor and the above agents is not recommended (see section "Special instructions").If simultaneous application is necessary (in case of confirmed hypokalemia), caution should be exercised and regular monitoring of potassium levels in the blood plasma and ECG parameters should be carried out.

Lithium preparations: while simultaneous use of lithium drugs and ACE inhibitors, there can be a reversible increase in lithium in the blood plasma and the associated toxic effects. Simultaneous use of perindopril and lithium preparations is not recommended. If this therapy is necessary, regular monitoring of lithium content in blood plasma (see section "Special instructions") is necessary.

Estramustine: simultaneous use of estramustine with ACE inhibitors is accompanied by an increased risk of angioedema.

Aliskiren: simultaneous use of perindopril and preparations containing aliskiren, in patients with diabetes mellitus or renal insufficiency with a CK of less than 60 ml / min is contraindicated.

Combination of medicines requiring special attention

Non-steroidal anti-inflammatory drugs (NSAIDs), including high doses of acetylsalicylic acid (more than 3 g / day): simultaneous application ACE inhibitors with NSAIDs (acetylsalicylic acid in a dose of anti-inflammatory effect, inhibitors of cyclooxygenase-2 (COX-2) and nonselective NSAIDs), can lead to a decrease in the antihypertensive effect of ACE inhibitors. The simultaneous use of ACE inhibitors and NSAIDs may lead to a deterioration of renal function, including the development of acute renal failure and increase in the potassium content in blood serum, especially in patients with reduced kidney function. Care should be taken when prescribing this combination, especially in elderly patients. Patients need to compensate for fluid loss and closely monitor kidney function, both at the beginning of treatment and during treatment.

Hypoglycemic agents (hypoglycemic agents for oral administration, sulfonylureas and insulin derivatives): ACE inhibitors can enhance the hypoglycemic effect of insulin and sulfonylurea derivatives in patients with diabetes mellitus. Hypoglycaemia occurs very rarely (likely due to the increase in glucose tolerance and reduce insulin requirements).

Combinations of medicines requiring attention

Diuretics (thiazide and "loop"): in patients receiving diuretics, especially with excess elimination of fluid and / or electrolytes, at the beginning of therapy with an inhibitor ACE can significantly decrease blood pressure, the risk of developing it can be reduce by eliminating the diuretic, introducing an increased amount of fluid and / or table salt, and also appointing perindopril in a low dose with further gradual increase.

Sympathomimetics: can attenuate the antihypertensive effect of ACE inhibitors. Preparations of gold: when using ACE inhibitors, including perindopril, for patients receiving intravenously a gold preparation (sodium aurotomy malate), was described symptom-complex, which includes: flushing of the facial skin, nausea, vomiting, arterial hypotension.

Allopurinol, cytostatic and immunosuppressive agents, corticosteroids (for systemic use) and procainamide: simultaneous application with ACE inhibitors may be accompanied by an increased risk of leukopenia.

Means for general anesthetics: simultaneous use of ACE inhibitors and agents for general anesthesia can lead to an increased antihypertensive effect.

Amlodipine

Not recommended combination of drugs

Dantrolene (intravenous): in laboratory animals cases of ventricular fibrillation with a lethal outcome and collapse were observed against verapamil and intravenous dantrolene, accompanied by hyperkalemia. Extrapolating the available data, combined use of dantrolene and amlodipine should be avoided.

Combination of medicines requiring special attention

Inductors of cytochrome CYP3A4 (rifampicin, preparations of St. John's wort, an anticonvulsant, such as carbamazepine, phenobarbital, phenytoin, phosphenytoin, primidon): it is possible to reduce the plasma concentration of amlodipine due to increased metabolism in the liver. Caution should be exercised with the simultaneous use of amlodipine and inducers of microsomal oxidation and, if necessary, adjust the dose of amlodipine.

Inhibitors of cytochrome isoenzymes CYP3A4

Simultaneous reception of amlodipine and strong or moderate inhibitors CYP3A4 (protease inhibitors, antifungal agents of the azole group, macrolides, eg, erythromycin or clarithromycin, verapamil or diltiazem) can lead to a significant increase in the concentration of amlodipine. Clinical manifestations of these pharmacokinetic abnormalities may be more pronounced in elderly patients. In this connection, it may be necessary to monitor the clinical state and dose adjustment.

Combinations of medicines requiring attention

Amlodipine enhances the antihypertensive effect of drugs with antihypertensive effect.

Other combinations of drugs:

In clinical trials of drug interactions amlodipine had no effect on the pharmacokinetics of atorvastatin, digoxin, warfarin, or cyclosporine. Simultaneous reception of amlodipine and the use of grapefruit or grapefruit juice is not recommended, due to the possible increase in the bioavailability of amlodipine in some patients, which in turn can lead to an increase in blood pressure lowering.

Amlodipine + Perindopril

Combination of medicines requiring special attention:

Baclofen: possibly increased antihypertensive effect. It is necessary to monitor blood pressure and kidney function, if necessary - adjust the dose of amlodipine.

A combination of drugs that requires attention:

Hypotensive drugs (eg, beta-blockers) and vasodilators:

it is possible to increase the antihypertensive effect of perindopril and amlodipine. Caution should be exercised when concomitant administration with nitroglycerin, other nitrates or other vasodilators, as this may further reduce blood pressure.

Corticosteroids (mineral and glucocorticosteroids), tetracosactide: decrease in antihypertensive action (fluid retention and sodium ions due to the action of corticosteroids).

Alpha-blockers (prazozin, alfuzosia, doxazosin, tamsulosin, terazosin):

increased antihypertensive action and increased risk of orthostatic hypotension.

Amifostin: it is possible to increase the antihypertensive effect of amlodipine.

Tricyclic antidepressants / antipsychotics / agents for general anesthesia: increased antihypertensive action and increased risk of orthostatic hypotension. prescribe the drug to patients with hereditary lactose intolerance, lactase deficiency and glucose galactose malabsorption.

Special instructions:

Special instructions pertaining to perindopril and amlodipine are applicable to the drug Parnavel Amlo.

Perindopril

Hypersensitivity / angioedema. When taking ACE inhibitors, including perindopril, in rare cases, development of an angioedema of the face, extremities, lips, mucous membranes, tongue, vocal cords and / or larynx can be observed (see section "Side effect"). When symptoms appear, taking the drug should be stopped immediately, and the patient should be observed until the signs of edema disappear completely. If the swelling affects only the face and lips, then its manifestations usually pass on their own, although antihistamines can be used to treat the symptoms. Angioedema, accompanied by swelling of the larynx, can lead to death. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction. When these symptoms occur, you should immediately enter epinephrine (epinephrine) subcutaneously and / or provide airway patency. The patient should be under medical supervision until the symptoms disappear completely and persistently.Patients with a history of Quinck's edema who are not associated with taking ACE inhibitors may be at increased risk of developing this drug when taking this drug (see "Contraindications").

In rare cases, against the background of therapy with ACE inhibitors, angioedema develops in the intestine. In this case, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases, without a prior angioedema and at a normal C1-esterase level. The diagnosis is established using computed tomography of the abdominal region, ultrasound or at the time of surgery. Symptoms disappear after stopping the intake of ACE inhibitors. Therefore, patients with abdominal pain receiving ACE inhibitors should take into account the possibility of angioedema edema development during differential diagnosis (see section "Side effect").

Anaphylactoid reactions during apheresis of LDL

In rare cases, in patients receiving ACE inhibitors, with life-threatening low-density lipoprotein (LDL) apheresis with dextran sulfate, life-threatening anaphlactoid reactions

To prevent anaphylactoid reaction, therapy with an ACE inhibitor should be temporarily discontinued before each apheresis procedure. Anaphylactoid reactions during desensitization. There are some reports of the development of anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy (for example, the venom of Hymenoptera insects). In the same patients, the anaphylactoid reaction could be avoided by the temporary withdrawal of ACE inhibitors, and if the drug was randomly taken, the anaphylactoid reaction occurred again.

Neutropenia / agranulocytosis / thrombocytopenia / anemia

Against the background of the administration of ACE inhibitors, neutropenia / agranulocytosis, thrombocytopenia and anemia can occur. In patients with normal renal function and in the absence of other aggravating factors, neutropenia develops rarely. With extreme caution should be applied perindopril in patients with diffuse connective tissue diseases, with the use of immunosuppressants, allopurinol or procainamide, especially in patients with impaired renal function. Some patients experienced severe infectious lesions, in some cases, resistant to intensive antibiotic therapy.When prescribing perindopril to such patients it is recommended to periodically monitor the number of white blood cells in the blood. Patients should inform the doctor of any signs of infectious diseases (eg, sore throat, fever).

Arterial hypotension

ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic arterial hypotension rarely develops in patients without concomitant diseases. The risk of excessive reduction in blood pressure is increased in patients with reduced circulating blood volume, which can be observed against diuretic therapy, with strict salt-free diet, hemodialysis, diarrhea and vomiting, as well as in patients with severe hypertension with high renin activity (see Sections "Interaction with other medicinal products"). Patients with an increased risk of developing symptomatic arterial hypotension should carefully monitor blood pressure, kidney function and potassium levels in the blood serum during drug therapy. Amlodipine + Perindopril This approach is also used in patients with angina and cerebrovascular diseases, in which severe arterial hypotension can lead to myocardial infarction or impaired cerebral circulation.In the case of development of arterial hypotension the patient should be transferred to the "lying" position on the back with raised legs. If necessary, replenish the volume of circulating blood by intravenous administration of 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle for further administration of the drug. After recovery of the volume of circulating blood and blood pressure, treatment can be continued. Mitral stenosis / aortic stenosis / hypertrophic cardiomyopathy

Parnavel Amlo, like other ACE inhibitors, should be administered with caution to patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as to patients with mitral stenosis.

Impaired renal function

Patients with renal insufficiency (KC less than 60 ml / min.) Are recommended individual selection of doses of perindopril and amlodipine. Such patients need regular monitoring of potassium and creatinine in the blood serum (see section "Side effect"). In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney in the presence of ACE inhibitor therapy, it is possiblean increase in the concentration of urea and creatinine in the blood serum, usually occurring when the therapy is withdrawn. More often this effect is observed in patients with renal insufficiency. The additional presence of reninvascular hypertension causes an increased risk of severe arterial hypotension and kidney failure in these patients. In some patients with hypertension without signs of renal vascular disease, an increase in the concentration of urea and creatinine in the blood serum, especially with the simultaneous administration of perindopril with a diuretic, is usually minor and transient. More often this effect is noted in patients with a previous impairment of kidney function.

Liver failure

In rare cases, when taking ACE inhibitors, cholestatic jaundice occurs. With the progression of this syndrome, fulminant liver necrosis develops, sometimes with a fatal outcome. The mechanism of development of this syndrome is unclear. When jaundice or a significant increase in the activity of "liver" enzymes against the background of taking ACE inhibitors should stop taking the drug and see a doctor (see section "Side effect").

Ethnic differences

In patients of the Negroid race, angioneurotic edema develops more often than in representatives of other races against the background of the administration of ACE inhibitors. Perindopril, like other ACE inhibitors, may have a less pronounced hypotensive effect in patients of the Negroid race compared with representatives of other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the Negroid race are more likely to have low renin activity.

Cough

On the background of therapy with an ACE inhibitor, dry cough may occur. Cough persists for a long time against the background of taking this group's drugs and disappears after their withdrawal. When dry cough occurs in patients, one should be aware of the possible iatrogenic nature of this symptom.

Surgery / general anesthesia

The use of ACE inhibitors in patients undergoing extensive surgery and / or general anesthesia can lead to a marked decrease in blood pressure if general anesthetics with hypotensive action are used. This is due to the blocking of the formation of angiotensin II against a background of compensatory enhancement of renin activity.If the development of arterial hypotension is associated with the described mechanism, you should increase the volume of circulating blood plasma. It is recommended to stop taking the drug 24 hours before surgery.

Hyperkalemia

Hyperkalemia can develop during treatment with ACE inhibitors, including, and perindopril. Risk factors for hyperkalemia are renal failure, elderly age (over 70 years), diabetes mellitus, certain concomitant conditions (dehydration, acute decompensation of chronic heart failure, metabolic acidosis), concomitant administration of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride), as well as preparations of potassium or potassium-containing substitutes for edible salt, as well as the use of other drugs that promote the increase of potassium in the blood plasma (for example, heparin). The use of potassium, potassium-sparing diuretics, potassium-containing salt substitutes can lead to a significant increase in potassium in the blood, especially in patients with reduced renal function.Hyperkalemia can lead to serious, sometimes fatal heart rhythm disturbances. If simultaneous administration of perindopril and the above drugs is required, treatment should be carried out with caution in the context of regular monitoring of potassium in the blood serum (see section "Interaction with other medicinal products").

Patients with diabetes mellitus

When the drug is prescribed for patients with diabetes mellitus, who receive hypoglycemic agents for ingestion or insulin, during the first month of therapy, the concentration of glucose in the blood should be carefully monitored (see section "Interaction with other medicinal products").

Amlodipine

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

Heart failure

Treatment of patients with heart failure should be done with caution. With the use of amlodipine in patients with chronic cardiac insufficiency III and IV functional class according to the classification of NYHA, the development of pulmonary edema is possible. Blocks of "slow" calcium channels, including amlodipine, should be used with caution in patients with chronic heart failure, due to the possible increase in the risk of development of adverse events from the cardiovascular system and mortality.

Liver failure

In patients with impaired liver function, T'L and AUC amlodipine increases. Admission of amlodipine should start with the lowest doses and observe precautions, both at the beginning of treatment, and with increasing doses. Patients with severe hepatic insufficiency should increase the dose gradually, providing a thorough control of the clinical condition.

Elderly patients

In elderly patients, T1 / 2 may increase, and amlodipine clearance may decrease. Dose changes are not required, but more careful monitoring of patients of this category is necessary. In patients with impaired renal function, monitoring of the condition is necessary.

Renal insufficiency

Patients with renal insufficiency can take amlodipine in standard doses. Changes in plasma concentrations of amlodipine do not correlate with the degree of renal failure. Amlodipine It is eliminated from the body by dialysis.

Parnavel Amlo

Excipients

Due to the presence of lactose in the drug should not be prescribed to patients with hereditary lactose intolerance, lactase deficiency and glucose-galactose malabsorption.

Effect on the ability to drive transp. cf. and fur:

In connection with the possible development of weakness and dizziness, drowsiness, care should be taken when driving vehicles and engaging in certain activities requiring increased concentration of attention and rapid motor reaction.

Form release / dosage:

Tablets 5 mg + 4 mg; 10 mg + 8 mg; 10 mg + 4 mg and 5 mg + 8 mg.

Packaging:

For 10, 20, 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

By 10, 20, 30, 40, 50 or 100 tablets in cans of polymeric for medicines. One jar or 1, 2, 3, 4, 5, 6 or 10 contour squares, together with the instructions for use, are placed in a cardboard package (bundle).

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002549

Date of registration:30.07.2014

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp15.01.2015

Illustrated instructions

Instructions

Parnavel Amlo (Parnavel amlo)