Composition, form of production and packaging
The tablets covered with a film cover of white color, round biconcave, with an engraving on one party "CE3"; on a cross-section of white color.
1 tab.
amlodipine besylate 6.944 mg,
which corresponds to the content of amlodipine 5 mg
atorvastatin lysinate 12.628 mg,
which corresponds to the content of atorvastatin 10 mg
Excipients: calcium carbonate - 81.2 mg, microcrystalline cellulose (type 102) - 87.948 mg, pregelatinized starch - 52.36 mg, sodium croscarmellose - 16.8 mg, calcium oxide - 0.84 mg, sodium carboxymethyl starch (type A) - 7 mg, giprolose - 1.4 mg, polysorbate 80 - 1.12 mg, silicon dioxide colloid - 1.96 mg, magnesium stearate - 1.4 mg.
The composition of the shell: opadrai II 85F18422 white - 8.4 mg (polyvinyl alcohol, partially hydrolyzed - 3.36 mg, titanium dioxide (E171) - 2.1 mg, macrogol 4000 - 1.697 mg, talc - 1.243 mg).
10 pieces. - blisters (3) - packs of cardboard.
The tablets covered with a film cover of white color, round biconcave, with engraving on one side "CE5"; on a cross-section of white color.
1 tab.
amlodipine besylate 13.888 mg,
which corresponds to the content of amlodipine 10 mg
atorvastatin lysinate 12.628 mg,
which corresponds to the content of atorvastatin 10 mg
Excipients: calcium carbonate - 72.256 mg, microcrystalline cellulose (type 102) - 87.948 mg, pregelatinized starch 52.36 mg, sodium cercararmellose 16.8 mg, calcium oxide 0.84 mg, sodium carboxymethyl starch (type A) 7 mg, giprolose 1.4 mg, polysorbate 80 - 1.12 mg, silicon dioxide colloid - 1.96 mg, magnesium stearate - 1.4 mg.
The composition of the shell: opadrai II 85F18422 white - 8.4 mg (polyvinyl alcohol, partially hydrolyzed - 3.36 mg, titanium dioxide (E171) - 2.1 mg, macrogol 4000 - 1.697 mg, talc - 1.243 mg).
10 pieces. - blisters (3) - packs of cardboard.
The tablets covered with a film shell of white color, oblong, biconcave, with engraving on one side "CE4"; on a cross-section of white color.
1 tab.
amlodipine besylate 6.944 mg,
which corresponds to the content of amlodipine 5 mg
atorvastatin lysinate 25.256 mg,
which corresponds to the content of atorvastatin 20 mg
Auxiliary substances: calcium carbonate - 169.344 mg, microcrystalline cellulose (type 102) - 175.896 mg, pregelatinized starch 104.72 mg, sodium croscarmellose 33.6 mg, calcium oxide 1.68 mg, sodium carboxymethyl starch (type A) 14 mg, giprolose 2.8 mg, polysorbate 80 - 2.24 mg, silicon dioxide colloid - 3.92 mg, magnesium stearate - 2.8 mg.
The composition of the shell: opadrai II 85F18422 white - 16.8 mg (polyvinyl alcohol, partially hydrolyzed - 6.72 mg, titanium dioxide (E171) 4.2 mg, macrogol 4000-3394 mg, talcum - 2.486 mg).
10 pieces. - blisters (3) - packs of cardboard.
The tablets covered with a film shell of white color, oblong, biconcave, with engraving on one side "CE6"; on a cross-section of white color.
1 tab.
amlodipine besylate 13.888 mg,
which corresponds to the content of amlodipine 10 mg
atorvastatin lysinate 25.256 mg,
which corresponds to the content of atorvastatin 20 mg
Excipients: calcium carbonate - 162.4 mg, microcrystalline cellulose (type 102) - 175.896 mg, pregelatinized starch 104.72 mg, sodium croscarmellose 33.6 mg, calcium oxide 1.68 mg, sodium carboxymethyl starch (type A) 14 mg, giprolose 2.8 mg, polysorbate 80 - 2.24 mg, silicon dioxide colloid - 3.92 mg, magnesium stearate - 2.8 mg.
The composition of the shell: opadrai II 85F18422 white - 16.8 mg (polyvinyl alcohol, partially hydrolyzed - 6.72 mg, titanium dioxide (E171) 4.2 mg, macrogol 4000-3394 mg, talcum - 2.486 mg).
10 pieces. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
Combined drug: atorvastatin is a lipid-lowering agent, inhibitor of HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, amlodipine-dihydropyridine derivative, slow calcium channel blocker (BCCC). Combination therapy results in a dose-dependent decrease in systolic and diastolic blood pressure and low-density lipoprotein cholesterol (LDL-C).
The effect on systolic and diastolic blood pressure or the concentration of LDL-C is not significantly different from monotherapy with amlodipine and atorvastatin.Within the framework of the Duplexer В® development program, a bioequivalence study was conducted in which the biological equivalence of a fixed combination of amlodipine and atorvastatin (Duplekor В® ) and a free combination of these drugs was demonstrated.
Amlodipine
Amlodipine blocks the flow of calcium ions through the membranes into the smooth muscle cells of the myocardium and vessels. The mechanism of hypotensive action of amlodipine is due to a direct relaxing effect on the smooth muscles of the vessels. The exact mechanism of action of amlodipine in angina is not definitively established, but amlodipine reduces ischemia in the following two ways:
1. Amlodipine dilates the peripheral arterioles and thus lowers the OPSS, i.e. afterload on the heart. Because The heart rate does not change, reducing the load on the heart leads to a reduction in energy consumption and oxygen demand.
2. The mechanism of action of amlodipine probably also includes expansion of the main coronary arteries and coronary arterioles both in unchanged and ischemic zones of the myocardium. Their dilatation increases the flow of oxygen into the myocardium in patients with vasospastic angina (Prinzmetal angina or variant angina).
In patients with arterial hypertension, the administration of amlodipine in a single daily dose provides a clinically significant reduction in blood pressure for 24 hours in both the prone position and the standing position. Due to the slow onset of action, amlodipine does not cause acute arterial hypotension.
In patients with angina, the use of amlodipine 1 time / day increases the exercise time, prevents the development of angina pectoris and ST-segment depression (by 1 mm), reduces the frequency of angina attacks and the number of short-acting nitroglycerin (sublingual) tablets taken.
Amlodipine does not adversely affect the metabolism and lipids of blood plasma and can be used in patients with bronchial asthma, diabetes and gout.
In patients with cardiac insufficiency II-IV functional class (according to the NYHA classification), amlodipine administration did not lead to a worsening of the clinical condition (exercise tolerance, left ventricular ejection fraction and clinical symptoms).
Atorvastatin
Atorvastatin selectively and competitively inhibits HMG-CoA reductase, which catalyzes the conversion of 3-hydroxy-3-methylglutarylcoenzyme A to mevalonic acid, a precursor of steroids, including cholesterol (Xc). Triglycerides and cholesterol in the liver are included in the Xc-VLDL, enter the blood plasma and transport to the peripheral tissues. X-LDL is formed from Xc-VLDL during interaction with Xc-LDL receptors characterized by high affinity for these lipoproteins.
Atorvastatin reduces the concentration of Xc and lipoproteins in the blood plasma by inhibiting HMG-CoA reductase and the synthesis of cholesterol in the liver and increasing the number of hepatic LDL-C receptors on the cell surface, which leads to increased capture and catabolism of LDL-C. Atorvastatin reduces the formation of LDL-C, provides a significant and persistent increase in activity of X-LDL receptors, coupled with a favorable change in the quality of LDL particles.
Reduces the concentration of total XC (30-46%), Xc-LDL (41-61%), apolipoprotein B (34-50%) and triglycerides (14-33%), while increasing the concentration of HDL cholesterol (HDL-C ) and apolipoprotein A1. These results are the same for patients with heterozygous hereditary hypercholesterolemia, non-hereditary forms of hypercholesterolemia, and mixed hyperlipidemia, including patients with type 2 diabetes.
Atorvastatin is effective in reducing the concentration of LDL-C in patients with homozygous hereditary hypercholesterolemia, i.e. a population usually resistant to therapy with other lipid-lowering agents. Reliably reduces the risk of the development of ischemic complications (including the lethal outcome of myocardial infarction) by 16%, the risk of repeated hospitalization for angina, accompanied by signs of myocardial ischemia - by 26%. The effect of atorvastatin on the risk of ischemic outcomes and mortality was independent of the initial concentration of LDL-C and was comparable in patients with myocardial infarction (MI) without Q wave and unstable angina, men and women, patients younger and older than 65 years.
Atorvastatin significantly reduced the development of the following complications.
Complications Risk Reduction
Coronary complications (IHD with fatal outcome and nonfatal MI) 36%
General cardiovascular complications and revascularization procedures 20%
Common coronary events 29%
Stroke (fatal and nonfatal) 26%
PHARMACOKINETICS
Amlodipine
Suction
After ingestion, amlodipine is well absorbed, C max in plasma is reached after 6-12 hours. Absolute bioavailability is 64-80%. Bioavailability of amlodipine does not change when eating.
Distribution
V d is approximately 21 l / kg. Approximately 97% of circulating amlodipine binds to plasma proteins. C ss of amlodipine in blood plasma are achieved after 7-8 days of regular intake of the drug.
Metabolism and excretion
Amlodipine is metabolized in the liver with the formation of inactive metabolites, 10% of unchanged amlodipine and 60% of metabolites are excreted by the kidneys.Excretion from the blood plasma is biphasic with a finite T 1/2 of 30-50 h.
Special populations of patients
The time required to achieve C max of amlodipine in blood plasma is practically independent of age. Patients in the elderly have a tendency to decrease the clearance of amlodipine, which leads to an increase in AUC and T 1/2 .
In patients of different age groups with chronic heart failure (CHF), an increase in AUC and T 1/2 was observed. A similar increase in AUC was noted in patients with hepatic insufficiency.
The concentrations of amlodipine in plasma do not depend on the degree of renal failure. Patients with impaired renal function may take usual initial doses of the drug.Amlodipine is not excreted by dialysis.
In patients with impaired hepatic function, T 1/2 increases.
Atorvastatin
Suction
Atorvastatin is rapidly absorbed after oral administration; C max in plasma are reached within 1-2 hours. The degree of absorption increases depending on the dose of atorvastatin. The absolute bioavailability of atorvastatin is approximately 12%, and the systemic bioavailability of inhibitory activity against HMG-CoA reductase is approximately 30%. Low systemic bioavailability is due to presystemic metabolism (absorption) in the mucosa of the gastrointestinal tract and / or metabolism during the "primary passage" through the liver.
Distribution
The mean V d of atorvastatin is approximately 381 liters. Atorvastatin binds more than 98% to plasma proteins.
Metabolism
Atorvastatin is metabolized by isoenzymes of the cytochrome P450 3A4 system to ortho and para-hydroxylated derivatives and various products of beta oxidation. In addition to other metabolic pathways, these products are further metabolized by conjugation with glucuronide. In vitro inhibition of HMG-CoA reductase by ortho- and para-hydroxylated metabolites is equivalent to the inhibition observed for atorvastatin. Approximately 70% decrease in the activity of HMG-CoA reductase occurs due to the action of active circulating metabolites.
Excretion
Atorvastatin is excreted mainly with bile after hepatic and / or extrahepatic metabolism. However, the drug does not appear to undergo significant intestinal hepatic recirculation. The average T 1/2 of plasma is approximately 14 hours. Due to the action of active metabolites, the half-life of the inhibitory activity of HMG-CoA reductase is approximately 20-30 hours.
Special populations of patients
The concentrations of atorvastatin and its metabolites in blood plasma in healthy elderly volunteers are higher than in healthy young volunteers, although lipolipidemic effects are comparable to those in young adults.
The concentration of atorvastatin in blood plasma in women differs from that in men (C max in women is about 20% higher and AUC 10% lower), however, clinically significant differences in the effect of the drug on lipid metabolism in men and women have not been revealed.
Pharmacokinetic data are not available for pediatric patients.
Kidney disease does not affect the concentration of atorvastatin in the blood plasma, so dose adjustments in patients with impaired renal function are not required. The concentrations of atorvastatin and its metabolites in blood plasma are significantly increased ( Cmax approximately 16-fold, AUC-11-fold) in patients with chronic liver disease caused by excessive drinking (Class B according to Child-Pugh classification).
INDICATIONS
Duplexer В® is intended for the treatment of arterial hypertension in patients with dyslipidemia, the condition of which is adequately controlled by the administration of amlodipine and atorvastatin at the same dosages that are included in the Duplexer В® preparation (with or without clinically expressed CAD) and having one of the following diseases:
- Primary hypercholesterolemia, including familial hypercholesterolemia (familial heterozygous hypercholesterolemia), or combined (mixed) hyperlipidemia (corresponding to type IIa and IIb according to Fredrickson classification);
homozygous familial hypercholesterolemia;
- when the hypolipidemic diet and other non-pharmacological methods of treating dyslipidemia are little or ineffective.
The drug is recommended to be used in those cases when combination therapy with amlodipine and low doses of atorvastatin is needed.
It is possible to use the drug with other antihypertensive and antianginal drugs.
DOSING MODE
Inside, 1 tab. 1 time / day at any time of the day, regardless of the time of ingestion.
Use Duplexer В® as a starting monotherapy is not recommended, tk. dose Duplekor В® should be determined by titrating the dose of individual components of the drug, taking into account the data on the doses and methods of using amlodipine and atorvastatin.
In accordance with the results of titration dose, the recommended dose is 1 tab. Duplekor В® 5 mg + 10 mg (amlodipine + atorvastatin, respectively), 1 tab. drug Duplekor В® 10 mg +10 mg (amlodipine + atorvastatin), 1 tab. Duplekor В® 5 mg + 20 mg (amlodipine + atorvastatin) or 1 tab. Duplexor В® 10 mg + 20 mg (amlodipine + atorvastatin) 1 time / day. The maximum daily dose is 1 tab. Duplexor В® 10 mg + 20 mg (amlodipine + atorvastatin) 1 time / day.
The drug is used in combination with non-medicated treatments, including diet, exercise, weight loss in obese patients, quitting.
When used in patients with hypertension in a dose of 5 mg + 10 mg (at the beginning of therapy), blood pressure control is necessary every 2-4 weeks and, if necessary, an increase in the dose to 10 mg + 10 mg 1 time / day is possible.
In IHD, the recommended dose (for amlodipine) is 5-10 mg / day.
Elderly patients
DuplexorВ® dosage adjustment is not required.
Children and teenagers under 18 years of age
The efficacy and safety of Duplexor В® in children and adolescents under the age of 18 years has not been adequately studied, therefore, administration of the drug to this category of patients is not recommended.
Patients with impaired hepatic function
Duplexer В® is contraindicated in patients with liver disease in the active phase or with a persistent increase in hepatic enzyme activity in the serum, which exceeds the VGN by a factor of 3.
Patients with impaired renal function
Correction of the dose of the drug is not required.
SIDE EFFECT
The undesirable effects that can occur when taking atorvastatin or amlodipine separately, can be considered as potential side effects when taking Duplexer В® .
The frequency of adverse reactions is given separately for atorvastatin and amlodipine. The data are classified according to the system-organ classes according to the MedDRA classification and with the following frequency: very often (? 1/10), often (? 1/100 to <1/10), infrequently (? 1/1 000 to <1 / 100), rarely (? 1/10 000 to <1/1000), very rarely (<1/10 000).
Atorvastatin
On the part of the hematopoiesis system: infrequently - thrombocytopenia.
Allergic reactions: often - hypersensitivity; very rarely - anaphylactic reactions, angioedema, bullous rash (including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis).
From the side of metabolism and nutrition: often - hyperglycemia; infrequently - hypoglycemia.
Mental disorders: infrequently - insomnia, nightmares.
From the nervous system: often - headache; infrequently - dizziness, hypoesthesia, dysgeusia, amnesia, paresthesia; rarely - peripheral neuropathy (without additional clarification).
From the side of the organ of hearing: infrequently - noise in the ears.
On the part of the respiratory system: often - chest pain, pain in the nasopharynx, nosebleeds.
On the part of the digestive tract: often - diarrhea, constipation, flatulence, nausea, dyspepsia, abdominal pain; infrequently - vomiting.
From the hepatobiliary system: rarely - hepatitis, cholestatic jaundice, pancreatitis; very rarely liver failure.
From the skin and subcutaneous fat: often - skin rash, itching; infrequently - alopecia.
From the musculoskeletal system: often - myalgia, arthralgia, back pain; infrequently - myopathy; rarely - myositis, rhabdomyolysis, muscle spasms.
On the part of the reproductive system and mammary glands: infrequently - erectile dysfunction; very rare - a gynecomastia.
General disorders: often - fatigue, asthenia; rarely - weakness; rarely - peripheral edema.
Laboratory parameters: often - increased activity of hepatic transaminases, increased CK activity in the blood serum; rarely - weight gain.
Amlodipine
From hemopoiesis system: very rarely - thrombocytopenia, leukopenia.
Allergic reactions: very rarely - hypersensitivity, urticaria, angioneurotic edema, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, photosensitivity.
On the part of metabolism and nutrition: very rarely - hyperglycemia.
Mental disorders:infrequently - insomnia, mood lability (including anxiety), depression; rarely - confusion.
From the nervous system: often - drowsiness, dizziness, headache (especially at the beginning of treatment); infrequently - syncope, tremor, hypoesthesia, dysgeusia, paresthesia; very seldom - muscular hypertonicity, peripheral neuropathy.
On the part of the organ of vision: rarely - visual disturbances (including diplopia).
On the part of the organ of hearing: rarely - ringing in the ears.
Cardio-vascular system:often - a rush of blood to the skin, peripheral edema of the ankles and feet; rarely - palpitations, marked reduction in blood pressure; very rare - myocardial infarction (including bradycardia, ventricular tachycardia and atrial fibrillation), vasculitis.
The respiratory system: rarely - dyspnea, rhinitis; very rarely - cough.
On the part of the digestive tract: often - abdominal pain, nausea; infrequently - vomiting, dyspepsia, disorders of bowel function (constipation or diarrhea), dryness of the oral mucosa; very rarely - pancreatitis, gastritis, hypertrophic gingivitis.
On the part of the hepatobiliary system: very rarely - hepatitis, cholestatic jaundice.
Skin and subcutaneous tissue:rare - alopecia, purpura, impaired pigmentation of the skin, rash, skin rash, pruritus, rash.
On the part of the musculoskeletal system: often - swelling of the ankles; Infrequent - arthralgia, myalgia, muscle spasms, pain in the back.
From the urinary system: rarely - a violation of urination, nocturia, pollakiuria.
Reproductive system and breast: infrequently - erectile dysfunction, gynecomastia.
General disorders: often - edema, increased fatigue; rarely - fatigue, chest pain, pain, malaise.
Laboratory findings: rare - increase or decrease in body weight; rarely - increased activity of hepatic transaminases.
CONTRAINDICATIONS
- severe hypotension (systolic blood pressure less than 90 mmHg);
- shock (including cardiogenic shock);
- hemodynamically unstable heart failure after acute myocardial infarction;
- Active liver disease or persistent elevation of liver enzymes more than 3 times higher than normal unclear etiology;
- the use in women of reproductive age who do not use adequate methods of contraception;
- combined use with itraconazole, ketokonozolom and telithromycin;
- age under 18 years (effectiveness and safety not established);
- Pregnancy;
- lactation period;
- increased sensitivity to amlodipine and other dihydropyridine derivatives, atorvastatin or any component of the formulation.
With caution:hypotension, acute myocardial infarction (and for 1 month thereafter), CHF nonischemic etiology III-IV functional class NYHA classification, SSS, hypertrophic obstructive cardiomyopathy, hepatic dysfunction, patients abusing alcohol and / or with a history of liver disease , patients with risk factors for the development of rhabdomyolysis (renal failure moderate / CC less than 60 ml / min /, severe water and electrolyte balance, endocrine and metabolic disorders, severe acute infectious tion / sepsis / uncontrolled epilepsy, extensive surgery, trauma, hypothyroidism, personal or family history of muscle diseases miotoksichnost in patients receiving other HMG-CoA reductase inhibitors or fibrates, condition,accompanied by an increase in the concentration of atorvastatin in the systemic circulation), age over 65 years, as with age increases the concentration of atorvastatin.
PREGNANCY AND LACTATION
Women of childbearing age should use reliable and adequate means of contraception. The drug can be administered to women of childbearing age only when the probability of pregnancy is low and the patient informed of the potential risk to the fetus.
Admission drug Duplekor В® is contraindicated in pregnancy. Safety of application of amlodipine and atorvastatin in pregnancy has not been established. In establishing pregnancy drug treatment Duplekor В® should be discontinued immediately and alternative therapy started if necessary.
Data on whether amlodipine and atorvastatin is released and their metabolites in breast milk are not available. Application Duplekor preparation В® lactation contraindicated.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with impaired renal function
Correction dose is not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Duplekor contraindicated in patients with liver disease in active phase or with persistent elevation of liver enzymes in serum, upper limit of normal (ULN) 3 times.
Before treatment with atorvastatin and periodically during treatment is necessary to control liver function. In case of increase in liver enzymes, exceeding the upper limit of normal (ULN) 3 times, it is advisable to reduce the dose or to stop its reception. In patients with impaired liver function the half-life of amlodipine is increased, and the drug Duplekor such patients should be used with caution.
Precautions should be prescribed Duplekor patients abusing alcohol and / or having a history of liver disease.
APPLICATION FOR CHILDREN
Contraindicated:
- age under 18 years (efficiency and safety not established).
APPLICATION IN ELDERLY PATIENTS
Precautions: age over 65 years, as with age increases the concentration of atorvastatin.
SPECIAL INSTRUCTIONS
Chronic heart failure (CHF)
in patients with CHF (III-IV NYHA functional class classification) with nonischemic etiology amlodipine exists the likelihood of pulmonary edema. Therefore, the drug to such patients should be used with caution.
Dysfunction of the liver
Before treatment with atorvastatin and periodically during treatment is necessary to control liver function. In case of increase in liver enzymes exceeding ULN 3 times recommended dose to reduce or terminate its reception. Patients with impaired liver function amlodipine half-life is increased, and the drug Duplekor В® such patients should be used with caution.
Precautions should be prescribed Duplekor В® patients abusing alcohol and / or having a history of liver disease.
muscle effects
Patients treated with atorvastatin was observed myalgia. The diagnosis of myopathy should be suspected in patients treated with HMG-CoA reductase, who observed: unexplained symptoms, such as pain or tenderness, muscle weakness or muscle cramps. In such cases, the need to control the activity of CK. CPK should not be measured following strenuous exercise or in the presence of plausible alternative reasons for the increase of CPK activity. If CK activity was significantly higher than normal (more than 5 times the ULN), CK activity should be determined regularly for 5-7 days to confirm the results.
Before the start of application of the drug Duplekor В®, While taking atorvastatin monotherapy in patients with risk factors for the development of rhabdomyolysis should be taken with caution. CPK should be determined before starting atorvastatin in the following situations:
- impaired renal function;
- hypothyroidism;
- their own or a family history of muscular disorders;
- a history miotoksichnosti in patients receiving other HMG-CoA reductase inhibitors or fibrates;
- history of liver disease and / or alcohol abuse;
- in elderly patients (> 65 years) in the case of the presence of risk factors for the development of rhabdomyolysis.
You should carefully weigh the potential benefits and risks of treatment and monitor patients regularly. If CPK activity increased more than 5 times in comparison with the ULN, treatment should not be initiated.
During treatment
It is recommended to inform the patients about the need to immediately report to the doctor about the sudden appearance of cases of muscle pain, muscle weakness or cramps, particularly in combination with malaise or fever.
If muscle pain, weakness or convulsions occur during treatment with Duplekor В® , should monitor CPK activity. If it is determined that CPK activity of more than 5 times higher than the ULN, treatment should cease.
If muscular symptoms are pronounced and cause daily discomfort throughout the day, even if the CPK activity increased less than 5 times in comparison with the ULN, treatment should be discontinued.
In the case of the disappearance of symptoms and return to normal activity of CK should consider re-appointment of the drug Duplekor В® with a smaller dose of atorvastatin and careful observation of the patient.
Increasing the activity of CK should be considered in the differential diagnosis of chest pain in assessing the likelihood of myocardial infarction. In the application of atorvastatin, as well as other drugs of this class are described in rare cases of rhabdomyolysis with acute renal failure caused by myoglobinuria.
Joint reception preparation Duplekor В® and dantrolene (solution for infusion), or other fibrate gemfibrozil not recommended.
When the joint application of cyclosporin, nicotinic acid as lipid-lowering doses (more than 1 g / day), fibric acid derivatives, macrolide antibiotics including erythromycin, clarithromycin, antifungal agents belonging to the azole (itraconazole, ketoconazole), nefazodone, and HIV protease inhibitors is increased the risk of myopathy during treatment with HMG-CoA reductase.
Impact on the ability to drive vehicles and manage mechanisms
Studies on the effect of the drug on the ability to drive vehicles and use machinery have not been conducted. Caution should be exercised when driving and the management mechanisms while taking the drug Duplekor В® , taking into account the possible development of an excessive reduction in blood pressure, dizziness and fainting.
OVERDOSE
Information about drug overdose not.
Amlodipine and atorvastatin is actively bound to plasma proteins, therefore, a significant increase in hemodialysis clearance combined formulation is unlikely.
Symptoms amlodipine overdose excessive peripheral vasodilatation leading to reflex tachycardia and marked and persistent reduction in blood pressure, including with the development of shock and death.
Symptoms of an overdose of atorvastatin is not described.
Treatment amlodipine overdose:administration of activated charcoal immediately or within 2 h after administration of amlodipine 10 mg leads to a significant delay drug absorption. In some cases, it may be an effective gastric lavage. Marked reduction in blood pressure caused by an overdose of amlodipine, requires active measures aimed at maintaining the function of the cardiovascular system, including the control parameters of the heart and lungs, exalted position of extremities and control of BCC and diuresis. For recovery of blood pressure and vascular tone can be advantageous to use the vasoconstrictive drug, if no contraindications to its purpose, to eliminate the effects of calcium channel blockade - in / in a calcium gluconate.
Atorvastatin Treatment of overdose:specific agents for the treatment of atorvastatin no overdose. In the case of an overdose should be symptomatic and supportive treatment, as appropriate. It is necessary to assess liver function and to determine the activity of serum CPK.
DRUG INTERACTION
It was shown that the pharmacokinetics of amlodipine 10 mg in combination therapy with atorvastatin 80 mg in healthy volunteers does not change. Amlodipine has no effect on the C max of atorvastatin, but caused an increase in AUC is 18%. Interaction preparation Duplekor В® with other drugs is not specifically studied, but research carried out each of the components individually.
A possible interaction with amlodipine
Application following drug combinations are not recommended
infusion solution dantrolene
The animals in / simultaneously administered verapamil and dantrolene commonly observed ventricular fibrillation. With this in mind, should avoid the simultaneous use of amlodipine and dantrolene.
The use of these combinations should be conducted with extreme caution
Baclofen
enhances the hypotensive effect. This may require monitoring of blood pressure and reduced dose hypotensive medicament.
Inhibitors of CYP3A4 isoenzyme
With simultaneous use of isozyme CYP3A4 inhibitor erythromycin young healthy volunteers and isoenzyme CYP3A4 inhibitor diltiazem elderly patients showed an increase in the plasma concentration of amlodipine is 22% and 50% respectively. However, the clinical significance of these data is unknown. It is possible that potent inhibitors of isoenzyme CYP3A4 (e.g., ketoconazole, itraconazole, ritonavir) may increase amlodipine plasma concentration to a greater extent than diltiazem.
Inducers of CYP3A4 isoenzyme
Antiepileptic agents (e.g., carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), rifampicin: due inducing amlodipine metabolism can be expected reduction in the concentration of calcium channel blockers slow (particularly amlodipine) in the blood plasma. In case of receiving the above isoenzyme CYP3A4 inducers recommended clinical observation and if necessary correction of the dose amlodipine otherwise simultaneous reception isoenzyme CYP3A4 inducer should be discontinued.
The use of the following combinations permissible
blockers? 1 -adrenoceptor (prazosin, alfuzosin, doxazosin, tamsulosin, terazosin): Can be expected to enhance the hypotensive effect of the risk of severe orthostatic hypotension.
Amifostine: increased hypotensive effect due to the manifestation of adverse effects of amifostine.
Tricyclic antidepressants / antipsychotics: increased risk of hypotension or orthostatic hypotension
