Pharmacological action Pharmacodynamics dihydropyridine derivative – blocker “slow” calcium channels (BCCI) II generation, has antianginal and antihypertensive effect. Communicating with the dihydropyridine receptors, blocking calcium channels, reduces the transmembrane passage of calcium ions into the cell (mainly in the vascular smooth muscle cells than in cardiomyocytes). Antianginal due to increased coronary and peripheral arteries and arterioles. When angina reduces the severity of myocardial ischemia; expanding peripheral arterioles, decreases total peripheral vascular resistance, decreases the preload on the heart, reducing myocardial oxygen demand. Expanding the coronary arteries and arterioles in the unaltered and ischemic myocardial areas, increases the supply of oxygen to the myocardium (especially in vasospastic angina); It prevents the development of coronary artery spasm (including those caused by smoking). In patients with stable angina single daily dose increases exercise tolerance, increases the time to onset of angina and “ischemic” ST segment depression, reduces the frequency of angina attacks and consumption of nitroglycerin and other nitrates. Has a long dose-dependent antihypertensive effect. Antigiperenzivnoe effect due to the direct vasodilating effect on vascular smooth muscle. When hypertension single dose provides a clinically significant reduction in blood pressure (BP) for 24 hours (in the position of the patient “lying” and “standing”). Orthostatic hypotension in the appointment of proviron cycle is quite rare. It does not cause a decrease in left ventricular ejection fraction. It reduces the degree of left ventricular hypertrophy. No effect on myocardial contractility and conductivity, does not cause reflex increase in heart rate (HR), inhibits platelet aggregation, increases glomerular filtration rate, has a weak natriuretic effect. In patients with coronary heart disease (CHD) (including coronary atherosclerosis with defeat one the vessel and to the stenosis 3 or more of the arteries and carotid atherosclerosis), myocardial infarction, percutaneous transluminal angioplasty of the coronary arteries (PTCA) or angina pectoris, proviron for sale prevents the development of thickening intima-media carotid arteries, reduces mortality from myocardial infarction, stroke, , PTCA, coronary bypass surgery, reduces the number of hospitalizations for unstable angina and progression of chronic heart failure, reduces the frequency of interventions aimed at restoring coronary blood flow.proviron cycle does not increase the risk of death or complications that lead to the deaths in patients with chronic heart failure (CHF) (III-IY functional class NYHA classification) during therapy with digoxin, diuretics and angiotensin-converting enzyme (ACE). In patients with chronic heart failure (III-IV functional class NYHA classification) non-ischemic etiology when using proviron cycle there is a possibility of occurrence of pulmonary edema. In diabetic nephropathy does not increase the severity of microalbuminuria. It does not have any adverse effect on the metabolism and the concentration of plasma lipids and can be used in the treatment of patients with asthma, diabetes and gout. Significant blood pressure reduction is observed in 6-10 hours duration of effect – 24 hours.
Following oral proviron cycle slowly absorbed from the gastrointestinal tract (GIT). The mean absolute bioavailability of 64%, the maximum concentration (C max ) in the blood serum is observed after 6-9 hours. The equilibrium concentrations are achieved after 7-8 days of treatment. Ingestion of proviron cycle does not affect the absorption.
The mean volume of distribution of 21 l / kg body weight, indicating that most of the drug is in the tissues, and smaller – in the blood. Most of the drug present in the blood (95%), bind to plasma proteins.proviron cycle undergoes slow but active metabolism (90%) in the liver in the absence of a significant effect of “first pass”. Metabolites not possess significant pharmacological activity.
After a single dose half-life (T ½ ) varies from 31 to 48 hours, with repeated use T ½ was about 45 hours. About 60% of an oral dose is excreted primarily by the kidneys as metabolites, 10% unchanged and 20-25% through the intestines with bile. The total clearance is proviron cycle OD 16 mL / s / kg (7 ml / min / kg and 0.42 L / h / kg).
In older patients (over 65 years) proviron cycle delayed excretion (T ½ of 65 hours) as compared to young patients, however, this difference has no clinical significance. Elongation T ½ in patients with hepatic failure it is assumed that the assignment for prolonged drug accumulation in the body is higher than (T ½ to 60 hours). Patients with impaired renal function changes proviron cycle plasma concentration does not correlate with the degree of renal failure. Perhaps a slight increase in the T ½ .
proviron cycle penetrates the blood-brain barrier into the breast milk. When hemodialysis is not removed.
Arterial hypertension (monotherapy or in combination with other antihypertensive agents);
Stable angina and vasospastic angina (Prinzmetal angina) (monotherapy or in combination with other antianginal drugs).
: Hypersensitivity to proviron cycle, to other dihydropyridine derivatives and other ingredients; severe hypotension (blood pressure sistolichnskoe less than 90 mm Hg); collapse, cardiogenic shock; acute myocardial infarction (during the first 28 days); unstable angina (except Prinzmetal’s angina); obstruction of the left ventricular outflow tract; clinically significant aortic stenosis; pregnancy and lactation; age of 18 years (effectiveness and safety have not been established).
Due to the fact that the product contains lactose, Amlodifarm ® is not recommended for patients with neperonosimostyu lactose, lactase deficiency, glucose-galactose malabsorption.
With caution: liver dysfunction, weakness syndrome sinus node (bradycardia, tachycardia), nonischemic etiology of heart failure III-IV NYHA functional class classification, hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (after 28 days), advanced age.
Pregnancy and lactation
The safety of proviron cycle medication during pregnancy and lactation has not been established, so the drug Amlodifarm ® should not be administered to pregnant and lactation.
Women of childbearing age during treatment should use reliable methods of contraception. When pregnancy occurs the drug should be discontinued immediately.
Dosing and Administration
Inside, once a day, drinking plenty of water (100 ml). The initial dose for the treatment of hypertension and angina is 5 mg once in one day. The dose may be increased to a maximum of 10 mg 1 time per day.Increasing the dose is recommended in 7-14 days after initiation of therapy (more rapid dose escalation requires close monitoring of the patient). In patients with impaired liver function the half-life of proviron cycle is increased. Recommendations on the dosage of the drug in this case has not been developed, so such patients the drug should be used with caution and under the supervision of the attending physician.
Elderly patients may increase the T ½ of proviron cycle and the decline in creatinine clearance (CC). Changes in dose is not required, but must be more careful monitoring of patients.
No dosage adjustment is required while the use of thiazide diuretics, beta-blockers and angiotensin-converting enzyme (ACE).
Not required dose modification in patients with renal insufficiency.
Classification of the incidence of side effects of the World Health Organization (WHO):
very often: more than 1/10;
common: more than 1/100 and less than 1/10;
uncommon: more than 1/1000 and less than 1/100;
rare: more than 1 / 10000 and less than 1/1000;
very rare: more than 1/10000, including isolated reports. Since the cardiovascular system : often – peripheral edema (ankles and feet), palpitations, hot feeling and “tides” of blood to the skin of the face ;infrequently – marked reduction in blood pressure, orthostatic hypotension, vasculitis; rarely – the development or exacerbation of congestive heart failure flow; very rarely – arrhythmias (bradycardia, ventricular tachycardia, atrial fibrillation), heart attack, chest pain. On the part of the central and peripheral nervous system : often – headache, dizziness, fatigue, drowsiness; rarely – fatigue, malaise, hypoesthesia, paresthesia, peripheral neuropathy, tremor, vertigo, syncope, insomnia, mood lability, abnormal dreams, anxiety, depression, anxiety; rarely – seizures, lethargy, agitation; rarely -ataksiya, amnesia. From the digestive system : often – nausea, stomach pain; rarely – vomiting, constipation or diarrhea, flatulence, dyspepsia, anorexia, dryness of the oral mucosa, thirst; rarely – gingival hyperplasia, increased appetite; very rarely – pancreatitis, gastritis, jaundice (caused by cholestasis), hyperbilirubinemia, increased activity of “liver” transaminases, hepatitis. From the hematopoietic system : very rarely – thrombocytopenic purpura, leukopenia, thrombocytopenia. From the urogenital system : rarely – frequent urination, painful urinary urgency, nocturia, impotence; very rarely – dysuria, polyuria. For the skin : rarely – dermatitis; very rarely – dermatoxerasia, violation of skin pigmentation. From the musculoskeletal system : rarely – arthralgia, muscle cramps, myalgia, back pain, arthritis; . rarely – myasthenia part of metabolism : rarely – hyperglycemia. The respiratory system : rarely – dyspnea, rhinitis; very rarely – cough. Allergic reactions : rarely – itching, rash (including erythematous, maculopapular rash); very rarely – urticaria, angioneurotic edema, erythema multiforme. Others : rare – alopecia, “ringing” in the ears, gynecomastia, increase / decrease in body weight, blurred vision, diplopia, disturbance of accommodation, xerophthalmia, conjunctivitis, eye pain, taste perversion, fever, nosebleeds; very rarely – parosmiya, “cold” sweat.
Overdose Symptoms : marked reduction of blood pressure with possible development of reflex tachycardia and excessive peripheral vasodilation (the risk of severe and persistent hypotension, including the development of shock and death). Treatment : gastric lavage, activated carbon (especially in the first 2 hours after the overdose), maintain the function of the cardiovascular system, the exalted position of the lower extremities, the control parameters of the heart and lung function, control of blood volume and diuresis. To restore vascular tone – use of a vasoconstrictor (in the absence of contraindications to their use); to eliminate the effects of calcium channel blockade – intravenous calcium gluconate. Hemodialysis is ineffective.
Interaction with other medicinal products
proviron cycle may be safely used for the treatment of hypertension with thiazide diuretics, alpha-blockers or angiotensin-converting enzyme (ACE). Patients with stable angina pectoris, proviron cycle can be combined with other antianginal drugs, such as nitrates, prolonged or short-acting.
Unlike other BCCI clinically significant proviron cycle interaction (II generation BCCI) was not in the combined use with nonsteroidal anti-inflammatory drugs (NSAIDs) in including indomethacin. Perhaps strengthening anti-anginal and anti-hypertensive action BCCI when combined with thiazide and “loop” diuretics, ACE and nitrate inhibitors, as well as strengthening their antihypertensive effect when used together with alpha 1-blockers.
Erythromycin in a joint application raises C max proviron cycle in young patients 22%, and the elderly -. 50%
Beta-blockers while the use of proviron cycle may cause exacerbation of chronic heart failure.
Although proviron cycle studying the negative inotropic effects are not usually observed, however, some BCCI may increase the severity of the negative inotropic effects antiarrhythmic agents causing prolongation of the interval QT (such as amiodarone and quinidine).
A single dose of 100 mg of sildenafil in patients with arterial hypertension has no effect on the pharmacokinetic parameters of proviron cycle.
Repeated administration of proviron cycle 10 mg and atorvastatin 80 mg is not accompanied by significant changes in indicators . pharmacokinetics of atorvastatin
ethanol (beverages containing alcohol): proviron cycle with single and repeated administration at a dose of 10 mg did not affect the pharmacokinetics of ethanol.
Antiretroviral drugs (ritonavir) increase the plasma concentrations of BCCI, including proviron cycle.
Antipsychotics and isoflurane – increased antihypertensive deytsivya priozvodnyh dihydropyridine.
calcium can reduce the effect of BCCI.
When combined with proviron cycle drugs lithium may increase neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus). proviron cycle does not change the pharmacokinetics of cyclosporine.
It has no effect on serum digoxin concentration and its renal clearance.
Do not have a significant influence on the effect of warfarin (prothrombin time). Cimetidine did not affect the pharmacokinetics of proviron cycle.
In in vitro proviron cycle studies did not affect the binding to plasma proteins, digoxin, phenytoin, warfarin and indomethacin.
Grapefruit juice: simultaneous single dose of 240 mg of grapefruit juice and 10mg proviron cycle inside is not accompanied by a significant change in the pharmacokinetics of proviron cycle.
aluminum- or magnesium-containing antacids: their single dose had no significant effect on the pharmacokinetics of proviron cycle.
During treatment with Amlodifarm is necessary to control body weight and sodium intake, shows the assignment of an appropriate diet.
It is necessary to maintain oral hygiene and seeing a dentist (prevention of pain, bleeding and gingival hyperplasia). In applying the drug Amlodifarm ® in patients with chronic heart failure III and IV functional class on classification NYHA may develop pulmonary edema.
Patients with hepatic impairment, if necessary, taking the drug Amlodifarm ® should be under the supervision of a physician.
Elderly patients can be prolonged half-life and reduced clearance drug. Changes in dosage is required, but requires careful monitoring of patients in this category.
The efficacy and safety of the drug for hypertensive crisis has not been established.
Despite the lack of BCCI syndrome “cancel”, the gradual reduction in dose is recommended before the termination of treatment.
Proviron cycle is considered one of the safest steroids of its kind. It causes only minor side effects in men. As a rule, they generally do not have a place. Nevertheless, the picture changes when we take into account its influence on the female body. He is more vulnerable to its consequences. As a rule, experts do not recommend using this steroid for the female cycle. There is a very high probability of problems with virilization. In most cases, it promotes abundant hair growth in different parts of the body and a sufficient expansion of the clitoris. In addition, it can make the voice deeper. Therefore, if women want to preserve femininity, it would be better to abandon the use of this steroid.
Effects on ability to drive vehicles and other complex mechanisms : In some patients, especially at the beginning of treatment or when changing dose regimen, due to the potential of significant decrease in blood pressure may experience drowsiness, dizziness and other side effects. If this happens, it is not recommended driving and using machinery that require high concentration and speed of psychomotor reactions . buy anabolic steroids online bruce lee’s workout anabolic steroids online uk