Pharmacological properties of the drug Felodip
Pharmacodynamics. Felodip is a dihydropyridine derivative, a selective blocker of L-type calcium channels. It has a high affinity for smooth muscle cells of peripheral arterioles and coronary arteries. Felodip dilates arterioles, reduces peripheral vascular resistance and blood pressure. In therapeutic doses it has virtually no effect on myocardial contractility. Felodip has an antianginal effect by reducing vascular resistance of the coronary vessels, improving coronary circulation and oxygen supply to the myocardium, and also reduces afterload on the heart, which leads to a decrease in myocardial oxygen demand. Felodip improves exercise tolerance and reduces the frequency of attacks in patients with stable angina, and has an anti-ischemic effect in vasospastic angina. The primary hemodynamic effect of Felodip is a decrease in general peripheral vascular resistance, thereby reducing blood pressure. This effect is dose dependent. As a rule, a decrease in blood pressure is observed 2 hours after a single dose and lasts for at least 24 hours, the T/P ratio (plateau/peak) reaches a value well above 50%. There is a positive relationship between the concentration of the drug in the blood plasma, the level of decrease in OPSS and the decrease in blood pressure. Felodip has a slight natriuretic and diuretic effect, since it reduces tubular reabsorption of sodium. Felodip does not affect the daily excretion of potassium. In patients with reduced renal function, glomerular filtration rate may increase during treatment with Felodip. Felodip is well tolerated by patients after kidney transplantation. The drug does not affect the concentration of glucose in the blood and the lipid profile. Pharmacokinetics. Felodip is completely absorbed into the gastrointestinal tract. Bioavailability is about 15% and does not depend on the dose taken (first pass effect through the liver). 99% of Felodipa binds to blood plasma proteins, mainly albumin. Due to the peculiarities of the dosage form, the prolonged release of felodipine extends the absorption phase and ensures its uniform concentration in the blood plasma over 24 hours. The drug penetrates the BBB and the placental barrier, and into breast milk. Felodipine is completely metabolized in the liver, all of its metabolites are inactive. The half-life of felodipine is 25 hours. With prolonged use, accumulation of the active substance does not occur. In elderly patients and with impaired liver function, plasma concentrations of felodipine are higher than in young patients. The pharmacokinetics of Felodip does not change in patients with impaired renal function, including those undergoing hemodialysis. About 70% of the dose taken is excreted in the urine, and 30% is excreted in the feces in the form of metabolites. 0.5% of the dose taken is excreted unchanged in the urine.
Felodipine 10 mg, 30 extended-release film-coated tablets (Ozone)
Registration Certificate Holder
ATOLL (Russia)
Dosage form
Medicine - Felodipine
Description
Extended-release film-coated tablets
light pink to pink, round, biconvex; a cross-section shows an almost white core and a filmy shell.
1 tab.
felodipine 10 mg
Excipients
: lactose monohydrate - 84 mg, hypromellose - 84 mg, macrogol stearate - 8 mg, colloidal silicon dioxide - 3 mg, magnesium stearate - 1 mg.
Tablet shell composition:
hypromellose - 2.9 mg, macrogol 4000 - 0.7 mg, titanium dioxide - 1.33 mg, red iron oxide dye - 0.07 mg.
10 pieces. — cellular contour packages (1) — cardboard packs. 10 pieces. — contour cell packaging (2) — cardboard packs. 10 pieces. — cellular contour packages (3) — cardboard packs. 10 pieces. — contour cell packaging (4) — cardboard packs. 10 pieces. — contour cell packaging (5) — cardboard packs. 10 pieces. — contour cell packaging (6) — cardboard packs. 10 pieces. — contour cell packaging (10) — cardboard packs. 30 pcs. — cellular contour packages (1) — cardboard packs. 30 pcs. — contour cell packaging (2) — cardboard packs. 30 pcs. — cellular contour packages (3) — cardboard packs. 30 pcs. — contour cell packaging (4) — cardboard packs. 30 pcs. — contour cell packaging (5) — cardboard packs. 30 pcs. — contour cell packaging (6) — cardboard packs. 30 pcs. — contour cell packaging (10) — cardboard packs. 10 pieces. - cans made of polyethylene terephthalate (1) - cardboard packs. 20 pcs. - cans made of polyethylene terephthalate (1) - cardboard packs. 30 pcs. - cans made of polyethylene terephthalate (1) - cardboard packs. 40 pcs. - cans made of polyethylene terephthalate (1) - cardboard packs. 50 pcs. - cans made of polyethylene terephthalate (1) - cardboard packs. 60 pcs. - cans made of polyethylene terephthalate (1) - cardboard packs. 100 pieces. - cans made of polyethylene terephthalate (1) - cardboard packs.
Indications
Arterial hypertension, angina pectoris (if beta-blockers and nitrates are ineffective), Raynaud's syndrome (as symptomatic therapy).
Contraindications for use
Acute myocardial infarction, decompensated chronic heart failure, age under 18 years, pregnancy, women of childbearing age with a high probability of pregnancy, hypersensitivity to felodipine.
pharmachologic effect
Selective class II calcium channel blocker from the group of dihydropyridine derivatives. Like other dihydropyridine derivatives, felodipine has a significantly higher affinity for the calcium channels of arterial smooth muscle cells than for the calcium channels of cardiomyocytes. By blocking calcium channels and disrupting the flow of calcium ions into the smooth muscle cells of arterial vessels, it causes their expansion, reduces peripheral vascular resistance and lowers blood pressure. Reduces afterload on the heart.
It has virtually no inhibitory effect on myocardial contractility and conductivity and causes moderate reflex tachycardia. Increases coronary blood flow.
Reduces the flow of extracellular calcium into cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries; in high doses reduces the release of calcium ions from intracellular stores. Reduces the number of functioning channels without affecting the time of their activation, inactivation and recovery. It uncouples the processes of excitation and contraction in the myocardium, mediated by tropomyosin and troponin, and in vascular smooth muscles, mediated by calmodulin.
In therapeutic doses, it normalizes the transmembrane calcium current, which is disturbed in a number of pathological conditions, primarily arterial hypertension. Reduces blood pressure due to vasodilation, reducing peripheral vascular resistance. It does not affect venous tone and adrenergic vasomotor innervation, and therefore does not cause orthostatic hypotension.
Has a dose-dependent anti-ischemic effect. Strengthens coronary blood flow, improves blood supply to ischemic areas of the myocardium without developing the “steal” phenomenon, activates the functioning of collaterals, protects against complications of reperfusion, and slightly increases heart rate. By dilating peripheral arteries, it reduces afterload.
Almost no effect on the sinoatrial and AV nodes. It has virtually no negative inotropic effect (a reflex increase in heart rate in response to vasodilation masks the negative inotropic effect).
Increases renal blood flow and has a moderate natriuretic and diuretic effect.
The action begins within 2-5 hours and continues for 24 hours. The severity of the effect correlates with the dose and plasma concentration.
Drug interactions
When used simultaneously with inhibitors of microsomal liver enzymes, it is possible to increase the concentration of felodipine in the blood plasma.
It is possible to reduce the concentration of felodipine in the blood plasma due to an increase in the intensity of its metabolism in the liver under the influence of carbamazepine, phenytoin and phenobarbital (which are inducers of microsomal liver enzymes) and accelerated excretion from the body.
When used simultaneously with digoxin, an increase in the concentration of digoxin in the blood plasma is possible.
When used simultaneously with itraconazole and ketoconazole, the metabolism of felodipine in the liver slows down, which leads to an increase in the concentration of felodipine in the blood plasma and an increased risk of side effects.
When used simultaneously with erythromycin, the bioavailability of felodipine increases. There is a report of increased therapeutic and side effects of felodipine in a patient receiving erythromycin.
Increases the bioavailability of propranolol. When used simultaneously with beta-blockers, the risk of developing chronic heart failure increases.
A decrease in the antihypertensive effect is observed with the simultaneous use of felodipine with NSAIDs, corticosteroids (sodium retention and blockade of prostaglandin synthesis by the kidneys) and estrogens (sodium retention), calcium preparations; The antihypertensive effect is enhanced when used simultaneously with inhaled anesthetics, beta-blockers, alpha-blockers, sympathomimetics and other antihypertensive drugs.
Drugs that cause QT prolongation potentiate the negative inotropic effect and may increase the risk of significant QT prolongation.
Dosage regimen
Used orally mainly in the form of dosage forms that provide constant release of the active substance - 5-10 mg 1 time / day, if necessary - 20 mg 1 time / day.
Maximum daily dose
is 20 mg.
Side effect
From the cardiovascular system:
flushes of blood to the facial skin, accompanied by facial hyperemia, tachycardia, swelling in the ankle joint (as a result of precapillary vasodilation), fainting, extrasystole, severe arterial hypotension, accompanied by reflex tachycardia and worsening angina, leukocytoclastic vasculitis.
From the side of the central nervous system:
headache, dizziness, feeling of fatigue, paresthesia.
From the digestive system:
nausea, abdominal pain, vomiting, increased activity of liver transaminases, hyperplasia of the gums, tongue mucosa, gingivitis.
From the musculoskeletal system:
rarely - arthralgia, myalgia.
Allergic reactions:
skin rash, itching, urticaria, angioedema of the lips or tongue, photosensitivity reaction.
Other:
impotence/sexual dysfunction, frequent urination, fever, hyperglycemia.
special instructions
Use with caution in patients with heart failure, blood pressure lability, renal failure, heart failure after myocardial infarction.
When used in patients with angina pectoris, it should be taken into account that in rare cases, felodipine can cause severe arterial hypotension, which leads to myocardial ischemia.
Use during pregnancy and breastfeeding
Restrictions during pregnancy - Contraindicated.
Contraindicated for use during pregnancy (including possible).
Use for renal impairment
Restrictions for impaired renal function - With caution.
Use with caution in patients with renal failure.
Use in children
Restrictions for children - Contraindicated.
Contraindicated in people under 18 years of age.
Use of the drug Felodip
AH (arterial hypertension) The dose is determined individually (including in elderly people). The initial dose is usually 5 mg 1 time per day. If necessary, the dose can be increased or another antihypertensive drug added. The maintenance dose is usually 5–10 mg once a day. To determine your individual dose, it is best to use 2.5 mg tablets. For use in the elderly, the initial dose is 2.5 mg/day. Stable angina. Treatment begins with a dose of 5 mg 1 time per day; if necessary, the dose can be increased to 10 mg 1 time per day. The maximum daily dose is 20 mg in 1 dose. In patients with severe liver dysfunction, the therapeutic dose should be reduced (the recommended initial dose is 2.5 mg/day). In patients with impaired renal function, changes in pharmacokinetics are insignificant, so dose adjustment of the drug is not required. It is better to take the drug in the morning before meals or after a light breakfast. Felodip tablets should not be chewed, divided or crushed. There is no experience with the use of Felodip in pediatrics.
Possibilities of felodipine in the treatment of arterial hypertension
About the article
9581
0
Regular issues of "RMZh" No. 21 dated September 25, 2008 p. 1416
Category: Cardiology
Author: Nedogoda S.V. 1 1 FSBEI HE Volgograd State Medical University of the Ministry of Health of Russia, Volgograd, Russia
For quotation:
Nedogoda S.V. Possibilities of felodipine in the treatment of arterial hypertension. RMJ. 2008;21:1416.
In Russia, felodipine, a representative of calcium antagonists (CA) from the subgroup of dihydropyridines, has not quite justifiably taken a backseat in the treatment of arterial hypertension (AH) compared to amlodipine, although throughout the world it continues to firmly occupy a leading position among a large number of antihypertensive drugs . This is due not only to the clinical and pharmacological characteristics of the drug [9,21,26], but also to the currently available large evidence base for its use in hypertension.
It seems that felodipine is going into the shadows in our country due to two most important reasons. Firstly, in Russia for a long time there were no high-quality generics of felodipine on the pharmaceutical market. And, secondly, in recent years, a number of large studies have been completed on another representative of this group of calcium antagonists - amlodipine, which, naturally, allowed it to come into the spotlight.
In contrast to non-dihydropyridine AKs - verapamil and diltiazem - dihydropyridine antagonists, including felodipine, have a slight effect on myocardial contractility and do not affect the function of the sinus node and atrioventricular conduction at all. These properties largely determine the features of clinical use [26]. Felodipine is a modern second-generation AK from the group of dihydropyridine derivatives. Moreover, felodipine has vascular selectivity 7–10 times greater than nifedipine [26].
When taken orally, felodipine is rapidly absorbed and its maximum concentration is observed after 1 hour. The relatively low bioavailability (about 15%) is due to the high rate of metabolism of the drug in the liver. In patients with liver cirrhosis, due to the high rate of presystemic elimination, it is necessary to reduce the daily dose of the drug. But for the same reason, in chronic renal failure there is no need to adjust the dose of felodipine. Up to 99% of felodipine is bound to protein. The half-life (T1/2) of felodipine averages about 14 hours, which ensures that its concentration in the blood remains constant. For the same reason, its use is much less likely to cause side effects typical of short-acting AKs. In terms of its pharmacokinetic parameters (Table 1), felodipine “loses” only to amlodipine [2], and clinical studies have not identified a “winner” [4,7,16,20,22–25,28].
The hypotensive effect develops within 15–45 minutes. after oral administration and has a dose-dependent nature, and its concentration in the blood plasma positively correlates with a decrease in vascular peripheral resistance and blood pressure (BP). At the beginning of treatment, a decrease in blood pressure may be accompanied by a transient increase in heart rate, but with long-term use, activation of the sympathetic-adrenal system is not observed [10,12,27]. Felodipine also has a mild diuretic effect (26). The optimal dosage regimen for felodipine for hypertension is considered to be 5–10 mg 1–2 times a day. It is important that during therapy with felodipine there is a significant regression of hypertrophied left ventricular myocardium (LVH). After several months of therapy, the mass of the myocardium, the thickness of the interventricular septum and the posterior wall of this ventricle decrease (according to echocardiography). Felodipine is a metabolically neutral drug, including in problematic patients with type 2 diabetes mellitus (DM) [5,13]. After stopping treatment with felodipine, no withdrawal syndrome is observed [3].
The undoubted advantages of felodipine include its antianginal effect [26].
The evidence base for the use of felodipine in hypertension is currently, of course, one of the most powerful.
First of all, it is necessary to remember that one of the fundamental studies in modern cardiology, HOT (Hypertension Optimal Treatment study), in which 18,790 patients took part, felodipine was used as the main drug. This study examined the effect of the degree of blood pressure reduction on the risk of developing cardiovascular diseases, as well as on mortality in patients with hypertension. The results of the HOT study [14] convincingly demonstrated that effective treatment of hypertension can be achieved using felodipine as the main antihypertensive drug. Thus, at the end of the study, 78% of patients continued to take felodipine as primary therapy, with only 41% of patients using it in combination with an angiotensin-converting enzyme inhibitor (ACE inhibitor) and 28% with the beta-blocker metoprolol. Consequently, for about four years, antihypertensive monotherapy was effective in almost half of the patients, which is undoubtedly a very good indicator. It was shown that the good antihypertensive efficacy and tolerability of felodipine were independent of age and concomitant pathology, and the incidence of cardiovascular diseases and complications during treatment including felodipine was significantly lower than in earlier studies using a diuretic or beta-blocker. , due to effective BP control in the HOT study.
The HOT study demonstrated the high effectiveness of the combination of felodipine with metoprolol, an ACE inhibitor and acetylsalicylic acid. The advisability of using felodipine for hypertension in the elderly was also once again confirmed [8], which was previously shown in the STOP–Hypertension 2 study (Swedish Trial in Old Patients with Hypertension 2).
Unfortunately, in Russia, practicing doctors are poorly informed about the results of the relatively recently completed large study FEVER (Felodipine EVEnt Reduction), although the most famous specialist in the field of hypertension Prof. Alberto Zanchetti put it in line with studies such as PROGRESS, ALLHAT and others [17,18]. This randomized, double-blind, placebo-controlled study assessed whether felodipine or placebo could reduce the risk of cardiovascular events in nearly 10,000 hypertensive patients with a baseline high risk of these events after their blood pressure had been significantly reduced by hydrochlorothiazide therapy. at a low dose, and felodipine was used to achieve its target level.
This study included hypertensive patients aged 50–79 years, of both sexes, with SBP/DBP <210/115 mmHg, on antihypertensive medication or with SBP 160–210 mmHg. or DBP 95–115 mm Hg. without antihypertensive therapy. Patients 50–60 years old had to have ≥2 risk factors or clinical manifestations of diseases, and patients 61–79 years old had to have ≥1 risk factor or clinical manifestations of diseases.
The main cardiovascular risk factors were male gender, smoking, total cholesterol ≥240 mg/dL during the last year or lipid-lowering therapy, compensated diabetes, LVH, proteinuria and excess body weight (BMI >27 kg/m2). Major cardiovascular events included myocardial infarction, stroke, stable angina or clinical manifestations of coronary artery disease, congestive heart failure, peripheral circulatory disorders and transient ischemic attacks.
Patients were initially treated with hydrochlorothiazide (HCTZ) 12.5 mg/day monotherapy for 6 weeks (other antihypertensives were excluded in 89% of previously treated patients), followed by 9800 patients with DBP 90–100 mmHg. and/or SBP 140–160 mmHg. were randomized into 2 groups: some received HCTZ plus felodipine 5 mg/day, others HCTZ plus placebo.
The addition of a diuretic or other antihypertensive drugs was allowed at the discretion of the study physician. The most commonly prescribed medications were diuretics, ACE inhibitors, and ACE inhibitors, but 66.1% of patients in the felodipine group and 57.7% in the placebo group remained on these medications throughout the study period. The study ended when the required number of primary endpoints (400) were recorded.
The mean SBP/DBP at screening was 159/93 mmHg. After 6 months of follow-up, the mean SBP/DBP was 142.5/85 mmHg. in the placebo group versus 137.3/82 mm Hg. in the felodipine group. These group differences remained constant throughout the study period for a mean reduction in SBP/DBP of 4/2 mmHg. By the end of follow-up (60 months), more patients in the felodipine + HCTZ group achieved SBP <140 mmHg. and DBP <90 mm Hg. compared with the placebo + HCTZ group (Table 2).
The FEVER study showed that the number of strokes (fatal and non-fatal) was significantly lower (–28%) in the felodipine group (Table 3). It should be noted that this reduction in the risk of stroke was detected while taking diuretics, which are considered one of the most effective means in reducing the risk of stroke.
Significant reductions in the felodipine + HCTZ group versus placebo were also found in the secondary outcomes of cardiovascular events (-28%), all cardiovascular events (-28%), all cardiac events (-34%), all-cause mortality (-30%), cardiac –vascular mortality (–32%), coronary events (–32%), HF (–24%) and cancer (–40%).
All treatment regimens in the study were well tolerated, although the felodipine group experienced more frequent hot flashes (1.4% vs. 0.2%, p<0.001) and leg swelling (1.0% vs. 0.37%, p< 0.001), but symptoms of fatigue were significantly less common (0.64% vs. 1.05%, p=0.037) compared to the placebo group. There were no differences in the incidence of dizziness, headache or palpitations between the two groups.
Commenting on the results of the FEVER study, prof. Alberto Zanchetti noted that even differences in SBP/DBP ratios of 4/2 mmHg. when comparing calcium antagonists versus placebo, may be accompanied by a further reduction in cardiovascular events, even in patients at low cardiovascular risk compared with patients in most recent studies (Syst-Eur, Syst-China, HOPE, PATS, PROGRESS, ALLHAT, SCOPE, LIFE , VALUE, INVEST, EUROPA, ACTION), in which patients with hypertension initially had a high risk of developing cardiovascular complications. Also noteworthy was a significant reduction in the incidence of cancer in patients in the felodipine group.
It seems important that felodipine demonstrated an increase in the hypotensive effect and a decrease in the incidence of side effects when combined with enalapril (Enalapril Felodipine ER Factorial Study), a slowdown in chronic kidney disease in patients with hypertension and non-diabetic nephropathy when combined with ramipril (The Nephros Study), a marked decrease LVH in combination with irbesartan (SILVER) and a decrease in blood pressure in people with refractory hypertension in whom therapy with two antihypertensive drugs was ineffective (Cooperative Study Group) [6].
Today, claims that therapy with amlodipine and other calcium antagonists are pharmacoeconomically preferable to treatment with felodipine seem unfounded [4,7,16,19, 22–25,28]. Thus, after transferring 238 patients from 10 mg of amlodipine to 10 mg of felodipine [20], a tendency to a further decrease in blood pressure and a significant decrease in the number of heartbeats was observed (Table 4). However, concomitant antihypertensive therapy did not change (Table 5).
After the appearance in Russia of a high-quality generic felodipine - FELODIP (Teva company), the possibilities of reducing treatment costs are significantly reduced, despite the fact that one of the most modern AKs with a large evidence base and experience in clinical use is used. It should be noted that in terms of its pharmacokinetic parameters, generic FELODIP is practically no different from the original drug, which is confirmed by the results of a randomized crossover study of 48 healthy individuals. At the same time, the difference from the original in most pharmacokinetic parameters did not exceed 2%, with an acceptable level of 10%.
Thus, felodipine significantly expands the possibilities of mono- and combination therapy with other drugs, primarily ACE inhibitors [1,11] not only in patients with only hypertension, but also such concomitant diseases as diabetes, coronary artery disease, gout, broncho-obstructive syndrome, COPD . In addition, there is evidence of the high effectiveness of the drug for the treatment of hypertension in pediatric practice [15] and in the prevention of nephropathy during contrast studies [29].
References 1. Bainbridge AD, Macfadyen RJ, Stark S. et al. The antihypertensive efficacy and tolerability of a low dose combination of ramipril and felodipine ER in mild to moderate essential hypertension // Brit. J. Clin. Pharmacology. – 1993. – Vol. 36. – P. 323–330. 2. Baranda AB, Mueller CA, Alonso RM et al. Quantitative determination of the calcium channel antagonists amlodipine, lercanidipine, nitrendipine, felodipine, and lacidipine in human plasma using liquid chromatography–tandem mass spectrometry // Ther. Drug Monit. – 2005. – Vol. 27. – P. 44–52. 3. Black HR, Elliott WJ, Weber MA et al. One–year study of felodipine or placebo for stage 1 isolated systolic hypertension // Hypertension. – 2001. – Vol. 38. – P. 1118–1123. 4. Blivin SJ, Pippins J., Annis LG, Lyons F. A comparative analysis of amlodipine and felodipine in a military outpatient population: efficacy, outcomes, and cost considerations // Mil. Med. – 2003. – Vol. 168. – P. 530–535. 5. Capewell S., Collier A., Matthews D. et al A trial of the calcium antagonist felodipine in hypertensive type 2 diabetic patients// Diabet–Med.– 1989. Vol. 6.– P. 809–12. 6. Cooperative Study Group. Felodipine vs hydralazine: a controlled trial as third line therapy in hypertension // Br J Clin Pharmacol. – 1986.– Vol. 21. P. 621–626. 7. Dimenas E, Dahlof C, Olofosson B, Wiklund I. An instrument for quantifying subjective symptoms among untreated and treated hypertensives: development and documentation // J Clin Res Pharmacoepidemiol. – 1990. –Vol. 4. P:205–17. 8. Ekbom T., Linjer E., Hedner T. et al. Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP–Hypertension–2 // Blood Press. – 2004. – Vol. 13. – P. 137–141. 9. Ernst ME, Dellsperger KC, Phillips BG. Comparison of amlodipine and felodipine on 24–hour ambulatory blood pressure in hypertensive patients [abstr] //Am J Hypertens. – 2001. – P.118A. 10. Ficek J., Kokot F., Chudek J. et al. Influence of antihypertensive treatment with perindopril, pindolol or felodipinon plasma leptin concentration in patients with essential hypertension // Horm. Metab. Res. – 2002. – Vol. 34. – P. 703–708. 11. Francischetti A., Ono H., Frohlich ED Renoprotective effects of felodipine and/or enalapril in spontaneously hypertensive rats with and without L–NAME // Hypertension. – 1998. – Vol. 31. – P. 795–801. 12. Grassi G., Seravalle G., Turri C. Short-versus long-term effects of different dihydropyridines on sympathetic and baroreflex function in hypertension // Hypertension. – 2003. – Vol. 41. – P. 558–562. 13. Hishikawa K., Luscher T. Felodipine inhibits free–radical production by cytokines and glucose in human smooth muscle cells // Hypertension. – 1998. – Vol. 32. – P. 1011–1015. 14. Jonsson B., Hansson L., Stalhammar NO Health economics in the Hypertension Optimal Treatment (HOT) study: costs and cost-effectiveness of intensive blood pressure lowering and low-dose aspirin in patients with hypertension // J. Intern. Med. – 2003. – Vol. 253. – P. 472–480. 15. Kotchen TA, Mansour G., Mansour AJ Calcium channel blockers (felodipine) and pediatric essential hypertension // Curr. Hypertens. Rep. – 2003. – Vol. 5. – P. 484–485. 16. Krantz SR, Rase RS, Peipho RW. Retrospective analysis of formulary transition at large metropolitan HMO: nifedipine GITS to felodipine ER // J Managed Care Pharm. – 1996.–Vol.2.– P.642–6. 17. Lisheng L, Yuqing Z, Guozhang L et al. FEVER study: a trial further supporting the concept of a blood pressure–independent stroke protective effect by dihydropyridines // Journal of Hypertension. – 2006. – Vol. 24. P.1215–1216. 18. Liu L, Zhang Y, Liu G, Li W, Zhang X, Zanchetti A. The Felodipine EVEnt Reduction (FEVER) study: A randomized long–term placebo controlled trial in Chinese hypertensive patients – design and principal results // J Hypertens . – 2005. Vol. 23(suppl 2).– S118: Abstract P1.347. 19. Mamdani MM, Reisig CJ, Stevenson JG. Cost analysis of therapeutic interchange of calcium channel blockers for the treatment of hypertension: unexpected results from a conversion program // J Managed Care Pharm. – 2000. – Vol.6.–P.390–4. 20. Manzo BA, Matalka MS, Ravnan SL Evaluation of a therapeutic conversion from amlodipine to felodipine // Pharmacotherapy. – 2003. – Vol. 23. – P. 1508–1512. 21. Mayer O. Calcium channel blockers in the treatment of hypertension and ischemic coronary disease. Conflicts in their evaluation // Cas. Lek. Cesk. – 1998. – Vol. 6. – P. 216–219. 22. Menzin J, Lang K, Elliott WJ et al. Adherence to calcium channel blocker therapy in older adults: a comparison of amlodipine and felodipine // J. Int. Med. Res. – 2004. – Vol. 32. – P. 233–239. 23. Oatis G, Stowers AD. Conversion from amlodipine to felodipine ER: did the change fulfill expectations? //Formulary.– 2000.Vol. 35.– P.435–42. 24. Ostergren J, Isaksson H, Brodin U, Schwan A, Ohman P. Effect of amlodipine versus felodipine extended release on 24-hour ambulatory blood pressure in hypertension // Am J Hypertens. – 1998. – Vol.11. – P.690–6. 25. Romito R., Pansini MI, Perticone F. et al. Comparative effect of lercanidipine, felodipine, and nifedipine GITS on blood pressure and heart rate in patients with mild to moderate arterial hypertension: the lercanidipine in adults (LEAD) study // J. Clin. Hypertension (Greenwich). – 2003. – Vol. 5. – P. 249–253. 26. Scholze JE Differential therapy with calcium antagonists // Herz. – 2003. – Vol. 28. – P. 754–763. 27. Smith SA, Mace PJ, Littler WA Felodipine, blood pressure, and cardiovascular reflexes in hypertensive humans // Hypertension. – 1986. – Vol. 8. – P. 1172–1178. 28. Walters J, Noel H, Folstad J, Kapadia V, White CM. Prospective evaluation of the therapeutic interchange of felodipine ER for amlodipine in patients with hypertension// Hosp Pharm.– 2000.– Vol. 35. – P.48–51. 29. Wongand GTC, Irwin MG Contrast-induced Nephropathy // Br J Anaesth. – 2007. – Vol.99. P474–483.
Side effects of the drug Felodip
Like other calcium antagonists, felodipine can cause facial flushing, headache, palpitations, dizziness, and fatigue. These reactions are temporary and occur more often at the beginning of treatment or when the dose is increased. Depending on the dose, edema in the ankle area may occur as a result of precapillary vasodilation. Patients with gum disease or periodontitis may experience mild swelling of the gums; this can be prevented by maintaining good oral hygiene. As with the use of other dihydropyridines, in some cases an increase in the manifestations of angina was noted, mainly at the beginning of treatment. Cardiovascular system: tachycardia, palpitations, rarely - syncope, peripheral edema, facial flushing. Central and peripheral nervous system: headache, dizziness, rarely - paresthesia. Gastrointestinal tract: nausea, abdominal pain, in isolated cases - hyperplasia, inflammation of the gums. Liver: in isolated cases, an increase in the level of liver transaminases is noted. Musculoskeletal system: rarely - pain in joints and muscles. Allergic reactions: facial flushing, skin rash, itching; rarely - urticaria; in isolated cases - photosensitivity, vasculitis. Urinary system: in isolated cases - pollakiuria. Other: rarely - fatigue, sexual dysfunction, impotence; in isolated cases - hypersensitivity reactions, for example angioedema, increased body temperature.
Felodipine-SZ extended-release tablets 5 mg 30 pcs.
Felodipine-SZ is a slow calcium channel blocker used to treat arterial hypertension and stable angina. Felodipine is a dihydropyridine derivative. The conductivity and contractility of vascular smooth muscle is inhibited by affecting the calcium channels of cell membranes. Due to its high selectivity for arteriole smooth muscle, felodipine in therapeutic doses does not have a negative inotropic effect on cardiac contractility or conduction. Felodipine relaxes the smooth muscles of the respiratory tract. Felodipine has been shown to have little effect on gastrointestinal motility. With long-term use, felodipine does not have any effect on patients with type 2 diabetes mellitus. When using felodipine for 6 months, no clinically significant effect was observed on the metabolic processes of glycosylated hemoglobin (HbA1c). Felodipine may also be prescribed to patients with reduced left ventricular function receiving standard therapy and to patients with asthma, diabetes mellitus, gout or hyperlipidemia. Hypotensive effect: a decrease in blood pressure when taking felodipine is due to a decrease in total peripheral vascular resistance. Felodipine effectively reduces blood pressure in patients with arterial hypertension both in the supine, sitting and standing positions, at rest and during physical activity. Since felodipine has no effect on venous smooth muscle or adrenergic vasomotor control, orthostatic hypotension does not occur. At the beginning of treatment, as a result of a decrease in blood pressure while taking felodipine, a temporary reflex increase in heart rate (HR) and cardiac output may be observed. An increase in heart rate is prevented by the simultaneous use of beta-blockers with felodipine. The effect of felodipine on blood pressure and peripheral vascular resistance correlates with the plasma concentration of felodipine. The therapeutic effect of the drug lasts for 24 hours. Treatment with felodipine leads to regression of left ventricular hypertrophy. Felodipine has natriuretic and diuretic effects and does not have a kaliuretic effect. When taking felodipine, tubular reabsorption of sodium and water decreases, which explains the absence of salt and fluid retention in the body. Felodipine reduces vascular resistance in the kidneys and increases renal perfusion. Felodipine has no effect on glomerular filtration and albumin excretion. For the treatment of arterial hypertension, Felodipine-SZ can be used in monotherapy or in combination with other antihypertensive drugs, such as beta-blockers, diuretics or angiotensin-converting enzyme (ACE) inhibitors. Anti-ischemic effect: The use of felodipine leads to an improvement in blood supply to the myocardium due to dilation of the coronary vessels. Reducing the load on the heart is achieved by reducing total peripheral vascular resistance, which leads to a decrease in myocardial oxygen demand. Felodipine relieves spasm of coronary vessels. Felodipine improves contractility and reduces the frequency of angina attacks in patients with stable angina pectoris. At the beginning of therapy, a temporary increase in heart rate may be observed, which can be stopped by the administration of β-blockers. The effect occurs after 2 hours and lasts for 24 hours. For the treatment of stable angina, felodipine can be used in combination with β-blockers or in monotherapy.
Special instructions for the use of the drug Felodip
During treatment with Felodip, you should refrain from engaging in potentially dangerous activities that require concentration and speed of psychomotor reactions. Patients with angina pectoris should take into account that the drug can cause arterial hypotension, which can cause the appearance or intensification of myocardial ischemia. If liver function is impaired, it is necessary to adjust the dose of the drug. Felodip does not affect the concentration of glucose in the blood plasma and the lipid profile. Felodipine should not be taken in combination with grapefruit juice due to the fact that the latter contains a flavonoid that increases the concentration of felodipine in the blood serum. Felodip is effective and well tolerated by patients regardless of gender and age, persons with asthma, other obstructive pulmonary diseases, impaired renal function, patients with diabetes mellitus, gout, hyperlipidemia, Raynaud's syndrome, and after lung transplantation. Felodip is prescribed with caution, especially in combination with β-adrenergic receptor blockers, to patients with severe heart failure.
Drug interactions Felodip
The hypotensive effect of Felodip is enhanced by other antihypertensive drugs (beta-adrenergic receptor blockers, ACE inhibitors, diuretics), tricyclic antidepressants, and alcohol. When using Felodip, β-adrenergic receptor blockers and organic nitrates, the antianginal effect of these drugs is summed up. When used simultaneously with NSAIDs Felodip, the antihypertensive effect of Felodip is not reduced. Inhibitors of microsomal enzymes (cimetidine, erythromycin, ranitidine, ketoconazole, itraconazole, ritonavir, saquinavir, quinidine) increase the concentration of felodipine in the blood plasma, therefore the prescribed dose of Felodipine should be reduced when used simultaneously with this group of drugs. Inducers of microsomal enzymes (for example, phenytoin, carbamazepine, rifampicin and barbiturates) can reduce the concentration of felodipine in the blood plasma, so the dose of Felodipine should be adjusted when these drugs are used in combination. When Felodip is used simultaneously with digoxin, the concentration of the latter increases, but no change in the dose of Felodip is required. Significant binding of felodipine to plasma proteins does not affect the particle free fractions of another drug, which is also characterized by significant binding to plasma proteins (for example, warfarin). Grapefruit juice, due to the presence of a flavonoid in it, increases the plasma level and bioavailability of felodipine, so it cannot be used together with Felodipine.
Felodip overdose, symptoms and treatment
Symptoms: arterial hypotension and bradycardia. Treatment: the stomach is washed, activated carbon is used, and the patient is subsequently placed in an intensive observation room to monitor the function of the cardiovascular and respiratory systems. In case of severe arterial hypotension, it is necessary to place the patient in a horizontal position with the lower limbs raised upward, increase the volume of blood plasma by administering a physiological solution of sodium chloride, glucose, dextran; introduce sympathomimetics: norepinephrine, mesaton, dopamine, dobutamine, as well as calcium chloride. In case of bradycardia, AV block of II–III degree, or the appearance of asystole, atropine sulfate, norepinephrine or calcium chloride is administered intravenously. If necessary and if indicated, an artificial pacemaker is used.
