Instructions for use NIFEDIPINE
The drug is prescribed with caution for very low blood pressure (severe hypotension with systolic blood pressure below 90 mm Hg), as well as for severe cardiac weakness (decompensated heart failure).
In case of severe arterial hypotension (systolic pressure below 90 mm Hg), severe cerebrovascular accidents, severe heart failure, severe aortic stenosis, diabetes mellitus, impaired liver and kidney function, Nifedipine can be used only under conditions of constant clinical monitoring, avoiding the appointment of high doses of the drug.
In elderly patients (over 60 years of age), the drug is dosed with great caution.
Features of application.
Nifedipine should be prescribed with particular caution to patients undergoing hemodialysis, as well as patients with malignant hypotension or hypovolemia (decreased blood volume), since dilation of blood vessels can cause a significant decrease in blood pressure in them.
Some in vitro experiments have revealed a relationship between the use of calcium antagonists, in particular nifedipine, and reverse biochemical changes in sperm that impair the latter’s ability to fertilize. When treating coronary vasospasm in the post-infarction period, treatment with Nifedipine should begin approximately 3-4 weeks after myocardial infarction and only if the coronary circulation is stabilized.
Grapefruit juice inhibits the metabolism of nifedipine, which causes an increase in the concentration of the latter in the blood plasma and potentiation of the hypotensive effect of the drug. The use of nifedipine may lead to falsely elevated results when spectrophotometrically determining the concentration of vanillin-mideic acid in urine (however, this effect is not observed when using the high-performance liquid chromatography method).
Use during pregnancy or breastfeeding.
Nifedipine passes into breast milk, so breastfeeding should be discontinued if the use of Nifedipine is necessary during lactation.
Children.
The drug is not used in children under 14 years of age.
The ability to influence the reaction rate when driving a vehicle or working with other mechanisms.
When using the drug, driving vehicles and working with other potentially dangerous mechanisms is not recommended.
Nifedipine 20 retard
From the cardiovascular system: tachycardia, arrhythmias, peripheral edema (ankles, feet, legs), manifestations of excessive vasodilation (asymptomatic decrease in blood pressure, “flushes” of blood to the facial skin, flushing of the facial skin, feeling of heat), excessive decrease in blood pressure (rarely), fainting , development or worsening of heart failure (usually worsening of an existing one). In some patients (especially with severe obstructive lesions of the coronary arteries), at the beginning of treatment or when the dose is increased, attacks of angina pectoris may occur, including the development of myocardial infarction (requires discontinuation of the drug).
From the nervous system: headache, dizziness, increased fatigue, asthenia, drowsiness. With long-term ingestion in high doses - paresthesia of the limbs, tremor, extrapyramidal (parkinsonian) disorders (ataxia, mask-like face, shuffling gait, stiffness of the arms or legs, tremor of the hands and fingers, difficulty swallowing), depression.
From the digestive system: dry mouth, increased appetite, dyspepsia (nausea, diarrhea or constipation); rarely - gum hyperplasia (bleeding, pain, swelling), with long-term use - liver dysfunction (intrahepatic cholestasis, increased activity of liver transaminases).
From the musculoskeletal system: rarely - arthralgia, swelling of the joints, myalgia.
From the hematopoietic organs: anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura, asymptomatic agranulocytosis.
From the urinary system: increased daily diuresis, deterioration of renal function (in patients with renal failure).
Allergic reactions: rarely - itching, urticaria, exanthema, autoimmune hepatitis.
Local reactions: burning at the site of intravenous administration.
Other: rarely - visual impairment (including transient loss of vision against the background of Cmax in plasma), gynecomastia (in elderly patients, completely disappearing after withdrawal), galactorrhea, hyperglycemia, pulmonary edema (difficulty breathing, cough, wheezing), weight gain. Overdose. Symptoms: headache, flushing of the facial skin, prolonged pronounced decrease in blood pressure, suppression of sinus node function, bradycardia, bradyarrhythmia.
Treatment: in case of severe poisoning (collapse, depression of the sinus node), gastric lavage is performed and activated charcoal is prescribed. The antidote is Ca2+ preparations: slow intravenous administration of 10% CaCl2 or calcium gluconate is indicated, followed by switching to a long-term infusion.
With a pronounced decrease in blood pressure, dopamine or dobutamine is administered intravenously. For conduction disorders - atropine, isoprenaline or an artificial pacemaker. With the development of heart failure - intravenous administration of strophanthin. Catecholamines should be used only when there is a threat to life (due to their reduced effectiveness, a high dosage is required, which increases the risk of developing arrhythmia). It is recommended to monitor blood concentrations of glucose (insulin release may decrease) and electrolytes (K+, Ca2+).
Hemodialysis is ineffective.
Long-acting nifedipine preparations in modern cardiology
AND
The history of nifedipine use in cardiology exceeds 30 years. In the 70s and 80s it was one of the most popular cardiac drugs. However, in the mid-90s, a significant number of publications appeared in the English-language literature indicating the unsafe use of nifedipine in patients with coronary heart disease (CHD). A higher incidence of myocardial infarction was found compared to patients receiving other antihypertensive drugs. In addition, it was indicated that nifedipine therapy increases the risk of bleeding and even cancer. These works caused wide discussion not only among doctors, but also in the media. Serious shortcomings of these studies were highlighted. First, the meta-analysis of published studies did not know the baseline status of the patients. It is possible that nifedipine was prescribed with a greater frequency than other drugs to patients with hypertension (HTN) who had angina pectoris. Secondly, the studies analyzed used very high doses (up to 120 mg of nifedipine per day, average 80 mg per day). Third, all patients received a rapidly absorbed, short-acting form of nifedipine. Since nifedipine is a vasodilator, when taking high doses, vasodilation was maximum, which was accompanied by pronounced compensatory stimulation of the sympathetic nervous system and, of course, could lead to exacerbation of ischemic heart disease. The result of this discussion was a revision of the indications for prescribing short-acting nifedipine; in particular, it was not recommended to prescribe it to patients with myocardial infarction and unstable angina.
The results of subsequent studies indicate good tolerability and high effectiveness of prolonged forms of nifedipine. A number of studies have revealed their beneficial effect on the structural and functional state of the heart, blood vessels and kidneys both in hypertension and parenchymal arterial hypertension.
Our experience with nifedipine retard
(Corinfar-retard AVD GmbH, Germany) is based on an analysis of the results obtained in 1311 patients with arterial hypertension (AH) and stable coronary artery disease. Among them were 174 patients with hypertension stages I–II (WHO classification, 1962), 16 patients with hypertension in chronic pyelonephritis, 261 patients with stable angina of functional classes II–IV (FC) and 722 patients with stable angina, combined with GB. The vast majority of patients received the drug on an outpatient basis and were observed by cardiologists in St. Petersburg clinics. Patients received the drug free of charge. All patients kept diaries that reflected the dynamics of their health, the number of angina attacks per day, the number of nitroglycerin tablets taken, and the presence of side effects. During the first month, visits to the doctor were weekly, subsequently – once every 2 weeks. The duration of observation was 3 months. For 6 months, 21 patients with hypertension received nifedipine retard. In all patients with hypertension, the drug was prescribed as monotherapy. If there was no proper antihypertensive effect, after a month the patients were transferred to combination therapy. Almost all patients with angina pectoris received nitrosorbide for a long time, and those with class III–IV angina received b-blockers (including those with concomitant hypertension). The indication for the use of nifedipine retard was the persistence of angina attacks.
The study did not include patients with diabetes mellitus, heart defects, atrial fibrillation, heart failure, as well as persons who had suffered a cerebrovascular accident.
For hypertension, the initial dose of the drug was 20 mg 2 times a day. Subsequently, taking into account the achieved effect, the dose was reduced (to 20 mg once a day). However, in 5 (2.6%) patients, normalization of blood pressure (BP) values was achieved only when prescribed 60 mg per day (in 3 doses). In patients with coronary artery disease, the effectiveness of therapy was compared when prescribing the drug at a dose of 20 mg 1 and 2 times a day.
In patients with hypertension who received the drug for 6 months before therapy and 6 months after its start, systemic and renal hemodynamics were assessed.
The research results indicate a clear antihypertensive effectiveness of nifedipine retard both in patients with isolated hypertension and when it is combined with coronary artery disease (Table 1). In patients who required a larger dose of the drug to normalize blood pressure, its initial level was higher, as well as in those who received nifedipine 2 times a day. The decrease in blood pressure in all treatment regimens was not accompanied by a statistically significant increase in heart rate.
Long-term therapy with nifedipine retard led to significant changes in central and regional renal hemodynamics. In particular, total peripheral vascular resistance (TPVR) decreased by 16.7% (p <0.05), while the cardiac index increased by 16.4% (p <0.05). Renal vascular resistance (RVR) decreased to a greater extent than TPVR; a decrease in PSS naturally led to an increase in effective renal blood flow (Fig. 1).
*EPC—effective renal blood flow. Rice. 1. Changes in systemic and renal hemodynamics during 6-month therapy with nifedipine retard
Six-month therapy was accompanied by a decrease in the left ventricular myocardial mass index (LVMI) by 9.3%, the posterior wall thickness (PVT) of the left ventricle by 9.8%, and the interventricular septum (IVS) by 6.5% in the absence of significant changes in the size of the left ventricular cavity and left ventricular ejection fraction (Table 2). The reduction in LVMI was greatest in individuals with the highest initial values and did not correlate with the degree of blood pressure reduction. Indicators of diastolic function (isovolumic relaxation time, E/A ratio) did not change significantly; only a tendency towards their improvement was noted. At the same time, the time of isovolumic relaxation decreased to a greater extent in patients with the most significant decrease in LVMI (r = 0.65, p < 0.005).
Nifedipine retard also had a beneficial effect on the course of angina pectoris, which was manifested in a decrease in the number of angina attacks. Initially, in patients without hypertension, the number of angina attacks was 29.38 ± 2.18 per month, in those with concomitant hypertension – 30.1 ± 1.7 per month. After 12 weeks of therapy, it decreased to 11.6 ± 1.37 and 11.9 ± 1.2 per month, respectively. The greatest antianginal effect was obtained with initially non-severe exertional angina (FC II), while at the same time, with severe exertional angina (FC III–IV), the effectiveness of therapy was less.
In 257 patients with coronary artery disease without hypertension, the effectiveness of therapy with nifedipine retard was compared with a single and double dose (20 mg once and twice a day). A two-time dose of the drug had a more pronounced antianginal effect, which was not accompanied by a significant increase in the number of side effects.
In 58 of 722 patients with coronary artery disease combined with hypertension, rhythm disturbances (low-grade extrasystoles) were recorded on the initial electrocardiograms. Therapy with nifedipine retard did not lead to an increase in the number of extrasystoles. On the contrary, in 32 patients who initially had extrasystole, it was no longer detected.
It should be noted that the drug is well tolerated. Among the observed side effects, palpitations (3.8%), headache (3.5%), facial flushing (3.9%), dizziness (1.28%), feeling of heat (1.28%), increased diuresis (1.5%) and edema (1.14%). The severity of side effects was maximum in the early stages after the start of therapy. In the majority of patients (n = 64), the tolerability of the drug subsequently improved while maintaining the same dose; in 14 patients, the dose of nifedipine was reduced due to side effects; 2.1% of patients were forced to stop taking the drug due to poor tolerability.
Thus, the results of the study indicate the high antihypertensive and antianginal effectiveness of nifedipine retard. The basis of the blood pressure-lowering effect of nifedipine is a decrease in peripheral vascular resistance
. It is known that when calcium antagonists are used, the degree of vasodilation in different vascular regions is different. Maximum vasodilation is observed in the vessels of skeletal muscles and coronary arteries, and to a lesser extent in the renal arteries. Skin vessels are practically insensitive to the action of dihydropyridines. H. Struyker-Bodier et al. indicate that differences in vascular sensitivity are determined by the initial vascular tone and the number of voltage-gated calcium channels. In the kidneys, maximum sensitivity to the action of calcium antagonists is inherent in afferent arterioles. In addition, these drugs inhibit the ability of preglomerular arterioles to constrict in response to both increased transmural pressure and impulses from the macula densa.
The antianginal effect of dihydropyridines is due to coronary dilatation and a decrease in heart function due to a decrease in pre- and afterload. Long-acting drugs and prolonged forms of short-acting compounds, including nifedipine, have minimal ability to stimulate the sympathetic nervous system, which can explain their lack of arrhythmogenic effect and beneficial effect on the course of angina pectoris.
The beneficial effect of these drugs on internal organs is due not only to the improvement of regional blood flow. The results of experimental studies indicate the ability of these compounds to cause relaxation of mesangial cells, reduce collagen synthesis by fibroblasts, increase tissue tolerance to ischemia, and improve intracellular calcium metabolism (reducing mitochondrial overload). The result of these changes is a slower progression of experimental nephrosclerosis.
So, long-acting nifedipine preparations can be recommended for patients with various forms of hypertension
. They can be used both for monotherapy and in combination with other drugs with a vasodilator effect (myotropic drugs, α-blockers). In chronic renal failure, as well as in patients with bilateral renal artery stenosis and Conn's syndrome, they have advantages over angiotensin-converting enzyme inhibitors.
In case of coronary artery disease, their use is justified in stable angina pectoris.
. P. Heidenreich et al. performed a meta-analysis of 90 studies on the use of long-acting nitrates, beta-blockers and calcium antagonists. The duration of follow-up in all studies exceeded a week, but in only two of them was 6 months. The authors found no differences in the antianginal effectiveness of calcium antagonists with b-blockers. When taking short-acting nifedipine, less antianginal activity was noted, although the number of nitroglycerin tablets taken and exercise tolerance changed equally with all drugs. The differences concerned only the rarer discontinuation of beta-blockers compared to calcium antagonists due to side effects, which allowed the authors to recommend beta-blockers as first-line drugs in the treatment of stable angina.
The results of the meta-analysis revealed another interesting feature: in the United States, long-acting nitrates are more often used for monotherapy of stable angina, while in Europe, calcium antagonists are used. Among patients with stable angina, there are patients in whom the administration of calcium antagonists has certain advantages over therapy with beta-blockers. In particular, calcium antagonists are most effective for vasospastic angina.
, as well as with a combination of dynamic and fixed coronary obstruction. The combination of long-acting nifedipine with b-blockers and nitrates is quite acceptable. In addition, these compounds should be prescribed to patients who have contraindications to beta-blockers (bronchial asthma, slowing of atrioventricular and sinoatrial conduction, intermittent claudication, Raynaud's syndrome, type I diabetes mellitus, etc.). They are preferable to beta-blockers in individuals with severe dyslipidemia and metabolic syndrome. Another initial indication for prescribing drugs in this group is bradycardia and sick sinus syndrome.
The list of references can be found on the website https://www.rmj.ru
Nifedipine retard –
Corinfar-retard (trade name)
(AWD)
References:
1. BMPsaty, SRNeckbert, TDKalpsell. et al. The risk of myocardial infarction associated with antihypertensive drug therapy // JAMA, 1995; 274:620–5.
2. CDFurberg, M.Pahor, BMPsaty. The unnecessary controversy//Eur. J.Heart. 1996; 17: 1142–7.
3. CDFurberg, BMPsaty. Calcium antagonists: not appropriate as first-line antihypertensive agents// Am. er., J.Hepertension, 1995; 9: 122–5.
4. Almazov V.A., Shlyakhto E.V. Arterial hypertension and kidneys. Publishing house of St. Petersburg State Medical University named after. acad. Pavlova I.P. St. Petersburg 1999; 296 pp.
5. Andreev N.A., Moiseev V.S. Calcium antagonists in clinical medicine. M., //RC “Pharmmedinfo”. 1995; 162 pp.
6. Ivleva A.Ya. The effect of calcium antagonists on hemodynamics and renal function in arterial hypertension // Klin., pharmacocol., ter., 1992; 1:49–55.
7. Kukes V.G., RUmyantsev A.S., Taratuta T.V., Alekhin S.N. Adalat, twenty years in the clinic: past, present, future // Cardiology, 1996; 1:51–6.
8. Dyadyk A.I., Bagriy A.E., Lebed I.A. and others. Changes in myocardial mass and diastolic function of the left ventricle in patients with chronic nephritis and arterial hypertension under the influence of therapy with calcium channel blockers // Nephrological Seminar-95. TNA, St. Petersburg, 1995; 170–1.
9. T.Yamakogo, S.Teramuro, T.Oonisti. et al. Regression of left ventricular hypertrophy with long-term treatment of nifedipine in systemic hypertension//Clin., Cardiol., 1994; 17: 615–8.
10. HAStruyker-Boudier, JFSmith, JGDeMey. Pharmacology of calcium antagonists: a review, 1990; 5 (4): 1–0.
11. RDLoutzenhiser, M.Epstein. The renal hemodynamic effects of calcium antagonists. Calcium Antagonists and the Kidney // Hanley a. Belfas., Philadelphia, 1990; 33–74.
12.HLElliot. Calcium antagonism: aldosteron and vascular responses to catecholamines and angiotensin II in man // J. Hypertension. 1993; V.11. suppl.6: 13–6.
13. T. Satura. Efficacy of amlodipine in the treatment of hypertension with renal impairment//J.Cardiovasc, Pharmacol, 1994; 24(B): 6–11.
14. PAHeidenreich, KMMcDonald, T.Hastie. et al. Meta-analysis of trials comparing B-blockers, calcium antagonists and nitrates for stable angina //JAMA, Russia, 2000, (3): 14–23.
Nifedipine film-coated tablets 10 mg No. 50
special instructions
During the treatment period it is necessary to refrain from taking ethanol.
The drug is discontinued gradually (risk of withdrawal syndrome).
It should be borne in mind that angina pectoris may occur at the beginning of treatment, especially after recent abrupt withdrawal of beta-blockers (the latter should be withdrawn gradually). The simultaneous administration of beta-blockers must be carried out under conditions of careful medical supervision, since this may cause an excessive decrease in LD, and in some cases, aggravation of symptoms of heart failure. In case of severe heart failure, the drug is dosed with great caution. The diagnostic criteria for prescribing the drug for vasospastic angina are: the classic clinical picture, accompanied by an increase in the ST segment, the occurrence of ergonovine-induced angina or coronary artery spasm, the detection of coronary spasm during angiography or the identification of an angiospastic component without confirmation (for example, with a different voltage threshold or with unstable angina, when electrocardiogram data indicate transient vasospasm).
For patients with severe obstructive cardiomyopathy, there is a risk of an increase in the frequency, severity and duration of angina attacks after taking nifedipine; in this case, discontinuation of the drug is necessary.
In patients on hemodialysis with high blood pressure, irreversible renal failure, and a decrease in circulating blood volume, the drug should be used with caution; a sharp drop in blood pressure may occur.
Patients with impaired liver function are closely monitored and, if necessary, reduce the dose of the drug and/or use other dosage forms of nifedipine.
If during therapy the patient requires surgical intervention under general anesthesia, it is necessary to inform the anesthesiologist about the nature of the therapy being performed.
During treatment, positive results are possible with direct Coombs test and laboratory tests for antinuclear antibodies.
Caution should be used when co-administering disopyramide and flecainide due to a possible increase in inotropic effect.
The use of the drug before 20 weeks of pregnancy is unsafe (risk of developing fetal abnormalities at the stage of organogenesis); after 20 weeks of pregnancy it is possible only with an acceptable benefit-risk ratio.
During in vitro fertilization, in some cases, blockers of slow calcium channels caused changes in the head of the sperm, which can lead to dysfunction of the sperm. In cases in which repeat in vitro fertilization has failed for an unknown reason, calcium channel blockers, including nifedipine, are considered a possible cause of failure.
When spectrophotometrically assessed, nifedipine may lead to false detection of increased levels of vanillyl mandelic acid in urine; it has no effect on high performance liquid chromatography (HPLC) studies.
