Nifedipine: instructions for use

Release forms

There are two main forms of release of Nifedipine - tablets and gel-emulsion. Most often, patients are prescribed tablets. They contain a high content of active substance. Gel emulsion is an auxiliary preparation.

Tablets weighing 10 g can be packaged in blisters of 10 pieces each. These blisters are packed in cardboard boxes. Also, tablets of 20 or 50 pieces can be placed in plastic jars.

The gel emulsion is stored in a tube weighing 40 g. This medicine in this form of release is used only for the treatment of hemorrhoids.

There is also Nifedipine in the form of a solution for intravenous injection, as well as in the form of boluses that are injected into the coronary vessels.

How it affects the body

The medicine is a calcium antagonist and belongs to the group of slow calcium channel blockers (SCBC). The substance slows down the process of calcium penetration into the muscle cells of the heart, as well as into the cells of vascular muscles. Under the influence of the drug, the myocardium consumes less oxygen. Nifedipine lowers blood pressure and total peripheral vascular resistance, and the ability of the myocardium to contract is also slightly reduced.

Thanks to the medicine, the tone of the smooth muscles located in the vessels slightly decreases, therefore the peripheral and coronary arteries dilate. Due to this, blood flow in the coronary vessels is normalized. Myocardial conductivity is not inhibited. But you need to remember that Nifedipine does not act against arrhythmia and does not normalize heart rhythm.

Nifedipine tablets 10 mg No. 50

Compound

1 tablet contains
the active substance:

nifedipine 10 mg,

excipients (core):

lactose monohydrate (milk sugar) - 58.0 mg, microcrystalline cellulose - 15.0 mg, potato starch - 5.6 mg, croscarmellose sodium - 2.0 mg, magnesium stearate - 0.9 mg, povidone (polyvinylpyrrolidone) - 3 .5 mg.

excipients (shell):

hypromellose - 2.38 mg, macrogol 4000 - 0.56 mg, titanium dioxide - 1.0 mg, quinoline yellow dye - 0.06 mg.

Pharmacokinetics

NIFEDIPINE is quickly and almost completely (from 92% to 98%) absorbed from the gastrointestinal tract. After oral administration, its bioavailability is 40-60%. Eating increases bioavailability. Has a first pass effect through the liver. The maximum concentration in blood plasma is observed after 1-3 hours and is 65 ng/ml. Communication with blood plasma proteins - 90%. Penetrates the blood-brain and placental barrier and is excreted in breast milk. Completely metabolized in the liver. The metabolism of the drug involves isoenzymes CYP3A4, CYP3A5 and CYP3A7. Excreted by the kidneys in the form of inactive metabolites (approximately 80% of the dose taken) and 20% with bile. The half-life (T1/2) is 2-4 hours. In patients with liver failure, total clearance decreases and T1/2 increases.

There is no cumulative effect. Chronic renal failure, hemodialysis and peritoneal dialysis do not affect pharmacokinetics. With long-term use (for 2-3 months), tolerance to the action of the drug develops. Plasmapheresis may enhance elimination.

Indications for use

- angina pectoris at exertion and at rest (including variant),

- arterial hypertension (as monotherapy or in combination with other antihypertensive drugs).

Contraindications

Symptoms:

headache, facial skin flushing, decreased blood pressure, suppression of sinus node activity, bradycardia, arrhythmia.

Treatment:

gastric lavage with the administration of activated carbon, symptomatic therapy aimed at stabilizing the activity of the cardiovascular system. The antidote is calcium; slow intravenous administration of 10% calcium chloride or calcium gluconate at a dose of 0.2 ml/kg (but not more than 10 ml) over 5 minutes is indicated; if ineffective, repeated administration is possible under the control of calcium concentration in the blood serum; if symptoms resume, it is possible switch to a constant infusion at a rate of 0.2 ml/kg/h, but not more than 10 ml/h.

With a pronounced decrease in blood pressure, intravenous administration of dopamine or dobutamine. In case of conduction disturbances, the administration of atropine, isoprenaline or the installation of an artificial pacemaker is indicated. With the development of heart failure - intravenous administration of strophanthin. Catecholamines should be used only in case of life-threatening circulatory failure (due to their reduced effectiveness, a high dosage is required, which increases the risk of increasing the tendency to arrhythmia due to intoxication). It is recommended to monitor blood glucose levels (insulin release may decrease) and electrolytes (potassium and calcium ions).

Hemodialysis is not effective.

Directions for use and doses

The dosage regimen is set individually, depending on the severity of the disease and the patient’s response to the therapy. It is recommended to take the drug orally during or after meals with a small amount of water.

Initial dose: 1 tablet (10 mg) 2-3 times a day. If necessary, the dose of the drug can be increased to 2 tablets (20 mg) - 1-2 times a day. The maximum daily dose is 40 mg. In elderly patients or patients receiving combination (antianginal or antihypertensive) therapy, as well as in patients with impaired liver function, in patients with severe cerebrovascular accidents, the dose should be reduced.

Storage conditions

List B. Store in a dry place, protected from light, at a temperature not exceeding 25C. Keep out of the reach of children.

Best before date

3 years. Do not use after expiration date.

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.

Description

Tablets are biconvex, film-coated, yellow in color, uniform in color at the break.

Conditions for dispensing from pharmacies

On prescription

Dosage form

film-coated tablets

Pharmacodynamics

NIFEDIPINE is a selective blocker of slow calcium channels, a 1,4-dihydropyridine derivative. It has a vasodilating, antianginal and hypotensive effect. Reduces the flow of extracellular calcium ions into cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries, and in high doses suppresses the release of calcium ions from intracellular depots. 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 current of calcium ions, which is disturbed in a number of pathological conditions, primarily in arterial hypertension. Does not affect the tone of the veins. Reduces spasm and dilates coronary and peripheral (mainly arterial) vessels, reduces blood pressure, total peripheral vascular resistance, reduces afterload, myocardial tone, myocardial oxygen demand and increases the duration of diastolic relaxation of the left ventricle. Increases coronary blood flow, improves blood supply to ischemic areas of the myocardium without developing the steal phenomenon, and activates the functioning of collaterals. It has virtually no effect on the sinoatrial and atrioventricular nodes and does not have antiarrhythmic activity. The negative chrono-, dromo- and inotropic effects are offset by reflex activation of the sympathoadrenal system and an increase in heart rate in response to peripheral vasodilation. Increases renal blood flow, causes moderate natriuresis. The onset time of the clinical effect is 20 minutes, the duration of the clinical effect is 4-6 hours.

Side effects

From the cardiovascular system:

manifestations of excessive vasodilation (asymptomatic decrease in blood pressure (BP), development or worsening of heart failure (usually worsening of existing ones), flushing of the face, facial flushing, feeling of heat), tachycardia, peripheral edema (ankles, feet, legs), arrhythmia , syncope, rarely - excessive decrease in blood pressure, fainting; in some patients, especially at the beginning of treatment, attacks of angina pectoris may occur, up to the development of myocardial infarction, which requires discontinuation of the drug.

From the nervous system:

headache, dizziness, increased fatigue, weakness, drowsiness, sleep disturbances (including insomnia), nervousness, anxiety, hypoesthesia, muscle cramps.

From the gastrointestinal tract, liver:

dry mouth, increased appetite, dyspeptic disorders (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:

arthritis, rarely - arthralgia, joint swelling, myalgia.

Allergic reactions:

skin itching, urticaria, exanthema, exfoliative dermatitis, photodermatitis, angioedema, anaphylactoid reactions, very rarely - autoimmune hepatitis,

From the hematopoietic organs:

anemia, asymptomatic agranulocytosis, leukopenia, thrombocytopenia, thrombocytopenic purpura.

From the urinary system:

increased daily diuresis, deterioration of renal function (in patients with renal failure), dysuria.

Others:

rarely - difficulty breathing, cough, very rarely - visual impairment (including transient blindness against the background of the maximum concentration of nifedipine in the blood plasma), gynecomastia (in elderly patients, completely disappearing after discontinuation of the drug), hyperglycemia, galactorrhea, pulmonary edema, bronchospasm, weight gain, chills, epistaxis, nasal congestion, erythema.

Use during pregnancy and breastfeeding

Prescription of nifedipine for pregnant women (after the 20th week) is indicated only if the expected benefit to the mother outweighs the potential risk to the fetus.

The drug is excreted in breast milk, so you must stop breastfeeding while taking it.

Interaction

The severity of the decrease in blood pressure increases with the simultaneous administration of nifedipine with other antihypertensive drugs, nitrates, cimetidine, ranitidine (to a lesser extent), inhalational anesthetics, diuretics and tricyclic antidepressants.

Medicines from the group of slow calcium channel blockers can further enhance the negative inotropic effect (lowering the force of heart contraction) of antiarrhythmic drugs such as amiodarone and quinidine.

Under the influence of nifedipine, the concentration of quinidine in the blood serum decreases significantly, which is apparently due to a decrease in the bioavailability of quinidine, the induction of enzymes that inactivate it, an increase in blood flow in the liver and kidneys, an increase in the volume of distribution of the drug, as well as changes in hemodynamics. When nifedipine is discontinued after its simultaneous use with quinidine, a transient increase in the concentration (approximately 2 times) of the latter in the serum is observed, which reaches a maximum level on days 3-4 after discontinuation, as well as a prolongation of the QT interval on the ECG.

In combination with nitrates, tachycardia and the hypotensive effect of nifedipine are enhanced. Calcium supplements may reduce the effect of slow calcium channel blockers. When used together with nifedipine, the anticoagulant activity of coumarin derivatives increases.

Combination with prazosin increases the risk of orthostatic hypotension. Procainamide, quinidine, and other drugs known to prolong the QT interval may increase the risk of significant QT prolongation.

Grapefruit juice suppresses the metabolism of nifedipine in the body, and therefore their simultaneous use is contraindicated.

Increases the concentration of digoxin in the blood plasma, and therefore the clinical effect and/or the content of digoxin in the blood plasma should be monitored.

Rifampicin weakens the effect of nifedipine (accelerates the metabolism of the latter due to the induction of liver enzyme activity).

Inhibitors of the CYP3A isoenzyme of the cytochrome P450 system, such as macrolides (for example, erythromycin), fluoxetine, nefazodone, peptidase inhibitors (for example, amprenavir, indinavir, nelfinavir, ritonavir or saquinavir), antifungals (ketoconazole, itraconazole or fluconazole) lead to increased levels nifedipine in blood plasma.

Taking into account the experience with the use of the slow calcium channel blocker nimodipine, the following interactions with nifedipine cannot be excluded: carbamazepine, phenobarbital - a decrease in the concentration of nifedipine in the blood plasma, valproic acid - an increase in the concentration of nifedipine in the blood plasma.

Nifedipine inhibits the elimination of vincristine from the body and may cause increased side effects of vincristine; if necessary, the dose of vincristine is reduced.

It can displace drugs characterized by a high degree of binding from protein binding (including indirect anticoagulants - coumarin and indanedione derivatives, anticonvulsants, quinine, salicylates, sulfinpyrazone), as a result of which their plasma concentrations may increase. Suppresses the metabolism of prazosin and other alpha-blockers, as a result of which the hypotensive effect may be enhanced. Simultaneous use with magnesium sulfate in pregnant women can cause blockade of neuromuscular synapses.

Overdose

Symptoms:

headache, facial skin flushing, decreased blood pressure, suppression of sinus node activity, bradycardia, arrhythmia.

Treatment:

Hemodialysis is not effective.

Impact on the ability to drive vehicles and operate machinery

During the treatment period, it is necessary to refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Indications for use

The doctor prescribes Nifedipine for the treatment of many diseases and pathological conditions:

angina pectoris, including vasospastic;
hypertension;
Raynaud's disease;
hypertension;
hypertensive crisis.

Nifedipine is necessary for the prevention and relief of angina attacks, as well as for lowering blood pressure.

The doctor may recommend that the patient take the medicine only once a day. This is due to the fact that Nifedipine is active throughout the day.

For hemorrhoids at any stage up to the 4th stage, the doctor can prescribe Nifedipine gel. This gel dilates blood vessels and normalizes blood flow, which means it will help with rectal bleeding.

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.

Instructions for use

The attending physician prescribes an individual dosage to the patient and selects the drug in a suitable release form.

How to take Nifedipine tablets - instructions:

At the beginning of the course of treatment, the doctor may prescribe 1 tablet (10 mg) 3-4 times a day.
Then it may be necessary to take 2 tablets (20 mg) 3-4 times a day.
In severe cases, the dose is increased to 3 tablets (30 mg) 3-4 times a day. This occurs with severe hypertension, as well as with variant angina.
In case of an acute attack of angina, it is recommended to take 1-2 tablets (10-20 mg) under the tongue.

An acute attack can be stopped with Nifedipine injections. Within 4–8 hours, injections of 5 mg of the drug are given.

For severe spasms of the coronary arteries, Nifedipine boluses of 100–200 mcg are used. They are injected directly into the vessels (intracoronary). To treat coronary stenosis, boluses of 50–100 mcg are taken.

You must take the medicine strictly in accordance with the recommendations and prescriptions of your doctor. You should not self-medicate, otherwise you can harm your health.

Nifedipine

Nifedipine

(lat.
Nifedipine
) - a selective blocker of slow calcium channels with a predominant effect on blood vessels, an antianginal, hypotensive agent. In gastroenterology it is sometimes used as a myotropic antispasmodic.

Nifedipine is a chemical compound

Chemically, nifedipine is 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester. The empirical formula of nifedipine is C17H18N2O2. Molecular weight - 346.335 g/mol. Yellow crystalline powder. Nifedipine is insoluble in water and poorly soluble in alcohol.

Nifedipine is a medicine

Nifedipine is the international nonproprietary name (INN) of the drug. According to the pharmacological index, nifedipine belongs to the group “Calcium channel blockers”. According to ATC, nifedipine is included in the group “C08 Calcium channel blockers” and has the code C08CA05. In addition, nifedipine is the trade name of the drug.

Indications for use of nifedipine

Nifedipine is indicated for:

arterial hypertension
hypertensive crises
prevention and treatment of angina pectoris
Raynaud's syndrome

Nifedipine in gastroenterology and proctology

In the 1980–90s, many studies were carried out regarding the effect of nifedipine on the gastrointestinal tract and the following results were obtained (Zimmerman Ya.S., Budnik Yu.B.):

using manometry of the sphincter of Oddi, it was found that nifedipine causes a significant decrease in the basal pressure of the sphincter of Oddi, the amplitude, duration and frequency of its phase contractions in both healthy people and in patients with biliary dyskinesia, which made it possible to recommend nifedipine for the treatment of biliary dyskinesia
nifedipine, compared with other calcium channel blockers, such as verapamil and gallopamil, inhibits the secretion of hydrochloric acid by parietal cells to a lesser extent
after taking nifedipine, the amplitude of contractions in the body of the stomach decreases, indicators of motor activity, motor index and work/rest ratio decrease; in the antrum, in addition, the frequency of gastric contractions decreases

during electrogastrography (EGG) of gastric motor function, it was found that nifedipine at a dose of 20 mg significantly reduces the initially increased frequency of gastric contractions, the average amplitude and the total power of biopotentials; This dose of nifedipine does not have a noticeable effect on initially low and normal EGG values; at a dose of 10 mg, nifedipine increases the initially reduced frequency of gastric contractions and, conversely, reduces it with an initial increase
nifedipine significantly increases blood flow in the wall of the stomach and duodenum, and more significantly in the duodenum.

However, nifedipine was not introduced into practical medicine as a treatment for diseases of the intestines and biliary tract, firstly, due to its non-selectivity in relation to the gastrointestinal tract and significant effects on the vascular system, and, secondly, due to the appearance calcium blockers pinaverium bromide and otilonium bromide, selective for smooth muscles of the abdominal organs.
Based on the fact that nifedipine has a moderate antispasmodic effect on the walls of the esophagus and the tone of the lower esophageal sphincter, it is used for esophagospasm (Sheptulin A.A.) and hypermotor dyskinesias of the esophagus (Trukhmanov A.S.).

The use of nifedipine in the treatment of chronic anal fissures is relevant. Nifedipine persistently reduces the tone of the internal anal sphincter both when used sublingually and orally. To achieve a clinical effect, 20 mg of nifepedin is prescribed twice a day or 40 mg of nifedipine retard once. The course of treatment is 8 weeks. Healing of chronic anal fissures is observed in 40–60% of patients. Side effects of nifedipine therapy include headache in 30% of patients, fever, redness of the skin in 60% of patients (Krylov N.N.).

Order of administration (administration) of nifedipine and dose

The dosage and duration of treatment with nifedipine are established by the attending physician individually,
taking into account the patient’s condition and the specific dosage form of the drug. Approximately:

When taken orally

. The initial dose is 10 mg of nifedipine 3-4 times a day, during or after meals, with a small amount of water. If necessary, the dose is gradually increased to 20 mg of nifedipine 3-4 times a day. In special cases, for a short time the dose can be increased to 30 mg 3-4 times a day. The daily dose should not exceed 120 mg.

For arterial hypertension, nifedipine is taken 3 times a day, 10 mg, if necessary, the dose is increased to 20–30 mg (3 times a day).

Sublingual

. For hypertensive crisis and angina attack, take 10–20 mg of nifedipine once. If necessary, nifedipine is repeated.

Intravenously

. In case of hypertensive crisis, 5 mg of nifedipine is administered over 4–8 hours. The maximum daily dose is 15–30 mg of nifedipine.

Intracoronary

when relieving acute spasms of the coronary arteries - 100-200 mcg.

Taking the maximum daily dose, depending on the dosage form and the patient’s condition, should be limited to several days. In elderly patients and those with other diseases, the maximum daily dose should be reduced.

In case of acute myocardial infarction, severe cerebrovascular accidents, impaired liver or kidney function, diabetes mellitus, nifedipine is used only in a clinical setting under the supervision of a physician.

It is necessary to stop taking nifedipine gradually, reducing the daily dose.

Problems of interaction of nifedipine with acid-lowering drugs

Nifedipine is metabolized by the cytochrome P450 isoenzyme CYP3A4 located in liver hepatocytes and apical membranes of small intestinal enterocytes.
With the help of this isoenzyme, the biotransformation of a large group of drugs occurs (about 60% of oxidized drugs). When two or more drugs metabolized by the same type of isoenzymes are taken simultaneously, “competition for resources” occurs and the metabolic process changes. In addition, various substances may inhibit or stimulate metabolism and other interactions, thereby altering the effects of drugs. Many of these mechanisms are not well understood. Proton pump inhibitors and nifedipine

. Metabolism of proton pump inhibitors is carried out with the participation of cytochrome P-450 isoforms. During metabolism, their monooxidase activity decreases, which underlies drug-drug interactions. The metabolism of omeprazole and, partially, lansoprazole slow down the metabolism of nifedipine. Among proton pump inhibitors, pantoprazole has the lowest affinity for the cytochrome P-450 system (Bordin D.S.). Therefore, if it is necessary to take nifedipine and a proton pump inhibitor for the treatment of synchronous diseases, pantoprazole should be prescribed, and not another PPI (Standards for the diagnosis and treatment of acid-dependent and Helicobacter pylori-associated diseases).

H2 blockers and nifedipine.

Cimetidine and ranitidine slow down biotransformation and increase the level of nifedipine in plasma.

Interaction of nifedipine with some other drugs

Nifedipine affects or is affected by many drugs. The following are just some of the interactions:

The simultaneous use of nifedimin with verapamil
enhances the effect of both drugs.
Octreotide
modifies the effects of nifedipine. When octreotide and nifedipine are co-administered, monitoring of blood pressure is necessary. It may be necessary to change the dose.
Rifampicin
accelerates the biotransformation of nifedipine and does not allow the creation of effective plasma concentrations of nifedipine. The simultaneous use of rifampicin and nifedipine is contraindicated.
Fluconazole
may increase the systemic exposure of nifedipine. Patients taking fluconazole and nifedipine at the same time have a significantly increased risk of side effects.

When combined with nifedipine, inhibitors of the cytochrome P450 CYP3A isoenzyme, such as fluconazole, itraconazole, clarithromycin, erythromycin, fluoxetine, saquinavir, indinavir, nelfinavir, may lead to increased nifedipine exposure. Caution should be exercised, patients' condition should be carefully monitored and the dosage of medications should be adjusted if necessary. When co-administered with CYP3A4 inhibitors, the dose of nifedipine should be selected as low as possible.

Professional medical articles addressing the use of nifedipine in gastroenterology and proctology

Zimmerman Ya.S., Budnik Yu.B. Prerequisites for the use of calcium antagonists in the treatment of diseases of the digestive system // Russian Journal of Gastroenterology, Hepatology, Coloproctology. – 1995. – No. 3. – p. 22–28.
Krylov N.N. Chronic anal fissure // Bulletin of surgical gastroenterology. - 2008, - No. 1, - p. 5-11.
Clinical recommendations for the diagnosis and treatment of adult patients with anal fissure // Association of Coloproctologists of Russia. Moscow. 2013 17 p.
Fomina L.A. Comorbid course of gastroduodenal ulcers in terms of calcium imbalance and slow calcium channel blockers in their treatment // Therapeutic archive. 2022. No. 2. P. 28–34.
Fomina L.A. Calcium imbalance in the pathogenesis of symptomatic gastoduodenal ulcers associated with non-steroidal anti-inflammatory drugs, and the effectiveness of slow calcium channel blockers in their treatment // Experimental. and clinical gastroenterology. 2022. Issue. 151. No. 3. pp. 58–63.

On the website in the literature catalog there is a section “Anspasmodics”, containing articles on the use of antispasmodics in the treatment of diseases of the gastrointestinal tract.

Use of nifedipine in pregnant women, nursing mothers and children

Nifedipine should not be used by pregnant, breastfeeding women and children.
Nifedipine is FDA Category C (animal studies have shown adverse effects on the fetus and there have been no adequate studies in pregnant women, but the potential benefits associated with the use of this drug in pregnant women may justify its use despite the risks ).

A certain amount of nifedipine is excreted into mother's milk and therefore breastfeeding should be suspended while the mother is being treated with nifedipine.

The safety and effectiveness of nifedipine in children has not been established.

Contraindications to the use of nifedipine

Arterial hypotension, tachycardia, the first 8 days of myocardial infarction, collapse, cardiogenic shock, severe heart failure, severe aortic stenosis, hypersensitivity to nifedipine.

Trade names of drugs containing the active ingredient nifedipine

The following drugs with the active substance nifedipine are (were) registered in Russia: Adalat, Adalat SL, Vero-Nifedipine, Calcigard retard, Cordafen, Cordaflex, Cordaflex, Cordipin, Cordipin XL, Cordipin retard, Corinfar, Corinfar retard, Corinfar UNO, Nicardia, Nicardia SD retard, Nifadil, Nifebene, Nifehexal, Nifedex, Nifedicap, Nifedicor, Nifedipine, Nifecard, Nifecard HL, Nifelat, Nifelat Q, Nifelat R, Nifesan, Osmo-Adalat, Sanfidipine, Sponif 10, Phenigidine.
In the United States, nifedipine is sold under the trade names: Adalat CC, Afeditab CR, Nifediac CC, Nifedical XL, Procardia, Procardia XL.

Instructions

Official instructions for the use of various drugs with the active substance nifedipine (pdf):

instructions, tablets 10 mg
Bayer Pharma instructions:
“Instructions for use of the drug for medical use Adalat”, solution for infusion, dated January 17, 2013.
“Instructions for use of the drug for medical use Osmo-Adalat”, tablets 30 and 60 mg, dated September 11, 2012.

instructions from Pliva Hrvatska d.o.o.:

“Instructions for medical use of the drug Corinfar”, extended-release film-coated tablets, 10 mg, dated June 24, 2009.
“Instructions for medical use of the drug Corinfar Retard,” extended-release film-coated tablets, 20 mg, dated May 14, 2009.
“Instructions for medical use of the drug Corinfar UNO”, modified-release film-coated tablets, 40 mg

instructions from the company Pharmaceutical S.A.: “Instructions for the medical use of the drug Cordafen”, film-coated tablets, 10 mg, dated September 10, 2008.

Pfizer US instructions (in English):

"Procardia (nifedipine) Capsules For Oral Use", August 2011
"Procardia XL (nifedipine) Extended Release Tablets For Oral Use", August 2011

general information

Nifedipine is a prescription medicine.
Nifedipine has contraindications, side effects and application features; before taking it, consultation with a specialist is necessary.

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Side effects

The medicine may cause some side symptoms. To relieve them, your doctor may prescribe additional medications.

Side effects:

increased heart rate;
skin redness;
feeling of warmth or heat on the skin;
hypotension;
slight swelling;
skin rash;
ventricular tachycardia;
slow heart rate;
increased attacks of angina pectoris;
cardiac arrest, asystole;
heartburn, nausea, diarrhea;
swelling of the gums;
liver dysfunction;
muscle pain;
headache;
sleep disorders;
tremor of the limbs;
visual disturbances;
thrombocytopenia;
leukopenia;
renal dysfunction;
increase in the daily amount of urine excreted;
sudden enlargement of the breast (gynecomastia).

After an intravenous injection, the patient may feel a burning sensation. After intracoronary administration of the drug, within the first minute the patient’s pulse may sharply increase and blood pressure may drop. These unpleasant sensations disappear after 5–15 minutes.

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.

Contraindications

There are many contraindications that prohibit the use of this drug for some patients:

collapse;
severe form of heart failure;
hypotension, in which systolic (upper) pressure falls below 90 mmHg;
cardiogenic shock;
the first 4 weeks after myocardial infarction (acute period);
aortic stenosis;
unstable form of angina;
lactose intolerance, lactase deficiency;
GGM syndrome - impaired absorption of glucose and galactose;
increased individual intolerance;
lactation period;
pregnancy less than 20 weeks;
children's age (up to 18 years).

For these diagnoses and conditions, it is necessary to prescribe other medications to the patient. Nifedipine is not suitable for long-term treatment.

Recently, cardiologists conducted a study in which they proved that Nifedipine increases the risk of sudden cardiac arrest, so this medicine must be taken with extreme caution.

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.

Carefully

Patients suffering from certain diseases should be extremely attentive to their health. They will have to drink Nifedipine with caution:

elderly patients;
hypertrophic obstructive cardiomyopathy;
severe liver diseases;
sick sinus syndrome;
kidney dysfunction;
mitral valve stenosis;
chronic heart failure;
diabetes;
stenosis of any part of the intestine;
disturbances in the functioning of cerebral vessels.

Taking the medication in these cases should be strictly under the control and supervision of the attending physician.

Overdose symptoms

You should not take more than 120 mg tablets per day. The maximum dose of intravenous solution is 30 mg.

Signs of overdose:

a sharp slowdown in heart rate;
bradyarrhythmia;
heart rhythm disturbances;
hypotension;
collapse;
cardiogenic shock;
convulsions;
loss of consciousness;
hypoxia;
acidosis;
slowing of cardiac conduction;
hyperglycemia;
coma.

Symptoms appear 3-4 hours after taking the tablets. In case of overdose, the patient's stomach is washed and activated charcoal is administered. He is then given intravenous injections of atropine with calcium gluconate, calcium chloride and norepinephrine to relieve intoxication. Due to proven ineffectiveness, hemodialysis is not performed.

Interaction with other drugs

Blood pressure drops sharply when Nifedipine is taken simultaneously with other antihypertensive drugs, as well as diuretics, diltiazem, and drugs based on phenothiazine and its derivatives.

Attention and memory may be affected when Nifedipine is used with anticholinergic medications.

This medicine should not be combined with beta-blockers, otherwise severe hypotension and even heart failure may occur.

In combination with magnesium salts, the patient experiences severe muscle weakness.

The effective effect against angina pectoris is enhanced when the drug is combined with nitrates.

Due to the intake of digoxin and theophylline, the amount of these substances in the blood increases.

You should not take Nifedipine together with medications containing calcium. These substances have opposite properties, which reduces their effectiveness. Side effects of the drug are enhanced in combination with fluoxetine and vincristine. Also, the effect of Nifedipine is reduced in combination with rifampicin, so these two drugs are incompatible with each other.

The level of nifedipine in the blood decreases if you take the medicine together with phenytoin, phenobarbital or carbamazepine. Conversely, concentrations increase in combination with itraconazole, cimetidine, fluconazole and ranitidine.

The QT interval on the ECG is prolonged when Nifedipine is taken simultaneously with quinidine. This occurs because the amount of quinidine in the blood decreases sharply, and when it is discontinued, it suddenly increases.

Severe hypotension, dizziness and other unpleasant symptoms occur if the patient drinks Nifedipine and drinks containing ethyl alcohol. This drug should not be combined with grapefruit juice.

Nifedipine

Medicines that affect nifedipine

Nifedipine is metabolized with the participation of the CYP3A4 isoenzyme of the cytochrome P450 system, located in the intestinal mucosa and in the liver.

Drugs that inhibit or induce this enzyme system may affect the first-pass effect (after oral administration) or clearance of nifedipine (see Special Instructions).

The strength of the interaction and the duration of this effect should be taken into account when taking nifedipine simultaneously with the following drugs

Rifampicin

Rifampicin greatly increases the activity of the CYP3A4 isoenzyme of the cytochrome P450 system, which leads to a significant decrease in the bioavailability and effectiveness of nifedipine, so their simultaneous use is contraindicated (see section Contraindications).

During simultaneous use of nifedipine with the following weak or moderate inhibitors of the CYP3A4 isoenzyme, blood pressure should be monitored and, if necessary, the dose of Nifedipine should be adjusted (see section Dosage and Administration).

Macrolides (eg, erythromycin)

No interaction studies have been conducted between nifedipine and macrolides. It is known that some macrolides can inhibit the CYP3A4 isoenzyme, which is involved in the metabolism of other drugs. Therefore, a potential increase in the concentration of nifedipine in the blood plasma cannot be excluded when taken simultaneously (see section Special instructions).

Azithromycin does not inhibit the CYP3A4 isoenzyme, although its structure is a macrolide antibiotic.

HIV protease inhibitors (eg, ritonavir, indinavir, nelfinavir, amprenavir)

Clinical studies of the interaction between nifedipine and HIV protease inhibitors are not presented. It is known that drugs of this class inhibit the CYP3A4 isoenzyme. This class of drugs has also been shown to inhibit the CYP3A4 isoenzyme in vitro, which determines the metabolism of nifedipine. When taken simultaneously with nifedipine, a significant increase in its concentration in the blood plasma cannot be ruled out due to a decrease in the “first pass” effect and a decrease in its elimination (see section Special instructions).

Azole antifungals (eg, ketoconazole, fluconazole, itraconazole)

Clinical studies of the interaction between nifedipine and azole antifungals have not yet been presented. It is known that drugs of this class inhibit the CYP3A4 isoenzyme. When taken orally with nifedipine simultaneously, a significant increase in its systemic bioavailability cannot be ruled out due to a decrease in the “first pass” effect (see section Special instructions).

Fluoxetine

Clinical studies of the interaction between nifedipine and fluoxetine are not presented. It is known that fluoxetine inhibits in vitro the isoenzyme CYP3A4, which determines the metabolism of nifedipine. Therefore, an increase in the concentration of nifedipine in the blood plasma cannot be excluded when taken simultaneously (see section Special instructions).

Nefazodone

Clinical studies of the interaction between nifedipine and nefazodone have not yet been reported. It is known that nefazodone inhibits the CYP3A4 isoenzyme, which determines the metabolism of nifedipine. Therefore, an increase in the concentration of nifedipine in the blood plasma cannot be excluded when taken simultaneously (see section Special instructions).

Quinupristin/Dalfopristin

Concomitant use of quinupristin/dalfopristin with nifedipine may lead to an increase in the concentration of nifedipine in the blood plasma (see section Special instructions).

Valproic acid

Clinical studies of the potential interaction between nifedipine and valproic acid are not presented. Since it has been found that valproic acid can increase the concentration of a structurally similar BMCA, nimodipine, in the blood plasma, an increase in the concentration of nifedipine in the blood plasma cannot be excluded and, as a result, an increase in its therapeutic effect (see section Special instructions).

Cimetidine

Due to the inhibition of the CYP3A4 isoenzyme, cimetidine increases the concentration of nifedipine in the blood plasma and may enhance the antihypertensive effect (see section Special instructions).

Other types of interaction

Cisapride

Concomitant use of cisapride and nifedipine may lead to an increase in the concentration of nifedipine in the blood plasma.

Inducers of the cytochrome P450 isoenzyme CYP3A4, including antiepileptic drugs such as phenytoin, carbamazette and phenobarbital

Phenytoin induces the CYP3A4 isoenzyme. With simultaneous use of nifedipine with phenytoin, the bioavailability of nifedipine is reduced and, thus, its effectiveness is reduced. When taking these drugs simultaneously, the clinical effect of nifedipine should be assessed and, if necessary, it is recommended to increase its dose. If the dose of nifedipine is increased during concomitant use of both drugs, a reduction in the dose of nifedipine is required after discontinuation of phenytoin. Clinical studies of the potential interaction between nifedipine and carbamazepine or phenobarbital are not presented. Since it was found that, due to enzyme induction, both drugs can reduce the concentration of BMCC, nimodipine, which is similar in structure, in the blood plasma, a decrease in the concentration of nifedipine in the blood plasma and, as a result, a decrease in its therapeutic effect cannot be ruled out.

Effect of nifedipine on other drugs:

Drugs that lower blood pressure

The combined use of nifedipine with other antihypertensive drugs can lead to a mutual enhancement of the antihypertensive effect, such drugs, for example, include:

Diuretics,
Beta blockers,
Angiotensin-converting enzyme inhibitors,
Angiotensin I receptor antagonists,
BMKK,
Alpha blockers,
Phosphodiesterase type 5 inhibitors,
Methyldopa,
Magnesium sulfate.

When using nifedipine and beta-blockers simultaneously, patients should be closely monitored, as in some cases the course of chronic heart failure may worsen.

Digoxin

The simultaneous use of nifedipine and digoxin may lead to a decrease in the clearance of digoxin and, as a result, to an increase in its concentration in the blood plasma. The patient should be carefully monitored for symptoms of digoxin overdose and, if necessary, reduce the dose of digoxin, taking into account its plasma concentration.

Quinidine

When combined with quinidine, its plasma concentration may decrease in some patients, and subsequently, when nifedipine is stopped, it may increase significantly. Therefore, when taking nifedipine concomitantly or discontinuing it after co-administration with quinidine, it is recommended to carefully monitor the concentration of quinidine in the blood plasma and, if necessary, adjust its dose. An increase in the concentration of nifedipine in the blood plasma has also been reported during the simultaneous use of drugs, while at the same time, in some patients there is no change in the pharmacokinetic parameters of nifedipine. When adding quinidine to nifedipine therapy, blood pressure should be monitored and, if necessary, it is recommended to reduce the dose of nifedipine.

Tacrolimus

Tacrolimus is metabolized by the cytochrome P450 isoenzyme CYP3A4. Recently published data indicate that the dose of tacrolimus when coadministered with nifedipine may be reduced in some patients. When taking drugs simultaneously, the concentration of tacrolimus in the blood plasma should be monitored, and if necessary, it is recommended to reduce its dose.

Grapefruit juice

Grapefruit juice inhibits the CYP3A4 isoenzyme of the cytochrome P450 system. Taking nifedipine with grapefruit juice may lead to increased plasma concentrations of nifedipine and prolongation of its action as a result of reduced first-pass metabolism or decreased clearance. This may lead to an increase in the antihypertensive effect of nifedipine. If you take grapefruit juice regularly, this effect can last at least 3 days after your last intake. You should avoid taking grapefruit juice while taking nifedipine (see Dosage and Administration).

Other forms of interaction
Nifedipine may cause a false increase in the concentration of vanillylmandelic acid in urine when determined by the spectrophotometric method, but does not affect the results of measurements using the high-performance liquid chromatography (HPLC) method.

special instructions

Nifedipine should be taken only under the strict supervision of doctors. Elderly patients are advised to reduce the dose. The medicine causes withdrawal symptoms, so it is discontinued gradually. It is necessary to discontinue the drug if the patient experiences chest pain.

If a person has stenosis of two coronary vessels, then the medicine cannot be administered intracoronarily into the third.

During the course of treatment it is forbidden to drink alcohol. It is advisable to refrain from working with machinery, driving a car or other types of transport, and also avoid dangerous work that requires great concentration.

Analogs

The following drugs are complete or partial analogues of Nifedipine:

"Calcigard Retard".
"Cordaflex".
"Cordipin Retard."
"Kordipin HL".
"Corinfar".
"Corinfar Retard".
"Nifecard HL".
"Phenigidine."

The doctor may prescribe these drugs instead of Nifedipine. They have similar properties.