Compound
Modified-release film-coated tablets.
Each modified-release film-coated tablet contains: core: nifedipine 30.00 mg/60.00 mg respectively; povidone 75.00/150.00 mg, sodium lauryl sulfate 2.40/4.80 mg, hypromellose (hydroxypropyl methylcellulose) 185.80/(-) mg, hypromellose (hydroxypropyl methylcellulose 2906) (-)/203.84 mg, hypromellose ( hydroxypropyl methylcellulose 2208) (-)/123.36 mg, *Ludipress 70.00/50.00 mg, magnesium hydrosilicate (talc) 6.00/6.00 mg, magnesium stearate 0.80/2.00 mg; shell: hypromellose phthalate (hydroxypropyl methylcellulose phthalate) 18,200/40,000 mg, triethyl citrate 1,800/4,000 mg, hypromellose (hydroxypropyl methylcellulose 2910) 3,000/4,500 mg, hyprolose (hydroxypropylcellulose) 3,000/4,500 mg, macrogol (poly ethylene glycol) 1.0/1.5 mg , magnesium hydrosilicate (talc) 0.500/0.750 mg, titanium dioxide 1.930/2.900 mg, iron dye yellow oxide 0.570/0.850 mg.
*Ludipress - is a mixture of lactose monohydrate, povidone, crospovidone in a ratio of 93:3.5:3.5.
Pharmacodynamics
Nifedipine is a selective blocker of “slow” calcium channels, a 1,4-dihydropyridine derivative. Has antianginal and antihypertensive effects. Reduces the flow of extracellular calcium into cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries; in high doses inhibits 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, 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. Strengthens coronary blood flow, improves blood supply to ischemic areas of the myocardium without developing the “steal” phenomenon, and activates the functioning of collaterals.
Improves myocardial function, reduces the force of heart contractions and myocardial oxygen demand. By dilating peripheral arteries, it lowers blood pressure (BP) and reduces total peripheral resistance and afterload on the heart. Almost no effect on the sinoatrial and atrioventricular nodes. Increases renal blood flow, causes moderate natriuresis.
Inhibits platelet aggregation and has antiatherogenic properties (especially with long-term use). Reduces pressure in the pulmonary artery and has a positive effect on the blood supply to the blood vessels of the brain.
Nifecard xl 30 mg 30 pcs. modified-release film-coated tablets
pharmachologic effect
Selective BMCC, a derivative of 1,4-dihydropyridine.
It has a vasodilating, antianginal and hypotensive effect. The use of Nifecard CL reduces the Ca2+ current in cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries; in high doses suppresses the release of Ca2+ 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 Ca2+ current, which is disturbed in a number of pathological conditions, primarily in arterial hypertension. Does not affect the tone of the veins.
Strengthens coronary blood flow, improves blood supply to ischemic areas of the myocardium without developing the “steal” phenomenon, and activates the functioning of collaterals. By dilating peripheral arteries, it reduces peripheral vascular resistance, myocardial tone, afterload, myocardial oxygen demand and increases the duration of LV diastolic relaxation. It has virtually no effect on the SA and AV nodes and does not have antiarrhythmic activity. Increases renal blood flow, causes moderate natriuresis. The negative chrono-, dromo- and inotropic effects are overlapped by reflex activation of the sympathoadrenal system and an increase in heart rate in response to peripheral vasodilation.
Time of onset of effect: 20 minutes - with oral administration of Nifecard CL, 5 minutes - with sublingual administration of capsule contents; duration of effect: 4-6 hours - for tablets and capsules, 12-24 hours - for prolonged forms.
Composition and release form Nifecard xl 30 mg 30 pcs. modified-release film-coated tablets
Tablets - 1 tablet:
- Active substance: nifedipine 30 mg;
- Excipients: povidone - 75 mg, sodium lauryl sulfate - 2.4 mg, hypromellose (hydroxypropyl methylcellulose) - 185.8 mg, Ludipress® (mixture of lactose monohydrate, povidone, crospovidone in the ratio 93:3.5:3.5) - 70 mg, talc (magnesium hydrosilicate) - 6 mg, magnesium stearate - 0.8 mg.
- Shell composition: hypromellose phthalate (hydroxypropyl methylcellulose phthalate) - 18.2 mg, triethyl citrate - 1.8 mg, hypromellose (hydroxypropyl methylcellulose 2910) - 3 mg, hyprolose (hydroxypropylcellulose) - 3 mg, macrogol (polyethylene glycol) - 1 mg, talc (magnesium hydrosilicate) - 0.5 mg, titanium dioxide - 1.93 mg, iron dye yellow oxide - 0.57 mg.
10 pieces. - blisters (3) - cardboard packs.
Description of the dosage form
Modified-release, light brownish-yellow to light brownish-orange, film-coated tablets, round, biconvex, with "NDP 30" debossed on one side; yellow in cross section.
Directions for use and doses
The dose of Nifecard HL is 1 tablet. 30 or 60 mg/day once. Dose selection begins with 30 mg/day, correction is carried out at intervals of 7-14 days.
The maximum daily dose is 90 mg.
Pharmacodynamics
Nifedipine is a selective CCB, a 1,4-dihydropyridine derivative. Has antianginal and antihypertensive effects. Reduces the flow of extracellular calcium into cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries; in high doses inhibits 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 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. Strengthens coronary blood flow, improves blood supply to ischemic areas of the myocardium without developing the steal phenomenon, and activates the functioning of collaterals.
Improves myocardial function, reduces the force of heart contractions and myocardial oxygen demand. By expanding peripheral arteries, it lowers blood pressure and reduces peripheral vascular resistance and afterload on the heart. Almost no effect on the sinoatrial and AV nodes. Increases renal blood flow, causes moderate natriuresis.
Inhibits platelet aggregation and has antiatherogenic properties (especially with long-term use). Reduces pressure in the pulmonary artery and has a positive effect on the blood supply to the blood vessels of the brain.
Pharmacokinetics
Nifecard® CL, due to the delayed release of the active substance, provides a gradual, controlled increase in plasma concentrations of nifedipine. The plasma concentration of nifedipine reaches a plateau after approximately 6 hours and is maintained with minor fluctuations for 24 hours. Nifedipine is rapidly and almost completely absorbed after oral administration (92–98%). Characterized by a high percentage of binding to blood plasma proteins (90%). T1/2 is approximately 2 hours. Metabolized in the liver. No active metabolites were identified. It is excreted in the form of inactive metabolites mainly by the kidneys (80%) and bile (20%).
Nifedipine penetrates the blood-brain barrier and the placental barrier and is excreted in breast milk.
There is no cumulative effect.
Chronic renal failure, hemodialysis and peritoneal dialysis do not affect pharmacokinetics.
If liver function is impaired, the clearance of nifedipine is reduced. In case of severe liver dysfunction, dose adjustment may be required.
In elderly patients, when administered intravenously, the clearance of nifedipine was reduced by 33% compared to young healthy volunteers.
With long-term use, the development of tolerance to nifedipine may occur.
Indications for use Nifecard xl 30 mg 30 pcs. modified-release film-coated tablets
Angina pectoris (tension, stable without vasospasm, stable vasospastic, unstable vasospastic with ineffectiveness of beta-blockers and nitrates); arterial hypertension (including renovascular), relief of hypertensive crisis; Raynaud's disease and syndrome; spasm of the coronary arteries (during diagnostic or therapeutic interventions - percutaneous transluminal coronary angioplasty, vascular recanalization or coronary artery bypass grafting); differential diagnosis between functional and organic stenosis of the coronary arteries; hypertension in the “lesser” circulation.
Contraindications
Hypersensitivity to the components of Nifecard CL, severe arterial hypotension (systolic blood pressure below 90 mm Hg), pregnancy, lactation.
Carefully. Severe stenosis of the aortic orifice or mitral valve, HOCM, severe bradycardia or tachycardia, SSSU, CHF, mild or moderate arterial hypotension, severe cerebrovascular accidents, myocardial infarction with LV failure, gastrointestinal obstruction (for sustained-release forms), liver failure, renal insufficiency (especially patients on hemodialysis - a high risk of excessive and unpredictable decrease in blood pressure), older age, children under 18 years of age (the effectiveness and safety of use have not been studied).
Application of Nifecard chl 30 mg 30 pcs. modified-release film-coated tablets during pregnancy and lactation
The drug is contraindicated for use during pregnancy and breastfeeding.
special instructions
During treatment with Nifecard CL, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
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.
Side effects Nifecard xl 30 mg 30 pcs. modified-release film-coated tablets
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 to the components of Nifecard HL: rarely - itching, urticaria, exanthema, autoimmune hepatitis.
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), increase in body weight.
Drug interactions
Reduces the concentration of quinidine in plasma.
The use of Nifecard CL increases the concentration of digoxin in plasma, and therefore the clinical effect and concentration of digoxin in plasma should be monitored.
Inducers of microsomal liver enzymes (rifampicin, etc.) reduce the concentration of Nifecard CL.
The severity of the decrease in blood pressure is enhanced by other antihypertensive drugs, nitrates, cimetidine (suppression of metabolism; ranitidine and famotidine do not have a significant effect on the metabolism of BMCC), inhalational anesthetics, diuretics and tricyclic antidepressants.
In combination with nitrates, tachycardia increases.
The hypotensive effect of Nifecard CL is reduced by sympathomimetics, NSAIDs (suppression of Pg synthesis in the kidneys and Na+ and fluid retention in the body), estrogens (fluid retention in the body).
Ca2+ preparations can reduce the effect of BMCC.
It can displace drugs characterized by a high degree of binding from their connection with proteins (including indirect anticoagulants - derivatives of coumarin and indanedione, anticonvulsants, NSAIDs, quinine, salicylates, sulfinpyrazone), as a result of which their concentrations in plasma may increase.
The use of Nifecard CL suppresses the metabolism of prazosin and other alpha-blockers, as a result of which the hypotensive effect may be enhanced.
Li+ preparations can enhance the toxic effects of Nifecard CL (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).
Procainamide, quinidine and other drugs that cause prolongation of the QT interval enhance the negative inotropic effect and may increase the risk of significant prolongation of the QT interval.
Pharmacokinetics
Nifecard CL, due to the delayed release of the active substance, provides a gradual, controlled increase in plasma concentrations of nifedipine. The plasma concentration of nifedipine reaches a plateau after approximately 6 hours and is maintained with minor fluctuations for 24 hours. Nifedipine is rapidly and almost completely absorbed after oral administration (92-98%). Characterized by a high percentage of binding to blood plasma proteins (90%). The half-life is approximately 2 hours. Metabolized in the liver. No active metabolites were identified. It is excreted in the form of inactive metabolites mainly by the kidneys (80%) and bile (20%).
Nifedipine penetrates the blood-brain and placental barrier and is excreted in breast milk.
There is no cumulative effect.
Chronic renal failure, hemodialysis and peritoneal dialysis do not affect pharmacokinetics.
If liver function is impaired, the clearance of nifedipine is reduced. In case of severe liver dysfunction, dose adjustment may be required.
In elderly patients, when administered intravenously, the clearance of nifedipine was reduced by 33% compared to young healthy volunteers.
With long-term use, the development of tolerance to nifedipine may occur.
Contraindications
- Hypersensitivity to nifedipine or components of the drug and other 1,4-dihydropyridine derivatives;
- Severe arterial hypotension (systolic blood pressure below 90 mmHg);
- Severe aortic valve stenosis with clinically significant hemodynamic disturbances;
- Unstable angina;
- Chronic heart failure in the stage of decompensation, cardiogenic shock (risk of developing myocardial infarction), acute period of myocardial infarction (during the first 4 weeks);
- Concomitant use of rifampicin;
- Rare hereditary forms of lactose intolerance, lactase deficiency or glucose/galactose malabsorption (because the composition contains lactose);
- Pregnancy up to 20 weeks, breastfeeding period;
- Age up to 18 years (efficacy and safety have not been established).
Carefully
Stenosis of the aortic orifice or mitral valve; hypertrophic obstructive cardiomyopathy; severe tachycardia; sick sinus syndrome; malignant arterial hypertension; myocardial infarction with left ventricular failure; cerebrovascular diseases; liver and/or kidney dysfunction; hemodialysis (risk of arterial hypotension); diabetes; intestinal obstruction; pregnancy after 20 weeks; simultaneous use of beta-blockers or cardiac glycosides, with inducers or inhibitors of the CYP3A4 isoenzyme.
Side effects
According to the World Health Organization (WHO), adverse reactions are classified according to their frequency of development as follows: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, < 1/100), rare (≥1/10000, <1/1000) and very rare (<1/10000); Frequency unknown - based on available data, it was not possible to determine the frequency of occurrence.
From the blood and lymphatic system
Frequency unknown: agranulocytosis, leukopenia, anemia, thrombocytopenia.
From the immune system
Uncommon: allergic reactions, allergic edema/angioedema;
Rarely: skin itching, skin rash, urticaria;
Not known: anaphylactic/anaphylactoid reaction, toxic epidermal necrolysis, exfoliative dermatitis, photodermatitis, autoimmune hepatitis, thrombocytopenic purpura.
Metabolism and nutrition
Frequency unknown: hyperglycemia.
From the nervous system
Often: headache;
Uncommon: dizziness, migraine, fatigue, tremor;
Rarely: paresthesia/dysesthesia of the limbs;
Frequency unknown: with long-term use in high doses - depression, anxiety, extrapyramidal (parkinsonian) disorders (ataxia, “mask-like” face, “shuffling” gait, stiffness in the movements of the arms and legs, tremor of the hands and fingers, difficulty swallowing, hyposthesia, drowsiness), increased excitability, sleep disturbance (including insomnia), night nightmares, decreased libido.
From the side of the organ of vision
Uncommon: visual impairment (transient);
Frequency unknown: pain in the eye area.
Hearing and labyrinth disorders
Uncommon: ringing in the ears, dysgeusia (taste disturbance).
From the cardiovascular system
Often: peripheral edema, increased symptoms of vasodilation (asymptomatic decrease in blood pressure, “flushes” of blood to the facial skin, flushing of the facial skin, feeling of heat);
Uncommon: tachycardia, palpitations, arrhythmia, excessive decrease in blood pressure (especially in patients on dialysis with malignant hypertension and reduced circulating blood volume), fainting, syncope;
Very rare: in some patients, especially at the beginning of treatment, angina attacks may occur, which requires discontinuation of the drug. Isolated cases of myocardial infarction have been described; frequency unknown: chest pain, worsening symptoms of heart failure.
From the respiratory system
Uncommon: nosebleeds, nasal congestion, cough, sinusitis, difficulty breathing, upper respiratory tract infections;
Frequency unknown: dyspnea, bronchospasm, pulmonary edema.
From the digestive system
Common: constipation;
Uncommon: dry oral mucosa, decreased appetite, dyspepsia (nausea, diarrhea), abdominal pain;
Rarely: gum hyperplasia (bleeding, pain, swelling);
Frequency unknown: dysphagia, erosive and ulcerative lesions of the intestinal mucosa, vomiting, insufficiency of the gastroesophageal sphincter, with long-term use - impaired liver function (intrahepatic cholestasis, increased activity of "liver" transaminases, jaundice), bezoars (lumps in the stomach from undigested food debris ).
From the musculoskeletal system and connective tissues
Uncommon: cramps of the upper and lower extremities, swelling of the joints, back pain, gout;
Frequency unknown: arthritis, arthralgia, myalgia.
From the genitourinary system
Uncommon: increase/decrease in daily diuresis, erectile dysfunction;
Rarely: gynecomastia (in elderly patients, completely disappearing after discontinuation of the drug);
Frequency unknown: galactorrhea, deterioration of renal function (in patients with renal failure).
From the skin and subcutaneous tissues
Uncommon: alopecia, increased sweating, hemorrhagic rash.
General and administration site disorders
Often: asthenia, weakness;
Uncommon: nonspecific pain, chills, facial swelling, periorbital edema, fever, weight gain.
Buy Nifecard HL tablets p.o 30 mg No. 30 in pharmacies
Instructions for use Nifecard HL tab p.o 30 mg No. 30
Dosage forms tablets 30 mg Synonyms Adalat Vero-Nifedipine Calcigard retard Cordafen Cordaflex Cordaflex RD Cordipin Cordipin retard Cordipin HL Corinfar Corinfar retard Corinfar Uno Nifedipine-FPO Nifecard CL Osmo-Adalat Phenigidine Group Calcium channel blockers of the dihydropyridine group International nonproprietary name Nifedipine Co becoming the Active substance - nifedipine. Manufacturers Lek DD (Slovenia) Pharmacological action Antianginal, hypotensive. Blocks calcium channels, inhibits the transmembrane flow of calcium ions into smooth muscle cells of arterial vessels and cardiomyocytes. Dilates peripheral, mainly arterial vessels, incl. coronary, lowers blood pressure, reduces total peripheral vascular resistance and afterload on the heart. Increases coronary blood flow, reduces the strength of heart contractions, heart function and myocardial oxygen demand. Improves myocardial function and helps reduce heart size in chronic heart failure. Reduces pressure in the pulmonary artery and has a positive effect on cerebral hemodynamics. Inhibits platelet aggregation, has antiatherogenic properties, improves post-stenotic circulation in atherosclerosis. Increases the excretion of sodium and water, reduces myometrial tone. When taken orally, it is quickly and completely absorbed. The bioavailability of all dosage forms is 40-60%. About 90% of the dose taken is bound to plasma proteins. After oral administration, the maximum concentration in plasma is created after 30 minutes, the half-life is 2-4 hours. It is excreted by the kidneys in the form of inactive metabolites and with feces. In small quantities it passes through the blood-brain barrier and the placental barrier and penetrates into breast milk. Does not have mutagenic or carcinogenic activity. Side effects From the cardiovascular system and blood (hematopoiesis, hemostasis: facial flushing with a feeling of heat, palpitations, tachycardia, hypotension (up to fainting), angina-like pain, very rarely - anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura. With from the nervous system and sensory organs: dizziness, headache, stunnedness, changes in visual perception, impaired sensitivity in the arms and legs. From the gastrointestinal tract: constipation, nausea, diarrhea, gum hyperplasia (with long-term treatment), increased activity of liver transaminases. side of the respiratory system: bronchospasm. From the musculoskeletal system: myalgia, tremor. Allergic reactions: itching, urticaria, exanthema, exfoliative dermatitis. Others: swelling and redness of the hands and feet, photodermatitis, hyperglycemia, gynecomastia (in elderly patients) , burning sensation at the injection site (with intravenous administration) Indications for use Arterial hypertension, including hypertensive crisis, prevention of angina attacks (incl. Prinzmetal's angina), hypertrophic cardiomyopathy (obstructive, etc.), Raynaud's disease, pulmonary hypertension, broncho-obstructive syndrome. Contraindications Hypersensitivity, acute period of myocardial infarction (first 8 days), cardiogenic shock, severe aortic stenosis, heart failure in the stage of decompensation, severe arterial hypotension, tachycardia, pregnancy, breastfeeding. Restrictions on use: You should refrain from using the drug in pediatric practice, since the safety and effectiveness of its use in children have not been determined. Method of administration and dosage Orally, during or after meals, in the form of tablets, capsules, dragees, adults - 10 mg 3-4 times a day. In special cases (variant angina, severe arterial hypertension), it is possible to increase the dose to 20 mg 4-6 times a day for a short time. The maximum daily dose is 120 mg. For arterial hypertension - 10 mg 3 times a day (if necessary, the dose is increased over 7-14 days to 20-30 mg per dose. To relieve a hypertensive crisis and an attack of angina, 10-20 mg sublingually or orally once, if necessary - through 10 minutes repeatedly in the form of capsules and tablets of prolonged action (it is recommended to first bite or puncture the capsule) - 20-40 mg 2 times a day (for Prinzmetal's angina - up to 120 mg / day); in the form of ultraretard tablets - 40-80 mg 1 once a day (the tablet is not chewed). Overdose Symptoms: severe bradycardia, bradyarrhythmia, arterial hypotension, in severe cases - collapse, conduction slowdown. When taking a large number of retard tablets, signs of intoxication appear no earlier than 3-4 hours later and may additionally expressed in loss of consciousness up to coma, cardiogenic shock, convulsions, hyperglycemia, metabolic acidosis, hypoxia.Treatment: gastric lavage, intake of activated charcoal, administration of norepinephrine, calcium chloride or calcium gluconate in atropine solution intravenously. Hemodialysis is ineffective. Interaction The hypotensive effect is enhanced by nitrates, diuretics, beta-blockers, tricyclic antidepressants, fentanyl, and alcohol. Increases the activity of theophylline, reduces the renal clearance of digoxin. Increases the side effects of vincristine (reduces excretion). Increases the bioavailability of cephalosporins (cefixime). Cimetidine and ranitidine increase plasma levels. Diltiazem slows metabolism (requires a reduction in the dose of nifedipine). Incompatible with rifampicin (accelerates biotransformation and does not allow creating effective concentrations). Grapefruit juice (large quantities) increases bioavailability. Increases the concentration of cardiac glycosides in the blood. Special instructions: Elderly patients are advised to reduce the daily dose (decreased metabolism). Use with caution while working for vehicle drivers and people whose profession involves increased concentration. The drug should be discontinued gradually. In patients with stable angina, at the beginning of treatment, a paradoxical increase in anginal pain may occur; with severe coronary sclerosis and unstable angina, aggravation of myocardial ischemia may occur. It is not recommended to use short-acting drugs for long-term treatment of angina or hypertension, because the development of unpredictable changes in blood pressure and reflex angina is possible. Storage conditions Store at room temperature, in a cool, dry place, away from children.
Interaction
Nifedipine is metabolized primarily by CYP3A4, and drugs that inhibit or induce this enzyme may alter the first-pass metabolism or clearance of nifedipine.
Inducers of the CYP3A4 isoenzyme
Rifampicin
Rifampin is a strong inducer of the CYP3A4 system. When used simultaneously with rifampicin, the bioavailability of nifedipine is significantly reduced and effective plasma concentrations cannot be achieved.
Phenytoin, carbamazepine, phenobarbital
Phenytoin induces the CYP3A4 isoenzyme. Can reduce the bioavailability of nifedipine and reduce its effectiveness. When using phenytoin and nifedipine simultaneously, the clinical effect of the latter should be assessed and, if necessary, its dose should be increased.
If the dose of nifedipine was increased during combination therapy, this must be taken into account when discontinuing phenytoin.
Reliable studies of the interaction of nifedipine and carbamazepine and phenobarbital with simultaneous use have not been conducted. In other studies, carbamazepine and phenobarbital reduce the plasma concentration of another “slow” calcium channel blocker, nimodipine, so the possibility of a decrease in the plasma concentration of nifedipine when used simultaneously with carbamazepine and phenobarbital cannot be excluded.
CYP3A4 isoenzyme inhibitors
The simultaneous use of nifedipine and drugs that have an inhibitory effect on the CYP3A4 isoenzyme causes an increase in the concentration of nifedipine in the blood plasma.
Blood pressure should be monitored and the dose of nifedipine reduced if necessary.
Macrolide antibiotics (eg, erythromycin)
Some macrolide antibiotics are known to inhibit the CYP3A4-mediated metabolism of other drugs. Therefore, a potential increase in plasma concentrations of nifedipine cannot be excluded when used together.
Azithromycin, although structurally close to the class of macrolide antibiotics, does not inhibit the CYP3A4 isoenzyme.
HIV protease inhibitors (eg, amprenavir, indinavir, nelfinavir, ritonavir, or saquinavir)
There are no reliable clinical studies examining drug interactions between nifedipine and HIV protease inhibitors. Drugs in this class are known to inhibit the CYP3A4 isoenzyme. In addition, in an in vitro study, drugs of this class were shown to inhibit the metabolism of nifedipine. With simultaneous use of nifedipine with HIV protease inhibitors, an increase in its plasma concentration cannot be ruled out.
Imidazole derivatives (eg, ketoconazole, itraconazole, or fluconazole)
Reliable studies on the interaction of nifedipine with azole antifungals have not been conducted, but it is known that the latter inhibit the CYP3A4 isoenzyme.
When administered orally with nifedipine simultaneously, an increase in its plasma concentration cannot be ruled out.
Fluoxetine
No reliable studies have been conducted on the interaction of nifedipine with fluoxetine.
In an in vitro study, fluoxetine was shown to inhibit the CYP3A4-mediated metabolism of nifedipine. Therefore, an increase in the plasma concentration of nifedipine when used together cannot be excluded.
Nefazodone
No reliable studies have been conducted on the interaction of nifedipine and nefadozone.
In an in vitro study, nefadozone was shown to inhibit the CYP3A4-mediated metabolism of nifedipine. Therefore, an increase in the plasma concentration of nifedipine when used together cannot be excluded.
Quinupristin/Dalfopristin
The simultaneous use of quinupristin/dalfopristin and nifedipine may lead to an increase in the plasma concentration of the latter.
Valproic acid
Reliable studies of the interaction of nifedipine and valproic acid during simultaneous use have not been conducted. In other studies, valproic acid reduced the plasma concentration of another “slow” calcium channel blocker, nimodipine, so the possibility of a decrease in the plasma concentration of nifedipine when used simultaneously with valproic acid cannot be excluded.
Cimetidine
Due to inhibition of the CYP3A4 isoenzyme, cimetidine increases plasma concentrations of nifedipine and may enhance the antihypertensive effect.
Therefore, when nifedipine is used concomitantly with cimetidine, quinupristine, dalfopristin, erythromycin, fluoxetine, nefazodone, valproic acid, HIV protease inhibitors (for example, amprenavir, indinavir, nelfinavir, ritonavir or saquinavir) and azole derivatives (ketoconazole, itraconazole or fluconazole) Blood pressure should be monitored, and if necessary, the dose of the drug should be reduced.
Other drugs that affect the metabolism of nifedipine
Cisapride
Concomitant use of cisapride and nifedipine may lead to an increase in plasma concentrations of nifedipine.
Diltiazem
Diltiazem reduces the clearance of nifedipine and therefore increases the plasma concentration of nifedipine. Therefore, caution should be exercised when using drugs in combination and the dose of nifedipine should be reduced if necessary.
Cyclosporine
Concomitant use may lead to increased plasma concentrations of nifedipine.
Effects of nifedipine on other drugs
Hypothetical drugs
Nifedipine may enhance the antihypertensive effect of diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, other “slow” calcium channel blockers, alpha-blockers, phosphodiesterase-5 (PDE-5) inhibitors, alpha-methyldopa.
When using nifedipine simultaneously with beta-blockers, careful monitoring of the patient is necessary, since the symptoms of heart failure may worsen (isolated cases have been described).
Digoxin
The simultaneous use of nifedipine and digoxin may cause an increase in the plasma concentration of digoxin, therefore the concentration of digoxin in the blood serum should be monitored and, if necessary, the dose of digoxin should be adjusted.
Quinidine
With the simultaneous use of nifedipine and quinidine, a decrease in the plasma concentration of quinidine occurs, and in some cases, when nifedipine was discontinued, an increase in its concentration in the blood plasma was noted. Therefore, if necessary, dose adjustment of quinidine is recommended. Some authors indicate an increase in plasma concentrations of nifedipine with simultaneous use of both drugs. Therefore, blood pressure should be carefully monitored and the dose of nifedipine should be reduced if necessary.
Tacrolimus
Cyclosporine has been shown to be metabolized by the CYP3A4 isoenzyme.
Published data indicate that it may be necessary to reduce the dose of tacrolimus when coadministered with nifedipine.
Vincristine
When used simultaneously with nifedipine, the excretion of vincristine is reduced and a dose reduction may be required.
Magnesium sulfate
It is necessary to carefully monitor blood pressure when administering intravenous magnesium sulfate to patients taking nifedipine, because a pronounced decrease in blood pressure is possible.
Cephalosporins
When used simultaneously with nifedipine, the plasma concentration of cephalosporins increases.
Phenytoin
Nifedipine may slow down the metabolism of phenytoin and increase its toxic effects.
In patients taking phenytoin, it is recommended that plasma concentrations of phenytoin be monitored when initiating treatment with nifedipine.
Nitrates
It is necessary to take into account the synergistic effect when using nifedipine and nitrates simultaneously.
Theophylline
Nifedipine increases the concentration of theophylline in blood plasma when used simultaneously.
Fentanyl
The simultaneous use of nifedipine and fentanyl can lead to severe arterial hypotension, therefore it is recommended to discontinue the use of nifedipine (if possible) at least 36 hours before anesthesia with fentanyl.
Indirect anticoagulants
Rare reports of increased prothrombin time have been reported when nifedipine is used concomitantly with indirect anticoagulants (for example, warfarin). The relationship to nifedipine therapy has not been established; the clinical significance of this effect is unknown.
Other forms of interaction
In the spectrophotometric determination of vanillylmandelic acid in urine, nifedipine may cause a false positive result. It is recommended to take other measurements.
Grapefruit juice
Grapefruit juice inhibits the CYP3A4 isoenzyme. When taken simultaneously, grapefruit juice increases the concentration of nifedipine in the blood plasma due to a decrease in first-pass metabolism. Due to the increased bioavailability of nifedipine in patients with severe arterial hypertension or stable angina, the development of ischemic complications (heart attack, unstable angina) is possible. Drinking grapefruit juice during treatment with nifedipine is not recommended.
With the simultaneous use of nifedipine and acetylsalicylic acid, benazepril, candesartan, debrisoquin, doxazosin, irbesartan, omeprazole, orlistat, pantoprazole, ranitidine, rosiglitazone and triamterene/hydrochlorothiazide, there is no effect on the pharmacokinetics of nifedipine.
How to take, course of administration and dosage
The tablets should be taken at the same time of day, without chewing, and should not be crushed or divided. The dosage regimen is set individually. Do not take tablets with grapefruit juice.
The dose of Nifecard CL is 1 tablet of the drug 30 mg or 60 mg per day once. Dose selection begins at 30 mg/day, correction is carried out at intervals of 7-14 days.
The maximum daily dose of Nifecard CL is 90 mg.
The elimination of nifedipine may be slower in elderly patients, so lower maintenance doses of the drug may be required compared to younger patients.
In patients with impaired liver function, the use of nifedipine should be carried out under close supervision and, if necessary, a dose reduction may be required.
In patients with impaired renal function, no dose adjustment is required.
Patients with severe cerebrovascular disease should be treated with a low dose.
If it is necessary to discontinue the drug Nifecard CL, the dose should be reduced gradually.
Nifecard HL tablet p/pl.ob. with control vysv. 60 mg per blister. in pack №10x3
Name
Nifecard HL tablet p/pl.ob. with control vysv. 60 mg per blister. in pack №10x3
Description
60 mg: Pale brownish-yellow to pale brownish-orange, round, biconvex, film-coated 60 mg tablets with “NDP 60” debossed on one side. Unevenness and roughness of the surface are allowed.
Main active ingredient
Nifedipine
Release form
Pills
Dosage
60mg
pharmachologic effect
Pharmacodynamics
Nifedipine is a 1,4-dihydropyridine type calcium channel blocker. It reduces peripheral vascular resistance and therefore blood pressure. Nifedipine dilates large coronary arteries and arterioles in both normal and ischemic areas of the myocardium, and also significantly reduces spasm of the coronary arteries. Nifedipine increases the supply of oxygen to the myocardium, which is responsible for its effectiveness in the treatment of angina pectoris.
Pharmacokinetics
Nifedipine is rapidly and almost completely absorbed after oral administration (> 90%). Bioavailability is approximately 86%. Due to the prolonged release of the active substance, Nifecard HL provides a gradual, controlled increase in the plasma concentration of nifedipine, reaching a plateau approximately 6 hours after taking the first dose. After subsequent doses are taken at 24-hour intervals, plasma concentrations are maintained at a plateau level with minimal fluctuations. The binding of nifedipine to plasma proteins depends on the concentration and varies between 92–98%. In patients with impaired renal or hepatic function, protein binding may be reduced. Nifedipine is largely metabolized in the liver. The metabolites are inactive, highly soluble in water and, along with trace amounts of unchanged nifedipine, are excreted in the urine, accounting for 60% to 80% of the administered dose. The rest of nifedipine is excreted in the feces in the form of metabolites excreted in bile. The pharmacokinetics of nifedipine depends little on the degree of renal dysfunction. With normal liver and kidney function, the half-life of nifedipine from plasma ranges from 2 to 5 hours (in standard dosage forms). Most of nifedipine is excreted in the urine. Nifedipine is practically not excreted by hemodialysis and hemosorption. Impaired renal function Pharmacokinetics are no different. Therefore, if renal function is impaired, there is no need to adjust the dose of the drug. Impaired liver function The half-life of the drug is significantly increased, and the overall clearance is reduced. An increase in half-life of up to 7 hours has been reported in patients with cirrhosis. Children Nifedipine exhibits antihypertensive effects, but the recommended dose, long-term safety and effects on the cardiovascular system remain unknown. There is no dosage form for children.
Indications for use
Nifecard CL is indicated for adults for the treatment of: - for the treatment of all degrees of arterial hypertension; - for the prevention of attacks of chronic stable angina, both as monotherapy and in combination with beta-blockers.
Directions for use and doses
Doses For mild to moderate arterial hypertension, the recommended starting dose is 20 mg once daily. For severe arterial hypertension, the recommended starting dose is 30 mg (1 tablet) once a day. If necessary, the dose can be increased according to individual indications to a maximum of 90 mg once a day. For the prevention of angina attacks, the recommended starting dose is 30 mg (1 tablet) once a day. According to individual indications, the dose can be increased to a maximum of 90 mg once a day. When patients are transferred from therapy with other calcium antagonists, such as diltiazem or verapamil, to therapy with Nifecard CL, the preventive antianginal effect is maintained. With this transition, the recommended initial dose of Nifecard CL is 30 mg once a day. According to clinical indications, the dose can be gradually increased. When used concomitantly with CYP3A4 inhibitors or inducers, nifedipine dose adjustment or drug discontinuation may be required. Duration of treatment Unlimited. Special categories of patients Children The safety and effectiveness of treatment with Nifecard HL in children under 18 years of age has not been established. Elderly patients No dose adjustment is required in patients over 65 years of age. Patients with impaired renal function No dose adjustment is required in patients with impaired renal function. Directions for use: For oral administration. The tablets are swallowed whole with a glass of water, regardless of meals, always at the same time of day, preferably in the morning. Nifecard HL tablets should be swallowed whole; they are not allowed to be broken, chewed or crushed. Nifecard XL should not be taken simultaneously with grapefruit juice.
Use during pregnancy and lactation
Fertility If in vitro fertilization fails repeatedly and there are no other explanations, the use of calcium channel blockers such as Nifecard XL may be a possible cause, since they can impair sperm function by causing reversible biochemical changes in the head of the sperm. Pregnancy Nifecard CL should not be used during pregnancy, except in cases where, due to the clinical condition of the patient, the use of this drug is necessary. The drug should be prescribed only to women with severe arterial hypertension when standard therapy is ineffective. Based on the available information, a negative effect of the drug on the fetus or newborn cannot be excluded. According to the available clinical data, no specific prenatal risk was identified. However, there was an increase in the number of perinatal asphyxias, caesarean sections, as well as premature births and intrauterine growth retardation. What exactly could have caused this increase—hypertension, its therapy, or the specific effect of the drug—has not been clarified. Blood pressure should be closely monitored, especially when used in combination with intravenous magnesium sulfate, due to the potential for excessive reduction in blood pressure, which may cause harm to both the mother and the fetus. Acute pulmonary edema has been observed when calcium channel blockers, including nifedipine, were used as a tocolytic during pregnancy, especially in pregnancies with two or more fetuses, with intravenous administration of the drug and/or concomitant use of beta-2 receptor agonists. Breastfeeding Nifedipine is excreted into breast milk. Its concentration in breast milk is almost similar to that in the mother's blood plasma. This drug is not recommended for use during breastfeeding.
Precautionary measures
Caution should be exercised in patients with severe hypotension (severe hypotension with systolic pressure less than 90 mmHg), symptomatic heart failure and severe aortic valve stenosis. For symptomatic heart failure caused by left ventricular systolic dysfunction, the drug is prescribed with caution. In patients with a left ventricular ejection fraction of less than 30%, the use of calcium channel antagonists is not recommended. The drug should not be used in patients with obstructive cardiomyopathy. In severe obstructive coronary artery disease, nifedipine may (although rarely) increase the frequency, severity and duration of angina attacks. In such cases, the drug is discontinued. With malignant arterial hypertension and hypovolemia in patients on hemodialysis, blood pressure (BP) may sharply decrease, which is the result of vasodilation. Nifedipine is metabolized by the CYP3A4 isoenzyme of the cytochrome P450 system. Drugs that inhibit or induce this enzyme may affect both the first pass of nifedipine through the liver and its clearance (see “Interactions with other medicinal products and other types of interactions”). Drugs that can inhibit the CYP3A4 isoenzyme of the cytochrome P450 system and, therefore, increase the concentrations of nifedipine in the blood plasma include: - macrolide antibiotics (eg, erythromycin); - HIV protease inhibitors (eg, ritonavir); - azole antifungal drugs (eg, ketoconazole); - antidepressants nefazodone and fluoxetine; - quinupristin/dalfopristin; - valproic acid; - cimetidine. When used together with the listed active substances, careful monitoring of blood pressure is required and, if necessary, a reduction in the dose of nifedipine. Use for liver failure If liver function is impaired, discontinuation of the drug is necessary (see “Contraindications”). Use in diabetes mellitus Prescribing Nifecard CL may require adjustment of hypoglycemic therapy. In patients with possible hyperglycemia, the drug is prescribed with caution. Use for severe cerebrovascular diseases Low doses should be used. When prescribing Nifecard CL tablets to patients with gastrointestinal tract (GIT) stenoses, due to the possible development of symptoms of obstruction or bezoar formation, caution should be exercised (see “Contraindications”). Isolated cases of the development of obstructive symptoms in the absence of any gastrointestinal disorders in the anamnesis have been described. When performing an X-ray examination using barium contrast, Nifecard CL tablets may cause false-positive results (for example, filling defects that can be mistakenly regarded as polyps). Information on some excipients The drug contains lactose monohydrate, so it should not be taken by patients with rare hereditary disorders such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.
Interaction with other drugs
Medicines affecting nifedipine Metabolism of nifedipine is mainly carried out through the CYP3A4 isoenzyme, localized in the liver and intestinal mucosa. Substances that inhibit or induce this enzyme may affect both the first passage of nifedipine through the liver (when administered orally) and its clearance (see "Special Instructions and Precautions for Use"). The strength and duration of drug interactions should be taken into account when nifedipine is co-administered with the following medicinal products. Drugs that induce the CYP3A4 isoenzyme Rifampicin is a highly active inducer of the CYP3A4 isoenzyme of the cytochrome P450 system. When used simultaneously with rifampicin, the bioavailability of nifedipine is significantly reduced, thereby reducing its effectiveness. Therefore, the use of nifedipine in combination with rifampicin is contraindicated (see “Contraindications”). Medicines that increase the exposure of nifedipine: - macrolide antibiotics (eg, erythromycin); - HIV protease inhibitors (eg, ritonavir); - azole antifungals (eg, ketoconazole); - fluoxetine; - nefazodone; - quinupristin/dalfopristin; - cisapride; - valproic acid; - cimetidine; - diltiazem. When used simultaneously with inducers of the CYP3A4 isoenzyme of the cytochrome P450 system, the clinical response to nifedipine should be monitored and, if necessary, an increase in the dose of nifedipine should be considered. If the dose of nifedipine was increased during concomitant therapy with these drugs, then when discontinuing them, a reduction in the dose of nifedipine should be considered. Medicines that reduce the exposure of nifedipine: - rifampicin (see above); - phenytoin; - carbamazepine; - phenobarbital. Effect of nifedipine on other drugs Nifedipine may enhance the hypotensive effect of concomitant antihypertensive drugs. When using nifedipine simultaneously with beta-blockers, the patient's condition requires careful monitoring, since in isolated cases heart failure has worsened. Digoxin. When used together, nifedipine may reduce the clearance of digoxin and, therefore, increase its plasma concentration. Therefore, as a precaution, it is necessary to monitor for signs of digoxin overdose and, if necessary, reduce the dose of this glycoside. Quinidine. With the simultaneous use of nifedipine and quinidine, a decrease in the concentration of the latter in the blood plasma may be observed, and after discontinuation of nifedipine, in some cases, a noticeable increase in the concentration of quinidine in plasma may be observed. Therefore, when prescribing or discontinuing nifedipine, it is recommended to monitor the level of quinidine in the blood plasma and, if necessary, adjust the dose of quinidine. Blood pressure should be carefully monitored and the dose of nifedipine reduced if necessary. Tacrolimus. Tacrolimus is metabolized by the CYP3A4 isoenzyme of the cytochrome P450 system. Published data indicate that when nifedipine and tacrolimus are used concomitantly, the dose of the latter can be reduced in selected cases. When using both drugs simultaneously, plasma concentrations of tacrolimus should be monitored and, if necessary, a dose reduction should be considered. Interaction with food Grapefruit juice inhibits the CYP3A4 isoenzyme of the cytochrome P450 system. Simultaneous administration leads to an increase in the concentration of nifedipine in the blood plasma, enhancing the hypotensive effect of nifedipine. With regular consumption of grapefruit juice, this effect can persist for another 3 days after its last use. During treatment with nifedipine, you should avoid eating grapefruits or grapefruit juice (see “Dosage and Administration”). Other interactions Nifedipine may cause a false increase in the spectrophotometric values of vanillyl mandelic acid without affecting HPLC readings.
Contraindications
- Hypersensitivity to the active substance, other dihydropyridines or to any of the excipients of the drug; - cardiogenic shock, aortic stenosis (clinically significant), unstable angina, myocardial infarction and in the first 4 weeks after it; - attack of angina pectoris; - malignant arterial hypertension (the safety of nifedipine has not been established); - liver dysfunction; — obstruction of the gastrointestinal tract, esophagus or narrowing of the lumen of the gastrointestinal tract of any degree in the anamnesis; — patients with valve ileostomy according to Kokk (ileostomy after proctocolectomy); - inflammatory bowel disease or Crohn's disease; — Nifecard CL cannot be used for secondary prevention of myocardial infarction; — Nifecard CL cannot be used in combination with rifampicin.
Compound
Each film-coated, controlled-release tablet contains 60 mg of nifedipine. Excipients Core: povidone, sodium lauryl sulfate, hypromellose, Ludipress® (a mixture of lactose monohydrate, povidone and crospovidone), talc, magnesium stearate. Shell: hypromellose phthalate, triethyl citrate, hypromellose, hydroxypropylcellulose, polyethylene glycol 400, talc, titanium dioxide (E171), iron oxide yellow (E172).
Overdose
In case of severe intoxication with nifedipine, the following symptoms are possible: impaired consciousness up to coma, drop in blood pressure, heart rhythm disturbances such as tachycardia or bradycardia, hyperglycemia, metabolic acidosis, hypoxia, cardiogenic shock with pulmonary edema. The main goal of treatment is to remove the active substance of the drug and achieve hemodynamic stability. In case of oral administration, gastric lavage is indicated, if necessary in combination with small intestinal lavage, especially in case of intoxication with slow-release drugs. Nifedipine is not eliminated by dialysis, but the use of plasmapheresis is recommended (due to the high degree of binding of nifedipine to plasma proteins and the relatively low volume of distribution). Heart rhythm disturbances such as bradycardia are treated symptomatically with β-sympathomimetics; Life-threatening cases of heart rhythm disturbances such as bradycardia require the installation of a temporary pacemaker. Hypotension in cardiogenic shock and arterial vasodilation should be treated with calcium preparations (10–20 ml of 10% calcium gluconate solution IV slowly, the administration can be repeated if necessary). As a result, serum calcium levels may reach or slightly exceed the upper limit of normal values. If the use of a calcium supplement fails to achieve the required increase in blood pressure, vasoconstrictor sympathomimetics such as dopamine or norepinephrine are additionally prescribed. The dose of these drugs is determined solely by the effect achieved. Due to the risk of cardiac overload, additional fluid and volume replacement solutions should be administered with caution.
Side effect
The following are adverse drug reactions (ADRs) observed in placebo-controlled studies of nifedipine (Clinical Trials Database (nifedipine n = 2661; placebo n = 1486; accessed February 22, 2006) and the ACTION study (nifedipine n = 3825 ; placebo n = 3840)). They are classified into frequency categories developed by CIOMS III. ADRs classified as “common” were observed with a frequency of less than 3%, with the exception of edema (9.9%) and headache (3.9%). The incidence of adverse reactions to drugs containing nifedipine is summarized below. Within each frequency category, adverse reactions are presented in order of decreasing severity. The frequency of reactions was determined as follows: frequent (≥1/100 and
Storage conditions
Keep out of the reach of children. Store in original packaging at a temperature not exceeding 25 °C.
Buy Nifecard HL tablet p/pl.ob. with control vysv. 60 mg per blister. in pack No. 10x3 in the pharmacy
Price for Nifecard HL tablet p/pl.ob. with control vysv. 60 mg per blister. in pack №10x3
Instructions for use for Nifecard HL tablet p/pl.ob. with control vysv. 60 mg per blister. in pack №10x3
Overdose
Symptoms: peripheral vasodilation with a pronounced and possibly prolonged pronounced decrease in blood pressure (headache, facial flushing, depression of the sinus node, bradycardia and/or tachycardia, bradyarrhythmia), hyperglycemia, metabolic acidosis, hypoxia, cardiogenic shock with the development of pulmonary edema. In case of severe poisoning – loss of consciousness, coma.
Treatment of overdose consists of standard procedures for removing the drug from the body (prescription of activated carbon, gastric lavage), restoration of stable hemodynamic parameters, careful monitoring of the activity of the heart, lungs and excretory system.
In cases of overdose of long-acting drugs, it is necessary to ensure the most complete removal of the drug from the body, and, if possible, lavage of the small intestine in order to prevent further absorption of the active substance. When using laxatives, it should be taken into account that blockers of “slow” calcium channels can cause a decrease in the tone of the intestinal muscles, up to intestinal atony.
Hemodialysis is not effective; plasmapheresis is recommended due to the high degree of protein binding and relatively small volume of distribution.
Treatment of bradyarrhythmias is symptomatic with the use of atropine and/or beta-sympathomimetics; in case of life-threatening bradyarrhythmias, a temporary pacemaker is necessary.
With a persistent pronounced decrease in blood pressure as a result of cardiogenic shock and arterial vasodilation, calcium (1-2 g of calcium gluconate, intravenously), dopamine (up to 25 mcg/kg/min), dobutamine (up to 15 mcg/kg/min), epinephrine ( adrenaline) or norepinephrine (norepinephrine). Doses of these drugs should be determined solely on the basis of the effect obtained.
Due to possible volume overload of the heart, infusion therapy is recommended to be carried out with caution under the control of hemodynamic parameters.
The antidote is calcium preparations. The clearance of nifedipine is increased in patients with impaired liver function.
Special instructions
It is recommended to discontinue treatment with Nifecard XL gradually.
It should be borne in mind that at the beginning of treatment an attack of angina may occur, especially after the recent abrupt withdrawal of beta-blockers (the latter should be withdrawn gradually).
The simultaneous use of beta-blockers must be carried out under conditions of careful medical supervision, since this may cause an excessive decrease in blood pressure, and in some cases, aggravation of the symptoms of heart failure.
In case of severe heart failure, the drug is dosed with great caution.
Rarely, in patients with severe coronary artery stenosis, at the beginning of therapy or with an increase in the dose of nifedipine, the frequency and severity of anginal pain may increase, up to the development of myocardial infarction.
Diagnostic criteria for the use of the drug for vasospastic angina are: the classic clinical picture, accompanied by an increase in the ST segment on the ECG, 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 pectoris, when electrocardiogram data indicate transient vasospasm).
For patients with severe hypertrophic obstructive cardiomyopathy, there is a risk of an increase in the frequency, severity and duration of angina attacks after the use of nifedipine; in this case, discontinuation of the drug is necessary.
In patients with diabetes mellitus, when using the drug Nifecard XL, it may be necessary to monitor the concentration of glucose in the blood plasma.
In patients on hemodialysis with high blood pressure and irreversible renal impairment, with a reduced 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.
In patients with severe stenosis of any part of the gastrointestinal tract, intestinal obstruction may develop. In very rare cases, bezoars may develop, which may require surgery to remove. In isolated cases, symptoms of intestinal obstruction can be observed in patients who do not have pathology in the gastrointestinal tract. The risk of developing bezoars is increased in patients with reduced intestinal motility (constipation, gastroesophageal reflux, obesity, hypothyroidism, diabetes mellitus), intestinal tumors, diverticulitis, inflammatory bowel changes, vertical gastroplasty, gastric bypass, after resection of the small intestine, colostomy, as well as simultaneous use with H2-histamine receptor blockers, opiates, non-steroidal anti-inflammatory drugs, anticholinergic drugs, neuromuscular blockers (muscle relaxants), laxatives (laxatives).
There are isolated reports of tablets “sticking” to the intestinal wall with the formation of ulcers that required hospitalization and surgery.
It should be borne in mind that an X-ray examination of the intestine with barium can reveal false-positive symptoms of a polyp (a “filling” defect).
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.
Nifedipine, like other blockers of “slow” calcium channels, inhibit platelet aggregation in vitro. A small number of reports support data on a statistically significant decrease in platelet aggregation and an increase in bleeding time. The clinical significance of this is not known.
During treatment, a positive result is possible when performing a direct Coombs reaction and an increase in the titer of antinuclear antibodies.
Impact on the ability to drive vehicles and machinery
During treatment with Nifecard HL, caution must be exercised when engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, and refrain from using alcohol.
Special precautions when disposing of unused drug
There is no need for special precautions when disposing of unused drug.
Nifecard XL 30 mg No. 30 tablet p.o.
Instructions for medical use of the drug Nifecard® CL Trade name Nifecard® CL ® International nonproprietary name Nifedipine Dosage form Film-coated tablets, 30 mg, 60 mg Composition One tablet contains the active substance - nifedipine 30.0 or 60.0 mg, auxiliary substances: povidone, sodium lauryl sulfate, hypromellose, ludipress®, talc, magnesium stearate, shell composition: hypromellose phthalate, triethyl citrate, hydroxypropylcellulose, macrogol 400, titanium dioxide, iron oxide (yellow). Description Brownish-yellow to pale brownish-orange, round, biconvex, film-coated tablets with “NDP 30” or “NDP 60” embossed on one side. Pharmacotherapeutic group Selective blockers of “slow” calcium channels with a predominant effect on blood vessels. Dihydropyridine derivatives. ATC code C08CA05 Pharmacological properties Pharmacokinetics Absorption Nifedipine is rapidly and almost completely absorbed after oral administration. Binding to blood plasma proteins is 90%. The half-life of elimination is approximately 2 hours. It is excreted mainly by the kidneys in the form of inactive metabolites. Nifecard®HL, due to the delayed release of the active component, provides a gradual, controlled increase in plasma concentrations of nifedipine. Nifedipine reaches a steady-state plasma concentration approximately 6 hours after taking each dose of the drug and remains at this concentration with minor fluctuations for 24 hours. Pharmacodynamics Nifedipine is a dihydropyridine derivative. The mechanism of action is the blockade of slow calcium channels. Inhibits the transport of calcium ions through the membranes of myocardial cells or vascular smooth muscle cells without affecting plasma calcium concentrations. The result of this action is dilatation of arteries and arterioles, a decrease in peripheral vascular resistance and, as a consequence, a decrease in blood pressure. Nifedipine causes dilatation of the main coronary arteries and arterioles in both normal and ischemic areas of the heart muscle and prevents spasm of the coronary arteries. Nifedipine increases the supply of oxygen to the myocardium while reducing the need for oxygen, which allows the drug to be used for the treatment of angina pectoris. Indications ¾ arterial hypertension ¾ coronary heart disease (CHD); stable, vasospastic angina. Method of administration and dosage. The drug is prescribed individually. The initial dose of the drug is 30 mg per day once. The tablets should be taken without chewing and should not be crushed or divided. Dose selection is carried out gradually, at intervals of 7 - 14 days. The average daily dose is 30 mg or 60 mg. The maximum daily dose is 90 mg. If it is necessary to discontinue the drug, the dosage is gradually reduced until complete withdrawal. Side effects Often - manifestations of excessive vasodilation (asymptomatic decrease in blood pressure, a feeling of a rush of blood to the facial skin, flushing of the facial skin, a feeling of heat), tachycardia, palpitations, arrhythmia, peripheral edema, chest pain - headache, dizziness, increased fatigue, weakness, drowsiness ; with long-term use in high doses - paresthesia of the limbs, depression, anxiety, extrapyramidal (parkinsonian) disorders (ataxia, mask-like face, shuffling gait, stiffness in the movements of the arms and legs, tremor of the hands and fingers, difficulty swallowing) - in the mouth, loss of appetite , dyspepsia (nausea, diarrhea or constipation) - anemia, asymptomatic agranulocytosis, thrombocytopenia, thrombocytopenic purpura, leukopenia - difficulty breathing Rarely - excessive decrease in blood pressure, fainting, syncope; angina pectoris - gum hyperplasia (bleeding, pain, swelling) - liver dysfunction (intrahepatic cholestasis, increased activity of hepatic transaminases) - skin itching, exanthema, exfoliative dermatitis, photodermatitis - arthralgia, swelling of the joints, myalgia, convulsions of the upper and lower extremities Very rarely - myocardial infarction - visual impairment (including transient blindness at the maximum concentration of nifedipine in the blood plasma) - pulmonary edema, bronchospasm - gynecomastia (in elderly patients, completely disappearing after discontinuation of the drug), hyperglycemia, galactorrhea, weight gain - autoimmune hepatitis Contraindications ¾ severe arterial hypotension (systolic blood pressure below 90 mm Hg) ¾ severe aortic valve stenosis ¾ chronic heart failure in the decompensation stage ¾ hypersensitivity to nifedipine, drug components and other 1,4-dihydropyridine derivatives ¾ acute period of myocardial infarction (during the first 4 weeks) ¾ myocardial infarction with left ventricular failure ¾ unstable angina ¾ cardiogenic shock with residual angina (risk of developing myocardial infarction) ¾ stenosis of the aortic orifice or mitral valve ¾ hypertrophic obstructive cardiomyopathy, severe tachycardia ¾ pregnancy and lactation ¾ malignant arterial hypertension tension ¾ severe disorders cerebral circulation, impaired liver and/or kidney function ¾ children and adolescents under 18 years of age ¾ during hemodialysis (risk of arterial hypotension) Drug interactions Due to the synergistic effect, caution is required when using nifedipine and other antihypertensive drugs, beta-blockers and nitrates simultaneously . The simultaneous administration of nifedipine and digoxin increases plasma concentrations of nifedipine; therefore, monitoring of plasma concentrations of digoxin and, if necessary, dose adjustment of digoxin is necessary. Nifedipine reduces the metabolism of phenytoin, while simultaneous administration of nifedipine with cyclosporine or cimetidine may cause an increase in the level of nifedipine in the blood. Concomitant administration of nifedipine and fentanyl may cause severe hypotension, therefore, it is recommended that nifedipine be discontinued at least 36 hours before anesthesia (if possible). In patients taking nifedipine, plasma concentrations of quinidine may decrease by 50%. Nifedipine causes an increase in the level of theophylline in the blood when administered simultaneously. Special instructions Prescribe with caution to patients with diabetes. For patients with severe obstructive coronary disease, there is a risk of increased frequency, severity and duration of angina attacks after taking nifedipine. In this case, discontinuation of the drug is necessary. If during treatment with Nifecard CL the patient requires surgery 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. The simultaneous administration of beta-blockers or cardiac glycosides must be carried out under conditions of careful medical supervision, as this may cause an excessive decrease in blood pressure, and in some cases, aggravation of symptoms of heart failure. Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms The effect of the drug on the ability to concentrate (driving a car, working with machinery) has not been studied. Overdose Symptoms - headache, flushing of the facial skin, prolonged pronounced decrease in blood pressure, depression of the sinus node, bradycardia and/or tachycardia, bradyarrhythmia; in severe cases - loss of consciousness, coma. Treatment is the administration of activated carbon, gastric lavage, restoration of stable hemodynamic parameters, careful monitoring of the activity of the heart, lungs and excretory system. Due to the high degree of binding to plasma proteins, hemodialysis is not effective. Release form and packaging Film-coated tablets, 30 mg and 60 mg No. 30. Primary packaging – Aluminum/Aluminium. blisters Secondary packaging – a cardboard box along with instructions for use Storage conditions Store at a temperature not exceeding +25° C. Keep out of the reach of children! Shelf life: 3 years Do not use the drug after the expiration date indicated on the package. Conditions for dispensing from pharmacies By prescription Manufacturer Lek pharmaceuticals d.d. Veroshkova 57,1526 Ljubljana Slovenia
