Nifecard XL pills 60mg №60

Mechanism of action

Pharmacological action - antianginal, hypotensive, blocking Calcium channels.

Pharmacodynamics

Nifedipine is a selective BPC, a derivative of 1,4-dihydropyridine. It has antianginal and antihypertensive effects. Reduces the current of extracellular calcium inside the cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries; in high doses inhibits the release of calcium ions from intracellular depots. Reduces the number of functioning channels without affecting the time of their activation, inactivation and recovery.

Separates the processes of excitation and contraction in the myocardium, mediated by tropomyosin and troponin, and in vascular smooth muscle, mediated by calmodulin. In therapeutic doses, it normalizes the transmembrane current of calcium ions, disturbed in a number of pathological conditions, especially in arterial hypertension. Does not affect the tone of the veins. Enhances coronary blood flow, improves blood supply to ischemic zones of the myocardium without developing the phenomenon of robbery, activates the functioning of collaterals.

It improves myocardial function, reduces the strength of heart contractions and the myocardial oxygen demand. Expanding peripheral arteries, lowers blood pressure and decreases round coronary artery disease and afterload on the heart.Almost no effect on sinoatrial and AV nodes. Strengthens a renal blood-groove, causes a moderate natriuresis.

Inhibits platelet aggregation, has anti-atherogenic properties (especially with long-term use). It lowers the pressure in the pulmonary artery, has a positive effect on the blood supply to the cerebral vessels.

Pharmacokinetics

Nifecard^® CL due to the slow release of the active substance provides a gradual controlled increase in plasma concentrations of Nifedipine. Plasma concentration of nifedipine reaches a plateau after about 6 hours and is maintained with slight fluctuations within 24 hours. Nifedipine is rapidly and almost completely absorbed after oral administration (92-98%). It is characterized by a high percentage of binding to plasma proteins (90%). T_1/2 approximately 2 hours. Metabolized in the liver. Active metabolites not detected. Excreted in the form of inactive metabolites mainly by the kidneys (80%) and with bile (20%).

Nifedipine penetrates the BBB and the placental barrier, excreted in breast milk.

No cumulative effect.

CRF, hemodialysis, and peritoneal dialysis do not affect the pharmacokinetics.

When abnormal liver function reduced clearance of nifedipine. In severe hepatic impairment, dose adjustment may be required.

In patients with advanced age, with n / a clearance of nifedipine was reduced by 33% compared with young healthy volunteers.

With long-term admission, the development of tolerance to nifedipine can be observed.

Indications drug Nifekard^® CL

arterial hypertension;

ischemic heart disease: stable exertional angina, vasospastic stenocardia (Prinzmetal stenocardia).

Contraindications

hypersensitivity to nifedipine or drug components and other 1,4-dihydropyridine derivatives;

severe hypotension (SBP below 90 mm Hg);

severe aortic valve stenosis with clinically significant impaired hemodynamics;

unstable angina;

chronic heart failure in the stage of decompensation, cardiogenic shock (risk of myocardial infarction), acute period of myocardial infarction (during the first 4 weeks);

simultaneous use of rifampicin;

rare hereditary forms of lactose intolerance, lactase deficiency or impaired glucose / galactose absorption (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 mouth of the aorta or mitral valve; hypertrophic obstructive cardiomyopathy; severe tachycardia; sick sinus syndrome; malignant arterial hypertension; myocardial infarction with left ventricular failure; cerebrovascular diseases; simultaneous use of beta-blockers or cardiac glycosides,inducers or inhibitors of the isoenzyme CY3A4; abnormal liver and / or kidney function; hemodialysis (risk of arterial hypotension); diabetes; intestinal obstruction; pregnancy after 20 weeks.

Use during pregnancy and lactation

Controlled studies on the use of nifedipine in pregnant women have not been conducted. Animal studies have shown teratogenicity and embryo / fetotoxicity of nifedipine. Use of the drug Nifekard^® CL to 20 weeks contraindicated. Use of the drug Nifekard^® CL after 20 weeks gestation is possible only if the intended benefit to the mother outweighs the potential risk to the fetus, and the drug should be used only in a hospital with appropriate monitoring of the mother and fetus (control of mother's blood pressure; regular ultrasound monitoring of fetal development and viability ). If anomalies occur, discontinue use of the drug.

Nifedipine penetrates into breast milk, so when used during lactation, it is necessary to solve the issue of stopping breastfeeding.

Fertility Some BPC studies, such as nifedipine, have led to reversible biochemical changes in the sperm head, which can impair their function. In men who repeatedly experience problems in conceiving a child with in vitro fertilization, the use of nifedipine should be considered as one of the possible reasons, if no other explanation can be found.

Side effects

Undesirable reactions are given in accordance with the WHO classification according to the frequency of their development as follows: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000); frequency is unknown - according to the available data it was not possible to establish the frequency of occurrence.

From the blood and lymphatic system: frequency is unknown - agranulocytosis, leukopenia, anemia, thrombocytopenia.

Immune system: infrequently - allergic reactions, allergic edema / angioedema; rarely - pruritus, skin rash, urticaria; unknown frequency - anaphylactic / anaphylactoid reaction, toxic epidermal necrolysis, exfoliative dermatitis, photodermatitis, autoimmune hepatitis, thrombocytopenic purpura.

Metabolism and nutrition: frequency unknown hyperglycemia.

Nervous system: often - headache; infrequently - dizziness, migraine, fatigue, tremor; rarely, paresthesia / dysesthesia of the extremities; frequency is unknown - with long-term use in high doses - depression, anxiety, extrapyramidal (parkinsonian) disorders (ataxia, mask-like face, shuffling gait, stiffness of arm and leg movements, tremor of hands and fingers, difficulty swallowing, hypostezia, drowsiness), increased excitability, sleep disturbance (including insomnia), nightmares, decreased libido.

Special senses: infrequently - visual impairment (transitory); frequency is unknown - pain in the eye area.

On the part of the organ of hearing and labyrinth disorders: infrequently - ringing in the ears, dysgeusia (a violation of taste).

From the CCC: often - peripheral edema, increased symptoms of vasodilation (asymptomatic decrease in blood pressure, flushing of the skin of the face, flushing of the skin of the face, feeling of heat); infrequently - tachycardia, a sensation of heartbeat, arrhythmia, excessive decrease in blood pressure (especially in patients on dialysis with malignant hypertension and reduced BCC), syncope, syncope; very rarely - in some patients, especially at the beginning of treatment, angina may occur, which requires discontinuation of the drug. Described isolated cases of myocardial infarction; frequency is unknown - chest pain, aggravation of symptoms of heart failure.

On the part of the respiratory system: infrequently - nasal bleeding, nasal congestion, cough, sinusitis, difficulty breathing, upper respiratory tract infections; frequency is unknown - dyspnea, bronchospasm, pulmonary edema.

From the digestive system: often - constipation; infrequently - dryness of the oral mucosa, loss of appetite, dyspepsia (nausea, diarrhea), abdominal pain; rarely - gingival hyperplasia (bleeding, soreness, swelling); frequency is unknown - dysphagia, erosive and ulcerative lesions of the intestinal mucosa, vomiting, insufficiency of the gastroesophageal sphincter,with prolonged use - impaired liver function (intrahepatic cholestasis), increased activity of hepatic transaminases, jaundice), bezoars (lumps in the stomach from undigested food residues).

From the musculoskeletal system and connective tissue: infrequently - spasms of the upper and lower extremities, swelling of the joints, back pain, gout; frequency is unknown - arthritis, arthralgia, myalgia.

From the genitourinary system: infrequently - an increase / decrease in daily diuresis, erectile dysfunction; rarely, gynecomastia (in elderly patients, completely disappearing after discontinuation of the drug); frequency is unknown - galactorrhea, deterioration of renal function (in patients with renal insufficiency).

Skin and Subcutaneous Tissues: infrequently - alopecia, increased sweating, hemorrhagic rash.

General disorders and disorders at the site of administration: often - asthenia, weakness; infrequently - non-specific pain, chills, swelling of the face, periorbital edema, fever, weight gain.

Interaction

Nifedipine is metabolized mainly by the CYP3A4 isoenzyme, therefore drugs that inhibit or induce this enzyme can alter the systemic metabolism or clearance of nifedipine.

Inductors of isoenzyme CYP3A4

Rifampicin. Rifampicin is a strong inducer of the CYP3A4 isoenzyme. With simultaneous use of rifampicin, the bioavailability of nifedipine is significantly reduced and the effective plasma concentration cannot be achieved.

Phenytoin, Carbamazepine, phenobarbital. Phenytoin induces a CYP3A4 isoenzyme.Able to reduce the bioavailability of nifedipine and reduce its effectiveness. With simultaneous use of phenytoin and nifedipine, the clinical effect of the latter should be evaluated and, if necessary, its dose should be increased. If the dose of nifedipine in combination therapy was increased, it is necessary to take this 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 BPC, nimodipine, therefore, the possibility of reducing the plasma concentration of nifedipine when used simultaneously with carbamazepine and phenobarbital cannot be excluded.

Inhibitors of the isoenzyme CYP3A4. 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, if necessary, reduce the dose of nifedipine.

Macrolide antibiotics (for example, erythromycin). Some macrolide antibiotics are known to inhibit the CYP3A4-mediated metabolism of other drugs. Therefore, we cannot exclude a potential increase in plasma concentrations of nifedipine when used together.

Azithromycin, although structurally close to the class of macrolide antibiotics, it does not inhibit the CYP3A4 isoenzyme.

HIV protease inhibitors (for example, amprenavir, indinavir, nelfinavir, ritonavir, or saquinavir). There are no reliable clinical studies on the drug interaction between nifedipine and HIV protease inhibitors. Drugs of this class are known to inhibit the CYP3A4 isoenzyme. Also in the study in vitro It was shown that drugs of this class inhibit the metabolism of nifedipine. With the simultaneous use of nifedipine with HIV protease inhibitors, an increase in its plasma concentration cannot be ruled out.

Imidazole derivatives (for example Ketoconazole, itraconazole or fluconazole). Reliable research on the interaction of nifedipine with azole antifungal drugs has not been conducted, but it is known that the latter inhibit the CYP3A4 isoenzyme. With simultaneous oral administration with nifedipine, an increase in its plasma concentration cannot be excluded.

Fluoxetine. Reliable studies on the interaction of nifedipine with Fluoxetine has not been conducted. In a study in vitro Fluoxetine has been shown to inhibit CYP3A4-mediated nifedipine metabolism. Therefore, an increase in the plasma concentration of nifedipine when used together cannot be excluded.

Nefazodone. Reliable studies on the interaction of nifedipine and nefadozona not been conducted. In a study in vitro It was shown that nefadozon inhibits the CYP3A4-mediated metabolism of nifedipine. Therefore, an increase in the plasma concentration of nifedipine when used together cannot be excluded.

Streptogramin B (quinupristin) / streptogramin A (dalfopristin). The simultaneous use of this combination and nifedipine may lead to an increase in plasma concentration of the latter.

Valproic acid. Reliable studies of the interaction of nifedipine and valproic acid with simultaneous use have not been conducted. In other studies, valproic acid reduced the plasma concentration of another BPC, nimodipine, therefore, the possibility of reducing the plasma concentration of nifedipine with simultaneous use with valproic acid cannot be ruled out.

Cimetidine Due to inhibition of the CYP3A4 isoenzyme, cimetidine increases plasma concentrations of nifedipine and may enhance the antihypertensive effect.

Thus, with simultaneous use of nifedipine with cimetidine, streptogramin B / streptogramin A, Erythromycin, fluoxetine, nefazodone, valproic acid, HIV protease inhibitors (for example, amprenavir, indinavir, nelfinavir, ritonavir, or heart patterns, to apply to the same token, to apply, to apply, to apply, to apply, to apply, to apply, to apply, to apply, to apply), to apply, to apply, to apply, to apply, to apply, to apply, to apply, to apply, to apply, to apply, to apply, to apply, to apply, to apply, to apply, to apply, to apply, to apply, to apply, to apply, to apply; blood pressure should be monitored, and if necessary, the dose should be reduced.

Other drugs that affect the metabolism of nifedipine

Cisapride. The simultaneous use of cisapride and nifedipine may lead to an increase in the plasma concentration of nifedipine.

Diltiazem. Diltiazem reduces the clearance of nifedipine and therefore increases the plasma concentration of nifedipine.Therefore, caution should be exercised when using the drugs in combination and, if necessary, reduce the dose of nifedipine.

Cyclosporine. Simultaneous use may lead to increased plasma concentrations of nifedipine.

Effects of Nifedipine on Other Drugs

Antihypertensive drugs. Nifedipine can enhance the antihypertensive effect of diuretics, beta-blockers, ACE inhibitors, ARA II, other BPCs, alpha blockers, PDE-5 inhibitors, alpha methyldopa.

When nifedipine is used simultaneously with beta-adrenergic blockers, careful monitoring of the patient is necessary, since worsening of the symptoms of the course of heart failure is possible (isolated cases are described).

Digoxin. The simultaneous use of nifedipine and Digoxin can cause an increase in plasma concentration of digoxin, therefore, the concentration of digoxin in the blood serum should be controlled, 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, with the withdrawal of nifedipine, an increase in its plasma concentration was noted. Therefore, if necessary, recommended dose adjustment of quinidine. Some authors indicate an increase in the plasma concentration of nifedipine with simultaneous use of both drugs. Thus, blood pressure should be carefully monitored, and if necessary, the dose of nifedipine should be reduced.