Nifedipine - instructions for use, dose, side effects, contraindications

core: microcrystalline cellulose - 51.00 mg, starch, corn - 58.25 mg, lactose monohydrate-36.20 mg, polysorbate-80 - 2.00 mg, magnesium stearate - 0.15 mg, hypromellose - 2.40 mg;

film aboutOphthalmic: hypromellose - 4.20 mg, macrogol-6000 - 1.40 mg, talcum 0.70 mg, titanium dioxide (E 171) - 1.00 mg, ferric iron oxide red (E 172) - 0.20 mg.

Description:Tablets of oblong form, grayish-red color, covered with a shell, with a risk on both sides.

Pharmacotherapeutic group:The blocker of "slow" calcium channels

ATX: & nbsp

C.08.C.A.05 Nifedipine

Pharmacodynamics:

Selective blocker of "slow" calcium channels, derivative of 1,4-dihydropyridine. Has vasodilating, antianginal and antihypertensive action.Reduces the current of calcium ions in cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries; in high doses, suppresses the release of calcium ions from the intracellular depot. 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 smooth muscle vessels, mediated kalmodulin. In therapeutic doses normalizes the transmembrane ion current calcium, disturbed in a number of pathological conditions, before total at arterial hypertension. Does not affect the tone of the veins. Strengthens coronary blood flow, improves blood supply to ischemic zones of the myocardium without development of the phenomenon "stealing", activates the functioning of collaterals. Expanding the peripheral arteries, reduces the overall peripheral resistance of the vessels, myocardial tone, postnagruzku, the need for myocardium in oxygen and increases the duration diastolic relaxation of the left ventricle. Virtually no effect on sinoatrial and atrioventricular nodes and does not have antiarrhythmic activity. It enhances kidney blood flow, causes a moderate natriuresis. Negative chrono-, dromo- and inotropic action is overlapped by a reflex activation of the sympathoadrenal system and an increase in the heart rate in response to peripheral vasodilation.

The time of the onset of the effect is 20 minutes, the duration of the effect is 12-24 hours.

Pharmacokinetics:

Absorption is high (more than 92-98%). Bioavailability is 40-60%. Eating increases bioavailability. Has the effect of "primary passage" through - the liver.

The prolonged form provides a gradual release of the active substance in the systemic circulation. Time to reach a maximum concentration of 1.6-4.2 h, the maximum concentration is 47-76 mg / ml. Connection with blood plasma proteins - 90%.

Penetrates through the blood-brain and placental barrier, excreted in breast milk.

It is completely metabolized in the liver. In the metabolism of the drug, isozymes participate CYP3A4, CYP3A5 and CYP3A7. The half-life is 3.8-16.9 hours. In patients with hepatic insufficiency decreases overall clearance and increases the period elimination half-life. It is excreted as inactive metabolites in the main kidney (80%) and with bile (20 %).

Do not cumulate.Chronic renal failure, hemodialysis and peritoneal dialysis do not affect the pharmacokinetics. At long reception (2-3 months) tolerance to action of a preparation develops.

Plasmapheresis can enhance elimination.

Indications:

Chronic stable angina (stress angina).

Vasospastic angina pectoris (Prinzmetal angina).

Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs).

Disease and Raynaud's syndrome.

Contraindications:Hypersensitivity to nifedipine or other components of the drug, arterial hypotension (systolic blood pressure below 90 mm Hg), cardiogenic shock, collapse, severe aortic or subaortic stenosis, acute heart failure, chronic heart failure in decompensation, unstable angina, acute period of myocardial infarction (within the first 4 weeks), hypertrophic obstructive cardiomyopathy, severe aortic stenosis, sinus node weakness syndrome, atrioventricular rnaya blockade II-III art. coincident rifampicin, pregnancy (prior to 20 weeks.), lactation, age 18 years (efficacy and safety have not been studied).The preparation contains lactose, therefore contraindicated for patients with rare hereditary diseases lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Carefully:

Mitral stenosis, bradycardia or tachycardia, congestive heart failure, severe cerebrovascular accident, myocardial infarction with left ventricular failure, obstruction of the gastrointestinal tract, liver failure, chronic renal failure (especially in patients who are on hemodialysis - a high risk of excessive and unpredictable reduction blood pressure), simultaneous reception of beta-adrenoblockers and cardiac glycosides, pregnancy (after 20 ned.), the elderly.

Pregnancy and lactation:

Controlled studies of drug use Nifedipine in pregnant women was not carried out.

Tests in animals showed the presence of embryotoxicity, placental toxicity, fetotoxicity and teratogenicity when taking nifedipine during and after the organogenesis period.

According to available clinical data, it is impossible to judge the specific perinatal risk. At the same time, there are data on the increase in the probability of perinatal asphyxia, cesarean section, premature birth and intrauterine growth retardation. It is unclear whether the listed cases are a consequence of the underlying disease (arterial hypertension), treatment performed, or a specific effect of the drug Nifedipine. The information available is insufficient to exclude the possibility of side effects, which are dangerous for the fetus and the newborn. Therefore, the drug Nifedipine after 20th week of pregnancy requires a careful individual assessment, risk-benefit for the patient, the fetus and / or newborn and can be considered only in cases where other treatments are ineffective or contraindicated.

It should be carefully monitored blood pressure in pregnant women with the drug Nifedipine simultaneously with intravenous magnesium injection sulphate because of the possibility of excessive reduction in blood pressure, which is dangerous to both the mother and the fetus and / or neonate.

Nifedipine is contraindicated in the lactation period, since it is excreted in breast milk. If Nifedipine therapy is absolutely necessary, it is recommended to stop breastfeeding.

Dosing and Administration:

Inside. Tablets should be swallowed whole, without chewing, during or after a meal, with a small amount of water.

The recommended dose of the drug is 20 mg twice a day. If the effect is insufficient, it is possible to increase the dose to 40 mg twice a day.

The maximum daily dose is 80 mg.

If the liver function is impaired, the daily dose should not exceed 40 mg.

In elderly patients or patients receiving combined (antianginal or antihypertensive) therapy, smaller doses are usually given.

If liver function is impaired in patients with severe impairment of cerebral circulation, the dose should be reduced.

Duration of treatment is determined in each case individually.

Side effects:

The frequency of these side effects is indicated in accordance with the WHO classification: very often - more 10%; often more 1% and less 10%; infrequently, more 0,1% and less 1%; rarely - more 0,01% and less 0,1%; very rarely - less than 0,01%, including individual cases.

From the cardiovascular system: often - peripheral edema (stop, ankles, shins), symptoms of vasodilation (redness of the face, heat sensation); infrequently - tachycardia, palpitations, marked decrease in blood pressure, fainting; in some cases - chest pain (angina pectoris) until the development of myocardial infarction, the development or aggravation of chronic heart failure, arrhythmia.

From the nervous system: very often - headache; often - dizziness, drowsiness; infrequently - asthenia, sleep disturbance (including insomnia), nervousness, increased fatigue, dysesthesia, tremor, mood lability.

From the digestive system: often - nausea; infrequently - Gastrointestinal and abdominal pain (pain in the stomach and intestines), diarrhea, constipation, dryness of the oral mucosa, increased appetite; rarely - gingival hyperplasia (bleeding, soreness, swelling). With prolonged admission: infrequently - violations of the liver (intrahepatic cholestasis, increased activity of "liver" transaminases), rarely - jaundice; in some cases - the lack of a cardiac sphincter.

From the respiratory system: infrequently - shortness of breath, rarely - pulmonary edema (difficulty respiratory depression, cough, and breathless breathing).

From the musculoskeletal system: rarely - arthralgia, puffiness of the joints, myalgia, muscle cramps.

From the hematopoiesis: rarely - anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura; very rarely - asymptomatic agranulocytosis.

From the urinary system: infrequently - an increase in daily diuresis, impaired renal function (in patients with renal insufficiency).

Allergic reactions: often erythema; rarely - skin itching, hives, exanthema, photosensitivity, autoimmune hepatitis; infrequently, angioedema; in some cases - toxic epidermal necrolysis.

Other: rarely - visual impairment (including transient "loss of vision against the maximum concentration of nifedipine in blood plasma), pain in the eyes, hyperglycemia, gynecomastia (in elderly patients, completely disappearing after drug withdrawal), galactorrhea, erectile dysfunction, increase, body weight, chills, nosebleeds, nasal congestion.

Overdose:

Symptoms: headache, hyperemia of the facial skin, prolonged pronounced decrease in arterial pressure, suppression of sinus node function, bradycardia, tachycardia, bradyarrhythmia. With severe poisoning - loss of consciousness, coma, metabolic acidosis, hypoxia, cardiogenic shock with pulmonary edema.

Treatment: when severe poisoning (collapse, suppression of the sinus, node) gastric lavage, appoint Activated carbon. The antidote is calcium: a slow intravenous route is indicated 10% calcium chloride or calcium gluconate in a dose of 0.2 ml / kg (but not more than 10 ml) for 5 minutes, if ineffectiveness is possible repeated introduction under the control the maintenance of ions of calcium in blood serum, at renewal of a symptomatology it is possible to pass to a constant infusion with speed 0.2 ml / kg / h, but not more than 10 ml/ h.

With a marked decrease in blood pressure - intravenous dopamine or dobutamine.

In the case of conduction disturbances - atropine, isoprenaline or an artificial pacemaker. With the development of heart failure - intravenous strophanthin. Catecholamines should be used only with a life threat (due to their reduced efficacy, a high dosage is required, which increases the risk of arrhythmia).It is recommended to monitor the blood glucose content (insulin release may decrease) and electrolytes (potassium ions, calcium ions).

Hemodialysis is ineffective.

Interaction:

Severity of lowering blood pressureincreases with the simultaneous use of nifedipine with other antihypertensive drugs, nitrates, cimetidine, ranitidine (to a lesser extent), inhalation anesthetics, diuretics and tricyclic antidepressants.

Under the influence of nifedipine, the concentration of quinidine in the blood plasma is significantly reduced. Increases the concentration of digoxin in the blood plasma, and therefore it is necessary to monitor the clinical effect and the content of digoxin in the blood plasma.

Rifampicin is a powerful inducer of isoenzyme СUR3А4. When combined with rifampicin, bioavailability of nifedipine is significantly reduced and, accordingly, its effectiveness decreases. The use of nifedipine in conjunction with rifampicin is contraindicated.

In combination with nitrates, tachycardia and antihypertensive effects of nifedipine are enhanced. Calcium preparations can reduce the effect of blockers of "slow" calcium channels.When combined with nifedipine, anticoagulant activity of coumarin derivatives increases.

Drugs that are characterized by a high degree of binding (including indirect anticoagulants - coumarin and indanedione derivatives, anticonvulsant drugs, quinine, salicylates, sulfinpyrazone) can be dislodged from the bond with proteins, so that their concentrations in the blood plasma can increase. It suppresses the metabolism of prazosin and other alpha-adrenoblockers, as a result of which the antagonistensive effect may increase.

Procainamide, quinidine and other drugs that cause lengthening of the interval QT, reinforce the negative inotropic effect and may increase risk of significant lengthening of the interval QT.

Simultaneous use with magnesium sulfate in pregnant women can cause blockade of neuromuscular synapses.

Inhibitors of the cytochrome P450 3A system, such as macrolides (for example, erythromycin), fluoxetine, nefazodone, protease inhibitors (eg, amprenavir, indinavir, nelfinavir, ritonavir or saquinavir), antifungal agents (ketoconazole, itraconazole or fluconazole) lead to an increase in the concentration of nifedipine in blood plasma.

Taking into account the experience of using a blocker of "slow" calcium channels nimodipine, the following interactions with nifedipine can not be ruled out: carbamazepine, phenobarbital - decrease in the concentration of nifedipine in blood plasma; quinupristin, delfopristin, valproic acid - increase in concentration nifedipine in blood plasma.

FROM caution should be given nifedipinesimultaneously with disopyramide and flecainide because of the possible enhancement of the inotropic effect.

Nifedipine inhibits the excretion of vincristine from the body and can cause an increase its side effects; if necessary, reduce the dose of vincristine.

Grapefruit juice inhibits the metabolism of nifedipine in the body, in connection with which their simultaneous reception is counter-indicative.

Special instructions:

During the treatment it is necessary to refrain from drinking alcohol.

Despite the absence of blockers "slow" calcium channel syndrome"cancellation", before the cessation of treatment is recommended a gradual decrease in doses.

Simultaneous administration of beta-blockers should be performed in conditions careful medical supervision, as this may cause an excessive decrease arterial pressure, and in some cases - aggravation of the phenomena of heart failure.

During treatment, positive results are possible with a direct reaction Coombs and laboratory tests for antinuclear antibodies.

Of great importance is the regularity of treatment, regardless of how it is, because the patient may not feel the symptoms of hypertension.

Diagnostic criteria for prescribing the drug for vasospastic angina are the classical clinical picture, accompanied by characteristic changes in the electrocardiogram (segment elevation ST); the occurrence of ergometrine-induced angina or spasm of the coronary arteries; coronarospasm detection with angiography or the detection of an angiospastic component, without confirmation (for example, with a different voltage threshold or with unstable angina, when the electrocardiogram data indicate a transient angiospasm).

For patients with severe hypertrophic cardiomyopathy, there is a risk of increased frequency,severity of manifestations and duration of angina attacks after taking nifedipine; in this case, it is necessary to cancel the drug.

In patients who are on hemodialysis, with high blood pressure, irreversible failure of kidney function, with a decrease in the volume of circulating blood, the drug should be used cautiously, as there may be a sharp fall in blood pressure.

Patients with impaired liver function are carefully monitored and, if necessary, reduce the dose of the drug and / or use other dosage forms of nifedipine.

It should be borne in mind that at the beginning of treatment can occur angina, especially after the recent abrupt abolition of beta-blockers (the latter is recommended to cancel gradually).

If during the therapy the patient is required to undergo surgery under general anesthesia, it is necessary to inform the anesthesiologist about the nature of the therapy.

In the spectrophotometric evaluation nifedipine can lead to incorrect detection of increased content of vanillyl-mandelic acid in urine, it does not influence the studies using high-performance liquid chromatography.

With in vitro fertilization in some cases, blockers of "slow" calcium channels caused changes in the head of the spermatozoa, which can lead to a violation of the functions of spermatozoa. In cases in which repeated in vitro fertilization was not performed for an unclear reason, blockers of "slow" calcium channels, including nifedipine, are considered a possible cause of failure.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when managing transport and other potentially hazardous activities, requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of prolonged action, film-coated, 20 mg.

Packaging:10 tablets per blister of polyvinylchloride film and aluminum foil. 5 or 10 blisters with instructions for medical use of the drug in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N013039 / 02-2001

Date of registration:26.08.2011

Expiration Date:Unlimited

Date of cancellation:2017-09-05

The owner of the registration certificate:SHTADA Artznajmittel AGSHTADA Artznajmittel AG Germany

Manufacturer: & nbsp

STADA Arzneimittel, AG Germany

Representation: & nbspNizhpharm, JSCNizhpharm, JSCRussia

Information update date: & nbsp23.06.2018

Illustrated instructions

Instructions

Nifedipine (Nifedipine)