Pharmacological properties

Pharmacodynamics. pharmadipin shows anti-anginal and antihypertensive action. blocks entry of calcium ions into cardiomyocytes and smooth muscle cells of coronary and peripheral arteries through slow potentsialzavisimy calcium channels of cell membranes. relaxes unstriated muscles of vessels, eliminates spasms and expands coronary and peripheral arteries, reducing opss, hell, an afterload and the need of a myocardium for oxygen; slightly reduces contractility of a myocardium, reduces aggregation of thrombocytes a little.

Pharmacokinetics. At intake the bioavailability — 40–60% is well soaked up in a digestive tract. Especially quickly (in 5–10 min.) the effect develops at sublingual reception. Usually the maximum of action is registered in 30–40 min. Meal significantly does not influence medicament absorption speed. The hemodynamic effect remains for 4–6 h. About 90% of nifedipine contact proteins of blood plasma. It is metabolized in a liver and brought out of an organism mainly in the form of inactive metabolites. The general clearance of nifedipine — 0.4-0.6 l/kg/h of T _½ is 2–4 h. At elderly people and patients with cirrhosis the metabolism of nifedipine slows down therefore their T _½ medicament can be extended almost twice that demands a dose decline and increase in intervals between administrations of drug. In an organism nifedipine does not kumulirut. In insignificant quantities gets through GEB and a placental barrier, it is allocated with breast milk.

Indication

Ag (for the purpose of treatment of hypertensive crises).

Use

Pharmadipin is applied to treatment of hypertensive crisis as medicament of emergency aid. it is not recommended to use medicament in this dosage form for course reception.

In need of carrying out a course of antihypertensive therapy medicament and a dosage form is selected by the doctor.

At sudden and substantial increase of the ABP the initial single dose for adults makes 3–5 drops (2-3.35 mg), for elderly people — no more than 3 drops (2 mg) under language or to drop on a piece of a cracker or sugar, as long as possible holding in a mouth. At insufficient efficiency the dose can gradually be raised to clinically significant effect. Further in cases of increase in the ABP it is necessary to be guided by this dose. If necessary (increase in the ABP to 190/100–220/110 mm Hg.) the single dose can be raised gradually in some cases till 10-15 drops (6.7-10 mg) taking into account individual changes of indicators of the ABP at the patient.

needs to consider individual sensitivity of certain patients to Pharmadipin. In such cases the dose is selected individually, since 3 drops and to increase gradually by 2–3 drops (1.34-2 mg) before achievement of clinical effect.

Exceeding an initial dose of medicament can lead

to sharp decrease in the ABP!

Contraindication

Acute myocardial infarction (first 4 weeks); cardiogenic shock; heavy aortal and mitral stenosis; unstable stenocardia; not to use for treatment of attacks of stenocardia, secondary prevention of a myocardial infarction; heart failure in a decompensation stage; arterial hypotension (systolic hell of 90 mm Hg.); ventricular tachycardias with the expanded qrs complex; sick sinus syndrome; Wolf's syndrome — Parkinson — Whyte (wpw), a syndrome of Loen — a genong — a levayn (lgl); av-blockade of ii and iii of degree; porphyria; the ileostoma established after a proktokolektomiya; pregnancy period; breastfeeding period; children's age; hypersensitivity to nifedipine and other components of drug; hypersensitivity to other dihydropyridines; not to accept along with rifampicin.

Side effects

At observance of recommendations about medicament use the by-effects are insignificant and passing, as a rule, do not demand therapy cancellation.

At frequent and uncontrollable use the side reactions characteristic of medicaments of this pharmacological group are possible

.

from a cardiovascular system: often — hypostasis, a vazodilatation, infrequently — tachycardia, the strengthened heartbeat, arterial hypotension, a syncope.

from the central and peripheral nervous system: often — a headache; infrequently — vertigo, migraine, dizziness, a tremor, sleep disorder, uneasiness; seldom — a short-term disorder of vision, excitement, paresthesias, dizesteziya.

from an endocrine system: a hyperglycemia (it is necessary to consider at patients with diabetes).

from digestive system: often — a constipation; infrequently — at use of the raised doses abdominal pain, the dispeptic phenomena, a meteorism, nausea, vomiting (very seldom), a hyperplasia of gums (at prolonged use), dryness in a mouth, tranzitorny increase in enzymes of a liver.

from an urinary system: infrequently — a polyuria, a dysuria.

from the system of a hemopoiesis: seldom — anemia, a leukopenia, thrombocytopenia.

Allergic reactions: infrequently — allergic reaction, allergic hypostasis / angiootek (including a laryngeal edema); seldom — an itching, urticaria, rash; very seldom — anaphylactic/anaphylactoid reactions.

Others: often — feeling sick; infrequently — nasal bleeding, congestion of a nose, an erythema; seldom — hypostases of a shin, a myotonia, hypostasis of joints, erectile dysfunction, nonspecific pain, fever, dispnoe.

Special instructions

Drug should be used only in the conditions of careful clinical observation of the patient: in unstable stenocardia, the expressed heart failure and a heavy aortal stenosis, heavy pulmonary hypertensia, a hypertrophic cardiomyopathy, heavy disturbances of cerebral circulation, diabetes, abnormal liver functions and kidneys and also patients of advanced age. at patients of advanced age the reduction of a cerebral blood-groove because of a sharp peripheral vazodilatation is more probable. at the patients with a malignant ag and a hypovolemia who are on a hemodialysis against the background of intake of nifedipine the considerable decrease hell can be observed. especially in an initiation of treatment and at simultaneous use of blockers of β-receptors the hypotension which some patients badly have can develop. behind a condition of such patients the careful observation is necessary. the patients accepting blockers of β-receptors in an initiation of treatment can have symptoms of stagnant heart failure. at patients with heavy coronary insufficiency because of reflex tachycardia the ischemic heart disease course can worsen, and together with they are to become more frequent stenocardia attacks. it is necessary to appoint with care nifedipine the patient with stenocardia or after the postponed heart attack. at emergence against the background of treatment of pain behind a breast nifedipine should be cancelled. it is not necessary to take alcohol and to smoke during treatment by nifedipine.

should be established to

Dose of other medicaments which are applied with nifedipine individually. Cardiac glycosides can be also applied during treatment by nifedipine. At nifedipine use perhaps false increase in results of spectrophotometric definition of concentration of vanililmindalny acid in urine.

with simultaneous in/in administration of magnesium of sulfate to pregnant women careful monitoring of the ABP because of a possibility of its decrease is necessary for

At use of nifedipine that can damage to mother and a fruit.

Patients from the liver broken by function demand careful monitoring, and in hard cases — dose declines.

Nifedipine is metabolized by

through the system of P450 3A4 cytochrome. In this regard medicaments which inhibit or induce this system of enzymes, can change effect of the first passing or clearance of nifedipine (see INTERACTIONS).

At the accompanying use of nifedipine with these medicaments needs to control the ABP and, in case of need, it is necessary to consider a question of a nifedipine dose decline.

Separate experiments of in vitro revealed interrelation between use of antagonists of calcium, in particular, of nifedipine, and the return biochemical changes of spermatozoa which worsen ability of the last to fertilization. If the attempt of fertilization of in vitro was unsuccessful in the absence of other explanations, antagonists of calcium, in particular, nifedipine, can be considered as the possible reason of this phenomenon.

Ability to influence speed of response at control of vehicles or work with other mechanisms. At use of medicament it is necessary to refrain from potentially dangerous types of activity which require special attention (control of vehicles, work with other mechanisms, etc.).

Use during pregnancy and feeding by a breast. It is contraindicated to apply nifedipine during pregnancy. Nifedipine gets into maternal milk therefore during use of medicament it is necessary to stop breastfeeding.

Children. Drug is not used for treatment of children.

Interaction

Nifedipin can increase expressiveness of antihypertensive effect of antihypertensive medicaments which are used at the same time, such as diuretics, blockers of β-receptors, inhibitors apf, antagonists of at1-receptors, other calcic antagonists, blockers of α-adrenoceptors, inhibitors fde-5, α-Methyldopum.

At combination with blockers of β-receptors, along with strengthening of hypotensive action, development of heart failure is in certain cases possible

.

Diltiazem slows down removal of nifedipine from an organism (if necessary the dose of nifedipine is reduced).

Amiodaronum and quinidine can enhance negative inotropic effect of nifedipine. In some cases at a combination of nifedipine and quinidine at intake there is a decrease in concentration of quinidine in blood plasma.

Combination of nifedipine with cardiac glycosides, theophylline are usually well transferred by patients, increase in level of digoxin and theophylline in blood plasma is seldom or never possible (it is necessary to control keeping of the last in blood plasma).

Nifedipin increases concentration of carbamazepine, Phenytoinum in blood plasma. The combined use of nifedipine and Cimetidinum can lead to increase in level of nifedipine in blood plasma.

Rifampitsin induces activity of enzymes of a liver, accelerating nifedipine metabolism that can lead to decrease in clinical effect of nifedipine (such combination is contraindicated).

Treatment by nifedipine should be stopped for 36 h to the planned anesthesia using fentanyl. Nifedipine is compatible to X-ray contrast means.

Nifedipin in a combination with in/in administration of magnesium of sulfate can cause neuromuscular blockade in pregnant women.

Nifedipine is metabolized by

through the system of P450 3A4 cytochrome which is in a mucous membrane of intestines and a liver. Proceeding from it medicaments which inhibit or induce this system of enzymes, can change effect of the first passing (after oral administration) or clearance of nifedipine. Simultaneous use of makrolidny antibiotics (for example erythromycin), inhibitors of anti-HIV protease (for example ritonavir), azolny antimycotics (for example ketakonazol), a nefazodona, fluoxetine, the hinupristina/dalfopristina, Cimetidinum, a tsizaprid and nifedipine can lead to increase in concentration of nifedipine in blood plasma.

Knows that valproic acid increases concentration in blood plasma of structurally similar blocker of calcium channels of a nimodipin owing to inhibition of enzymes. Therefore it is impossible to exclude increase in concentration and efficiency of nifedipine in blood plasma.

Knows that takrolimus is metabolized through the system of P450 3A4 cytochrome.

Published data indicate

that in some cases the dose of a takrolimus at simultaneous use with nifedipine can be lowered. At simultaneous use of two medicaments it is necessary to carry out monitoring of concentration of a takrolimus in blood plasma and, in case of need, to consider a question of a dose decline of a takrolimus.

Grapefruit juice inhibits the system of P450 3A4 cytochrome. Consumption of grapefruit juice at use of nifedipine leads to increase in concentration of medicament in blood plasma and to increase in duration of effect of nifedipine owing to decrease in metabolism at the first passing or decrease in clearance. Because of it antihypertensive effect of medicament can amplify. After regular consumption of grapefruit juice this effect can last within 3 days after the last use of juice.

Therefore during therapy by nifedipine needs to avoid consumption of grapefruits / grapefruit juice.

Use of nifedipine can result

in false results at spectrophotometric definition of concentration of vanililmindalny acid in urine (at use of a method of highly effective liquid chromatography this effect was not observed).

Overdose

Symptoms of acute intoxication nifedipine: disturbance of consciousness up to a coma, decrease hell, tachycardia/bradycardia, a hyperglycemia, a metabolic acidosis, a hypoxia, cardiogenic shock which is followed by a fluid lungs.

Treatment. Actions for rendering emergency aid first of all have to be directed to removal of medicament from an organism and restoration of a stable hemodynamics.

recommends to clean

After oral administration completely a stomach, in case of need — in a combination with washing of a small intestine.

As high extent of linking with proteins of blood plasma and rather low volume of distribution are characteristic

nifedipine, the hemodialysis is inefficient, but carrying out a plasma exchange is recommended.

Bradycardia can be eliminated with

by means of β-sympathomimetics. At delay of a warm rhythm, life-threatening, use of an artificial pacemaker is recommended.

can eliminate Hypotension which arose owing to cardiogenic shock and a vazodilatation with calcium medicaments (10–20 ml of 10% of solution of Calcii chloridum or a gluconate enter in/in slowly, then repeat in case of need). Thereof calcium level in blood plasma can reach the upper bound of norm or to be a little raised. If administration of calcium is insufficiently effective, reasonable use of such sympathomimetics as a dopamine or Norepinephrinum. Doses of these medicaments select taking into account the reached medical effect.

should approach

additional input of the fluid very carefully as it increases danger of an overload of heart.

Storage conditions

B the dry, protected from light place at a temperature not above 25 °C. after opening of a bottle, medicament is stored 28 days.