Osmo-Adalat - instructions for use, dose, side effects, contraindications

active layer: active vethe substance nifedipine 33 mg or 66 mg, sopmogatelnye substances hypromellose 8.2 mg or 16.4 mg, magnesium stearate 0.4 mg or 0.8 mg, macrogol 122.2 mg or 244.4 mg; waspsMitotic layer: hypromellose 4.1 mg or 8.2 mg, magnesium stearate 0.2 mg or 0.4 mg,sodium chloride 23.9 mg or 47.8 mg, macroa goal of 52.9 mg or 105.8 mg, an iron dyeoxide red 0.8 mg or 1.6 mg; sheath: film sheath - cellulose acetate 32.3 mg or 38.0 mg, macrogol 1.7 mg or 2.0 mg; light barrier - giprolose 7.1 mg or 12.8 mg, titanium dioxide 5.0 mg or 9.1 mg, hypromellose 2.3 mg or 4.1 mg, propylene glycol 1.3 mg or 2.4 mg, an iron dye oxide red 0.3 mg or 0.6 mg; polishing layer, inscription - hypromellose 1.5 mg or 2.5 mg, black ink Opacode S-1-17823 (trace amounts).

Description:

Round biconvex tablets of pink color; with one side of the tablet black the font is marked "Adalat 30" / "Adalat" 60 ", on the surface of the tablet with any from the sides with an arbitrary arrangement relative to the center there is a pore in the form of a hole of irregular shape with a diameter of up to 1 mm.

Pharmacotherapeutic group:blocker of "slow" calcium channels.

ATX: & nbsp

C.08.C.A.05 Nifedipine

Pharmacodynamics:Nifedipine is a selective blocker of "slow" calcium channels (BCCC), a derivative of 1,4-dihydropyridine. Has antianginal and antihypertensive effect. Reduces the current of calcium ions through the "slow" calcium channels inside the cells, mainly inside the cardiomyocytes, smooth muscle cells of the coronary and peripheral arteries, while reducing the overall peripheral vascular resistance (OPSS) and expanding coronary arteries, especially large vessels, as well as intact segment walls of partially stenosed vessels. Besides, nifedipine reduces the tone of the smooth muscles of the coronary arteries; thereby preventing angiospasm, poststenotic blood flow improves with atherosclerotic obstruction, and oxygen delivery to the myocardium increases,the need for myocardium in oxygen decreases due to a decrease in the total peripheral vascular resistance (afterload); with prolonged use nifedipine is able to prevent the development of new atherosclerotic lesions in the coronary arteries.
Nifedipine reduces the tone of the smooth muscle arterioles, thereby reducing the increased OPSS and, consequently, blood pressure (BP). At the beginning of treatment with nifedipine, a temporary reflex increase in the heart rate (heart rate) and, as a consequence, cardiac output can occur. However, this increase is not so significant as to compensate for the dilatation of blood vessels. Besides, nifedipine with short-term and long-term use increases the excretion of sodium and water ions from the body. Antihypertensive effect of nifedipine is especially pronounced in patients with arterial hypertension. In patients with hypertension and the presence of at least one other risk factor for cardiovascular disease; nifedipine reduces the incidence of cardiovascular and cerebrovascular episodes to the same extent as with a combination of diuretics.

Pharmacokinetics:

Suction

After oral administration nifedipine almost completely absorbed from the gastrointestinal tract. The bioavailability of nifedipine after ingestion in capsules of immediate release is 45-56 % due to the effect of "primary transmission" through the liver, compared to what the bioavailability of nifedipine after ingestion in controlled release tablets is 68-86%. The intake of food slightly reduces the initial absorption rate, but does not affect the bioavailability. Nifedipine is released from the Osmo-Adalat® tablet through a special osmotic gradient membrane with a zero-order rate constant, with a controlled increase in plasma nifedipine concentration, which reaches a plateau approximately 6-12 hours after ingestion of the first dose of Osmo-Adalat® . Within 24 hours a constant concentration of nifedipine, in blood plasma, is maintained. The release rate of nifedipine is independent of the pH of the environment and the motility of the gastrointestinal tract. When administered Osmo-Adalat® the maximum: plasma concentration (C_mOh) nifedipine withleaves respectively 20-21 mg / ml and 43-55 mg / ml, and the time to reach C max is 12-15 h and 7-9 h, respectively.

Distribution

The association with plasma proteins (albumin) is about 95 %.

Metabolism

After oral administration nifedipine is metabolized in the intestinal wall and in the liver, mainly as a result of oxidative processes. Metabolites do not possess pharmacological activity.

Excretion

The plasma concentration of Osmo-Adalat® is maintained at a constant level throughout the release and absorption period, and only after the last dose of nifedipine has been released its plasma conethe centralization begins to decline; T1 / 2 is 1.7 to 3.4 h. Nifedipine is excreted as inactive metabolites mainly through the kidneys, and only 5-15% through the intestine with bile. Unchanged in the urine in small amounts (less than 0.1%). Penetrates through the blood-brain and placental barrier, excreted in breast milk.

Hemodialysis and peritoneal dialysis do not affect the pharmacokinetics of nifedipine, plasmapheresis enhances its excretion.

During passage through the digestive tract, the biologically inactive components of the tablet remain unchanged and are removed from the body in as an insoluble shell.

When the renal function is impaired, the pharmacokinetics of Osmo-Adalat® does not altergt;

When the liver function is impaired, the clearance of nifedipine is reduced. In severe violations of liver function, if necessary, correction of the dosing regimen is required.

Indications:Ischemic heart disease: prevention of attacks of stable angina pectoris.

Arterial hypertension.

Contraindications:

■ Hypersensitivity to nifedipine or any other component of the drug.

■ Pregnancy (up to 20 weeks) and lactation.

■ Cardiogenic shock.

■ Simultaneous use with rifampicin.

■ Presence of ileostomy after proctocolectomy (Kok's pocket).

■ Age to 18 years (effectiveness and safety not established).

Carefully:Severe arterial hypotension (systolic blood pressure less than 90 mm Hg), acute heart failure, severe aortic stenosis, hepatic insufficiency, pregnancy (after 20 weeks), in patients with severe stenosis of any part of the gastrointestinal tract, since the development of intestinal obstruction ; in patients with malignant hypertension and hypovolemia, in patients on hemodialysis.

Pregnancy and lactation:

The use of Osmo-Adalat® is contraindicated in pregnancy up to 20 weeks.Controlled clinical studies of Osmo-Adalat® in pregnant women have not been conducted; accordingly, the data of controlled clinical trials of the efficacy and safety of Osmo-Adalat® in pregnant women are not available.

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

According to available clinical data, it is impossible to judge the specific prenatal 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 these cases are due to a major disease (arterial hypertension), treatment or a specific effect of Osmo-Adalat®.

The available information is not enough to exclude the possibility of side effects, which are dangerous for the fetus and the newborn. Therefore, the use of Osmo-Adalat® after the 20th week of pregnancy requires a careful individual assessment of the ratiorisk and benefit to the patient, fetus and / or newborn and can only be considered if other treatments are contraindicated or ineffective.

Nifedipine is secreted into breast milk, so if Osmo-Adalat® is needed during lactation, breastfeeding should be discontinued.When Osmo-Adalat® is used together with intravenous administration of magnesium sulfate solution in pregnant women, careful monitoring of blood pressure is necessary due to the possibility of excessive reduction in blood pressure, which is dangerous for the mother and fetus and / or the newborn.

Dosing and Administration:

Take inside. The tablet of Osmo-Adalat® should be swallowed whole, washed down with a small amount of liquid (not washed down with grapefruit juice), taken irrespective of the time of ingestion, it can not be chewed or broken, should be protected from light and removed from the foil immediately before the reception.

The dose of the drug is selected individually. In each case, the initial dose of the drug should be increased gradually, depending on the clinical picture of the disease.

With angina pectoris or hypertension, the initial dose is 30 mg once a day. If the therapeutic effect is insufficient, the dose can be increased to 60 mg once a day. Depending on the severity of the disease and the individual reaction of the patient, the dose can be increased to 120 mg once a day.

Special patient groups

Children and teens

The safety and effectiveness of Osmo-Adalat® in children and adolescents under the age of 18 years are not established.

Patients of advanced age (over 60 years)

In elderly patients, dose adjustment is not required.

Patients with hepatic impairment

In patients with impaired liver function, the drug is used with caution, monitoring the function of the liver. In severe violations of the liver, depending on the tolerance, the doctor can reduce the dose of the drug.

Patients with impaired renal function

In patients with impaired renal function, dose adjustment is not required.

Side effects:

When nifedipine was used, side effects were evaluated in placebo-controlled studies.

The following undesirable reactions were classified as follows: often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10,000, <1/1000). Degree of gratitudeof adverse reactions "often" was estimated as less than 3%, except for peripheral edema (9.9%) and headache (3.9%). Side effects, which were noted only during post-marketing observations, and whose frequency was not assessed, are designated as "frequency unknown."

Systems of organs	Often	Infrequently	Rarely	Frequency unknown
Disorders from the hematopoietic system				Agranulocytosis Leukopenia
Impaired immune system disorders		Allergic reactions Allergic edema / angioedema (including laryngeal edema¹)	Hives Cutaneous pruritus Rash	Anaphylactic / anaphylactoid reactions
Disorders from the psyche		Sleep Disorders Anxiety
Disturbances from the nervous system	Head pain	Dizziness Migraine Tremor Vertigo	Paresthesia Diesgesia	Hypesesia Drowsiness
Metabolic disorders				Hyperglycaemia
Disturbances on the part of the organ of sight		Visual disturbances		Pain in the eyes
Disorders from the cardiovascular system	Peripheral edema (due to vasodilation)	Tachycardia Palpitation Marked decrease in blood pressure Syncope (syncope)		Pain in the chest (angina pectoris)
Disturbances from the respiratory system		Nasal bleeding Nasal congestion		Dispno (shortness of breath)
Disorders from the digestive system	Constipation	Gastrointestinal and abdominal pain Nausea Indigestion Swelling of the abdomen Dryness of the oral mucosa	Hyperplasia of gums	Bezoars (lumps in the stomach from undigested food residues) Dysphagia Intestinal obstruction Ulcer of the intestine Vomiting Insufficiency of the gastroesophageal sphincter
Disorders from the side of the liver		Transient increase in the activity of "liver" transaminases		Transit jaundice
Disturbances from the skin		Erythema		Lyell's syndrome Photosensitivity Allergic reactions Purpura
Disturbances from the musculoskeletal system		Muscle cramps Puffiness of the joints		Arthralgia Mialgia
Disorders from the urinary system		Polyuria Dizuria
Disorders from the reproductive system		erectile disfunction
Common violations	Bad feeling	Nonspecific pain Chills

1- can be life-threatening

In patients with malignant hypertension and hypovolemia and those on dialysis, a decrease in blood pressure may be due to hypovolemia.

Overdose:

Symptoms: marked decrease in blood pressure, loss of consciousness until the development of coma, tachycardia / bradycardia, hyperglycemia, metabolic acidosis, hypoxia, cardiogenic shock accompanied by pulmonary edema. .

Treatment

Activities to provide emergency assistance in case of an overdose should first of all be aimed at removing nifedipine from the body and restoring stable parameters of hemodynamics. It is recommended to wash the stomach and, if necessary, irrigation of the small intestine to prevent further absorption of the drug. Measures to remove the drug from the body should be as complete as possible (including the small intestine) in order to prevent further absorption of the drug. Conducting hemodialysis is not advisable, because nifedipine not deleted

characterized by a high degree of binding to plasma proteins and a relatively small volume of distribution).

With bradycardia - ß-sympathomimetics, with life-threatening bradycardia - staging a temporary artificial pacemaker.

With a marked decrease in blood pressure, which developed as a result of cardiogenic shock and vasodilation,a slow intravenous injection of 10-20 ml of a 10% solution of calcium gluconate is recommended (before the calcium upper limit is reached or slightly exceeded, a repeated administration is permissible), in case of ineffectiveness of which - dopamine or norepinephrine. Doses of these drugs are selected depending on the therapeutic effect obtained.

The introduction of fluid should be done with caution in connection with the risk of cardiac overload.

Interaction:Nifedipine is metabolized by isoenzyme CYP3A4 cytochrome systems P4S0, located in the intestinal mucosa and in the liver. Therefore, drugs that inhibit or induce this isoenzyme can interact with nifedipine when ingested, disrupting the clearance or the effect of "primary transmission" through the liver.

Rifapicin

Refers to powerful isoenzyme inducers CYP3A4 systems of cytochrome P450. When combined with rifampicin, the bioavailability of nifedipine is significantly reduced and, accordingly, its effectiveness is reduced. Therefore, the use of rifampicin in combination with Osmo-Adalat® is contraindicated.

Simultaneous use of nifedipine with weak and moderate isoenzyme inhibitors CYP3A4 cytochrome P450 systems requires regular monitoring of blood pressure and, if necessary, reducing the dose of nifedipine. The preparations of this group include:

Antibiotics-macrolides (for example, erythromycin)

Clinical studies on the interaction of nifedipine and macrolide antibiotics have not been conducted. It is known that antibiotics-macrolides are inhibitors of the isoenzyme CYP3A4. Therefore, it is impossible to exclude the possibility of an increase in plasma concentrations of nifedipine when it is used simultaneously with antibiotic-macrolides. Azithromycin, belonging to the macrolide group, does not inhibit the isoenzyme CYP3A4.

HIV protease inhibitors (eg, ritonavir)

Clinical studies on the interaction of nifedipine and HIV protease inhibitors have not been conducted. It is known that preparations of this groups inhibit fromenzyme CYP3A4. HIV protease inhibitors inhibit isoenzyme-mediated CYP3A4 Nifedipine metabolism in vitro. With simultaneous use, a significant increase in plasma concentrations of nifedipine is possible due to a decrease in the effect of "primary passage" through the liver and delayed excretion.

Antifungal preparations of the azole group (for example, ketoconazole)

Clinical studies on the interaction of nifedipine and antifungal agents of the azole group were not carried out. It is known that these drugs inhibit the isoenzyme CYP3A4. With simultaneous application with nifedipine, a significant increase in systemic bioavailability of nifedipine is possible due to a decrease in the effect of "primary passage" through the liver.

Fluoxetine

Clinical studies on the possible interaction of nifedipine and fluoxetine have not been conducted. It is known that fluoxetine in vitro inhibits the metabolism of nifedipine due to the action of the isoenzyme CYP3A4. With simultaneous application with nifedipine, an increase in the plasma concentration of nifedipine is possible due to a decrease in the effect of "primary passage" through the liver.

Nefazodone

Clinical studies on the possible interaction of nifedipine and navezodon were not carried out. It is known that nefazodone inhibits the metabolism of nifedipine due to the action of the isoenzyme CYP3A4. With simultaneous application with nifedipine, an increase in the plasma concentration of nifedipine is possible due to a decrease in the effect of "primary passage" through the liver.

Quinupristine / dalfofustin

Simultaneous use of quinupristin / delfopristine with nifedipine may lead to an increase in plasma concentrations of nifedipine.

Valproic acid

Clinical studies on the possible interaction of nifedipine and valproic acid have not been conducted. Because the valproic acid causes an increase in the plasma concentration of nimodipine, BCCC, in a structure close to nifedipine, it can not be ruled out that the plasma concentration of nifedipine can be increased and its effectiveness increased.

Cimetidine

Cimetidine inhibits isoenzyme CYP3A4 and causes an increase in plasma concentrations of nifedipine, thereby increasing its antihypertensive effect.

Other studies:

Cisapride

The simultaneous use of cisapride with nifedipine may lead to an increase in plasma concentrations of nifedipine.

Antiepileptic drugs that induce isoenzyme CYP3A4 systems of cytochrome P450 (for example, phenytoin, carbamazepine, phenobarbital)

Phenytoin

Fentoin induces isoenzyme CYP3A4. With the simultaneous use of nifedipine and phenytoin, there is a decrease in the bioavailability of nifedipine and a decrease in its effectiveness.When using this combination, you should monitor the effectiveness of nifedipine and, if necessary, increase its dose. After the withdrawal of phenytoin, the dose of nifedipine should be reduced.

Kapbamazepine, phenobarbital

Clinical studies on the possible interaction of nifedipine and carbamazepine or phenobarbital were not performed. Since both drugs reduce plasma concentrations of nimodipine, in a structure close to nifedipine, it can not be ruled out that the plasma concentration of nifedipine can be reduced and its effectiveness decreased.

Influence of nifedipine on other drugs

The antihypertensive effect of nifedipine may increase while the use of drugs to lower blood pressure, such as diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, other BCCI, alpha blockers, inhibitors of phosphodiesterase-5 (PDE 5), alpha-methyldopa.

Digoxin

Nifedipine reduces the clearance of digoxin, which leads to an increase in its plasma concentration, so patients should establish a thorough clinical and ECG observation for the earlyidentifying symptoms digoxin overdose, if necessary, depending on the plasma concentrations of digoxin, the dose should be reduced.

Quinidine

In some cases, the simultaneous use of nifedipine and quinidine observed decrease in plasma concentrations of quinidine, as well as a marked increase in plasma concentrations after cancellation quinidine quinidine. Therefore, when using and / or removing nifedipine, the plasma concentration of quinidine should be monitored and, whennecessary, adjust its dose. In some cases, the application of this combination reported increase plasma concentrations of nifedipine, however when indicated the dose should be reduced. During the period of simultaneous therapy, it is necessary to monitor the plasma concentration of quinidine and AD.

Tacrolimus

Tacrolimus is metabolized with the participation of isoenzyme CYP3A4. In some cases with simultaneous use with nifedipine, a dose reduction of tacrolimus may be required. When using this combination, you should monitor the plasma concentration of tacrolimus and, if necessary, reduce its dose.

Magnesium sulfate

When Osmo-Adalat® is used together with intravenous administration of magnesium sulfate solution, careful monitoring of blood pressure is necessary because of the possibility of excessive reduction in blood pressure, which is dangerous for both the mother and fetus and / or newborn.

Food

Grapefruit juice inhibits isoenzyme CYP3A4, increases the plasma concentration of nifedipine and prolongs its effect due to a decrease in the effect of "primary passage" through the liver and a decrease in its clearance. At the same time, there is a antihypertensive action of nifedipine. With the regular use of grapefruit juice, this effect can persist for 3 days after the last intake of juice. In the future, it is recommended to avoid the simultaneous use of grapefruit or grapefruit juice with nifedipine.

Other types of interaction

Aimalin, benazepril, candesartan, debris, doxazosin, irbesartan, omeprazole, orlistat, pantoprazole, ranitidine, rosiglitazone, talinolol, triamterene +hydrochlorothiazide do not affect the pharmacokinetics of nifedipine.

Acetylsalic acid

Nifedipine does not affect the antiaggregant properties of acetylsalicylic acid (ASA) at a dose of 100 mg (platelet aggregation and bleeding time). ASA, in turn, does not affect the pharmacokinetic parameters of nifedipine.

Special instructions:

In patients with severe stenosis of any part of the gastrointestinal tract possibly development of intestinal obstruction. In very rare cases, bezoar can develop, for the removal of which may require surgical intervention. AT Single cases of symptoms of intestinal obstruction can be observed in patients who do not have pathology on the part of the gastrointestinal tract.

It should be borne in mind that during the X-ray study of the intestine with barium, false-positive symptoms of the polyp (filling defect) can be detected.

Patients with violations of liver function, the drug is used with caution, controlling the function of the liver. In severe violations of the liver, depending on the tolerance, the doctor can reduce the dose of the drug.

When simultaneous application of the drug Osmo-Adalat® and beta-blockers patients require careful observation, since it is possible to develop a marked decrease in blood pressure and worsen the symptoms of heart failure.

When simultaneous use with grapefruit juice, it is possible to enhance the anti-hypertensive effect of nifedipine, which persists, within 3 days after the last use of the juice.

Nifedipine can cause a false-positive increase in the concentration of vanillyl-mandelic acid in urine when determined spectrophotometrically, but does not affect the measurement results when using the high-performance liquid chromatography (HPLC) method.

Isozyme inhibitory drugs CYP3A4 cytochrome P450 systems, such as antibiotics-macrolides (for example, erythromycin), HIV protease inhibitors (for example, ritonavir), azole derivatives (e.g., ketoconazole), antidepressants (nefazodone and fluoxetine), quinupristin / delfopristin, valproic acid, cimetidine, with simultaneous application with nifedipine may increase the plasma concentration of nifedipine. Therefore, when using these combinations, the plasma concentration of nifedipine should be monitored and, if necessary, the dose of Osmo-Adalat® should be reduced.

The maximum daily dose of nifedipine, equal to 120 mg, contains 2 mmol sodium chloride.This should be taken into account when used in patients on a low-salt or salt-free diet.

Simultaneous use of nifedipine and intravenous administration of a magnesium sulfate solution can lead to an excessive decrease in blood pressure, which necessitates careful monitoring of blood pressure.

In Vitro Fertilization

AT Single cases of in vitro fertilization with BCCC, in particular Osmo-Adalat®, showed reversible biochemical changes in the sperm head, which led to a disruption of the sperm function.

With unsuccessful attempts at in vitro fertilization and with the exclusion of other causes of infertility, one should take into account the probability of influencing semen of BCCC, in particular nifedipine, provided they are used.

Influence on the ability to drive vehicles and moving machinery

During the treatment period (especially at the beginning of treatment or when changing the dose), care must be taken when driving a car, engaging in potentially dangerous activities requiring increased attention and speed of psychomotor reactions, and refraining from the use of ethanol.

Form release / dosage:

Controlled-release tablets coated with a film coat of 30 and 60 mg.

For 14 tablets per blister of Al / PP, 2 blisters together with instructions for use in a cardboard pack.

Storage conditions:Store at a temperature not exceeding 30°C.

Keep out of the reach of children!

Shelf life:4 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N014946 / 01

Date of registration:16.05.2008

The owner of the registration certificate:Bayer Pharma AGBayer Pharma AG Germany

Manufacturer: & nbsp

BAYER PHARMA, AG Germany

Representation: & nbspBAYER, AOBAYER, AO

Information update date: & nbsp26.02.2014

Illustrated instructions

Instructions

Osmo-Adalat® (Osmo-Adalat)