2010/06/24

Osmo-Adalat

Composition, structure and packing

Enteric-coated controlled release.

1 tab. Nifedipine - 30 mg.

Enteric-coated controlled release.

1 tab. Nifedipine - 60 mg.

Auxiliary substances: gipromelloza, magnesium stearate, polyethylene oxide, sodium chloride, iron oxide red, cellulose acetate, polyethylene glycol-4000, opadray OY-S-24914 (iron oxide + titanium dioxide, red).

Clinico-pharmacological group: blocker "slow" calcium channels.

Mechanism of action.

Reduces the current of calcium ions through the "slow" calcium channels within cells, primarily into cardiomyocytes, smooth muscle cells of coronary and peripheral arteries, lowering the peripheral vascular resistance and increasing coronary arteries, particularly the larger supplying vessels, and even intact segments of the walls partially stenosed vessels. In addition, the nifedipine lowers the tone of smooth muscles of coronary arteries, thus prevents angiospasm, increases blood flow in poststenotic regions of the vessels and increases oxygen delivery to the myocardium, decreases myocardial oxygen demand by reducing peripheral vascular resistance (afterload), and prolonged admission, he capable of preventing the development of new atherosclerotic lesions in coronary arteries.

Nifedipine lowers the tone of smooth muscles of arterioles, thereby reducing the increased peripheral vascular resistance and hence blood pressure (BP). In the early treatment of nifedipine may be a temporary reflex increase in heart rate and, consequently, the values of cardiac output. However, this increase is not so much to compensate for the expansion of blood vessels. In addition, nifedipine at short and long-term use increases the excretion of sodium and water from the body.

Hypotensive effect of nifedipine is especially pronounced in patients with arterial hypertension. In patients with arterial hypertension and the presence, at least to, another risk factor, reduces the incidence of cardiovascular disease and cerebrovascular episodes in the same degree as the combination of diuretics.

Pharmacokinetics

Absorption

After oral administration nifedipine is almost completely absorbed from the gastrointestinal tract. Bioavailability of nifedipine with uncontrolled the release of 45-56%, owing to the effect "first pass" through the liver. Bioavailability of Osmo-Adalat on such uncontrolled release of nifedipine is 68-86%. Eating slightly reduces the initial rate of absorption, but no effect on the bioavailability. Nifedipine is allocated from pill Osmo-adalat in a special membrane to the osmotic gradient with a rate constant of zero order, in this case is controlled by increasing drug concentration in blood plasma, which reaches a plateau after about 6-12 hours after taking the tablets. Within 24 hours, maintained a constant concentration of drug in blood plasma. Release rate of nifedipine does not depend on pH environment and motility of the gastrointestinal tract. When you receive Osmo-adalat in a dose of 30 mg. and 60 mg. maximum concentration (C max.) in blood plasma was respectively 20-21 ng / ml. and 43-55 ng / ml, and the time necessary to reach this concentration - 12-15 hours and 7-9 hours respectively. Relationship to plasma proteins (albumin) is 95%.

Metabolism.

Following oral nifedipine metabolized in the wall of the intestine and liver to inactive metabolites.

Withdrawal

Half life (T 1 / 2) the uncontrolled release nifedipine is 1,7 -3,4 hours. The concentration of Osmo-adalat in blood plasma is maintained as a plateau during the entire period of release and absorption, and only after releasing the last dosage of pills, its concentration in the plasma starts to decrease, and T 1 / 2 corresponds to that of nifedipine with an uncontrolled release. Nifedipine excreted as inactive metabolites via the kidneys, only 5-15% of the bile through the intestines. Unchanged nifedipine is present in the urine in small quantities (less than 0,1%).

It penetrates through the blood and the placenta, is excreted in breast milk.

Hemodialysis and peritoneal dialysis does not affect the pharmacokinetics of nifedipine, plasmapheresis enhances its elimination.

During the passage of the digestive tract of biologically inactive components tablets remain unchanged and excreted in the form of an insoluble shell.

Statement
Coronary heart disease: stable angina (angina);
hypertension.

Dosage regimen

Ingest. Osmo-Adala pill should be swallowed whole, washed down with a small amount of fluid taken irrespective of food intake, it can not chew or crush, must protect against moisture and remove the foil immediately prior to the reception.

The initial dose of 30 mg 1 time per day. Later, the dose may remain equal to 30 mg 1 every day or it can be gradually increased to 60 mg 1 time a day and even up to 120 mg 1 time a day depending on the severity of the disease and individual patient response.

Duration of treatment is determined by your doctor.

Side effect

asthenia, facial swelling around the eyes.

Since the cardiovascular system:

palpitation, peripheral edema, vasodilatation (hot flushes, blood-to-face).

Of the nervous system:

dizziness, headache.

The part of the digestive system:

constipation.

Contraindications
Hypersensitivity to nifedipine;
pregnancy and lactation;
cardiogenic shock;
co-administration with rifampicin severe arterial hypotension (systolic blood pressure below 90 mm Hg);
presence of ileostomy after proktokolektomii;
age of 18 years (effectiveness and safety are not established).

The drug is used with caution in: heart failure, severe aortic stenosis, subaortalnom stenosis, acute myocardial infarction with left ventricular failure, pronounced bradycardia, hepatic failure, severe cerebral circulatory disorders, mild to moderate hypotension, stenosis of any of the gastrointestinal tract in elderly age, in patients with malignant hypertension and hypovolaemia which are on hemodialysis.

Pregnancy and lactation

The use of nifedipine is contraindicated during the entire period of pregnancy as possible embryotoxic, fetotoksicheskoe and teratogenic effect of the drug.

Nifedipine penetrates into breast milk, so if you receive Osmo-Adalat is needed, then breastfeeding should be discontinued.

Cautions

Nifedipine Extreme caution should be considered in patients with marked stenosis of any of the gastrointestinal tract, as possible the development of intestinal obstruction.

In some cases, the symptoms of intestinal obstruction may occur in patients without pathology of the gastrointestinal tract. Bear in mind that, in conducting bowel barium X-ray may reveal false-positive polyp symptoms (filling defect).

When liver failure is recommended monitoring of the patient, if necessary, reduce the dose of the drug or use it in other dosage forms.

With simultaneous application of the drug and β-adrenoceptor blockers, patients require careful monitoring, as may the development of significant decrease of blood pressure and worsening symptoms of heart failure.

At the same time taking with grapefruit juice may strengthen the hypotensive action that lasts for 3 days after the last reception of juice.

Nifedipine causes false positive increase in the concentration of vanillylmandelic acid in urine in the determination of the spectrophotometric method and does not affect the result of this reaction using the method of high performance liquid chromatography (HPLC).

During the period of treatment must be careful when engaging in potentially hazardous activities that require high concentration and speed of psychomotor reactions, and to refrain from the use of ethanol.

Overdose

Symptoms: loss of consciousness up to coma and marked reduction of blood pressure, tachycardia / bradycardia, hyperglycemia, metabolic acidosis, hypoxia, cardiogenic shock, accompanied by pulmonary edema.

Treatment: removal of nifedipine from the body and restore hemodynamic stability. Recommended gastric lavage and, if necessary irrigation of the small intestine to prevent further absorption of the drug.

Hemodialysis is pointless, because nifedipine is not displayed during dialysis, recommended the appointment of plasmapheresis (since nifedipine is characterized by a high degree of binding to plasma proteins and the relatively small volume of distribution).

When bradycardia - β-sympathomimetic, in life-threatening bradycardia - implantation of temporary artificial pacemaker.

In marked decrease in blood pressure should slow intravenous injection of 10-20 ml of 10% solution of calcium gluconate (allowed re-introduction), the inefficiency of which the appointment vasoconstrictor sympathomimetic dopamine or norepinephrine. The doses of these drugs are selected depending on the obtained therapeutic effect. Introduction of fluid should be limited to the risk of overloading the heart

Drug Interactions

Antihypertensive effect of nifedipine could worsen, while the use of drugs to lower blood pressure, as well as inhalation anesthetics, prazozina and other alpha-blockers. Antihypertensive effect of reducing sympathomimetic, non-steroidal anti-inflammatory drugs (NSAIDs) because of the suppression of the synthesis of prostaglandins in the kidneys and the delay of sodium and fluids in the body, estrogens (fluid retention in the body), and calcium preparations. Nifedipine is metabolized by the enzyme system cytochrome P450 3A4, so drugs that inhibit or induce these enzymes may interact with nifedipine in its ingestion, breaking ground clearance or the effect of "first pass' through the liver.

Digoxin

Nifedipine reduces the clearance of digoxin, which leads to an increase in its concentration in blood plasma, so patients require close monitoring for symptoms of an overdose of cardiac glycosides, and the dose if necessary, should be reduced.

Quinidine

Nifedipine reduces the concentration of quinidine in blood plasma, however, with its abolition content quinidine may increase substantially, requiring adjustments to the dose. In some cases, may increase the concentration of nifedipine in blood plasma, so if the testimony should reduce its dosage. During concomitant therapy is necessary to monitor the concentration of quinidine in blood plasma and blood pressure level. In simultaneous reception with nifedipine increases the risk of lengthening the interval QT.

Procainamide

When combined with procainamide risk long QT interval and increased the negative inotropic effect of both drugs.

Phenytoin

Induces enzymes cytochrome P450 3A4 and reduces the bioavailability of nifedipine and, consequently, reduces its effectiveness, which may require increasing the dose.

Cimetidine

Inhibits cytochrome P450 3A4 systems and causes an increased concentration of nifedipine in blood plasma, thereby enhancing its hypotensive action.

Rifampicin

Refers to a potent inducer of liver enzymes, accelerating the metabolism of nifedipine, which leads to a weakening of its effectiveness.

Diltiazem

Slows the removal of nifedipine from the body, so the combination therapy should be very cautiously, if necessary, reducing the dose of nifedipine.

Tsizaprid

Increasing concentrations of nifedipine in blood plasma, so you should monitor blood pressure and if necessary to reduce the dose of nifedipine.

Grapefruit juice inhibits cytochrome P450 3A4 system and increases the concentration of nifedipine in plasma, owing to decrease the effect of "first pass" through the liver.

Valproic acid

Because valproic acid causes an increase in plasma concentrations of nimodipine, the structure is close to nifedpinu blocker "slow" calcium channels, it is not excluded increase in plasma concentrations of nifedipine and increased its effectiveness.

Acetylsalicylic acid

Nifedipine does not alter the antiplatelet effect of acetylsalicylic acid in a dose of 100 mg (platelet aggregation and the duration of bleeding). Acetylsalicylic acid, in turn, does not affect the pharmacokinetic parameters of nifedipine.

Carbamazepine, Phenobarbital

Since carbamazepine and fenabarbital cause a reduction in plasma concentration of nimodipine, the structure close to the blocker nifedipine "slow" calcium channels, it may decrease the plasma concentrations of nifedipine and decrease its effectiveness. Nifedipine may displace from its association with proteins, drugs, characterized by a high degree of binding (indirect anticoagulants - derivatives of coumarin and indandiona, quinine, sulfinpirazon, anticonvulsants, salicylates, NSAIDs), followed by the possible increase of their concentration in plasma. Since erythromycin, fluoxetine, ritonavir, indinavir, amprenavir, nelfinavir, saquinavir, ketoconazole, itraconazole, fluconazole, inhibits the enzyme cytochrome R4503A4, it is not ruled out increasing the concentration of nifedipine in blood plasma as a result of their interaction. It is recommended to control blood pressure level and if necessary to reduce the dose of nifedipine.

In case of simultaneous use with possible enhancement dizopiramid negative inotropic effect. Products containing Li +, when combined with nifedipine may cause neurotoxic symptoms (nausea, vomiting, diarrhea, ataxia, tremor and / or tinnitus). Aymalin, omeprazole, benazepril, irbesartan, orlistat, ranitidine, rosiglitazone, doxazosin, pantoprazole, talinolol, triamterene, hydrochlorothiazide did not affect the pharmacokinetics of nifedipine.

Terms and Conditions of storage

Store in dry protected from light, at temperatures not above 25 ° C, out of reach of children.

Shelf life - 4 years.