Eighth-Adalia

Active material: Nifedipine
When ATH: C08CA05
CCF: Kalьcievыh channel blocker
ICD-10 codes (testimony): I10, i20
When CSF: 01.03.02
Manufacturer: BAYER HealthCare AG (Germany)

DOSAGE FORM, COMPOSITION AND PACKAGING

Pills, coated, controlled release, round, lenticular, pinkish, napechatkoy with black ink “ADALAT 30” one side; on the tablet surface on either side with an arbitrary location relative to the center tablets at a time to coated wells with a diameter of up irregularly 1 mm.

Excipients: gipromelloza, magnesium stearate, polyethylene oxide, sodium chloride, iron oxide red, cellulose acetate, polyethylene glycol 4000, опадрай OY-S-24 914 (iron oxide red, Titanium dioxide).

14 PC. – blisters (2) – packs cardboard.

Pills, coated, controlled release, round, lenticular, pinkish, napechatkoy with black ink “ADALAT 60” one side; on the tablet surface on either side with an arbitrary location relative to the center tablets at a time to coated wells with a diameter of up irregularly 1 mm.

Excipients: gipromelloza, magnesium stearate, polyethylene oxide, sodium chloride, iron oxide red, cellulose acetate, polyethylene glycol 4000, опадрай OY-S-24 914 (iron oxide red, Titanium dioxide).

14 PC. – blisters (2) – packs cardboard.

Pharmacological action

Selective calcium channel blockers slow, 1,4-dihydropyridine derivative. It has antianginal and hypotensive action.

Reduces current of calcium ions through the slow calcium channels into the cells, mostly cardiomyocytes, smooth muscle cells of coronary and peripheral arteries, while lowering systemic vascular resistance and increasing coronary arteries, large vessels and intact wall segments partially stenosed vessels. Nifedipine reduces the tone of smooth muscles of coronary arteries, thereby preventing vasoconstriction, It increases blood flow in vessels poststenotic parts and increases the delivery of oxygen to the myocardium. It reduces myocardial oxygen demand by reducing systemic vascular resistance (afterload), and chronic administration is capable of preventing the development of new atherosclerotic lesions in the coronary arteries. Nifedipine reduces the smooth muscle tone of the arterioles, thereby, reducing high PR and, Consequently, FROM.

Early treatment with nifedipine may be a temporary increase in heart rate and reflex, Consequently, cardiac output. However, this increase is not so much, to compensate for the dilation of blood vessels. Besides, nifedipine, and with short-term, and long-term use increases the excretion of sodium and water from the body. The antihypertensive effect of nifedipine is particularly pronounced in patients with hypertension. In patients with hypertension and the presence of, at least, Another risk factor, reduces the incidence of cardiovascular and cerebrovascular events in the same degree, how a combination diuretikov.

Pharmacokinetics

Absorption and distribution

After oral administration nifedipine is almost completely absorbed from the gastrointestinal tract. The bioavailability of nifedipine from tablets 45-56% due to the effect “first pass” through the liver. The bioavailability of nifedipine from tablets of controlled release tablets was relatively 68-86%. Eating slightly reduces the initial rate of absorption, but it does not affect the bioavailability of. Nifedipine is released from the tablet controlled through a special membrane vysvozhdeniem at the osmotic gradient with zero-order rate constant, thus there is a controlled increase in the concentration of nifedipine in the blood plasma, which reaches a plateau after about 6-12 h after administration. During 24 h is kept constant drug concentration in blood plasma. The rate of release of nifedipine is independent of pH and gastrointestinal motility. In eighth-Adalia^® dose 30 mg 60 mg C_max plasma is respectively 20-21 ng / ml 43-55 ng / ml achieved after 12-15 and h 7-9 h, respectively. The binding to plasma proteins (albumin) – about 95% .Pronikaet the BBB and placental barrier, excreted in breast milk.

Metabolism

After oral administration of nifedipine is metabolized in the gut wall and liver to inactive metabolites.

Deduction

T_1/2 while taking nifedipine tablets is 1.7-3.4 no. The concentration of nifedipine in tablet-controlled release in plasma is maintained as a plateau throughout the period of release and absorption, and only after the last dose of nifedipine release from controlled release tablets plasma concentrations begin to decline, and T_1/2 It corresponds to that upon receipt of nifedipine in tablet form. Nifedipine is excreted as inactive metabolites via the kidneys, only 5-15% – the bile through the intestines. In unaltered nifedipine is present in small quantities in urine (less 0.1%). Hemodialysis and peritoneal dialysis do not affect the pharmacokinetics of nifedipine, plasmapheresis enhances its excretion.

During passage through the digestive tract of biologically inactive components of the tablet remain unchanged and excreted as an insoluble shell.

Pharmacokinetics in special clinical situations

If the kidney function does not change the pharmacokinetics.

If abnormal liver function decreases the clearance of nifedipine.

Testimony

- CHD: stable angina (angina);

- Arterial hypertension.

Dosage regimen

The initial dose is 30 mg 1 time / day. Subsequently, the dose can, if necessary can be gradually increased to 60 mg 1 time / day and even up to 120 mg 1 times / day depending on the severity of the disease and the individual response of the patient. The duration of treatment is determined by a physician.

Tablets should be swallowed whole, without chewing or breaking a, drinking a small amount of liquid, taken regardless of meals, Protect from moisture and remove the foil just before the reception.

At hepatic dysfunction, severe shall adjust the dosing regimen.

Side effect

Cardio-vascular system: ≥1-<10% – feeling flares (vasodilation), heartbeat, peripheral edema; ≥0.1-<1% – hypotension (incl. orthostatic), fainting, tachycardia; ≥0.01-<0.1% – angina.

From the digestive system: ≥1-<10% – constipation; ≥0.1-<1% – abdominal pain, diarrhea, dry mouth, dyspepsia, flatulence, nausea; ≥0.01-<0.1% – anorexia, belching, gingivitis, giperplaziya right, increase in liver transaminases (GOLD, IS, GGT), vomiting; <0.01% – ʙezoar (clumps of undigested food remains in the stomach), dysphagia, esophagitis, ileus, intestinal ulcers, jaundice.

From the central and peripheral nervous system: ≥1-<10% – dizziness, headache; ≥0.1-<1% – nervousness, paresthesia, insomnia, drowsiness; ≥0.01-<0.1% – gipesteziya, tremor.

On the part of the endocrine system: <0.01% – giperglikemiâ, weight loss, gynecomastia.

The respiratory system: ≥0.1-<1% – breathlessness; ≥0.01-<0.1% – nosebleeds.

From the urinary system: ≥0.1-<1% – nocturia, polyuria; ≥0.01-<0.1% – dizurija, frequent urination, worsening of renal function (in patients with renal insufficiency).

On the part of the musculoskeletal system: ≥0.1-<1% – cramps in the calf muscles; ≥0.01-<0.1% – arthralgia, myalgia.

Dermatological reactions: ≥0.1-<1% – itching, rash (rash, эritema, hives); ≥0.01-<0.1% – angioedema, macular-papular, pustular, vesicles bullous rash, hives; <0.01% – photodermatitis, exfoliative dermatitis, purpura.

From the hematopoietic system: <0.01% – leukopenia.

From the senses: ≥0.01-<0.1% – diplopia, amblyopia, Pain in the eyeballs; <0.01% – blurred vision.

Other: ≥1-<10% – asthenia, facial swelling (incl. Eye); ≥0.1-<1% – pain in the chest, melosalgia, malaise, Pain uncertain localization; ≥0.01-<0.1% – allergic reactions (swelling of the tongue, decrease in blood pressure, tachycardia, fever), chills, chest pain; <0.01% – anaphylactic reactions.

When receiving nifedipine there are also side effects, both asymptomatic agranulocytosis, thrombocytopenia, development or exacerbation of congestive heart failure, rarely – pulmonary edema (difficulty breathing, cough or stridor), transient loss of vision, swelling of joints.

Contraindications

- Cardiogenic shock;

- Severe hypotension (systolic blood pressure <90 mmHg.);

- Ileostomy, installed after proctocolectomy;

- Simultaneous use of rifampicin;

- Pregnancy;

- Lactation (breast-feeding);

- Childhood and adolescence up 18 years (efficacy and safety have not been established);

- Hypersensitivity to nifedipine.

FROM caution should be prescribed the drug for heart failure, severe aortic stenosis, subaortic stenosis, acute myocardial infarction with left ventricular failure, bradycardia, hepatic insufficiency, stenosis of any GI, severe violations of cerebral circulation, mild or moderate hypotension, elderly patients, patients with malignant hypertension and hypovolaemia, hemodialysis.

Pregnancy and lactation

Eighth-Adalat^® contraindicated during pregnancy, tk. possible fetotoxic, foetotoxic and teratogenic effect of the drug.

Nifedipine passes into breast milk, so if you need to use Osmo-Adalat^® lactation breastfeeding should be discontinued.

Cautions

Nifedipine is necessary with extreme caution in patients with severe stenosis of any GI, since it is possible the development of bowel obstruction. In some cases, symptoms of intestinal obstruction may occur in patients without a pathology of the gastrointestinal tract.

It should be understood, that during bowel barium x-ray can reveal false positive symptoms of the polyp (filling defect).

When liver failure is recommended to monitor patients, if required dose reduction or the use of the drug in other dosage forms.

In an application Osmo-Adalat^® and α-adrenergic blockers, patients require careful monitoring, It may develop as significant decrease in blood pressure and worsening symptoms of heart failure.

At simultaneous reception with grapefruit juice may increase the hypotensive action, that persists for 3 days after the last dose juice.

Nifedipine causes false positive increase vanillylmandelic acid concentration in urine when determining the spectrophotometric method does not affect the result of the reaction using HPLC (HPLC).

Effects on ability to drive vehicles and management mechanisms

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

Overdose

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

Treatment: measures for emergency assistance in overdose should primarily be aimed at elimination of nifedipine from the body and restore stable hemodynamics. It is recommended gastric lavage and if necessary irrigation of the small intestine to prevent further absorption of the drug. Hemodialysis inappropriate, as nifedipine is not displayed during dialysis; It recommended the appointment of plasmapheresis (tk. nifedipine for a high degree of binding to plasma proteins and the relatively small V_d).

If bradycardia prescribed β-agonists, when life-threatening bradycardia – implantation of a temporary pacemaker.

In marked decrease in blood pressure is recommended in a slow / introduction 10-20 ml 10% solution of calcium gluconate (permitted the re-introduction), the ineffectiveness – appointment of vasoconstrictor norepinephrine or dopamine sympathomimetic (doses are selected depending on the therapeutic effect obtained).

The introduction of the liquid to be limited due to the risk of overloading the heart.

Drug Interactions

The hypotensive effect of nifedipine may increase while the use of drugs, lower blood pressure, as well as with inhaled anesthetics, prazosin and other alpha-blockers.

The hypotensive effect of nifedipine reducing sympathomimetic, NSAIDs due to the suppression of prostaglandin synthesis in kidney, and sodium and fluid retention in the body, Estrogens (due to retention of fluids) and calcium supplements.

Nifedipine is metabolised via CYP3A4, however preparations, which induce or inhibit these enzymes, may interact with nifedipine when swallowed, or effect of violating the clearance “'First pass” through the liver.

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

Nifedipine reduces quinidine concentration in blood plasma, However, when the abolition of the content of quinidine can increase significantly, that the dose requires adjustment. In some cases it may increase the concentration of nifedipine in the blood plasma, so if there is evidence of its dose should be reduced. During combination therapy necessary to control the concentration of quinidine plasma levels and blood pressure. At simultaneous reception with nifedipine increases the risk of QT interval prolongation.

When combined with procainamide there is a risk of QT prolongation and increased negative inotropic effect of both drugs.

Nifedipine induces CYP3A4 and reduces the bioavailability of nifedipine and, consequently, reduces its effectiveness, which may require increasing the dose.

Nifedipine inhibits CYP3A4 and causes an increase in the concentration of nifedipine in the blood plasma, thereby enhancing its hypotensive effect.

Nifedipine is a potent inducer of liver enzymes, speeding up the metabolism of nifedipine, which weakens its effectiveness.

Diltiazem slows down the body of nifedipine, therefore, combination therapy should be very carefully, if necessary, reducing the dose of nifedipine.

Cisapride increases the concentration of nifedipine in the blood plasma, therefore, blood pressure should be monitored and, if necessary, reduce the dose of nifedipine.

Grapefruit juice inhibits CYP3A4 and increases the concentration of nifedipine in the plasma, due to a reduction effect “first pass” through the liver.

Because valproic acid causes an increase in plasma concentrations of nimodipine, structure close to nifedpinu blocker of slow calcium channels, it is not ruled out an increase in the plasma concentration of nifedipine, and enhancement of its efficiency.

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

Because carbamazepine and fenabarbital cause a decrease in plasma concentrations of nimodipine, structure close to the blocker nifedipine slow calcium channels, it is possible to decrease the concentration of nifedipine in plasma and reducing its effectiveness.

Nifedipine can displace from its association with protein drugs, characterized by a high degree of binding (indirect anticoagulants – coumarin and derivatives indandiona, quinones, sulfinpirazon, anticonvulsants, salicilaty, NSAIDs) followed by a possible increase in the plasma concentration.

Since erythromycin, fluoxetine, ritonavir, indinavir, amprenavir, Nelfinavir, saquinavir, ketoconazole, itraconazole, fluconazole ingibiruyut izoferment CYP3A4, it is not ruled out increasing the concentration of nifedipine in the plasma as a result of their interaction. It is recommended to monitor blood pressure and if necessary to reduce the dose of nifedipine.

In the case of simultaneous application of disopyramide may increase the negative inotropic effect. Preparations, containing lithium, in combination with nifedipine may cause neurotoxic symptoms (nausea, vomiting, diarrhea, ataksiyu, tremors and / or ringing in the ears).

Ajmalin, omeprazole, benazepril, irbesartan, Orlistat, ranitidine, Rosiglitazone, doksazozin, pantoprazole, talinolol, hydrochlorothiazide triamterene not affect the pharmacokinetics of nifedipine.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored in a dry, inaccessible to children at temperature not exceeding 25 ° C. Shelf life – 4 year.