Corinfar UNO - instructions for use, doses, side effects, contraindications

1 tablet contains: active substance nifedipine 40.00 mg; Excipients: cellulose microcrystalline 48.50 mg, cellulose 10.00 mg, lactose monohydrate 30.00 mg, hypromellose-4000 cp 20.00 mg, magnesium stearate 1.50 mg, silicon dioxide colloid 0.75 mg; shell: (E 172) 0.90 mg, titanium dioxide (E 171) 2.00 mg, talcum 1 , 00 mg.

Description:

Round biconvex tablets, covered with a film membrane of a red-brown color.

Pharmacotherapeutic group:The 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 vasodilating and antihypertensive effect. Reduces the flow of calcium ions into cardiomyocytes and smooth muscle cells of coronary andperipheral arteries, in high doses inhibits the release of calcium ions from the intracellular depot. Reduces the number of functional 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 muscles of vessels, mediated by calmodulin. In therapeutic doses normalizes the transmembrane current of calcium ions, disturbed by pathological conditions, especially in hypertension. Does not affect the tone of the veins. Strengthens coronary blood flow, improves blood flow of ischemic zones of the myocardium without the development of the phenomenon "stealing", activates the functioning of collaterals. Expanding the peripheral arteries, reduces the overall peripheral vascular resistance, myocardial tone, postnagruzku, myocardial oxygen demand and increases the duration of diastolic relaxation of the left ventricle. Almost does not affect the sinoatrial and atrioventricular nodes, does not have antiarrhythmic activity. It enhances kidney blood flow, causes a moderate natriuresis.Negative chrono-, dromo- and inotropic action is blocked by reflex activation of the sympathoadrenal system in response to peripheral vasodilation. At the beginning of treatment, there is a reflex increase in the heart rate (heart rate) and an increase in cardiac output, which is not significant enough to compensate for vasodilation. In the long-term administration of the drug, cardiac output decreases to its original value.

The time of onset of the clinical effect is 30 minutes, the duration is 24 hours.

Pharmacokinetics:

Absorption at ingestion on an empty stomach is high (more than 90%). Bioavailability is 50-70%. The drug has the effect of "primary passage" through the liver. Eating increases bioavailability. The shell of the tablet has the property of ensuring a uniform slow release of nifedipine, which allows for 24 hours to maintain the concentration of nifedipine in blood plasma at a constant level. Therefore, the elimination half-life is not an important parameter. The maximum concentration in the blood plasma is achieved after 2.3-7.7 hours and its value is 17-41.4 mg / ml.

Penetrates through the blood-brain and placental barrier, stands out with themilk. The connection with blood plasma proteins is 95-98%, mainly with albumin. The volume of distribution is 0.77-1.12 l / kg. Completely metabolized mainly through oxidative processes. In the metabolism involved isoenzymes CYP3A4, CYP3A5 and CYP3A7. Metabolites do not have pharmacological activity.

The half-life is 15.7 (± 6.1) h, it may be slightly prolonged in patients with renal insufficiency. It is excreted mainly through the kidneys in the form of metabolites, about 5-15% is excreted through the intestine. Not metabolized nifedipine (less than 0.1%) is excreted by the kidneys.

In patients with hepatic insufficiency, the overall clearance decreases and the half-life increases.

Do not cumulate. With long-term admission (2-3 months), tolerance to the action of nifedipine develops. Decreased kidney function, hemodialysis and peritoneal dialysis do not affect the pharmacokinetics of nifedipine. Plasmapheresis can enhance elimination.

Indications:Arterial hypertension.

Contraindications:

Hypersensitivity to nifedipine, other derivatives of 1,4-dihydropyridine and othercomponents of the drug; severe arterial hypotension (systolic blood pressure (BP) below 90 mm Hg); cardiogenic shock; acute myocardial infarction (in the first 4 weeks after myocardial infarction); unstable angina; pronounced aortaalveolar stenosis; hypertrophic obstructive cardiomyopathy; atrioventricular blockade II and III degree; obstruction of the esophagus, obstruction of the intestine or narrowing of the lumen of the gastrointestinal tract (GIT) in the anamnesis; Permanent valve stoma with reservoir (Kok pocket) onileal gut after total proctocolectomy; inflammatory bowel disease; Crohn's disease; simultaneous use with rifampicin (see section "Interaction with other medicinal products"); lactose intolerance, lactase deficiency, malabsorption and glucose-galactose syndrome; pregnancy up to 20 weeks; the period of breastfeeding; age to 18 years (efficacy and safety not established).

Carefully:

Light and moderate hypotension; chronic heart failure; mitral stenosis; severe bradycardia or tachycardia; syndrome of weakness of the sinus node; severe disorders of cerebral circulation; abnormal liver function; in patients,who are on hemodialysis; diabetes; pregnancy more than 20 weeks; elderly age.

Pregnancy and lactation:

The use of Corinfar® is contraindicated in pregnancy up to 20 weeks. Controlled clinical studies of the use of Corinfar® DNA in pregnant women were not conducted.

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 prenatal risk. At the same time, there are data on the increase in the probability of perinatal asphyxia, caesarean section, premature birth and delay - intrauterine development of the fetus. It is unclear whether the cases listed are the consequence of a major disease (arterial hypertension), treatment performed, or a specific effect of the preparation Corinfar® DNA. The information available is insufficient foro to exclude the possibility of side effects, which are dangerous for the fetus and the newborn.Therefore, the use of Corinfar® DNA after the 20th week of pregnancy requires a careful individual assessment of the risk-benefit ratio for the patient, fetus and / or newborn and can only be considered if other therapies are contraindicated or ineffective.

Careful monitoring of blood pressure in pregnant women should be performed with Corinfar ® OOH simultaneously with intravenous (iv) magnesium sulfate administration due to the possibility of excessive blood pressure lowering, which is dangerous for the mother and fetus and / or newborn.

Nifedipine is excreted in breast milk; therefore, if the use of Corinfar® OOH is necessary during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Dosing and Administration Inside, 30 minutes before meals, without breaking and chewing, with enough water, at the same time of day (ie with a 24-hour interval), preferably in the morning (morning).

1 tablet (40 mg) 1 time per day.

Side effects:

The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0,01%,but less than 0.1%; very rarely - less than 0.01%, including individual reports.

On the part of the blood and lymphatic system: rarely - anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura; very rarely - agranulocytosis.

From the cardiovascular system: Often - peripheral edema (feet, ankles, shins), symptoms of vasodilation (redness of the face, heat sensation); infrequently - tachycardia, palpitations, fainting, marked decrease in blood pressure; 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: aboutchen often - a headache, especially at the beginning of treatment; often - dizziness, general weakness, drowsiness, insomnia; infrequently paresthesia, tremor, hypoesthesia, dysesthesia, increased excitability, migraine, vertigo; rarely - anorexia, emotional lability, depression.

From the side of the organ of vision: infrequently - impaired vision, pain in the eyes.

From the digestive system: often - nausea; infrequently - dyspepsia, diarrhea, abdominal pain, constipation, flatulence, vomiting,dryness of the oral mucosa, cholestasis; rarely - jaundice, flatulence, belching, gingival hyperplasia, disappearing after drug withdrawal; very rarely - the formation of bezoars, dysphagia, ulcers of the intestine, insufficiency of the gastroesophageal sphincter; in some cases - intestinal obstruction.

From the respiratory, thoracic and mediastinal organs: infrequently - shortness of breath, nosebleed; rarely - laryngeal edema, bronchospasm, nasal congestion.

From the musculoskeletal system and connective tissue: infrequently - arthralgia, myalgia, muscle spasm, muscle cramps.

From the skin and subcutaneous tissues: often erythema, especially at the beginning of treatment; infrequently - itching, rash, exanthema, angioedema edema, increased sweating; rarely - hives, photosensitivity, purpura; very rarely - exfoliative dermatitis, toxic epidermal necrolysis.

From the side of the kidneys and urinary tract: infrequently - transient renal failure in patients with initially decreased renal function, sudden urge to urinate, nocturia, polyuria.

From the genitals and mammary glands: rarely - gynecomastia, disappearing after drug withdrawal, impotence.

Laboratory data: infrequently - increased activity of "hepatic" transaminases in the blood serum; rarely - hyperglycemia

Other: infrequently - nonspecific pain; rarely - fever, chills.

Overdose:

Symptoms: marked decrease in blood pressure, bradycardia, tachycardia, hyperglycemia, metabolic acidosis, hypoxia. When severe poisoning - cardiogenic shock with pulmonary edema, impaired consciousness, coma.

Treatment: gastric lavage, intake, activated charcoal, the appointment of laxatives.

Antidote are calcium preparations, shown in / in the administration of a 10% solution of calcium chloride or calcium gluconate, followed by a switch to a long infusion.

With a pronounced decrease in blood pressure, a slow intravenous injection of dopamine, dobutamine, epinephrine, or norepinephrine is indicated.

In the case of conduction disturbances - atropine, isoprenaline or staging of an artificial pacemaker. It is recommended to monitor the concentration of glucose in the blood (insulin release may decrease) and the content of electrolytes (potassium, calcium). Hemodialysis is ineffective,but plasmapheresis reduces the concentration of nifedipine in the blood plasma.

Interaction:

Drugs affecting the metabolism of nifedipine. Nifedipine is metabolized by isoenzyme CYP3A4 a system of cytochrome P450, localized in the liver and intestinal mucosa. Consequently, drugs that inhibit or induce this enzyme system can affect the effect of "primary passage" through the liver of nifedipine (when ingesting it) and clearance. Nifedipine - a drug with high clearance. Since hepatic clearance is mainly determined by the volume of hepatic blood flow, the possible interactions listed below that may affect the pharmacokinetic performance of nifedipine when administered concomitantly can not be compared with interactions with nifedipine in the form of a solution for infusion.

Rifampicin - powerful isoenzyme inducer CYP3A4. With simultaneous use with rifampicin, the bioavailability of nifedipine is significantly reduced and, accordingly, its effectiveness decreases. The use of nifedipine simultaneously with rifampicin is contraindicated (see.section "Contraindications").

Simultaneous reception of nifedipine with mild and moderate isoenzyme inhibitors CYP3A4 requires regular monitoring of blood pressure and, if necessary, reducing the dose of nifedipine. Clinical studies of the interaction of nifedipine with antibiotics of the macrolide group (eg, erythromycin) not conducted. It is known that some macrolides are inhibitors of the isoenzyme CYP3A4. As a result, the possibility of increasing the concentration of nifedipine in blood plasma can not be ruled out when these drugs are used together.

Azithromycin, belonging to the macrolide group, is not an inhibitor of the isoenzyme CYP3A4.

Clinical studies of the interaction of nifedipine with inhibitors of HIV protease (eg, ritonavir) not conducted. It is known that the preparations of this group are inhibitors of the isoenzyme CYP3A4. These drugs inhibit the conditioned isoenzyme CYP3 A4 metabolism of nifedipine in vitro. In the case of combined use with nifedipine, a significant increase in the concentration of nifedipine in the blood plasma is possible due to a delayed metabolism during the "primary passage" through the liver and delayed excretion.

Clinical studies of the interaction of nifedipine with antifungal agents from the azole group (eg, ketoconazole) not conducted. It is known that the preparations of this group are inhibitors of the isoenzyme CYP3A4. In the case of concomitant use with nifedipine, a noticeable increase in the concentration of nifedipine in the blood plasma can not be excluded due to delayed metabolism during the "primary passage" through the liver.

Clinical studies of the interaction of nifedipine with fluoxetine not conducted. It is known that fluoxetine is an inhibitor of the isoenzyme CYP3A4. Fluoxetine inhibits isoenzyme-mediated CYP3A4 Nifedipine metabolism in vitro. In the case of simultaneous application with nifedipine, a significant increase in the concentration of nifedipine in blood plasma is possible.

Clinical studies of the interaction of nifedipine with nefazodone not conducted. It is known that nefazodone is an isoenzyme inhibitor CYP3A4. In the case of simultaneous application with nifedipine, a significant increase in the concentration of nifedipine in blood plasma is possible.

Due to inhibition of the isoenzyme CYP3A4 quinupristin or dalfopristine their simultaneous use with nifedipine may lead to an increase in the concentration of nifedipine in the blood plasma.

Clinical studies of the interaction of nifedipine with valproic acid not conducted. Since it was shown that valproic acid increases the concentration in the blood plasma of the nemodipine "slow" calcium channel blocker structurally similar to nifedipine by inhibiting microsomal liver enzymes, it is impossible to exclude the possibility of increasing the concentration of nifedipine in the blood plasma.

Due to inhibition of the isoenzyme CYP3A4 cimetidine simultaneous application with nifedipine may lead to an increase in the concentration of nifedipine in blood plasma.

Grapefruit juice inhibits isoenzyme CYP3A4 and increases the concentration of nifedipine in plasma.

Other studies. Simultaneous application cisapride and nifedipine may lead to an increased concentration of nifedipine in the blood plasma, which requires regular monitoring of blood pressure and if necessary to reduce the dose of nifedipine.

Antiepileptic agents - inducers of isoenzyme CYP3A4 (phenytoin, carbamazepine, phenobarbital)

Phenytoin induces isoenzyme CYP3A4 and reduces the bioavailability of nifedipine and, as a consequence, reduces its effectiveness, which requires clinical observation and,if necessary, increase its dose. If the dose of nifedipine was increased during co-administration, after stopping the use of phenytoin, the dose of nifedipine should be reduced to the initial dose.

Clinical studies of the interaction of nifedipine with carbamazepine and phenobarbital not conducted. Since it has been shown that both drugs reduce the concentration in the blood plasma of the nimodipine "slow" calcium channels structurally similar to nifedipine due to the induction of microsomal liver enzymes, one can not exclude the possibility of reducing the concentration of nifedipine in plasma and, consequently, reducing its effectiveness.

Influence of nifedipine on other drugs. Nifedipine can enhance the antihypertensive effect when used simultaneously with others - antihypertensive agents, such as: diuretics, beta-blockers, inhibitors angiotensin converting enzyme, angiotensin II receptor antagonists, other "slow" calcium channel blockers, alpha-adrenoblockers, phosphodiesterase 5 (PDE5) inhibitors, methyldopa.

With the simultaneous use of nifedipine with magnesium sulfate (intravenous administration) may develop neuromuscular blockade (gustatory movements, difficulty swallowing, paradoxical breathing and muscle weakness) and a marked decrease in blood pressure.

With simultaneous application. nifedipine with beta-blockers it is necessary to monitor patients, because in some cases, the progression of chronic heart failure may be aggravated.

Nifedipine reduces clearance digoxin, which leads to an increase in the concentration of digoxin in the blood plasma. Therefore, patients should be carefully monitored and ECG monitored for early detection of an overdose of digoxin; if necessary, the dose of digoxin should be reduced taking into account its concentration in the blood plasma.In some cases, simultaneous use of nifedipine and quinidine there was a decrease in the concentration of quinidine in the blood plasma, as well as a marked increase in the concentration of quinidine in blood plasma after quinidine discontinuation. Therefore, in the case of joint application nifedipine as an additional agent,or withdrawal from nifedipine should monitor the concentration of quinidine in the blood plasma and, if necessary, a dose adjustment of quinidine is required. In some cases, the combined use of nifedipine and quinidine may increase the concentration of nifedipine in the blood plasma. Therefore, it is necessary to monitor blood pressure and, if necessary, reduce the dose of nifedipine.

Tacrolimus is metabolized by isoenzyme CYP3A4. In some cases, an increase in tacrolimus concentration in the blood plasma is possible with simultaneous application with nifedipine. Therefore, in case of simultaneous use, it is necessary to monitor the concentration of tacrolimus in the blood plasma and, if necessary, reduce the dose of tacrolimus.

Medicines, do not affect the pharmacokinetics of nifedipine: Aymalin, benazepril, debrisochin, doxazose, irbesartan, omeprazole, orlistat, pantoprazole, ranitidine,, rosiglitazone, talinolol, triamterene / hydrochlorothiazide, acetylsalicylic acid and candesartan.

Simultaneous use of nifedipine and acetylsalicylic acid in a dose of 100 mg does not affect the pharmacokinetics of nifedipine; nifedipine, in turn, does not change the antiaggregant properties of acetylsalicylic acid in a dose of 100 mg (platelet aggregation and bleeding time).

Simultaneous use of nifedipine and candesartan does not affect the pharmacokinetics of both drugs.

Special instructions:

It is necessary to monitor blood pressure while using Corinfar® DNA with beta-blockers and other antihypertensive agents, since an additive effect accompanied by a pronounced decrease in blood pressure and, in some cases, worsening of heart failure may appear.

It should be borne in mind that the preparation Corinfar® UNO will not be able to prevent a possible significant increase in blood pressure with a sharp reversal of other antihypertensive therapy, which was used concomitantly with the preparation Corinfar® UNO.

At the beginning of treatment with Corinfar® OOO, angina may occur, especially after the recent abrupt abolition of beta-blockers (the latter should be abolished gradually).

The regularity of treatment with Korifar® OOO is important, regardless of how it feels, since the patient may not feel the symptoms of hypertension.

In patients with severe arterial hypertension and hypovolemia who are on hemodialysis, with the use of Corinfar® OOO, a marked decrease in blood pressure can occur.

With severe heart failure, Corinfar® DNA is dosed with great care.

The preparation Corinfar® DNA is metabolized by isoenzyme CYP3A4 systems of cytochrome P450. Medicines that inhibit or induce this enzyme system can affect the effect of the "primary passage" through the liver of nifedipine (when ingested) and its clearance. These drugs include antibiotics of the macrolide group (for example, erythromycin), HIV protease inhibitors (for example, ritonavir), antifungal agents from the azole group (eg, ketoconazole), antidepressants, fluoxetine, nefazodone, quinupristin, delfopristin, valproic acid and cimetidine (see the section "Interaction with other medicinal products"). Simultaneous administration of Corinfar® OOO with these drugs requires regular monitoring of blood pressure and, if necessary, a reduction in the dose of nifedipine. If during the therapy the patient is required to undergo a surgicalintervention under general anesthesia, it is necessary to inform the surgeon / anesthesiologist about the nature of the therapy.

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

In patients with impaired liver function, the drug is used with an island, controlling the function of the liver.

During treatment, it is possible to obtain false positive results when performing a direct Coombs reaction and laboratory tests for antinuclear antibodies.

During the application of Corinfar® UNO by spectrophotometry, it is possible to determine the increased content of vanillylmandelic acid in urine.Caution should be exercised in elderly patients due to the highest likelihood of age-related renal dysfunction.

In patients with diabetes, it is recommended to control the glycemia and the content of potassium and calcium.

As a possible cause of unsuccessful attempts at in vitro fertilization, reversible changes in spermatozoa and reduced spermatogenesis associated with the intake of calcium antagonists, including Corinfar® UNO, are considered.

Discontinue treatment with Corinfar® UNO is recommended gradually.

Effect on the ability to drive transp. cf. and fur:During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of prolonged action, film-coated 40 mg.

Packaging:

For 10 tablets in a blister of PVC / PVDC / aluminum foil.

For 2, 5 or 10 blisters together with instructions for use in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001381

Date of registration:19.09.2011 / 12.12.2012

Expiration Date:Unlimited

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

ARENA PHARMACEUTICALS, GmbH Switzerland

Representation: & nbspTeva Teva Israel

Information update date: & nbsp04.02.2018

Illustrated instructions

Instructions

Corinfar® UNO (Corinfar® UNO)