Kordinik tablets 10mg, No. 60

Symptomatic treatment of stable angina pectoris in adult patients in case of insufficient efficacy, contraindications to the use or intolerance of first-line antianginal drugs (such as beta-blockers and / or slow calcium channel blockers)

Inside, without chewing, drinking water, regardless of the time of the meal.

The effective therapeutic dose of the drug and the frequency of administration are selected individually, depending on the severity of the symptoms of the disease, response to treatment and tolerance. The maximum daily dose of nicorandil is 80 mg.

The drug is usually prescribed in a dose of 10 to 20 mg 2-3 times a day. What is the recommended starting dose for nicorandil? 10 mg 2 times a day.

In patients prone to headache, the initial dose of the drug can be reduced to 5 mg 2 times a day.

Special patient groups

Elderly There are no
special requirements for the dosage regimen of nicorandil in elderly patients, but it is recommended to use the drug CordinicЃ in the lowest effective dose.

Patients with impaired liver and / or kidney function
In patients with impaired liver and / or kidney function, dose adjustment of CordinicЃ is not required.

active substance : nicorandil - 10 mg;

excipients : potato starch - 5 mg, microcrystalline cellulose type 102 - 84 mg, calcium stearate - 1 mg;

• hypersensitivity to nicorandil or any of the components of the drug;

• patients in shock (including cardiogenic shock), severe hypotension or left ventricular failure with low filling pressure or cardiac decompensation;

• simultaneous use with phosphodiesterase-5 inhibitors (sildenafil, vardenafil, tadalafil);

• concomitant use with soluble guanylate cyclase inhibitors (such as riociguat);

• hypovolemia;

• pulmonary edema;

• pregnancy and the period of breastfeeding (see section 'Use during pregnancy and during breastfeeding');

• children under 18 years of age (efficacy and safety have not been established).

Carefully

arterial hypotension; heart rhythm disturbances; atrioventricular block I degree; Prinzmetal's angina; impaired liver and / or kidney function; angle-closure glaucoma; anemia; hyperkalemia; simultaneous use with tricyclic antidepressants, glucocorticosteroids, nonsteroidal anti-inflammatory drugs (including acetylsalicylic acid) and drugs that can increase the potassium content in the blood; diverticular bowel disease; deficiency of glucose-6-phosphate dehydrogenase.

Trade name of the drug:

CordinicЃ

International non-proprietary name:

nicorandil

Dosage form:

pills

Composition:

1 tablet contains:

for a dosage of 10 mg:

active substance : nicorandil - 10 mg;

excipients : potato starch - 5 mg, microcrystalline cellulose type 102 - 84 mg, calcium stearate - 1 mg;

for a dosage of 20 mg:

active substance : nicorandil - 20 mg;

auxiliary substances : potato starch - 10 mg, microcrystalline cellulose type 102 - 168 mg, calcium stearate - 2 mg.

Description:

Dosage 10 mg: round flat-cylindrical tablets of white color with a slight grayish-yellowish tinge with a chamfer and a dividing line on one side.

Dosage 20 mg : round flat-cylindrical tablets of white with a faint grayish-yellowish shade of color with a bevel.

Pharmacotherapeutic group:

other peripheral vasodilators used in the treatment of heart disease

ATX code:

—01DX16

Pharmacological properties

Pharmacodynamics

Nicorandil (an ester of N- (2-hydroxyethyl) nicotinamide and nitric acid) is a double-acting vasodilator that relaxes the smooth muscle cells of arterial and venous vessels.

Has the ability to open ATP-dependent potassium channels. By activating ATP-dependent potassium channels, nicorandil causes hyperpolarization of the membranes of smooth muscle cells of the vascular wall, reduces the flow of Ca2 + ions into the cytosol, which leads to relaxation of smooth muscles, dilation of arteries and a decrease after exercise. In addition, activation of ATP-dependent potassium channels in mitochondria leads to cardioprotective effects by mimicking ischemic preconditioning.

Due to the presence in the composition of the nitrate group, nicorandil also relaxes smooth muscles (especially in the venous system) by increasing the intracellular cyclic guanosine monophosphate (cGMP). This leads to an increase in the volume of the capacitive blood vessels and a decrease in preload.

It has been shown that nicorandil has a direct effect on the coronary arteries (both unchanged and stenotic segments), without leading to the development of the 'steal' phenomenon. In addition, lowering end-diastolic pressure and wall stress decreases the extravascular component of coronary vascular resistance. Ultimately, this leads to improved oxygenation and increased blood flow in the post-stenotic areas of the myocardium.

In addition, in in vitro and in vivo studies, it was found that nicorandil has antispasmodic activity and eliminates coronary artery spasm caused by methacholine or norepinephrine.

Nicorandil has no direct effect on the contractile function of the myocardium. Nicorandil does not affect lipid metabolism and glucose metabolism.

Pharmacokinetics

Nicorandil is rapidly absorbed from the gastrointestinal tract, reaching a maximum plasma concentration in 30-60 minutes. The absolute bioavailability is 75%. Not subject to the 'first pass' effect through the liver.

When the drug is taken 2 times a day, the equilibrium concentration of nicorandil in the blood plasma is reached within 4Ц5 days.

After intravenous administration, the volume of distribution is 1.04 l / kg. Nicorandil slightly binds to blood plasma proteins. The free fraction in blood plasma is about 75%.

Nicorandil is mainly metabolized in the liver by denitration to form several metabolites with no pharmacological activity.

The elimination of nicorandil from plasma is biphasic. In the fast phase, the half-life (T?) Is approximately 1 hour; in the final phase when taking the drug orally at a dose of 20 mg 2 times a day T? is approximately 12 hours.

Nicorandil is excreted by the kidneys, mainly in the form of metabolites.

Special patient groups

There were no significant changes in the pharmacokinetics of nicorandil in the elderly, in patients with liver disease or chronic renal failure.

Indications for use

Symptomatic treatment of stable angina pectoris in adult patients in case of insufficient efficacy, contraindications to the use or intolerance of first-line antianginal drugs (such as beta-blockers and / or slow calcium channel blockers)

Contraindications

• hypersensitivity to nicorandil or any of the components of the drug;

• patients in shock (including cardiogenic shock), severe hypotension or left ventricular failure with low filling pressure or cardiac decompensation;

• simultaneous use with phosphodiesterase-5 inhibitors (sildenafil, vardenafil, tadalafil);

• concomitant use with soluble guanylate cyclase inhibitors (such as riociguat);

• hypovolemia;

• pulmonary edema;

• pregnancy and the period of breastfeeding (see section 'Use during pregnancy and during breastfeeding');

• children under 18 years of age (efficacy and safety have not been established).

Carefully

arterial hypotension; heart rhythm disturbances; atrioventricular block I degree; Prinzmetal's angina; impaired liver and / or kidney function; angle-closure glaucoma; anemia; hyperkalemia; simultaneous use with tricyclic antidepressants, glucocorticosteroids, nonsteroidal anti-inflammatory drugs (including acetylsalicylic acid) and drugs that can increase the potassium content in the blood; diverticular bowel disease; deficiency of glucose-6-phosphate dehydrogenase.

Application during pregnancy and during breastfeeding

Pregnancy Experience with nicorandil preparations in pregnant women is limited or absent. Animal studies have not demonstrated direct or indirect adverse effects on reproductive function. As a precautionary measure, CordinicЃ should not be used during pregnancy.

Breastfeeding period

Animal studies have shown that nicorandil is excreted in small amounts in breast milk. It is not known whether nicorandil is excreted in human breast milk, and therefore the use of CordinicЃ during breastfeeding is contraindicated.

Method of administration and dosage

Inside, without chewing, drinking water, regardless of the time of the meal.

The effective therapeutic dose of the drug and the frequency of administration are selected individually, depending on the severity of the symptoms of the disease, response to treatment and tolerance. The maximum daily dose of nicorandil is 80 mg.

The drug is usually prescribed in a dose of 10 to 20 mg 2-3 times a day. What is the recommended starting dose for nicorandil? 10 mg 2 times a day.

In patients prone to headache, the initial dose of the drug can be reduced to 5 mg 2 times a day.

Special patient groups

Elderly There are no
special requirements for the dosage regimen of nicorandil in elderly patients, but it is recommended to use the drug CordinicЃ in the lowest effective dose.

Patients with impaired liver and / or kidney function
In patients with impaired liver and / or kidney function, dose adjustment of CordinicЃ is not required.

Side effect

Adverse reactions are listed in accordance with the damage to organs and systems and the frequency of occurrence. The frequency of occurrence is determined as follows: very often ( > 1/10), often (from > 1/100 to <1/10), infrequently (from > 1/1000 to <1/100), rarely (from > 1 / 10,000 to <1 / 1,000), very rare (<1 / 10,000), frequency unknown (cannot be estimated from available data).

Metabolic and nutritional disorders : very rarely - hyperkalemia.

Nervous system disorders : very often - headache; often - dizziness.

Violations of the organ of vision : very rarely - corneal ulcer, conjunctival ulcer, conjunctivitis; frequency unknown - diplopia.

Heart disorders : often - increased heart rate.

Vascular disorders : often - vasodilation of the skin with a feeling of 'hot flashes'; infrequently - a decrease in blood pressure.

Disturbances from the gastrointestinal tract : often - nausea, vomiting, rectal bleeding ; infrequently - an ulcer of the oral mucosa ; rarely - gastrointestinal ulcers (stomatitis, aphthous stomatitis, ulcer of the oral mucosa, ulcer of the tongue, ulcer of the small intestine, ulcer of the large intestine, anal ulcer); very rarely - abdominal pain *; frequency unknown - gastrointestinal bleeding.

Liver and biliary tract disorders: very rarely - liver dysfunction (such as hepatitis, cholestasis, or jaundice).

Violations of the skin and subcutaneous tissues : rarely - itching, skin rash; infrequently - angioedema *; very rarely - angioedema, ulceration of the skin and mucous membranes (mainly perianal ulcers, genital ulcers and parastomal ulcers).

Musculoskeletal and connective tissue disorders : infrequently * / rarely - myalgia.

General disorders and disorders at the injection site : often - a feeling of weakness.

* adverse reactions were reported in a clinical study when nicorandil was used in addition to standard antianginal therapy in patients with stable angina pectoris and a high risk of cardiovascular complications.

Description of selected adverse reactions

Complications of gastrointestinal ulcers have been reported, such as perforation, fistula, or abscess formation, sometimes leading to gastrointestinal bleeding and weight loss.

Overdose

Symptoms: The expected manifestations of an acute overdose of nicorandil are peripheral vasodilation, a marked decrease in blood pressure and reflex tachycardia.

Treatment : it is recommended to monitor the parameters of the cardiovascular system and general supportive measures (for example, transferring the patient to the 'lying' position with raised legs or with the head end of the bed lowered). In the absence of effect, it is recommended to replenish the circulating plasma volume by intravenous administration of plasma-substituting solutions. In the case of the development of life-threatening conditions, the use of vasopressors is possible.

Interaction with other medicinal products

Phosphodiesterase-5 inhibitors . The simultaneous use of nicorandil with phosphodiesterase-5 inhibitors (sildenafil, vardenafil, tadalafil) is contraindicated due to the risk of severe arterial hypotension.

Soluble guanylate cyclase inhibitors . The simultaneous use of nicorandil with soluble guanylate cyclase inhibitors (such as riociguat) is contraindicated, as it can lead to a pronounced decrease in blood pressure.

Blood pressure lowering drugs . Nicorandil in therapeutic doses can lower blood pressure. With the simultaneous use of nicorandil with antihypertensive drugs or other drugs that lower blood pressure (for example, vasodilators, tricyclic antidepressants, alcohol), an increase in the antihypertensive effect is possible.

Dapoxetine should be administered with extreme caution at the same time as nicorandil due to the possibility of orthostatic hypotension.

With the simultaneous use of nicorandil with the drug sapropterin, it is possible to lower blood pressure below normal.

Glucocorticosteroids . Cases of perforation of the gastrointestinal tract with the combined use of nicorandil and glucocorticosteroids have been described. If necessary, the simultaneous administration of nicorandil and corticosteroids should be used with extreme caution.

Non-steroidal anti-inflammatory drugs (NSAIDs) . Patients concurrently taking nicorandil and NSAIDs (including acetylsalicylic acid in both anti-inflammatory and cardioprotective doses) have an increased risk of developing severe complications from the gastrointestinal tract, such as gastrointestinal ulcers, perforation and bleeding.

Medicines that can increase the amount of potassium in the blood . Care should be taken when using nicorandil in combination with drugs that can increase the potassium level in the blood (risk of hyperkalemia).

Other interactions. Cimetidine (an inhibitor of CYP1A2, CYP2D6 and CYP3A4 / 5) and rifampicin (an inducer of CYP3A4) do not significantly affect the metabolism of nicorandil. Nicorandil does not affect the pharmacodynamics of warfarin and acenocoumarol.

In clinical studies, pharmacodynamic and / or pharmacokinetic interactions of nicorandil with beta-blockers, blockers of 'slow' calcium channels, digoxin, a combination of digoxin with furosemide, acenocoumarol, rifampicin and cimetidine were not identified.

The current clinical experience indicates that nitrates in the form of prolonged-release tablets, when used simultaneously with nicorandil, do not affect the clinical tolerance of the latter. However, due to the fact that the nicorandil molecule contains a nitrate group, caution should be exercised when administered together with nitrates due to the possibility of potentiating the antihypertensive action.

special instructions

Ulceration and ulceration. When using nicorandil preparations, the occurrence of ulcerations (ulcers) of the gastrointestinal tract, skin and mucous membranes has been described.

язвенные поражени¤ органов желудочно-кишечного тракта (? “). »зъ¤звлени¤, св¤занные с приемом никорандила, могут возникать в разных отделах ? “ у одного и того же пациента. язвы резистентны к лечению и, в большинстве случаев, заживают только после отмены никорандила. ¬ случае по¤влени¤ изъ¤звлений (¤зв) органов ? “ прием препарата  ординикЃ должен быть немедленно прекращен.

ћедицинские работники должны быть осведомлены о важности своевременной диагностики ¤зв, вызванных никорандилом, и быстрого прекращени¤ приема препарата в случае возникновени¤ таких ¤зв. —огласно имеющейс¤ информации изъ¤звлени¤ (¤звы) могут по¤витьс¤ как вскоре после начала приема никорандила, так и через несколько лет после начала лечени¤.

?сть сообщени¤ о развитии желудочно-кишечного кровотечени¤ как осложнени¤ ¤звенных поражений органов ? “ при приеме никорандила. ѕациенты, одновременно принимающие ацетилсалициловую кислоту или нестероидные противовоспалительные препараты (Ќѕ¬ѕ), имеют повышенный риск развити¤ таких т¤желых осложнений, как желудочно-кишечное кровотечение. ѕоэтому рекомендуетс¤ соблюдать особую осторожность при одновременном применении ацетилсалициловой кислоты или Ќѕ¬ѕ с никорандилом.

ѕри прогрессировании ¤зв могут возникать перфораци¤, свищи или абсцессы. ѕациенты с дивертикул¤рной болезнью кишечника имеют особенно высокий риск образовани¤ свищей или перфорации кишечника при приеме препаратов никорандила.

ќписаны случаи перфорации органов ? “ при одновременном применении никорандила и глюкокортикостероидов. ѕоэтому совместное применение указанных препаратов следует осуществл¤ть с особой осторожностью.

»зъ¤звлени¤ глаз. ќписаны очень редкие случаи конъюнктивита, конъюнктивальной ¤звы и ¤звы роговицы, св¤занные с применением никорандила. ѕациенты должны быть предупреждены о симптомах поражени¤ роговицы и необходимости контролировать состо¤ние глаз. ¬ случае по¤влени¤ изъ¤звлений (¤зв) роговицы прием препарата  ординикЃ необходимо прекратить.

јртериальна¤ гипотензи¤. Ќикорандил в терапевтических дозах обладает антигипертензивным действием. —ледует с осторожностью примен¤ть никорандил в сочетании с другими лекарственными средствами, снижающими артериальное давление.

’роническа¤ сердечна¤ недостаточность. ¬ св¤зи с отсутствием опыта клинического применени¤ противопоказано назначение никорандила пациентам с хронической сердечной недостаточностью III?IV ‘  по NYHA.

vиперкалиеми¤. ѕри применении никорандила описаны очень редкие случаи развити¤ т¤желой гиперкалиемии. Ќикорандил следует примен¤ть с осторожностью в сочетании с другими лекарственными препаратами, которые могут увеличить содержание кали¤ в крови, особенно у пациентов с умеренной и т¤желой почечной недостаточностью.

?ефицит глюкозо-6-фосфатдегидрогеназы. ѕрепарат  ординикЃ следует примен¤ть с осторожностью у пациентов с дефицитом глюкозо-6-фосфатдегидрогеназы. ‘армакологическое действие никорандила частично обусловлено наличием в составе органической нитратной группы. ¬ результате метаболизма органических нитратов возможно образование нитритов, которые могут вызвать метгемоглобинемию у пациентов с дефицитом глюкозо-6-фосфатдегидрогеназы.

¬ли¤ние на способность управл¤ть транспортными средствами и механизмами

Ќикорандил, как и другие сосудорасшир¤ющие препараты, может снижать артериальное давление, вызывать головокружение и ощущение слабости, и, таким образом, оказывать вли¤ние на способность управл¤ть транспортными средствами, механизмами. Ёти эффекты могут усиливатьс¤ при одновременном применении с другими лекарственными средствами, снижающими артериальное давление (например, вазодилататорами, трициклическими антидепрессантами). Ќеобходимо соблюдать осторожность при управлении транспортными средствами и зан¤ти¤х другими потенциально опасными видами де¤тельности, требующими повышенной концентрации внимани¤ и быстроты психомоторных реакций.

‘орма выпуска

“аблетки 10 мг и 20 мг.

ѕо 10 таблеток в контурную ¤чейковую упаковку из пленки поливинилхлоридной и фольги алюминиевой.

2, 3 or 6 blisters, together with instructions for use, are placed in a carton box.

Storage conditions

In a dark place at a temperature not exceeding 25 ? C.

Keep out of the reach of children.

Shelf life

2 years. Do not use after the expiration date.

Vacation conditions

Dispensed by prescription.

Manufacturer

LLC 'PIK-PHARMA LEK', Russia, 308519, Belgorod region, Belgorod region, pos. North, st. Birch, 1/19.

The owner of the registration certificate
PIK-PHARMA LLC, Russia, 125047, Moscow, per. Oruzheiny, 25, bldg. 1.

Organization accepting consumer claims
PIK-PHARMA LLC, Russia, 125047, Moscow, per. Oruzheiny, 25, bldg. 1.