Instructions for use Kardiket retard prolonged-release tablets 20 mg blister No. 50
Composition
active ingredient: isosorbide dinitrate;
1 prolonged-release tablet contains 20 mg or 40 mg or 60 mg of isosorbide dinitrate;
excipients: lactose monohydrate; talc; magnesium stearate; polyvinyl acetate; potato starch.
Dosage form
Extended-release tablets.
Main physicochemical properties: the upper side is flat with a chamfer and a break line; on one side of the break line there is a stamp “IR”, on the other side – “20” or “40” or “60”. The reverse side is convex, with the inscription “SCHWARZ PHARMA”.
Pharmacotherapeutic group
Vasodilators used in cardiology.
ATX code C01D A08.
Pharmacological properties
Pharmacodynamics.
Mechanism of action: Like all organic nitrates, isosorbide dinitrate (ISDN) acts as a nitric oxide (NO) donor. NO causes relaxation of vascular smooth muscle by stimulating guanylate cyclase and subsequently increasing the concentration of intracellular cyclic guanylate monophosphate (cGMP). This stimulates (cGMP)-dependent protein kinase, which in turn alters the phosphorylation of various proteins in the smooth muscle cell. This in turn leads to dephosphorylation of myosin light chains and a decrease in contractility.
INR causes relaxation of vascular smooth muscle, resulting in vasodilation. Venous dilation promotes venous "pooling" of blood and reduces venous return to the heart; thus, ventricular end-diastolic pressure and volume (preload) are reduced.
The action on arteries, and at higher doses on arterioles, leads to a decrease in systemic vascular resistance (afterload). This, in turn, improves heart function.
The effect on both preload and afterload leads to a decrease in oxygen consumption by the heart.
In addition, ISDN causes a redistribution of blood flow to the subendocardial regions of the heart in conditions of atherosclerotic lesions. The latter effect is probably due to selective dilation of large coronary vessels. Dilation of collateral arteries caused by nitrates can improve myocardial perfusion in vascular stenosis. In addition, nitrates counteract the appearance and eliminate coronary spasms.
In patients with congestive heart failure, nitrates improve hemodynamics at rest and during exercise. The main factor for this positive effect is the improvement of heart valve function (by reducing ventricular dilatation) and the reduction of myocardial oxygen demand.
Reducing oxygen demand and simultaneously increasing oxygen supply to the heart helps reduce the area of damage during myocardial infarction. This makes it possible to use the drug in the treatment of such patients.
It acts on the smooth muscles of other organs, including the bronchi, gastrointestinal tract, biliary and urinary tracts; there are reports of a relaxing effect on the smooth muscles of the uterus.
Pharmacokinetics.
In the digestive tract, isosorbide dinitrate is released from a prolonged-release tablet, 20/40/60 mg slowly, over several hours. The drug is rapidly absorbed, starting from the oral mucosa (the onset of therapeutic action is already after 1 min, 2 min, 5 min, respectively), the maximum therapeutic concentration in the blood plasma is reached after 6 min, 10 min, 15 min, respectively. In the gastrointestinal tract, absorption is somewhat slower (the onset of the drug's action is after 15-30 min), the maximum concentration (Cmax) is from 15 min to 1-2 hours. Absorption of the active substance is high. Binding to blood plasma proteins is 30%. Bioavailability when administered orally is about 80% compared to tablets that do not have a prolonged-release effect, after the first pass through the liver, the bioavailability is 15-30%. ISDN is metabolized in the liver to form isosorbide-2-mononitrate (T1/2 – 1.5-2 hours) and isosorbide-5-mononitrate (T1/2 – 4-6 hours). Both metabolites have pharmacological activity.
Indication
Prevention and long-term treatment of angina pectoris.
Contraindication
The drug is contraindicated:
- with hypersensitivity to isosorbide dinitrate, other nitrate compounds or to any of the excipients;
- in acute circulatory failure (shock, vascular collapse);
- in cardiogenic shock (if appropriate measures do not maintain a sufficient level of end-diastolic pressure);
- with hypertrophic obstructive cardiomyopathy;
- with constrictive pericarditis;
- with cardiac tamponade;
- with severe hypotension (systolic blood pressure below 90 mm Hg);
- with severe anemia;
- in severe hypovolemia.
Phosphodiesterase inhibitors, such as sildenafil, tadalafil, vardenafil, should not be used during nitrate therapy.
Interaction with other medicinal products and other types of interactions
The hypotensive effect of the drug is enhanced when taken simultaneously with phosphodiesterase inhibitors (e.g., sildenafil, tadalafil, vardenafil), which can lead to life-threatening cardiovascular complications. Isosorbide dinitrate therapy should not be used simultaneously with phosphodiesterase inhibitors (e.g., sildenafil, tadalafil, vardenafil).
There are reports that simultaneous use of the drug with dihydroergotamine may lead to an increase in the concentration of dihydroergotamine in the blood and thus enhance its effect.
Application features
The drug should be used with extreme caution and under the supervision of a physician in the following cases:
- at low filling pressure, including acute myocardial infarction with impaired left ventricular function (left ventricular failure). It is necessary to maintain the pressure not lower than 90 mm Hg.
- with aortic and/or mitral stenosis;
- with orthostatic dysfunction;
- in diseases associated with increased intracranial pressure (further increase is possible. Until now, such symptoms have only been observed after intravenous administration of high doses of nitroglycerin).
The drug is not intended for the treatment of acute attacks of angina pectoris.
The development of tolerance (reduced efficacy) has been described, as well as cross-tolerance to other nitrate-type drugs (reduced effect if the patient has previously taken another nitrate). To prevent a decrease or loss of effect, prolonged use of high doses (120 mg per day) should be avoided.
Patients on maintenance therapy with the drug should be advised not to take drugs containing phosphodiesterase inhibitors (e.g. sildenafil, tadalafil, vardenafil) due to the risk of developing uncontrolled arterial hypotension.
Due to the fact that the drug contains lactose, it cannot be prescribed to patients with rare genetic diseases such as galactose intolerance, Lapp hereditary lactase deficiency, glucose-galactose malabsorption.
Sapropterin (tetrahydrobiopterin, BH4) is a cofactor of nitric oxide synthase. Use with caution preparations containing sapropterin with any drugs that have a vasodilating effect due to nitric oxide metabolism or contain nitric oxide donors (including nitroglycerin (GTN), isosorbide dinitrate (ISDN), isosorbide mononitrate).
Use during pregnancy or breastfeeding
There are no adequate and controlled studies in pregnant women. If the benefit of use outweighs the potential risk, the drug should be used during pregnancy only in case of extreme necessity and under the constant supervision of a physician.
It is not known whether isosorbide dinitrate passes into breast milk, therefore it is not recommended to prescribe the drug to women during breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
The drug may affect the reaction speed when driving or working with other mechanisms.
Method of administration and doses
The drug should be taken without chewing and with sufficient water.
Cardiket® retard 20: 1 tablet 2 times a day (equivalent to 40 mg of isosorbide dinitrate). With increased need for nitro drugs, the daily dose can be increased to 1 tablet 3 times a day (equivalent to 60 mg of isosorbide dinitrate), the last dose is recommended to be taken around 6 pm.
The second/next dose should be taken no earlier than 6-8 hours after the first dose.
Cardiket® retard 40: 1 tablet once a day (equivalent to 40 mg isosorbide dinitrate). With increased need for nitro drugs, the daily dose can be increased to 1 tablet 2 times a day (equivalent to 80 mg isosorbide dinitrate). The second/next dose should be taken no earlier than 6-8 hours after the first dose.
Cardiket® retard 60: 1 tablet once a day (equivalent to 60 mg of isosorbide dinitrate). With increased need for nitro drugs, the daily dose can be increased to 1 tablet 2 times a day (equivalent to 120 mg of isosorbide dinitrate). The second/next dose should be taken no earlier than 6-8 hours after the first dose.
Treatment should be started with the lowest doses, gradually increasing the dose to the maximum effective. The duration of the course of treatment is determined by the doctor. Reducing the dose or changing the dosage may lead to a decrease or loss of effectiveness.
Since CARDIKET® RETARD 20/40/60 mg are matrix tablets, in some cases, the matrix frame of the tablet, which does not contain the active substance, may be released.
There is no evidence that dosage adjustments are necessary for elderly patients.
Children
Do not use on children.
Overdose
Symptoms:
· decrease in blood pressure ≤ 90 mm Hg;
· pallor;
· increased sweating;
· weak pulse filling;
· tachycardia;
· dizziness (orthostatic reactions when changing body position);
headache;
· asthenia;
weakness;
· dizziness
nausea;
vomiting;
· Cases of methemoglobinemia have been reported in patients taking other nitrates. During the biotransformation of isosorbide dinitrate, nitrite ions are released, which can induce methemoglobinemia and cyanosis with subsequent tachypnea, anxiety, loss of consciousness and cardiac arrest. The possibility of this adverse reaction in case of overdose of isosorbide dinitrate cannot be excluded;
Excessive doses may increase intracranial pressure, sometimes causing cerebral symptoms.
General measures:
· stop the drug from entering;
· general measures used in case of nitrate-induced arterial hypotension:
- give the patient a horizontal position with his head down, the headboard low and legs raised;
- ensure the supply of oxygen;
- increase plasma volume (intravenous infusion);
- conduct special anti-shock therapy (the patient must be in the intensive care unit).
Special events.
· In the event of a severe drop in pressure, it is necessary to take steps to increase it;
· vasopressor (vasoconstrictor) drugs should be used in cases where the patient does not have an adequate effect on fluid therapy.
· Treatment of methemoglobinemia
– Restorative therapy with vitamin C, methylene blue or toluidine blue of your choice;
– use of oxygen (if necessary);
– artificial ventilation, blood replacement (if necessary).
– hemodialysis (if necessary).
· Resuscitation measures
In case of signs of respiratory or circulatory arrest, resuscitation measures should be taken immediately.
Adverse reactions
Adverse effects can be defined as very common (more than 10%), common (1% to 10%), uncommon (0.1% to 1%), rare (0.01% to 0.1%) and rare (less than 0.01%).
The following undesirable effects may occur when using the drug.
From the nervous system: very often - headache ("nitrate headache"); often - dizziness, drowsiness.
From the side of the cardiovascular system: often - tachycardia; infrequently - increased symptoms of angina pectoris.
From the vascular system: often - orthostatic hypotension; infrequently - vascular collapse (sometimes accompanied by bradyarrhythmia and loss of consciousness); rare - hypotension.
On the part of the digestive tract: infrequently - nausea, vomiting; rarely - heartburn.
Skin and subcutaneous tissue disorders: infrequently - allergic skin reactions (e.g. rash), rarely - angioedema, Stevens-Johnson syndrome; in rare cases - exfoliative dermatitis.
General disorders: often - asthenia.
Severe hypotensive reactions have been reported with the use of organic nitrates, accompanied by nausea, vomiting, restlessness, pallor and increased sweating. During drug therapy, transient hypoxemia may occur due to relative redistribution of blood flow to the alveolar areas with hypoventilation. In particular, in patients with ischemic heart disease, this may lead to myocardial hypoxia.
Expiration date
Cardiket® retard, prolonged-release tablets, 20 mg – 5 years.
Cardiket® retard, prolonged-release tablets, 40 mg – 5 years.
Cardiket® retard, prolonged-release tablets, 60 mg – 5 years.
Storage conditions
Keep out of reach of children.
Cardiket® retard, prolonged-release tablets, 20 mg and Cardiket® retard, prolonged-release tablets, 40 mg:
does not require special storage conditions.
Cardiket® retard, prolonged-release tablets, 60 mg:
Store at a temperature not exceeding 25 ºС.
Packaging
10 tablets in a blister, No. 50 (10x5) in a pack.
Vacation category
According to the recipe.
Producer
Responsible for the release of the series
Aesica Pharmaceuticals GmbH, Germany.
Location of the manufacturer and its business address
Alfred-Nobel-Str. 10, 40789 Monheim am Rhein, North Rhine-Westphalia, Germany/Alfred-Nobel-Str. 10, 40789 Monheim am Rhein, North Rhine-Westphalia, Germany.
Applicant
UCB Pharma GmbH, Germany.
Applicant's location
Alfred-Nobel-Strasse, 10, 40789 Monheim, Germany/Alfred-Nobel-Strasse 10, 40789 Monheim, Germany.
