Cordipraz film-coated tablets 10 mg blister No. 30

Instructions Cordipraz film-coated tablets 10 mg blister No. 30

Composition

active ingredient: prasugrel;

1 film-coated tablet contains 5 mg or 10 mg of prasugrel as prasugrel hydrobromide;

excipients: core: microcrystalline cellulose, mannitol (E 421), hypromellose, low-substituted hydroxypropylcellulose, glycerol dibehenate, sucrose stearate;

film coating for 5 mg tablets: partially hydrolyzed polyvinyl alcohol, titanium dioxide (E 171), polyethylene glycol 3350, talc, yellow iron oxide (E 172), red iron oxide (E 172), black iron oxide (E 172);

film coating for 10 mg tablets: partially hydrolyzed polyvinyl alcohol, titanium dioxide (E 171), polyethylene glycol 3350, talc, yellow iron oxide (E 172), red iron oxide (E 172).

Dosage form

Film-coated tablets.

Main physicochemical properties:

film-coated tablets, 5 mg: yellow oval film-coated tablets, embossed with “P5” on one side, plain on the other side;

Film-coated tablets, 10 mg: beige oval film-coated tablets, embossed with “P10” on one side and with a breakline on the other side.

Pharmacotherapeutic group

Platelet aggregation inhibitors, excluding heparin. ATC code B01AC22.

Pharmacological properties

Pharmacodynamics

Mechanism of action: Prasugrel is an inhibitor of platelet activation and aggregation by irreversible binding of its active metabolite to the P2Y12 adenosine diphosphate (ADP) receptor on platelets. Since platelets are involved in the initiation and/or progression of thrombotic complications of atherosclerosis, inhibition of platelet function may reduce the incidence of cardiovascular events such as death, myocardial infarction, or stroke. After a loading dose of 60 mg of prasugrel, inhibition of ADP-induced platelet aggregation occurs within 15 minutes (5 μM ADP) and 30 minutes (20 μM ADP). The maximal inhibition of ADP-induced platelet aggregation by prasugrel was 83% (5 μM ADP) and 79% (20 μM ADP), with at least 50% inhibition of platelet aggregation achieved at 1 hour in both healthy subjects and patients with stable atherosclerosis. Prasugrel-mediated inhibition of platelet aggregation showed low inter-subject (9%) and intra-subject (12%) variability (both at 5 μM ADP and 20 μM ADP). The mean inhibition of platelet aggregation at steady state was 74% and 69% for 5 μM ADP and 20 μM ADP, respectively, and was achieved after 3-5 days of a 10 mg maintenance dose of prasugrel with a 60 mg loading dose. Over 98% of subjects had ≥20% inhibition of platelet aggregation at maintenance dosing. Platelet aggregation gradually returned to baseline values 7-9 days after a single 60 mg loading dose of prasugrel and 5 days after discontinuation of the maintenance dose at steady state.

Switching data. After clopidogrel 75 mg once daily for 10 days, 40 healthy subjects were switched to prasugrel 10 mg once daily with or without a 60 mg loading dose. Similar or greater inhibition of platelet aggregation was observed with prasugrel. Switching directly to a 60 mg loading dose of prasugrel resulted in the fastest onset of greater platelet inhibition. After a loading dose of 900 mg clopidogrel (with acetylsalicylic acid (ASA)), 56 subjects with acute coronary syndrome (ACS) were treated with either prasugrel 10 mg once daily or clopidogrel 150 mg once daily for 14 days and then switched to either clopidogrel 150 mg once daily or prasugrel 10 mg once daily for an additional 14 days. Greater inhibition of platelet aggregation was observed in patients switched to prasugrel 10 mg compared with patients receiving 150 mg clopidogrel. In a study of 276 patients with ACS undergoing percutaneous coronary intervention (PCI), switching from an initial loading dose of 600 mg of clopidogrel or placebo taken after hospitalization and before coronary angiography to a 60 mg loading dose of prasugrel taken at the time of PCI resulted in a similar increased inhibition of platelet aggregation over the 72 hours of the study.

Pharmacokinetics

Absorption: Prasugrel is rapidly absorbed and metabolized, with peak plasma concentrations of the active metabolite (Cmax) occurring within approximately 30 minutes. Exposure to the active metabolite (AUC) increases proportionally over the therapeutic dose range. In a study in healthy subjects, the administration of a high-fat, high-calorie meal had no effect on the AUC of the active metabolite, but there was a 49% decrease in Cmax and an increase in the time to Cmax (Tmax) from 0.5 to 1.5 hours. In the TRITON study, prasugrel was administered without regard to food intake. Therefore, prasugrel can be administered without regard to food intake, but administration of a loading dose of prasugrel on an empty stomach may provide the most rapid onset of action.

Distribution: The binding of the active metabolite to human serum albumin is 98%.

Biotransformation. After oral administration, prasugrel is not detected in plasma. It is rapidly hydrolyzed in the intestine to the thiolactone, which is then converted to the active metabolite by cytochrome P450 isoenzymes, mainly CYP3A4 and CYP2B6, and to a lesser extent, CYP2C9 and CYP2C19. The active metabolite is metabolized to two inactive compounds by S-methylation or conjugation with cysteine. In healthy subjects, patients with stable atherosclerosis, and patients with ACS who received prasugrel, no relevant effect of genetic variations in CYP3A5, CYP2B6, CYP2C9, or CYP2C19 on the pharmacokinetics of prasugrel or its inhibition of platelet aggregation was found.

Elimination: Approximately 68% of a prasugrel dose is excreted in the urine and 27% in the feces as inactive metabolites. The half-life of the active metabolite is approximately 7.4 hours (range 2 to 15 hours).

Pharmacokinetics in special populations

Elderly patients. In a study in healthy subjects aged 20 to 80 years, age did not significantly affect the pharmacokinetics of prasugrel or its inhibition of platelet aggregation. In a large phase 3 clinical study, the mean estimated exposure (AUC) of the active metabolite was 19% higher in subjects aged ≥75 years compared to subjects aged ≥75 years.

Hepatic impairment. No dose adjustment is required for patients with mild or moderate hepatic impairment (Child-Pugh class A and B). The pharmacokinetics of prasugrel and its inhibitory effect on platelet aggregation were similar in subjects with mild or moderate hepatic impairment compared to healthy subjects. The pharmacokinetics and pharmacodynamics of prasugrel in patients with severe hepatic impairment have not been studied. Prasugrel should not be used in patients with severe hepatic impairment.

Renal impairment. No dose adjustment is required in patients with renal impairment, including patients with end-stage renal disease (ESRD). The pharmacokinetics of prasugrel and its inhibitory effect on platelet aggregation are similar in patients with moderate renal impairment (glomerular filtration rate 30-2) and healthy subjects. Prasugrel-mediated inhibition of platelet aggregation was also similar in ESRD patients requiring hemodialysis and healthy subjects, although Cmax and AUC of the active metabolite were reduced by 51% and 42%, respectively, in ESRD patients.

Body weight: The mean exposure (AUC) of the active metabolite of prasugrel is approximately 30-40% higher in healthy subjects and patients with a body weight

Ethnicity: In clinical studies, the AUC of the active metabolite after adjustment for body weight was approximately 19% higher in subjects of Chinese, Japanese, and Korean ethnicity compared to Caucasians, which is mainly due to higher exposure in subjects of Mongoloid race.

Gender: In healthy subjects and patients, the pharmacokinetics of prasugrel are similar in men and women.

Children: The pharmacokinetics and pharmacodynamics of prasugrel have not been studied in children.

Indication

Cordipraz in combination with acetylsalicylic acid is indicated for the prevention of atherothrombotic events in adult patients with acute coronary syndrome, i.e.:

– unstable angina (UA),

– non-ST segment elevation myocardial infarction (NSTEMI) or

– ST-segment elevation myocardial infarction (STEMI),

who are undergoing primary or delayed percutaneous coronary intervention.

See also the section "Pharmacological properties".

Contraindication

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Active pathological bleeding.

History of stroke or transient ischemic attack (TIA).

Severe hepatic impairment (Child-Pugh class C).

Interaction with other medicinal products and other types of interactions

Warfarin: Concomitant use of prasugrel with coumarin derivatives other than warfarin has not been studied. Caution should be exercised when warfarin (or other coumarin derivatives) and prasugrel are co-administered due to a possible increased risk of bleeding (see section 4.4).

Prasugrel can be used concomitantly with drugs that are metabolized by cytochrome P450 enzymes (including statins), or with drugs that are inducers or inhibitors of cytochrome P450 enzymes. Prasugrel can also be used concomitantly with ASA, heparin, digoxin, and drugs that increase gastric pH, including proton pump inhibitors and H2 blockers.

Although specific interaction studies have not been performed, in a clinical study prasugrel was used concomitantly with low molecular weight heparin, bivalirudin, and glycoprotein IIb/IIIa inhibitors (no information is available on the type of glycoprotein IIb/IIIa inhibitor used), with no evidence of clinically significant adverse interactions.

Effects of other medicinal products on prasugrel

Acetylsalicylic acid. Prasugrel should be used with ASA. Although there is a potential for an increased risk of bleeding with a pharmacodynamic interaction with ASA, the efficacy and safety of prasugrel have been demonstrated in patients receiving prasugrel concomitantly with ASA.

Heparin. A single intravenous bolus dose of unfractionated heparin (100 U/kg) did not significantly alter prasugrel-mediated inhibition of platelet aggregation. Similarly, prasugrel did not significantly alter the effect of heparin on coagulation parameters. Therefore, both drugs can be used concomitantly. Concomitant use of prasugrel with heparin may increase the risk of bleeding.

Statins: Atorvastatin (80 mg daily) did not alter the pharmacokinetics of prasugrel or its inhibition of platelet aggregation. Therefore, statins that are substrates of CYP3A are not expected to affect the pharmacokinetics of prasugrel or its inhibition of platelet aggregation.

Drugs that increase gastric pH. Daily concomitant administration of ranitidine (an H2 blocker) or lansoprazole (a proton pump inhibitor) did not alter the AUC and Tmax of the active metabolite of prasugrel, but decreased Cmax by 14% and 29%, respectively. In the clinical study, prasugrel was administered without consideration of concomitant use of a proton pump inhibitor or H2 blocker. Administration of a 60 mg loading dose of prasugrel without concomitant use of a proton pump inhibitor may provide the fastest onset of action.

CYP3A4 inhibitors: Ketoconazole (400 mg daily), a selective and potent inhibitor of CYP3A4 and CYP3A5, had no effect on prasugrel-mediated inhibition of platelet aggregation or on the AUC and Tmax of the active metabolite of prasugrel, but decreased Cmax by 34-46%, respectively. Therefore, CYP3A4 inhibitors, such as azole antifungals, HIV protease inhibitors, clarithromycin, telithromycin, verapamil, diltiazem, indinavir, ciprofloxacin, and grapefruit juice, are not expected to have a significant effect on the pharmacokinetics of the active metabolite.

Cytochrome P450 inducers: Rifampicin (600 mg daily), a potent inducer of CYP3A and CYP2B6 and an inducer of CYP2C9, CYP2C19, and CYP2C8, did not significantly alter the pharmacokinetics of prasugrel. Therefore, known CYP3A inducers such as rifampicin, carbamazepine, and other cytochrome P450 inducers are not expected to significantly affect the pharmacokinetics of the active metabolite.

Morphine and other opioids. In patients with ACS receiving morphine, delayed and decreased exposure to oral P2Y12 inhibitors, including prasugrel and its active metabolite, has been observed. This interaction may be related to decreased gastrointestinal motility and may be relevant to other opioids. The clinical significance is unknown, but available data suggest that prasugrel efficacy may be reduced in patients receiving prasugrel and morphine concomitantly. In patients with ACS who cannot discontinue morphine therapy and for whom rapid inhibition of P2Y12 is considered critical, the use of a parenteral P2Y12 inhibitor may be considered.

Effect of prasugrel on other medicinal products

Digoxin: Prasugrel has no clinically significant effect on the pharmacokinetics of digoxin.

Medicinal products metabolised by CYP2C9: Prasugrel does not inhibit CYP2C9 as it did not affect the pharmacokinetics of S-warfarin. Due to the potential for increased bleeding risk, warfarin and prasugrel should be co-administered with caution (see section 4.4).

Medicinal products metabolized by CYP2B6. Prasugrel is a weak inhibitor of CYP2B6. In healthy subjects, prasugrel reduced the exposure of hydroxybupropion, a metabolite of bupropion formed by CYP2B6, by 23%. This effect is likely to be clinically relevant only when prasugrel is co-administered with medicinal products that are metabolized exclusively by CYP2B6 and have a narrow therapeutic index (e.g., cyclophosphamide, efavirenz).

Application features

Bleeding risk. In clinical trials (TRITON), key exclusion criteria for patients were increased bleeding risk, anemia, thrombocytopenia, and history of intracranial pathology. In patients with ACS undergoing PCI and treated with prasugrel and ASA, an increased risk of major and minor bleeding was observed according to the TIMI (Thrombolysis In Myocardial Infarction) classification system. Therefore, the use of prasugrel in patients at increased bleeding risk should only be considered when the benefit of preventing ischemic events outweighs the risk of major bleeding.

This is especially true for patients:

• with a tendency to bleed (for example, due to recent trauma, recent surgery, recent or recurrent gastrointestinal bleeding, or active peptic ulcer disease);

• with body weight

• who are taking concomitant medications that may increase the risk of bleeding, including oral anticoagulants, clopidogrel, NSAIDs, and fibrinolytics.

For patients with active bleeding who need to counteract the pharmacological effects of prasugrel, platelet transfusion may be appropriate.

While taking Cordipraz, the intensity of menstruation may increase. In this case, it is recommended to consult a doctor. You should not cancel the drug on your own.

Prasugrel is generally not recommended for use in patients ≥75 years of age. It should only be used with caution after a careful individual benefit/risk assessment by the physician if the benefit of preventing ischemic events outweighs the risk of serious bleeding. In a clinical trial, such patients were at increased risk of bleeding, including fatal bleeding, compared with patients aged 75 years. If prescribed, a lower maintenance dose (5 mg) should be used - a maintenance dose of 10 mg is not recommended.

There is limited therapeutic experience with prasugrel in patients with renal impairment (including ESRD) and in patients with moderate hepatic impairment. These patients may be at increased risk of bleeding. Therefore, prasugrel should be used with caution in these patients.

Patients should be advised that during treatment with prasugrel (in combination with ASA) it may take longer than usual to stop bleeding and that they should report any unusual bleeding (site or duration) to their doctor.

Bleeding risk related to timing of loading dose in STEMI. In a clinical trial (ACCOAST) in patients with STEMI who were scheduled to undergo coronary angiography within 2-48 hours of randomization, a loading dose of prasugrel administered on average 4 hours before coronary angiography increased the risk of major and minor periprocedural bleeding compared with a loading dose of prasugrel administered during PCI. Therefore, patients with STEMI/STEMI who undergo coronary angiography within 48 hours of admission should receive a loading dose at the time of PCI (see sections 4.2 and 4.8).

Surgery. Patients should be advised to inform their physicians and dentists that they are taking prasugrel before any planned surgery and before starting any new medicinal product. If the patient requires elective surgery and the antiplatelet effect is undesirable, prasugrel should be discontinued at least 7 days before surgery. In patients undergoing coronary artery bypass grafting (CABG) within 7 days of stopping prasugrel, there may be an increase in the frequency (up to 3-fold) and severity of bleeding (see section 4.8). The benefits and risks of using prasugrel should be carefully weighed against the risks in patients whose coronary anatomy has not been determined and who may be undergoing emergency CABG.

Hypersensitivity, including angioedema. Hypersensitivity reactions, including angioedema, have been reported in patients taking prasugrel, including patients with a history of hypersensitivity reactions to clopidogrel. It is recommended to monitor patients with a history of hypersensitivity reactions to thienopyridines for signs of hypersensitivity (see section 4.8).

Thrombotic thrombocytopenic purpura (TTP). TTP has been reported with prasugrel. TTP is a serious condition that requires immediate treatment.

Morphine and other opioids: Reduced efficacy of prasugrel has been observed in patients receiving prasugrel and morphine concomitantly (see section 4.5).

Sucrose stearate: Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Use during pregnancy or breastfeeding

Clinical studies involving pregnant or breastfeeding women have not been conducted.

Pregnancy: Animal studies do not indicate direct harmful effects with respect to pregnancy, embryonal/fetal development, parturition, or postnatal development. Because animal reproductive toxicity studies are not always predictive of human response, prasugrel should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

Breast-feeding. It is not known whether prasugrel is excreted in human milk. Animal studies have shown that prasugrel is excreted in human milk. Prasugrel is not recommended for use during breast-feeding.

Fertility: Prasugrel had no effect on the fertility of male and female rats when administered orally at doses providing exposures approximately 240 times the recommended daily human maintenance dose (based on mg/m2).

Ability to influence reaction speed when driving vehicles or other mechanisms

Prasugrel is expected to have no or negligible influence on the ability to drive and use machines.

Method of administration and doses

Dosage

Adults: Prasugrel should be initiated with a single 60 mg loading dose, followed by 10 mg once daily. Patients with ACS/STEMI undergoing coronary angiography within 48 hours of admission should receive a loading dose only at the time of PCI. Patients receiving prasugrel should also receive daily ASA (75-325 mg).

In patients with acute coronary syndrome who have undergone PCI, premature discontinuation of any antiplatelet agent, including prasugrel, may increase the risk of thrombosis, myocardial infarction, or death from the underlying disease. It is recommended that treatment be continued for up to 12 months unless there are indications for discontinuation of prasugrel.

Patients ≥75 years of age. The use of prasugrel in patients ≥75 years of age is generally not recommended. If, after careful individual benefit/risk assessment, the physician determines that treatment is necessary in a patient ≥75 years of age, a reduced maintenance dose of 5 mg should be administered after a loading dose of 60 mg. Patients ≥75 years of age have a greater susceptibility to bleeding and higher exposure to the active metabolite of prasugrel.

Patients with body weight Prasugrel is prescribed as a single loading dose of 60 mg, then 5 mg once a day. A maintenance dose of 10 mg is not recommended. This is due to increased exposure to the active metabolite of prasugrel in the blood and an increased risk of bleeding in patients with body weight

Renal impairment: No dose adjustment is required in patients with renal impairment, including patients with end-stage renal disease. Therapeutic experience in patients with renal impairment is limited.

Hepatic impairment. No dose adjustment is necessary for subjects with mild or moderate hepatic impairment (Child-Pugh class A and B). Therapeutic experience in patients with mild or moderate hepatic impairment is limited. Prasugrel is contraindicated in patients with severe hepatic impairment (Child-Pugh class C).

Method of administration and doses

For oral use. Cordipraz may be taken with or without food. Taking a loading dose of prasugrel 60 mg on an empty stomach may provide the most rapid onset of action.

The 5 mg tablet should not be broken or crushed. The 10 mg tablet can be divided into equal doses by breaking it only once; the tablet should not be crushed.

Children.

The safety and efficacy of prasugrel in children (under 18 years of age) have not been established. Limited data are available in children with sickle cell disease.

Overdose

Overdose of prasugrel may lead to prolonged bleeding time and subsequent bleeding complications. There is no evidence to reverse the pharmacological effect of prasugrel, however, if rapid correction of prolonged bleeding time is required, transfusion of platelets and/or other blood products may be considered.

Adverse reactions

Safety in patients with ACS undergoing PCI was evaluated in one clopidogrel-controlled study (TRITON), in which 6741 patients were treated with prasugrel (loading dose of 60 mg and maintenance dose of 10 mg once daily) for a median of 14.5 months (5802 patients were treated for more than 6 months, 4136 patients for more than 1 year). The rate of per-protocol discontinuation due to adverse events was 7.2% for prasugrel and 6.3% for clopidogrel. Bleeding was the most common adverse reaction leading to discontinuation for both drugs (2.5% for prasugrel and 1.4% for clopidogrel).

Bleeding not related to CABG

Table 1 shows the incidence of non-CABG-related bleeding in patients enrolled in the TRITON trial. The incidence of major (TIMI) non-CABG-related bleeding, including life-threatening and fatal, and minor (TIMI) bleeding was statistically significantly higher in subjects treated with prasugrel compared with clopidogrel in the ACS/STEMI population and in the population that included all ACS patients. No significant differences were observed in the STEMI group. Spontaneous bleeding was most common in the gastrointestinal tract (1.7% for prasugrel and 1.3% for clopidogrel), and provoked bleeding was most common at the site of arterial puncture (1.3% for prasugrel and 1.2% for clopidogrel).

Table 1

Non-CABG-related bleeding rate (% of patients)

a Determined by TIMI criteria.

b Other standard therapy was used as needed.

c Any intracranial hemorrhage or any bleeding with clinical manifestations with a decrease in hemoglobin level ≥5 g/dL.

d Life-threatening bleeding is a subgroup of major bleeding according to TIMI, which includes the following types. Patients may be included in more than one category.

e ICH = intracranial hemorrhage.

f Clinically manifest bleeding with a decrease in hemoglobin level ≥3 g/dL, but

Patients aged ≥75 years

Table 2

Incidence of major or minor bleeding (by TIMI) not related to CABG

* TRITON study in patients with ACS undergoing PCI.

** TRILOGY-ACS study in patients who did not undergo PCI.

a 10 mg prasugrel; 5 mg prasugrel at body weight

Patients

Table 3

Incidence of major or minor bleeding (by TIMI) not related to CABG

* TRITON study in patients with ACS undergoing PCI.

** TRILOGY-ACS study in patients who did not undergo PCI.

a 10 mg prasugrel; 5 mg prasugrel if age ≥75 years.

Patients ≥60 kg and aged

In patients with body weight ≥60 kg and age

Bleeding associated with CABG

In phase 3 clinical trials, 437 patients underwent CABG. In these patients, the incidence of major or minor bleeding (TIMI) associated with CABG was 14.1% in the prasugrel group and 4.5% in the clopidogrel group. The increased risk of bleeding in patients treated with prasugrel persisted for up to 7 days after the last dose of study drug. In patients who received a thienopyridine within 3 days prior to CABG, major or minor bleeding (TIMI) occurred at a rate of 26.7% (12 of 45 patients) in the prasugrel group compared with 5.0% (3 of 60 patients) in the clopidogrel group. In patients who received their last thienopyridine dose 4 to 7 days before CABG, the bleeding rate decreased to 11.3% (9 of 80 patients) in the prasugrel group and 3.4% (3 of 89 patients) in the clopidogrel group. After 7 days of drug withdrawal, the rate of CABG-related bleeding was similar between treatment groups.

Bleeding risk associated with the timing of the loading dose in STEMI

In a clinical trial (ACCOAST) of patients with STEMI scheduled for coronary angiography within 2 to 48 hours of randomization, patients who received a loading dose of 30 mg a median of 4 hours before coronary angiography followed by a loading dose of 30 mg during PCI had an increased risk of periprocedural bleeding not related to CABG, with no additional benefit compared with patients who received a loading dose of 60 mg during PCI.

Table 4

Bleeding rates (by TIMI) not related to CABG observed in patients over 7 days

a Other standard therapy was used as needed. The clinical trial protocol required all patients to receive aspirin and a daily maintenance dose of prasugrel.

b Any intracranial hemorrhage or any bleeding with clinical manifestations with a decrease in hemoglobin level ≥5 g/dL.

c Life-threatening bleeding is a subgroup of major bleeding according to TIMI, which includes the following types. Patients may be included in more than one category.

d ICH = intracranial hemorrhage.

e Clinically manifest bleeding with a decrease in hemoglobin level ≥3 g/dL, but

The following are summary of the haemorrhagic and non-haemorrhagic adverse reactions observed in the TRITON study or reported spontaneously. Adverse reactions are listed by system organ class and frequency. Adverse reactions are classified according to frequency as follows: very common (≥1/10); common (≥1/100,

From the blood and lymphatic system: often - anemia; rarely - thrombocytopenia; frequency unknown - thrombotic thrombocytopenic purpura (see section "Special instructions").

Immune system disorders: uncommon: hypersensitivity, including angioedema.

On the part of the organs of vision: infrequently - hemorrhage in the eye.

Vascular disorders: often – hematoma.

From the respiratory system, thoracic organs and mediastinum: often - epistaxis; infrequently - hemoptysis.

Gastrointestinal: often - gastrointestinal bleeding; infrequently - retroperitoneal bleeding, rectal bleeding, hematochezia, bleeding gums.

Skin and subcutaneous tissue disorders: often – rash, ecchymosis.

Renal and urinary disorders: often – hematuria.

General disorders and administration site complications: common: hematoma at the site of vascular puncture, bleeding at the site of puncture.

Injury, poisoning and procedural complications: common: contusion; uncommon: post-procedural bleeding; rare: subcutaneous hematoma.

Table 5

Stroke incidence during a clinical trial in patients with or without a history of TIA or stroke (see section 4.4)

*ICH = intracranial hemorrhage.

Reporting of suspected adverse reactions. All cases of suspected adverse reactions and lack of efficacy of the drug should be reported via the link: https://aisf.dec.gov.ua/.

Expiration date

2 years.

Storage conditions

Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Packaging

10 tablets in a blister, 3 or 9 blisters in a cardboard box.

Vacation category

According to the recipe.

Producer

PLIVA Hrvatska d. o. at.

Location of the manufacturer and address of its place of business.

Prilaz baruna Filipovića 25, 10000 Zagreb, Croatia.