Xarelto, 2.5 mg, film-coated tablets, 28 pcs.

Xarelto is a direct-acting anticoagulant. This means that it suppresses platelet activation, and therefore it is prescribed when it is necessary to treat and prevent thrombosis, thromboembolism, and myocardial infarction. A doctor can prescribe Xarelto after diagnosing and excluding contraindications, the list of which is impressive. In 2019, Xarelto was not included in the list of preferential drugs approved by the Ministry of Health of the Russian Federation.

Figure 1 — Drug Xarelto

Pharmacological properties of the drug Xarelto

Pharmacodynamics. Rivaroxaban is a highly selective direct factor Xa inhibitor with sufficient oral bioavailability. Activation of factor X to form factor Xa (Fxa) through intrinsic and extrinsic pathways plays a central role in the coagulation cascade. Pharmacodynamic effects. Rivaroxaban has a dose-dependent effect on prothrombin time and correlates closely with plasma concentrations (r=0.98) when the Neoplastin kit is used for analysis. Results will vary if other reagents are used. The device should be read in seconds because the INR (International Normalized Ratio) is calibrated and validated only for coumarins and cannot be used for other anticoagulants. In patients undergoing major orthopedic surgery, the 5/95th percentile for prothrombin (Neoplastin) 2 to 4 hours after tablet administration (that is, at the time of maximum effect) ranges from 13 to 25 s. Rivaroxaban also dose-dependently increases activated partial thromboplastin time (aPTT) and Heptest results, however, these parameters are not recommended for use in assessing the pharmacodynamic effects of rivaroxaban. Rivaroxaban affects anti-factor Xa activity, although standards for calibration are lacking. During treatment with rivaroxaban, monitoring of blood coagulation parameters is not necessary. Clinical efficacy and safety Prevention of venous thromboembolic events in patients undergoing extensive orthopedic interventions on the lower extremities.
The clinical program was designed to demonstrate the effectiveness of rivaroxaban for the prevention of venous thromboembolism (VTE), that is, proximal and distal deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients undergoing major orthopedic surgery of the lower extremities. The RECORD program, a controlled, randomized, double-blind phase 3 clinical trial, studied more than 9,500 patients (7,050 total hip replacement patients and 2,531 total knee replacement patients). A comparison was made of rivaroxaban at a dose of 10 mg once a day, which patients began to receive no earlier than 6 hours after surgery, with enoxaparin 40 mg once a day, treatment of which began 12 hours before surgery. In all three phase 3 studies (see table), rivaroxaban significantly reduced the incidence of composite major VTE (any venographically detected or symptomatic DVT, nonfatal PE) and advanced VTE events (proximal DVT, nonfatal PE associated with VTE), which were the specified primary and major secondary efficacy endpoints. Moreover, in all three studies, the incidence of symptomatic VTE (DVT, PE without VTE-related death) was lower in the rivaroxaban group than in the enoxaparin group. The incidence of major bleeding, the primary safety endpoint, was comparable among patients who received rivaroxaban 10 mg and enoxaparin 40 mg. Table. Results of efficacy and safety assessment in phase 3 clinical trials.

Analysis of pooled results from phase 3 studies confirmed data obtained from individual studies, which showed a greater reduction in the incidence of all VTE, major VTE and symptomatic VTE in the rivaroxaban 10 mg once daily group compared with the enoxaparin 40 mg once daily group. day. Pharmacokinetics. Absorption and bioavailability. The absolute bioavailability of rivaroxaban after taking a dose of 10 mg is high and amounts to 80–100%. Rivaroxaban is rapidly absorbed; the maximum concentration is reached 2–4 hours after taking the tablet. Taking rivaroxaban 10 mg tablet with food does not affect the AUC and Cmax of rivaroxaban. Rivaroxaban 10 mg can be taken with or without food. The pharmacokinetics of rivaroxaban are characterized by moderate variability; individual variability (coefficient of variation) is 30–40%, except on the day of surgery and the next day after surgery, when variability is high (70%). Distribution. In the human body, most of rivaroxaban (92–95%) is bound to plasma proteins, the main binding component being serum albumin. The volume of distribution is average, approximately 50 liters. Metabolism and excretion from the body. Rivaroxaban is excreted primarily in the form of metabolites (approximately 2/3 of the administered dose), half of which are excreted by the kidneys and the other half in the feces. 1/3 of the administered dose is excreted directly in the urine as unchanged active substance, approximately mainly via active renal secretion. Rivaroxaban is metabolized by isoenzymes CYP 3A4, CYP 2J2, as well as enzymes independent of the cytochrome P450 system. The main participants in biotransformation are the morpholine group, which undergoes oxidative decomposition, and the amide groups, which undergo hydrolysis. According to in vitro data, rivaroxaban is a substrate for the transporter proteins P-gp (P-glycoprotein) and BCR-P (breast cancer resistance protein). Unchanged rivaroxaban is the most significant compound in human plasma; no active circulating metabolites have been identified in blood plasma. Rivaroxaban, whose systemic clearance is approximately 10 L/h, can be classified as a drug with a low clearance rate. When rivaroxaban is eliminated from plasma, the terminal half-life is 5–9 hours in young patients and 11–13 hours in elderly patients. Gender/old age (over 65 years old). In elderly patients, plasma concentrations of rivaroxaban are higher than in young patients, the mean AUC value is approximately 1.5 times higher than the corresponding values ​​in young patients, mainly due to reduced total and renal clearance. No clinically relevant differences in pharmacokinetics were identified in men and women. Too little or too much body weight (≤50 kg and 120 kg) has only a small effect on rivaroxaban plasma concentrations (difference ≤25%). Childhood. There are no data available for this age group. Interethnic features. Clinically relevant differences in pharmacokinetics and pharmacodynamics were not observed in patients of Caucasian, African American, Hispanic, or Asian ethnicity. Patients with Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics of rivaroxaban was studied in subjects who were categorized according to the Child-Pugh classification according to standard procedures in clinical development. The primary purpose of the Child-Pugh classification is to assess the prognosis of chronic liver disease, mainly cirrhosis. In patients prescribed anticoagulants, a critical aspect of liver dysfunction is decreased synthesis of normal clotting factors in the liver. Because this aspect is covered by only one of the 5 clinical/biochemical definitions included in the Child-Pugh classification system, patients' bleeding risk may not clearly correlate with this classification scheme. Given this, the decision to treat patients with anticoagulants should be made regardless of the Child-Pugh classification. Rivaroxaban is contraindicated in patients with liver disease associated with coagulopathy that carries a clinically relevant risk of bleeding. In patients with cirrhosis with mild hepatic impairment (Child-Pugh class A), the pharmacokinetics of rivaroxaban differed only slightly from the corresponding (average increase in rivaroxaban AUC by 1.2 times) parameters in the control group of healthy volunteers. In patients with cirrhosis and moderate hepatic impairment (Child-Pugh class B), the mean AUC of rivaroxaban was significantly increased (2.3-fold) compared to healthy volunteers due to a significant decrease in drug clearance. The AUC of the unbound substance increased 2.6-fold. There are no data available in patients with severe hepatic impairment. The inhibition of factor Xa activity was more pronounced (2.6-fold difference) than in healthy volunteers. Prothrombin time was also (2.1 times) higher than that of healthy volunteers. Patients with moderately severe hepatic impairment were more sensitive to rivaroxaban, resulting in a steeper pharmacokinetic and pharmacodynamic relationship between concentration and prothrombin time. There are no data available for patients with Child-Pugh class C hepatic impairment. Renal failure There was an increase in rivaroxaban exposure, which was inversely correlated with a decrease in renal function (determined according to creatinine clearance - creatinine clearance). In subjects with mild (CR ≤80–50 ml/min), moderate (CR ≤50–30 ml/min) or severe (CR ≤30–15 ml/min) renal impairment, rivaroxaban plasma concentrations (AUC) were in 1.4; 1.5 and 1.6 times higher compared to healthy volunteers. The corresponding increase in pharmacodynamic effect was more pronounced. In individuals with mild, moderate or severe renal impairment, the overall suppression of factor Xa activity was 1.5; 1.9 and 2.0 times more, respectively, compared to healthy volunteers; prothrombin time increased by 1.3; 2.2 and 2.4 times respectively. There are no data available for patients with creatinine clearance ≤15 ml/min. It is not recommended to use the drug in patients with CC ≤15 ml/min. Rivaroxaban should be used with caution in patients with severe renal failure with CC 15–30 ml/min.

Use of the drug Xarelto

In order to prevent VTE during extensive orthopedic interventions, it is recommended to prescribe 1 tablet of 10 mg 1 time per day. The duration of treatment is determined by the type of orthopedic intervention. After hip replacement surgery, treatment should be continued for 5 weeks. After knee replacement, the drug should be continued for 2 weeks. Method and frequency of use Take 1 tablet of Xarelto 10 mg 1 time per day, regardless of meals. The first dose should be taken 6–10 hours after surgery, provided there is effective hemostasis. If a tablet is missed, the patient should take rivaroxaban immediately and continue treatment the next day, 1 tablet per day, as before the missed tablet.

Analogs

Figure 5 - Analogues of the drug Xarelto

We remind you that before changing your medicine, you should consult your doctor. Popular analogues of Xarelto are: Clexane, produced in the form of injections, is a direct anticoagulant, the indications for use of which are identical to Xarelto. Also on the market are Pradaxa capsules with anticoagulant and antithrombic effects, which are used in recovery after major orthopedic surgeries.

Side effects of the drug Xarelto

The safety of rivaroxaban 10 mg was assessed in three phase 3 studies involving 4571 patients undergoing major lower extremity orthopedic surgery (total knee or total hip replacement) and receiving treatment for up to 39 days. Adverse reactions are classified by frequency and by organs and systems; they must be assessed taking into account the surgical situation. Classification based on the frequency of adverse reactions included the following categories: common - (≥1%–≤10%) or (≥1/100–≤1/10); uncommon - (≥0.1%–≤1%) or (≥1/1000–≤1/100); less common - (≥0.01%–≤0.1%) or (≥1/10,000–≤1/1000); rare - (≤0.01%) or (≤1/10,000). Given the pharmacological mechanism of action, the use of rivaroxaban may be accompanied by an increased risk of latent or overt bleeding from any organ or tissue, which can lead to post-hemorrhagic anemia. Signs, symptoms, and severity (including the possibility of death) will vary depending on the location and severity or duration of bleeding. The risk of bleeding may be increased in certain patient groups, such as patients with uncontrolled severe hypertension (arterial hypertension) and/or patients taking drugs that affect hemostasis (see PRECAUTIONS). Hemorrhagic complications may manifest as weakness, asthenia, pallor, dizziness, headache or swelling of unknown etiology. Therefore, when assessing the condition of a patient receiving anticoagulants, it is necessary to assess the likelihood of bleeding. Below are the adverse reactions that occurred during treatment in patients and were recorded by investigators in three phase 3 studies, classified by organ system (Meddra) and frequency. From the circulatory and lymphatic system : common (≥1%–≤10%) - anemia; uncommon (≥0.1%–≤1%) - thrombocythemia. From the cardiovascular system : common (≥1%–≤10%) — post-procedural hemorrhages (including postoperative anemia and bleeding from the wound; uncommon (≥0.1%–≤1%) — tachycardia, hypotension (including hypotension during procedures), hemorrhage (including hematomas and rare cases of muscle hemorrhage), gastrointestinal hemorrhage (including hemetomesis, bleeding gums, rectal bleeding, hematuria, bloody discharge from the genital tract, nosebleeds).Gastrointestinal tract: common (≥ 1%–≤10%) — nausea; uncommon (≥0.1%–≤1%) — constipation, diarrhea, abdominal pain, stomach discomfort, dyspeptic symptoms, dry mouth, vomiting. Systemic disorders and conditions associated with the site of drug use : uncommon (≥0.1%–≤1%) - localized or peripheral edema, fatigue, weakness, asthenia, fever Hepatobiliary disorders : uncommon (≥0.01%–≤0.1%) - liver dysfunction. Immune system disorders : less common (≥0.01%–≤0.1%) - allergic dermatitis. From the nervous system : uncommon (≥0.1%–≤1%) - dizziness, headache, syncope. From the musculoskeletal system : uncommon (≥0.1%–≤1%) - pain in the extremities. From the skin and subcutaneous tissue : uncommon (≥0.1%–≤1%) - itching (including cases of generalized itching), skin rashes, urticaria (including cases of generalized urticaria). From the kidneys and urinary tract : uncommon (≥0.1%–≤1%) - renal failure (increased blood levels of creatinine, urea). Laboratory data : common (≥1%–≤10%) - increased LDH levels, increased ALT and AST levels; uncommon (≥0.1%–≤1%) - increased levels of lipase, amylase, blood bilirubin, alkaline phosphatase levels; less common (≥0.01%–≤0.1%) - increased levels of conjugated bilirubin (with or without a concomitant increase in liver transaminases).

Special instructions for the use of Xarelto

Patients with renal failure Rivaroxaban should be used with caution when treating patients with moderate renal failure (creatinine clearance 30–49 ml/min) who are undergoing concomitant therapy with drugs that lead to increased plasma concentrations of rivaroxaban. In patients with severe renal impairment, plasma concentrations of rivaroxaban may be significantly increased, which may lead to an increased risk of bleeding. Therefore, given the limited clinical data in patients with renal failure (creatinine clearance ≤30–15 ml/min), rivaroxaban should be used with caution in such patients. There are no clinical data on the use of the drug in patients with severe renal failure (creatinine clearance ≤15 ml/min). Taking this into account, the use of rivaroxaban in such patients is not recommended. Patients with severe renal impairment or an increased risk of bleeding and patients receiving concomitant systemic therapy with azole antifungals or HIV protease inhibitors should be closely monitored after initiation of treatment to ensure timely detection of bleeding complications. Such monitoring may include regular physical examination of the patient, close monitoring of surgical wound drainage, and periodic determination of hemoglobin levels. Hip fracture surgery Rivaroxaban has not been studied in clinical trials in patients undergoing hip fracture surgery. Risk of Bleeding Antithrombotics, including rivaroxaban, should be used with caution in patients with an increased risk of bleeding, including those who have:

• congenital or acquired diseases leading to bleeding;
• uncontrolled hypertension (arterial hypertension) severe;
• peptic ulcer of the gastrointestinal tract in the acute stage;
• recent peptic ulcer of the gastrointestinal tract;
• vascular retinopathy;
• recent intracranial or intracerebral hemorrhage;
• intraspinal or intracerebral vascular pathology;
• recent neurosurgical (surgery on the brain and spinal cord) or ophthalmological intervention.

Caution should be exercised when prescribing rivaroxaban to patients receiving medications that affect hemostasis, such as NSAIDs, platelet aggregation inhibitors, or other antithrombotics (see INTERACTIONS). If there is an unexplained decrease in hemoglobin or blood pressure, bleeding must be excluded. Spinal (epidural/spinal) anesthesia When performing a spinal (epidural/spinal) puncture in patients receiving antithrombotic agents to prevent thromboembolic complications, there is a risk of developing an epidural or spinal hematoma, which can lead to prolonged paralysis. The risk of these complications increases with the use of indwelling epidural catheters or the concomitant use of medications that affect hemostasis. Trauma from an epidural or spinal tap or repeat puncture may also increase the risk of complications. Patients should be monitored for signs or symptoms of neurological impairment (eg, numbness or weakness of the legs, bowel or bladder dysfunction). If neurological symptoms are detected, urgent diagnosis and appropriate therapy are necessary. Clinicians should weigh the potential benefits and risks before performing spinal surgery in patients receiving anticoagulants or who are preparing to receive anticoagulants to prevent thrombosis. The epidural catheter is removed no earlier than 18 hours after the last dose of rivaroxaban. Rivaroxaban should not be administered earlier than 6 hours after removal of the epidural catheter. In case of traumatic puncture, the prescription of rivaroxaban should be postponed for 24 hours. Women of reproductive age There are no data on the use of rivaroxaban in the treatment of women during pregnancy. Experiments on rats and rabbits showed pronounced toxicity of rivaroxaban for the maternal body and changes in the placenta associated with the pharmacological action of the drug (for example, hemorrhagic complications in the form of hemorrhages). The primary teratogenic effect of the drug has not been identified. Data obtained from studies conducted in experimental animals showed that rivaroxaban crosses the placenta. In this regard, rivaroxaban is contraindicated for women during pregnancy. Women of reproductive age should use effective methods of contraception during treatment with rivaroxaban. There are no data on the use of rivaroxaban in women during breastfeeding. Studies in rats have shown that rivaroxaban is excreted in breast milk. Taking this into account, rivaroxaban can only be used after breastfeeding has stopped. There are no clinical data regarding the use of the drug in children. The ability to influence reaction speed when driving vehicles or working with other mechanisms. There are no reports of the effect of rivaroxaban on the ability to drive or operate machines.

Contraindications

The drug is contraindicated for pregnant heart patients

This product has a number of contraindications that you should pay attention to during treatment:

1. Due to the fact that taking Xarelto for cardiac arrhythmias can cause bleeding, this drug is not used after recent surgery, childbirth, or intracranial hemorrhage.
2. The product is also not recommended for those patients who have not reached the age of majority, pregnant and lactating women.
3. Xarelto is contraindicated in patients suffering from decompensated cirrhosis.
4. If the patient has low creatinine clearance (up to 15 ml/min), the drug is not prescribed.
5. Persons with severe pathologies of the liver and kidneys are usually prescribed one of the Xarelto analogue drugs.
6. Lactose intolerance and vascular aneurysm are also absolute contraindications to taking the drug.

In addition, there are relative contraindications in which the drug is prescribed with caution. We are talking about the following diseases:

• pathologies of cerebral vessels;
• severe stages of hypertension;
• peptic ulcer;
• bronchiectasis.

Xarelto drug interactions

Pharmacokinetic interactions Rivaroxaban is eliminated mainly through hepatic metabolism mediated by the cytochrome P450 system (CYP 3A4, CYP 2J2) and renal excretion of unchanged drug with the participation of the P-gp/BCRP transport systems. Inhibition of cytochrome isoenzymes Rivaroxaban does not inhibit the CYP 3A4 isoenzyme and other important cytochrome isoforms. Induction of cytochrome isoenzymes Rivaroxaban does not induce the CYP 3A4 isoenzyme and other important cytochrome isoforms. Compounds that affect the pharmacokinetics of rivaroxaban: Concomitant use of rivaroxaban and strong inhibitors of CYP 3A4 and P-gp may result in decreased renal and hepatic clearance and thus significantly increase the systemic exposure of the drug. The combined use of rivaroxaban and the azole antifungal drug ketoconazole (400 mg once daily), which is a strong inhibitor of CYP 3A4 and P-gp, led to a 2.6-fold increase in the average steady-state AUC of rivaroxaban and a 1.7-fold increase in the average Cmax of rivaroxaban , which is accompanied by a significant increase in the pharmacodynamic effects of the drug. The combined administration of rivaroxaban and the HIV protease inhibitor ritonavir (600 mg 2 times a day), which is a strong inhibitor of CYP 3A4 and P-gp, led to a 2.5-fold increase in the average steady-state AUC of rivaroxaban and a 1.6-fold increase in the average Cmax of rivaroxaban. which is accompanied by a significant increase in the pharmacodynamic effects of the drug. Therefore, rivaroxaban should be used with caution when treating patients concomitantly receiving systemic azole antifungals or HIV protease inhibitors. Clarithromycin (500 mg twice daily), a potent CYP3A4 inhibitor and moderate-intensity P-gp inhibitor, caused a 1.5-fold increase in mean AUC values ​​and a 1.4-fold increase in Cmax of rivaroxaban. This increase in AUC and increase in Cmax is within the normal range and is considered clinically irrelevant. Erythromycin (500 mg 3 times daily), a moderate inhibitor of CYP 3A4 and P-gp, caused a 1.3-fold increase in the mean steady-state AUC and Cmax values ​​of rivaroxaban. This increase in AUC and increase in Cmax is within the normal range and is considered clinically irrelevant. Co-administration of rivaroxaban and rifampicin, a potent inducer of CYP 3A4 and P-gp, resulted in an approximately 50% decrease in the mean AUC of rivaroxaban and a parallel decrease in its pharmacodynamic effects. Concomitant use of rivaroxaban with other strong CYP3A4 inducers (e.g. phenytoin, carbamazepine, phenobarbital or St. John's wort) may also result in decreased plasma concentrations of rivaroxaban. A decrease in rivaroxaban plasma concentrations is considered clinically irrelevant. Pharmacodynamic interactions After the combined administration of enoxaparin (single dose 40 mg) and rivaroxaban (single dose 10 mg), an additive effect was observed regarding the activity of antifactor Xa, which was not accompanied by additional effects regarding blood coagulation parameters (prothrombin time (PT), aPTT). Enoxaparin did not change the pharmacokinetics of rivaroxaban (see PHARMACOLOGICAL PROPERTIES). There was no pharmacokinetic interaction between rivaroxaban and clopidogrel (loading dose of 300 mg followed by a maintenance dose of 75 mg), but in a subgroup of patients there was a relevant increase in bleeding time, which did not correlate with platelet aggregation and P-selectin or GPIIb/IIIa receptor levels. No clinically relevant prolongation of bleeding time was observed after coadministration of rivaroxaban and 500 mg naproxen. However, a more pronounced pharmacodynamic response is possible in some individuals. Interaction with food: Rivaroxaban 10 mg can be taken with food or alone. Effect on laboratory tests: the effect on blood coagulation parameters (PT, APTT, Hep-Test) is as expected given the mechanism of action of rivaroxaban.

What to do to naturally thin the blood

No pills will help you if you don’t move enough. Movement is a major part of the prevention of blood clots and various venous diseases. Only physical activity makes blood and lymph circulate faster, dilates blood vessels, and increases the flow of nutrients to the cells of the body. No pills will help you if you don’t drink enough water or don’t drink enough water. Proper drinking regime is the basis of metabolism and body function. Only water is the only and irreplaceable solvent in nature. There is no other substance of similar effect for a living organism. You can chemically force the molecules of a substance not to stick together (temporarily), but not to dissolve it. It is necessary to eliminate bad habits and try to eat right. Smoking constricts blood vessels and slows down metabolic processes. As for proper nutrition, one of the steps towards this is eliminating or reducing harmful foods. You can only have a hamburger for lunch once a month or drink beer and chips on the weekend, but regular consumption of such products will lead to disastrous consequences. The main bad dietary habits are excessive consumption of alcohol, coffee, salt, and sugar. It’s easy for doctors to simply prohibit something, realizing that most likely no one will do it. I am not a doctor. I understand that complete restriction in everything will not only impoverish and complicate life and relationships, but can lead to a dangerous breakdown, which will have an even more negative impact on health. But if you at least know what is harmful and what is not and try to reduce what is harmful, then there will already be benefits. It must be remembered that blood thickening is often caused by taking various medications, such as diuretics (diuretics). Therefore, if you are taking any medications, you should know whether they have such an effect and compensate for it with other methods and preventive measures. Psycho-emotional states and uncontrolled releases of stress hormones also slow down metabolism, constrict blood vessels, which also leads to blood thickening

Therefore, when exposed to numerous stresses, pay attention to natural sedatives or teas - this will also be useful and not only for problems with blood thickening.

As you can see, it's not all that complicated. These are the basic principles of a healthy lifestyle. At least for me. And the most interesting thing is that these simple rules are not only the fight against blood thickening and thrombosis, but also the beginning of the fight against any disease.

But let's move on to the means that can replace Xarelto and use it to avoid blood thickening and viscosity and thereby reduce the risk of blood clots.

Xarelto overdose, symptoms and treatment

An overdose of rivaroxaban can lead to hemorrhagic complications due to its pharmacodynamic properties. There is no specific antidote. In case of overdose, activated charcoal may be used to reduce the absorption of rivaroxaban. The use of activated carbon within 8 hours after an overdose can reduce the absorption of rivaroxaban. Given the high binding to plasma proteins, it can be expected that rivaroxaban is not excreted from the body by dialysis. If bleeding occurs, the following measures can be taken to eliminate it: delay the next dose of rivaroxaban or stop treatment depending on the situation (the half-life of rivaroxaban is about 5-13 hours); Provide appropriate symptomatic treatment (eg, consider mechanical compression for severe bleeding, surgical intervention if necessary, fluid and hemodynamic support, transfusion of blood or blood components. If the above measures do not resolve the bleeding, there may be one of the following procoagulants is prescribed:

• activated prothrombin complex concentrate;
• prothrombin complex concentrate;
• recombinant factor VIIa (rf VIIa).

However, to date there is no experience with the use of these drugs in overdose of rivaroxaban. Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of rivaroxaban. There is no scientific basis for or experience with the use of systemic hemostatic agents (e.g. desmopressin, aprotinin, tranexamic acid, aminocaproic acid) to reverse rivaroxaban overdose.