Drug Monograph
Full clinical overview, indications, dosage references & safety notes.
Drug class: Factor Xa inhibitor (oral anticoagulant)
Main indication: Prevention and treatment of thromboembolic disease
Available forms2 forms · 5 strengths documentedShow all ↓
Oral · solid
Tablet 2.5 mg XareltoTablet 10 mgTablet 15 mgTablet 20 mg
Oral · liquid
Reconstituted suspension 1 mg/mL
Overview
Rivaroxaban (Xarelto®) is an oral anticoagulant used in dogs and cats for the prevention and treatment of thromboembolic disease. It provides a prompt and predictable anticoagulant effect and may be an alternative to traditional anticoagulant therapies in selected patients.
In dogs, rivaroxaban has been used for thromboembolic disease and may be preferred over unfractionated heparin because of its reliable pharmacokinetics and ease of oral administration. Direct factor Xa inhibitors may also be considered in cats because of their favorable pharmacokinetic and safety profiles.
Mechanism of Action (MOA): Rivaroxaban directly inhibits activated clotting factor Xa (FXa) and prothrombinase activity. Its anticoagulant effect does not require a cofactor and it indirectly inhibits thrombin-induced platelet aggregation.
Indications
Rivaroxaban is used in dogs and cats for the prevention and treatment of thromboembolic disease.
- Antithrombotic therapy: Used in patients considered at high risk for thrombus formation – including dogs with immune-mediated hemolytic anemia, protein-losing nephropathy or heartworm disease, and cats with hypertrophic cardiomyopathy.
- Arterial thromboembolism: Used for the treatment and prevention of arterial thromboembolism in dogs and cats.
Dosage (Reference)
Dog
Rivaroxaban has been used as an antithrombotic agent in dogs for the prevention and treatment of thromboembolic disease.
| Clinical use | Route | Dose | Frequency | Notes |
|---|---|---|---|---|
| Antithrombotic therapy | PO | 0.5-1 mg/kg | q24h | Published extra-label dosage range. |
| Antithrombotic therapy – assessment-based alternative | PO | 0.5-1 mg/kg | q12h | Based on in vivo coagulation assessments, administration every 12 hours may be more appropriate |
| Antithrombotic therapy – higher published range | PO | 1-2 mg/kg | q24h | Higher of the two published canine ranges; described as proposed. |
Important dosing notes (dogs):
• After a 1 mg/kg oral dose in healthy dogs the drug is rapidly absorbed with 60 to 85% bioavailability, peak concentrations at about 30 minutes and an elimination half-life of about 1 hour; peak anti-factor Xa activity occurs 2 to 4 hours after administration.
• Canine factor Xa has a lower in-vitro affinity for rivaroxaban than human factor Xa; a concentration of 0.4 micrograms/mL was required to inhibit 50% of thrombin generation.
• In reported canine use the average dose was 0.89 mg/kg once daily and was well tolerated, although the therapeutic benefit compared with traditional anticoagulants is not known; 0.5 mg/kg PO q24h has also been described for chronic therapy.
• After a 1 mg/kg oral dose in healthy dogs the drug is rapidly absorbed with 60 to 85% bioavailability, peak concentrations at about 30 minutes and an elimination half-life of about 1 hour; peak anti-factor Xa activity occurs 2 to 4 hours after administration.
• Canine factor Xa has a lower in-vitro affinity for rivaroxaban than human factor Xa; a concentration of 0.4 micrograms/mL was required to inhibit 50% of thrombin generation.
• In reported canine use the average dose was 0.89 mg/kg once daily and was well tolerated, although the therapeutic benefit compared with traditional anticoagulants is not known; 0.5 mg/kg PO q24h has also been described for chronic therapy.
Cat
Rivaroxaban has been used as an antithrombotic agent in cats either alone or in combination with clopidogrel.
| Clinical use | Route | Dose | Frequency | Notes |
|---|---|---|---|---|
| Antithrombotic therapy | PO | 1.25 mg/cat | q24h | Provided less than 12 hours of anti-FXa activity in healthy cats. |
| Antithrombotic therapy (combination protocol) | PO | 2.5 mg/cat | q24h | Administered with clopidogrel 18.75 mg/cat PO q24h. |
| Antithrombotic therapy – weight-based protocol | PO | 0.5-1 mg/kg | q12-24h | Weight-based feline regimen. Extra-label – there is no veterinary-labeled product. |
| Antithrombotic therapy – fixed per-cat protocol | PO | 2.5-5 mg/cat | q24h | The 2.5-5 mg amounts are fixed per-cat doses; human tablet strengths are 2.5, 10, 15 and 20 mg. Extra-label – there is no veterinary-labeled product. |
Important dosing notes (cats):
• The fixed feline protocols are expressed as mg/cat, not mg/kg; the weight-based feline regimen is expressed as mg/kg.
• After a single 2.5 mg per cat oral dose in healthy cats, peak concentrations are reached at about 2.5 hours and the elimination half-life is about 7.5 hours; peak anti-factor Xa activity occurs 2 to 3 hours after administration.
• In cats that had recovered from cardiogenic arterial thromboembolism, rivaroxaban 2.5 mg per cat orally was given as sole anticoagulant therapy for up to 2 years; either rivaroxaban or clopidogrel may be used as a single agent to delay recurrence.
• The fixed feline protocols are expressed as mg/cat, not mg/kg; the weight-based feline regimen is expressed as mg/kg.
• After a single 2.5 mg per cat oral dose in healthy cats, peak concentrations are reached at about 2.5 hours and the elimination half-life is about 7.5 hours; peak anti-factor Xa activity occurs 2 to 3 hours after administration.
• In cats that had recovered from cardiogenic arterial thromboembolism, rivaroxaban 2.5 mg per cat orally was given as sole anticoagulant therapy for up to 2 years; either rivaroxaban or clopidogrel may be used as a single agent to delay recurrence.
Warnings & Precautions
Rivaroxaban should not be used in patients with active bleeding. In other patients, recommendations range from avoiding anticoagulants when the bleeding risk is high to cautious use in those with minor bleeding, bleeding disorders, or coagulopathies. Use cautiously in patients with significant renal or hepatic dysfunction.
- Uncontrolled bleeding: Contraindicated in patients that are actively bleeding or have uncontrolled pathologic bleeding.
- Hypersensitivity: Contraindicated in patients with known hypersensitivity to rivaroxaban.
- Hepatic disease: Guidance in hepatic disease is inconsistent. Avoid rivaroxaban in severe hepatic disease or hepatic disease associated with coagulopathy. In less severe hepatic impairment, recommendations range from cautious use to complete avoidance. Human labeling also advises avoiding use in moderate or severe hepatic impairment.
- Renal impairment: Guidance differs in significant renal dysfunction: one reference advises avoiding use, while another advises caution. A lower dose is recommended in patients with moderate renal impairment.
- Thrombocytopenia: Use anticoagulant therapy cautiously when the platelet count is below 40,000 platelets/L.
- Neuraxial anesthesia and spinal procedures: Patients undergoing neuraxial anesthesia or spinal puncture are at increased risk for epidural or spinal hematoma.
- Discontinuation: Thrombotic events have been reported following discontinuation in humans. Gradual tapering before discontinuation has been suggested.
- Perioperative use: Discontinue rivaroxaban at least 24 hours before surgery or other high-risk procedures and resume only after hemostasis has been established.
- Pregnancy and lactation: Safety has not been established in animals. Use only when maternal benefits outweigh potential risks to offspring.
- Lactation: Rivaroxaban is excreted into the milk of rats; use it with caution in lactating animals.
- Reproductive findings: Rivaroxaban crosses the placenta in rats and rabbits; animal studies reported maternal hemorrhage and death, decreased fetal weights, postimplantation pregnancy loss, increased resorption and fetal death.
- Rebound risk after discontinuation: In humans with atrial fibrillation, a rebound risk of stroke has been reported after discontinuation; alternative anticoagulant cover may be needed during that period, and product guidance should be followed when transitioning to or from another anticoagulant.
- Hepatic monitoring: Closer monitoring of dogs receiving factor Xa inhibitors has been advocated. If hepatotoxicity is suspected and no other cause is identified, weigh the risks and benefits and consider discontinuing rivaroxaban or changing anticoagulant.
- Monitoring: Routine coagulation monitoring is not required, but prothrombin time and thromboelastography can be considered, together with a complete blood count with platelets, renal and hepatic function, clinical efficacy, and observation for signs of bleeding such as lethargy, dyspnoea or collapse.
Drug Interactions
In humans rivaroxaban is a substrate of CYP3A4 and P-glycoprotein; specific interactions have not been identified in animals. Concurrent medications may either increase the risk of bleeding or reduce rivaroxaban’s anticoagulant effect and increase the risk of thrombosis, depending on the mechanism involved.
- Azole antifungals (e.g., itraconazole, ketoconazole, voriconazole): May substantially increase rivaroxaban exposure and the risk of bleeding; one reference instead reports that cytochrome P450 and P-glycoprotein inhibitors can reduce its efficacy.
- Other anticoagulants (e.g., heparins, warfarin): May increase the risk of bleeding.
- Antiplatelet agents (e.g., aspirin, clopidogrel): May increase the risk of bleeding.
- CYP3A4 inducers (e.g., rifampin, phenobarbital): May increase rivaroxaban metabolism and increase the risk of thrombotic events.
- Fluoxetine: May increase the risk of bleeding.
- Macrolide antibiotics (e.g., clarithromycin, erythromycin): May substantially increase rivaroxaban exposure and increase the risk of bleeding.
- NSAIDs (e.g., carprofen, deracoxib, firocoxib, meloxicam, robenacoxib): May increase the risk of bleeding.
- Weighing an interaction: Unless stated otherwise, concurrent use is not necessarily contraindicated; weigh the potential risks and carry out additional monitoring where appropriate.
- Laboratory interference: Rivaroxaban may cause a falsely decreased factor VIII:C level through assay interference, and falsely elevated INR values have been reported.
Side Effects & Overdose
Side Effects
Rivaroxaban is generally well tolerated in dogs and cats, although clinical experience remains limited.
- Bleeding: The most common adverse effect in humans; in veterinary patients minor bleeding has been reported, and excessive bleeding is the principal concern. Minor bleeding episodes may occur.
- Epistaxis: Reported in treated animals.
- Hematemesis: Reported in treated animals.
- Hematuria: Reported in treated animals.
- Hematochezia: Reported in treated animals.
- Anemia: May occur secondary to bleeding.
- Vomiting: Reported in dogs and cats receiving rivaroxaban.
- Gastrointestinal effects: Nausea, vomiting, and diarrhea have been reported in humans.
- Hepatic effects: Increased liver enzyme activity has been reported in humans.
- Dermatologic effects: Pruritus and rash have been reported in humans but are uncommon.
Overdose
Overdosage is expected to increase the risk of hemorrhage. Treatment is primarily supportive and guided by clinical signs.
- Hemorrhage: Increased risk of bleeding is the primary concern following overdose, although overdoses in humans have not been universally associated with significant bleeding.
- Monitoring: PT, INR, aPTT, thromboelastography, and thrombin generation testing may be useful when available.
- Recent ingestion: Gastrointestinal decontamination may be considered following recent oral exposure.
- Supportive care: Treatment is supportive and based on clinical signs.
- Blood products: Hemorrhagic complications may be treated with appropriate blood products.
- Dialysis: Rivaroxaban is not dialyzable.
- Factor Xa antidote: A specific factor Xa antidote, andexanet alfa, is available for human use and may be considered, although it is expensive and untested in animals; one reference states that no reversal agent is available.
- Poison control: For a known or suspected overdose, consult a 24-hour poison control service that provides veterinary-specific advice.
Key Notes
Practical clinical points for the use of rivaroxaban in dogs and cats:
- Predictable anticoagulation: Provides a prompt and predictable anticoagulant effect following oral administration.
- No cofactor required: Unlike heparins, its anticoagulant activity does not require a cofactor.
- Oral administration: Oral dosing may offer a practical alternative to injectable anticoagulants in selected patients.
- Cost considerations: Treatment cost may be a limiting factor in some patients.
- Duration of effect: Its shorter half-life than clopidogrel may be an advantage when treatment must be stopped because of a bleeding complication or an invasive procedure.
- Human pharmacokinetics: In humans, rivaroxaban is 95% bound to albumin, and the drug and its metabolites are eliminated renally with an elimination half-life of 5 to 9 hours.
- Comparative evidence: Rivaroxaban has not been proven to be either safer or more effective than other available anticoagulants. In one feline trial, arterial thromboembolism recurred in 10 of 26 cats receiving rivaroxaban and 7 of 19 receiving clopidogrel.
- Administration: Give at the same time each day, with or without food. Tablets may be crushed and mixed with food immediately before dosing, or crushed and suspended in 50 mL of water for administration through a nasogastric or gastric feeding tube; preparations mixed in water or applesauce are stable for up to 4 hours.
- Storage: Store at room temperature in a tightly sealed container, protected from light, and out of reach of children and animals.
- Effect on coagulation tests: If coagulation tests are performed, rivaroxaban prolongs the activated partial thromboplastin time; a rivaroxaban-specific anti-factor Xa assay can be used for monitoring in veterinary patients.
- Regulatory status: There is no veterinary-labeled rivaroxaban product; all use in dogs and cats is extra-label use of a human medicine.
- Other drugs in this class: Apixaban and edoxaban share the same mechanism of action, but have received considerably less attention in veterinary medicine than rivaroxaban.
- Client information: Advise owners that the animal may bruise or bleed more easily and to make contact immediately if they see bleeding or suspect internal bleeding; a missed dose should be given as soon as it is remembered and the regular schedule then resumed; and the medicine should not be stopped without veterinary advice.
- Handling: Normal handling precautions apply.
