Apixaban

The dosage of apixaban varies significantly based on the condition being treated. It is critical to adhere to the specific regimen prescribed by your healthcare provider.

• Nonvalvular Atrial Fibrillation (Stroke Prevention): The standard dose is 5 mg taken orally twice daily. However, a reduced dose of 2.5 mg twice daily is required if a patient meets at least two of the following 'ABC' criteria: Age ≥ 80 years, Body weight ≤ 60 kg, or Serum creatinine ≥ 1.5 mg/dL.
• Treatment of DVT and PE: The initial 'loading' dose is 10 mg taken orally twice daily for the first 7 days. Following this first week, the dose is reduced to 5 mg twice daily for the remainder of the treatment course (typically 3 to 6 months).
• Reduction in the Risk of Recurrent DVT and PE: For long-term prevention after the initial treatment, the dose is 2.5 mg taken orally twice daily.
• DVT Prophylaxis Following Hip Replacement: 2.5 mg twice daily for 35 days. The first dose is typically given 12 to 24 hours after surgery.
• DVT Prophylaxis Following Knee Replacement: 2.5 mg twice daily for 12 days. The first dose is typically given 12 to 24 hours after surgery.

As of 2026, the safety and effectiveness of apixaban in pediatric patients (under the age of 18) have not been fully established for the primary indications of stroke prevention or DVT treatment. While clinical trials (such as the SAXOPHONE study) have investigated DOACs in children for specific conditions like congenital heart disease, apixaban is currently not FDA-approved for pediatric use. Parents should consult a pediatric hematologist for anticoagulation options in children.

Renal Impairment

Apixaban is partially cleared by the kidneys. For patients with mild to moderate renal impairment, no dose adjustment is generally necessary unless they meet the 'ABC' criteria for Atrial Fibrillation. For patients with End-Stage Renal Disease (ESRD) on hemodialysis, the recommended dose is 5 mg twice daily, though 2.5 mg twice daily is used if the patient is ≥ 80 years old or weighs ≤ 60 kg.

Hepatic Impairment

No dose adjustment is required for patients with mild hepatic impairment (Child-Pugh class A). For moderate impairment (Child-Pugh B), apixaban should be used with caution as there is limited clinical data. It is not recommended for patients with severe hepatic impairment (Child-Pugh C) due to the increased risk of bleeding associated with coagulopathy (clotting disorders) related to liver failure.

Elderly Patients

Age alone does not require a dose adjustment unless the patient is part of the Atrial Fibrillation population and meets the criteria for the 2.5 mg dose. However, elderly patients are at higher risk for falls and bleeding, requiring closer clinical monitoring.

• Consistency: Take apixaban at the same time every morning and evening (approximately 12 hours apart) to maintain steady levels in the blood.
• Food: You may take the tablets with or without food.
• Swallowing: If you cannot swallow the tablet whole, it can be crushed and mixed with water, apple juice, or applesauce. The mixture should be consumed immediately.
• Storage: Store at room temperature (20°C to 25°C / 68°F to 77°F) in a dry place.

If you miss a dose of apixaban, take it as soon as you remember on the same day. Then, take your next dose at the regular scheduled time. Do not double the dose to catch up for a missed one. If it is almost time for your next dose, skip the missed dose and resume your normal schedule.

An overdose of apixaban increases the risk of life-threatening bleeding. Symptoms of overdose may include unusual bruising, red or black stools, pink or brown urine, or coughing up blood. In the event of an overdose, seek emergency medical attention immediately. A specific reversal agent called Andexanet alfa (Andexxy) is available in hospital settings to neutralize the effects of apixaban in cases of life-threatening bleeding.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop taking apixaban without medical guidance, as this significantly increases your risk of a stroke or blood clot.

The most frequent side effects of apixaban are related to bleeding. Because the medication thins the blood, minor injuries may bleed more than usual.

• Easy Bruising (Ecchymosis): Small bumps or minor contact may result in larger-than-normal bruises. These typically resolve on their own.
• Minor Bleeding: This includes occasional nosebleeds (epistaxis) or bleeding from the gums after brushing teeth.
• Nausea: Some patients report mild stomach upset shortly after starting the medication, though this often diminishes as the body adjusts.

• Anemia: Chronic, microscopic bleeding (often in the GI tract) can lead to a drop in red blood cell counts, causing fatigue, pale skin, and shortness of breath.
• Heavy Menstrual Periods (Menorrhagia): Women of childbearing age may experience significantly heavier or longer menstrual cycles.
• Gastrointestinal Hemorrhage: This may manifest as bright red blood in the stool or 'coffee-ground' vomit.
• Post-Surgical Bleeding: Increased drainage or bleeding from a surgical incision site.

• Hypersensitivity Reactions: This includes skin rash, hives, or severe allergic reactions (anaphylaxis).
• Intracranial Hemorrhage: Bleeding inside the brain. While rare (and occurring less frequently with apixaban than with warfarin), this is a life-threatening emergency.
• Syncope: Fainting or feeling lightheaded, often associated with a drop in blood pressure or blood loss.

> Warning: Stop taking Apixaban and call your doctor or emergency services immediately if you experience any of the following:

1. 1Signs of Internal Bleeding: Red, pink, or brown urine; bright red or black, tarry stools; coughing up blood or vomit that looks like coffee grounds.
2. 2Signs of a Stroke: Sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, or vision changes. (Note: This may occur if the drug is stopped prematurely).
3. 3Spinal/Epidural Hematoma Symptoms: Numbness, muscle weakness, or tingling in the legs and back, especially if you have recently had a spinal tap or epidural anesthesia.
4. 4Severe Allergic Reaction: Swelling of the face, lips, tongue, or throat; difficulty breathing; or sudden wheezing.
5. 5Uncontrolled Bleeding: Any bleeding that will not stop after applying pressure for 10-15 minutes.

Apixaban is generally well-tolerated for long-term use (years). Unlike warfarin, it does not appear to increase the risk of osteoporosis or significant vascular calcification. The primary long-term risk remains the cumulative risk of a major bleeding event. Periodic blood tests to monitor kidney and liver function are required to ensure the drug continues to be cleared safely from the body.

The FDA has issued two critical 'Black Box Warnings' for apixaban:

1. 1Premature Discontinuation Increases Risk of Thrombotic Events: Stopping apixaban before your doctor tells you to increases the risk of having a stroke or forming a blood clot. When discontinuing for reasons other than pathological bleeding or completion of a course of therapy, your doctor should consider coverage with another anticoagulant.
2. 2Spinal/Epidural Hematoma: Patients taking apixaban who undergo spinal puncture or epidural anesthesia are at risk of developing a blood clot (hematoma) in the spine. This can cause long-term or permanent paralysis. The risk is higher if the patient has an indwelling epidural catheter, takes other NSAIDs, or has a history of traumatic spinal procedures.

Report any unusual symptoms or persistent side effects to your healthcare provider immediately.

Apixaban is a high-alert medication because it significantly alters the blood's ability to clot. Patients must be aware that they will bleed more easily and for longer periods. It is essential to inform all healthcare providers, including dentists and surgeons, that you are taking apixaban before any procedure is scheduled.

1. Risk of Stroke After Stopping Apixaban: There is an increased risk of stroke and systemic embolism if apixaban is discontinued prematurely. If apixaban must be stopped for a reason other than bleeding, your healthcare provider may need to start another blood thinner during the gap.

2. Spinal/Epidural Hematoma: For patients receiving neuraxial anesthesia (spinal or epidural) or undergoing spinal puncture, apixaban increases the risk of a spinal hematoma. This is a medical emergency that can lead to permanent paralysis. Monitoring for neurological impairment (e.g., numbness or weakness in the legs) is mandatory.

• Bleeding Risk: Apixaban increases the risk of serious, potentially fatal bleeding. Use with caution in patients with conditions that increase bleeding risk, such as active GI ulcers, recent brain surgery, or bleeding disorders.
• Prosthetic Heart Valves: Apixaban is not recommended for patients with prosthetic (mechanical) heart valves. Studies have shown that DOACs may not provide adequate protection against clots on mechanical valves compared to warfarin.
• Triple Positive Antiphospholipid Syndrome (APS): Patients with APS (especially those who are triple positive for lupus anticoagulant, anticardiolipin, and anti-beta 2-glycoprotein I antibodies) should generally not use apixaban, as it may increase the risk of recurrent thrombotic events compared to warfarin.
• Surgery and Procedures: Apixaban should typically be stopped 24 to 48 hours before elective surgery, depending on the bleeding risk of the procedure and the patient's kidney function. Do not stop the medication without specific instructions from your surgeon.

Unlike warfarin, apixaban does not require routine PT/INR monitoring. However, the following should be monitored:

• Renal Function (Creatinine/CrCl): At least once a year, or more frequently in patients with baseline kidney disease, as dose adjustments may be needed.
• Hepatic Function: Baseline liver enzymes should be checked.
• Complete Blood Count (CBC): To check for signs of occult (hidden) bleeding (e.g., dropping hemoglobin).
• Anti-Xa Levels: In emergency situations (like trauma or urgent surgery), a specialized 'Apixaban-calibrated Anti-Xa assay' may be used to determine the amount of drug in the system.

Apixaban does not typically affect the ability to drive or operate machinery. However, if you experience dizziness or fainting due to blood loss or anemia, avoid these activities until you have consulted your doctor.

Moderate alcohol consumption is generally acceptable, but excessive alcohol (binge drinking) should be avoided. Alcohol can irritate the stomach lining, increasing the risk of gastrointestinal bleeding while on a blood thinner. Furthermore, heavy alcohol use can lead to falls, which are more dangerous while taking apixaban.

Never stop taking apixaban abruptly. If you must stop the medication (e.g., for a colonoscopy), follow your doctor's exact 'bridge' instructions. Stopping even a few doses can leave you unprotected against a stroke or pulmonary embolism.

> Important: Discuss all your medical conditions, especially any history of bleeding or kidney disease, with your healthcare provider before starting Apixaban.

Certain medications significantly increase the levels of apixaban in the blood, leading to an unacceptable risk of hemorrhage. These include strong dual inhibitors of CYP3A4 and P-glycoprotein (P-gp):

• Ketoconazole and Itraconazole: Systemic antifungal medications.
• Ritonavir: An antiviral used in the treatment of HIV.
• Clarithromycin: Though interactions vary, strong macrolide inhibitors can increase apixaban exposure.

Clinical Consequence: These drugs block the primary enzymes and transporters responsible for breaking down and removing apixaban, potentially doubling the drug's concentration in the blood.

• Strong Dual Inducers of CYP3A4 and P-gp: Medications like Rifampin, Carbamazepine, Phenytoin, and Phenobarbital can decrease apixaban levels by approximately 50%. This makes the medication less effective and increases the risk of a stroke or blood clot.
• Other Anticoagulants: Using apixaban with heparin, warfarin, or other DOACs (like rivaroxaban) is generally avoided except during a transition period, as it massively increases bleeding risk.
• Antiplatelet Agents: Using apixaban with Aspirin, Clopidogrel (Plavix), or Prasugrel increases the risk of major bleeding. This 'dual therapy' is sometimes necessary after a heart stent, but it must be managed carefully by a cardiologist.

• NSAIDs (Non-Steroidal Anti-inflammatory Drugs): Common over-the-counter drugs like Ibuprofen (Advil/Motrin) and Naproxen (Aleve) interfere with platelet function and can irritate the stomach lining. Taking these with apixaban significantly increases the risk of GI bleeds. Use Acetaminophen (Tylenol) for pain relief instead, unless directed otherwise.
• SSRIs and SNRIs: Antidepressants like Fluoxetine, Sertraline, or Venlafaxine can slightly increase bleeding risk by affecting platelet serotonin uptake.

• Grapefruit and Grapefruit Juice: Unlike some other medications, grapefruit does not have a clinically significant effect on apixaban levels at normal consumption amounts.
• General Diet: There are no 'Vitamin K' restrictions with apixaban. You can eat green leafy vegetables (spinach, kale) without worrying about interfering with the drug's efficacy.

• St. John’s Wort: This herbal supplement is a strong inducer of CYP3A4 and P-gp. It can significantly lower apixaban levels, increasing the risk of a stroke. Do not take St. John's Wort with apixaban.
• Ginkgo Biloba, Garlic, Ginger, and Ginseng: These supplements may have mild antiplatelet effects and should be used with caution.
• Vitamin E: High doses of Vitamin E may increase bleeding risk.

Apixaban will affect several coagulation assays:

• PT and aPTT: These tests may be slightly prolonged, but the change is inconsistent and cannot be used to monitor the drug's effect.
• Anti-Xa Assay: This is the only reliable way to measure apixaban's activity, but it must be specifically calibrated for apixaban.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including 'natural' remedies and vitamins.

Apixaban must NEVER be used in the following circumstances:

1. 1Active Pathological Bleeding: If a patient has an ongoing major bleed (such as a bleeding stomach ulcer or a brain hemorrhage), adding an anticoagulant will prevent the body from stopping the bleed, leading to potential death.
2. 2Severe Hypersensitivity: Patients who have had a documented severe allergic reaction (anaphylaxis or angioedema) to apixaban or any of the inactive ingredients in the tablet.
3. 3Prosthetic Mechanical Heart Valves: Clinical trials (such as RE-ALIGN) for DOACs were stopped early because patients with mechanical valves had more strokes and more bleeding on DOACs than on warfarin.
4. 4Severe Hepatic Impairment (Child-Pugh C): Because these patients often have baseline clotting deficiencies, the risk of catastrophic bleeding is too high.

These conditions require a careful risk-benefit analysis by a specialist:

• Pregnancy and Lactation: Due to a lack of safety data and the risk of maternal/fetal hemorrhage.
• Triple Positive Antiphospholipid Syndrome: Increased risk of arterial thrombosis.
• Active Malignancy: While apixaban is often used for cancer-associated DVT, certain cancers (like gastric or esophageal cancer) carry a very high risk of bleeding.
• Recent Brain or Spinal Surgery: The risk of a hematoma in these sensitive areas may outweigh the benefit of anticoagulation for a period post-surgery.

There is no known cross-sensitivity between apixaban and warfarin or heparin. However, patients who have had allergic reactions to other Factor Xa inhibitors (like rivaroxaban or edoxaban) should be monitored closely, as the chemical structures share some similarities.

> Important: Your healthcare provider will evaluate your complete medical history, including any history of 'thin blood' or bleeding disorders, before prescribing Apixaban.

Apixaban is generally not recommended during pregnancy. It is classified by some authorities as Category B or C, meaning there is insufficient data from well-controlled human studies. Animal studies have shown that apixaban crosses the placenta. The primary concern is the risk of pregnancy-related hemorrhage for both the mother and the fetus, particularly during delivery. If anticoagulation is required during pregnancy, healthcare providers typically switch patients to Low Molecular Weight Heparin (LMWH), which does not cross the placenta.

It is unknown whether apixaban is excreted in human milk, though animal studies have shown excretion in rat milk. Because of the potential for serious adverse reactions (bleeding) in the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Apixaban is not approved for use in children. The pharmacokinetics, safety, and dosing for the pediatric population are still being studied. Most pediatric anticoagulation is managed with heparin or warfarin under the guidance of a specialist.

In the ARISTOTLE clinical trial, over 30% of participants were 75 years or older. Apixaban was found to be particularly effective and safer (less bleeding) than warfarin in this age group. However, elderly patients are at a higher risk for:

• Falls: Leading to traumatic bleeds.
• Renal Decline: Requiring dose adjustments.
• Polypharmacy: Increasing the risk of drug interactions.

Apixaban is the DOAC most frequently used in patients with renal impairment because only 27% is renally cleared.

• Mild to Moderate (CrCl 30-80 mL/min): Usually no dose change unless the 'ABC' criteria are met.
• Severe (CrCl 15-29 mL/min): Use with caution; for AFib, the 2.5 mg dose is often used if other criteria are met.
• ESRD/Dialysis: FDA labeling allows for 5 mg BID (or 2.5 mg BID if elderly/low weight), but clinical data in this population is still emerging.

• Child-Pugh A: No adjustment.
• Child-Pugh B: Use with caution; monitor liver function and coagulation markers.
• Child-Pugh C: Avoid use.

> Important: Special populations require individualized medical assessment and frequent follow-up with a vascular or hematology specialist.

Apixaban is a direct, reversible inhibitor of the enzyme Factor Xa. Factor Xa is the pivotal protease that occupies the junction of the intrinsic and extrinsic pathways of the coagulation cascade. By binding to the active site of Factor Xa, apixaban prevents it from interacting with Factor Va to form the prothrombinase complex. This inhibition prevents the conversion of prothrombin (Factor II) to thrombin (Factor IIa). Without thrombin, the final step of clot formation—the conversion of soluble fibrinogen to insoluble fibrin—cannot occur.

The pharmacodynamic effect of apixaban is directly correlated with its plasma concentration. It does not require antithrombin III for activity. It inhibits both free Factor Xa and Factor Xa that is already bound within a clot. While apixaban prolongs tests like PT and aPTT, these changes are small and highly variable. The most accurate measure of its pharmacodynamic effect is the inhibition of Factor Xa activity, measured by an anti-Xa assay.

| Parameter | Value |

|---|---|

| Bioavailability | ~50% |

| Protein Binding | ~87% (primarily albumin) |

| Half-life | ~12 hours (range 8–15h) |

| Tmax | 3 to 4 hours |

| Metabolism | CYP3A4 (primary), P-gp substrate |

| Excretion | Fecal ~56%, Renal ~27% |

• Molecular Formula: C25H25N5O4
• Molecular Weight: 459.5 g/mol
• Solubility: Apixaban is a white to pale-yellow powder. It is non-ionizable and has low aqueous solubility across the physiological pH range.
• Structure: It is a pyrazole derivative, specifically 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide.

Apixaban is classified as a Direct Oral Anticoagulant (DOAC) and a Factor Xa Inhibitor. Related medications in this class include Rivaroxaban (Xarelto), Edoxaban (Savaysa), and Betrixaban (Bevyxxa). It is distinct from Direct Thrombin Inhibitors like Dabigatran (Pradaxa).