Edoxaban

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Edoxaban is a prescription medication used to reduce the risk of stroke and blood clots in patients with atrial fibrillation (abnormal heart rhythm)that is not caused by a heart valve problem.

Edoxaban also has been approved to treat deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients who have already been treated with an anti-clotting drug administered by injection or infusion, for 5 to 10 days.

DVT is a blood clot that forms in a vein deep in the body, usually in the lower leg or thigh. A potentially deadly condition called PE results when a blood clot in a deep vein breaks off and travels to an artery in the lungs and blocks blood flow.

Edoxaban belongs to a group of drugs called direct factor Xa inhibitors, which are anti-clotting medications. These work by blocking the action of a certain natural substance that helps blood clots to form.

Edoxaban comes in tablet form and is taken once daily.

Common side effects of edoxaban include bleeding and anemia.

Take edoxaban exactly as prescribed.

Edoxaban comes in tablet form and is taken once daily. It can be taken with or without food.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take 2 doses of edoxaban at the same time.

You should not use edoxaban if you are allergic to it, or if you have:

• an artificial heart valve; or

• active or uncontrolled bleeding.

You may not be able to use edoxaban if you have normal kidney function (your doctor will check your kidneys before you start taking edoxaban).

Edoxaban can cause a very serious blood clot around your spinal cord if you undergo a spinal tap or receive spinal anesthesia (epidural). This type of blood clot could cause long-term paralysis, and may be more likely to occur if:

• you have a genetic spinal defect;

• you have a spinal catheter in place;

• you have a history of spinal surgery or repeated spinal taps;

• you have recently had a spinal tap or epidural anesthesia;

• you take a blood thinner--heparin, warfarin, Coumadin, Jantoven;

• you take aspirin or medicines that contain aspirin (including cough or cold medicine);

• you take an NSAID--aspirin, Advil, Aleve, Motrin, Celebrex, and others; or

• you are using other medicines to treat or prevent blood clots.

Edoxaban may cause you to bleed more easily, especially if you have:

• a bleeding disorder that is inherited or caused by disease;

• hemorrhagic stroke;

• uncontrolled high blood pressure;

• stomach or intestinal bleeding or ulcer; or

• if you take certain medicines such as aspirin, heparin, warfarin (Coumadin, Jantoven), or clopidogrel (Plavix).

To make sure you can safely take edoxaban, tell your doctor if you have kidney or liver disease.

It is not known whether this medicine will harm an unborn baby. However, this medicine could cause bleeding complications during childbirth. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether edoxaban passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using edoxaban.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take edoxaban with or without food.

Edoxaban increases your risk of bleeding, which can be severe or life-threatening. Call your doctor or seek emergency medical attention if you have bleeding that will not stop, if you have black or bloody stools, or if you cough up blood or vomit that looks like coffee grounds.

Tell any doctor who treats you that you are using edoxaban. If you need surgery or dental work, tell the surgeon or dentist ahead of time that you are taking edoxaban. If you need anesthesia for a medical procedure or surgery, you may need to stop using edoxaban for a short time.

Do not change your dose or stop taking edoxaban without first talking to your doctor. Stopping suddenly can increase your risk of blood clot or stroke.

Use edoxaban regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Store at room temperature away from moisture and heat.

Usual Adult Dose for Atrial Fibrillation:

60 mg orally once a day

Use: Prevention of stroke and systemic embolism in nonvalvular atrial fibrillation

Usual Adult Dose for Deep Vein Thrombosis:

60 mg orally once a day following 5 to 10 days of initial therapy with a parenteral anticoagulant

Uses: Treatment of deep venous thrombosis and pulmonary embolism following 5-10 days of initial parenteral anticoagulant therapy

Usual Adult Dose for Pulmonary Embolism:

60 mg orally once a day following 5 to 10 days of initial therapy with a parenteral anticoagulant

Uses: Treatment of deep venous thrombosis and pulmonary embolism following 5-10 days of initial parenteral anticoagulant therapy

Take edoxaban exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. When your supply of edoxaban is running low, contact your doctor or pharmacist ahead of time. Do not allow yourself to run out of edoxaban.

edoxaban comes with a Medication Guide. It is very important that you read and understand this information. Be sure to ask your doctor if you have any questions.

You may take edoxaban with or without food.

If you are using another medicine to thin the blood (eg, heparin, warfarin, Coumadin®, Jantoven®), your doctor will give you very specific instructions about how to switch to edoxaban. Carefully follow the instructions and ask your doctor if you have any questions.

Dosing

The dose of edoxaban will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of edoxaban. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For prevention of strokes and blood clots in patients with nonvalvular atrial fibrillation:
    • Adults—60 milligrams (mg) once a day.
    • Children—Use and dose must be determined by your doctor.
  • For treatment of deep venous thrombosis and pulmonary embolism:
    • Adults—60 milligrams (mg) once a day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of edoxaban, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists. This medicine may need to be stopped before certain types of surgery as your doctor has told you. If edoxaban is stopped, your doctor will tell you when to start taking this medicine again after your surgery or procedure.
• Do not stop taking edoxaban without calling the doctor who ordered it for you.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
• Very bad and sometimes deadly bleeding problems have happened with this medicine. Talk with the doctor.
• If you fall or hurt yourself, or if you hit your head, call your doctor right away. Talk with your doctor even if you feel fine.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using edoxaban while you are pregnant.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Savaysa: 15 mg, 30 mg, 60 mg

Edoxaban, a selective factor Xa inhibitor, inhibits free factor Xa and prothrombinase activity and inhibits thrombin-induced platelet aggregation. Inhibition of factor Xa in the coagulation cascade reduces thrombin generation and thrombus formation.

Distribution

Vdss: 107 L

Metabolism

Minimal via hydrolysis, conjugation and oxidation by CYP3A4; predominant metabolite (M-4) is active (<10% of parent compound)

Excretion

Urine (primarily unchanged); renal clearance: ~50% of total clearance.

Time to Peak

1 to 2 hours

Half-Life Elimination

10 to 14 hours

Protein Binding

~55%

The International Society on Thrombosis and Haemostasis (ISTH) 2016 guideline suggests avoiding the use of edoxaban (and other direct oral anticoagulants) in patients with a BMI >40 kg/m2 or weight >120 kg due to the lack of clinical data in this population. If used in a patient with a BMI >40 kg/m2 or weight >120 kg, ISTH suggests measuring peak and trough levels using an antifactor Xa assay or mass spectrometry. If drug level is below the expected range, ISTH suggests changing to a vitamin K antagonist rather than adjusting the dose of edoxaban (ISTH [Martin 2016]).

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Monitor therapy

Anticoagulants: Edoxaban may enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment. Exceptions: Acenocoumarol; Warfarin. Avoid combination

Antiplatelet Agents (P2Y12 Inhibitors): May enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: Carefully consider the anticipated risks and benefits of this combination. If combined, increased monitoring for bleeding is recommended. Consider therapy modification

Apixaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Aspirin: May enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Aspirin may increase the serum concentration of Edoxaban. Management: Carefully consider the anticipated risks and benefits of this combination. If combined, increased monitoring for bleeding is recommended. Consider therapy modification

Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy

Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Deoxycholic Acid: Anticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy

Estrogen Derivatives: May diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of estrogens against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Exceptions: Tibolone. Consider therapy modification

Factor X (Human): Anticoagulants (Inhibitors of Factor Xa) may diminish the therapeutic effect of Factor X (Human). Monitor therapy

Hemin: May enhance the anticoagulant effect of Anticoagulants. Avoid combination

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Consider therapy modification

Ibritumomab: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to an increased risk of bleeding. Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy

Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Monitor therapy

Lumacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

MiFEPRIStone: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of bleeding may be increased. Avoid combination

Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

NSAID (Nonselective): May enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of edoxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Consider therapy modification

Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy

Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Avoid combination

Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification

Progestins: May diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of progestins against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Consider therapy modification

Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Monitor therapy

RifAMPin: May decrease the serum concentration of Edoxaban. Avoid combination

Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Salicylates: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Telavancin: May diminish the therapeutic effect of Anticoagulants. Specifically, telavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses. Monitor therapy

Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Management: See full drug monograph for guidelines for the use of alteplase for acute ischemic stroke during treatment with oral anticoagulants. Monitor therapy

Tibolone: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Tositumomab and Iodine I 131 Tositumomab: Anticoagulants may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse effects may be increased. Monitor therapy

Urokinase: May enhance the anticoagulant effect of Anticoagulants. Avoid combination

Vitamin E (Systemic): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Avoid combination

Concerns related to adverse effects:

• Bleeding: May increase the risk of bleeding; serious, potentially fatal bleeding may occur. Concomitant use of drugs that affect hemostasis (eg, aspirin, other antiplatelet agents, other antithrombotic agents, fibrinolytic therapy, chronic NSAID use, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors) may increase the risk of bleeding. Monitor for signs and symptoms of bleeding. Discontinue therapy with active pathological hemorrhage and promptly evaluate for bleeding source. No specific antidote exists for edoxaban reversal; hemodialysis does not have a substantial impact on edoxaban clearance and protamine sulfate, vitamin K, and tranexamic acid are not expected to reverse the anticoagulant effect of edoxaban. The use of 4-factor prothrombin complex concentrate (PCC) (KCentra or Beriplex P/N) was shown to dose dependently reverse the effects of edoxaban on bleeding following punch biopsy (Zahir 2015). Other procoagulant reversal agents (eg, activated prothrombin complex concentrate [APCC], recombinant factor VIIa [rFVIIa]) may be considered but has not been evaluated; if PCCs are used, monitoring for anticoagulation effect of edoxaban using clotting test (PT, INR, or aPTT) or anti-FXa activity is not useful and is not recommended.

• Thromboembolic events: [US Boxed Warning]: Premature discontinuation of any oral anticoagulant, including edoxaban, in the absence of adequate alternative anticoagulation increases the risk of ischemic events. If edoxaban is discontinued for reasons other than pathological bleeding or completion of a course of therapy, consider the use of another anticoagulant.

Disease-related concerns:

• Hepatic impairment: Use is not recommended in patients with moderate or severe hepatic impairment (Child-Pugh class B and C) due to intrinsic coagulation abnormalities.

• Nonvalvular atrial fibrillation: [US Boxed Warning]: Do not administer to nonvalvular atrial fibrillation (NVAF) patients with CrCl >95 mL/minute (calculated using the Cockcroft-Gault formula). In clinical trials, these patients had an increased rate of ischemic stroke with edoxaban 60 mg once daily compared to patients treated with warfarin; use another anticoagulant in these patients.

• Renal impairment: In patients with CrCl of 15 to 50 mL/minute (calculated using the Cockcroft-Gault formula), dosage reduction is necessary. Use is not recommended in patients with CrCl <15 mL/minute (limited clinical data).

• Valvular disease: Safety and efficacy have not been established in patients with mechanical heart valves or moderate to severe mitral stenosis; use is not recommended. Nonvalvular atrial fibrillation is defined as atrial fibrillation that occurs in the absence of rheumatic mitral valve disease, mitral valve repair, or prosthetic heart valve (AHA/ACC/HRS [January, 2014]).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Body weight: In patients with venous thromboembolism (DVT and/or PE) and body weight ≤60 kg, dosage reduction is necessary.

• Spinal or epidural hematoma: [US Boxed Warning]: Spinal or epidural hematomas resulting in long-term or permanent paralysis may occur with neuraxial anesthesia (epidural or spinal anesthesia) or spinal/epidural puncture; the risk is increased by the use of indwelling epidural catheters, concomitant administration of other drugs that affect hemostasis (eg, NSAIDS, platelet inhibitors, other anticoagulants), in patients with a history of traumatic or repeated epidural or spinal punctures, a history of spinal deformity or surgery, or if optimal timing between the administration of edoxaban and neuraxial procedures is not known. Consider the potential benefits and risks prior to neuraxial intervention in patients who are anticoagulated or scheduled to be anticoagulated. Monitor frequently for signs and symptoms of neurologic impairment (eg, numbness/weakness of legs, bowel/bladder dysfunction). If neurologic impairment is noted, urgent treatment is necessary.

- In patients who receive both edoxaban and neuraxial anesthesia, avoid removal of epidural or intrathecal catheter for at least 12 hours following last edoxaban dose; avoid edoxaban administration for at least 2 hours following catheter removal.

• Surgery and invasive procedures: Discontinue edoxaban at least 24 hours prior to elective surgery or invasive procedures. If surgery cannot be delayed, the risk of bleeding should be weighed against the urgency of intervention. Reinitiate edoxaban when adequate hemostasis has been achieved unless oral therapy cannot be administered, then consider administration of a parenteral anticoagulant.

Patients who weigh 60 kg or less:
-Treatment of deep venous thrombosis or pulmonary embolism: 30 mg orally once a day

Patients taking certain concomitant P-gp inhibitors (verapamil and quinidine or short-term azithromycin, clarithromycin, erythromycin, oral itraconazole, or oral ketoconazole):
-Treatment of deep venous thrombosis or pulmonary embolism: 30 mg orally once a day

SWITCHING FROM ANOTHER ANTICOAGULANT TO EDOXABAN:
Switching from vitamin K antagonist (VKA) therapy to edoxaban: Discontinue VKA and start edoxaban when the INR is 2.5 or less

Switching from an oral anticoagulant other than VKA therapy to edoxaban: Discontinue current therapy and start edoxaban at the time of the next scheduled dose of the discontinued anticoagulant

Switching from low molecular weight heparin (LMWH) to edoxaban: Discontinue LMWH and start edoxaban at the time of the next scheduled LMWH dose

Switching from unfractionated heparin to edoxaban: Discontinue the infusion and start edoxaban 4 hours later

SWITCHING FROM EDOXABAN TO ANOTHER ANTICOAGULANT:
Switching from edoxaban to VKA therapy (oral option):
-For patients taking 60 mg of edoxaban, reduce the dose to 30 mg and begin concomitant VKA therapy
-For patients taking 30 mg of edoxaban, reduce the dose to 15 mg and begin concomitant VKA therapy
-Measure INR at least weekly and just prior to the daily dose of edoxaban
-Once INR is stable and measured at 2 or above, discontinue edoxaban and continue VKA therapy

Switching from edoxaban to VKA therapy (parenteral option):
-Discontinue edoxaban and administer a parenteral anticoagulant and VKA therapy at the time of the next scheduled edoxaban dose
-Once INR is stable and measured at 2 or above, discontinue the parenteral anticoagulant and continue VKA therapy

Switching from edoxaban to an oral anticoagulant other than VKA therapy: Discontinue edoxaban and start the other oral anticoagulant at the time of the next scheduled edoxaban dose

Switching from edoxaban to parenteral anticoagulant therapy: Discontinue edoxaban and start the parenteral anticoagulant at the time of the next scheduled edoxaban dose

DISCONTINUATION FOR SURGERY AND OTHER INTERVENTIONS:
-If clinically possible, therapy should be stopped at least 24 hours prior to the procedure and restarted after the procedure as soon as hemostasis has been established.
-If a decision needs to be made whether to delay a procedure until 24 hours after the last dose of this drug, the increased risk of bleeding should be weighed against the urgency of the intervention.

SPINAL OR EPIDURAL ANESTHESIA OR PUNCTURE:
-An epidural catheter must not be removed earlier than 12 hours after the last dose of this drug. The next dose should be administered at least 2 hours after the catheter is removed.

Data not available