Acova

Name: Acova

What should I discuss with my health care provider before receiving Acova (argatroban)?

You should not receive this medicine if you are allergic to argatroban, or if you have any major bleeding from a surgery, injury, or other medical trauma.

To make sure argatroban is safe for you, tell your doctor if you have:

  • a stomach ulcer or bleeding;

  • liver disease;

  • a bleeding or blood clotting disorder (such as hemophilia);

  • untreated or uncontrolled high blood pressure (hypertension);

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

  • if you have recently had major surgery (especially eye surgery, brain surgery, or spinal cord surgery).

Argatroban is not expected to be harmful to an unborn baby. However, aspirin is sometimes given with argatroban, and taking aspirin during late pregnancy may cause bleeding in the mother or the baby during delivery. Tell your doctor if you are pregnant while taking aspirin.

It is not known whether argatroban passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

What happens if I miss a dose?

Since argatroban is given by a healthcare professional, you are not likely to miss a dose.

What other drugs will affect Acova (argatroban)?

Tell your doctor about all other medications you use or have recently received to prevent blood clots, such as:

  • a blood thinner such as heparin or warfarin (Coumadin, Jantoven);

  • abciximab (ReoPro), anagrelide (Agrylin), cilostazol (Pletal), clopidogrel (Plavix), dipyridamole (Persantine, Aggrenox), eptifibatide (Integrelin), prasugrel (Effient), ticlopidine (Ticlid), tirofiban (Aggrastat);

  • dabigatran (Pradaxa), bivalirudin (Angiomax), lepirudin (Refludan);

  • dalteparin (Fragmin), enoxaparin (Lovenox), fondaparinux (Arixtra), tinzaparin (Innohep); or

  • alteplase (Activase), tenecteplase (TNKase), urokinase (Abbokinase).

This list is not complete. Other drugs may interact with argatroban, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Acova Overview

Acova is a prescription medication used to prevent or treat a blood clot in patients with a specific condition called heparin-induced thrombocytopenia (HIT). Acova belongs to a group of drugs called direct thrombin inhibitors. It works by preventing blood clots from forming in the body.

This medication comes in an injectable form to be given directly into a vein (IV) by a healthcare professional.

Common side effects of Acova include bleeding, fever, decreased blood pressure, and diarrhea.

 

Dosing & Uses

Dosage Forms & Strengths

injectable solution

  • 100mg/mL

ready-to-use injectable

  • 50mg/50mL 0.9% NaCl
  • 125mg/125mL 0.9% NaCl

Thrombocytopenia

Indicated as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia

Initial: 2 mcg/kg/min IV continuous infusion over 1-3 hours until steady-state aPTT is 1.5-3 times initial baseline value 

Not to exceed infusion rate of 10 mcg/kg/min

Dosing considerations

  • Check aPTT and adjust dose until target aPTT is achieved

Percutaneous Coronary Intervention

Indicated as an anticoagulant in patients with or at risk for heparin-induced thrombocytopenia undergoing percutaneous coronary intervention (PCI)

Initial: 25 mcg/kg/min IV infusion, AND 

A bolus of 350 mcg/kg IV over 3-5 minutes via large-bore IV line

Check activated clotting time (ACT) 5-10 minutes after bolus dose is completed; procedure may proceed if ACT is >300 seconds

If ACT is <300 seconds, administer additional IV bolus dose of 150 mcg/kg, increase infusion dose to 30 mcg/kg/min, and check ACT 5-10 minutes later

If ACT >450 seconds, decrease infusion rate to 15 mcg/kg/min, and check ACT 5-10 minutes later

After therapeutic ACT (300-450 sec) achieved, continue this infusion dose for duration of procedure

Dosing Modifications

Hepatic impairment

  • Approximately 4-fold decrease in clearance relative to those with normal hepatic function, so dosing modification warranted; monitor aPTT and adjust dosage as clinically indicated
  • Thrombocytopenia: Decrease initial dose to 0.5 mcg/kg/min IV 
  • PCI: Avoid use in patients with clinically significant hepatic disease or AST/ALT levels >3 x ULN

Safety and efficacy not established

For Healthcare Professionals

Applies to argatroban: intravenous solution

Hematologic

Hematologic side effects including overt bleeding or hemorrhage are the most common complications of argatroban (the active ingredient contained in Acova) therapy. Major hemorrhagic events reported by the manufacturer include gastrointestinal bleeding (2.3%), intracranial bleeding (about 1% in patients receiving both argatroban and thrombolytic therapy), genitourinary bleeding and hematuria (0.9%), decreases in hemoglobin/hematocrit (0.7%), multisystem hemorrhage/DIC (0.5% ), and limb/below the knee amputation (0.5%). Minor hemorrhagic events reported by the manufacturer include gastrointestinal bleeding (14.4%), genitourinary bleeding and hematuria (11.6%), minor decreases in hemoglobin/hematocrit (10.4%), groin bleeding (5.4%), hemoptysis (2.9%), brachial bleeding (2.4%).[Ref]

In a study of patients given argatroban for the treatment of heparin-induced thrombocytopenia or heparin-induced thrombocytopenia and thrombosis syndrome, one patient experienced intracranial hemorrhage 4 days after the discontinuation of argatroban therapy and following urokinase and oral anticoagulation therapy.[Ref]

Cardiovascular

Cardiovascular side effects include hypotension (7.2%), cardiac arrest (5.8%), ventricular tachycardia (4.8%), atrial fibrillation (3.0%) and cerebrovascular disorder (2.3%).[Ref]

Gastrointestinal

Gastrointestinal side effects include diarrhea (6.2%), nausea (4.8%), vomiting (4.2%), and abdominal pain (2.6%).[Ref]

Respiratory

Respiratory effects include dyspnea (8.1%), pneumonia (3.3%) and coughing (2.8%).[Ref]

General

General side effects include fever (6.9%), sepsis (6.0%) and pain (4.6%).[Ref]

Genitourinary

Genitourinary side effects include urinary tract infection (4.6%).[Ref]

Immunologic

Immunological side effects include infection (3.7%).[Ref]

Some side effects of Acova may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Liver Dose Adjustments

Moderately impaired hepatic function:
Initial: 0.5 mcg/kg/min administered as a constant infusion.

Maintenance: The infusion rate may be adjusted as needed (not to exceed 10 mcg/kg/min) until the steady state aPTT value is 1.5 to 3 times the initial baseline value (not to exceed 100 seconds). Dosage adjustments should be based on aPTT results from blood samples obtained at least 2 hours after the most recent infusion rate change.

Infants and children 16 years or younger:
Note: Limited data available; dosing regimens not established.
Initial dose: 0.2 mcg/kg/minute
Maintenance dose: Measure aPTT after 2 hours; adjust dose until the steady-state aPTT is 1.5 to 3 times the initial baseline value, not exceeding 100 seconds; adjust in increments of not greater than 0.05 mcg/kg/minute.

Precautions

Concomitant use of argatroban with antiplatelet agents, thrombolytics, and other anticoagulants may increase the risk of bleeding.

In patients with moderate hepatic dysfunction (Child-Pugh score greater than 6), hepatic dysfunction was associated with about a 4-fold decrease in systemic clearance and a 3-fold increase in elimination half-life of argatroban.

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