Initiating oral anticoagulant therapy

Once the decision is made to initiate oral anticoagulant therapy, it is important to recognize the potential for combined effects on the INR with coadministration of Argatroban and warfarin (see Effect on International Normalized Ratio).[2,9,10]

•	A loading dose of warfarin should not be used.
•	Initiate therapy using the expected daily dose of warfarin.
•	To avoid prothrombotic effects and to ensure continuous anticoagulation when initiating warfarin, it is recommended to overlap therapy with Argatroban and warfarin.
•	There are insufficient data available to recommend the duration of the overlap.

Figure 1. Conversion to Oral Anticoagulant Therapy[2]

Effect on INR

•	Coadministration of Argatroban and warfarin produces a combined effect on the laboratory measurement of INR values[2]
•	The combination of Argatroban and warfarin does not cause further reduction in vitamin K-dependent factor Xa activity than that which is seen with warfarin alone
•	The previously established relationship between INR and bleeding risk is altered during combination therapy.[2] For example, an INR of 4 on cotherapy does not have the same bleeding risk as an INR of 4 on warfarin monotherapy
•	In a retrospective analysis of patients receiving Argatroban who were converted to warfarin, increased INR were not associated with an increase in major bleeding[12]

Coadministration of warfarin and Argatroban at doses up to 2 mcg/kg/min

The INR value for warfarin alone (INRW) can be calculated from the INR value for the combination regimen of Argatroban and warfarin as described in Effect on International Normalized Ratio.[2] The INR should be measured daily while Argatroban and warfarin are coadministered. In general, with doses of Argatroban up to 2 mcg/kg/min, Argatroban can be discontinued when the INR is >4 on combined therapy.[2]

After Argatroban is discontinued, repeat the INR measurement in 4 to 6 hours.[2] If the repeat INR is below the desired therapeutic range, resume the infusion of Argatroban and repeat the procedure daily until the desired therapeutic range on warfarin alone is reached.[2] The relationship between INR obtained on combined therapy and INR obtained on warfarin alone is dependent on both the dose of Argatroban and the thromboplastin reagent used (see Effect on International Normalized Ratio in the FAQs).[2]

Coadministration of warfarin and Argatroban at doses greater than 2 mcg/kg/min

For doses greater than 2 mcg/kg/min, the relationship between INR on warfarin alone and warfarin plus Argatroban is less predictable (see Effect on International Normalized Ratio).[2] To predict the INR on warfarin alone, temporarily reduce the dose of Argatroban to a dose of 2 mcg/kg/min. Repeat the INR on Argatroban and warfarin 4 to 6 hours after reduction of Argatroban, and follow the process outlined above for dosing Argatroban at up to 2 mcg/kg/min.[2]

Indications
Argatroban is indicated as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia.

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

Important Safety Information

As with all anticoagulants, bleeding is a serious concern. Argatroban is contraindicated in patients with overt major bleeding or those with hypersensitivity to the product or any of its components. Argatroban should be used with extreme caution in disease states or other circumstances in which there is an increased risk of hemorrhage. Overall major bleeding was reported in 5.3% of patients with HIT treated with Argatroban versus 6.7% of the historical controls. Overall major bleeding was reported in 1.8% of patients undergoing PCI treated with Argatroban versus 3.1% of the historical controls. Intracranial bleeding was not observed in the 568 patients treated with Argatroban for HIT (with or without thrombosis) or in the 91 patients who underwent PCI. The most common nonhemorrhagic side effects in HIT patients, regardless of the relationship to treatment, were dyspnea, hypotension, and fever. In patients undergoing PCI, the nonhemorrhagic side effects, regardless of the relationship to treatment, included chest pain, hypotension, and back pain. Please see full Prescribing Information for additional safety information on Argatroban.