Mitsubishi Pharma Europe Ltd

Mitsubishi Pharma Europe Ltd
Mitsubishi Tanabe Pharma Group

Mitsubishi Tanabe Pharma Group

August 27, 2013 08:14 ET

Exembol® Receives Acceptance from the Scottish Medicines Consortium (SMC)

Mitsubishi Pharma Europe's anticoagulant Exembol® (argatroban) receives acceptance from the Scottish Medicines Consortium (SMC) as treatment for patients with heparin-induced thrombocytopenia type II (HIT)

EDINBURGH, SCOTLAND--(Marketwired - Aug. 27, 2013) -

SMC Guidance 12th August 2013
Mitsubishi Pharma Europe's drug argatroban (Exembol®) is accepted for use within NHS Scotland for anticoagulation in adult patients with heparin-induced thrombocytopenia type II who require parenteral antithrombotic therapy. Argatroban produces anticoagulant effects in adults with heparin induced thrombocytopenia type II. However, there is limited evidence that the anticoagulant effects are associated with a reduction in thrombosis and deaths due to thrombosis.

Exembol® is a selective direct thrombin inhibitor that reversibly inhibits both free and clot-bound thrombin [1]. Anticoagulant effects are produced rapidly with a predictable dose response effect [2]. Exembol® has a short half-life [1] and its anticoagulant effects are rapidly reversible [2].

Studies have shown that Exembol® is generally well tolerated and improves patient outcomes in HIT [3]. A study of 497 HIT patients demonstrated that Exembol® therapy significantly reduced the risk of new thrombosis and death due to thrombosis in patients with HIT compared to a historical control group [3]. In addition the Exembol® treated patients had a more rapid recovery of platelet count. These benefits were realised without an increased bleeding risk compared with historical control group patients who received standard treatment at that time [3]. Exembol® has also been shown to provide effective anticoagulation in patients with renal dysfunction or failure [4], conditions often associated with HIT patients in an intensive care unit setting.

The SMC's decision means that adult patients with suspected or confirmed heparin-induced thrombocytopenia type II (HIT) who require parenteral antithrombotic therapy, will now be able to more readily get access to Exembol® on the NHS in Scotland. Treatment with Exembol® is included in the British Society for Haematology guidelines for patients with HIT [5].

"HIT is relatively uncommon, but it is a real issue with potentially devastating outcomes for patients," says Professor Nigel Webster, ICU Physician, Aberdeen. "The SMC guidance represents a therapeutic advance in management of HIT, and Exembol® is a welcome addition to the category."

For more details, visit: http://www.scottishmedicines.org.uk.

NOTES TO EDITORS

BACKGROUND TO HIT:

Heparin-Induced Thrombocytopenia type II is an antibody-mediated adverse drug reaction that can lead to devastating thromboembolic complications, including pulmonary embolism, ischemic limb necrosis necessitating limb amputation, acute myocardial infarction, and stroke. Initial treatment involves the immediate cessation of all forms of heparin treatment. However, the highest risk of thrombosis occurs in the first few days after stopping heparin treatment. An alternative non-heparin, rapidly acting anticoagulant therapy is recommended once a clinical diagnosis of HIT has been made [5].

ARGATROBAN 100 mg/mL concentrate for solution for infusion. Abbreviated Prescribing Information.

  • Contains argatroban as argatroban monohydrate 100 mg/mL.
  • Indication: Argatroban is indicated for the anticoagulation of adult patients with heparin-induced thrombocytopenia type II who require parenteral antithrombotic therapy. Diagnosis should be confirmed by the HIPAA (heparin-induced platelet activation assay) or an equivalent test. However, such confirmation must not delay the start of treatment.
  • Contraindications: Argatroban is contraindicated in patients with uncontrolled bleeding, severe hepatic impairment or hypersensitivity to argatroban or its excipients.
  • Dosage: Argatroban is supplied as a concentrate (250 mg/2.5 mL) which must be diluted 100-fold prior to infusion to a final concentration of 1 mg/mL. The initial starting infusion rate for adults is 2 μg/kg/min but the starting infusion rate should be reduced to 0.5 μg/kg/min for adults with moderate hepatic impairment, post-cardiac surgery or critically ill/ICU patients. The infusion rate is monitored by the aPTT. Two hours after the initial dose of argatroban, the dose is adjusted based on the aPTT until it is within the desired therapeutic range (1.5 to 3.0 times the initial baseline value but not exceeding 100 seconds) and 2 hourly thereafter until the aPTT is within the desired therapeutic range. In case of an elevated aPTT (exceeding 3 times baseline or 100 seconds), the infusion should be discontinued until the aPTT is within the desired range of 1.5 to 3 times baseline (typically within 2 hours of discontinuation of infusion), and the infusion may be restarted at one half of the previous infusion rate. The aPTT should be checked again after 2 hours. For switching to oral anticoagulants, co-therapy for at least 5 days is recommended. INR should be monitored daily. Consult the SmPC for detailed recommendations.
  • Precautions and warning: Argatroban causes a generally increased tendency to bleeding. A fall in haematocrit, a fall in blood pressure or any other unexplained symptom should lead to a consideration of a haemorrhagic event. All parenteral anticoagulants should be stopped for 1-2 hours before starting argatroban. Contains ethanol and sorbitol.
  • Undesirable effects: Bleeding. Consult SmPC for adverse event profile.
  • Overdose: There is no specific antidote for argatroban.
  • Basic NHS price: £248.50.
  • Legal classification: Medicine only available on prescription.
  • Marketing authorisation number: PL 20012/0008.
  • Marketing Authorisation Holder: Mitsubishi Pharma Europe Ltd, Dashwood House, 69 Old Broad Street, London EC2M 1QS, UK for the following countries; Sweden, Norway, Denmark, Finland, Iceland, Netherlands, Italy, Germany, Austria, France, UK and Spain. All adverse events should be reported to the appropriate Competent Authority.
  • Date: May 2012 (UK)
  • Adverse events should be reported: Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Mitsubishi Pharma Europe Ltd on 0207 382 9000.

About Mitsubishi Pharma Europe:

Mitsubishi Pharma Europe acts as the European Headquarters, a consolidated subsidiary of one of Japan's leading pharmaceutical companies, Mitsubishi Tanabe Pharma Corporation. Based in London, the company is dedicated to the clinical development of new drugs for the European markets and conducts trials in the following therapeutic areas; cardiovascular, diabetes and renal conditions. Mitsubishi Pharma Europe is the marketing authorisation holder for Exembol® (argatroban) and supports commercial operations for other in-house products. For more information go to: http://www.mitsubishi-pharma.eu.

REFERENCES:

[1] Exembol (argatroban) Summary of Product Characteristics. 2012

[2] Swan SK, Hursting MJ. The pharmacokinetics and pharmacodynamics of argatroban: effects of age, gender and hepatic or renal dysfunction. Pharmacotherapy 2000;20(3):318-329

[3] Lewis BE et al. Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia. Circulation 2001;103:1838-1843

[4] Hursting MJ, Murray PT. Argatroban anticoagulation in renal dysfunction: a literature analysis. Nephron Clin Pract 2008;109:c80-c94

[5] Watson et al. Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition. Br J Haematol. 2012 Dec:159(5): 528-40 doi: 10.1111/bjh.12059. Epub 2012 Oct 9

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