Nice Approves Pradaxa(R)(Dabigatran Etexilate) - 1st New Oral Anticoagulant In UK For Over 50 Years
November 08, 2017
Clinicians and patient groups have welcomed today's announcement by the
National Institute of Health and Clinical Excellence (NICE) recommending
Pradaxa(R) (dabigatran etexilate) as an option for the primary prevention of
venous thrombembolic events in adults who have undergone elective total hip
or total knee replacement surgery.(1) This positive NICE appraisal coincides
with the recent publication of a government venous thromboembolism (VTE) risk
assessment tool recommended for all patients admitted to hospital in England
by the Department of Health.(2) Routine risk assessment is a fundamental step
in ensuring patients at risk of developing VTE receive the appropriate
therapy and management. VTE is a potentially fatal blood clotting disease
which includes deep vein thrombosis (DVT) and pulmonary embolism (PE).
VTE is the most common cause of preventable hospital death in the UK.(3)
Up to 32,000 patients die every year in the UK(4) after developing blood
clots in hospital and a recent analysis by the All Party Parliamentary
Thrombosis Group revealed that over 10,700 UK hospital patients may have died
from blood clots in just seven months during 2007 as a result of clinical
guidelines not being implemented.(3)
Until now, anticoagulant therapy to prevent blood clots after major
orthopaedic surgery has generally required administration by injection.
Pradaxa(R) is the first new oral anticoagulant to be launched in the UK for
over 50 years. It is a fixed dose, once daily capsule that may be taken with
or without food.(5) NICE concluded that Pradaxa(R), as an oral therapy,
without the need for monitoring, would reduce National Health Service (NHS)
administration costs and may support adherence to treatment.(1)
The charity AntiCoagulation Europe welcomed NICE's recommendation. Chief
Executive, Eve Knight, said:
"We are delighted with today's NICE announcement, and also very pleased
that the long awaited Risk Assessment Tool has finally been published. It is
appalling that patients are still developing and dying from VTE, which could
be prevented by risk assessing every patient on admission to hospital and
giving preventative treatment where needed. Pradaxa, a once daily oral
therapy for use in post orthopaedic surgery, will enhance the treatment
options available and enable clinicians and patients to make decisions on
choice of treatment appropriate to their clinical needs."
Key facts
- NICE has recently reported that approximately 30 per cent of surgical
patients are affected by DVT(6)
- During 2006/7, 131,378 patients underwent hip and knee replacement
surgery in the UK(7)
- Total deaths (32,000) following development of blood clots in hospital,
including those related to hip and knee replacement, exceed the combined
total deaths from breast cancer, AIDS and road traffic accidents and equate
to more than 25 times the annual deaths from MRSA(4)
- In contrast to the number of deaths, the NHS spends ten times as much
on MRSA prevention as prevention of VTE from all causes(3)
- VTE is estimated to cost the NHS a total of GBP640 million every year
to manage. 60 - 80 per cent of this could be saved through preventative
measures(4)
- Although guidelines recommend preventative therapy for 10-35 days,(8)
clinical practice varies widely and therapy is often not maintained following
hospital discharge.(6)
VTE is known internationally as the 'silent killer' as often the first
manifestation may be a potentially fatal PE.(3) This means risk assessment
and prevention strategies are crucial. The new Department of Health risk tool
aims to create a standardised national preventive strategy to make the goal
of reducing death from VTE in all patients more attainable, potentially
saving thousands of lives every year.
On confirmation of the NICE recommendation, Des Turner, Member of
Parliament for Brighton Kemptown and Secretary of the All Party Parliamentary
Thrombosis Group commented:
"Currently lives are being lost because of inadequate clot-prevention
therapy. Research by the All Party Parliamentary Group on Thrombosis showed
that over 10,700 UK hospital patients may have died from blood clots in just
seven months during 2007 as a result of clinical guidelines not being
implemented. NICE approval for Pradaxa will provide a real boost to patients
undergoing hip and knee replacement surgery where potentially fatal clotting
is a real risk. I will continue to campaign to ensure VTE is given the
political and public prioritisation it deserves."
Pradaxa(R) was approved by the EMEA for marketing in all EU member
countries in March 2008 and since then swift progress has been made with
positive recommendations from local Health Technology Assessment bodies in
Scotland (Scottish Medicines Committee), Denmark (Danish Medicines Agency)
and The Netherlands (The Health Care Insurance Board).(9-11) To date,
Pradaxa(R) has been launched in a total of eleven countries.
Pradaxa(R) is one of a new class of drugs to tackle DVT and PE called
direct thrombin inhibitors (DTI). DTIs directly block the enzyme thrombin
which is central to the clotting process.(12)
Full details of the NICE guidance can be accessed via
nice
Wording of today's NICE announcement
Dabigatran etexilate, within its marketing authorisation, is recommended
as an option for the primary prevention of venous thromboembolic events in
adults who have undergone elective total hip replacement surgery or elective
total knee replacement surgery.
The Committee acknowledged that oral administration of dabigatran
etexilate, without the need for monitoring, would reduce administration costs
and may support adherence to treatment. The Committee therefore concluded
that dabigatran etexilate should be recommended as an option in the
circumstances in which LMWH (or fondaparinux as an alternative) may be
offered.
Standard Recommended Dosage of Pradaxa(R) in VTE Prevention
The standard recommended dosage of Pradaxa(R) in VTE prevention is a
fixed oral dose of 220 mg given once daily.(5) A single capsule of 110 mg
(half-dose) is administered orally between 1 and 4 hours following surgery,
continuing with 2 capsules once daily thereafter for a total of 10 days in
total knee replacement patients and 28-35 days in total hip replacement
patients.(5) A second approved dosage of 150 mg taken as two capsules of 75
mg is recommended for specific patient populations, including patients over
75 years of age and those with moderate renal impairment.(5)
Further Indications Under Investigation
Boehringer Ingelheim continues to evaluate the efficacy and safety of
Pradaxa(R) within the global RE-VOLUTION(TM) clinical trial programme which
involves over 38,000 patients. Pradaxa(R)'s efficacy and safety is being
assessed for:
- Stroke prevention in atrial fibrillation (SPAF) in the RE-LY(TM) trial
- the largest SPAF trial to date
- Enrollment of a total of 18,113 patients for the RE-LY(TM) trial
Was completed in December 2007
- Results are expected in 2009
- Treatment of acute VTE - results expected in 2009
- Secondary prevention of VTE
- Prevention of cardiac events in patients with acute coronary syndrome
About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading
pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates
globally with 135 affiliates in 47 countries and 39,800 employees. Since it
was founded in 1885, the family-owned company has been committed to
researching, developing, manufacturing and marketing novel products of high
therapeutic value for human and veterinary medicine.
In 2007, Boehringer Ingelheim posted net sales of 10.9 billion euro while
spending one fifth of net sales in its largest business segment Prescription
Medicines on research and development.
For more information please visit
boehringer-ingelheim
References
(1) nice/
(2) Hospital patients to be assessed for risk of blood clots.
Publication of Risk Assessment, Department of Health (National), 19 September
2008. Available at dh/VTE
(3) Thrombosis: Awareness, Assessment, Management and Prevention. An
Audit of Acute Hospital Trusts. November 2007. All Party Parliamentary
Thrombosis Group. Available at: dvtreport
(4) The House of Commons Health Committee Report on the Prevention of
Venous Thromboembolism in Hospitalised Patients - Second Report of Session
2004-05. The Stationery Office. February 2005. Available
here.
(5) Pradaxa, Summary of Product Characteristics, 2008
(6) Venous Thromboembolism: Reducing the risk of venous thromboembolism
(deep vein thrombosis and pulmonary embolism) in inpatients undergoing
surgery. April 2007. Commissioned by the National Institute for Health and
Clinical Excellence. Available at
nice/nicemedia/pdf/VTEAppendices.pdf
(7) National Joint Registry for London and Wales. 4th Annual Report.
2007. Available at njrcentre
(8) Geerts WH et al. Prevention of venous thromboembolism: American
College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th
Edition). Chest. 2008;133(6 Suppl):381S-453S
(9) emea.europa.eu/humandocs/Humans/EPAR/pradaxa/pradaxa.htm
Last accessed 23 July 2008
(10) scottishmedicines/smc/6093.htmlLast accessed 23
July 2008
(11) medicinpriser.dk/Default.aspx?Navn=Pradaxa Last accessed
23 July 2008
(12) Di Nisio M et al. Direct thrombin inhibitors. N Eng J Med.
2005;353:1028-1040
Prescribing Information (UK)
PRADAXA(R)*
Capsules containing 75mg or 110mg dabigatran etexilate (as mesilate)
Action: Direct thrombin inhibitor Indication: Primary prevention of venous
thromboembolic events in adult patients who have undergone elective total hip
or knee replacement surgery Dose and administration: Initial dose 110mg
within 1-4 hours of completed surgery, then 220mg once daily. In moderate
renal impairment (Cr Cl 30-50 ml/min) or patients greater than 75 years
reduce dose: initial dose 75mg, then 150mg once daily. After knee replacement
surgery continue treatment for a total of 10 days; after hip replacement
surgery for 28-35 days. Delay initiation of treatment if haemostasis is not
secured. If treatment is not started on the day of surgery initiate with 220
mg (or 150mg) once daily. Contra-indications: hypersensitivity to any
component; severe renal impairment (CrCl less than 30 ml/min); clinically
significant bleeding; organic lesion at risk of bleeding; impairment of
haemostasis; hepatic impairment or liver disease expected to have any impact
on survival; concomitant quinidine Warnings & precautions: Not recommended if
liver enzymes are greater than 2 ULN; measure ALT in pre-operative
evaluation. Close clinical surveillance (signs of bleeding or anaemia) is
recommended throughout the treatment period, especially when haemorrhagic
risk is increased: diseases associated with a risk of bleeding such as
coagulation disorders, thrombocytopenia or functional platelet defects,
active ulcerative GI disease, recent biopsy or major trauma, recent ICH or
brain, spinal or ophthalmic surgery, bacterial endocarditis, concomitant
NSAIDs (t1/2 greater than 12 hours). Patients less than 50 kg or greater than
110 kg; the elderly; patients at high surgical mortality risk and with
intrinsic risk factors for thromboembolic events. If severe bleeding occurs,
discontinue treatment and investigate the source of the bleeding. Avoid or
use with caution agents which may increase the risk of haemorrhage. Not
recommended in patients undergoing anaesthesia with postoperative indwelling
epidural catheters; the first dose should be given a minimum of 2 hours after
catheter removal; these patients require frequent observation for
neurological signs and symptoms. Contains Sunset Yellow (E110) which may
cause allergic reactions Interactions: anticoagulants and platelet
aggregation agents; amiodarone (reduce Pradaxa dose to 150mg); caution with
strong P-glycoprotein inhibitors (e.g. verapamil, clarithromycin) or inducers
(e.g. rifampicin, St John's wort). Pregnancy and lactation: avoid pregnancy
during treatment. Do not use in pregnancy unless clearly necessary.
Discontinue breast-feeding during treatment Undesirable effects: Most common
is bleeding (14%); major bleeds, including wound site bleeding, less than 2%.
Common (greater than/equal to 1/100, less than1/10): anaemia; haematoma
(including traumatic or postprocedural); wound, gastrointestinal, skin or
post procedural haemorrhage; haematuria; decreased haemoglobin; wound
secretion, postoperative or postprocedural anaemia, postprocedural discharge.
See SPC for details of these and other undesirable effects. Pack sizes, NHS
price and MA numbers: 75mg 10 capsules GBP21.00 EU/1/08/442/001; 60 capsules
GBP126.00 EU/1/08/442/003 110mg 10 capsules GBP21.00 EU/1/08/442/005; 60
capsules GBP126.00 EU/1/08/442/007 Legal category POM Marketing Authorisation
Holder: Boehringer Ingelheim International GmbH, D-55216 Ingelheim am Rhein,
Germany. Prescribers should consult the Summary of Product Characteristics
for full prescribing information. Prepared in July 2008.
Adverse events should be reported. Reporting forms and information can be
found at yellowcard . Adverse events should also be
reported to Boehringer Ingelheim Drug Safety on 0800-328-1627 (freephone).
Prepared from SPC1 for Pradaxa 75mg capsules and 110mg capsules, both
dated March 2008. Updated with revised AE wording July 2008
* due to technological reason the black triangle cannot be displayed.
However, as with all new medicines special reporting is required in relation
to adverse events.
National Institute of Health and Clinical Excellence
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