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Actions for Commissioning Teams
Prescribing for chronic non-cancer and
neuropathic pain
March 2013
www.pctsla.org
Actions for Commissioning Teams
What are we covering?
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The following slides provide information on analgesics for the
pharmacological management of non-cancer chronic pain (including
neuropathic pain), focussing on key current prescribing issues in the
West Midlands.
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Background
Prevalence of chronic pain
General approach to the management of chronic pain
Selection of a pharmacological agent
Paracetamol
NSAIDs
Weak opioids
Tramadol
Strong opioids
Opioid transdermal patches
Tapentadol SR
Pharmacological management of neuropathic pain
The presentation does not cover:
o Management of cancer-related pain, or the use of analgesia during
palliative care.
Actions for Commissioning Teams
Background
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The International Association for the Study of Pain (IASP)
defines pain as “an unpleasant sensory and emotional
experience associated with actual or potential tissue damage
or described in terms of such damage”.1
Chronic pain has been defined as continuous, long-term pain
of more than 12 weeks or after the time that healing would have
been thought to have occurred after trauma or surgery.2
Chronic pain is a subjective experience influenced and
modulated by psychological factors as well as physical factors.
Chronic pain has a negative impact on general health and
social and psychological well-being. It is also associated with
increased mortality, particularly in those who are unable to be
active.3
Actions for Commissioning Teams
Prevalence of chronic pain
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In a UK survey (2005) approximately 20% of respondents
reported experiencing pain most days or every day.4
Among those reporting chronic pain on at least some days,
56% stated that it had affected their lives (e.g. time off work,
less active, depressed, sex life).4
A systematic review (2013) of recent key studies on the
prevalence of chronic pain found3:
o chronic pain has a weighted average prevalence in adults of 20%;
7% have neuropathic pain and 7% severe pain.
o chronic pain impedes activities of daily living, work and work
efficiency, and reduces quality of life.
o effective pain therapy (pain intensity reduction of at least 50%)
results in consistent improvements in fatigue, sleep, depression,
quality of life and work.
Actions for Commissioning Teams
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General approach to treatment of
chronic pain
Effective treatment involves an evaluation of the cause, duration, and
intensity of the pain and selection of an appropriate treatment (this
may include non-drug) for the pain.
Drug treatment should be used only as part of a wider management
plan aimed at improving quality of life and reducing disability.
Non-drug therapies (e.g. CBT based modalities, TENS, acupuncture
and physical therapy) should be considered where appropriate.
Pharmacological measures may include paracetamol, non steroidal
anti-inflammatory drugs (NSAIDs), weak opioids, strong
opioids, antidepressants and anticonvulsants.
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Patients should be given information and instruction about pain and
pain management and be encouraged to take an active role in their
pain management
Actions for Commissioning Teams
Selection of a pharmacological
agent5
Step 1
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• Non-opioid (paracetamol and/or NSAID) ± adjuvant medication
Persistent or increasing pain
• Opioid for mild to moderate pain
Step 2 • ± non opioid (paracetamol and/or NSAID) ± adjuvant medication
Persistent or increasing pain
• Opioid for moderate to severe pain
Step 3 • ± non opioid (paracetamol and/or NSAID) ± adjuvant medication
Adjuvant drugs may be
considered at any step of the
ladder. Choice of agent
depends on the cause of pain,
contraindications and adverse
effects. Antidepressants or
anticonvulsants may be
considered for neuropathic
pain.
Constipation is a long term
side effect for the majority of
patients taking opioids.
Therefore regular laxatives
should be prescribed.
Encourage regular fluid intake.
Antiemetics may also be
required.
Review pain control and side
effects regularly depending on
clinical need. Consider
compliance
Actions for Commissioning Teams
Paracetamol
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Paracetamol is the first line analgesic for most types of
nociceptive pain
o Low cost, high bioavailability, quick onset of action
o Less likely to cause side effects than NSAIDs at therapeutic
doses.
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Several combined paracetamol and weak opioid preparations
are available (e.g. co-codamol, tramacet, co-dydramol).
o Reduce the scope for effective titration of the individual
components
o May be convenient for some patients
o If combinations are used, give therapeutic doses (e.g.
paracetamol 500 mg or codeine 30 mg per tablet/capsule).
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Effervescent or soluble formulations contain high
concentrations of sodium and are expensive. Avoid unless
specific indications (e.g. difficulty swallowing).
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Actions for Commissioning Teams
NSAIDs
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Although NSAIDs are effective analgesics for mild to moderate pain
their use is limited because of adverse effects and contraindications.
NSAIDS (standard and coxibs) are associated with CV adverse
outcomes, gastrointestinal adverse events and renal adverse
events.6,7
Prescribing should be based on safety profiles of individual NSAIDs
and individual patient risk profiles.8
If an NSAID is necessary, use ibuprofen (≤1,200 mg/day) as first line
and naproxen (≤ 1,000 mg/day) as second line. Use the lowest
effective dose for the shortest time necessary. Diclofenac and coxibs
have a higher risk of CV adverse events.8
Osteoarthritis of the knee or hand- consider topical NSAID.8
Consider a proton pump inhibitor (e.g. omeprazole or lansoprazole)
for patients requiring gastroprotection (as advised by NICE).8
Actions for Commissioning Teams
Weak opioids
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Opioids are sometimes used for chronic non-cancer pain:
o Local and national prescribing guidance should be followed
carefully
o Benefits must be carefully balanced against the risk of tolerance,
dependence, addiction and side effects.
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Weaker/low potency opioids can be prescribed for patients with
moderate pain in conjunction with paracetamol /NSAIDs (Step 2
of WHO analgesic ladder).
Weaker/low potency opioids include:
o Codeine
o Dihydrocodeine
o Tramadol
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Dihydrocodeine may be preferred to codeine (capacity to
metabolise codeine varies considerably and many patients will
not respond optimally).9
Actions for Commissioning Teams
Tramadol
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Prescribing of tramadol is increasing in the West Midlands. The
number of defined daily doses increased from approx 11.3 million in
2008 to nearly 15 million in 2012 (a 31.9% increase).
Tramadol produces analgesia via two mechanism: an opioid effect and
an enhancement of serotonergic and adrenergic pathways.9 Although
not currently a controlled drug, it is a potent analgesic.10
Fewer typical opioid side effects BUT there are significant risks:9,11
o Psychiatric reactions have been reported.
o Potential to produce serotonin syndrome when prescribed with
antidepressants.
o Can be sought by drug abusers and people with addiction disorders and
may be subject to criminal diversion.
o Misuse or abuse may result in overdose and death.
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Advisory Council on the Misuse of Drugs have recently recommended
that the UK government should make tramadol a controlled class C
substance.11
Actions for Commissioning Teams
Strong opioids
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Stronger opioids should only be considered at Step 3 of the pain ladder. Strong
opioids should not normally be used as first line therapy for chronic pain.
Efficacy and safety of long-term strong opioid treatment for chronic noncancer pain is uncertain (few trials have assessed this).12
Generally, if a strong opioid is required, oral morphine is the first-choice for
most people because of familiarity, cost, and the available range of
formulations.
o Once the dose of morphine has been effectively titrated to the patient’s
pain, where possible use regular dosing with modified release
preparations (immediate release opioids may be associated with tolerance
and problem drug abuse).
o Modified release tablets and capsules should be prescribed by brand
name due to variations in release profiles.13 Zomorph® capsules are
currently less expensive than MST Continus® tablets.
Predictable side effects of opioids should be anticipated and managed with
laxatives, anti-emetics etc. as appropriate.
Patient education is vital when prescribing strong opioids. A patient
information booklet on strong opioids is a available at
http://www.britishpainsociety.org/book_opioid_patient.pdf
Actions for Commissioning Teams
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Strong opioid prescribing advice for
chronic pain14,15
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Comprehensive assessment is important. Patients with psychiatric or
psychological co-morbidity will require additional support and
monitoring.
Agree goals of therapy. Treatment should be reviewed at least every
three months (more often if there are concerns) to ensure that it is
effective and still required.
An opioid should be given at the lowest dose that gives maximal
control of pain and should not be used longer than necessary.
Requests for dose increases need careful evaluation.
NEVER prescribe opioid injections or pethidine for persistent noncancer pain (unless on specialist advice).
If care is shared between hospital and community, be clear who is
responsible for prescribing.
Actions for Commissioning Teams
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Strong opioid prescribing advice for
chronic pain
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Prescriptions should not exceed 30 days supply for Schedule 2,3 and
4 Controlled Drugs (CDs).
Ideally, within a GP practice, only one prescriber should sign repeat
prescriptions for opioids.
Before a repeat prescription for an opioid is issued, recent opioid use
should be assessed for evidence of over-ordering (this may indicate
lack of efficacy or potential misuse).
Ensure all staff that issue repeat prescriptions are aware of which
drugs are controlled drugs (CDs). If over ordering is suspected, the
prescriber should be notified before a prescription is issued.
If apparent dependence is developing, consider decreasing dose
steadily or issue weekly prescriptions. Put a flag on the system to
prevent prescriptions being ordered too early.16
Actions for Commissioning Teams
Opioid transdermal patches
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Prescribing of opioid transdermal preparations is increasing in the
West Midlands - cost and safety implications.
Fentanyl patches and buprenorphine patches are much more
expensive than oral morphine at equivalent doses (see next slide).
Oral analgesics should be preferred. Patches should generally only
be used in limited number of patients with stable pain (not for
unstable pain) who require a strong opioid if:
o Oral route is unacceptable (e.g. dysphagia, malabsorption/bowel
obstruction)
o Compliance problems
o Intolerable side effects with morphine
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If patches are considered necessary:
o Initial dose should be based on patient’s opioid history.
o Apply to healthy, non-hairy skin.
o Temperature increases (e.g. due to fever or external heat) may increase
delivery of drug causing increased side effects.9
o If serious adverse events are experienced remove patches immediately
and monitor for up to 24 hours after patch removal.17
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Actions for Commissioning Teams
Annual Cost Comparison
Butrans patch 5mcg/hr or equivalent
£42
Butrans patch 10mcg/hr or equivalent
£42
15
£229
£410
£84
Butrans patch 20mcg/hr or equivalent
£747
£143
Transtec patch 35mcg/hr or equivalent
£411
£202
Transtec patch 52.5mcg/hr or equivalent
£617
£286
Transtec patch 70mcg/hr or equivalent
£0
£100
£200
£300
Morphine (Zomorph®)
£822
£400
£500
£600
£700
£800
£900
Buprenorphine patches
£42
Fentanyl patch 12mcg/hr or equivalent
£216
£101
Fentanyl patch 25mcg/hr or equivalent
£576
£197
Fentanyl patch 50mcg/hr or equivalent
£576
£298
Fentanyl patch 75mcg/hr or equivalent
£804
£709
Fentanyl patch 100mcg/hr or equivalent
£991
£0
£200
Morphine (Zomorph®)
£400
£600
£800
£1,000
£1,200
Fentanyl patches
The information presented on this slide is to aid price comparison and
should not be used to switch patients under any circumstances.
Actions for Commissioning Teams
Fentanyl transdermal patches
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In 2012, the West Midlands spent nearly £5 million on Fentanyl
patches.
Fentanyl is a strong opioid. NOT for opioid-naïve patients. Follow
MHRA safety advice.17
o Reports of serious and fatal overdose from dosing errors, accidental
exposure and inappropriate use of fentanyl patches.
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Patches differ between brands depending on the type of patch (matrix
or reservoir). Prescribe by brand.13
o Fencino® and Matrifen® patches are currently the lowest cost fentanyl
formulations (MIMS, March 2013).
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MTRAC guidance (2012) for fentanyl patches in non cancer pain18:
o Evidence for fentanyl patches is relatively weak. Cost compared with oral
morphine gives it a low place in therapy.
o Fentanyl patches should only be initiated by a specialist or a specialist
pain management service.
o Patients receiving fentanyl should be assessed frequently for efficacy of
treatment, functional status improvements, compliance and adverse
effects.
Actions for Commissioning Teams
Buprenorphine transdermal patches
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In 2012, the West Midlands spent approx £4.2 million on
buprenorphine patches .
o £1.2 million on Butrans® (low dose buprenorphine, licensed for moderate,
non malignant pain and similar in efficacy to co-codamol or tramadol).
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MTRAC guidance (2012) for buprenorphine patches (Transtec® ,
Butrans®) in chronic non cancer pain:19
o Buprenorphine patches should only be initiated by a specialist or a
specialist pain management service.
o Patients receiving buprenorphine should be assessed frequently (e.g.
after two weeks) for the efficacy of treatment, improvements in functional
status, compliance and adverse effects.
o An RCT found low dose buprenophine (Butrans ® ) to be non-inferior to
tramadol MR. A further trial found buprenorphine patches plus
paracetamol to be non-inferior to co-codamol.
o Costs compared with oral morphine give buprenorphine patches a low
place in therapy.
Actions for Commissioning Teams
Tapentadol SR
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Prolonged release tapentadol (tapentadol SR) is an opioid receptor
agonist and inhibitor of noradrenaline reuptake. Licensed since 2011
for severe chronic pain that can only be adequately managed with
opioid analgesics.20
RCTs have found that tapentadol SR (100 mg to 250 mg bd): 21
o provides comparable pain relief to oxycodone controlled release
(20 to 50 mg bd) in osteoarthritis or low back pain.
o is associated with better gastrointestinal tolerability than
oxycodone controlled release .
Controlled release oxycodone is a high-cost comparator drug. No
comparisons with lower cost opioid analgesics such as modified
release morphine.
In 2011 Scottish Medicines Consortium accepted tapentadol SR for
patients in whom morphine sulphate modified release has failed to
provide adequate pain control or is not tolerated.22
Actions for Commissioning Teams
Management of neuropathic
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pain23
Neuropathic pain develops as a result of damage to, or
dysfunction of, the system that normally signals pain.
It may arise from a heterogeneous group of disorders that
affect the peripheral and central nervous systems. Common
examples include:
o painful diabetic neuropathy
o post-herpetic neuralgia
o trigeminal neuralgia
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A number of drugs are used to manage neuropathic pain
including:
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antidepressants
anticonvulsant drugs
opioids
topical treatments such as capsaicin and lidocaine.
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Actions for Commissioning Teams
NICE CG 96 (under review): Pharmacological
treatment of neuropathic pain23
People with painful diabetic neuropathy
First-line treatment
• Offer oral duloxetine
• Offer oral amitriptyline (if duloxetine is
contraindicated)
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People with other neuropathic pain conditions
First-line treatment
• Offer oral amitriptyline or pregabalin (note: many NHS bodies
recommend gabapentin in preference to pregabalin)
• If satisfactory pain reduction is obtained with amitriptyline but the
person cannot tolerate the adverse effects, consider oral
imipramine or nortriptyline as an alternative
If satisfactory pain reduction is reached continue treatment and consider gradually reducing dose over time if
improvement is sustained. If unsatisfactory pain reduction at maximum tolerated dose, move to next step.
Second-line treatment
• Offer treatment with another drug instead of or in
combination with the original drug, after informed
discussion with the person:
• If first-line treatment was with duloxetine, switch
to amitriptyline or pregabalin, or combine with
pregabalin
• If first-line treatment was with amitriptyline,
switch to or combine with pregabalin
Second-line treatment
• Offer treatment with another drug instead of or in combination
with the original drug, after informed discussion with the person
• If first-line treatment was with amitriptyline (or imipramine or
nortriptyline), switch to or combine with pregabalin
• If first-line treatment was with pregabalin, switch to, or combine
with, amitriptyline (or imipramine or nortriptyline as an
alternative if amitriptyline is effective but the person cannot
tolerate the adverse effects)
If satisfactory pain reduction is reached continue treatment and consider gradually reducing dose over time if
improvement is sustained. If unsatisfactory pain reduction at maximum tolerated dose, move to next step.
Third-line treatment
• Refer the person to a specialist pain service and/or a condition-specific service
• While waiting for referral:
• Consider oral tramadol instead of or in combination with second-line treatment. Do not use other opioids without assessment
by pain clinic
• Consider topical lidocaine for treatment of localised pain for people who are unable to take oral medication because of
medical conditions and/or disability
Actions for Commissioning Teams
Pregabalin or gabapentin?
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Pregabalin and gabapentin are structurally related and have a similar
pharmacological action and adverse events.
Limited data - no published head-to-head RCTs comparing gabapentin
and pregabalin in post-herpetic neuralgia or diabetic neuropathy. One
small trial in neuropathic cancer pain.
Pregabalin is much more expensive than gabapentin (see next slide)
o In 2012, the NHS in West Midlands spent nearly £19 million on pregabalin .
Although it has other indications, the majority of pregabalin prescriptions
are for neuropathic pain. If half of the pregabalin prescriptions had been
prescribed as gabapentin, this could have saved more than £8 million.
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Current NICE guidance for neuropathic pain recommends pregabalin
as a first line option but does not recommend gabapentin.23
o NICE concluded that pregabalin is more effective than gabapentin based
on indirect comparisons of the two treatments. Pregabalin vs. gabapentin,
has lower number needed to treat (NNT) values for at least 30% pain
reduction and 50% pain reduction.
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Decision by NICE to recommend pregabalin over gabapentin has been
heavily criticised because of the associated costs to the NHS; NICE
have agreed to review their decision.
Actions for Commissioning Teams
Annual cost comparison for
pregabalin and gabapentin
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Pregabalin 300 mg bd
(Lyrica®)
£839.50
Pregabalin 150 mg bd
(Lyrica®)
£839.50
Pregabalin 75 mg bd
(Lyrica®)
£839.50
Gabapentin 900 mg tds*
(generic capsules)
£127.13
Gabapentin 600 mg tds*
(generic capsules)
£84.75
Gabapentin 300 mg tds
(generic capsules)
£42.38
£0
£100 £200 £300 £400 £500 £600 £700 £800 £900
Annual Cost per Patient
* Doses are a guide. Gabapentin costs are based on 300 mg capsules
Actions for Commissioning Teams
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Pregabalin or gabapentin potential
abuse and addiction
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Cases of abuse and addiction have been reported with both
pregabalin and gabapentin.24,25
Both drugs act via GABA pathways and may cause
euphoria.24,25
Healthcare professionals should be aware of the possibility of
abuse.
o Benefits must be carefully balanced against risk and should be
discussed with patients before prescribing
o Frequent monitoring is important for those with a history of abuse
o Be alert to over ordering of these drugs
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When necessary, offer assistance with tapering off the
medication.25
Actions for Commissioning Teams
References (1)
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IASP Pain Terminology. International Association for the Study of Pain. 2009. http://www.iasppain.org/AM/Template.cfm?Section=Pain_Definitions&Template=/CM/HTMLDisplay.cfm&ContentID=1728
The British Pain Society. http://www.britishpainsociety.org/media_faq.htm
Andrew R, Derry S, Taylor RS et al. The Costs and Consequences of Adequately Managed Chronic Non-Cancer Pain and Chronic
Neuropathic Pain. Pain Pract 2013.
NOP pain poll. British Pain Society. 2005 . http://www.britishpainsociety.org/media_surveys.htm
WHO's pain ladder. World Health Organisation. http://www.who.int/cancer/palliative/painladder/en/
Nonsteroidal anti-inflammatory drugs (standard or coxibs) - prescribing issues. 2011 Clinical Knowledge Summaries.
http://www.cks.nhs.uk/nsaids_prescribing_issues/in_the_right_clinical_topic
Non-steroidal anti-inflammatory drugs: reminder on renal failure and impairment. Drug Safety Update. Volume 2 Issue 10. 2009
Medicines and Healthcare products Regulatory Agency. http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON088004
Non-steroidal anti-inflammatory drugs. Key Therapeutics Topics: Medicines management options for local implementation’. January
2013 http://publications.nice.org.uk/non-steroidal-anti-inflammatory-drugs-ktt13/options-for-local-implementation
British National Formulary. 64th edition. September 2012.
Opioid Analgesics: Approximate Potency Equivalence with Oral Morphine. Mims online. February 2013
http://www.mims.co.uk/news/1146201/Opioid-Analgesics-Approximate-Potency-Equivalence-Oral-Morphine
Mayor S. Drug experts call for stronger regulation of tramadol to reduce misuse. BMJ 2013;346:f1264
Manchikanti L, Ailinani H, Koyyalagunta D et al. A systematic review of randomized trials of long-term opioid management for chronic
non-cancer pain. Pain Physician 2011;14:91-121.
Which medicines should be considered for brand-name prescribing in primary care? From the National Electronic Library for Medicines.
2011 www.nelm.nhs.uk
Opioids for persistent pain. Summary of guidance on good practice from the British Pain Society. 2010
http://www.britishpainsociety.org/book_opioids_recommendations.pdf
Pain and substance misuse: improving the patient experience. 2007. British Pain Society.
http://www.britishpainsociety.org/book_drug_misuse_main.pdf
Guidance on the safe prescribing and dispensing controlled drugs . October 2012. Northamptonshire Primary Care Trust.
http://www.neneccg.nhs.uk/resources/uploads/files/TP%20Extra%20Safe%20Prescribing%20and%20Dispensing%20of%20CDs.pdf
Fentanyl patches: serious and fatal overdose from dosing errors, accidental exposure, and inappropriate use. Drug Safety Update .Sept
2008, Vol 2 issue 2: 2. http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087796
Fentanyl Transdermal Patch For the treatment of chronic intractable non-cancer pain. Midlands Therapeutics Review and Advisory
Committee. January 2012
http://www.keele.ac.uk/media/keeleuniversity/fachealth/fachealthsop/mtrac/documents/summary/Fentanyl%20TD%20SUM%206.pdf
Actions for Commissioning Teams
References (2)
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19) Buprenorphine Transdermal Patch (Transtec® , Butrans®) for the treatment of chronic non-cancer pain . Midlands Therapeutics Review
and Advisory Committee. January 2012
http://www.keele.ac.uk/media/keeleuniversity/fachealth/fachealthsop/mtrac/documents/esca/Bupren%20SUM5.pdf
20) Palexia SR 100 mg prolonged-release tablets . Summary of Product Characteristics. 2011 Electronic Medicines Compendium.
http://www.medicines.org.uk/EMC/medicine/24390/SPC/Palexia+SR+100+mg+prolonged-release+tablets/#INDICATIONS
21) Afilalo M, Morlion B. Efficacy of tapentadol ER for managing moderate to severe chronic pain. Pain Physician 2013;16:27-40.
22) Tapentadol prolonged release tablets, Resubmission. Scottish Medicines Consortium, 2011
http://www.scottishmedicines.org.uk/files/advice/tapentadol_Palexia_SR_RESUBMISISON_FINAL_MAY_2011_for_website.pdf
23) Neuropathic pain. CG96. 2010 National Institute for Health and Clinical Excellence. http://www.nice.org.uk/CG96
24) Lyrica Capsules. Summary of Product Characteristics. Electronic Medicines Compendium.
http://www.medicines.org.uk/EMC/medicine/14651/SPC/Lyrica+Capsules/
25) Gabapentin and pregabalin: abuse and addiction. Prescrire Int 2012;21:152-4.