Update on Chronic
Neuropathic Pain Medications
Joyce Côté, BSc Pharm ACPR
Pharmacist, Chronic Pain Centre
January 16, 2013
Calgary Neuropathy Association Presentation
Outline
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Medication Goals and Patient’s Toolbox
Antidepressants
Anticonvulsants
Opioids
Cannabinoids
Medical marijuana
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Goals of Medication Therapy
• 30% pain relief may be expected
• Increase function
• Balance pain relief with acceptable side effects
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Patient’s Toolbox
Knowledge
Nutrition
Rehabilitation
Medications
SelfManagement
Self-Monitoring
Pacing
Relaxation
Self-Talk
Communication
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ANTIDEPRESSANTS –
TRICYCLIC
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Antidepressants – Tricyclic
• Amitriptyline (Elavil®), Nortriptyline (Aventyl®),
Desipramine (Norpramin®)
• 1st line for neuropathic pain
• Increase levels of serotonin and norepinephrine
• May also be helpful for sleep, mood, and migraine
prevention
• Side Effects:
– Drowsiness, dizziness, blurred vision, constipation,
difficulty urinating, weight gain
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Amitriptyline
Alberta Blue Cross – Regular Benefits
•10 mg tablet $0.06
•25 mg tablet $0.12
•50 mg tablet $0.23
•75 mg tablet $0.36
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Nortriptyline
Alberta Blue Cross – Regular Benefits
•10 mg capsule $0.09
•25 mg capsule $0.18
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Desipramine
Alberta Blue Cross – Regular Benefits
•10 mg tablet $0.38
•25 mg tablet $0.38
•50 mg tablet $0.67
•75 mg tablet $0.89
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ANTIDEPRESSANTS –
SNRI
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Antidepressants – SNRI
• SNRI = Serotonin and Norepinephrine Reuptake
Inhibitor
• Increase serotonin and norepinephrine
• Venlafaxine (Effexor®), duloxetine (Cymbalta®)
• Side Effects:
– Nausea, headache, increased blood pressure
• Withdrawal effects are common with venlafaxine
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Venlafaxine
Alberta Blue Cross – Regular Benefits
•37.5 mg capsule $0.35
•75 mg capsule $0.70
•150 mg capsule $0.73
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Duloxetine
• Health Canada Indications
– Major depressive disorder
– Diabetic peripheral neuropathic pain
– General anxiety disorder
– Fibromyalgia
– Chronic low back pain
– Osteoarthritis of the knee (July 2012)
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Duloxetine
Alberta Blue Cross – Regular Benefit
•30 mg capsule $1.88
•60 mg capsule $3.75
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ANTIEPILEPTICS –
1ST LINE
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Antiepileptics – 1st Line
• Gabapentin (Neurontin®), pregabalin (Lyrica®)
• 1st line for neuropathic pain
• Side Effects:
– Drowsiness, dizziness, unsteadiness, unable to think
clearly, weight gain
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Gabapentin
Alberta Blue Cross – Regular Benefits
•100 mg capsule $0.16
•300 mg capsule $0.39
•400 mg capsule $0.46
Alberta Blue Cross – Not Benefits
•600 mg tablet ~$1.30
•800 mg tablet ~$1.74
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Pregabalin
• Health Canada Indications
– Diabetic peripheral neuropathy
– Postherpetic neuralgia
– Spinal cord injury neuropathic pain
– Fibromyalgia
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Pregabalin
Alberta Blue Cross – Not Benefits
•25 mg capsule ~$0.85
•50 mg capsule ~$1.30
•75 mg capsule ~$1.74
•150 mg capsule ~$2.39
•300 mg capsule ~$2.41
Generics expected to be
available ~Sept 2013
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ANTIEPILEPTICS –
OTHER
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Antiepileptics – Other
• Topiramate (Topamax®), lamotrogine (Lamictal®),
carbamazepine (Tegretol®), oxcarbazepine (Trileptal®),
divalproex (Epival®)
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Topiramate (Topamax®)
• Also useful for prevention of migraine headaches
• Side Effects:
– Drowsiness, dizziness
– Memory difficulties, confusion
– Loss of appetite, nausea
– Burning/tingling/numbness in hands/feet
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Topiramate
Alberta Blue Cross – Regular Benefits
•25 mg tablet $0.48
•50 mg tablet (PMS Only – pale yellow) $1.07
•100 mg tablet $0.91
•200 mg tablet $1.36
•15 mg sprinkle capsule $1.17
•25 mg sprinkle capsule $1.23
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OPIOIDS
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Opioids
• Canadian Opioid Guidelines
– “Opioids showed only small to moderate benefits for
neuropathic pain.”
• Some opioids are marketed specifically for neuropathic
pain due to additional mechanisms of action
– Tramadol
– Tapentadol
– Methadone
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Opioids
• Common side effects:
– Drowsiness, dizziness, nausea, constipation, itching
• Serious side effects:
– Breathing slows down
• Long-term complications:
– Sleep apnea
– Decrease in sex hormones
– Opioid-induced hyperalgesia
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Tramadol Long-Acting
• Also increases serotonin and norepinephrine
• Ralivia®
• Tridural®
– 25% immediate-release
• Zytram XL®
• Durela®)
– 17 to 25% immediate-release
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Ralivia®
• 100 mg tablet ~$1.32
• 200 mg tablet ~$2.39
• 300 mg tablet ~$3.48
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Tridural®
• 100 mg tablet ~$1.26
• 200 mg tablet ~$2.31
• 300 mg ~$3.26
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Zytram XL®
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75 mg tablet ~$0.91
100 mg ~$1.18
150 mg ~$1.71
300 mg ~$3.26
400 mg ~$4.28
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Durela®
• 100 mg capsule ~$1.22
• 200 mg capsule ~$2.23
• 300 mg capsule ~$3.23
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Tapentadol CR (Nucynta CR®)
• Moderate-severe pain
• Mu-opioid agonist plus norepinephrine reuptake
inhibition (NRI)
• Possibly better GI tolerability
• Possibly more norepinephrine-like side effects
• Maximum dose
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Tapentadol CR
Alberta Blue Cross – Not a Benefit
•50 mg CR ~$1.03
•100 mg CR
•150 mg CR
•200 mg CR
•250 mg CR ~$3.71
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Methadone (Metadol®)
• Two distinct indications:
– Pain
– Opioid-dependence / addiction
For pain:
• Opioid activity
• Serotonin and norepinephrine reuptake inhibition
• NMDA receptor antagonist
NMDA = N-methyl-D-aspartate
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Methadone
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Long-acting
Inexpensive
Electrocardiogram required
Requires frequent monitoring while adjusting the dose
Lots of drug interactions
Risk of overdose is higher
Physician requires a special license
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Methadone
Alberta Blue Cross – Regular Benefit
•1 mg tab $0.17
•5 mg tab $0.56
•10 mg tab $0.90
•25 mg tab $1.69
•1 mg/mL oral solution $0.10/mL
•10 mg/mL oral solution $0.37/mL
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CANNABINOIDS
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Cannabinoids
• Nabilone (Cesamet®), tetrahydrocannabinolcannabidiol (Sativex®)
• Side effects:
– Drowsiness, dizziness, unsteadiness, dry mouth
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Nabilone (Cesamet®)
• Health Canada indicated for nausea and vomiting
associated with chemotherapy
• Studied in fibromyalgia (1 mg twice daily x 4 weeks)
• Studied in diabetic peripheral neuropathic pain (1-4
mg/day x 9 weeks)
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Nabilone
Alberta Blue Cross – Regular Benefits
•0.5 mg capsule $3.10 (generic $1.17)
•1 mg capsule $6.21 (generic $2.33)
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Tetrahydrocannabinol-cannabidiol (Sativex®)
• Spray under tongue or inside cheek
• Usually 8 sprays/day
• Alberta Blue Cross – Not a Benefit
• Vials of 48 sprays = ~$125
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MEDICAL MARIJUANA
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Medical Marijuana
• Health Canada:
– “Marijuana is not an approved therapeutic product”
– “Its safety and efficacy have not been established”
– “Use… involves risks to health, some of which may
not be known or fully understood”
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Medical Marijuana
• What it does:
– Often produces euphoria, relaxation, time-distortion,
perception of enhanced sensory experiences, and
loss of inhibitions
• What the active ingredients might be:
– Tetrahydrocannabinol (THC)
– Cannabinol
– Cannabidiol
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Medical Marijuana
• What the other ingredients might be:
– There may be more than 60 other cannabinoids
– Many of the substances found in tobacco smoke
have been found in marijuana smoke
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Medical Marijuana
• Warnings:
– Heart disease
– Asthma, chronic obstructive pulmonary disease
– Alcohol/drug abuse or dependence
– Serious mental disorders
• Administration by smoking is not recommended
– Some people use in food, tea, or with a vaporizer
• May impair your ability to drive
– Can last up to 24 hours after consuming
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Medical Marijuana
• Side Effects:
– Mood reactions such as anxiety, paranoia, agitation,
amnesia, delusions or hallucinations
– Fast heartbeat
– Facial flushing or red eyes
– Dizziness or feeling faint
• Long-Term Complications:
– Wheezing or chronic cough if smoked
– May impair short-term memory, attention, and
concentration
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Medical Marijuana
• Drug Interactions
– Any drugs that slow down the central nervous
system, causing drowsiness
• E.g. sleeping pills
– Antiviral drugs used in the treatment of AIDS
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Medical Marijuana
Application Process
•Two Categories
– Category 1 – specialist not needed
– Category 2 – specialist required
•Authorization renewal required yearly
•Marihuana Medical Access Division:
– www.healthcanada.gc.ca/mma or 1-866-337-7705
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Medical Marijuana
• Distribution
– Delivery every month by courier to your home or
doctor’s office
• Cost
– 30 seeds = $20
– Dried marijuana = $5/gram
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Medical Marijuana
• College of Physicians and Surgeons of Alberta Jan
2012:
– “marijuana remains an illegal drug; one that is not on
any formulary and one that has no human evidence
as to efficacy, dose or safety.”
– “In the absence of evidence as to efficacy, we will
continue to counsel our members not to authorize (or
‘prescribe’) [medical marijuana] for medical
purposes.”
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Medical Marijuana
Proposed changes December 16, 2012
• Removes Health Canada as a gatekeeper
• Doctors fill out a medical document similar to a
prescription
• No specialist consult doctor required
• Patients takes document to a licensed producer
• Removal of home production
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Medical Marijuana
• Canadian Medical Association:
– “There’s a huge potential for harm to patients and the
federal government’s decision is equivalent to asking
doctors to prescribe while blindfolded.”
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Medical Marijuana
• Currently > 26, 000 patients across Canada with
authorized use (<500 patients in 2002)
• Cost will increase to ~ $8.80/gram (from $1.80 to
$5/gram)
• Federal Health Minister Leona Aglukkaq:
– “Individuals will be able to choose their licensed
producer based on strength, price, quality and
customer service”
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Medical Marijuana
• Health Canada will keep its current contract until March
31, 2014 to continue current patients
• Health Canada will align the price of its own supply
once licensed producers are approved
• No new applications after October 1, 2013
• April 1, 2014: Health Canada would no longer
produce/sell marijuana
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Medical Marijuana
• Producers are subject to security requirements,
inspections, and good manufacturing practices
– Indoor production site (not a private residence)
– Restricted access
– 24/7 camera security system and alarm system
– Valid security clearance
– Notify local police, fire, and government officals
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Medical Marijuana
• Government’s goal is to have new guidelines by March
31, 2013, and full implementation by April 2014
• Canadians have the opportunity to comment before Feb
28, 2013.
• Comments or concerns you might have regarding the
proposed changes can be submitted to Health Canada
via email to consultations-marihuana@hc-sc.gc.ca.
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TOPICAL ANALGESICS
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Topical Lidocaine
• 5% ointment commercially available, 30 grams
– Applied 3-4 times daily as needed
– Requires prescription
– May be compounded with other drugs and using
different bases
Alberta Blue Cross – Regular Benefit
– $0.15/gram topical ointment
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Topical Capsaicin
• Capsaicin 0.075% cream (Zostrix HP)
– Painful diabetic foot neuropathy
– Applied four times daily regularly
– Decreases pain intensity
– Well tolerated after initial few days
– Available over-the-counter ~$31 per 60 grams
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Topical Ketamine
• Requires a triplicate prescription
• Needs to be made by a compounding pharmacy
• Helpful for:
– Allodynia (pain produced by a stimulus which does
not normally cause pain, e.g. light touch)
– Hyperalgesia (increased sensitivity to pain)
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PATIENT RESOURCES
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Patient Resources
• Chronic Pain Centre Public Lectures
www.albertahealthservices.ca/2790.asp
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Introduction to pain
This is your body
Medications
The role of exercise in managing pain
Attention and memory
Nutrition
Pacing in pain management
Anxiety, depression and chronic pain
Sleep
Understanding medical investigations and the health care system
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Pain Resources
• Canadian Pain Coalition
www.canadianpaincoalition.ca
– Conquering Pain for Canadians booklet
– Pain Resource Centre
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THANK YOU!
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