1. Update on Chronic Neuropathic Pain Medications
Joyce Côté, BSc Pharm ACPR
Pharmacist, Chronic Pain Centre
January 16, 2013
Calgary Neuropathy Association Presentation

2. Outline Medication Goals and Patient’s Toolbox Antidepressants
Anticonvulsants
Opioids
Cannabinoids
Medical marijuana

3. Goals of Medication Therapy
30% pain relief may be expected
Increase function
Balance pain relief with acceptable side effects
It is important to be realistic about how much pain relief you would expect to get with medications. Unfortunately, there is no “magic pill” that will take away all your pain. Often, only 30% pain relief would be expected with the use of medications. For example, if you have severe pain, it might be reasonable to decrease that pain from severe to moderate, perhaps from 9/10 down to 6/10 on the pain scale that we saw on the previous slide.
We also hope to increase your level of function with medications, so that you are able to do more of the day-to-day activities you used to do before you were in pain.
Because all medications can cause side effects, we need to balance your pain relief with side effects that are acceptable to you.

4. Patient’s Toolbox Knowledge Medications Nutrition Self-Monitoring
Although medications can be helpful, you can see that they are not likely to completely take away all your pain. So it is important to note that medications are only one tool in your toolbox. Your other tools may include knowledge, nutrition, rehabilitation and exercise, and most-importantly self-management skills, which include self-monitoring, pacing, relaxation, self-talk and communication.
Self-Monitoring
Pacing
Relaxation
Self-Talk
Communication
Rehabilitation
Self-Management

5. ANTIDEPRESSANTS – TRICYCLIC

6. 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

7. Amitriptyline Alberta Blue Cross – Regular Benefits 10 mg tablet $0.06

8. Nortriptyline Alberta Blue Cross – Regular Benefits
10 mg capsule $0.09
25 mg capsule $0.18

9. Desipramine Alberta Blue Cross – Regular Benefits 10 mg tablet $0.38

10. ANTIDEPRESSANTS – SNRI

11. 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

12. Venlafaxine Alberta Blue Cross – Regular Benefits
37.5 mg capsule $0.35
75 mg capsule $0.70
150 mg capsule $0.73

13. 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)

14. Duloxetine Alberta Blue Cross – Regular Benefit 30 mg capsule $1.88

15. ANTIEPILEPTICS – 1ST LINE

16. Antiepileptics – 1st Line
Gabapentin (Neurontin®), pregabalin (Lyrica®)
1st line for neuropathic pain
Side Effects:
Drowsiness, dizziness, unsteadiness, unable to think clearly, weight gain

17. Gabapentin Alberta Blue Cross – Regular Benefits 100 mg capsule $0.16
Alberta Blue Cross – Not Benefits
600 mg tablet ~$1.30
800 mg tablet ~$1.74

18. Pregabalin Health Canada Indications Diabetic peripheral neuropathy
Postherpetic neuralgia
Spinal cord injury neuropathic pain
Fibromyalgia

19. Pregabalin Alberta Blue Cross – Not Benefits 25 mg capsule ~$0.85
Generics expected to be
available ~Sept 2013

20. ANTIEPILEPTICS – OTHER

21. Antiepileptics – Other
Topiramate (Topamax®), lamotrogine (Lamictal®), carbamazepine (Tegretol®), oxcarbazepine (Trileptal®), divalproex (Epival®)

22. 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

23. 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

24. OPIOIDS

25. 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

26. 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

27. Tramadol Long-Acting Also increases serotonin and norepinephrine
Ralivia®
Tridural®
25% immediate-release
Zytram XL®
Durela®)
17 to 25% immediate-release

28. Ralivia® 100 mg tablet ~$1.32 200 mg tablet ~$2.39

29. Tridural®
100 mg tablet ~$1.26
200 mg tablet ~$2.31
300 mg ~$3.26

30. Zytram XL® 75 mg tablet ~$0.91 100 mg ~$1.18 150 mg ~$1.71

31. Durela® 100 mg capsule ~$1.22 200 mg capsule ~$2.23

32. 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

33. Tapentadol CR Alberta Blue Cross – Not a Benefit 50 mg CR ~$1.03

34. 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

35. Methadone 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

36. Methadone Alberta Blue Cross – Regular Benefit 1 mg tab $0.17
1 mg/mL oral solution $0.10/mL
10 mg/mL oral solution $0.37/mL

37. cannabinoids

38. Cannabinoids
Nabilone (Cesamet®), tetrahydrocannabinol-cannabidiol (Sativex®)
Side effects:
Drowsiness, dizziness, unsteadiness, dry mouth

39. 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)

40. Nabilone Alberta Blue Cross – Regular Benefits
0.5 mg capsule $3.10 (generic $1.17)
1 mg capsule $6.21 (generic $2.33)

41. Tetrahydrocannabinol-cannabidiol (Sativex®)
Spray under tongue or inside cheek
Usually 8 sprays/day
Alberta Blue Cross – Not a Benefit
Vials of 48 sprays = ~$125

42. Medical marijuana

43. 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”

44. 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

45. 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

46. 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

47. 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

48. 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

49. Medical Marijuana Application Process Two Categories
Category 1 – specialist not needed
Category 2 – specialist required
Authorization renewal required yearly
Marihuana Medical Access Division: or

50. Medical Marijuana Distribution
Delivery every month by courier to your home or doctor’s office
Cost
30 seeds = $20
Dried marijuana = $5/gram

51. 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.”

52. 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

53. 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.”

54. 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”

55. 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

56. 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

57. 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

58. Topical analgesics

59. 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

60. 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
Clinical Reviews: Diabetic Neuropathy Clinical studies demonstrate the effectiveness of the active ingredient present in Zostrix® Diabetic Foot Pain Relieving Cream in treating diabetic foot pain when used as part of a treatment regiment under the supervision of a physician.
The effectiveness of treating diabetic foot pain is one reason why Doctors and Pharmacists recommend Zostrix®.
Below we briefly review a key clinical study highlighting the effectiveness of 0.075% Capsaicin Cream in relieving diabetic foot pain. Study references are also provided if you wish to read the published article in its entirety.
Treatment of Painful Diabetic Neuropathy with Topical Capsaicin
Study Description: A multicenter study was conducted to establish the efficacy of topical 0.075% capsaicin cream in relieving the pain associated with diabetic neuropathy. 252 patients were enrolled in an 8 week randomized, double-blind trial study, comparing 0.075% capsaisin with a placebo. Capsaicin or the placebo cream was applied to painful areas four times per day for 8 weeks in patients randomly assigned to one of the two groups. Patients returned at weeks 2, 4, 6 and 8 weeks for efficacy and safety evaluations during the treatment period.
Key Findings: Pain intensity and relief were recorded at 2-week internals using physician’s global evaluation and visual analog scales. Analysis at final visit for 252 patients showed statistical significance favoring capsaicin compared with placebo for the following: 69.5% vs 53.4% pain improvement by the physician’s global evaluation scale, 38.1% vs 27.4% decrease in pain intensity, and 58.4% vs 45.3% improvement in pain relief. Capsaicin was well tolerated, and study results suggest that topical capsaicin cream is safe and effective in treating painful diabetic neuropathy.
Reference: The Capsaicin Study Group. Treatment of Painful Diabetic Neuropathy with Topical Capsaicin: a multicenter, double-blind, vehicle-controlled study. Arch Intern Med. 1991; 151:

61. 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)

62. Patient resources

63. Patient Resources
Chronic Pain Centre Public Lectures
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

64. Pain Resources Canadian Pain Coalition www.canadianpaincoalition.ca
Conquering Pain for Canadians booklet
Pain Resource Centre

65. Thank You!