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Update on Chronic Neuropathic Pain Medications Joyce Côté, BSc Pharm ACPR Pharmacist, Chronic Pain Centre January 16, 2013 Calgary Neuropathy Association Presentation Outline • • • • • • Medication Goals and Patient’s Toolbox Antidepressants Anticonvulsants Opioids Cannabinoids Medical marijuana 2 Goals of Medication Therapy • 30% pain relief may be expected • Increase function • Balance pain relief with acceptable side effects 3 Patient’s Toolbox Knowledge Nutrition Rehabilitation Medications SelfManagement Self-Monitoring Pacing Relaxation Self-Talk Communication 4 ANTIDEPRESSANTS – TRICYCLIC 5 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 6 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 7 Nortriptyline Alberta Blue Cross – Regular Benefits •10 mg capsule $0.09 •25 mg capsule $0.18 8 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 9 ANTIDEPRESSANTS – SNRI 10 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 11 Venlafaxine Alberta Blue Cross – Regular Benefits •37.5 mg capsule $0.35 •75 mg capsule $0.70 •150 mg capsule $0.73 12 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) 13 Duloxetine Alberta Blue Cross – Regular Benefit •30 mg capsule $1.88 •60 mg capsule $3.75 14 ANTIEPILEPTICS – 1ST LINE 15 Antiepileptics – 1st Line • Gabapentin (Neurontin®), pregabalin (Lyrica®) • 1st line for neuropathic pain • Side Effects: – Drowsiness, dizziness, unsteadiness, unable to think clearly, weight gain 16 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 17 Pregabalin • Health Canada Indications – Diabetic peripheral neuropathy – Postherpetic neuralgia – Spinal cord injury neuropathic pain – Fibromyalgia 18 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 19 ANTIEPILEPTICS – OTHER 20 Antiepileptics – Other • Topiramate (Topamax®), lamotrogine (Lamictal®), carbamazepine (Tegretol®), oxcarbazepine (Trileptal®), divalproex (Epival®) 21 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 22 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 23 OPIOIDS 24 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 25 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 26 Tramadol Long-Acting • Also increases serotonin and norepinephrine • Ralivia® • Tridural® – 25% immediate-release • Zytram XL® • Durela®) – 17 to 25% immediate-release 27 Ralivia® • 100 mg tablet ~$1.32 • 200 mg tablet ~$2.39 • 300 mg tablet ~$3.48 28 Tridural® • 100 mg tablet ~$1.26 • 200 mg tablet ~$2.31 • 300 mg ~$3.26 29 Zytram XL® • • • • • 75 mg tablet ~$0.91 100 mg ~$1.18 150 mg ~$1.71 300 mg ~$3.26 400 mg ~$4.28 30 Durela® • 100 mg capsule ~$1.22 • 200 mg capsule ~$2.23 • 300 mg capsule ~$3.23 31 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 32 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 33 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 34 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 35 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 36 CANNABINOIDS 37 Cannabinoids • Nabilone (Cesamet®), tetrahydrocannabinolcannabidiol (Sativex®) • Side effects: – Drowsiness, dizziness, unsteadiness, dry mouth 38 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) 39 Nabilone Alberta Blue Cross – Regular Benefits •0.5 mg capsule $3.10 (generic $1.17) •1 mg capsule $6.21 (generic $2.33) 40 Tetrahydrocannabinol-cannabidiol (Sativex®) • Spray under tongue or inside cheek • Usually 8 sprays/day • Alberta Blue Cross – Not a Benefit • Vials of 48 sprays = ~$125 41 MEDICAL MARIJUANA 42 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” 43 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 44 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 45 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 46 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 47 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 48 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 49 Medical Marijuana • Distribution – Delivery every month by courier to your home or doctor’s office • Cost – 30 seeds = $20 – Dried marijuana = $5/gram 50 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.” 51 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 52 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.” 53 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” 54 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 55 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 56 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 [email protected]. 57 TOPICAL ANALGESICS 58 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 59 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 60 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) 61 PATIENT RESOURCES 62 Patient Resources • Chronic Pain Centre Public Lectures www.albertahealthservices.ca/2790.asp – – – – – – – – – – 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 63 Pain Resources • Canadian Pain Coalition www.canadianpaincoalition.ca – Conquering Pain for Canadians booklet – Pain Resource Centre 64 THANK YOU! 65