Update on ChronicNeuropathic Pain Medications

Joyce Côté, BSc Pharm ACPR

Pharmacist, Chronic Pain Centre

January 16, 2013

Calgary Neuropathy Association Presentation

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Outline

• 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

Rehabilitation

Self-MonitoringPacingRelaxationSelf-TalkCommunication

Self-Management

Medications

Knowledge

Nutrition

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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®

• 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

• 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®), tetrahydrocannabinol-cannabidiol (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

– 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!