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Pain Pearls: Focus on Pharmacotherapy

Annie Ottney, PharmD, BCPS

September 22, 2021

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Today’s Agenda

  • Migraine medications
  • Buprenorphine for chronic pain
  • Diabetic neuropathy
  • NSAID review

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New Drugs for the Treatment of Migraines

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CGRP Antagonist Mechanism of Action

Image from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4187032/

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CGRP Antagonists-Prophylaxis

Drug Name

FDA Approval Date

Target

Route

Frequency

Erenumab (Aimovig)

May 2018

Blocks CGRP receptor

Autoinjector

Once monthly

Fremanezumab

(Ajovy)

September 2018

Binds CGRP

Autoinjector and prefilled syringe

Once monthly or once every 3 months

Galcanezumab

(Emgality)

September 2018

Binds CGRP

Auto-injector and prefilled syringe

Once monthly

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CGRP Antagonists

  • “G-pants”-still target CGRP

Drug Name

Acute (max)

Prophylaxis

Max doses per month

Rimegepant

(Nurtec ODT)

75 mg/ 24 hours

75 mg every other day

18

Ubrogepant

(Ubrelvy)

200 mg/ 24 hours

N/a

8

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CGRP Antagonist-Warnings

*Erenumab (Aimovig) associated with elevations in blood pressure (up to 40 mmHg systolic and 30 mmHg diastolic)*

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CGRP Antagonist-Warnings

  • Use in pregnancy/lactation

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    • Safety unknown 🡪 consider discontinuation 3 to 5 half-lives before conception

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Drug

Half Life

Time to Discontinue Before Conception

Aimovig

28 days

3 to 5 months

Ajovy

31 days

3 to 5 months

Emgality

27 days

3 to 5 months

Nurtec

11 hours

1 to 2 days

Ubrelvy

5 to 7 hours

1 to 2 days

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Migraine Medications

  • Overall comparative efficacy/safety

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  • Can a patient use both a triptan and a “G-pant” for the treatment of acute migraine?

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Migraine: Patient Case

  • Considering efficacy and safety, for which one of the following patients would it be best to recommend a CGRP monoclonal antibody(mAb) for migraine prevention?

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    • 32-year-old woman with an average of one migraine/month with no contraception present who is in a same-sex relationship

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    • 45-year-old woman with fibromyalgia for whom duloxetine did not reduce migraine frequency after an adequate trial who has a high-deductible insurance plan

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    • 37-year-old woman who has an intrauterine device, no plans for pregnancy, and for whom adequate trials of topiramate and Botox have failed

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    • 68-year-old man with recent coronary artery disease with stent placement 3 months ago who also has uncontrolled hypertension and for whom adequate trials of divalproex and metoprolol have failed

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Migraine: Patient Case

  • TJ is a 48-year-old woman (BMI 28 kg/m2, blood pressure 122/60 mm Hg, heart rate 62 beats/minute) with a history of migraine headaches, tremor, irritable bowel syndrome, and a history of nephrolithiasis. Her current medications include propranolol 20 mg by mouth twice daily, sumatriptan 100 mg as needed, and a levonorgestrel intrauterine device. She has no history of any medication trial for migraine prevention.
  • Which one of the following migraine preventives is best to recommend for this patient?

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    • Erenumab
    • Divalproex
    • Topiramate
    • Venlafaxine

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Buprenorphine in Chronic Pain Management

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Put Me in Coach

  • Buprenorphine rotation

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    • Systematic review evaluating benefits and risks of transition to buprenorphine from mu agonists in patients on long-term opioids for chronic pain

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Powell VD, et al. JAMA Netw Open.2021;4:e2124132.

Pain control similar to mu agonists

Fewer adverse effects

Improvements in depression scores and insomnia

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Put Me in Coach

  • Buprenorphine
    • Partial mu agonist
      • Stimulates mu receptors, but has a “ceiling effect”
      • Limits respiratory depression, but not analgesia
        • Combining buprenorphine with benzos and/or alcohol overcomes this protective effect

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    • Kappa antagonist
      • Reduces stress-induced drug seeking behavior
      • Antidepressant/anti-anxiety effect

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    • Very high affinity for opioid receptors
      • Incomplete dissociation from receptor = prolonged duration of action

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Benefits of Buprenorphine

Less constipation

Ceiling effect with respiratory depression, not analgesia

Not immunosuppressive

Not associated with hypogonadism

Safe in renal dysfunction and dialysis

Davis MP. J Support Oncol.2012;10:209-219.

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Buprenorphine Formulations

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Approved for Pain

Approved for OUD

Buprenorphine buccal film (Belbuca)

X

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Buprenorphine weekly transdermal patch (Butrans)

X

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Buprenorphine/naloxone sublingual film (Suboxone)

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X

Buprenorphine sublingual tablet (Subutex)

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X

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Buprenorphine: Patient Case

  • Pretend you have a 76-year-old female patient who is currently taking hydrocodone 5/325 mg-1 tablet by mouth every 4 hours scheduled for osteoarthritis of her knees.

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  • You would like to switch the patient to buprenorphine to improve safety and tolerability.

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  • How would you make the transition from hydrocodone to buprenorphine? Which formulation of buprenorphine would you plan to use?

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Review of Treatment for Diabetic Peripheral Neuropathy

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Diabetic Peripheral Neuropathy

  • Role of glucose control in prevention of DPN

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    • Tight glucose control NOT associated with reduction in symptoms of neuropathy once developed

↓ risk of neuropathy by 78% in people with Type 1 diabetes

“Tight” blood glucose control early in treatment

(target A1c < 7%)

↓ risk of neuropathy by 5-9% in people with Type 2 diabetes

Pop-Busui R, et al. Diabetes Care.2017;40:136-154.

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Diabetic Peripheral Neuropathy

  • “Treatments/interventions do not change underlying pathology and natural history of the disease process, but may have a positive impact on quality of life.”

--ADA Standards of Care

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Diabetic Peripheral Neuropathy

  • American Diabetes Association Guidelines

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BOLD = FDA approved for indication

Level of Evidence

Medication

A

Pregabalin, duloxetine

B

Gabapentin, tricyclic antidepressants (e.g. amitriptyline, nortriptyline)

E

Opioids (tramadol, tapentadol)

Pop-Busui R, et al. Diabetes Care.2017;40:136-154.

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Diabetic Peripheral Neuropathy

  • GABA analog comparison

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Controlled Substance?

Typical Dose

Absorption

Adverse Effects

Pregabalin (Lyrica)

Yes (C-5)

300-450 mg/day

Not saturable; linear

Sedation, peripheral edema, weight gain

Gabapentin (Neurontin)

Yes in Michigan (C-5), not federal

1800-3600 mg/day

Saturable; non-linear

Sedation, dizziness

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Diabetic Peripheral Neuropathy

  • Tapentadol (Nucynta, Nucynta ER)

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    • Mu agonist + norepinephrine reuptake inhibitor

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    • Unlike tramadol, no effect on serotonin reuptake

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    • $$$$ and may need PA from insurance

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NSAID Review

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NSAID Review

  • Which NSAID should not be administered for more than 5 consecutive days?

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    • Ibuprofen
    • Diclofenac
    • Ketorolac
    • Naproxen

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NSAID Facts

Anti-inflammatory

Analgesic

Antipyretic

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NSAID Facts

COX-1

COX-2

COX-3

  • “Housekeeping” function
  • Cytoprotection of gastric mucosa
  • Renal hemodynamics
  • Platelet aggregation
  • Induced by increased inflammation
  • Production of prostacyclin

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  • Located in the central nervous system only
  • Mediates central analgesia and antipyretic activity only

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Image from: https://www.onlinecjc.ca/article/S0828-282X(21)00349-4/fulltext

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NSAID Kahoot