1. 1 Off-Label Use of Medications in Workers Compensation Matthew Foster, PharmD, BCPS PMSI Clinical Services

2. 2 Objectives Overview of off-label prescribing Overview of off-label prescribing Common off-label medications in workers compensation Common off-label medications in workers compensation Off-label prescribing versus off-label promotion Off-label prescribing versus off-label promotion Strategies to ensure appropriate use of off-label medications Strategies to ensure appropriate use of off-label medications

3. 3 (+)-(S)-N-methyl-γ-(1-naphthyloxy)-2- thiophenepropylamine hydrochloride

4. 4 Overview of off-label prescribing FDA focuses on market entry for prescription drugs FDA focuses on market entry for prescription drugs Does not specifically regulate prescribing practices Does not specifically regulate prescribing practices Prescribers can write for any medication aside from the FDA approval (therefore, off-label) Prescribers can write for any medication aside from the FDA approval (therefore, off-label) Non-approved indications may not receive same degree of scrutiny as those submitted to FDA Non-approved indications may not receive same degree of scrutiny as those submitted to FDA

5. 5 Overview of off-label prescribing What defines off-label specifically? What defines off-label specifically? Age? Antidepressants in children Age? Antidepressants in children Pregnancy? Zofran for nausea Pregnancy? Zofran for nausea Comorbid conditions? Cancer/non-cancer Comorbid conditions? Cancer/non-cancer Dose ranges? Dose ranges? Duration? Duration? Studies are often VERY narrow populations Studies are often VERY narrow populations i.e. Actiq/Fentora: Cancer pain! i.e. Actiq/Fentora: Cancer pain! i.e. Cymbalta/Lyrica: Diabetic neuropathic pain i.e. Cymbalta/Lyrica: Diabetic neuropathic pain

6. 6 Overview of off-label prescribing Overall 21% of medication use is off-label (Arch Intern Med. 2006; 166:1021-1026) Overall 21% of medication use is off-label (Arch Intern Med. 2006; 166:1021-1026) Neurontin (83%), Elavil (81%) Neurontin (83%), Elavil (81%) Study finds 90% of Actiq prescriptions are off- label (Prime Therapeutics Jan 16, 2007) Study finds 90% of Actiq prescriptions are off- label (Prime Therapeutics Jan 16, 2007) In 2002, 94% of Neurontin sales for off-label use (USA Today 8-16-2004) In 2002, 94% of Neurontin sales for off-label use (USA Today 8-16-2004)

7. 7 Common off-label medications in workers compensation Medication FDA indication Off-label use Neurontin Anticonvulsant; Shingles pain Neuropathic pain Lidoderm Shingles pain Neuropathic pain Actiq/Fentora Acute cancer pain Acute pain (non-cancer) Ambien Short-term use sedative Long-term use sedative Lyrica Anticonvulsant; diabetic neuropathic pain Neuropathic pain Cymbalta Antidepressant; diabetic neuropathic pain Neuropathic pain

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10. 10 Off-label prescribing versus off-label promotion Where the pharma industry has gone wild Where the pharma industry has gone wild Neurontin, Actiq, and Oxycontin Neurontin, Actiq, and Oxycontin Generally, sales reps can speak on package insert approved information; everything else has to be requested specifically through their clinical affairs departments Generally, sales reps can speak on package insert approved information; everything else has to be requested specifically through their clinical affairs departments Not well defined criteria; education versus promotion; company policies Not well defined criteria; education versus promotion; company policies How the information is solicited How the information is solicited

11. 11 Education vs. Promotion FDA Office of Criminal Investigations FDA Office of Criminal Investigations $430 million fine to Warner Lambert (Pfizer) due to off-label promotion of Neurontin $430 million fine to Warner Lambert (Pfizer) due to off-label promotion of Neurontin Paid physicians to detail other physicians Paid physicians to detail other physicians Long-list of off-label treatments promoted Long-list of off-label treatments promoted $700 million fine to Purdue (Oxycontin) $700 million fine to Purdue (Oxycontin) Promotion that it was less addictive, less prone to withdrawal Promotion that it was less addictive, less prone to withdrawal TBD: Actiq, Fentora promotions TBD: Actiq, Fentora promotions

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14. 14 Cymbalta ads and website

15. 15 Cymbalta indications (from package insert) Cymbalta is indicated for the treatment of major depressive disorder (MDD). Cymbalta is indicated for the treatment of major depressive disorder (MDD). A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least 5 of the following 9 symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, or a suicide attempt or suicidal ideation. A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least 5 of the following 9 symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, or a suicide attempt or suicidal ideation. But wait: Body map included: stomach ache, aches & pains, headaches!!!! But wait: Body map included: stomach ache, aches & pains, headaches!!!!

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17. 17 Strategies to ensure appropriate use of off-label medications Treatment plans Treatment plans Defined goals in therapy Defined goals in therapy Doesnt just apply to FDA approved indications Doesnt just apply to FDA approved indications Provide evidence for use Provide evidence for use can prescribe versus should prescribe can prescribe versus should prescribe Informed consent Informed consent Educating patients on their treatments Educating patients on their treatments Early referral to specialists Early referral to specialists Washington State guidelines on opioid therapy Washington State guidelines on opioid therapy

18. 18 Conclusion Off label medication use will continue to make up a substantial portion of medication use, especially in workers compensation Off label medication use will continue to make up a substantial portion of medication use, especially in workers compensation Ensure appropriate use through case management and referral to specialists Ensure appropriate use through case management and referral to specialists