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Off-Label Use of Off-Label Use of Medications in Medications in

Workers’ Workers’ CompensationCompensation

Matthew Foster, PharmD, Matthew Foster, PharmD, BCPSBCPS

PMSI Clinical ServicesPMSI Clinical Services

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ObjectivesObjectives

Overview of off-label prescribingOverview of off-label prescribing Common off-label medications in Common off-label medications in

workers’ compensationworkers’ compensation Off-label prescribing versus off-label Off-label prescribing versus off-label

promotionpromotion Strategies to ensure appropriate use Strategies to ensure appropriate use

of off-label medicationsof off-label medications

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(+)-(S)-N-methyl-γ-(1-naphthyloxy)-2-

thiophenepropylamine hydrochloride

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Overview of off-label Overview of off-label prescribingprescribing

FDA focuses on market entry for FDA focuses on market entry for prescription drugsprescription drugs Does not specifically regulate prescribing Does not specifically regulate prescribing

practicespractices Prescribers can write for any medication Prescribers can write for any medication

aside from the FDA approval (therefore, aside from the FDA approval (therefore, off-label)off-label)

Non-approved indications may not Non-approved indications may not receive same degree of scrutiny as receive same degree of scrutiny as those submitted to FDAthose submitted to FDA

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Overview of off-label Overview of off-label prescribingprescribing

What defines “off-label” specifically?What defines “off-label” specifically? Age?Age? Antidepressants in children Antidepressants in children Pregnancy?Pregnancy? Zofran for nausea Zofran for nausea Comorbid conditions?Comorbid conditions? Cancer/non-cancer Cancer/non-cancer Dose ranges?Dose ranges? Duration?Duration?

Studies are often VERY narrow Studies are often VERY narrow populations populations i.e. Actiq/Fentora: i.e. Actiq/Fentora: CancerCancer pain! pain! i.e. Cymbalta/Lyrica: i.e. Cymbalta/Lyrica: DiabeticDiabetic neuropathic neuropathic

painpain

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Overview of off-label Overview of off-label prescribingprescribing

Overall 21% of medication use is off-Overall 21% of medication use is off-label label (Arch Intern Med. 2006; 166:1021-1026)(Arch Intern Med. 2006; 166:1021-1026)

Neurontin (83%), Elavil (81%)Neurontin (83%), Elavil (81%) Study finds 90% of Actiq Study finds 90% of Actiq

prescriptions are off-label prescriptions are off-label ((Prime Therapeutics Prime Therapeutics Jan 16, 2007)Jan 16, 2007)

In 2002, 94% of Neurontin sales for In 2002, 94% of Neurontin sales for off-label use off-label use ((USA Today 8-16-2004)USA Today 8-16-2004)

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Common off-label Common off-label medications in workers’ medications in workers’

compensationcompensationMedicationMedication FDA indicationFDA indication Off-label useOff-label use

NeurontinNeurontin Anticonvulsant; Anticonvulsant; Shingles painShingles pain

Neuropathic painNeuropathic pain

LidodermLidoderm Shingles painShingles pain Neuropathic painNeuropathic pain

Actiq/Actiq/FentoraFentora

Acute cancer painAcute cancer pain Acute pain (non-Acute pain (non-cancer)cancer)

AmbienAmbien Short-term use Short-term use sedativesedative

Long-term use Long-term use sedativesedative

LyricaLyrica Anticonvulsant; Anticonvulsant; diabetic neuropathic diabetic neuropathic

painpain

Neuropathic painNeuropathic pain

CymbaltaCymbalta Antidepressant; Antidepressant; diabetic neuropathic diabetic neuropathic

painpain

Neuropathic painNeuropathic pain

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Off-label prescribing versus Off-label prescribing versus off-label promotionoff-label promotion

Where the pharma industry has gone Where the pharma industry has gone wildwild Neurontin, Actiq, and OxycontinNeurontin, Actiq, and Oxycontin

Generally, sales reps can speak on Generally, sales reps can speak on package insert approved information; package insert approved information; everything else has to be everything else has to be requestedrequested specifically through their clinical affairs specifically through their clinical affairs departmentsdepartments Not well defined criteria; education versus Not well defined criteria; education versus

promotion; company policiespromotion; company policies How the information is solicitedHow the information is solicited

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Education vs. PromotionEducation vs. Promotion

FDA Office of Criminal InvestigationsFDA Office of Criminal Investigations $430 million fine to Warner Lambert $430 million fine to Warner Lambert

(Pfizer) due to off-label promotion of (Pfizer) due to off-label promotion of NeurontinNeurontin

Paid physicians to detail other physiciansPaid physicians to detail other physicians Long-list of off-label treatments promotedLong-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 Promotion that it was less addictive, less prone

to withdrawalto withdrawal TBD: Actiq, Fentora promotionsTBD: Actiq, Fentora promotions

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Cymbalta ads and Cymbalta ads and websitewebsite

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Cymbalta indications Cymbalta indications (from package insert)(from package insert)

Cymbalta is indicated for the treatment of major Cymbalta is indicated for the treatment of major depressive disorder (MDD). depressive disorder (MDD).

A major depressive episode (DSM-IV) implies a A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, mood that usually interferes with daily functioning, and includes at least 5 of the following 9 symptoms: and includes at least 5 of the following 9 symptoms: depressed mood, loss of interest in usual activities, depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired worthlessness, slowed thinking or impaired concentrationconcentration, or a suicide attempt or suicidal , or a suicide attempt or suicidal ideation. ideation.

But wait: Body map included: stomach ache, But wait: Body map included: stomach ache, aches & pains, headaches!!!!aches & pains, headaches!!!!

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Strategies to ensure Strategies to ensure appropriate use of off-label appropriate use of off-label

medicationsmedications Treatment plansTreatment plans

Defined goals in therapyDefined goals in therapy Doesn’t just apply to FDA approved indicationsDoesn’t just apply to FDA approved indications

Provide evidence for useProvide evidence for use ““can” prescribe versus “should” prescribecan” prescribe versus “should” prescribe

Informed consentInformed consent Educating patients on their treatmentsEducating patients on their treatments

Early referral to specialistsEarly referral to specialists Washington State guidelines on opioid therapyWashington State guidelines on opioid therapy

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ConclusionConclusion

Off label medication use will Off label medication use will continue to make up a substantial continue to make up a substantial portion of medication use, especially portion of medication use, especially in workers’ compensationin workers’ compensation

Ensure appropriate use through case Ensure appropriate use through case management and referral to management and referral to specialistsspecialists