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Therapeutics Update Cymbalta / Pristiq

Therapeutics Update Cymbalta / Pristiq. K.M. O’Keeffe, MD, FRCPC MCFP Annual Scientific Assembly April 22, 2010. Conflict of Interest Declaration. Speaker’s honoraria have been received from: Bristol – Myers – Squibb Manitoba College of Family Physicians Organon Saint Boniface Hospital

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Therapeutics Update Cymbalta / Pristiq

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  1. Therapeutics UpdateCymbalta / Pristiq K.M. O’Keeffe, MD, FRCPC MCFP Annual Scientific Assembly April 22, 2010

  2. Conflict of Interest Declaration Speaker’s honoraria have been received from: • Bristol – Myers – Squibb • Manitoba College of Family Physicians • Organon • Saint Boniface Hospital • SmithKline – Beecham • University of Manitoba

  3. Conflict of Interest Declaration Advisory board honoraria have been received from: • Astra – Zeneca • Biovail • Wyeth

  4. Conflict of Interest Declaration Your Name Here Call (204) 237-2335 for exciting sponsorship opportunities!

  5. Cymbalta / Pristiq SNRI Antidepressants Shared mechanism of action implies some commonalities…

  6. Cymbalta / Pristiq Side effects: “the usual suspects” • nausea • headache • sexual dysfunction • fatigue • tremor

  7. Cymbalta / Pristiq Side effects: “norepinephrine-related” • sweating • dry mouth • constipation • insomnia • loss of appetite (but weight loss is rare…)

  8. Cymbalta / Pristiq Rarer risks: “the usual suspects” • paradoxical emotional worsening • easy bruising / bleeding • SIADH (elderly)

  9. Cymbalta / Pristiq Rarer risks: “norepinephrine-related” • avoid in glaucoma • hypertension: monitor bp & HR • average increase < 5 mmHg / bpm

  10. Cymbalta / Pristiq No / minimal dose titration • vs. venlafaxine

  11. Cymbalta / Pristiq Additional non-psychiatric uses: • Cymbalta: pain modulation in diabetic neuropathy fibromyalgia : female stress incontinence • Pristiq: menopausal hot flashes

  12. Cymbalta (duloxetine) Usual dose = 60 mg od • some patients start on 30 mg od t ½ = 12 hours

  13. Cymbalta (duloxetine) CyP inhibitor of: 2D6 (use caution) CyP substrate of: • 2D6 : use caution with inhibitors • 1A2 : AVOID with inhibitors

  14. Cymbalta (duloxetine) Hepatotoxicity: 1 – 2 per 100,000 • no requirement for ongoing LFT’s • avoid with risk factors • alcoholism • pre-existing liver disease

  15. Pristiq (desvenlafaxine) Usual dose = 50 mg od • some patients require 100 mg od t ½ = 11 hours

  16. Pristiq (desvenlafaxine) Excretion a combination of: • renal filtration • direct hepatic conjugation • minimal CyP 450 involvement (3A4) Little interaction vulnerability

  17. Pristiq (desvenlafaxine) Reduce to 50 mg eod in renal disease No modification required in hepatic impairment Like venlafaxine, no CyP450 inhibition

  18. Limitations Equivalent to SSRI in treating pain if part of a major depression • as opposed to a chronic pain condition Krebs, 2008

  19. Limitations Comparative efficacy vs. SSRI’s • some meta-analyses slightly favour SNRIs • NNT’s = 10 – 24 • no particular advantage in largest study Cipriani, 2009

  20. Limitations Cost : not regular benefit under Pharmacare Cymbalta ~ $141 per month Pristiq ~ $106 per month

  21. References Arnold et al, Arthritis Rheum 2004, 50: 2974-84 Bymaster et al, Neuropsychopharm 2001, 25: 871-80 Cipriani et al, Lancet 2009, 373: 746-58 Deecher et al, J Pharmacol Exp Ther 2006, 318: 657-65 Gartlehner et al, Drug Saf 2009, 32: 1159-73 Krebs et al, Psychosomatics 2008, 49: 191-8 Lunn et al, Cochrane Data Syst Rev 2009, 4: CD007115 Mariappan et al, Eur Urol 2007, 51: 67-74 Oganesian et al, Psychopharm Bull 2009, 42: 47-63 Papakostas et al, Biol Psych 2007, 62: 1217-27 Raskin et al, Pain Med 2005, 6: 346-56 Speroff et al, Obs Gyn 2008, 111: 77-87 Wernicke et al, Curr Drug Saf 2008, 3: 143-53

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