Obesity Treatment: Qsymia vesus Generic Phentermine and Generic Topiramate

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A discussion comparing using Qsymia (phentermine & topiramate) to using combinations of generic phentermine and generic topiramate.

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  • With the approval of Qysmia we now have 4 alternatives
  • Kim & Kang papers Korean patients. US – my own patients

    * ≥10% weight loss for the US study is @52 weeks not 12 weeks

    Kim = Kim KK, Cho HJ, Kang HC, Youn BB, Lee KR. Effects on weight reduction and safety of short-term phentermine administration in korean obese people. Yonsei medical journal. Oct 31 2006;47(5):614-625.

    Kang = Kang JG, Park CY, Kang JH, Park YW, Park SW. Randomized controlled trial to investigate the effects of a newly developed formulation of phentermine diffuse-controlled release for obesity. Diabetes, Obesity and Metabolism. 2010;12(10):876-882.

    US = Hendricks EJ, Greenway FL, Westman EC, Gupta AK. Blood pressure and heart rate effects, weight loss and maintenance during long-term phentermine pharmacotherapy for obesity. Obesity (Silver Spring). Dec 2011;19(12):2351-2360. This is a study of patients in my own practice.

    Korean trial conclusions: phentermine effective (Panbsey effective)and safe for short term weight loss.

    We couldn’t pass up the opportunity to comment on phentermine blood pressure effects. Hendricks EJ, Rothman RB. Phentermine therapy for obesity does not elevate blood pressure. Diabetes, Obesity and Metabolism. 2011;13:963-964.

    US study retrospective, not a clinical trial.
    Wt loss for Korean trials was calculated on ITT; US is for completers at one year – 10% wt loss not calculated at 12 weeks. Reason US had 50% greater wt loss at 12 wks? The diet – all treated with LCKD
    Blood pressure changes due to weight loss and diet – not thought to be a direct effect of phentermine


  • Each column represents one patient’s weight loss.

    Our study: Hendricks EJ, Greenway FL, Westman EC, Gupta AK. Blood pressure and heart rate effects, weight loss and maintenance during long-term phentermine pharmacotherapy for obesity. Obesity (Silver Spring). Dec 2011;19(12):2351-2360.

    A retrospective study of 300 continuing patients, all treated with phentermine and LCKD (Low carbohydrate Ketogenic diet with protein intake set at ~2X RDA) LCKD the diet of choice for many US obesity treatment specialists. Known to produce better fat loss, better preservation of lean tissue, lower dropout rates, better compliance, better diabetes improvements, & lower BP, etc.
  • Reference: Hendricks, Obesity. 2011
    Note scale – 1-40 weeks, then 1-7 years.
    Note 15% weight loss at 12 weeks and 18% weight loss at one year.
    10% weight loss out to 7 years.
    Note that although average patient regained some weight, SBP changes persisted. DBP also persisted but to less extent.
    The heart rate changes were not significant

    Phentermine-untreated patients followed on the same LCKD had less weight loss but slightly greater decreases in SBP and DBP. However these BP decreases vanished by year 3 as the patients regained most of the weight lost.
  • Bray, Obes Res. 2003;11(6):722-33
  • Remember topiramate is a carbonic anhydrase inhibitor and therefore a diuretic. The blood pressure lowering effect is therefore due to both weight loss and diuretic effects.
  • EQUATE STUDY; Vivus did a comparison study Qnexa vs generic combination
  • 15 mg phentermine; 100 mg topiramate
  • Vivus, FDA EMDAC Presentation; July 15, 2010
    Placebo, Qysmia Low, Qysmia high dose
  • P <0.05, ♮
    Vivus, FDA EMDAC Presentation, July 15, 2010
  • EQUATE STUDY: Qysmia comap
  • Obesity Treatment: Qsymia vesus Generic Phentermine and Generic Topiramate

    1. 1. Phentermine, Topiramate and Qsymia Ed J. Hendricks, M.D., F.A.S.B.P. ASBP 62nd Annual Symposium Orlando Florida October 27, 2012
    2. 2. Overview • Phentermine Mono-therapy • Topiramate Mono-therapy • Qsymia • Generic Combination
    3. 3. Phentermine • Approved for treating obesity1959 • Most widely used anti-obesity drug in U.S. • 6 million prescriptions per year • Classed as C – IV controlled substance • FDA label not a modern label • Stigmatized drug, restrictions on use • Stigma based on presumptions • Safer than is commonly assumed
    4. 4. Phentermine clinical trials & studies Kim Kang U.S. N (Rx Arm) 28 37 269 Duration (wks) 14 12 @12 Weight Loss 10% 9.3% 15% ≥ 10 % Loss* 58% 53% 83% SBP Δ mm -2 -1 -7.7 DBP Δ mm + 3.7 -1 -3.9 Mean SBP mm 125 124 125 Dropouts 20% 19% ?
    5. 5. -45.0% -40.0% -35.0% -30.0% -25.0% -20.0% -15.0% -10.0% -5.0% 0.0% 5.0% Wt Loss, P Rx, 52 Wk, N 1755 5% Wt Loss – 97% 10% Loss - 83% 20% Loss - 32% Hendricks, Obesity. 2011;19(12):2351-2360.
    6. 6. -20 -15 -10 -5 0 5 0 1 2 3 4 8 12 26 40 1 2 3 4 5 6 7 Weeks/Years All Phentermine Treated % Wt Loss Delta SBP Delta DBP Delta HR Hendricks, Obesity. 2011;19(12):2351-2360.
    7. 7. Phentermine, ASEs • Most common ASEs – Dry Mouth, constipation – anti-cholinergic – Insomnia – early • Presumed ASEs – Adverse cardiovascular effects – Increased blood pressure – Increased heart rate – Addiction
    8. 8. Using Phentermine Alone • Start with A.M. dose ½ 37.5 mg tablet. • If 1st dose tolerated add ½ tablet at 12 Noon. • Adjust timing if needed. • Some patients prefer capsules for slower onset of action & lower stimulant effect. • Dose-to-effect titration where effect is control of eating behavior. • Higher doses typically well tolerated.
    9. 9. Topiramate • Approved for seizures in 1996 • Approved for migraine prevention in 2004 • Mono-therapy not approved for obesity • Doses – Epilepsy: 400 mg/day – Migraine prevention: 100 mg/day – Obesity: 25 – 100 mg/day • Starting Rx 25 mg/hs, titrate dose slowly
    10. 10. Topiramate Weight Loss by Week Bray, Obes Res. 2003;11(6):722-33
    11. 11. Topiramate BP Effects Bray, Obes Res. 2003;11(6):722-33
    12. 12. Topiramate Astrup, Obes Res. 2004;12(10):1658-69.
    13. 13. Topiramate, ASEs • Paraesthesias, Dysgusia • Attention difficulty, Memory loss • Fatigue, Somnolence • Depression, Anxiety, Suicidal Ideation • Acute Myopia & Angle Closure Glaucoma • Increased risk of oral clefts if taken during pregnancy in first trimester
    14. 14. Using Topiramate Alone • Start with 25 mg/day; best given h.s. at first • Stay at 25 mg/day at least 2 weeks • Evaluate for ASEs, cravings, binge eating • If marked improvement stay at 25 mg/day • If no ASEs consider increase to 50 mg h.s. • If ASEs either reduce dose or continue at 25 • If no cravings or binge eating look for weight loss +/or changes in eating behavior.
    15. 15. Qsymia Dosing Name Phentermine Topiramate Titration 3.25 mg 23 mg Recommended 7.5 mg 46 mg Transition 11.25 mg 69 mg High Dose 15 mg 92 mg
    16. 16. Phentermine & Topiramate Vivus, FDA EMDAC Presentation; July 15, 2010
    17. 17. Qsymia Clinical Trial
    18. 18. Qysmia & BP
    19. 19. Qsymia Pros & Cons Advantages • Approved for long term use • May be lower cost for insured patients Disadvantages • Higher Cost for self-pay patient • Fixed low dose of phentermine
    20. 20. Using Generic Phentermine/Topiramate • 2008 ASBP Survey: 20% using combination • 2012 ASBP Survey: 28% using combination • Start 37.5 mg tab/ 30 mg cap phentermine first • Evaluate for phentermine efficacy and ASEs • Add topiramate at 2 weeks or later • Evaluate for topiramate efficacy & ASEs • Titrate dose-to-effect; either or both
    21. 21. -25.0% -20.0% -15.0% -10.0% -5.0% 0.0% 5.0% 10.0% Weight Loss on Phentermine Average Wt. Loss = 9.6%
    22. 22. -30.0% -25.0% -20.0% -15.0% -10.0% -5.0% 0.0% 5.0% 10.0% Added Weight Loss added Topiramate Average Wt. Loss = 4.5%
    23. 23. -50.0% -40.0% -30.0% -20.0% -10.0% 0.0% 10.0% 20.0% Cumulative Wt Loss P+T Average = 11.9%
    24. 24. Generic Pros & Cons Advantages • Ability to titrate each drug • Practitioner may have better control of drug compliance • Dispensing docs can profit from sale of drugs Disadvantages • Not approved for long-term use – Off-Schedule • Topiramate is not slow release • patient must take 2 or more pills daily
    25. 25. Advice • QSYMIA is a giant step forward. • Vivus staff have performed a huge service to Obesity Medicine for us, and for our patients. • Qysmia approval is a re-affirmation that obesity is a medical problem – that those afflicted should seek medical help. • Prescribe Qsymia whenever feasible. • Combination of generics – Off-schedule and therefore second choice.
    26. 26. Patients New to Pharmacotherapy • First, discuss & offer Qsymia alone • Discuss costs and comparative costs in the context of insurance coverage and copays • If appropriate, discuss Qsymia with added phentermine (an off-schedule use) • Discuss generic combination if appropriate – IF you and patient are OK with off-schedule drug use.
    27. 27. Patients on Pharmacotherapy • Notify patients Qsymia is available. For indicated and interested patients: • Discuss efficacy and safety issues. • Discuss costs, and comparative costs. • If patient balks at cost and is already on either phentermine or topiramate, discuss off- schedule use of generic combination.

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