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

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. Overview
• Phentermine Mono-therapy
• Topiramate Mono-therapy
• Qsymia
• Generic Combination

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. 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. -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. -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. 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. 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. 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. Topiramate Weight Loss by Week
Bray, Obes Res. 2003;11(6):722-33

11. Topiramate BP Effects
Bray, Obes Res. 2003;11(6):722-33

12. Topiramate
Astrup, Obes Res. 2004;12(10):1658-69.

14. 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

15. 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.

16. 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

17. Phentermine & Topiramate
Vivus, FDA EMDAC Presentation; July 15, 2010

18. Qsymia Clinical Trial

19. Qysmia & BP

20. 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

21. 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

22. -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%

23. -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%

24. -50.0%
-40.0%
-30.0%
-20.0%
-10.0%
0.0%
10.0%
20.0%
Cumulative Wt Loss P+T
Average = 11.9%

25. 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

26. 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.

27. 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.

28. 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.