Phentermine, Topiramate and Qsymia
Ed J. Hendricks, M.D., F.A.S.B.P.
ASBP 62nd Annual Symposium
Orlando Florida
October 27, 2012
Overview
• Phentermine Mono-therapy• Topiramate Mono-therapy• Qsymia• Generic Combination
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
Phentermine clinical trials & studiesKim Kang U.S.
N (Rx Arm) 28 37 269Duration (wks) 14 12 @12Weight Loss 10% 9.3% 15%≥ 10 % Loss* 58% 53% 83%SBP Δ mm -2 -1 -7.7 DBP Δ mm + 3.7 -1 -3.9Mean SBP mm 125 124 125Dropouts 20% 19% ?
-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.
0 1 2 3 4 8 12 26 40 1 2 3 4 5 6 7
-20
-15
-10
-5
0
5 All Phentermine Treated
% Wt Loss
Delta SBP
Delta DBP
Delta HRWeeks/Years
Hendricks, Obesity. 2011;19(12):2351-2360.
Phentermine, ASEs
• Most common ASEs– Dry Mouth, constipation – anti-cholinergic– Insomnia – early
• Presumed ASEs– Adverse cardiovascular effects– Increased blood pressure– Increased heart rate– Addiction
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.
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
Topiramate Weight Loss by Week
Bray, Obes Res. 2003;11(6):722-33
Topiramate BP Effects
Bray, Obes Res. 2003;11(6):722-33
Topiramate
Astrup, Obes Res. 2004;12(10):1658-69.
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
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.
Qsymia Dosing
Name Phentermine TopiramateTitration 3.25 mg 23 mgRecommended 7.5 mg 46 mgTransition 11.25 mg 69 mgHigh Dose 15 mg 92 mg
Phentermine & Topiramate
Vivus, FDA EMDAC Presentation; July 15, 2010
Qsymia Clinical Trial
Qysmia & BP
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
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
-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%
-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%
-50.0%
-40.0%
-30.0%
-20.0%
-10.0%
0.0%
10.0%
20.0%
Cumulative Wt Loss P+T
Average = 11.9%
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
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.
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.
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.