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.