1. The Skinny On Weight Loss Drugs Siggi Ming, ARNP, NP-C Weight Loss Center of Oklahoma

2. Objectives Learner will be able to identify pharmacological agents currently approved by the FDA for the treatment of obesity Learner will be able to identify pharmacological agents currently approved by the FDA for the treatment of obesity Learner will be able to identify indications for the use of pharmacological agents when treating overweight/obese patients Learner will be able to identify indications for the use of pharmacological agents when treating overweight/obese patients Learner will be able to discuss the use of pharmacological agents in combination with behavior modification, nutrition, and use of supplements in the treatment of overweight/obesity Learner will be able to discuss the use of pharmacological agents in combination with behavior modification, nutrition, and use of supplements in the treatment of overweight/obesity

3. Definition of Overweight/Obesity Overweight: BMI of 25.0 – 29.9 kg/m2 Overweight: BMI of 25.0 – 29.9 kg/m2 Obese: BMI of 30.0 – 39.9 kg/m2 Obese: BMI of 30.0 – 39.9 kg/m2 Morbidly Obese: BMI of 40.0 kg/m2 and > Morbidly Obese: BMI of 40.0 kg/m2 and >

4. When to Treat Any time comorbidities are present, i.e. DM II, hyperlipidemias, heart disease, GERD, hypertension, metabolic syndrome, sleep apnea, stress incontinence Any time comorbidities are present, i.e. DM II, hyperlipidemias, heart disease, GERD, hypertension, metabolic syndrome, sleep apnea, stress incontinence Any time the patient requests help with weight loss efforts Any time the patient requests help with weight loss efforts

5. How Is Overweight/Obesity Treated? Behavior Modification and Lifestyle Changes Behavior Modification and Lifestyle Changes Nutritional Counseling Nutritional Counseling Exercise Counseling Exercise Counseling Correcting Endocrine Imbalances Correcting Endocrine Imbalances Supplements Supplements Prescription Medications Prescription Medications

6. Pharmacologic Agents Orlistat  The only FDA approved drug for long term use term use  Lipase Inhibitor; inhibits absorption of dietary fat  Minimal systemic absorption  Tmax approx. 8 hrs  Half life approx. 1-2 hrs  Metabolism occurs mainly in GI wall  Elimination via fecal route (97%)

7. Orlistat Indications & Dosage Obesity Management Obesity Management Weight Loss Weight Loss Weight maintenance Weight maintenance 120 mg po tid with or < 1 hr after fat containing meal 120 mg po tid with or < 1 hr after fat containing meal Omit if meal is non-fat Omit if meal is non-fat

8. Orlistat Contraindications Hypersensitivity Hypersensitivity Chronic malabsorption syndromes Chronic malabsorption syndromes Cholestasis Cholestasis Hx of calcium oxalate kidney stones Hx of calcium oxalate kidney stones Hx of Anorexia or bulimia Hx of Anorexia or bulimia Hx of organ transplant Hx of organ transplant

9. Orlistat Adverse Reactions Serious: Hypersensitivity (anaphylaxis) Hypersensitivity (anaphylaxis) Angioedema Angioedema Vitamin deficiencies (fat soluble vit) Vitamin deficiencies (fat soluble vit) hepatotoxicity hepatotoxicity

10. Orlistat Adverse Reactions Common: Oily spotting Oily spotting Flatulence with fecal discharge Flatulence with fecal discharge Fecal urgency and incontinence Fecal urgency and incontinence Fatty, oily stools Fatty, oily stools Abdominal discomfort Abdominal discomfort

11. Orlistat Drug Interactions Warfarin: Watch for increased INR due to decreased Vitamin K absorption Warfarin: Watch for increased INR due to decreased Vitamin K absorption Cyclosporine: Decreased levels Cyclosporine: Decreased levels Amiodarone: Decreased levels Amiodarone: Decreased levels Fat soluble vitamins (K, A, D, E): Decreased absorption Fat soluble vitamins (K, A, D, E): Decreased absorption Thyroid hormone: Decreased absorption Thyroid hormone: Decreased absorption

12. Orlistat Safety Pregnancy Category B Pregnancy Category B Lactation safety unknown Lactation safety unknown Monitoring: no routine testing recommended Monitoring: no routine testing recommended

13. Drugs approved for short term use Phentermine Phentermine Diethylpropion Diethylpropion Phendimetrazine Phendimetrazine

14. Phentermine FDA approved for short term use (up to 12 weeks) FDA approved for short term use (up to 12 weeks) Sympathomimetic; stimulates CNS activity; stimulates catecholamine release, thereby decreasing hunger Sympathomimetic; stimulates CNS activity; stimulates catecholamine release, thereby decreasing hunger Rapidly absorbed from GI tract Rapidly absorbed from GI tract Half life approx. 24 hrs Half life approx. 24 hrs Excretion: 70-80% unchanged in urine Excretion: 70-80% unchanged in urine

15. Phentermine Indications & Dosage Short term treatment of obesity Short term treatment of obesity 37.5 mg po qd before 1000 to avoid insomnia 37.5 mg po qd before 1000 to avoid insomnia Start with ½ strength Start with ½ strength Increase dosage to full strength if ½ strength not causing enough appetite suppression Increase dosage to full strength if ½ strength not causing enough appetite suppression

16. Phentermine Contraindications Hypersensitivity Hypersensitivity MAOI use MAOI use Arteriosclerosis Arteriosclerosis Cardiovascular disease Cardiovascular disease Hyperthyroidism Hyperthyroidism Glaucoma Glaucoma Agitation Agitation Hx of drug abuse Hx of drug abuse Pregnancy Pregnancy Breastfeeding Breastfeeding

17. Phentermine Adverse Reactions Serious: Dependency Dependency Psychosis Psychosis Tachycardia Tachycardia Hypertension Hypertension Pulmonary hypertension Pulmonary hypertension Valvular heart disease Valvular heart disease

18. Phentermine Adverse Reactions Common: Palpitations Palpitations Tachycardia Tachycardia Restlessness Restlessness Insomnia Insomnia Diarrhea Diarrhea Xerostomia Xerostomia Hypertension Hypertension Euphoria Euphoria Headache Headache

19. Phentermine Drug Interactions Anorexiants/stimulants (increased risk of CV, CNS stimulation) Anorexiants/stimulants (increased risk of CV, CNS stimulation) MAOIs (hypertensive crisis) MAOIs (hypertensive crisis) Linezolid (increased risk for HTN) Linezolid (increased risk for HTN) Effexor (additive effect) Effexor (additive effect)

20. Phentermine Safety Pregnancy Category C Pregnancy Category C Lactation: possibly unsafe Lactation: possibly unsafe CV evaluation at baseline (ECG, BP, physical CV exam; consider echo at baseline and after dc) CV evaluation at baseline (ECG, BP, physical CV exam; consider echo at baseline and after dc) Schedule IV Schedule IV

21. Diethylpropion FDA approved for short term use (up to 12 weeks) FDA approved for short term use (up to 12 weeks) Sympathomimetic; stimulates CNS activity; stimulates catecholamine release, thereby decreasing hunger Sympathomimetic; stimulates CNS activity; stimulates catecholamine release, thereby decreasing hunger Rapidly absorbed Rapidly absorbed Half life 4-6 hrs Half life 4-6 hrs Excretion: urine Excretion: urine

22. Diethylpropion Indications & Dosage Short term treatment of obesity Short term treatment of obesity 25 mg po up to tid; 75 mg ER qd 25 mg po up to tid; 75 mg ER qd 25 mg approx. 1 hr before “hungriest” time of day; may take up to tid 25 mg approx. 1 hr before “hungriest” time of day; may take up to tid Do not take after 1600 to avoid insomnia Do not take after 1600 to avoid insomnia 75 mg ER q am 75 mg ER q am

23. Diethylpropion Contraindications Hypersensitivity Hypersensitivity Pulmonary hypertension Pulmonary hypertension Severe hypertension Severe hypertension Agitation Agitation Valvular heart disease Valvular heart disease Heart murmur Heart murmur Cardiovascular disease Cardiovascular disease Seizure disorder Seizure disorder Advanced arteriosclerosis Advanced arteriosclerosis

24. Diethylpropion Adverse Reactions Serious: Tachycardia Tachycardia Hypertension Hypertension Pulmonary hypertension Pulmonary hypertension Valvular heart disease Valvular heart disease Hallucinations Hallucinations Psychosis Psychosis Leukopenia Leukopenia

25. Diethylpropion Adverse Reactions Common: Dry mouth Dry mouth Diarrhea/constipation Diarrhea/constipation Restlessness Restlessness Anxiety Anxiety Insomnia Insomnia Headache Headache Hypertension Hypertension Palpitations Palpitations Arrhythmias Arrhythmias

26. Diethylpropion Drug Interactions Anorexiants/stimulants (increased risk of CV and CNS stimulation Anorexiants/stimulants (increased risk of CV and CNS stimulation MAOIs (hypertensive crisis) MAOIs (hypertensive crisis) Linezolid (increased risk of HTN) Linezolid (increased risk of HTN) Effexor (additive effects) Effexor (additive effects)

27. Diethylpropion Safety Pregnancy Category B Pregnancy Category B Lactation safety unknown Lactation safety unknown Cardiovascular evaluation at baseline; ECG, BP, physical CV exam) Cardiovascular evaluation at baseline; ECG, BP, physical CV exam) Consider echo periodically and after dc Consider echo periodically and after dc Schedule IV Schedule IV

28. Phendimetrazine FDA approved for short term use (up to 12 weeks) FDA approved for short term use (up to 12 weeks) Sympathomimetic; stimulates CNS activity; stimulates catecholamine release, thereby decreasing hunger Sympathomimetic; stimulates CNS activity; stimulates catecholamine release, thereby decreasing hunger Rapidly absorbed Rapidly absorbed Half life 2 hrs (10 hrs ER) Half life 2 hrs (10 hrs ER) Excretion: urine Excretion: urine

29. Phendimetrazine Indications & Dosage Short term treatment of obesity Short term treatment of obesity 17.5-35 mg po bid-tid; 1 hr ac 17.5-35 mg po bid-tid; 1 hr ac Do not give after 1600 to avoid insomnia Do not give after 1600 to avoid insomnia 105 mg ER po q am 30-60 mins ac 105 mg ER po q am 30-60 mins ac

30. Phendimetrazine Contraindications Hypersensitivity Hypersensitivity Symptomatic cardiovascular disease Symptomatic cardiovascular disease Moderate/severe hypertension Moderate/severe hypertension Hyperthyroidism Hyperthyroidism Agitation Agitation MAOI use MAOI use Valvular heart disease Valvular heart disease Pregnancy Pregnancy Glaucoma Glaucoma Advanced arteriosclerosis Advanced arteriosclerosis

31. Phendimetrazine Adverse Reactions Serious: Hypertension Hypertension Tachycardia Tachycardia Pulmonary hypertension Pulmonary hypertension Withdrawal if abrupt dc after long term high-dose use Withdrawal if abrupt dc after long term high-dose use

32. Phendimetrazine Adverse Reactions Common: Palpitations Palpitations Tachycardia Tachycardia Restlessness Restlessness Hypertension Hypertension Insomnia Insomnia Agitation Agitation Dizziness Dizziness Headache Headache Flushing Flushing Sweating Sweating Tolerance Tolerance Diarrhea/constipation Diarrhea/constipation

33. Phendimetrazine Drug Interactions Anorexiants/stimulants (increased risk of CV and CNS stimulation Anorexiants/stimulants (increased risk of CV and CNS stimulation MAOIs (hypertensive crisis) MAOIs (hypertensive crisis) Linezolid (increased risk of HTN) Linezolid (increased risk of HTN) Effexor (additive effects) Effexor (additive effects)

34. Phendimetrazine Safety Pregnancy Category C Pregnancy Category C Lactation possibly unsafe Lactation possibly unsafe Cardiovascular evaluation at baseline; ECG, BP, physical CV exam Cardiovascular evaluation at baseline; ECG, BP, physical CV exam Consider echo periodically and after dc Consider echo periodically and after dc Schedule III Schedule III

35. Drugs Used Off Label Pristiq Antidepressant (SNRI) Antidepressant (SNRI) Side effects include decreased appetite, weight loss Side effects include decreased appetite, weight loss Seems to decrease cravings Seems to decrease cravings

36. Drugs Used Off Label Topamax  For migraine/headache; seizure disorders  Side effects include weight loss, anorexia  Many undesirable side effects

37. Drugs Used Off Label Spironolactone  Decreases CHO cravings  Useful prior to menses  Start the day premenstrual S/S begin, stop when menstrual flow ceases

38. Drugs Used Off Label Pindolol  Weak beta blocker  Use with phentermine, diethylpropion to block stimulant effect without affecting anorectic effect

39. hCG Human chorionic gonadotropin Human chorionic gonadotropin Hormone secreted by the female body in response to pregnancy Hormone secreted by the female body in response to pregnancy Used off and on since the 1950s in conjunction with a very low calorie diet (usually 500 kcal/day) Used off and on since the 1950s in conjunction with a very low calorie diet (usually 500 kcal/day)

40. hCG No evidence that hCG is associated with weight loss No evidence that hCG is associated with weight loss No evidence that the use of hCG is safe No evidence that the use of hCG is safe ASBP strongly discourages the use of hCG for weight loss ASBP strongly discourages the use of hCG for weight loss

41. Supplements Good quality supplements can aid weight loss efforts by Good quality supplements can aid weight loss efforts by - raising resting metabolic rate - raising resting metabolic rate - increasing lipid metabolism - increasing lipid metabolism - curbing hunger - curbing hunger - raising energy levels - raising energy levels

42. Combined Effort Nutrition Nutrition Behavior Behavior Lifestyle Lifestyle Medications/Supplements Medications/Supplements