What is the use of Phentermine (Adipex), an appetite suppressant?

From the Guidelines

Phentermine should be used with lifestyle modifications in adults with obesity or overweight with weight-related complications, as it has been suggested by the AGA with a conditional recommendation and low-quality evidence 1.

Key Points

• Phentermine is approved by the FDA for short-term use (12 weeks) but is often used off-label for longer periods due to the chronic nature of weight management 1.
• The recommended dosage of phentermine is 15 to 37.5 mg orally once daily in the morning 1.
• Phentermine works by suppressing appetite through stimulation of the central nervous system, specifically by increasing norepinephrine levels in the brain.
• Common side effects include dry mouth, insomnia, constipation, increased heart rate, and elevated blood pressure.
• Phentermine is contraindicated in patients with cardiovascular disease, hyperthyroidism, glaucoma, history of drug abuse, or during pregnancy.
• Patients should avoid taking it late in the day to prevent sleep disturbances and should have regular monitoring of vital signs while on this medication.
• Abrupt discontinuation after prolonged use may cause fatigue and depression, so gradual tapering may be recommended.

Considerations

• Phentermine should be used alongside diet and exercise, not as a standalone treatment.
• Patients who have anxiety or insomnia might feel their condition is exacerbated by phentermine, and would not be ideal candidates 1.
• Blood pressure and heart rate should be monitored periodically while taking phentermine 1.
• Phentermine is classified as a Schedule IV controlled substance due to its potential for dependence.

Monitoring and Follow-up

• Regular monitoring of vital signs is necessary while on phentermine.
• Gradual tapering may be recommended to prevent fatigue and depression after prolonged use.
• Patients should be educated on the potential side effects and the importance of adherence to the prescribed regimen.

From the FDA Drug Label

Phentermine Hydrochloride, USP 15 mg and 30 mg is indicated as a short-term (a few weeks) adjunct in a regimen of weight reduction based on exercise, behavioral modification and caloric restriction in the management of exogenous obesity for patients with an initial body mass index greater than or equal to 30 kg/m 2, or greater than or equal to 27 kg/m 2 in the presence of other risk factors (e.g., controlled hypertension, diabetes, hyperlipidemia). The primary use of phentermine is for short-term weight reduction in patients with a body mass index (BMI) of 30 kg/m2 or higher, or 27 kg/m2 or higher with other risk factors.

• Key points:
  • Indicated for exogenous obesity
  • Short-term use (a few weeks)
  • Adjunct to exercise, behavioral modification, and caloric restriction
  • BMI greater than or equal to 30 kg/m2, or greater than or equal to 27 kg/m2 with other risk factors 2

From the Research

Phentermine Overview

• Phentermine is an internationally recognised amphetamine derivative with significant appetite-suppressing properties 3
• It is indicated for the short-term management of obesity, but long-term use may be associated with severe cardiovascular side-effects, abuse, and dependence 3

Potential Drug-Drug Interactions

• A retrospective analysis found that long-term phentermine use may be associated with potential drug-drug interactions (PDDIs), which may result in adverse drug reactions (ADRs) 3
• The top 20 drugs co-prescribed with phentermine in this study population demonstrated no mild PDDI, 15 (75%) moderate PDDIs, and 5 (25%) severe PDDIs 3
• The most common co-prescribed drug in the moderate group was dextromethorphan, and the least co-prescribed was formoterol 3
• Among the drug group 'severe PDDIs', tramadol was most frequently prescribed, whereas phenylpropanolamine was the least prescribed to patients in this group 3

Efficacy and Safety

• Recent research on phentermine is sparse and consists primarily of observational studies with methodologic limitations 4
• These studies suggest that phentermine use is associated with clinically significant weight loss in adults and that the medication is generally well tolerated 4
• Large-scale observational studies evaluating phentermine's safety have not identified an increased risk of cardiovascular events or elevations in blood pressure 4
• There is no data to support the notion that phentermine is addictive 4

Weight Loss and Blood Pressure

• Weight loss is strongly associated with improvement in blood pressure, but the mechanism of weight loss can impact the magnitude and sustainability of blood pressure reduction 5
• Phentermine/topiramate has been shown to lower blood pressure, while orlistat reduces systolic and diastolic blood pressure, and sibutramine increases diastolic blood pressure 6
• A study using electronic health record data found that longer-term phentermine use was associated with greater weight loss without increased risk of incident cardiovascular disease or death 7

Long-Term Effects

• Long-term trials assessing the effect of phentermine on mortality and morbidity are unavailable and needed 6
• A study found that patients using phentermine continuously for more than 12 months lost 7.4% more weight than the referent group at 24 months, with no significant difference in hazard ratios for composite cardiovascular disease or death 7