What are the guidelines for using phentermine (phentermine) for weight loss?

Phentermine for Weight Loss

The AGA recommends using phentermine with lifestyle modifications for adults with obesity or overweight with weight-related complications, though the evidence quality is low and the recommendation is conditional. 1

FDA Approval and Dosing

• Phentermine is FDA-approved only for short-term use (12 weeks) as an adjunct to caloric restriction, exercise, and behavioral modification in patients with BMI ≥30 kg/m² or ≥27 kg/m² with comorbidities 2
• Standard dosing: 15-37.5 mg orally once daily in the morning to minimize insomnia risk 1
• Lower doses (8 mg) can be taken up to 3 times daily, approximately 30 minutes before meals, and can be split to as low as 4 mg 1
• Some patients respond adequately to quarter tablet (9.375 mg) or half tablet (18.75 mg) doses 1

Off-Label Long-Term Use

Despite FDA approval for only 12 weeks, many practitioners prescribe phentermine for longer durations off-label given the chronic nature of obesity. 1

• When using long-term, document specific benefits, tolerance, adverse effects, and inform patients about off-label use and limited supporting data 1
• Confirm with state licensure authorities regarding local laws and regulations, as phentermine is a Schedule IV controlled substance 1
• Discontinue if 5% weight loss is not achieved after 12 weeks on maximum dose 3

Mechanism and Expected Weight Loss

• Phentermine is an adrenergic agonist that increases norepinephrine release, causing appetite suppression and increased resting energy expenditure 1
• Patients with higher baseline hunger and lower cognitive restraint are more likely to achieve significant weight loss with phentermine 4
• Mean weight loss typically ranges from 5-6% of initial body weight 4, 5

Absolute Contraindications

Avoid phentermine in patients with: 1

• History of cardiovascular disease or uncontrolled hypertension
• During or within 14 days of MAOI use
• Hyperthyroidism (untreated)
• Glaucoma
• Pregnancy or nursing
• Agitated states or history of drug abuse
• Concomitant use with other sympathomimetic amines

Cardiovascular Safety Monitoring

Blood pressure and heart rate must be monitored periodically while taking phentermine, especially in the first 12 weeks. 1

• Observational data from phentermine monotherapy do not show significant increases in blood pressure or heart rate in treated individuals 1
• The cardiovascular concerns with fenfluramine-phentermine (fen-phen) were related to fenfluramine's serotonergic effects on cardiac tissue, not phentermine itself 1
• Large cardiovascular outcome trial data for long-term phentermine monotherapy are lacking, so caution remains warranted 1

Common Side Effects

Most frequently reported adverse effects include: 1

• Dry mouth
• Constipation
• Insomnia and irritability
• Palpitations
• Dizziness

Critical Pitfalls to Avoid

• Do not confuse phentermine monotherapy safety with the withdrawn fen-phen combination - the valvulopathies and pulmonary hypertension were caused by fenfluramine's serotonergic effects, not phentermine 1
• Do not use in patients with active cardiovascular disease despite observational safety data, as no large outcome trials exist 1
• Do not prescribe without checking for MAOI use within the past 14 days due to risk of hypertensive crisis 1
• Do not assume addiction potential - there is no data supporting that phentermine is addictive despite its Schedule IV classification 6

Special Populations

• Phase 3 trials enrolled subjects up to age 70, but no high-quality data guide use in geriatric populations 1
• Avoid in patients with untreated hyperthyroidism due to concerns for arrhythmias and seizures 1

Drug Interactions

• Phentermine has no pharmacologic interaction with corticosteroids 7
• No interaction with JAK inhibitors like upadacitinib (Rinvoq), though cardiovascular monitoring remains important 3