What are the guidelines for using phentermine (anorexiant) for weight loss in adults with a body mass index (BMI) of 30 or higher or those with a BMI of 27 or higher and at least one weight-related condition?

Phentermine for Weight Loss

Phentermine is FDA-approved as a short-term adjunct (a few weeks) for weight loss in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with weight-related comorbidities, though many practitioners use it off-label for longer durations (3-6 months or more) when patients achieve at least 5% weight loss without cardiovascular contraindications. 1

Patient Selection Criteria

Eligible patients include:

• Adults with BMI ≥30 kg/m² regardless of comorbidities 1
• Adults with BMI ≥27 kg/m² with at least one weight-related condition (controlled hypertension, diabetes, hyperlipidemia) 1

Absolute Contraindications

Never prescribe phentermine to patients with: 1

• History of cardiovascular disease (coronary artery disease, stroke, arrhythmias, congestive heart failure, uncontrolled hypertension) 1
• Current or recent (within 14 days) monoamine oxidase inhibitor use 1
• Hyperthyroidism 1
• Glaucoma 1
• Agitated states or history of drug abuse 1
• Pregnancy or nursing 1
• Known hypersensitivity to sympathomimetic amines 1

Pre-Treatment Assessment

Before initiating phentermine, obtain: 2

• Baseline blood pressure and heart rate measurements 2
• Cardiovascular risk assessment and consider baseline EKG 2
• Complete blood count (CBC) 3
• Comprehensive metabolic panel (liver function, kidney function, electrolytes) 3
• Lipid panel 3
• Thyroid stimulating hormone (TSH) to exclude hyperthyroidism 2, 3
• Pregnancy test for women of reproductive potential 2

Dosing and Administration

Standard dosing: 1

• Start with 15-37.5 mg orally once daily in the morning, approximately 2 hours after breakfast 1
• Alternative: 8 mg up to 3 times daily (at 1:00 PM and 4:00 PM) for patients who skip breakfast and eat more in afternoon/evening 2, 4
• Avoid late evening administration due to insomnia risk 1
• Can be taken with or without food 2

Renal dosing adjustments: 1

• Limit to 15 mg daily for severe renal impairment (eGFR 15-29 mL/min/1.73 m²) 1
• Avoid use in end-stage renal disease requiring dialysis 1

Expected Weight Loss Outcomes

Efficacy data shows: 5, 6

• Mean weight loss of 3.75% at 12 weeks with phentermine monotherapy 5
• When combined with topiramate: 5.1% weight loss with lower dose (3.75/23 mg), 10.9% with higher dose (15/92 mg) at 56 weeks 7
• Phentermine monotherapy produces more weight loss than lorcaserin or naltrexone-bupropion 5

Monitoring Requirements

During treatment, monitor at every visit: 2, 8

• Blood pressure and heart rate (phentermine causes mild increases through sympathetic activation) 2, 8
• Body weight to assess efficacy 2
• For women of reproductive potential: monthly pregnancy testing may be warranted 2

Discontinuation Criteria

Stop phentermine if: 8

• Patient has not lost at least 5% of body weight after 12 weeks on maximum tolerated dose 8
• Patient has not lost at least 3% of body weight after 12 weeks at standard dose 8
• New cardiovascular symptoms develop (dyspnea, angina, syncope, lower extremity edema) 1
• Tolerance develops (usually within a few weeks) 1
• Unacceptable side effects occur 1

Treatment Duration Considerations

FDA approval vs. real-world practice: 2, 8

• FDA-approved for short-term use (a few weeks, typically 12 weeks) 1
• Many practitioners prescribe off-label for 3-6 months or longer given obesity's chronic nature 2, 8
• If continuing beyond 12 weeks, base decision on achieving ≥5% weight loss and absence of cardiovascular contraindications 2, 8
• Document specific benefits, tolerance profile, and counsel patients regarding off-label use 2
• Some patients who don't respond at 3 months may achieve ≥5% weight loss by 6 months 8

Common Side Effects

Patients should be counseled about: 1, 6

• Dry mouth (most common) 7, 6
• Insomnia (avoid late evening dosing) 1, 6
• Constipation 6
• Dizziness 6
• Increased heart rate and blood pressure 2
• Potential impairment of ability to operate machinery or drive 1

Serious Adverse Events (Rare)

Be vigilant for: 1

• Primary pulmonary hypertension 1
• Serious regurgitant cardiac valvular disease 1
• These risks were historically associated with fenfluramine (in "fen-phen" combination), not phentermine monotherapy 2

Drug Interactions

Avoid or use with extreme caution: 1

• Monoamine oxidase inhibitors (risk of hypertensive crisis) 1
• Other sympathomimetic amines 1
• Alcohol (consider potential interaction) 1
• Insulin and oral hypoglycemics (may require dose reduction) 1
• Adrenergic neuron blocking drugs (phentermine may decrease hypotensive effect) 1

Combination Therapy Considerations

Phentermine-topiramate combination: 7

• FDA-approved in 2012 for obesity 7
• Produces greater weight loss than phentermine monotherapy (10.9% vs 3.75% at 56 weeks) 7, 5
• Superior to orlistat and naltrexone-bupropion in systematic reviews 7
• Consider for patients with obesity and comorbid migraine headaches 7
• Safety and efficacy of combining phentermine with other weight loss drugs (including over-the-counter or herbal products) has not been established 1

Comparison to Newer Agents

When considering alternatives: 7

• GLP-1 receptor agonists (semaglutide 2.4 mg, tirzepatide) produce superior weight loss (20.9% with tirzepatide 15 mg at 72 weeks) 7
• GLP-1 agonists have cardiovascular benefits (semaglutide reduced CV events by 20% in SELECT trial) 7
• GLP-1 agonists lack the cardiovascular risks associated with sympathomimetic agents 2
• Phentermine remains the most commonly prescribed anti-obesity medication in the USA due to lower cost and wide availability 8, 9

Special Populations

Renal impairment: 1

• Phentermine is substantially renally excreted 1
• Limit to 15 mg daily for eGFR 15-29 mL/min/1.73 m² 1
• Avoid in end-stage renal disease 1

Pediatric use: 1

• Not recommended for patients under 16 years of age 1

Geriatric use: 1

• Use with caution due to substantial renal excretion 1

Common Pitfalls to Avoid

Critical considerations: 2

• Do not confuse phentermine monotherapy with the discontinued "fen-phen" combination (phentermine-fenfluramine) 2
• Valvular heart disease and pulmonary hypertension risks were attributed to fenfluramine, not phentermine 2
• Do not routinely cycle phentermine on/off based on calendar time alone; base decisions on efficacy and safety 8
• Do not prescribe to patients with any history of cardiovascular disease, even if "stable" 2, 1
• Do not exceed recommended doses if tolerance develops; discontinue instead 1

Abuse Potential

Controlled substance considerations: 1

• Phentermine is Schedule IV controlled substance 1
• Prescribe or dispense the least amount feasible at one time to minimize overdosage risk 1
• Large-scale observational studies have not identified addiction as a significant concern 9