What is the proper use and management of Phentermine (anorexiant) for weight loss?

Phentermine for Weight Loss: Proper Use and Management

Indication and Patient Selection

Phentermine is FDA-approved only as a short-term adjunct (a few weeks, typically up to 12 weeks) for weight reduction in patients with BMI ≥30 kg/m² or BMI ≥27 kg/m² with obesity-related comorbidities, and must be combined with exercise, behavioral modification, and caloric restriction. 1

• Despite FDA approval for short-term use only, many clinicians prescribe phentermine for longer durations as off-label therapy, though this requires careful documentation of benefits, tolerance, and adverse effects 2, 3
• The limited usefulness of phentermine should be weighed against inherent risk factors before prescribing 1

Pre-Treatment Assessment Requirements

Before prescribing phentermine, you must complete the following screening:

• Cardiovascular assessment: Obtain baseline blood pressure and heart rate measurements, as phentermine causes mild increases through sympathetic nervous system activation 2, 1
• Pregnancy screening: Assess pregnancy status in all females of reproductive potential, as phentermine is absolutely contraindicated in pregnancy 2, 1
• Renal function: Evaluate kidney function, as phentermine undergoes substantial renal excretion 1
• Contraindication screening: Rule out hyperthyroidism, glaucoma, agitated states/anxiety disorders, and history of drug abuse 2, 1
• Medication review: Confirm patient is not taking MAOIs or has not taken them within the past 14 days (risk of hypertensive crisis) 2, 1

Absolute Contraindications

Phentermine is contraindicated in patients with: 1

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

Dosing Regimen

Start with the lowest effective dose and titrate based on response: 2

• Standard dosing: 15-37.5 mg orally once daily in the morning 2
• Low-dose option: 8 mg up to three times daily 2
• Renal impairment: Limit to 15 mg daily for patients with severe renal impairment (eGFR 15-29 mL/min/1.73 m²) 1
• Timing: Avoid late evening administration due to risk of insomnia 1
• Food: Can be taken with or without food 1

Monitoring During Treatment

Discontinue phentermine if 5% weight loss is not achieved after 12 weeks on maximum dose. 2

• Monitor blood pressure and heart rate periodically throughout treatment 2, 3
• Assess for common side effects: dry mouth, insomnia, dizziness, irritability, constipation, and headache 2, 3
• Watch for serious adverse events requiring immediate discontinuation: new unexplained dyspnea, angina pectoris, syncope, or lower extremity edema (potential primary pulmonary hypertension) 1
• Monitor for tolerance development, which typically occurs within a few weeks; if tolerance develops, discontinue rather than increase dose 1

Treatment Hierarchy in Current Guidelines

Phentermine is not first-line therapy for obesity management:

• First-line: GLP-1 receptor agonists (semaglutide) with superior efficacy (14.9% weight loss) 4
• Second-line: Phentermine/topiramate ER combination (9.8% weight loss at 15/92 mg dose) 4
• Third-line: Orlistat, particularly for patients with cardiovascular concerns or contraindications to stimulants 4
• Phentermine monotherapy: Achieves approximately 5-10% body weight loss when combined with lifestyle interventions, with 46% achieving ≥5% weight loss versus 15.5% with placebo 3

Critical Safety Considerations

• Cardiovascular effects: Phentermine increases blood pressure and heart rate through sympathetic activation; use with extreme caution even in mild hypertension 2, 1
• Pulmonary hypertension: Rare cases of primary pulmonary hypertension have been reported 1
• Valvular heart disease: Rare cases of serious regurgitant cardiac valvular disease have occurred (note: phentermine monotherapy should be distinguished from the withdrawn "fen-phen" combination that was strongly associated with valvular disease) 3, 1
• Drug interactions: Significant potential for moderate and severe drug-drug interactions, particularly with tramadol, dextromethorphan, and other sympathomimetics 5
• Abuse potential: Phentermine is a Schedule IV controlled substance with risk of dependence; prescribe the least amount feasible at one time 1
• Impaired activities: May impair ability to operate machinery or drive 1

Special Populations

• Diabetes patients: Insulin or oral hypoglycemic medication doses may require reduction during phentermine therapy 1
• Hypertensive patients: Even patients with controlled hypertension require careful blood pressure monitoring 2
• Geriatric patients: Use with caution due to substantial renal excretion 1
• Pediatric patients: Safety and effectiveness not established 1

Patient Counseling Points

Inform patients that: 1

• Phentermine is approved only for short-term use as part of a comprehensive weight management program including diet, exercise, and behavioral modification
• Co-administration with other weight loss drugs is not recommended
• They must avoid alcohol during treatment 1
• They should report immediately any chest pain, shortness of breath, swelling of legs, or fainting
• The medication carries risk of dependence and must be stored securely
• Selling or giving away phentermine is illegal 1

Alternative Considerations

For patients with cardiovascular risk factors or contraindications to phentermine, orlistat is a safer alternative as it works by inhibiting gastrointestinal lipases rather than affecting the sympathetic nervous system, blocking absorption of approximately 30% of ingested fat. 2, 4