What are the indications and guidelines for prescribing phentermine (anorexiant) for weight loss in patients with a body mass index (BMI) of 30 or higher, or those with a BMI of 27 or higher and weight-related health conditions, such as hyperthyroidism, glaucoma, or heart disease?

Phentermine for Weight Loss

Phentermine is indicated as a short-term adjunct to diet, exercise, and behavioral modification for weight loss in patients with BMI ≥30 kg/m² or BMI ≥27 kg/m² with obesity-related comorbidities such as controlled hypertension, diabetes, or hyperlipidemia—but it is absolutely contraindicated in patients with cardiovascular disease, uncontrolled hypertension, hyperthyroidism, or glaucoma. 1

FDA-Approved Indications

Phentermine is FDA-approved only for short-term use (up to 12 weeks) as an adjunct to caloric restriction, exercise, and behavioral modification for weight management. 1, 2

BMI Thresholds

• BMI ≥30 kg/m² regardless of comorbidities 1, 2
• BMI ≥27 kg/m² with at least one weight-related comorbidity including:
  • Controlled hypertension 1, 2
  • Type 2 diabetes or prediabetes 1, 2
  • Hyperlipidemia/dyslipidemia 1, 2
  • Abdominal obesity 3

Absolute Contraindications

Before prescribing phentermine, you must screen for and exclude the following absolute contraindications: 1, 2

• History of cardiovascular disease (coronary artery disease, stroke, arrhythmias, congestive heart failure) 1, 2
• Uncontrolled hypertension 1, 2
• Hyperthyroidism 1, 2
• Glaucoma 1, 2
• Agitated states or anxiety disorders 1, 2
• Current or recent (within 14 days) MAOI use 1, 2
• Pregnancy or inadequate contraception in women of childbearing potential 1, 2
• Breastfeeding 1
• History of drug abuse 1, 2
• Known hypersensitivity to sympathomimetic amines 1

Pre-Treatment Requirements

Obtain the following baseline assessments before initiating phentermine: 4, 2

• Blood pressure and heart rate (phentermine causes sympathetic activation with mild increases in both parameters) 2
• Pregnancy test in all females of reproductive potential 2, 4
• Thyroid function (to exclude hyperthyroidism) 4
• Cardiovascular history and risk assessment 4, 2
• Screen for glaucoma, anxiety disorders, and substance abuse history 4, 2
• Renal function (dose adjustment required in severe renal impairment) 1

Dosing Recommendations

Start with the lowest effective dose and titrate based on response and tolerability: 1, 4

• Starting dose: 15 mg once daily in the morning, approximately 2 hours after breakfast 1
• Maximum dose: 37.5 mg once daily 1
• Alternative low-dose option: 8 mg up to 3 times daily (for patients requiring lower doses) 4
• Avoid late evening dosing due to risk of insomnia 1, 2
• Can be taken with or without food 4

Renal Dosing Adjustments

• Severe renal impairment (eGFR 15-29 mL/min/1.73 m²): Maximum 15 mg daily 1
• End-stage renal disease or eGFR <15 mL/min/1.73 m²: Avoid use 1

Expected Weight Loss Outcomes

Phentermine produces clinically meaningful weight loss when combined with lifestyle interventions: 2, 5

• Mean weight loss: 3.6-4.74 kg (3.6-5.7% total body weight) over placebo at 12-24 weeks 4, 5
• 62% of patients achieve ≥5% weight loss (compared to 21% with placebo; RR 4.12) 4
• Patients with higher baseline hunger and lower cognitive restraint achieve greater weight loss 6

Monitoring Requirements

Monitor the following parameters at every visit throughout treatment: 2, 4

• Blood pressure and heart rate (phentermine causes mild sympathomimetic effects) 2
• Weight loss progress 2, 4
• Adverse effects (dry mouth, insomnia, dizziness, irritability, anxiety) 2, 1
• Monthly pregnancy testing in females of reproductive potential (if using beyond 12 weeks off-label) 4

Discontinuation Criteria

Discontinue phentermine if any of the following occur: 2, 4

• <5% weight loss after 12 weeks on maximum tolerated dose 2, 4
• Development of cardiovascular disease or uncontrolled hypertension 4
• Intolerable side effects that don't resolve with dose reduction 4
• Pregnancy or planning pregnancy 4, 1
• New contraindications develop 4

Duration of Treatment: FDA Approval vs. Clinical Practice

The FDA approves phentermine only for short-term use (≤12 weeks), but many experienced clinicians use it for longer durations (3-6 months or more) as off-label therapy given the chronic nature of obesity. 2, 4, 2

Off-Label Extended Use Considerations

• Recent Mexican guidelines (2024) support phentermine use for 6 months or more in most patients, with treatment decisions based on efficacy rather than arbitrary time limits 4
• Continue beyond 12 weeks if: patient achieves ≥5% weight loss, no cardiovascular contraindications develop, blood pressure and heart rate remain controlled, and medication is well-tolerated 4
• No mandatory washout period required between treatment courses if previously discontinued for non-safety reasons 4
• Document the rationale for off-label extended use including specific benefits, tolerance profile, and counsel patients regarding limited long-term safety data 4

Critical Safety Note

The historical concerns about phentermine's cardiovascular safety stemmed from its combination with fenfluramine ("fen-phen"), but subsequent investigations implicated fenfluramine—not phentermine—as the risk factor for valvular heart disease and pulmonary hypertension. 4

Common Pitfalls to Avoid

• Do not confuse phentermine monotherapy with the discontinued "fen-phen" combination—the cardiovascular risks were attributed to fenfluramine, not phentermine 4
• Do not prescribe phentermine to patients with ANY history of cardiovascular disease, even if currently stable—this is an absolute contraindication 1, 2
• Do not use phentermine as monotherapy without concurrent lifestyle interventions—it must be combined with dietary modification, exercise, and behavioral therapy 1, 2
• Do not continue phentermine beyond 12 weeks if inadequate weight loss (<5%) is achieved—consider alternative therapies 2, 4
• Do not prescribe to patients with controlled hypertension without intensive monitoring—blood pressure must be checked at every visit 2, 4

Alternative and Combination Therapies

For patients with contraindications to phentermine or inadequate response, consider: 2

• Orlistat (lipase inhibitor, safer cardiovascular profile) 2
• GLP-1 receptor agonists (semaglutide 2.4 mg, liraglutide 3.0 mg) for superior efficacy and cardiovascular safety, especially in patients with type 2 diabetes 2, 4
• Phentermine/topiramate ER combination (FDA-approved for long-term use with greater weight loss: 8.6-9.3% at 1 year) 2, 3
• Naltrexone-bupropion ER 2, 5

Patient Counseling Points

Counsel patients on the following before initiating phentermine: 4, 1

• FDA approval is for short-term use (12 weeks), though off-label longer duration is common in clinical practice 4
• Common side effects: dry mouth, insomnia, dizziness, irritability, constipation, anxiety 2, 1
• Phentermine is a Schedule IV controlled substance with potential for abuse and dependence 2, 1
• Avoid late evening dosing to minimize insomnia 1
• Women of childbearing potential must use effective contraception—phentermine is contraindicated in pregnancy 1, 4
• Report immediately: chest pain, palpitations, shortness of breath, severe headache, or vision changes 1