What are the indications, recommended dosing, contraindications, common adverse effects, and monitoring requirements for phentermine in adult obesity management?

Phentermine for Adult Obesity Management

Indications

Phentermine is FDA-approved as a short-term adjunct (a few weeks, up to 12 weeks) for weight reduction in adults with BMI ≥30 kg/m², or BMI ≥27 kg/m² with comorbidities (hypertension, diabetes, hyperlipidemia, abdominal obesity), when combined with caloric restriction, exercise, and behavioral modification. 1

However, clinical practice has evolved beyond the FDA label:

• Many experienced obesity specialists prescribe phentermine for 3-6 months or longer off-label, recognizing obesity as a chronic metabolic disease requiring long-term management 2
• The American Gastroenterological Association explicitly acknowledges that phentermine can be used beyond 12 weeks in carefully selected patients without cardiovascular disease 2
• Mexican clinical practice guidelines support phentermine use for 6 months or more, with treatment decisions based on efficacy rather than predetermined cycling schedules 2

Recommended Dosing

Start with 15 mg orally once daily in the morning to minimize insomnia risk, and titrate to 37.5 mg daily based on response and tolerability. 2, 1

Available formulations and dosing options:

• Standard dosing: 15 mg, 30 mg, or 37.5 mg capsules once daily 1
• Low-dose option: 8 mg tablets up to 3 times daily (can be scored to 4 mg) 2
• Timing: Administer early in the morning; avoid late evening dosing due to insomnia risk 1
• Food: Can be taken with or without food 2, 1
• Renal impairment: Limit to 15 mg daily for severe renal impairment (eGFR 15-29 mL/min/1.73 m²) 1

Efficacy Expectations

• Mean weight loss of approximately 5.1% at 28 weeks with 15 mg daily 2
• 46% of patients achieve ≥5% weight loss 2
• 20.8% achieve ≥10% weight loss 2
• At 1 year, mean weight loss is 6.1% versus 1.2% with placebo 3

Absolute Contraindications

Never prescribe phentermine to patients with any of the following: 1

• Cardiovascular disease: Coronary artery disease, stroke, arrhythmias, congestive heart failure, or uncontrolled hypertension 1
• MAOI use: Current use or within 14 days of discontinuation (risk of hypertensive crisis) 1
• Hyperthyroidism 1
• Glaucoma 1
• Agitated states or severe anxiety disorders 1
• History of drug abuse 1
• Pregnancy (Category X) 1
• Nursing mothers 1
• Known hypersensitivity to sympathomimetic amines 1

Relative Contraindications Requiring Caution

• Controlled hypertension: May be considered with intensive blood pressure monitoring, as clinical trials showed blood pressure generally declined with treatment 2
• Diabetes: Insulin or oral hypoglycemic requirements may decrease; monitor closely 1

Pre-Treatment Assessment

Before prescribing phentermine, complete the following screening: 2

• Cardiovascular assessment: Baseline blood pressure and heart rate 2
• Exclude active coronary disease: Younger patients without active coronary disease are more appropriate candidates 2
• Pregnancy screening: Assess pregnancy status in all women of reproductive potential and provide contraception counseling 2
• Thyroid screening: Exclude hyperthyroidism 2
• Ophthalmologic history: Screen for glaucoma 2
• Psychiatric assessment: Evaluate for agitated states or anxiety disorders 2
• Medication review: Confirm no MAOI use within 14 days 2
• Renal function: Assess eGFR for dose adjustment 1

Common Adverse Effects

The most frequent side effects include: 4

• Dry mouth (most common) 4
• Insomnia (minimize by morning dosing) 4
• Dizziness 4
• Irritability and anxiety 4
• Constipation 4
• Dysgeusia (altered taste) 4
• Mild increases in heart rate and blood pressure 4

Serious Adverse Events

• Hypertensive crisis: When combined with MAOIs 4
• Primary pulmonary hypertension: Rare; discontinue if new dyspnea, angina, syncope, or lower extremity edema develops 1
• Cardiac valvulopathy: Rare cases reported 1

Critical distinction: Do not confuse phentermine monotherapy with the discontinued "fen-phen" combination (phentermine-fenfluramine). The valvular heart disease and pulmonary hypertension risks were attributed to fenfluramine, not phentermine. 2

Monitoring Requirements

During Treatment

Monitor blood pressure and heart rate at every visit throughout treatment, especially when using phentermine beyond 12 weeks. 2, 4

• Baseline: Blood pressure, heart rate, weight 2
• Ongoing: Blood pressure and heart rate at each visit 2
• 12-week assessment: Evaluate weight loss response 2
• Women of reproductive potential: Consider monthly pregnancy testing if prescribed beyond 12 weeks 2
• Diabetes patients: Monitor glucose and adjust antidiabetic medications as needed 1

Discontinuation Criteria

Stop phentermine if: 2

• Less than 5% weight loss after 12 weeks on maximum dose 2
• Development of cardiovascular disease or uncontrolled hypertension 2
• New absolute contraindications emerge 2
• Intolerable side effects that don't resolve with dose reduction 2
• Pregnancy or planning pregnancy 2
• Tolerance develops (anorectic effect diminishes within a few weeks) 1

Continuation Criteria for Extended Use

Continue phentermine beyond 12 weeks if: 2

• ≥5% weight loss achieved 2
• No cardiovascular contraindications develop 2
• Blood pressure and heart rate remain controlled 2
• Patient tolerates medication without serious adverse effects 2

Treatment Duration Algorithm

For off-label extended use beyond 12 weeks: 2

1. Document: Specific benefits, tolerance profile, adverse effects 2
2. Counsel: Inform patients about off-label use and limited long-term safety data 2
3. No mandatory cycling: No required gap or "washout period" between courses; treatment decisions based on efficacy and ongoing cardiovascular safety monitoring 2
4. Restarting: If previously discontinued for non-safety reasons, repeat baseline cardiovascular assessment and screen for new contraindications before restarting 2

Special Considerations

Safer Alternatives for High-Risk Patients

For patients with cardiovascular concerns or contraindications to phentermine, consider: 2

• GLP-1 receptor agonists (semaglutide 2.4 mg or liraglutide 3.0 mg): Superior efficacy with different safety profiles; do not carry sympathomimetic cardiovascular risks 2
• Orlistat: Works by inhibiting gastrointestinal lipases rather than affecting the sympathetic nervous system 2

Drug Interactions

• MAOIs: Absolute contraindication; risk of hypertensive crisis 1
• Other sympathomimetic amines: Avoid concurrent use 1
• Alcohol: Consider potential adverse drug reaction 1
• Adrenergic neuron blocking drugs: Phentermine may decrease hypotensive effect 1
• Insulin/oral hypoglycemics: Dose reduction may be required 1

Abuse Potential

• Phentermine is a Schedule IV controlled substance 1
• Prescribe or dispense the least amount feasible at one time to minimize overdosage risk 1
• History of drug abuse is a contraindication 1

Driving and Operating Machinery

Phentermine may impair the ability to engage in potentially hazardous activities such as operating machinery or driving; counsel patients accordingly. 1