What dose, duration, and monitoring are recommended for phentermine in an adult (≥18 years) with a body‑mass index ≥ 30 kg/m² (or ≥ 27 kg/m² with an obesity‑related comorbidity) after failed lifestyle modification, and what are its contraindications?

Phentermine Dosing for Weight Loss

For adults with BMI ≥30 kg/m² (or ≥27 kg/m² with obesity-related comorbidities), start phentermine 15–37.5 mg orally once daily in the morning, continue only if ≥5% weight loss is achieved after 12 weeks, and monitor blood pressure and heart rate at every visit throughout treatment. 1, 2, 3

Dosing Regimen

• Standard dose: 15–37.5 mg orally once daily in the morning to minimize insomnia risk. 1, 2, 3
• Low-dose option: 8 mg tablets can be administered up to three times daily (scored tablets allow doses as low as 4 mg). 2
• Renal impairment: Limit dosage to 15 mg daily for patients with severe renal impairment (eGFR 15–29 mL/min/1.73 m²). 3
• Food: Phentermine can be taken with or without food. 2, 3

Treatment Duration

• FDA approval: Phentermine is approved for short-term use (12 weeks maximum). 1, 3
• Off-label extended use: Many clinicians prescribe phentermine for 3–6 months or longer because obesity is a chronic metabolic disease requiring long-term management. 1, 2
• Continuation criteria: Continue phentermine beyond 12 weeks only if the patient achieves ≥5% weight loss after 12 weeks of therapy. 1, 2
• Discontinuation criteria: Stop phentermine if <5% weight loss after 12 weeks on the maximum tolerated dose. 1, 2

Pre-Treatment Evaluation

Before prescribing phentermine, complete the following assessments:

• BMI verification: Confirm BMI ≥30 kg/m² or ≥27 kg/m² with at least one weight-related comorbidity (hypertension, dyslipidemia, diabetes, prediabetes, or abdominal obesity). 1, 2
• Cardiovascular screening: Obtain baseline blood pressure and heart rate; exclude any history of cardiovascular disease (coronary artery disease, stroke, arrhythmias, congestive heart failure, or uncontrolled hypertension). 1, 2, 3
• Pregnancy screening: Verify negative pregnancy test in all women of reproductive potential; phentermine is FDA pregnancy category X. 2, 3
• Medication review: Identify recent MAOI exposure (within 14 days), other sympathomimetics, and alcohol use. 2, 3
• Medical history: Exclude hyperthyroidism, glaucoma, agitated states, psychiatric disorders (anxiety, agitation), and substance-use disorders. 2, 3

Absolute Contraindications

Phentermine must never be prescribed to patients with:

• Cardiovascular disease: Any history of coronary artery disease, stroke, arrhythmias, congestive heart failure, or uncontrolled hypertension. 1, 2, 3
• MAOI use: Current use or use within 14 days of monoamine oxidase inhibitors (risk of hypertensive crisis). 2, 3
• Pregnancy or inadequate contraception: Phentermine is contraindicated throughout pregnancy and in women of childbearing potential without reliable contraception. 2, 3
• Hyperthyroidism: Untreated hyperthyroidism (risk of arrhythmias). 2, 3
• Glaucoma: Angle-closure glaucoma (sympathomimetic effects worsen intraocular pressure). 2, 3
• Psychiatric conditions: Agitated states or history of drug abuse. 2, 3
• Other sympathomimetics: Concomitant use of other sympathomimetic amines. 2, 3

Monitoring Protocol

During Treatment

• Blood pressure and heart rate: Measure at every clinical visit throughout phentermine therapy. 1, 2
• Weight assessment: Monthly for the first 3 months, then at least every 3 months thereafter. 2
• Pregnancy testing: Consider monthly pregnancy testing in women of reproductive potential when prescribing beyond 12 weeks. 2

Expected Cardiovascular Effects

• Despite sympathomimetic activity, observational data show that blood pressure often decreases during phentermine therapy (approximately −7.3 mmHg systolic and −5.4 mmHg diastolic at 52 weeks), likely secondary to weight loss. 2
• Clinical trials of phentermine-topiramate ER demonstrated overall declines in blood pressure with only modest increases in heart rate at higher doses. 2

Use in Controlled Hypertension

• Phentermine may be prescribed to patients whose hypertension is well-controlled (systolic <140 mmHg and diastolic <90 mmHg) on antihypertensive therapy that does not include MAO inhibitors. 1, 2
• Blood pressure and heart rate must be monitored at every visit. 1, 2

Expected Weight Loss Outcomes

• Mean weight loss: Approximately 3.6–4.74 kg (3.63–5.1% total body weight loss) at 12–28 weeks. 1, 4
• Clinically significant response: 46% of patients achieve ≥5% weight loss and 20.8% achieve ≥10% weight loss with 15 mg daily at 28 weeks. 1, 2
• Real-world effectiveness: Patients lose an average of 3.75% body weight after 12 weeks in clinical practice. 4

Lifestyle Integration

Phentermine must be combined with:

• Caloric restriction: Approximately 500 kcal daily deficit (total 1200–1800 kcal/day). 1, 2
• Physical activity: ≥150 minutes per week of moderate-intensity aerobic activity (e.g., walking 30 minutes most days). 1, 2

Common Adverse Effects

• Central nervous system: Overstimulation, restlessness, dizziness, insomnia, irritability, headache. 2, 3
• Gastrointestinal: Dry mouth (13–21%), unpleasant taste, constipation (15–17%), diarrhea. 2, 3, 5
• Cardiovascular: Palpitations, tachycardia, modest blood pressure elevation. 2, 3
• Neurologic: Paresthesia (14–21% in combination products). 5

Critical Safety Misconception

• Phentermine monotherapy should not be confused with the discontinued "fen-phen" combination (phentermine-fenfluramine). 1, 2
• The valvular heart disease and pulmonary hypertension associated with fen-phen were caused by fenfluramine, not phentermine. 1, 2

Alternative Medications for High-Risk Patients

If phentermine is contraindicated due to cardiovascular disease or significant cardiovascular risk:

• GLP-1 receptor agonists: Semaglutide 2.4 mg weekly (≈10–12% weight loss at 68 weeks) or liraglutide 3.0 mg daily (≈5.6% weight loss at 1 year) offer superior efficacy and favorable cardiovascular safety profiles. 2, 6, 7
• Orlistat: 120 mg three times daily with meals (≈2.89 kg weight loss at 12 months) is appropriate for patients with cardiovascular contraindications, though efficacy is lower. 1, 2

No Mandatory Washout Period

• If phentermine was previously discontinued for non-safety reasons, no mandatory waiting period is required before restarting. 2
• Repeat baseline cardiovascular assessment and screen for new contraindications before restarting. 2

Laboratory Monitoring

• Routine metabolic panels, lipid profiles, liver function tests, or other laboratory studies are not mandated by current phentermine monitoring guidelines. 2
• Focus should remain on cardiovascular parameters (blood pressure, heart rate) and weight-loss efficacy. 2