What is the recommended dosing for Diethylpropion (amfepramone) for obesity treatment?

Diethylpropion Dosing for Obesity Treatment

Diethylpropion is dosed as either 25 mg immediate-release tablets three times daily before meals, or as 75 mg extended-release tablets once daily in the morning. 1

Standard Dosing Regimens

Immediate-Release Formulation

• 25 mg three times daily, administered before meals 1
• Timing before meals optimizes appetite suppression during eating periods 1

Extended-Release Formulation

• 75 mg once daily in the morning 1
• Morning administration reduces risk of insomnia and aligns with circadian activity patterns 2

Treatment Duration Considerations

FDA-Approved Duration

• Officially approved for short-term use (12 weeks maximum) 1
• FDA approval dates to 1959 when obesity was incorrectly viewed as an acute, curable condition 1

Real-World Clinical Practice

• Many practitioners use diethylpropion longer than 12 weeks off-label given obesity's chronic nature 1
• The AGA acknowledges this extended off-label use as common practice 1
• Recent evidence supports 84-day (12-week) treatment cycles showing 9.5 kg weight loss with preserved muscle mass 3

Patient Selection Criteria

Appropriate Candidates

• Adults with BMI ≥25 kg/m² with weight-related complications, or BMI ≥30 kg/m² 4
• Patients who have not responded adequately to lifestyle interventions alone 1
• Must be used adjunctively with caloric restriction and increased physical activity 1

Absolute Contraindications

• History of cardiovascular disease (coronary artery disease, stroke, arrhythmias, congestive heart failure) 1
• Untreated hyperthyroidism due to concerns for arrhythmias and seizures 1
• Uncontrolled hypertension 1

Monitoring Requirements

Cardiovascular Surveillance

• Monitor blood pressure and heart rate periodically at every visit throughout treatment 1
• This is particularly critical given diethylpropion's sympathomimetic properties 1
• Recent data showed no significant blood pressure increases during 12-week treatment, though mild elevations occurred after 70 days 3

Efficacy Assessment

• Evaluate weight loss response at 12 weeks 5
• Discontinue if inadequate response (though specific thresholds for diethylpropion are less defined than for phentermine) 5

Common Adverse Effects to Anticipate

• Constipation, dry mouth, insomnia, headache, and irritability are most frequently reported 1
• Insomnia, irritability, or anxiety are the most common reasons for treatment discontinuation 1
• Serious adverse events occur at rates <1 in 1000, similar to phentermine 1

Critical Clinical Considerations

Abuse Potential

• Classified as Schedule IV controlled substance due to concerns for abuse and dependence 1
• Chemical modification of the molecule results in less CNS stimulation potential compared to other amphetamine derivatives 1

Perioperative Management

• Manage similarly to phentermine-topiramate ER before procedures requiring general anesthesia due to sympathomimetic effects 1

Pulmonary Hypertension Risk

• Historical concerns exist, though most affected patients also used fenfluramine 1
• Risk appears lower with diethylpropion monotherapy 1

Expected Outcomes

Weight Loss Efficacy

• Mean absolute weight loss of 4.74 kg compared to placebo 1
• Patients 3.51 times more likely to achieve 5% total body weight loss 1
• Patients 14.48 times more likely to achieve 10% total body weight loss 1
• Recent real-world data showed 9.5 kg (10%) weight loss at 84 days with significant fat loss (11.5 kg) and preserved muscle mass 3

Body Composition Changes

• Significant fat mass reduction (20.5%) without significant muscle mass loss when combined with dietary intervention 3
• Waist circumference reductions of approximately 5.6 cm, though not always statistically significant 3

Evidence Quality Caveat

The overall certainty of evidence supporting diethylpropion is low due to short study durations (mostly 3-6 months versus the desired 48+ weeks), small sample sizes, and methodological limitations in older trials 1. Despite this, the AGA made a conditional recommendation favoring its use because undesirable effects are infrequent and not serious, while desirable effects are of moderate magnitude 1.