What are the indications, dosing, contraindications, adverse effects, and monitoring requirements for Adipex (phentermine) in adults with obesity or overweight?

Adipex (Phentermine) Clinical Guide

Indications

Phentermine is FDA-approved as a short-term adjunct (a few weeks) for weight reduction in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with weight-related comorbidities such as hypertension, type 2 diabetes, dyslipidemia, or obstructive sleep apnea. 1, 2

• Must be combined with caloric restriction, exercise, and behavioral modification—never prescribed as monotherapy 2
• Despite FDA approval for short-term use only, many experienced clinicians prescribe phentermine off-label for 3–6 months or longer because obesity is now understood as a chronic metabolic disease requiring long-term management 3

Dosing

Standard dosing is 15–37.5 mg orally once daily in the morning to minimize insomnia risk. 1, 3

• Available formulations: 15 mg, 30 mg, and 37.5 mg capsules; 8 mg and 37.5 mg tablets 3, 2
• Low-dose 8 mg tablets can be dosed up to 3 times daily and are scored for doses as low as 4 mg 3
• Start with the lowest effective dose (15 mg or lower) and titrate based on efficacy and tolerability 1, 3
• Can be taken with or without food 3, 2
• Renal impairment: Limit to 15 mg daily in severe renal impairment (eGFR 15–29 mL/min/1.73 m²) 2

Absolute Contraindications

Phentermine must never be prescribed to patients with any history of cardiovascular disease, including coronary artery disease, stroke, arrhythmias (including atrial fibrillation), congestive heart failure, or uncontrolled hypertension. 1, 4, 2

Additional absolute contraindications include:

• Current use or within 14 days of monoamine oxidase inhibitors (MAOIs) due to risk of hypertensive crisis 1, 4, 2
• Pregnancy or inadequate contraception in women of childbearing potential—phentermine is teratogenic 1, 4, 2
• Untreated hyperthyroidism due to risk of arrhythmias and seizures 1, 4, 2
• Glaucoma due to sympathomimetic effects 1, 2
• Agitated states or severe anxiety disorders that may be exacerbated by stimulant properties 1, 2
• History of drug abuse—phentermine is a Schedule IV controlled substance with abuse and dependence potential 1, 4, 2
• Nursing mothers—discontinue drug or nursing 2
• Known hypersensitivity to sympathomimetic amines 2

Use in Controlled Hypertension

Phentermine may be prescribed to patients whose hypertension is well-controlled (systolic <140 mmHg, diastolic <90 mmHg) on antihypertensive therapy that does NOT include MAO inhibitors. 3

• Clinical trials enrolling participants with controlled baseline hypertension found that blood pressure generally decreased during phentermine therapy (average reductions of approximately -7.3 mmHg systolic and -5.4 mmHg diastolic at 52 weeks), likely secondary to weight loss 3
• Blood pressure and heart rate must be monitored at every clinical visit throughout treatment 1, 3

Adverse Effects

Common adverse effects (occurring in ≥5% of patients): 1, 2

• Dry mouth (most common—21% at higher doses)
• Paresthesia
• Constipation
• Insomnia and difficulty sleeping
• Dizziness
• Irritability and anxiety
• Nausea, vomiting, diarrhea
• Dysgeusia (altered taste)

Serious but rare adverse effects: 2

• Primary pulmonary hypertension—discontinue immediately if new unexplained dyspnea, angina pectoris, syncope, or lower extremity edema develops 2
• Serious regurgitant cardiac valvular disease (rare cases reported) 2
• Increased heart rate and blood pressure through sympathetic nervous system activation 1, 3

Important clarification: Phentermine monotherapy should NOT be confused with the discontinued "fen-phen" combination; valvular heart disease and pulmonary hypertension associated with fen-phen were attributed to fenfluramine, not phentermine 3

Pre-Treatment Screening

Before prescribing phentermine, obtain: 3

• Complete cardiovascular history, including remote history of arrhythmias or structural heart disease 4
• Baseline blood pressure and heart rate measurements 3
• Pregnancy status assessment in all women of reproductive potential 3
• Thyroid function assessment to exclude hyperthyroidism 3, 4
• Screen for glaucoma 3
• Medication history to identify MAOI use 3
• Assessment for anxiety disorders, agitated states, or history of substance abuse 3, 4
• Renal function evaluation 3

Graded exercise stress testing is recommended before phentermine initiation in: 4

• Adults ≥35 years with diabetes mellitus, ≥2 cardiovascular risk factors (elevated cholesterol, hypertension, smoking, family history of premature coronary disease), or any cardiovascular symptoms 4
• Men ≥45 years and women ≥55 years with diabetes or ≥2 cardiovascular risk factors who intend to engage in moderate-to-vigorous exercise 4
• Any patient with cardiovascular symptoms such as exertional chest pain, dyspnea, palpitations, or unexplained fatigue 4

Monitoring Requirements

Baseline monitoring: 3

• Blood pressure and heart rate
• Weight and BMI
• Pregnancy test in women of reproductive potential

Ongoing monitoring: 1, 3

• Blood pressure and heart rate at every clinical visit throughout treatment—this is the most critical monitoring parameter 3
• Weight assessment at least monthly for the first 3 months, then at least every 3 months 1
• Discontinue phentermine if <5% weight loss after 12 weeks on maximum dose 1, 3
• Monthly pregnancy testing may be considered in women of reproductive potential when using phentermine beyond 12 weeks 3
• Monitor for psychiatric symptoms (anxiety, insomnia, irritability) 5

No routine laboratory monitoring is required—metabolic panels, lipid profiles, or liver function tests are not mandated by current guidelines; focus remains on cardiovascular parameters and weight-loss efficacy 3

Treatment Duration

FDA approval is technically for short-term use (up to 12 weeks), but this reflects historical regulatory constraints rather than safety concerns specific to phentermine monotherapy. 3

• Many experienced clinicians prescribe phentermine off-label for 3–6 months or longer based on efficacy and cardiovascular safety rather than arbitrary time limits 3
• Continue phentermine if ≥5% weight loss is achieved at 12 weeks and no cardiovascular contraindications develop 3
• No mandatory washout period is required between treatment courses if prior discontinuation was for non-safety reasons 3
• When prescribing beyond 12 weeks, document specific benefits, tolerance profile, adverse effects, and counsel patients regarding off-label use and limited long-term safety data 3

Discontinuation criteria: 3

• <5% weight loss after 12 weeks on maximum dose
• Development of cardiovascular disease or uncontrolled hypertension
• Intolerable side effects that don't resolve with dose reduction
• Pregnancy or planning pregnancy
• Development of other absolute contraindications

Drug Interactions

Critical interactions: 1, 2

• MAOIs: Contraindicated during or within 14 days of MAOI use due to risk of hypertensive crisis 1, 2
• Other sympathomimetic amines: Avoid concurrent use 1, 2
• Alcohol: Concomitant use may result in adverse drug reactions 2
• Insulin and oral hypoglycemics: Dose reduction may be required in diabetic patients 1, 2
• Adrenergic neuron blocking drugs: Hypotensive effect may be decreased by phentermine 2

Psychiatric medication considerations: 5

• Use caution with SSRIs (e.g., escitalopram/Lexapro)—monitor blood pressure and heart rate closely at every visit due to potential additive cardiovascular effects 5
• Avoid in patients requiring benzodiazepines (e.g., lorazepam/Ativan) due to compounding CNS effects and increased sedation/respiratory depression risk 5
• Naltrexone-bupropion should not be used with opioid medications (e.g., buprenorphine/Suboxone) 5

Special Populations

Pregnancy (Category X): Absolutely contraindicated 1, 2

Nursing mothers: Discontinue drug or nursing, taking into consideration importance of drug to mother 2

Pediatric use: Safety and effectiveness not established 2

Geriatric use: Use with caution due to substantial renal excretion 2

Patients with type 2 diabetes: Consider GLP-1 receptor agonists (semaglutide 2.4 mg or liraglutide 3.0 mg) as first-line agents, which have superior efficacy and cardiovascular safety data 1, 3

Safer Alternatives for High-Risk Patients

In patients with cardiovascular disease or significant cardiovascular risk factors, avoid phentermine entirely and consider: 1, 3, 5

• Orlistat (lipase inhibitor)—safer alternative with no sympathomimetic activity 1, 4
• Lorcaserin (5-HT2C receptor agonist)—safer in cardiovascular disease 1
• GLP-1 receptor agonists (semaglutide 2.4 mg or liraglutide 3.0 mg)—superior efficacy (≈21% weight loss with tirzepatide at 72 weeks) and favorable cardiovascular profile 3, 5

Expected Outcomes

Mean weight loss with phentermine 15 mg daily: 5.1% at 28 weeks 1

• 46% of patients achieve ≥5% weight loss 3
• 20.8% achieve ≥10% weight loss 3
• Significant reductions in waist circumference, total cholesterol, and LDL-C 6

Common Pitfalls to Avoid

• Failing to obtain complete cardiovascular history, including remote arrhythmias or structural heart disease 4
• Prescribing to patients with any history of cardiovascular disease—this is an absolute contraindication regardless of current stability 1, 4
• Confusing phentermine monotherapy with "fen-phen"—the cardiac risks were from fenfluramine, not phentermine 3
• Assuming "spacing out" doses eliminates interaction risks with other CNS-active medications—pharmacodynamic interactions persist regardless of timing 5
• Inadequate thyroid function assessment before initiation 4
• Continuing therapy beyond 12 weeks without documented ≥5% weight loss 1, 3
• Failing to monitor blood pressure and heart rate at every visit when using beyond 12 weeks 3
• Prescribing as stand-alone treatment without lifestyle interventions 5