Introduction
Phentermine is a sympathomimetic amine anorectic that has been used clinically for weight management since its FDA approval in 1959. It is one of the most commonly prescribed medications for short-term obesity treatment, typically used as an adjunct to diet and exercise in appropriate patients.
Mechanism of Action
Phentermine acts primarily as a norepinephrine-releasing agent in the central nervous system. It stimulates the hypothalamus to release neurotransmitters that suppress appetite, particularly in the lateral hypothalamic feeding center. The drug may also have some effects on metabolic rate, though its primary therapeutic effect is appetite suppression through central nervous system stimulation.
Indications
- FDA-approved as short-term adjunct (a few weeks) in the management of exogenous obesity
- For use in patients with an initial body mass index (BMI) ≥30 kg/m² or ≥27 kg/m² in the presence of other risk factors (hypertension, diabetes, hyperlipidemia)
- Must be used in conjunction with a reduced-calorie diet and exercise program
Dosage and Administration
Adults:- 15-37.5 mg orally once daily, usually before breakfast or 1-2 hours after breakfast
- Lower doses (15 mg) may be adequate for some patients
- Avoid administration in the evening due to potential insomnia
- Renal impairment: Use with caution; consider lower doses
- Hepatic impairment: Use with caution
- Geriatric patients: Consider lower starting doses due to increased sensitivity
- Pediatrics: Not recommended for use in children under 16 years
- Short-term therapy only (typically up to 12 weeks)
- Limited data support use beyond 12 weeks
Pharmacokinetics
Absorption: Well absorbed from the gastrointestinal tract Distribution: Widely distributed throughout body tissues Metabolism: Hepatic metabolism via cytochrome P450 system Elimination: Renal excretion; elimination half-life approximately 19-24 hours Onset of action: Within 1-2 hours after administration Duration of effect: 12-14 hoursContraindications
- History of cardiovascular disease (coronary artery disease, arrhythmias, congestive heart failure)
- History of cerebrovascular disease
- Moderate to severe hypertension
- Hyperthyroidism
- Glaucoma
- History of drug abuse
- During or within 14 days following MAO inhibitor therapy
- Known hypersensitivity to sympathomimetic amines
- Agitated states
- Pregnancy and breastfeeding
Warnings and Precautions
- Cardiovascular effects: May increase blood pressure and heart rate; monitor regularly
- Valvular heart disease: Some association with phentermine-fenfluramine combination (not used with phentermine monotherapy)
- Pulmonary hypertension: Rare cases reported
- Tolerance: May develop within a few weeks; do not exceed recommended dose
- Abuse potential: Schedule IV controlled substance with potential for psychological dependence
- psychiatric effects: May exacerbate anxiety, agitation, or psychosis
- Withdrawal: Fatigue and depression may follow abrupt discontinuation after prolonged use
Drug Interactions
Major interactions:- MAO inhibitors: Risk of hypertensive crisis (contraindicated within 14 days)
- Other sympathomimetic agents: Additive cardiovascular effects
- SSRIs/SNRIs: Increased risk of serotonin syndrome
- Blood pressure medications: May reduce effectiveness of antihypertensives
- Insulin/oral hypoglycemics: May alter blood glucose control
- Alcohol: May increase adverse CNS effects
- Caffeine: Additive stimulant effects
Adverse Effects
Common (≥5%):- Dry mouth
- Insomnia
- Constipation
- Headache
- Dizziness
- Irritability
- Tachycardia
- Hypertension
- Pulmonary hypertension
- Valvular heart disease (primarily with combination therapy)
- Psychiatric disturbances (anxiety, depression, psychosis)
- Cardiovascular events (palpitations, tachycardia, hypertension)
- Visual disturbances
- Allergic reactions
Monitoring Parameters
- Weight: Weekly measurements initially
- Blood pressure: Baseline and regular monitoring (every 2-4 weeks)
- Heart rate: Baseline and regular monitoring
- Mental status: Assessment for mood changes, anxiety, or depression
- Glucose levels: In diabetic patients
- Adherence: Regular assessment of compliance with diet and exercise program
- Efficacy: Evaluate after 4 weeks; discontinue if weight loss inadequate
Patient Education
- Take exactly as prescribed, typically in the morning to avoid insomnia
- Do not crush or chew extended-release formulations
- Report any chest pain, palpitations, shortness of breath, or dizziness immediately
- Maintain reduced-calorie diet and regular exercise program
- Avoid alcohol and other CNS stimulants
- Be aware of potential for dry mouth and maintain good oral hygiene
- Do not suddenly stop medication without medical supervision
- Understand that this is a short-term treatment adjunct
- Report any mood changes, anxiety, or unusual behaviors
- Keep medication secured and away from others due to abuse potential
References
1. FDA Prescribing Information: Phentermine Hydrochloride 2. Kang JG, Park CY. Anti-Obesity Drugs: A Review about Their Effects and Safety. Diabetes Metab J. 2012;36(1):13-25. 3. Kim KK, Cho HJ, Kang HC, et al. Effects on Weight Reduction and Safety of Short-Term Phentermine Administration in Korean Obese People. Yonsei Med J. 2006;47(5):614-625. 4. Bray GA. Pharmacological treatment of obesity. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. 5. National Institutes of Health. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. NIH Publication No. 98-4083, 1998. 6. Lexicomp Online, Phentermine Monograph. Wolters Kluwer Clinical Drug Information, Inc. 7. American Society of Health-System Pharmacists. AHFS Drug Information. Phentermine Hydrochloride.