What are the guidelines for prescribing Phentermine to patients with a history of cardiovascular disease, glaucoma, or hyperthyroidism?

Phentermine Prescribing Guidelines for High-Risk Patients

Phentermine is absolutely contraindicated in patients with any history of cardiovascular disease (including coronary artery disease, stroke, arrhythmias, or congestive heart failure), untreated hyperthyroidism, and glaucoma, according to FDA labeling and major gastroenterology guidelines. 1, 2

Absolute Contraindications

Cardiovascular Disease

• Any history of cardiovascular disease represents an absolute contraindication, including remote history of coronary artery disease, stroke, arrhythmias, structural heart disease, or congestive heart failure 1, 2
• Uncontrolled hypertension is an absolute contraindication; phentermine may further elevate blood pressure through sympathetic nervous system activation 1, 3, 2
• The American Gastroenterological Association explicitly states that phentermine should be avoided in patients with cardiovascular disease due to lack of large cardiovascular outcome trial data for long-term use 3, 2

Hyperthyroidism

• Untreated hyperthyroidism is an absolute contraindication due to concerns for arrhythmias and seizures when combined with phentermine's sympathomimetic effects 1, 3, 2
• Thyroid function must be assessed before initiating phentermine therapy 2, 4

Glaucoma

• Glaucoma is an absolute contraindication due to phentermine's sympathomimetic effects, which can worsen intraocular pressure 1, 3
• This applies particularly to acute angle-closure glaucoma 3

Additional Absolute Contraindications

Drug Interactions

• Phentermine must not be used during or within 14 days of monoamine oxidase inhibitor (MAOI) administration due to risk of hypertensive crisis 1, 3, 2
• Concomitant use with other sympathomimetic amines is contraindicated 1, 3

Psychiatric and Substance Use History

• History of drug abuse is an absolute contraindication, as phentermine is a Schedule IV controlled substance with abuse and dependence potential 1, 3, 2
• Agitated states and anxiety disorders are contraindications, as phentermine's stimulant properties may exacerbate these conditions 1, 3

Pregnancy and Lactation

• Pregnancy is an absolute contraindication 1, 3, 2
• Nursing mothers must discontinue either the drug or breastfeeding 1
• Women of childbearing potential require counseling about reliable contraception and potentially monthly pregnancy testing 3, 2

Pre-Treatment Screening Algorithm

Mandatory Assessments Before Prescribing

• Obtain complete cardiovascular history, including any remote history of arrhythmias, structural heart disease, coronary disease, or stroke 2, 4
• Measure baseline blood pressure and heart rate to establish cardiovascular stability 2, 4
• Assess thyroid function to exclude hyperthyroidism before starting therapy 2, 4
• Evaluate renal function (eGFR) as phentermine requires dose adjustment or avoidance in renal impairment 2, 1
• Screen for glaucoma, particularly in older patients or those with risk factors 2, 4
• Assess pregnancy status in all women of reproductive potential 3, 2, 4
• Evaluate for history of substance abuse or psychiatric conditions 1
• Review all current medications for potential drug interactions, particularly MAOIs, other sympathomimetics, and serotonergic agents 3, 1

Monitoring Requirements During Treatment

Cardiovascular Monitoring

• Blood pressure and heart rate must be monitored at every visit throughout treatment, as phentermine causes mild increases through sympathetic nervous system activation 3, 2, 4
• Discontinue immediately if new cardiovascular symptoms develop, including palpitations, chest pain, or dyspnea 1

Efficacy Assessment

• Discontinue phentermine if patient has not lost at least 5% of body weight after 12 weeks on maximum dose 2, 4, 5

Common Pitfalls to Avoid

Historical Confusion

• Do not confuse phentermine monotherapy with the discontinued "fen-phen" combination (phentermine-fenfluramine), which was associated with valvular heart disease and pulmonary hypertension—these risks were attributed to fenfluramine, not phentermine 4
• While rare cases of valvular heart disease and primary pulmonary hypertension have been reported with phentermine alone, the association remains unclear 1

Inadequate Screening

• Failing to obtain a complete cardiovascular history, including remote events, is a critical screening error that may expose patients to serious harm 2
• Inadequate assessment of thyroid function before initiation is a critical error that can lead to life-threatening arrhythmias 2

Controlled Hypertension

• Even patients with controlled hypertension require caution, as phentermine may increase blood pressure 1
• Younger patients without active coronary disease are more appropriate candidates 4

Dosing Considerations in Special Populations

Renal Impairment

• Limit dosage to 15 mg daily for patients with severe renal impairment (eGFR 15-29 mL/min/1.73 m²) 1
• Avoid use in patients with eGFR less than 15 mL/min/1.73 m² or end-stage renal disease requiring dialysis 1

Timing of Administration

• Administer early in the day (approximately 2 hours after breakfast) to minimize insomnia risk 1
• Late evening administration should be avoided 3, 1