What are the cardiac effects of phentermine (anorexiant) on the heart?

Cardiac Effects of Phentermine

Phentermine should be avoided in patients with a history of cardiovascular disease or uncontrolled hypertension due to potential cardiac risks including palpitations, tachycardia, blood pressure elevation, and rare but serious risks of valvular heart disease and pulmonary hypertension. 1

Primary Cardiac Effects

• Phentermine is a sympathomimetic amine that works by increasing norepinephrine levels in the central nervous system, which can affect cardiovascular function 1
• Common cardiovascular effects include palpitations and tachycardia 2
• Potential for blood pressure elevation, though observational data from phentermine monotherapy shows minimal significant increases in blood pressure in most treated individuals 1, 3
• Small increases in heart rate may occur, particularly at higher doses 1

Serious Cardiovascular Concerns

Pulmonary Hypertension

• Rare cases of primary pulmonary hypertension have been reported with phentermine use 2
• Patients should be monitored for new or unexplained symptoms of dyspnea, angina pectoris, syncope, or lower extremity edema 2
• If these symptoms develop, phentermine should be discontinued immediately 2

Valvular Heart Disease

• Rare cases of serious regurgitant cardiac valvular disease have been reported 2
• The historical association with valvular heart disease was primarily linked to the combination of fenfluramine-phentermine ("fen-phen"), with fenfluramine being the primary culprit 1, 4
• Fenfluramine metabolites directly activated serotonin receptors (5-hydroxytryptamine type 2B) in cardiac tissues 1
• While phentermine alone has not been definitively linked to valvulopathy, the possibility cannot be completely ruled out 2, 5

Clinical Monitoring and Contraindications

• Blood pressure and heart rate should be monitored periodically during phentermine treatment 1
• Phentermine is contraindicated in patients with:
  • History of cardiovascular disease 1
  • Uncontrolled hypertension 1
  • Patients taking monoamine oxidase inhibitors (or within 14 days of discontinuation) due to risk of hypertensive crisis 1, 2
  • Untreated hyperthyroidism (due to concerns for arrhythmias and seizures) 1, 2

Long-term Cardiovascular Safety

• There are currently no large cardiovascular outcome trial data for long-term use of phentermine monotherapy 1
• In a study of phentermine-treated patients over 92 weeks (mean duration), systolic and diastolic blood pressure actually declined from baseline, and heart rate changes were not significant 3
• Phentermine is FDA-approved only for short-term use (≤12 weeks), though many clinicians use it off-label for longer periods 1

Special Considerations

• Use with extreme caution in elderly patients, who are more likely to have decreased cardiac function 2
• Consider starting at lower doses (as low as 4-8 mg) in patients with cardiac risk factors 1
• Phentermine should be taken earlier in the day to minimize insomnia 1
• Patients should be advised to report any deterioration in exercise tolerance immediately 2

Practical Recommendations

• Prior to initiating phentermine, conduct a thorough cardiovascular risk assessment 1, 2
• Start with the lowest effective dose in patients with any cardiac risk factors 1
• Monitor blood pressure and heart rate at baseline and periodically during treatment 1
• Discontinue phentermine if any new cardiac symptoms develop or if there are significant increases in blood pressure or heart rate 2
• Avoid use in combination with other weight loss medications unless specifically approved combinations 2