What are the potential side effects of phentermine (Adipex-P)?

Phentermine Side Effects

Phentermine causes a well-documented spectrum of adverse effects across multiple organ systems, with cardiovascular, central nervous system, and gastrointestinal effects being most common, though serious complications including primary pulmonary hypertension and valvular heart disease remain rare but critical concerns.

Cardiovascular Side Effects

The cardiovascular system bears significant risk with phentermine use:

• Elevated blood pressure and heart rate are among the most common cardiovascular effects, occurring frequently enough to warrant caution even in patients with mild hypertension 1, 2
• Palpitations and tachycardia represent common sympathomimetic effects that patients should be counseled about before initiating therapy 1, 2
• Primary pulmonary hypertension is a rare but potentially fatal complication that requires immediate discontinuation if new dyspnea, angina, syncope, or lower extremity edema develops 2
• Ischemic cardiac events have been documented, including cases of colon ischemia attributed to vasoconstriction from inappropriate long-term use 2, 3
• Valvular heart disease (regurgitant cardiac valvular disease affecting mitral, aortic, and/or tricuspid valves) has been reported, though the role of phentermine alone versus combination therapy remains unclear 2, 4

Central Nervous System Effects

Phentermine's sympathomimetic properties produce numerous CNS manifestations:

• Insomnia is one of the most frequently reported side effects alongside headache 1, 2
• Overstimulation, restlessness, and anxiety occur commonly due to norepinephrine and dopamine release 1, 2
• Dizziness and tremor are documented adverse effects that may impair daily functioning 1, 2
• Euphoria and dysphoria can occur, reflecting the drug's amphetamine-like properties 1, 2
• Psychosis represents a rare but serious psychiatric complication requiring immediate discontinuation 1, 2
• Cognitive impairment (concentration and memory issues) has been noted, particularly with combination phentermine/topiramate therapy 1

Gastrointestinal Effects

GI side effects are common but generally manageable:

• Dry mouth is the most frequently reported gastrointestinal complaint 1, 2
• Constipation occurs commonly and should be anticipated 1, 2
• Unpleasant taste, diarrhea, and other GI disturbances have been documented 1, 2

Endocrine and Sexual Effects

• Changes in libido and impotence have been reported as endocrine-related adverse effects 1, 2
• Hypoglycemia risk increases in patients with type 2 diabetes treated with insulin or sulfonylureas, necessitating dose adjustments of antidiabetic medications 1, 2

Allergic and Dermatologic Reactions

• Urticaria represents the primary documented allergic reaction to phentermine 1, 2

Ocular Effects

• Blurred vision can occur and requires immediate medical attention 5
• Acute myopia and ocular pain are particular concerns with phentermine/topiramate combination therapy 1, 5
• Contraindication in glaucoma patients exists due to risk of acute angle-closure glaucoma, especially with combination products 1, 5

Abuse and Dependence Potential

• Pharmacological tolerance typically develops within weeks, at which point the drug should be discontinued rather than increasing the dose 1, 2
• Chemical similarity to amphetamine creates theoretical abuse potential, though recent data does not support that phentermine is addictive in clinical practice 2, 6
• Withdrawal symptoms may occur following prolonged high-dose administration 2

Important Safety Considerations

Contraindications and high-risk scenarios require particular attention:

• Pregnancy (Category X) represents an absolute contraindication as weight loss offers no benefit and may cause fetal harm 2
• MAOI use within 14 days is contraindicated due to hypertensive crisis risk 2
• History of cardiovascular disease, uncontrolled hypertension, hyperthyroidism, glaucoma, or anxiety disorders represent contraindications 1
• Alcohol use should be avoided as concomitant use may result in adverse drug reactions 2

Clinical Context and Monitoring

Recent observational data suggests that among nearly 14,000 individuals, prolonged phentermine use (>12 months) does not significantly increase major cardiovascular events at 24 months, and 92.9% of adverse events in a 6-month study were mild 1. However, these findings come from observational studies with methodologic limitations rather than rigorous randomized controlled trials 6.

Common pitfalls to avoid:

• Do not exceed recommended doses when tolerance develops; discontinue instead 2
• Do not prescribe to patients taking antidepressants without careful consideration of drug interactions 1
• Do not ignore new cardiovascular symptoms (dyspnea, chest pain, edema) which mandate immediate discontinuation 2
• Do not use in elderly patients without dose adjustment and renal function monitoring 2