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 the most common being dry mouth, insomnia, and constipation, while the most serious include cardiovascular complications such as elevated blood pressure, tachycardia, primary pulmonary hypertension, and valvular heart disease. 1

Cardiovascular Side Effects

The cardiovascular system bears the most serious risks with phentermine use:

• Elevated blood pressure and heart rate are common sympathomimetic effects, though these may be less pronounced when adequate weight loss occurs 2, 1
• Palpitations and tachycardia occur frequently due to norepinephrine release 2, 1
• Primary pulmonary hypertension represents a rare but life-threatening complication requiring immediate discontinuation if patients develop new dyspnea, angina, syncope, or lower extremity edema 1
• Valvular heart disease (particularly affecting mitral, aortic, and tricuspid valves) has been reported, though the causal relationship with phentermine monotherapy remains uncertain 1
• Ischemic cardiac events can occur, particularly in patients with underlying cardiovascular disease 2, 1

Phentermine is contraindicated in patients with uncontrolled hypertension, history of heart disease, and hyperthyroidism. 2

Central Nervous System Effects

Phentermine's stimulant properties produce multiple CNS manifestations:

• Insomnia is one of the three most common side effects 2, 1
• Headache occurs frequently across patient populations 2, 1
• Overstimulation, restlessness, and anxiety result from sympathomimetic activity 2, 1
• Dizziness and tremor are documented adverse effects 2, 1
• Euphoria or dysphoria may develop during treatment 1
• Psychosis represents a rare but serious complication 2, 1
• Impaired cognitive function including effects on concentration, memory, and ability to operate machinery or drive vehicles 1

Phentermine is contraindicated in patients with anxiety disorders or agitated states. 2, 3

Gastrointestinal Effects

GI side effects are among the most commonly reported:

• Dry mouth is one of the three most frequent adverse effects 2, 1
• Constipation completes the triad of most common side effects 2, 1
• Unpleasant taste and diarrhea occur in some patients 1
• Ischemic colitis has been reported with inappropriate long-term use beyond the approved 12-week period 4

Ocular Effects

Visual disturbances require immediate attention:

• Blurred vision can occur and warrants immediate medical evaluation 5
• Acute myopia and ocular pain are particular concerns with phentermine/topiramate combination therapy 2, 5
• Acute angle-closure glaucoma risk necessitates contraindication in patients with pre-existing glaucoma 2, 5

Patients should undergo baseline visual acuity testing and be questioned about visual disturbances at each monthly visit, with immediate discontinuation if visual toxicity develops. 5

Psychiatric and Mood Effects

Mental health monitoring is essential:

• Depression or worsening of pre-existing depression requires monitoring, particularly with phentermine/topiramate combination 3
• Anxiety and panic attacks may emerge during treatment 2
• Changes in mood should prompt evaluation 3

Endocrine and Sexual Effects

Hormonal and sexual function may be affected:

• Impotence has been reported 2, 1
• Changes in libido (increases or decreases) can occur 2, 1

Allergic Reactions

• Urticaria represents the primary allergic manifestation 2, 1

Metabolic Considerations

• Hypoglycemia risk in diabetic patients requires dose reduction of insulin or oral hypoglycemic medications 2, 1

Tolerance and Dependence

Critical long-term considerations include:

• Pharmacological tolerance typically develops within weeks, at which point the drug should be discontinued rather than increasing the dose 2, 1
• Potential for abuse and dependence exists due to phentermine's chemical relationship to amphetamine, though recent data suggests actual addiction risk may be lower than historically believed 1, 6
• Withdrawal symptoms can occur following prolonged high-dose administration 1

The least amount feasible should be prescribed at one time to minimize overdosage risk. 1

Drug Interactions

Several critical interactions require attention:

• MAOIs are absolutely contraindicated within 14 days of phentermine use due to hypertensive crisis risk 2, 1
• Alcohol use may result in adverse drug reactions and should be avoided 1
• Adrenergic neuron blocking drugs may have reduced efficacy 1
• Tramadol represents the most frequently co-prescribed medication with severe drug-drug interaction potential 7
• Dextromethorphan is commonly co-prescribed with moderate interaction risk 7

Special Populations

Phentermine is pregnancy category X and absolutely contraindicated in pregnancy and breastfeeding. 1

Elderly patients require cautious dosing starting at the low end of the range due to decreased renal function and higher risk of toxic reactions. 1

Pediatric use is not recommended as obesity requires long-term treatment but phentermine is only approved for short-term (<12 weeks) use. 2, 1

Critical Monitoring Parameters

Patients require surveillance for:

• Blood pressure and heart rate at each visit 2
• New cardiovascular symptoms (dyspnea, chest pain, edema) 1
• Visual changes with baseline and ongoing assessment 5
• Mood and psychiatric symptoms 3
• Exercise tolerance deterioration 1

The medication should be discontinued immediately if primary pulmonary hypertension, valvular disease, or visual toxicity is suspected. 5, 1