What are the contraindications for Phenteramine (phentermine) in patients with various medical conditions, including cardiovascular disease, substance abuse, and other health issues?

Phentermine Contraindications

Phentermine is absolutely contraindicated in patients with any history of cardiovascular disease (including coronary artery disease, stroke, arrhythmias, or congestive heart failure), uncontrolled hypertension, hyperthyroidism, glaucoma, history of drug abuse, during pregnancy or nursing, in agitated states, and in patients currently taking or within 14 days of discontinuing monoamine oxidase inhibitors. 1

Absolute Cardiovascular Contraindications

• Any history of cardiovascular disease including coronary artery disease, stroke, arrhythmias, or congestive heart failure represents an absolute contraindication to phentermine use, as there are no large cardiovascular outcome trial data for long-term safety. 2, 1

• Uncontrolled hypertension is an absolute contraindication, as phentermine's sympathomimetic effects can elevate blood pressure through norepinephrine release. 2, 1

• Even patients with controlled hypertension require extreme caution, as phentermine may increase blood pressure despite baseline control. 1

• Case reports document serious cardiovascular events including coronary vasospasm-induced myocardial infarction and atrial fibrillation in previously healthy patients taking phentermine, underscoring the cardiovascular risk even without pre-existing disease. 3, 4

Endocrine and Metabolic Contraindications

• Untreated hyperthyroidism is an absolute contraindication due to concerns for arrhythmias and seizures when combined with phentermine's sympathomimetic effects. 2, 1

• Thyroid function must be assessed and any hyperthyroidism treated before initiating phentermine therapy. 5

Ophthalmologic Contraindications

• Glaucoma is an absolute contraindication due to phentermine's sympathomimetic effects on intraocular pressure. 1

Psychiatric and Substance Use Contraindications

• History of drug abuse represents an absolute contraindication, as phentermine is a Schedule IV controlled substance with abuse and dependence potential. 5, 1

• Agitated states are contraindicated, as phentermine's stimulant properties may exacerbate anxiety disorders and agitation. 1

• However, research demonstrates that when prescribed appropriately for obesity, phentermine does not induce psychological dependence, drug craving, or amphetamine-like withdrawal symptoms, even after long-term use up to 21 years. 6

Critical Drug Interactions - Absolute Contraindications

• Monoamine oxidase inhibitors (MAOIs): Phentermine is absolutely contraindicated during or within 14 days of MAOI administration due to risk of hypertensive crisis. 2, 5, 1

• Other sympathomimetic amines: Concomitant use should be avoided due to potential serious interactions and additive sympathomimetic effects. 1

Pregnancy and Lactation - Absolute Contraindications

• Pregnancy is an absolute contraindication to phentermine use. 1

• Nursing/lactation is an absolute contraindication; the drug must be discontinued or nursing discontinued considering the importance of the drug to the mother. 1

• Women of childbearing potential require counseling about reliable contraception, particularly when phentermine is combined with topiramate (which is teratogenic), and monthly pregnancy testing should be considered. 2

Renal Contraindications

• Severe renal impairment (eGFR 15-29 mL/min/1.73 m²) requires dose limitation to maximum 15 mg daily due to substantial renal excretion. 1

• End-stage renal disease requiring dialysis or eGFR less than 15 mL/min/1.73 m²: avoid phentermine use entirely. 1

Hypersensitivity Contraindications

• Known hypersensitivity or idiosyncrasy to sympathomimetic amines is an absolute contraindication. 1

High-Risk Situations Requiring Special Consideration

• Patients requiring general anesthesia need special management considerations when taking phentermine, though specific protocols are not detailed in current guidelines. 5

• Seizure disorders warrant extreme caution, particularly when phentermine is combined with other medications that lower seizure threshold. 5

• History of significant nephrolithiasis requires caution, especially with phentermine-topiramate combinations, due to carbonic anhydrase inhibitor properties increasing kidney stone risk. 2

Critical Screening Errors to Avoid

• Failing to obtain complete cardiovascular history including remote history of arrhythmias or structural heart disease is a critical error, as even resolved cardiovascular conditions represent contraindications. 5

• Inadequate thyroid function assessment before initiation represents a dangerous oversight. 5

• Not screening for MAOI use within the past 14 days can result in life-threatening hypertensive crisis. 5, 1

• Failing to assess pregnancy status in women of reproductive potential is a critical error given the absolute contraindication in pregnancy. 5

Additional Safety Considerations

• A case report documents subarachnoid hemorrhage in a patient taking phentermine, likely secondary to drug-induced hypertension or vasculopathy, highlighting the serious neurologic risks. 7

• Concomitant alcohol use may result in adverse drug reactions and should be avoided. 1

• Analysis of long-term phentermine users reveals frequent co-prescribing with medications causing moderate (75%) and severe (25%) drug-drug interactions, with tramadol being the most common severe interaction. 8