Why is phentermine contraindicated within 14 days of MAOI use?

Phentermine is contraindicated within 14 days of monoamine oxidase inhibitor (MAOI) use primarily because this combination poses a significant risk of hypertensive crisis. MAOIs are medications that inhibit the monoamine oxidase enzyme, which plays a critical role in the breakdown of neurotransmitters such as norepinephrine, serotonin, and dopamine. When phentermine, a sympathomimetic amine that acts as an appetite suppressant, is taken after MAOIs, it can lead to excessive release of norepinephrine.

This excess norepinephrine can lead to vasoconstriction and significantly elevate blood pressure, resulting in a hypertensive crisis, a potentially life-threatening condition characterized by severely elevated blood pressure along with symptoms such as headache, palpitations, and possible organ damage. The risk is particularly concerning given that phentermine itself can already elevate blood pressure and heart rate. Thus, using these two classes of drugs in close proximity can create dangerous synergistic effects, requiring a strict contraindication.

In contrast, while other risks like seizures, gastrointestinal bleeding, or arrhythmias can be associated with various drug interactions or underlying health conditions, they are not the primary concern in this specific scenario when combining phentermine and MAOIs. Understanding this