4-FA

Any pre-existing cardiovascular condition (coronary artery disease, cardiomyopathy, arrhythmia, heart failure) represents an absolute contraindication. The exaggerated hypertensive response documented in both controlled and emergency department settings creates unacceptable risk of acute cardiac events.

Uncontrolled or poorly controlled hypertension is an absolute contraindication. The sustained blood pressure elevation can trigger hemorrhagic stroke even in normotensive individuals; elevated baseline BP further increases this risk.

Personal or family history of psychotic disorders (schizophrenia, schizoaffective disorder, psychotic features of bipolar disorder) represents a relative contraindication. No 4-FA-specific psychotic episode has been documented, but the risk is pharmacologically expected from the amphetamine class.

Pregnancy is an absolute contraindication based on class-level pharmacology. No reproductive or developmental toxicity studies exist for 4-FA. The sustained cardiovascular stress poses direct risk to placental perfusion.

Concurrent use of any monoamine oxidase inhibitor (phenelzine, tranylcypromine, moclobemide, selegiline, linezolid, methylene blue, Syrian rue/harmaline) is an absolute contraindication. This is the primary pharmacokinetic interaction risk identified in the systematic review by Inan et al. 2020.

Concurrent use of serotonergic medications (SSRIs, SNRIs, tramadol) or serotonergic recreational drugs (25C-NBOMe, other NBOMe series, MDMA) is contraindicated. Severity ranges from relative (SSRIs reducing entactogenic effects) to absolute (documented fatal outcomes with 25C-NBOMe).

Patients on CYP2D6-inhibiting antiretrovirals face pharmacokinetic risk of intensified and prolonged 4-FA effects. While CYP2D6 involvement in 4-FA metabolism is inferred rather than confirmed, this interaction was specifically flagged by Inan et al. 2020.