Phentermine

Coronary artery disease, Stroke history, Arrhythmias, Congestive heart failure, Uncontrolled hypertension

Phentermine is absolutely contraindicated in patients with established cardiovascular disease including coronary artery disease, history of stroke, cardiac arrhythmias, congestive heart failure, and uncontrolled hypertension. The sympathomimetic mechanism increases heart rate, blood pressure, and myocardial oxygen demand, which can trigger acute coronary events, arrhythmias, or hemodynamic decompensation in vulnerable individuals.

Agitated states

Phentermine is absolutely contraindicated in individuals in agitated states. The CNS stimulant properties — mediated by central norepinephrine release — can worsen agitation, precipitate psychosis, or destabilise pre-existing psychiatric conditions.

History of drug abuse

A history of drug abuse is an absolute contraindication. Controlled abuse liability studies (Jasinski 2008) demonstrate that phentermine produces recognisable stimulant subjective effects in stimulant-preferring drug abusers. Although the intensity is lower than prototypical stimulants, the recognised subjective profile creates misuse risk in this population.

Hyperthyroidism

Hyperthyroidism is an absolute contraindication. Excess thyroid hormones amplify the cardiovascular effects of sympathomimetic amines, producing additive risk of tachyarrhythmias and hypertensive crisis when combined with phentermine's norepinephrine-releasing activity.

Sympathomimetic amine hypersensitivity

Known hypersensitivity to phentermine or other sympathomimetic amines is an absolute contraindication due to risk of allergic or anaphylactic reaction.

Pregnancy

Pregnancy is an absolute contraindication. The phentermine/topiramate combination (Qsymia) carries a mandatory REMS programme due to topiramate's established teratogenicity. For phentermine monotherapy, no controlled human data exist — the substance is presumed unsafe based on sympathomimetic class pharmacology and the absence of safety data.

Lactation, Breastfeeding

Use during lactation is contraindicated. Phentermine excretion in breast milk has not been studied, and the potential for sympathomimetic effects (stimulation, appetite suppression, cardiovascular activation) in the nursing infant cannot be excluded.

Concurrent MAOI use, MAOI use within prior 14 days

Concurrent or recent use (within 14 days) of any monoamine oxidase inhibitor is absolutely contraindicated. Phentermine triggers carrier-mediated norepinephrine efflux; when MAO-mediated catecholamine degradation is simultaneously blocked, the resulting catecholamine surge can produce a potentially fatal hypertensive crisis.

Glaucoma

Glaucoma is an absolute contraindication. Phentermine's sympathomimetic activity causes pupil dilation (mydriasis), which can mechanically obstruct the trabecular meshwork outflow pathway in susceptible eyes, precipitating an acute angle-closure crisis with risk of permanent vision loss.