Possible Interaction: Caffeine and Phenylpropanolamine

“Coadministration of caffeine and phenylpropanolamine produced an additive increase in blood pressure.”

“This effect could not be explained by any pharmacokinetic interaction between the two drugs and occurred even though phenylpropanolamine attenuated the epinephrine and renin response to caffeine.”

“Norepinephrine levels increased after the administration of 150‐mg phenylpropanolamine and 75‐mg phenylpropanolamine plus 400‐mg caffeine ; norepinephrine increases correlated with phenylpropanolamine levels (r = .34, P<.0001).”

“Significant BP increases after ingestion of 75 mg PPA and after 400 mg caffeine were less frequent.”

“We suggest physicians inform patients who are likely consumers of PPA (i.e., those with allergies, those with eating disorders, overweight persons, women during … stroke (i.e., the elderly and hypertensive patients) of the risks of taking more than the recommended amounts of PPA and of combining caffeine … PPA.”

“Some evidence also exists on the additive effects of the co-ingestion of phenylpropanolamine and caffeine.”

“We therefore undertook a study to demonstrate that a significant health risk can be caused by a double dose of a typical over-the-counter (OTC) diet aid (i.e., 150 mg phenylpropanolamine) and also when 75 mg phenylpropanolamine is taken with caffeine.”

“Treatment with norephedrine increased the permeation of caffeine and hydrocortisone by two- to fourfold, while absorption of indomethacin declined an order of magnitude.”

“In addition, PPA increases caffeine plasma levels and decreases theophylline clearance.”

“In 1985, the combined studies of phenylpropanolamine (PPA) and PPA with caffeine gave 0.27 kg/wk more weight loss than placebo, but since 1985, this difference has dropped to 0.14 kg/wk in the combined studies with PPA.”

“Clinical studies have shown that using greater than recommended doses of PPA and using PPA in combination with caffeine may increase the risk of ADRs.”

“Because caffeine levels can be increased greatly when certain other drugs are coconsumed, these data indicate that phenylpropanolamine may enhance absorption or inhibit elimination of caffeine and may explain increased side effects reported after their combined use.”

“In subjects receiving 400 mg caffeine plus 75 mg phenylpropanolamine , the mean (± SEM) peak plasma caffeine concentration of 8.0 ± 2.2 μg/ml was significantly greater than after 400 mg caffeine alone (2.1 ± 0.3 μg/ml; t[24] = 2.4; p < 0.01).”

“The mechanism is unclear but could result from several factors: chronic or paroxystic high blood pressure, immuno-allergic vasculitis, arterial spasm, direct "toxic" effect of the P.P.A. on the arterial wall may be increased by other drugs and caffeine.”