The Pharmaceutical Journal Vol 265 No 7122 p709
November 11, 2000 Clinical

Is phenylpropanolamine in UK products really unsafe?

Following the United States Food and Drug Administration’s announcement this week that it is taking steps to remove phenylpropanolamine from all drug products, the Committee on Safety of Medicines met on November 8 to review the situation in the United Kingdom. No decision had been made as The Journal went to press.
However, the debate over the safety of phenylpropanolamine may be irrelevant because the compound used in the US is different from that used in Europe. As a result, US trial data on phenylpropanolamine may not apply to UK products.
Professor Tony Moffat (chief scientist, Royal Pharmaceutical Society) pointed out the difference to The Journal. In Europe, a different isomer of phenylpropanolamine known as norpseudoephedrine is used, while in the US it is ±norephedrine. In other words, they are two different drugs, he said. The difference is described in Martindale, which says that phenylpropanolamine exists in four isomeric forms: d- and l-norephedrine and d- and l-norpseudo-
ephedrine. It continues: “Of the isomers, d-norpseudoephedrine is the most potent stimulant of the central nervous system and is contained in European phenylpropanolamine preparations; however, in North America only the racemic mixture of d,l-norephedrine is used. This consideration of the isomers present in a given preparation may partly explain why many of the adverse drug reactions reported in Europe describe an alteration of mental status whereas those in North America are more often compatible with hypertension.”
The FDA’s decision to remove phenylpropanolamine from drug products followed a meeting in October at which researchers from Yale university, US, presented study results showing that phenylpropanolamine increased the risk of haemorrhagic stroke (PJ, October 28, p642).
The study will be published in the New England Journal of Medicine in December but is available now on the journal’s website (www.nejm.org).
In the US, phenylpropanolamine is marketed in both cold remedies and in appetite suppressants, which are not available in the UK. The Yale study gave a much higher odds ratio for the association between haemorrhagic stroke and use of phenylpropanolamine in appetite suppressants than in cold preparations (15.92 in appetite suppressants and 1.23 in cold and cough remedies).
The FDA says that it has requested that all drug companies discontinue marketing products containing phenylpropanolamine. It adds that, although the risk of stroke is very low, the conditions for which phenylpropanolamine is used do not justify the risk of serious events and, consequently, it advises consumers not to use any phenylpropanolamine-containing products.
In the UK, the Department of Health said on November 7 that patients who were concerned about products containing phenylpropanolamine should contact their pharmacist for advice or suggestions of alternative products which did not contain the drug.
A spokesperson for the Department told The Journal: “Over-the-counter cold and ’flu remedies on the market in the UK have a lower maximum daily dose than similar products in the US.” The spokesperson added that phenylpropanolamine has sympathomimetic effects and should not be recommended to a number of patients, including those with high blood pressure, diabetes and coronary heart disease.
The Medicines Control Agency published a list of products containing phenylpropanolamine in the UK on its website on November 8. The list contained a number of inaccuracies and has now been removed. Products containing phenylpropanolamine are listed in the panel above; Aller-eze Plus and some pack sizes of Triogesic and Triominic have been discontinued (PJ, October 28, p666) but have been included in the panel for completeness.
A number of pharmacies reacted to the news by removing products from display. Lloyds Pharmacy, for example, had temporarily withdrawn phenylpropanolamine-containing products from its pharmacies as The Journal went to press.