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http://www.pharmj.com/Editorial/20001202/letters/Moffat.html)
Phenylpropanolamine
Putting the record straight From Professor A. C. Moffat, FRPharmS, and others
SIR,—In The Pharmaceutical Journal of November 11 the article on phenylpropanolamine
1 correctly reported the information given to you by one of us (Professor Moffat) and contained in Martindale.
2 Since then, we have been checking the original sources of that information and have found a number of inaccuracies. We now wish to put the record straight.
The important fact to note is that the drug named phenylpropanolamine is the same in the United States as it is in Europe. The European Pharmacopoeia
3 (and, therefore, the British Pharmacopoeia
4) defines it as (1RS,2SR)-2-amino-1-phenyl- propanol, whereas the United States Pharmacopeia
5 defines it as benzenemethanol, alpha-(1-aminoethyl)-(R*,S*)-(±). The common name of this material is (±)-norephedrine, ie, it is a racemic mixture of the two enantiomers of norephedrine. It is therefore different from (±)-norpseudoephedrine. (The pairs of enantiomers of norephedrine and norpseudoephedrine are diastereoisomers.)
Thus, both European and United States preparations that contain phenylpropanolamine contain the same drug, namely, (±)-norephedrine. The European Pharmacopoeia gives a two-dimensional representation of the formula for phenylpropanolamine whereas the British Pharmacopoeia gives a three-dimensional representation of the formula. However, the formula in the British Pharmacopoeia depicts the wrong isomer (norpseudoephedrine instead of norephedrine). Now that this has been recognised, the correct graphic formula (as published in British Approved Names 1999) will be included in the British Pharmacopoeia 2001.
Concerning the statement in Martindale that "d-norpseudo-ephedrine is the most potent stimulant of the CNS and is contained in European phenylpropanolamine preparations”, we no longer believe this to be true. The statement comes directly from the 1990 paper by Lake
6 who obtained that information from the chapter by Morgan
7 published in 1985. While there may have been some truth in it in 1985, it is certainly not true today. The statement will be amended in the next printed and CD-ROM versions of Martindale.
We apologise for any confusion that may have arisen as a result of quoting information from these published sources, but that information is now being corrected.
The Committee on Safety of Medicines has recently advised that the evidence of a link between UK products containing phenylpropanolamine and haemorrhagic stroke is weak and
mainly associated with indications that are not licensed in the UK.
8 This followed articles in the media referring to a study carried out in the United States. There therefore does not appear to be any extra known risk in taking such preparations within the label instructions although the usual precautions should continue to be taken.
Tony Moffat Chief Scientist, Royal Pharmaceutical Society
Sean Sweetman Editor, Martindale
Marie Rabouhans Editor-in-Chief, British Pharmacopoeia
References
1. Is phenylpropanolamine in UK products really unsafe?
Pharm J 2000;265:709. 2. Parfitt K (editor).
Martindale — The Complete Drug Reference. 32nd edition. London: Pharmaceutical Press; 1999. pp1067-8. 3. Council of Europe.
European Pharmacopoeia, 3rd edition. Strasbourg: Council of Europe; 1997. pp1325-6. 4. British Pharmacopoeia Commission.
British Pharmacopoeia 2000, Vol I. London: Stationery Office; 2000. pp1215-6. 5. United States Pharmacopeial Convention.
The United States Pharmacopeia 24. Rockville: United States Pharmacopeial Convention; 2000. p1319. 6. Lake CR, et al. Adverse drug effects attributed to phenylpropanolamine: a review of 142 case reports.
Am J Med 1990;89:195-208. 7. Morgan JP. Norephedrine and norpseudoephedrine: pharmacologically and clinically distinct isomers of phenylpropanolamine. In: Morgan JP, Kagan DV, Brody JS (editors).
Phenylpropanolamine. Risks, benefits and controversies. New York: Praeger; 1985. pp180-94. 8. Committee on Safety of Medicines.
Drug Safety Information EL(00)A/32. London: Medicines Control Agency; 2000. pp1-4.