The New Straits Times, November 19, 2000
By Prof Dzulkifli Abdul Razak
THE recent swift action by the Health Ministry to halt the sale of more than 40 products containing the phenylpropanolamine (PPA) must be lauded.
It demonstrates yet again the deep concern that the Ministry has for the Malaysian public. This is especially so when it decided to proactively withdraw such items (see list at http://www.prn.usm.my/phenyl/index.html) from the market even as many countries are still contemplating doing just that.
PPA is an 'old' substance used as an active ingredient in many over-the-counter (OTC) and prescription medications for the symptomatic relief of nasal congestion (running nose) as in cough and cold remedies, or to suppress appetite as in OTC weight loss products.
Given the wide range of PPA-containing products marketed, and their easy access as OTC items, millions have been exposed to PPA annually.
The first warning signs about PPA came more than 20 years ago. One source cited that studies since 1979, documented more than 30 case reports describing the occurrence of bleeding in the brain after the ingestion of PPA. Most commonly affected were adolescent girls or young women between the ages of 17 and 45 years whowere using PPA-containing appetite suppressants, often for the first time.
And between 1969 and 1991, the US Food and Drug Administration (FDA) received additional 22 spontaneous reports of stroke due to the busting of blood vessels in the brain (hemorrhagic stroke) associated with PPA in appetite suppressants (in 16 cases) or cough and cold remedies (in 6 cases). In the past 30 years FDA"s own records show a total of 44 cases of haemorrhagicstroke.
In response to this concern, in 1992, Yale University researchers in collaboration with FDA and manufacturers of PPA designed the Haemorrhagic Stroke Project _ a 5-year case-control study of men and women of ages between 18 and 49 years of age. On reviewing the result, the Nonprescription Drugs Advisory Committee of FDA concluded that "PPA cannot be considered to be safe for continued use". This is followed by a public advisory warning, alerting the risk of haemorrhagic stroke associated with PPA. Earlier this month, the FDA took steps to remove PPA from all medicinal products.
While the risk of a haemorrhagic stroke is very small to an individual user, the effect is often devastating and deadly. Haemorrhagic strokes, though rare for ages below 50, typically occur in the elderly. However, even in the 1980s, biomedical literature already reported several dozen young women who suddenly had strokes days after taking their first PPA-containing weight control pill.
Risk was highest with the higher doses _ more than 75mg daily _ that dieters normally used. It is estimated that PPA could be blamed for 200 to 500 strokes yearly just in Americans under age 50.
The stroke is said to be due to further increase in blood pressure causing the smaller vessels in the brain to burst. Nobody knows why, although first-time PPA use sometimes temporarily raises blood pressure. The effect wanes as the body gets used to the drug.
Consumers therefore should be alerted if PPA is found in the both brand names and generic products. They are advised to discuss the use of such OTC and prescription products with their health care provider, and given safer alternatives. For relief of cold, one safe alternative is pseudoephedrine.
In general it would be wise for anyone who has high blood pressure, the elderly or those who are overweight and therefore liable to have blocked or "hardened" arteries to refrain from using any PPA-containing products.
There are other important lessons and useful reminders that came out of the PPA experience.
Firstly, no drugs are completely safe. All of them have inherent risks, especially when used improperly. Even though a particular drug is deemed "safe" after being subjected to a battery of pre-clinical and clinical tests, the long-term effects are usually less understood, until millions are exposed to it over a number of years. In theory, as long as a drug remains in the market there will always be some potential risks yet to be discovered as illustrate in the case of PPA.
Secondly, judicious use is an absolute must. This means a drug should not be used longer than necessary or without regular consultation with health professionals. Similarly, the recommended dose must be strictly adhered to since it could lead to even greater risks.
Thirdly, knowing drug names, especially when intending to use them, is essential. In cases of a drug being withdrawn as in the case of PPA, many would face a higher risk if the drug name or its active ingredients remains obscure to the users. Worse still if it is for life-threatening ailments and needs to be substituted to save life.
Fourthly, never use drugs (especially when their identity is unknown) in combination with others or when there are other underlying diseases, without first checking with health professionals.
In order to make all these possible, information about the drug must be completely revealed to the patient and consumer. This could be done through complete labelling of the item, in particular when dispensed to patients or sold to consumers.
The minimum labelling requirement should include the following: drug name(s), its strength or dose, exact directions for use (amount, how and when), common side-effects and the remedial steps to be taken, possible interactions with food and other drugs. Also important are information on storage and disposal.
Lastly, patients and consumers must be counselled about the drugs they are given based on the above listing, at least on the first use of the item.
But many of the above suggestions are not in practice in this country. Drugs are still poorly labelled in many private clinics and pharmacies, made worse by inadequate dispensing and counselling practices at such outlets.
In other words, there is an acute shortage of information on drug use in the community. The Malaysian public is consistently being exposed to unwarranted dangers. Professional ethics and practices about drug use should be strictly adhered to.
It is now time that the Ministry of Health gave this aspect a serious thought to further safeguard public interest. The consumer has the right to know about medication, and this must be placed above any parochial interest. If necessary legislation and regulations on the labelling of drugs should be promulgated and implemented.
This is long overdue as we enter the knowledge and information era. Good and adequate information will go a long way to make medicines work better, and prevent hazards.
Recommended website: www.fda.gov/cder/drug/infopage/ppa/default.htm.
