Learning How to Use Drugs (Especially New Ones) Safely – And Why It Matters
THOMAS QUASTOFF: PHARMACO-EPIDEMIOLOGY'S FIRST FACE
In 1957, an anti-convulsive medication came on the market. In the late 1950s, thousands of German and other European women used this apparently safe anti-nausea/anti-convulsive and sleep medication during pregnancy. By 1960, this drug was marketed in 46 countries, with sales nearly matching those of Aspirin. In 1961, this drug was withdrawn from the market after being found to be a cause of “Phocomelia” – a birth defect so severe that it caused children to be born without properly developed arms or legs. The drug was Thalidomide. It is estimated that the number of individuals that were directly affected by Thalidomide was between 10,000 and 20,000. It was a tragedy of enormous proportions, and our first full understanding of the fact that drugs can be toxic. The field of Pharmaco-Epidemiology was born in tragedy.
Today, it is estimated that adverse drug side effects and drug interactions account for over 200,000 deaths each year in the U.S. alone – which equals approximately 4000 weekly fatalities. This estimate is according to the Alliance for Aging Research’s Report to Congress that was made in 2001. This number supports a previous estimate made by The Journal of the American Medical Association (JAMA) in 1995 that reported deaths from adverse drug events to be at 180,000 per year at that time. The JAMA esimate was considered conservative even then in light of the rapid introduction of new drugs on the market.
More recently, the tragedies surrounding the use of Rofecoxib (Brand name – Vioxx) and several other drugs have raised concerns about the safe use of newly emerging drugs. For example, when Vioxx was withdrawn from the market in September 2004, 80 million people worldwide were using this drug for conditions such as arthritis and acute pain. This was one of the most widely used drugs ever to be withdrawn from the market, with revenues of U.S. $2.5 billion in the year before its withdrawal. The fact that this drug had very serious and potentially fatal side effects was learnt after it had been on the market for a period of time and was fully in use.
The tragedies surrounding Thalidomide, Vioxx, and numerous other drugs (not mentioned here) give us pause to re-consider how to use drugs safely, especially if they are new to the market. There are times when it may be promising to consider the use of a new drug for a specific condition or conditions, but is there a way we can be aware of certain cautions we must keep in mind while doing so? While this topic is by itself a very large field of study, there are certain principles and hard lessons that have been learnt over time through the study of Epidemiology that everyone should know about, and I will share these with you in this post. These principles help us to use new drugs with greater awareness and objectivity, and also increase our understanding of how we may be able to circumvent a crisis in the event of an adverse drugs event and/or a drug interaction.
When using a new drug (or multiple drugs), a patient or physician must at first draw an informal inference in the event of an unexpected drug side-effect or an unanticipated drug interaction problem. Here are the critical criteria on the factors involved in doing so – I will explain what they mean at the end of the table below:
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Informal inference When it’s easy Very short time interval Prior hypothesis Known mechanism No alternative explanation Simple exposure
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Informal inference When it’s hard Symptoms are delayed Unanticipated No known mechanism Expected in absence of drug Multiple treatment modalities YOU CANNOT AFFORD TO NOT BE ALERT |
While the contents of the above table may seem esoteric at first, this is information that ALL individuals must take a little time to understand and learn:
1) The column on the left defines the criteria using which we can determine that there may be a problem with a new drug you have taken. If immediately or soon after taking a new drug, you feel unusual symptoms that make you feel perceptibly uncomfortable or anxious; if there is a prior hypothesis or known mechanism indicating that such a symptom or symptoms may occur (usually such factors are mentioned on the inserts that come with the drug), and if the new drug is the ONLY new item you have added to your intake - It is time to draw the informal inference that there may be a problem with this drug’s use for you. At such a time, rather than taking another dose of the same drug on the prescribed schedule, you should discontinue use of this drug and contact your doctor immediately to make him/her aware of your concerns.
2) Sometimes, however, it is not so easy to determine if a new drug you have taken is causing a problem, or if there are other factors that may be involved. The column on the right defines the factors that make the drawing of an informal inference hard with respect to the true effects of a new drug. For example, the effects of a new drug may be delayed; they may be unanticipated, and there may be no prior known mechanism or hypothesis vis-a-vis the symptoms you are experiencing (i.e., they may be readily expected even in the absence of the drug). Further, you may be taking multiple drugs and it may be impossible to know which one of the drugs is causing a problem (or if drug-interactions are involved). A good example of when informal inference was hard was what happend with Thalidomide – Its effects were delayed, unanticipated, and no one knew of any prior hypothesis or mechanism that indicated that its use might result in the culmination of a tragedy.
So, what can you do to protect yourself from an unanticipated crisis that might happen with the use of a new drug or while using multiple drugs? First, use the criteria above as a guide to develop greater awareness surrounding drug use. Be alert at all times for any and all unsusual symptoms, especially when using multiple drugs. Here are additional guidlelines you should keep in mind:
- Have a trusted primary care physician (PCP) whom you can contact without hesitation in case of an emergency.
- Have serious respect for drugs; Do not take any drug casually or without due awareness.
- Ask and research information regarding drug interactions.
- It may not always be possible, but when it is, choose drugs that have been on the market for at least 5 years, or drugs that have a long history of safe use.
- Read all directions, precautions and potential adverse reactions – This information is made available when drugs are purchased, but few individuals take the time to read it seriously.
- Follow-up on ALL physician recommended lab work! – Too many patients refuse to follow-up on recommended blood work or lab tests that have been recommended. This can be potentially fatal.
- If you suspect any unusual reaction, don’t wait – follow-up with your PCP immediately.
- Don’t take Over the Counter (OTC) medications or herbal therapies lightly.
- Know when OTC drugs are contra-indicated.
- Consult and inform your physician and pharmacist when taking OTC’s.
- Finally, do not self-medicate to address an unexpected problem, and do not self-diagnose. Obtain confirmation from your doctor with regard to the correct action to take in the event of an unexpected crisis.
Arriving from thin data to causal knowledge with respect to the true effects of a drug, or of drug-related interactions, can sometimes take years and expert epidemiologists often study extensively to understand this difficult field of study. The point of this post, however, is simply to draw your attention to the fact that simple awareness and even a cursory level of knowledge with respect to the important factors you should bear in mind – can sometimes be sufficient to avert a crisis. It is also important to know and take advantage of useful resources that can keep you well-informed and on the alert with respect to potential drug-interactions and/or news pertaining to safety issues involved with new drugs. I have listed a couple of the most useful resources on this subject at the end of this post.
Finally, as this subject is both critically important and very vast, no single blog post can do full justice to it. For this reason, I will post a video series on this topic in the upcoming days or weeks. Stay tuned for that. Until then, please feel free to pass on this post and the resources provided to all who may benefit.
RESOURCES:
Drug Interaction Table (Indiana University Division of Clinical Pharmacology)
