Adverse drug reactions.

Physicians are confronted daily with new information about new drugs, old drugs, using these agents in different ways, at different doses and comprehending the safety profiles with all of these medications. These medications may be completely new drug entities, structurally diverse compounds, new formulations of older drugs and even "me-too" drugs which are of the same chemical class and possess the same pharmacologic profile as previously approved medications, although they have slight structural alterations. This "drug-use process" is truly dynamic and health care providers are mandated to be proficient in their knowledge of these drugs, as they relate to their scope of practice. (1)

In this issue of the Southern Medical Journal, Jeffrey Greene, MD, presents a report documenting a potential adverse drug reaction (ADR): isotretinoin-induced pancreatitis. (2) Although this is an uncommon side effect of this compound, it illustrates an extremely important point; all drugs and compounds possess both the potential to effectively treat certain disease states and also the potential to harm.

Physicians must be thoughtful in recognizing and identifying adverse reactions to drugs. Adverse reactions can be classified into many different categories: immunologic or non-immunologic; predictable or unpredictable; common or rare. However classified or defined, ADRs should be considered before a medication is started rather than after the fact. Not only must the therapeutic efficacy of a drug be monitored after initiation, but a plan to monitor the potential toxicity of the drug must also be formulated. This needs to occur for each medication a patient is taking. (3-5)

In an article in Postgraduate Medicine in 1999, Jay S. Cohen, MD provided some excellent, common-sense recommendations for preventing ADRs. (4) First, the same dose may not be acceptable for all patients. Because adverse reactions are often dose (or drug concentration) related, prescribing the appropriate dose for each patient is absolutely essential. Elderly patients, patients with renal or hepatic dysfunction, or even patients who have a history of being quite sensitive to various drugs should be dosed judiciously and appropriately monitored for adverse effects. The monitoring plan may include various laboratory tests, serum drug concentration assessment or, simply discussing with the patient how he/she is responding to the medication.

Secondly, clinicians should not depend solely on the manufacturer's written information. The Physician's Desk Reference (PDR) may provide quick information about a large number of products regarding dosing and side effects, but it is lacking in evidence-based, well-referenced pharmacologic information. There are other sources of information (eg, AHFS Drug Information available at http://www.ashp.org/ahfs/print/ahfs-di.cfm) which provide up-to-date, nonbiased (not written by the pharmaceutical industry) information regarding medications which may provide clinicians with more comprehensive information. Related to this point, the health care provider should keep in mind that pharmacologic information regarding new medications may be sufficient to gain approval by the United States Food and Drug Administration (FDA), but a large amount of effective information will not be available until the drug is widely used in the general population. This postmarketing information is extremely valuable to the practitioner, as many drug-related problems may be identified which were not present in premarketing trials.

Finally, potential side effects should be discussed with patients, so they can distinguish drug-related toxicity from other comorbidities. Taking a thorough "drug-reaction" history, especially with new patients, will help assess how particular patients react to medications. This can help in formulating an effective dosing plan. In the future, predicting ADRs in particular patients may be impacted by the role of pharmacogenetics, where an individual's genetic make-up can be assessed and utilized to predict their response to a particular drug. (3)

All that being said, the ADR reported by Dr. Greene was quite rare and very difficult to predict. Unfortunately, these types of rare, idiosyncratic reactions will always be part of the pharmacotherapy utilization process. More common drug reactions and toxicities must be recognized, anticipated and dealt with. The large pharmacotherapeutic armamentarium now available to physicians makes it absolutely essential that health care providers consider adverse drug reactions when a treatment plan is considered. (1-5)

References

1. Joshi MC, Prayag S. Handling drug reactions in a systematic way. Available at: http://www.pharmabiz.com/article/detnews.asp?articleid=30684&sectionid=46.

2. Greene J. An adolescent with abdominal pain taking isotretinoin for severe acne. South Med J 2006; 99:992-994.

3. Manno MS. Preventing adverse drug events. Nursing 2006;36:56-61.

4. Cohen JS. Ways to minimize adverse drug reactions. Individualized doses and common sense are key. Postgrad Med 1999;106:163-172.

5. Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam Physician 2003;68:1781-1790.

James Wooten, PharmD

From the Section of Clinical Pharmacology, Department of Medicine, University of Missouri, Kansas City School of Medicine, Kansas City, MO.

Reprint requests to James Wooten, PharmD, University of Missouri, Kansas City School of Medicine, Department of Medicine, Section of Clinical Pharmacology, Gold 4 Unit, 2411 Holmes Street, Kansas City, MO 64108. Email: [e-mail]

Accepted April 21, 2006.