The Pharmacist’s Awareness of “Drug Induced Disease” in Their Patients is a Critical Factor in the Patient’s Care Plan.
Roger S. Klotz, R.Ph., BCNSP, FASCP, FACA, FCPhA, CDM
Recently, the FDA has sent out alerts to healthcare professionals warning them of an increased risk of serious adverse effects and death in patients receiving a number of drugs. The alerts will lead to “Black Box” warnings in the FDA, approved labeling for darbepoetin, epoetin alfa, linezolid, and omalizumab. It is interesting to note that all of these drugs are available as parenteral therapies and have life-threatening adverse outcomes. Therefore, pharmacists must be keenly aware of the risks associated with these parenteral therapies and other drugs administered to more acute patients. Understanding the risks associated with parenteral therapies and the diseases that created the need for their administration must become a critical part of the patient’s care plan. Whether a patient has additional risk factors (i.e. renal disease, cardiac disease, polypharmacy, pharmacogenomic) or evaluating inappropriate dosing is also critical and must be included in the patient’s care plan.
The anemia drugs (darbepoetin and epoetin alfa) have been reported to produce an increased risk of serious adverse cardiovascular events and death when these products are administered to target hemoglobin of greater than 12G/dl. Therfore, it is critical to monitor the patient’s hemoglobin and stop the therapy when it reaches 12G/dl. The new “Black Box” warning advises professionals to use the lowest possible dose of these agents to gradually increase the hemoglobin concentration to the lowest level sufficient to avoid the need for red-blood-cell transfusions. The new warning also indicates that the use of higher than recommended dosages results in shortened time to tumor progression in patients with advanced head and neck cancer receiving radiation therapy. It can also lead to shortened overall survival and increase deaths attributed to disease progression at 4 months in patients with metastatic breast cancer receiving chemotherapy.
Linezolid has been linked to an increased risk of mortality in patients treated for catheter-related bloodstream infections as compared to patients receiving vancomycin, oxacillin, or dicloxacillin according to the FDA. This was particularly true in patients being treated for gram-negative infections. The risk increased to about double for patients with a combination of gram-negative and gram-positive infections. The FDA points out that linezolid is not approved for the treatment of catheter-related infections. It is interesting to note that linezolid is associated with the development of “Serotonin Syndrome” particularly when combined with other agents that increase serotonin levels.
The omalizumab “Black Box” warning indicated that it can be associated with potentially life-threatening allergic reactions. This drug is used in the treatment of asthma. These patients do have a high risk of allergic reactions and therefore, the risk-benefit ratio must be carefully weighed when beginning this therapy.
The whole concept of assuring that pharmacists are fully aware of newly reported adverse reactions and patient risk is exemplified by a recent article in the New England Journal of Medicine (2007, 356(9): 904-910). This article reports on a study which found that vancomycin-induced immune thrombocytopenia occurred in 34 patients who had developed thrombocytopenia while on vancomycin. The analysis of patients, who developed thrombocytopenia while on vancomycin, was done by the group by looking for vancomycin-dependent antibodies in these patients. They did find that severe bleeding can occur in patients with vancomycin-induced immune thrombocytopenia. This finding is very surprising when one considers how long vancomycin has been used in home infusion therapy and thus, the extremely large number of patients that have been exposed to this risk. It is therefore critical that we add to the vancomycin treated patient’s care plan this potential problem and the appropriate monitoring requirements.
I have found that unknown symptoms in patients are many times associated with the patient’s drug therapy. In my practice I have patients self refer because they have symptoms/complaints that cannot be explained by their disease or the presence of an additional disease. The physician looks for pathology and cannot find any pathological reason for the symptoms/complaints. When the patient comes to me I look at the pharmacology, pharmacokinetics, and the pharmacogenetics. In most cases, I find that the patients are suffering from an adverse effect that may be associated with inappropriate dosing (dose related toxicity), a drug interaction not picked up by the drug interaction software programs, inappropriate drug for the patient’s clinical disease, or physiological variance related to age or sex. I have therefore, begun to use the term “Drug Induced Disease” to explain the cause of the symptoms/complaints. I do this to help physicians fully understand the risks associated with drug therapy. The above examples are definitely examples of “Drug Induced Disease” and the severe negative outcomes that can occur.
Healthcare professionals and consumers continue to be surprised by the finding of severe life-threatening adverse reactions occurring as a result of drug therapies commonly utilized and that have been utilized for many years. Vioxx was definitely a wake up call, but as we see in the above examples, we continue to be surprised. The old medical adage of “first of all, do no harm” is now needed more then ever. Careful management of a patient’s drug therapy in a collaborative practice approach is critical to maximizing the benefits of modern drug therapy, while at the same time minimizing the serve life-threatening risks associated with modern drug therapy. The pharmacist’s direct involvement in the patient’s care plan is critical to achieving the goal of providing safe and effective therapy to our patients. Keeping up with the literature is also critical, so that we can minimize surprises associated with drug therapy. As the drug therapy sophistication and effectiveness increases we will unfortunately see an increase in the risks associated with drug therapy. Pharmacists must increase their vigilance and their participation in the patient’s care to assure that positive outcomes of therapy occur. Also, pharmacists may have to be involved in the differential diagnosis in order to eliminate pharmacologic causes of symptoms/complaints and eliminate “Drug Induced Disease”.