1. Shastay, Ann MSN, RN, AOCN

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Caution when prescribing Xarelto to first-time patients. The recommended dose of XARELTO (rivaroxaban) for treatment of deep vein thrombosis (DVT) or pulmonary embolism is 15 mg twice a day for the first 21 days, followed by 20 mg once daily for at least 60 days. This requires two different tablet strengths, two frequencies, and two prescriptions for first-time patients.


A patient with a DVT was discharged from a hospital with two prescriptions for Xarelto-one for 15 mg and another for 20 mg. Neither the prescription directions nor the discharge instructions made it clear the 20 mg tablets were to be started after the 15 mg tablets were finished.


The patient mistakenly took both prescriptions concurrently (50 mg total). Fortunately there was no serious bleeding, but he did report vision changes and was referred to an ophthalmologist. That also turned out to be unremarkable. The proper instructions were discussed with the patient, and proper therapy resumed.


Although the U.S. Food and Drug Administration (FDA)-approved dose calls for two different strengths and directions, and although it may be more convenient for prescribers and patients to have both prescriptions dispensed at the same time, the safety of this practice is in question unless clear directions are provided. Prescribers should include instructions for the 20 mg tablets to begin after the 15 mg tablet supply is exhausted. The statement, "Begin taking after [date]" should be included in the Xarelto 20 mg directions. It's time for the boards of pharmacy in all states to mandate patient education by pharmacists for selected high-alert drugs, such as anticoagulants.


The Institute for Safe Medicine Practices (ISMP) has contacted the manufacturer of Xarelto, Janssen, to ask the company to consider providing patient education regarding this potential problem. A "Starting Dose" Pack and "Continuing Dose" pack that illustrate how to take the drug properly would also be helpful.


Compounded pain creams and adverse effects. Some pharmacies are preparing compounded pain creams and ointments that contain a combination of potent medications. Many include drugs that can cause central nervous system depression or cardiac effects. These include: ketamine, baclofen, cyclobenzaprine, lidocaine, tricyclic antidepressants, gabapentin, cloNIDine, and NIFEdipine. Most of these drugs have not been FDA-approved for topical use (although off-label use of medications is routine). Some compounding pharmacies fill prescriptions for these pain creams for patients.


Patients may be unaware of potential dangers with these creams. The products, which are not packaged in containers with a safety closure, may not be carefully stored in order to avoid accidental child exposures. For example, the Philadelphia Poison Control Center received a call about a child who became severely ill after applying his mom's topical fibromyalgia medication to his body-gabapentin, ketamine, diclofenac, cloNIDine, NIFEdipine, bupivacaine, menthol, and cyclobenzaprine-that was compounded at a pharmacy. Pediatric patients may also be at risk of toxicity if the creams are applied to their skin intentionally for a skin condition. Severe toxicity occurred in an 18-month-old child when his father's compounded ointment was used to treat a diaper rash. Compounded pain creams need prominent warnings on labels that describe the potential for toxicity. Physicians who prescribe these drugs, as well as pharmacists who compound and dispense them, must assure patients are provided with instructions about adverse effects, safe storage, and proper use.


Because safety issues can arise with any compounded, unapproved formulations of medications, regulatory or licensing oversight is necessary. With compounded pain creams and ointments, we are specifically concerned about some compounding company statements that may be unproven, such as the products' safe use with children. However, underfunded state boards of pharmacy are ill-equipped to provide such oversight, and the current Drug Quality and Security Act of 2013 (compounding legislation) does not give FDA oversight for traditional compounding pharmacies. It's unclear how the Act's requirement to develop a list of drugs that should never be compounded might affect certain currently compounded products.


Leg laceration following EpiPen use. EPINEPHrine autoinjectors provide life-saving treatment of anaphylaxis. Prompt treatment in the community is associated with decreased morbidity and mortality. Many hospitals stock autoinjectors to enable rapid access to the medication in emergencies. Most often, autoinjectors are used successfully without complications. However, the ISMP received two reports of leg lacerations following EPIPEN JR (EPINEPHrine) autoinjector use.


A 4-year-old boy at day care had an allergic reaction. The staff administered EpiPen Jr by holding the injector against the child's exposed lateral thigh. The child was standing with a day-care staff member behind him for support. Another staff member held the child's leg and administered the injection. The child kicked during administration, resulting in a leg laceration. Believing the device had not been held in place long enough to deliver the drug (instructions call for the needle to remain in place for 10 seconds), the staff member attempted to reinject the child using the same needle, which remained exposed. This resulted in a second laceration (Figure 1). The child's symptoms improved without additional EPINEPHrine. Radiographic imaging and inspection of the needle showed it was bent, which likely prevented the needle cover from locking back in place when the needle was initially kicked free of the patient (Figure 2).

Figure 1 - Click to enlarge in new windowFigure 1. First and second laceration visible on child's leg.
Figure 2 - Click to enlarge in new windowFigure 2. Radiographic image of EpiPen Jr showed that needle was bent.

In a very similar case, a 3-year-old boy with an allergic reaction during day care was given a dose of EpiPen Jr in his exposed left lateral thigh. The child jerked his leg and sustained a 4 cm laceration. The day-care worker then subdued the child with her body weight and attempted to reinject the same EpiPen Jr into his leg a second time to complete the 10-second administration period and ensure the drug had been fully delivered. The child was transported to the hospital, where his symptoms improved without additional EPINEPHrine and the laceration was repaired.


These cases highlight features of the EpiPen and EpiPen Jr design and instructions for use that may have contributed to injuries. The instructions direct the user to hold the EpiPen and push firmly against the outer thigh, holding it in place for approximately 10 seconds. The needle stays under the skin until the EpiPen is removed. Because of this, people may believe it takes 10 seconds for the medicine to be injected. However, the median time to inject the EPINEPHrine is much shorter, less than 3 seconds in most cases. The instructions don't say, "Never reinsert the same needle" or "Don't worry if the needle comes out in less than 10 seconds. The drug is still likely delivered." The instructions for EpiPen use also do not mention patient restraint or the risk of injury with movement.


Providers using or prescribing EPINEPHrine autoinjectors for children should pay close attention to patient restraint prior to injection, as the child may move once aware of the injector or the initial discomfort during injection. This is particularly true for EpiPen Jr and other similar EPINEPHrine autoinjectors where the needle remains in the thigh for 10 seconds. If the needle is dislodged, reinsertion should never be attempted. If it was in place for at least 3 seconds, it is likely that EPINEPHrine was delivered.


ISMP thanks Julie Brown, MDCM, MPH, of Seattle Children's Hospital for providing the contents of this article based on errors that happened outside the facility in which she works.