1. Shastay, Ann MSN, RN, AOCN

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Clear Instructions and Patient Education Key for Xarelto

XARELTO (rivaroxaban), an oral anticoagulant, is approved for a number of indications, including the treatment of deep vein thrombosis (DVT) and pulmonary embolism. For these two indications, the patient initially takes 15 mg twice daily with food. After 21 days on this dose, the patient switches to 20 mg once daily with food for the remainder of treatment. However, we have received reports in which patients have been dispensed and taken both doses concurrently.


We first heard about this situation in 2014. A patient with a diagnosis of DVT was discharged from a hospital and provided with two prescriptions for Xarelto-one for 15 mg and another for 20 mg. Neither the prescription directions nor the discharge instructions given to the patient made it clear that the 20 mg tablets were not to be started until the 15 mg tablets were finished. The prescriptions were dispensed together at the patient's community pharmacy as neither the prescription benefit manager, pharmacy computer system, nor the pharmacist flagged the potential for duplicate therapy. The patient took the two prescriptions concurrently and was fortunate to not have any serious bleeding.


In 2018, ISMP received another report of this type of error that resulted in patient harm. During a clinic visit, an elderly patient was given two Xarelto prescriptions-Xarelto 15 mg twice daily for 21 days and Xarelto 20 mg daily with a start date of 21 days later. Similar to the first case, both prescriptions were dispensed at the same time by a community pharmacy. The patient was admitted to a local hospital 3 weeks later with a subdural hematoma. The patient had been taking both strengths of Xarelto each day since the prescriptions were filled. The health system identified a few factors that contributed to the event, including 1) insufficient patient education at the time of prescribing and dispensing; 2) the labeling of the 20 mg daily prescription did not clearly indicated that the medication should not be taken until the 15 mg twice daily prescription was completed; and 3) limited use of the manufacturer's starter pack that guides patients to proper dosing for the first 30 days of treatment.


Although it may be convenient for both prescriptions to be issued and dispensed at the same time, the safety of this practice is in question. Ideally, as the situation and patient conditions allow, the prescription for the 20 mg daily dose should not be communicated to the pharmacy until a few days before it is to start. If prescribers must prescribe both dosing regimens at the same time, provide clear directions to the patient and ensure they are understood. Prescribers should include prescription instructions for the 20 mg tablets to begin after the 15 mg tablet prescription supply is exhausted (after 21 days). The statement, "Begin taking after [date]" should be included in the Xarelto 20 mg directions. Pharmacists should make sure the patient has received these explicit instructions verbally and in writing.


For certain high-alert drugs and drug classes, improved computer warnings that are not easy to bypass are required. Payer systems should also have an automated method to decline payment for prescriptions that may cause an overdose, like in this case with Xarelto.


Unfortunately, in many pharmacies today, more emphasis is placed on increasing prescription dispensing and vaccine administration volumes rather than ensuring the provision of proper, pharmacist-led patient education when dispensing new prescriptions. It is time for this paradigm to change and for patient education by pharmacists for selected high-alert drugs, such as anticoagulants, to be mandated.


Home care clinicians play a key role in educating patients and caregivers about how to correctly take Xarelto and monitor the dosing schedule. A patient education leaflet about Xarelto can be found at: Additional medicine education leaflets (Figure 1) are available at:

Figure 1 - Click to enlarge in new windowFigure 1. Examples of the ISMP high-alert medication learning guides for consumers.

Warning! Dilute Sertraline Oral Concentrate

Sertraline is a selective serotonin reuptake inhibitor antidepressant. The drug is available in an oral liquid concentrate (20 mg per mL). The solution must be diluted before use to make the preparation more palatable. Direct administration of the undiluted, concentrated solution is harsh tasting and may numb the tongue and mouth for at least a day, even if the mouth is rinsed extensively. That's exactly what happened to a resident in an assisted living facility when he was given the undiluted concentrate. The pharmacy label did not include instructions to dilute the solution before administration.


It appears that most of the commercially available sertraline products include a warning to dilute before use on the main panel of the manufacturer's carton and bottle (Figure 2). The manufacturer cartons and container labels also include mixing instructions on side panels. However, an informal poll of practitioners found that many were not familiar with the product or the need to dilute it before administration. Prescribers who are unaware of the need to dilute the medication may only provide dosing instructions for the mg or mL amount of the oral concentrate.

Figure 2 - Click to enlarge in new windowFigure 2. The warning to dilute before use is more prominent on Pfizer's ZOLOFT (sertraline) label (left) than other manufacturers' labels.

The solution must be diluted immediately before administration by mixing it with 4 oz (1/2 cup or approximately 120 mL) of water, ginger ale, lemon/lime soda, lemonade, or orange juice only. Other liquids should not be used to dilute this medication. A slight haze may appear after mixing, which is normal. Pharmacy should also place an auxiliary label on the product, instructing nurses and caregivers to dilute the solution immediately prior to administration.


Prescribers, pharmacists, and nurses should use the teach-back method to educate patients and caregivers how to prepare and administer the medication at home. Ensure patients and caregivers have explicit instructions, beyond those found on the manufacturer labels, on how to properly dilute the oral concentrate including the acceptable diluents to use.


It Is Time for Metric Only for Oral Liquids

Some prescribers and community pharmacists continue to believe it is helpful to provide patients with prescription liquid dosing instructions in household measures (e.g., teaspoon). However, the use of household measures has been known to introduce the risk of misinterpretation and error. ISMP alone has received well over 50 reports of teaspoon-tablespoon, milliliter (mL)-teaspoon, and apothecary unit errors. An example of this type of error follows. A prescriber wrote a prescription for a patient to receive 2 teaspoons of amoxicillin suspension 2 times per day. The community pharmacy staff mistakenly entered the directions as 2 tablespoons twice daily. A threefold overdose occurred.


A variety of organizations, including ISMP, the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, the National Council for Prescription Drug Programs, the American Academy of Pediatrics, and the Consumer Healthcare Products Association, have called for doses of all liquid medications to be expressed in mL only. It is time for all practitioners to adopt this practice and designate oral liquid doses in metric (mL) units.