You may not be aware that there is a methotrexate oral solution (XATMEP) that is meant for pediatric use. The drug is indicated for the treatment of pediatric patients with acute lymphoblastic leukemia (ALL) as part of a multiphase, combination chemotherapy maintenance regimen. The product is also approved for use in pediatric patients with polyarticular juvenile idiopathic arthritis who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full-dose nonsteroidal anti-inflammatory agents. Each mL of the solution contains 2.5 mg of methotrexate. Given that parents sometimes measure liquid doses incorrectly, especially when using teaspoons that vary in volume and dosing cups that may have a nonmetric scale, it is frightening to dispense a 120 mL bottle of methotrexate (2.5 mg/mL) for home use.
All oral liquids should be dispensed with an appropriate dosing device, such as an oral syringe that measures in metric units only, so parents can measure liquid medications accurately. It would be nice if the manufacturer provided an oral syringe. Also, it is critically important to educate parents about dose measurement using the teach-back method to demonstrate how they will measure each dose accurately. If parents are given a prescription for oral methotrexate liquid to be filled at a community pharmacy, product labeling recommends telling them to ask their pharmacist for a proper measuring device and demonstration. However, from a patient safety standpoint, this drug is best provided to parents in compounded, prefilled oral syringes containing the exact dose. Because community pharmacies are rarely set up to fill and dispense pharmacy-prepared syringes of oral methotrexate (four syringes per month when dosed weekly), this may fall upon the hospital pharmacy or would need to be arranged through an outsourcer. When educating parents or caregivers, healthcare practitioners should emphasize that the recommended dose should be taken one time weekly (for either labeled indication, ALL, and polyarticular juvenile idiopathic arthritis) and that daily use of the recommended dose has led to fatal toxicity.
Given that this is a chemotherapeutic agent and a hazardous drug, there are concerns with manipulating the drug and discarding unused drug and used syringes. This is a subject beyond the scope of this safety brief but nevertheless a concern, especially with parents handling the drug in the home.
Tragic Error Involving FentaNYL Nasal Spray
The Drug Commission of the German Medical Association communicated through the International Medication Safety Network's member-only blog about a tragic error that happened with INSTANYL, a brand of fentaNYL nasal spray available in Europe. It is intended to be used in cancer patients with breakthrough pain. LAZANDA (fentaNYL nasal spray) is a similar product available in the U.S. Unfortunately, in Germany, a 28-year-old man accidentally took 2 sprays of his partner's fentaNYL nasal spray after confusing it as a nasal spray he was using for a cold. Both nasal spray bottles looked very similar. He experienced respiratory depression and loss of consciousness. Despite resuscitation attempts, he did not survive.
The product in Germany is supplied in a childproof package, including a storage case, to prevent confusion and accidental usage by children or others (Figure 1). However, as happened in Germany, that does not mean the nasal spray bottle will always be placed back into the case after use, as it should. Lazanda, available in the United States, is supplied in a glass bottle in a child-resistant container (Figure 2) and is only available through a restricted program called the Transmucosal Immediate Release FentaNYL (TIRF) Risk Evaluation and Mitigation Strategy (REMS). Pharmacies, distributors, and healthcare professionals who prescribe to outpatients are required to enroll in the program. The purpose of the TIRF REMS access program is to mitigate the risk of misuse, abuse, addiction, overdose, and serious complications due to medication errors. However, this program cannot prevent inadvertent use of the product when confused as another nasal spray.
Outpatient prescribers of TIRF medicines are required to complete a Patient-Prescriber Form with their patients to inform them about the risks, the need to properly store the drug at all times, and how to properly dispose of unneeded medicine. Possible mix-ups with other nasal spray products should be reviewed as a warning, and patients should be reminded of the dangerous adverse effects if fentaNYL nasal spray is used by those for whom the medication has not been prescribed. Detailed educational material for physicians and patients is available for Instanyl, which explicitly refers to risks when used by other persons. Although not stated in the U.S. product labeling for Lazanda, prescribing and dispensing an adequate supply of naloxone is highly recommended for patients receiving opioids at home.
The KIDs List
To create a standard of care for the safe use of medications in pediatric patients, the Pediatric Pharmacy Association commissioned a group of pediatric pharmacists to evaluate the literature and compile a list of potentially inappropriate drugs for pediatric patients. This "KIDs List" is the first list of drugs that should be "avoided" or "used with caution" in all or a subset of pediatric patients. It is akin to the well-known Beers Criteria for older adults but for pediatric patients. ISMP served as a reviewer for the project. The list was published in March 2020 in the Journal of Pediatric Pharmacology and Therapeutics (Meyers et al., 2020; http://www.ismp.org/ext/459).
Legacy Feeding Tubes, Administration Sets, and Transition Adapters Going Away
The Global Enteral Device Supplier Association (GEDSA) announced that its member manufacturers ended production of legacy feeding tubes and cross-application connectors on July 1, 2021, as scheduled, to support the transition to safer ENFit enteral feeding devices (http://www.ismp.org/ext/733). On January 1, 2022, GEDSA members will end production of transition sets and adaptors sold separately from other devices. Individual GEDSA members will continue to provide legacy devices until their supplies run out. GEDSA recommends that all U.S. hospitals convert to ENFit by the end of the year.
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