Watch those units of measurement: Mistakes with compounded clonidine products send children to hospital: ISMP Canada

A child received 1,000 times the intended dose of clonidine and was admitted to a pediatric intensive care unit, ISMP Canada (ISMPC) said in a safety bulletin warning about continuing clonidine errors.It came from a mix-up between micrograms and milligrams while someone prepared the suspension. ISMPC has issued previous warnings about clonidine harming children, and it’s continuing despite these being “never events.” Compounding is inherently high-risk, and other compounded pediatric prescriptions have harmed children.In another case involving clonidine, a child had severe drowsiness and was hospitalized after taking a dose of compounded clonidine suspension over 10 times more concentrated than it should have been, partly due to inaccurate trituration of clonidine powder. Read: ISMP report warns of aspiration in patients undergoing anesthesia who take GLP-1 receptor agonists for weight lossClonidine is an adjunct to stimulant therapy for ADHD and is also used off-label for things such as tic disorders (including Tourette syndrome), hypertension and pain. Making things more difficult, clonidine isn’t commercially available in a pediatric formulation. Therapeutic doses for pediatric patients can be less than the available tablet strengths, which means the drug needs to be compounded into a liquid form. Further complicating things, pediatric doses are often prescribed in micrograms, not the milligrams that would be used for adults. In addition, many pharmacy weigh scales measure in grams or milligrams, but none can measure in micrograms. Read: ISMP clarifies difference between vaccine expiry and beyond-use datesChildren can have a severe overdose from ingesting just 10 mcg of clonidine per kilogram of body weight (200 mcg or 0.2 mg for a 5-year-old weighing 20 kg). Signs of clonidine toxicity are bradycardia, hypotension and central nervous system or respiratory depression. It can also be fatal. To help prevent these errors, ISMPC has several suggestions. For pharmacy managers, pharmacists and pharmacy technicians, it recommends they use a formula that incorporates commercially available tablets instead of the API powder unless the patient is allergic to the tablet excipients. (All of the incidents described in ISMP Canada Safety Bulletins around clonidine involve APIs, not tablets.) A warning in the pharmacy software system should also be used and might include wording such as “Dose/concentration errors up to 1000-fold have been reported with the use of API-based clonidine formulations. Use a tablet-based clonidine formula whenever possible.” Read: ISMP analysis highlights errors that can happen with look-alike high-alert medicationsPharmacies should require documentation of compounded products on a standardized worksheet that follows this guidance. That should include a signed independent double-check from pharmacists or registered technicians of the selected product, calculations and amount/weight. If pharmacies are using trituration, they should treat that as a separate compound that contains its own master formula and compounding record. That should include double-checking calculations, amount/weight and preparation accuracy. Community pharmacies that are outsourcing compounding to specialty compounding pharmacies should perform their own independent double-checking of the calculations and amounts/weights. To do this, they must request the master formula sheet and compounding worksheet be returned along with the compounded product. Read: 10 ways to make repackaged APIs safer: ISMPPharmacists should ensure that weighing equipment they use is calibrated for accuracy daily or before each use and that it’s maintained in keeping with the manufacturer’s recommendations. Using weigh scales that print the weight of the ingredients used in compounding is strongly recommended. Staff members should have their compounding skills and competency evaluated at least once a year through a standard assessment process. Staff who are inexperienced or students should have comprehensive training and supervision. That should include examples of errors from safety bulletins. Finally, pharmacists should encourage parents to report to their pharmacists anything that seems off in their refills, including an appearance, taste or instructions that are different than what they previously received. Parents should be educated about why compounding is complex, the safety procedures in place, and the side effects that might show their child has had an over- or under-dose. The newsletter “Tips for Parents when Medications Need to Be Compounded” should be shared with caregivers as well. Read: Errors related to ADHD medication rose by nearly 300% since 2000: studyThere was also advice for prescribers, including discussing therapeutic alternatives with caregivers, as well as the risks and benefits of each one. If they’re prescribing clonidine, they should show the dose in an amount (not volume). They should also not use dangerous abbreviations. To describe the amount of a dose, they should write “microgram,” or at least “mcg,” instead of “µg.” The doses may be clearer in an electronic prescription than a handwritten one. They should also include the indication and the patient’s weight on the prescription to facilitate therapeutic checks. Pharmaceutical manufacturers should prioritize the development of pediatric formulations for commonly used medications that are not commercially available, such as pediatric clonidine suspension.Read: Watch out for these three common errors with diabetes medicationsFinally, API manufacturers and formula developers should update their formulas for clonidine suspension to recommend using tablets instead of API powder. They should also include a warning statement that says, “Dose/concentration errors up to 1000-fold have been reported with the use of API-based clonidine formulations. Use a tablet-based clonidine formula whenever possible.” In addition, they should consider developing a diluted clonidine API powder, which would reduce pharmacies' need to compound titrations and the risk of calculation and weighing errors.Having diluted products that are commercially available could ensure uniformity and potency testing. They should also pay attention to labelling design for API powders to prevent selection errors, especially between similar products.Read: Pediatric drug shortage led to dosing errors in Ontario children

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