Michael J. Gaunt, PharmD

Patients often incorrectly use the product called medicated urethral suppository for erection (MUSE), a urethral alprostadil suppository prescribed for erectile dysfunction.

The medication is available preloaded in an applicator system (see 

) and is administered by inserting the stem into the urethra after urination to ensure the urethra is wet and pressing the applicator button. Each applicator system is wrapped in a foil pouch. Six applicator systems are packaged in a carton. Patients have reported confusion regarding how to properly use this product, resulting in ineffective medication and sometimes leading to urethral hemorrhage.

One factor contributing to these errors has been the lack of adequate verbal patient education. Patients have reported that neither the prescriber nor the dispensing pharmacist explained how to administer the medication. In 1 case, the patient used the product with the protective cover still in place.

Another factor for confusion has been a breakdown in providing written instructions for use.

Despite the professional package insert stating that “a patient package insert [PPI] must be given to each patient at the initiation of therapy,” patients are not always given one.

This gap can be attributed to several issues. First, the manufacturer’s information intended for patients, including step-by-step patient instructions for administration, is printed at the end of the professional package insert meant for health care professionals. Both patients and pharmacists could easily miss these essential patient instructions, and pharmacists may not give the patient what appears to be a professional package insert.

Also, this information is confusingly referred to as “patient information” and not a “patient package insert,” as stated in the professional package insert.

Another issue is that not all prescriptions are written for a quantity of 6 applicator systems, resulting in patients being dispensed individual foil pouches and not the full carton. As there appears to be just 1 package insert in the carton of 6 applicator systems, some patients will not receive the patient package insert when the carton contents are split. The professional package insert with the included patient information could substitute for a separate PPI if there were enough of them and they were handed to each patient.

Still, it would be far better if the “patient package insert” was a document separate from the professional package insert and there were enough copies of the patient document to accommodate situations when individual pouches are dispensed.

For patients who do not receive the patient information, there are instructions on the back of each foil pouch that direct patients to 2 external manufacturer resources for information: a phone number to the company’s medical information center and the product-specific website (muserx.net). However, at press time, this website did not appear to be working, and the phone number did not lead to a direct line that walks patients through the administration process. Also, the website for the manufacturer listed in the product labeling, Meda Pharmaceuticals of Somerset, New Jersey, does not include separate updated instructions identified as a PPI.

It is critical for prescribers and dispensing pharmacists to familiarize themselves with the administration process for MUSE. They must teach patients how to administer the drug safely and verify the patient’s understanding. They also must provide patients with the manufacturer’s professional package insert with the included patient information if it is available. Other than diagrams in the product labeling, the manufacturer does not appear to provide additional information to help patients properly use MUSE. YouTube, however, has several useful videos about MUSE, including this: youtube.com/ watch?v=2sfOG6YfBCM. But the instructions may be challenging to find on YouTube with the search feature, because other products and at least 1 musical artist use the name “Muse.” It helps to include something else about the product in the search, such as “MUSE suppository” or “MUSE alprostadil.”

The Institute for Safe Medication Practices has been in contact with the FDA about this product and the issues with the patient instructions. It
is worth noting that there are other medications and dosage forms packaged in cartons containing multiple units that may not be accompanied by an adequate number of PPIs if the carton is split to accommodate prescriptions for quantities less than a full carton. For products that are routinely dispensed in quantities less than a full carton, including MUSE, manufacturers should consider including additional copies of patient instructions for each individual drug product that might be dispensed. The FDA should take this into account when interacting with manufacturers.

is a medication safety analyst and the editor of ISMP Medication Safety Alert! Community/Ambulatory Care newsletter at the Institute for Safe Medication Practices in Horsham, Pennsylvania.

Articles

Pharmacists should provide both verbal education and written instructions, so mistakes do not occur.

Patients Report Confusion With Use of Alprostadil Urethral Inserts

Parents who are told to give their child or infant OTC ibuprofen oral suspension may not be aware that 2 different concentrations are available.

An infant’s formulation (for infants aged 6-23 months or weighing 5.5- 10.5 kg or 12-23 lbs) contains 50 mg/1.25 mL (40 mg/mL). This is twice as concentrated as the children’s formulation (for children aged 2-11 years or weighing 10.9-43.1 kg or 24-95 lbs), which contains 100 mg/5 mL (20 mg/ mL). Community pharmacies, grocery stores, and mass merchandisers routinely stock both concentrations. Also, the labeling and packaging of the 2 concentrations can sometimes look similar.

Staff members at pediatric hospitals might be familiar with this and
have often made a point of educating parents about this issue at discharge. However, for many reasons, staff members have informed the Institute for Safe Medication Practices (ISMP) about mix-ups that sometimes occur after discharge. One reason is that some hospital computer systems sometimes convert oral liquid doses to a metric volume to help parents measure each dose using a dosing cup or oral syringe. However, the concentration parents might already have at home or purchase is often unknown.

One hospital reported a close call involving a child who was discharged from an ambulatory-surgery unit. The child’s mother was concerned because she was familiar with giving her child (who weighed 8.6 kg) less than 2 mL of ibuprofen, as per the manufacturer’s label instructions.

The discharge instructions, however, said to give 4.3 mL, or 86 mg of the 100-mg/5-mL concentration. After confirming that the mother had the 50-mg/1.25-mL concentration at home and not the 100-mg/5-mL concentration, the hospital was able to tell the mother the appropriate volume of ibuprofen to administer to her child for each dose.

In another case, a child was prescribed ibuprofen 70 mg every 6 hours. The child’s mother was told to give 3.5 mL of the medication for each dose, with the expectation that the 100-mg/5-mL suspension would be used. However, the child’s mother purchased ibuprofen suspension 50 mg/1.25 mL (200 mg/5 mL) and gave her child the 3.5 mL per dose as instructed. So instead of receiving 70 mg, the child received 140 mg per dose.

Fortunately, we are not aware of any serious adverse outcome resulting from this 2-fold overdose, but the possibility of adverse effects is likely increased. An overdose might lead to diarrhea, headache, kidney damage, nausea, stomach bleeding, and vomiting.

This situation is similar to an issue that has since been resolved with oral liquid acetaminophen (Tylenol) products, which, for many years, existed in 2 concentrations: a less concentrated liquid (160 mg/5 mL) for children and a more concentrated liquid (100 mg/mL) for infants.

When the 100-mg/mL concentration was accidentally administered to children in volumes appropriate for the 160-mg/5-mL product, there were accidental deaths and serious injuries to children. Faced with this evidence, manufacturers voluntarily withdrew the more concentrated infant product and agreed to only provide the 160-mg-per-5-mL concentration that is available today (some manufacturers label their products as 500 mg/15 mL).

Dosing errors have occurred when parents and practitioners mix up children’s ibuprofen (100 mg/5 mL), left, and infant concentrated ibuprofen (50 mg/1.25 mL), right.

Because of the potential for harm and the continuing nature of these ibuprofen errors, the ISMP has asked the FDA to look into the matter to determine whether the more concentrated product is necessary. One of the children’s hospital nurses who spoke with the ISMP queried colleagues about this, and the overwhelming response was, “Why isn’t there just 1 concentration of liquid ibuprofen similar to acetaminophen?”

Ideally, Johnson & Johnson Consumer Health, the original sponsor of Children’s Motrin (ibuprofen) for children aged 2 to 11 years, would modify the infant concentration to match the children’s concentration as was done for acetaminophen, with other ibuprofen manufacturers to follow.

For now, the ISMP recommends that health care providers counsel parents about the availability of the 2 liquid ibuprofen strengths and that the 100-mg/5-mL strength includes “children’s ibuprofen” in the name and the more concentrated 200/per-5-mL (50 mg/1.25 mL) strength is referred to as “concentrated infant drops.”

Also be sure that parents understand that the dose in mL (volume) must be based on which concentration they are using.

It is time to standardize to a single formulation to avoid mix-ups that can lead to adverse effects.

Concentrations of Ibuprofen Suspensions Are Error Prone

Two labeling and packaging errors are worth noting to protect patients.

A dispensing error occurred when a pharmacist misinterpreted a prescription for sacubitril-valsartan (Entresto), a product used to treat heart failure that contains different amounts of sacubitril and valsartan (ie, 24/26 mg, 49/51 mg, and 97/103 mg). The prescription listed the strength as 100 mg, which the patient was supposed to take twice daily. However, none of the 3 available strengths of sacubitril-valsartan include a 100-mg strength. The pharmacist dispensed what he thought was closest to the strength prescribed, the 97/103-mg product, and instructed the patient to take the medication twice daily.

A few months later, the patient's physician increased the dose to 200 mg twice daily, and the pharmacist dispensed the 97/103-mg strength with instructions to take 2 tablets twice daily. However, that dose soon led the patient to experience severe adverse effects, including intense lethargy and hypotension. At that point, the pharmacist discovered that the patient had received twice the intended dose because of a dispensing error. The prescriber had added the dose amounts of the 2 ingredients together in the original prescription, so sacubitril-valsartan 49/51 mg (100 mg total) was the original intended dose (figure 1). Even though the product label lists the ingredients separately, the package insert suggests that dosing in clinical trials was based on the total amount of both components of the agent: sacubitril-valsartan 24/26 mg, 49/51 mg, and 97/103 mg were referred to as 50 mg, 100 mg, and 200 mg, respectively. Also, instructions for preparing a suspension from eight 49/51-mg tablets indicate the final concentration in terms of the combined strengths of the ingredients, 800 mg/200 mL.

Such confusion by the pharmacist is easy to understand. Most combination tablets in the United States are prescribed according to the strengths of each respective drug, not the total strength of all active ingredients. For example, the anti-Parkinson drug Sinemet (carbidopa-levodopa) lists the ingredients separately on the label and in the package insert, and the product is prescribed according to the strengths of each respective drug (ie, carbidopa-levodopa 10-100, 10 mg carbidopa and 100 mg levodopa; carbidopa- levodopa 25-100, 25 mg carbidopa and 100 mg levodopa; and carbidopa-levodopa 25-250, carbidopa 25 mg and levodopa 250 mg), not the combined total of both drugs. Ideally, the way strengths are expressed for multi-ingredient products and how these drugs are prescribed should be standardized to prevent confusion. For now, inform pharmacy staff members and prescribers about this potential for error. If there is uncertainty as to which strength was ordered, the pharmacist should contact the prescriber.

Alpelisib labeling confusion and wrong quantity error. 

Alpelisib (Piqray) is prescribed along with fulvestrant to treat specific forms of advanced or metastatic breast cancer. The standard dose is 2 alpelisib 150-mg tablets (300 mg) daily.

For this dose, the tablets are packaged in a carton or calendar pack with a principal display panel that notes, “Two 14-day blister packs each containing 28 tablets.” The label also states that this is a “28-day supply.”

However, the label fails to state the total number of tablets (56) contained inside the carton (FIGURE 2). This led to dispensing an extra carton of tablets during monthly refills for 2 patients. In these cases, the reporter explained that pharmacy staff members saw “28-day supply” on the carton and assumed they would need 2 boxes to reach the intended quantity of 56 tablets. The staff members did not recognize that “Two 14-day blister packs each containing 28 tablets” meant there were 56 tablets within the carton. In fact, some computer listings indicate “28” as the quantity.

It is important to note that alpelisib also is available in other monthly carton configurations and tablet strengths to accommodate dose reductions for certain adverse effects. These include a 250-mg total daily dose (one 200-mg tablet with one 50-mg tablet daily) carton and a 200-mg total daily dose (one 200-mg tablet daily) carton.

Organizations that prescribe or dispense alpelisib should ensure that the electronic health record and pharmacy software correctly indicate the tablet strength, daily dose, and correct quantity per carton. Educate staff members about potential confusion related to the correct quantity and dose. For the 300-mg and 250-mg total daily dose cartons, use flags or reminders to indicate that 1 box contains 56 tablets and that only 1 box is needed for a 28-day supply.

Companies and practitioners should take important steps to protect patients from these mistakes.

Labeling and Packaging Issues Contribute to Dose, Quantity Errors

The Institute for Safe Medication Practices (ISMP) regularly receives reports of medication errors directly from patients. Often these reports describe errors that occurred in community pharmacies. Although they are concerned about the errors, the patients reporting them are usually more upset about the response, or lack of, from the pharmacist or pharmacy management team. Below is an actual case reported to the ISMP Consumer Medication Errors Reporting Program:

I picked up a prescription for temazepam to help me sleep. The pills didn’t work, and I felt worse taking them. Over the course of 4 days, I only slept about 5 hours total. I had heart palpitations, chest tightness, and feelings of panic and agitation. Concerned, I brought the medication back to the pharmacy, and the pharmacist identified the pills as Adderall, not temazepam. The pharmacist immediately became defensive and refused to answer questions about what I should do. He just told me I need to switch pharmacies.

When medication errors happen, especially those that result in serious patient harm, practitioners can experience extreme anxiety and stress. Fear of litigation may cause health care organizations and practitioners to view the patient as an adversary or threat.

When this happens, the organization’s or practitioner’s first inclination may be to deny and defend. Unfortunately, this approach can alienate patients and close the organization’s eyes to the risks that contributed to the event and patient response.

Instead, responding to victims of errors with honesty and transparency puts the patients’ interests and safety first. It encourages open communication about errors and supports system improvements. Most importantly, it is the right thing to do.

Every pharmacy should have written policies and procedures for handling medication errors. Discuss and review these procedures with the pharmacy team, including float, newly hired, and part-time staff members, so that the process is clearly understood. Regularly review the procedures for appropriateness and update them to reflect changes in technology and workflow. The policies and procedures should contain specific guidance about what to do and say, what not to do or say, who should be contacted, particularly when all the facts of the case may not be immediately known, and who will follow up.

General principles include the following:

Create a written policy on disclosure and apology to caregivers, patients, and others, as necessary, that is agreed upon and followed by management and staff.

Decide how to report the event (eg, using the pharmacy’s internal reporting system) and when to notify regulatory bodies as required, risk management employees, supervisors, and upper management.

Define management and staff roles in response to an actual or possible medication error.

Document the event and response, and include the date, details, and time of the event. Make a note in the patient’s profile, so that other staff members are aware.

Establish a continuous quality-improvement program to detect, document, and assess errors to determine the causes, develop an appropriate response, and implement risk-reduction strategies.

Outline a process to follow up with patients and staff to provide investigation results.

Practice and role-play possible scenarios with all staff members using established guidelines and procedures.

Report the event confidentially to the ISMP (ismp.org/report-medication-error), when appropriate, to help others prevent similar errors.

Respond immediately with compassion and empathy. Be direct and open with the patient reporting the error. The goal is to correct the error and minimize any harm or negative impact to the patient.

Share and discuss events, prevention strategies, and procedural changes with staff members.

Support staff members who are involved in the incident by consoling them and offering those involved with the error access to employee assistance programs if necessary.

To help health care organizations and practitioners avoid adversarial responses to harmful events, the Agency for Healthcare Research and Quality has published the Communication and Optimal Resolution (CANDOR) toolkit (ahrq.gov/patient-safety/capacity/candor/index.html). The CANDOR process is designed to help organizations and practitioners respond to harmful events in a just and thorough manner, emphasizing transparent disclosure of adverse events and a more proactive method to achieve a fair resolution for the organization, patients, and practitioners. The process is also designed to support organizations’ efforts to fully investigate and analyze harmful events, improve quality of care and safety, and prevent patient harm. The toolkit includes multiple modules, including a disclosure checklist to help guide organizational discussion and implementation of the CANDOR process.

Practitioners should approach all patients reporting actual or potential medication errors with empathy and transparency. Keep in mind that attention and concern demonstrated to the patient and family members through admission of and apology for an error as well as follow-up discussion of what will be done to prevent future occurrences can help achieve an amicable, fair resolution for all involved.

Excuse me, I think there is an error with my prescription: practitioners should respond with empathy and honesty. Institute for Safe Medication Practices. February 27, 2021. Accessed April 16, 2021. https://www.ismp.org/resources/excuse-me-i-think-there-error-my-prescription-practitioners-should-respond-empathy-and

When patients report pharmacy errors, respond with empathy and transparency to avoid alienating them.