Hospital Pharmacy - June 2018 - 144

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Hospital Pharmacy 53(3)
and adults and provide staff with clear recipes that include
the oral suspension vehicle (eg, Ora-Plus and Simple
Syrup, not water) to use along with detailed directions for
preparing the suspension. A Michigan statewide initiative
has created recipes with standardized concentrations for
pediatric oral compounded liquids.2 These recipes, including one for tacrolimus, are freely available at: http://www.
mipedscompounds.org/standard-formulation. They include
directions for preparation, data on stability, and storage
information. The American Society of Health-System
Pharmacists is also currently working on a project to provide standardized concentrations for intravenous and oral
liquid medications (https://www.ashp.org/-/media/assets/
pharmacy-practice/s4s/docs/s4s-ashp-oral-compound-liquids.ashx).

Figure 1. "ONCE-DAILY" has been misinterpreted by patients
as meaning take only 1 capsule per dose, rather than following the
directions on the prescription label.

undetectable level. The patient had been taking only 1 mg of
the drug daily, not the 6 mg dose. Instead of following the
correct directions on the pharmacy label, the patient had
been following what she thought were directions for use on
the manufacturer's label that stated, "ONCE-DAILY," listed
right below the drug name and dose (Figure 1).

Compounding Errors
Errors during the compounding of tacrolimus oral liquid
formulations were also reported, including 10-fold overdoses and underdoses when the incorrect capsule strength
was used for preparation (ie, 0.5 mg instead of 5 mg), inappropriate substitution of a generic product for a brand
name product, incorrect preparation of the suspension, and
incorrect storage conditions. In 2 of the cases, a tacrolimus
suspension was created using the wrong suspending agent.
Tacrolimus is poorly soluble in water, so it is recommended
to compound an oral suspension using Ora-Plus and Simple
Syrup.1 Ora-Plus contains suspending agents, which prevent drug particles from aggregating and settling. This
allows for the creation of a homogeneous suspension and
uniform concentration. One of the patients who received
an incorrectly compounded suspension, for which OraPlus was not used, experienced problems with extreme
fluctuations in his tacrolimus levels. The outcome for the
second patient is unknown.

Safe Practice Recommendations
Standardize Compounding Concentrations and
Recipes
If oral liquid formulations of tacrolimus must be compounded, establish a standard concentration for pediatrics

Avoid Leading Decimal Point Doses
Always include a leading zero when expressing tacrolimus
doses less than 1 mg on computer screens, device screens,
pharmacy labels, shelf markers, and other paper and electronic formats. Whenever possible, avoid fraction doses
greater than 1 mg by rounding the dose to the nearest whole
number.

Monitor Patients Frequently
Tacrolimus has a narrow therapeutic index, so trough levels
should be obtained for monitoring to prevent organ rejection
(from levels that are subtherapeutic) and nephrotoxicity
(from supratherapeutic levels).

Use Brand Names
Display the brand name of tacrolimus extended-release formulations (ie, Astagraf XL, Envarsus XR) on drug ordering
and verification screens to help differentiate these formulations from regular-release tacrolimus (ie, Prograf, generics).
When prescribing regular-release tacrolimus, use only the
brand or generic name, without any modifiers such as "IR"
for immediate-release.

Add to Look-Alike List
Consider including tacrolimus and tamsulosin on your organization's look-alike drug name list, and increase the situational awareness of staff regarding the risk of potential
mix-ups. (The drug name pair will be added to ISMP's List of
Confused Drug Names with the next update.)

Stock Needed Strengths
Stock all available strengths of tacrolimus that might be prescribed in your facility and use the simplest single strength or
combination of strengths to match the patient's prescribed
dose when dispensing the product.

http://www.mipedscompounds.org/standard-formulations http://www.mipedscompounds.org/standard-formulations https://www.ashp.org/-/media/assets/pharmacy-practice/s4s/docs/s4s-ashp-oral-compound-liquids.ashx https://www.ashp.org/-/media/assets/pharmacy-practice/s4s/docs/s4s-ashp-oral-compound-liquids.ashx https://www.ashp.org/-/media/assets/pharmacy-practice/s4s/docs/s4s-ashp-oral-compound-liquids.ashx

Table of Contents for the Digital Edition of Hospital Pharmacy - June 2018