*Please add “[mgPE]” for “milligrams of Phenytoin Equivalents”

[timbrisc]

Issue migrated from trac ticket # 5791

component: unit definitions | priority: blocker | keywords: prodrug phenytoin equivalents

2021-05-14 16:00:31: psschluter@gmail.com created the issue

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Fosphenytoin is a prodrug of phenytoin. Because the molecular weight differences, 1 mg of fosphenytoin is not equal to 1 mg of phenytoin. To avoid dosing confusion, the recommended dosing unit for fosphentyoin is mgPE (i.e. no dosing adjustments are needed using mgPE). This UOM would be limited to only fosphenytoin and other prodrugs of phenytoin.

The FDA stipulates the following guidance regarding phenytoin sodium equivalents (PE) in https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/076886s000lbl.pdf :

“IMPORTANT NOTE: Throughout all fosphenytoin product labeling, the amount and concentration of fosphenytoin is expressed in terms of phenytoin sodium equivalents (PE). Fosphenytoin’s weight is expressed as phenytoin sodium equivalents to avoid the need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses. Fosphenytoin should always be prescribed and dispensed in phenytoin sodium equivalent units (PE). (See DOSAGE AND ADMINISTRATION.)”

Although the proposed [mgPE] unit is primarily intended for drug administration rather than laboratory observations, Table 19 in §45 chemical and biochemical units would be the most appropriate location for this unit. Although [mgPE] is specific to phenytoin and related prodrugs used for pharmacy dispensing, it is viewed as an essential addition to both UCUM and IEEE 11073 by the IHE Patient Care Device (PCD) community.

The suggested entries in Table 19 in §45 chemical and biochemical units are shown below but are certainly open for further discussion.

|| name || milligrams of phenytoin sodium equivalents || || kind of quantity || mass equivalent (of a prodrug of phenytoin) || || print || mgPE || || c/s || [mgPE] || || c/I || [MGPE] || || M || no || || definition value || || || definition unit || ||

Examples of use:

English: drug strength is “50 mg PE/mL” with the note (PE=phenytoin sodium equivalents)\ UCUM: value # 50, units[mgPE]/mL

English: a single dose of “400 mg PE”\ UCUM: value # 400, units[mgPE]

[timbrisc]

2021-05-25 17:01:07: mitchbre@regenstrief.org commented

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Hi Paul,

Thank you for the request and supporting information. We will discuss the addition of mgPE to the UCUM standard at our next committee meeting, which has yet to be scheduled. I will keep you up to date with any questions the committee has and/or what the final decision is.

Thanks again, Brenee Mitchell Regenstrief Institute/LOINC

Replying to [#5791 Paul Schluter]:

Fosphenytoin is a prodrug of phenytoin. Because the molecular weight differences, 1 mg of fosphenytoin is not equal to 1 mg of phenytoin. To avoid dosing confusion, the recommended dosing unit for fosphentyoin is mgPE (i.e. no dosing adjustments are needed using mgPE). This UOM would be limited to only fosphenytoin and other prodrugs of phenytoin.

The FDA stipulates the following guidance regarding phenytoin sodium equivalents (PE) in https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/076886s000lbl.pdf :

“IMPORTANT NOTE: Throughout all fosphenytoin product labeling, the amount and concentration of fosphenytoin is expressed in terms of phenytoin sodium equivalents (PE). Fosphenytoin’s weight is expressed as phenytoin sodium equivalents to avoid the need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses. Fosphenytoin should always be prescribed and dispensed in phenytoin sodium equivalent units (PE). (See DOSAGE AND ADMINISTRATION.)”

Although the proposed [mgPE] unit is primarily intended for drug administration rather than laboratory observations, Table 19 in §45 chemical and biochemical units would be the most appropriate location for this unit. Although [mgPE] is specific to phenytoin and related prodrugs used for pharmacy dispensing, it is viewed as an essential addition to both UCUM and IEEE 11073 by the IHE Patient Care Device (PCD) community.

The suggested entries in Table 19 in §45 chemical and biochemical units are shown below but are certainly open for further discussion.

|| name || milligrams of phenytoin sodium equivalents || || kind of quantity || mass equivalent (of a prodrug of phenytoin) || || print || mgPE || || c/s || [mgPE] || || c/I || [MGPE] || || M || no || || definition value || || || definition unit || ||

Examples of use:

English: drug strength is “50 mg PE/mL” with the note (PE=phenytoin sodium equivalents)\ UCUM: value # 50, units[mgPE]/mL

English: a single dose of “400 mg PE”\ UCUM: value # 400, units[mgPE]

[timbrisc]

2021-11-02 21:00:22: mitchbre@regenstrief.org changed title from Please add “[mgPE]” for “milligrams of Phenytoin Equivalents” to *Please add “[mgPE]” for “milligrams of Phenytoin Equivalents”

[timbrisc]

2021-11-11 01:21:53: mitchbre@regenstrief.org commented

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Brenée,

Our meeting regarding the proposed UCUM [mgPE] unit-of-measure went very well today. After looking into this over the past several days, Dr. Steven Dain agreed with our approach since ‘mgPE’ is already widely used on drug labels and clinicians and systems already use this as an informal unit. We recommend that you proceed with the UCUM Committee review for this proposal.

We would like to modify the original proposal captured in UCUM ticket URL https://ucum.org/trac/ticket/5791 by removing ’sodium’ in the suggested entries in UCUM Table 19 in §45 chemical and biochemical units, as shown below. This will eliminate any confusion regarding the reference substance and molecular weight for Phenytoin = C15H11N2O2 and 252.268 g/mol [PubChem CID: 1775].

I would need additional guidance from you and your colleagues regarding the content of definition value and definition unit. Please do not hesitate to contact me if you have any questions or comments.

Thanks and regards,

Paul Schluter, PhD

IHE DEV Rosetta Working Group Chair

email: psschluter@gmail.com cell: (414) 702-2026

The suggested entries in Table 19 in §45 chemical and biochemical units are shown below but are certainly open for further discussion.

name: milligrams of phenytoin equivalents kind of quantity: mass equivalent (of a prodrug of phenytoin) print: mgPE c/s:[mgPE] c/I:[MGPE] M: no definition value: definition unit:

Examples of use:

English: drug strength is “50 mg PE/mL” with the note (PE=phenytoin equivalents)
UCUM: value # 50, units[mgPE]/mL

English: a single dose of “400 mg PE”
UCUM: value # 400, units[mgPE]

[timbrisc]

2021-11-16 22:01:07: mitchbre@regenstrief.org commented

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Please see attachment for Paul's updated request...essentially, sodium has been reintroduced for the name "milligrams of phenytoin sodium equivalents", mgPE.

[timbrisc]

2021-11-16 22:03:06: mitchbre@regenstrief.org uploaded file [mgPE] discussion - CORRECTION.pdf (308.8 KiB)

Email from Paul Schluter with information supporting the addition of "mgPE - milligrams of phenytoin sodium equivalents" to UCUM

[timbrisc]

2022-03-23 20:47:59: mitchbre@regenstrief.org commented

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Hi Paul,

The UCUM Committee reviewed the request to add mgPE to the UCUM specification as well as the supporting documentation. Ultimately, the decision was not to include [mgPE] in UCUM and that the reference substance should be used in the expression.

Thank you, Brenee

Replying to [#5791 Paul Schluter]:

Fosphenytoin is a prodrug of phenytoin. Because the molecular weight differences, 1 mg of fosphenytoin is not equal to 1 mg of phenytoin. To avoid dosing confusion, the recommended dosing unit for fosphentyoin is mgPE (i.e. no dosing adjustments are needed using mgPE). This UOM would be limited to only fosphenytoin and other prodrugs of phenytoin.

The FDA stipulates the following guidance regarding phenytoin sodium equivalents (PE) in https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/076886s000lbl.pdf :

“IMPORTANT NOTE: Throughout all fosphenytoin product labeling, the amount and concentration of fosphenytoin is expressed in terms of phenytoin sodium equivalents (PE). Fosphenytoin’s weight is expressed as phenytoin sodium equivalents to avoid the need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses. Fosphenytoin should always be prescribed and dispensed in phenytoin sodium equivalent units (PE). (See DOSAGE AND ADMINISTRATION.)”

Although the proposed [mgPE] unit is primarily intended for drug administration rather than laboratory observations, Table 19 in §45 chemical and biochemical units would be the most appropriate location for this unit. Although [mgPE] is specific to phenytoin and related prodrugs used for pharmacy dispensing, it is viewed as an essential addition to both UCUM and IEEE 11073 by the IHE Patient Care Device (PCD) community.

The suggested entries in Table 19 in §45 chemical and biochemical units are shown below but are certainly open for further discussion.

|| name || milligrams of phenytoin sodium equivalents || || kind of quantity || mass equivalent (of a prodrug of phenytoin) || || print || mgPE || || c/s || [mgPE] || || c/I || [MGPE] || || M || no || || definition value || || || definition unit || ||

Examples of use:

English: drug strength is “50 mg PE/mL” with the note (PE=phenytoin sodium equivalents)\ UCUM: value # 50, units[mgPE]/mL

English: a single dose of “400 mg PE”\ UCUM: value # 400, units[mgPE]

[colin-e-hscic]

Possibly naive question, but does the word "of" in a proposed unit not immediately suggest that this is referring to something that belongs in the Procedure or Component (measurand) side of a measurement, not in the unit?

We all understand that "tonnes of coal" and "tonnes of iron" are describing different physical items, but the tonne as a unit is not unique to each measurand.

Is something like-

mass concentration of XXX as phenytoin sodium equivalent = YYY mg/L

not what is being described here?

[chgessner]

The problem that is raised here is related to drug prescription, dispense, and administration and it is apparently a serious threat to patient safety. While LOINC can be used to discriminate lab values of Phenytoin mass vs. Fosphenytoin mass concentration as measured in Serum or Plasma, LOINC is not used (and not usable) for drug dosing and administration. As a result, the "unit" data field is apparently the only place where prescribers and administrators can document, check and verify that they indeed talk about concentration of Phenytoin, and not Fosphenytoin.

[colin-e-hscic]

Our situation in the UK is different. We are aiming to use SNOMED pretty much everywhere (in time) so in principle we ought to be able to keep the measurand where it belongs, in the test / procedure / substance or whatever code.

While I appreciate the real-world problem that is being faced here, it does seem like a request to abuse the codesystem to address a problem somewhere else.

I also realise that a lot of existing systems basically use the "thing (description), amount (number), unit (UoM)" triplet to describe everything, and given that the amount is often constrained to be a number the poor old units field tends to be the dumping ground for any information that doesn't fit anywhere else.

If the Phenytoin vs. Fosphenytoin distinction is relevant only to a human reader (clinician, pharmacist, patient) then maybe this is a case where an annotation could be used. However i'm not a fan of annotations in general, and especially not for information that's not just semantically relevant, but in this case as you've said safety-critical.