1

1

Presented by: Thao T Nguyen, PharmDPGY1 Pharmacy ResidentThe Children’s Hospital at Saint Francis Tulsa, OklahomaMay 20, 2019

EVALUATION OF THERAPEUTIC MONITORING PRACTICES FOR PATIENTS CONTINUING ANTIEPILEPTIC MEDICATIONS UPON HOSPITAL ADMISSION

Abstract 20IRB Approved

DISCLOSURE

• Thao Nguyen• Potential conflicts of interest: none • Sponsorship: none• Proprietary information or results of ongoing research may

be subject to different interpretations • Speaker’s presentation is educational in nature and

indicates agreement to abide by the non-commercialism guidelines provided

2

LEARNING OBJECTIVES

• Review indications for antiepileptic therapeutic drug monitoring (TDM)

• Evaluate the current antiepileptic TDM at the health system

3

BACKGROUND

4

INTERNATIONAL LEAGUE AGAINST EPILEPSY (ILAE)

• Recommends TDM for some antiepileptic drugs (AEDs)

• Individualized therapy

• Indications for serum concentrations monitoring

– Initiation and dose adjustment

– Concentration-related toxicity

– Persistent seizures

– Unexpected change in clinical response

– Poor adherence

5

Patsalos, P. N. Epilepsia; 49(7): 1239-1276.

CURRENT THERAPEUTIC MONITORING OF ANTIEPILEPTIC DRUGS AT SAINT FRANCIS HOSPITAL

• Only phenytoin & fosphenytoin have prescribing panels to co-order laboratory tests

• Corrected total phenytoin calculator available

6

fosphenytoin Loading fosphenytoin Maintenancefosphenytoin (Cerebyx) ANDPhenytoin Level, Total Timed, Once First occurrence (2 days after load) at 0600

ANDAlbumin LevelTimed, Once First occurrence (2 days after load) at 0600

fosphenytoin (Cerebyx) ANDPhenytoin Level, Total Timed, Weekly First occurrence (2 days after load) at 0600

ANDAlbumin LevelTimed, Weekly First occurrence (2 days after load) at 0600

2

CURRENT THERAPEUTIC MONITORING OF ANTIEPILEPTIC DRUGS AT SAINT FRANCIS HOSPITAL

• No prompt to order serum concentration for other antiepileptic therapy

• No formal pharmacy monitoring

• No standard protocol and/or order set for antiepileptic drugs

• No notification in the electronic medical record (EMR) to notify physician of critical serum concentration

7

STUDY DESIGN AND METHODS

8

STUDY PURPOSE

• Evaluate the current TDM practice for patients continued on study antiepileptic upon admission

9

PRIMARY OBJECTIVE

• Assess the incidence of antiepileptic TDM in study population

10

SECONDARY OBJECTIVES

• Incidence of lab ordering panel utilization

• Incidence of appropriate collection

• Classify appropriately collected serum trough concentrations: subtherapeutic, therapeutic, or supratherapeutic

• Incidence of appropriate pertinent laboratory monitoring during the patient stay

11

STUDY SETTING

12

• Saint Francis Health System (SFHS)

– Saint Francis Hospital (SFH)– The Children’s Hospital at Saint Francis (SFCH)

• Tulsa, Oklahoma• 1,112-bed tertiary center

• 45,460 annual admissions

3

DESIGN & METHODS

• Randomized, retrospective chart review

• Inpatient orders data

• Pertinent laboratory values: CBC, Albumin, SCr, BUN, AST, ALT, CrCl, pregnancy status for valproate orders (if applicable)

13

Agents Accrual Goals (N = 200)carbamazepine n = 50

phenobarbital/primidone n = 50

valproate n = 50

phenytoin/fosphenytoin n = 50

PATIENT SELECTION CRITERIA

• Inclusion

– Any inpatient on study medications

– Length of stay (LOS) of ≥ 48 hours

• Exclusion

– Antiepileptic drug indication

• mood disorder

• neonatal abstinence syndrome (NAS)

• treatment of parenteral nutrition associated cholestasis

• migraine

• one-time dose for status epilepticus

14

PATIENT RANDOMIZATION

15

Admitted patient randomly

assessed for inclusion (N = 637)

Included in final analysis (N = 200)

carbamazepine (n = 50)

phenobarbital/primidone (n = 50)valproate (n = 50)

phenytoin/fosphenytoin (n = 50)

Excluded (N = 437)

carbamazepine (n = 40)

phenobarbital/primidone (n = 130)valproate (n = 133)

phenytoin/fosphenytoin (n = 134)

DATA COLLECTION

• Medication ordered from 7/1/17 to 6/30/18

• Age & gender • LOS

• Admitting diagnosis • Serum concentrations drawn

– At admission

– After dose/dosage form changes (up to 3)

• Drug therapy & serum concentration order source• Pertinent labs collected

16

CRITERIA FOR APPROPRIATE THERAPY

17

Agents Therapeutic Range(mcg/mL)

Appropriate Serum Concentration Monitoring

Appropriate Pertinent Laboratory Monitoring

carbamazepine 4-12Within 7 days after dose

change CBC, Albumin, SCr, BUN, AST, ALT, and CrCl at least weekly

Pregnancy status for valproate orders (if applicable) onadmission

phenobarbital 15-40 Within 4 weeks after dose change primidone 5-12

valproate 50-125Within 48 hours after dose

changephenytoin/fosphenytoin

10-20

Lexi-Lab. Lexicomp

Patsalos, P. N., et al. ILAE Commission on Therapeutic Strategies.

• Serum trough concentration: dosing interval (Q) – 1 hour

• Extra drug monitoring frequency: more serum concentration obtained than needed

RESULTS

4

Baseline Demographics (N = 200 patients)

Characteristic carbamazepine(n = 50)

phenobarbital/primidone

(n = 50)

valproate (n = 50)

phenytoin/fosphenytoin

(n = 50)

Male n (%) 26 (52%) 24 (48%) 30 (60%) 30 (60%)

Age, years n (%)0-11-1718 and older

0 (0%)1 (2%)

49 (98%)

9 (18%)13 (26%)28 (56%)

0 (0%)15 (30%)35 (70%)

0 (0%)3 (6%)

47 (94%)Average LOS (days) range 7 (2-27) 6 (2-15) 8 (2-36) 8 (2-35)

Average duration of therapy (days) range 6 (1-26) 6 (1-13) 7 (2-30) 8 (2-35)

Seizure admission n (%) 5 (10%) 11 (22%) 16 (32%) 12 (24%)

Total number of medication orders (n) 77 68 76 109

Total number of levels ordered (n) 25 43 50 88

19

PRIMARY OBJECTIVE

INCIDENCE OF BASELINE TDM IN PATIENTS CONTINUED ON AED UPON ADMISSION (N = 200)

21

INCIDENCE OF BASELINE TDM IN PATIENTS CONTINUED ON AED UPON ADMISSION OF EACH AED (N = 200)

22

No Serum Concentration Obtained Serum Concentration Obtained

THERAPEUTIC CLASSIFICATION OF SERUM CONCENTRATION DRAWN AT ADMISSION (N = 200)

23

INCIDENCE OF CONCENTRATION DRAWN AT ADMISSION BASED ON ADMITTING DIAGNOSIS (N = 200)

24

No Serum Concentration Obtained Serum Concentration Obtained

5

SECONDARY OBJECTIVES

INCIDENCE OF INDICATED PHENYTOIN SERUM CONCENTRATION COLLECTION (N = 108)

26

INCIDENCE OF PHENYTOIN MONITORING UTILIZING LAB ORDERING PANEL (N = 51)

27

THERAPEUTIC CLASSIFICATION OF SERUM CONCENTRATIONS

28

carbamazepine(n = 5)

phenobarbital/primidone

(n = 10)

valproate (n = 12)

phenytoin/fosphenytoin

(n = 51)

Subtherapeutic 0 0 4 0

Therapeutic 0 10 0 0

Supratherapeutic 2 0 0 0

Random concentration 3 0 8 51

INCIDENCE OF APPROPRIATE PERTINENT LABORATORY MONITORING DURING THE PATIENT STAY (N = 200)

29

Pertinent labs: CBC, Albumin, SCr, BUN, AST, ALT, and CrCl

pregnancy status for valproate orders (if applicable)

SUMMARY

6

LIMITATIONS

• Retrospective chart review

• Small number of patients

• Unknown dosing times prior to admission

• Definition of appropriate monitoring time interval

• No data collected to determine if increased frequency of dose change was appropriate (i.e., change in clinical status)

31

SUMMARY OF FINDINGS

• More than half of patients admitted to the health system did not have initial serum concentration collected

• Prescribing order panels are being utilized

• Timing of serum trough concentration obtained are not optimized

• There is a need for prescribing order panel improvement

32

FUTURE APPLICATION

• Optimization of prescribing panel – Default administration time – Adjusted serum concentration collection time

• Audit of prescribing panel performance after implementation of changes

33

CONCLUSION

• The International League Against Epilepsy recommends therapeutic drug monitoring for dose initiation and change, to provide individualized therapy, and determine concentration-related toxicity.

• The current prescribing panel at the health system have been shown to increase the incidence of serum concentration monitoring and added safety benefit to patients on phenytoin and fosphenytoin.

34

POST-TEST SELF-ASSESSMENT

1. The International League Against Epilepsy recommends therapeutic drug monitoring for which of the following indications?

a. Dose adjustment

b. Individualized therapeutic range

c. Poor compliance

d. All of the above

35

POST-TEST SELF-ASSESSMENT

1. The International League Against Epilepsy recommends therapeutic drug monitoring for which of the following indications?

a. Dose adjustment

b. Individualized therapeutic range

c. Poor compliance

d. All of the above

36

7

POST-TEST SELF-ASSESSMENT

2. Utilization of prescribing panel to co-order laboratory tests has been shown to

a. Increase incidence of serum concentration monitoring b. Decrease sub-therapeutic concentration c. Increase dose titration d. Decrease incidence of pharmacist intervention

37

POST-TEST SELF-ASSESSMENT

2. Utilization of prescribing panel to co-order laboratory tests has been shown to

a. Increase incidence of serum concentration monitoring

b. Decrease sub-therapeutic concentration c. Increase dose titration d. Decrease incidence of pharmacist intervention

38

39

Presented by: Thao T Nguyen, PharmDPGY1 Pharmacy ResidentThe Children’s Hospital at Saint Francis Tulsa, OklahomaMay 20, 2019

EVALUATION OF THERAPEUTIC MONITORING PRACTICES FOR PATIENTS CONTINUING ANTIEPILEPTIC MEDICATIONS UPON HOSPITAL ADMISSION

Abstract 20IRB Approved

REFERENCES

1. Patsalos, P. N., et al. (2008). Antiepileptic drugs best practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia; 49(7): 1239-1276.

2. Lertsinudom S, Chaiyakum A, Tuntapakul S, et al. Therapeutic drug monitoring in epilepsy clinic: a multi-disciplinary approach. Neurology International. 2014;6(4).

40