C3.1 R4(e): Perform & document a pharmacokinetic interpretation (OTHER drug)

ID: 72 yo female with bipolar type II disorder and mild Alzheimer’s

s/o:

  • Taking divalproex EC 1000mg po daily at 800hr since Sept 28, 2016 (no compliance issue in hospital)
    • As per P’net, patient was also on divalproex EC 1000mg po daily PTA (but likely non-compliant as valproic acid level on admission (Sept 26) was 36 umol/L)
  • Valproic acid level: 513 umol/L (350-835 umol/L)
    • Taken on Oct 5, 2016 (12 hours post 800 hr dose)
      SPH lab bases on 12 hr-post dose trough concentration, regardless of dosing frequency as studies have shown that its best for interpretation
  • Oct 5, 2016 Labs:
    Alb: 30g/L, AST = 20, ALT = 12, GGT = 8, ALP = 57, total bilirubin = 5 umol/L
  • As of Oct 6, 2016 – patient denies any concerns or side effects with divalproex (e.g. no tremors, weakness, dizziness, stomach upset). Patient feels that her mood is stable (denies low or elevated mood, issues with sleep and energy)

A:

  1. Level is drawn appropriately and at steady state
  2. Level is within therapeutic range. However, albumin is slightly low and also considering her age the protein binding to valproic acid might be lower and total valproic acid level might noe be reflective that free valproic acid level is within therapeutic range. Her free valproic acid level is likely higher than someone who is younger and have normal albumin levels.
  3. Patient denies any issues with her mood and there are no significant safety concerns with divalproex

P:

  1. Continue current dose of divalproex 1000mg EC po daily
  2. Monitor for adverse reactions of divalproex (e.g. tremors, dizziness, insomnia, stomach upset)

C3.1 R4(e): Perform & document a phenytoin pharmacokinetic interpretation

Clinical Pharmacy Note RE: Phenytoin Levels

ID: 47 yo male with history of seizure disorders (?type of seizure ?unclear history)
(As per nurse, patient reports that last seizure, which was a petit mal seizure, was 2 months ago)

wt = 105.9kg, ht = 5 ft 10 inches, BMI = 33.4 kg/m2

Current regular medications:

  • Phenytoin 200mg extended release capsules PO BID (800hr, 2200hr)
    • Started on Sept 23, 2016 at HS
    • Was on same dose PTA but as per team care binder, did not take it on Sept 21/22
    • As per nurse, no issue swallowing capsules
  • Divalproex EC 250mg PO BID
    • Started on Sept 28, 2016 at HS
    • Dose ↑ on Sept 29, 2016 (today) to 250mg AM (same )and 500mg HS (↑)
  • Paliperidone 100mg IM q 4 weeks
  • Olanzapine 15mg PO HS
  • Nicotine Replacement Therapy

Phenytoin Levels (Target: 40-80 umol/L):

  • Sept 23, 2016: 5 umol/L (prior to 1st dose in hospital)
  • Sept 29, 2016: 11 umol/L at 1000hr (prior to Sept 29 AM dose)

Sept 29, 2016: Alb: 37 g/L        Sept 23, 2016:  sCr: 89umol/L,  eGFR: 92 mL/min

A:

  1. As per nurse, patient has not had a seizure during hospital stay.
  2. All doses given appropriately and on time.
  3. Phenytoin trough concentration drawn appropriately (12 hours post-dose)
  4. Level is likely not at steady state but trending upwards (average half-life: ~22 hrs, but can range from 7 to 42 hrs due to saturation kinetics. Time to steady state can range from 3 to 50 days)
  5. Using IBW (as patient is obese), maintenance dose should be 365-512 mg/day
  6. Drug interactions with phenytoin (Lexicomp):
    – Divalproex may ↓ the protein binding of phenytoin (as both compete for binding to albumin). This may lead to an initial ↑ in free phenytoin and to a ↓ in total phenytoin concentrations. With long-term concurrent use, total phenytoin concentrations may ↑.
    – Phenytoin may ↓ the serum concentration of divalproex. There is also a potential for hepatotoxicity due to the ↑ concentration of a hepatotoxic valproic metabolite if phenytoin dose is increased.
    – Phenytoin may ↓ the concentration of paliperidone and trazodone
    – Trazodone may ↑ the concentration of phenytoin
  7. As divalproex dose is being increased to pre-admission dose, total phenytoin levels may not accurately indicate that patient is on a therapeutic dose.

P: Suggest

  1. Continue current phenytoin dose, and monitor patient closely for seizures
  2. Monitor phenytoin concentrations weekly. Level next week will reflect a concentrations closer to steady state.
  3. Consider doing free phenytoin levels to assess efficacy and safety, if levels continue to remain subtherapeutic.
  4. Monitor AEs of phenytoin: ataxia, confusion, dizziness, somnolence, headache, slurred speech, N/V, nystagmus

C3.1 R4(e): Perform & document a vancomycin or aminoglycoside pharmacokinetic interpretation

Sept 6: Dosing

ID: AIA is a 30 yo female [163cm (5 feet 4 inches), 66.3 kg] admitted on for meningitis (Listeria).

ID consult – orders to:

  • Discontinue dexamethasone, acyclovir, ceftriaxone and vancomycin
  • Continue Ampicillin 2g IV Q4H x 20 days
  • Start Gentamicin 100mg IV Q8H x 5 days – Pharmacy to dose

s/o:
4 day history of severe headache, neck pain, diffuse myalgias, multiple episodes of emesis throughout the day, mild sore throat and rhinorrhea.
x cough x photophobia x fevers/chills

Sept 6/2016
Vitals: Temp 36.4,  BP 98/59,  HR 69,  RR 18,  O2Sats 98% RA

Labs:
↓ WBC (Sept 5: 11.1 → Sept 6: 9.5)
eGFR: >120mL/min/1.73m2 (stable)
↓ sCr: (Sept 4: 49  → Sept 5: 40 → Sept 6: 35)
Calculated CrCl (CG): 217.46 mL/min

Micro:

  • 02/09: Lumbar puncture – CSF: No growth
    CSF WBC: 471 (H), Cloudy appearance (Tubes 1+2), CSF RBC 12(H), Neutrophils 6%, Glucose 2.5 (N), LDH 31 (H), Total Protein 2559 (H)
  • 02/09: Lumbar puncture – CSF: Viral Cx, Fungal Cx, Mycobacterial Cx Pending
  • 03/09: Blood Cx: No growth after 48 hours incubation
  • 04/09: Lumbar puncture – CSF: Pending
  • Sent cultures off-site for PCR: Listeria Meningitis

A/Checklist:

  1. Is this drug indicated?: Yes
    IDSA 2004 Guidelines: Aminoglycosides could be considered in addition to Ampicillin or Penicillin G for Listeria monocytogenes
    Sanford’s: Listeria meningitis: Ampicillin 2gm IV Q4H + gentamicin 2mg/kg IV loading dose then 1.7mg/kg IV Q8H
    Treat for 21 days.
    ID consult – determined that gentamicin should be added on for synergy
  2. Is the dose appropriate?: Yes
    Usual conventional dose is 1-2mg/kg/dose every 8 hours (5mg/kg/day divided every 8 hours falls under this range). Sanford’s provides a dose of LD of 2mg/kg IV then 1.7mg/kg IV Q8H.
    LD determined to be unnecessary by ID.
    ? Duration of 5 days for synergy
  3. Is the dosing interval appropriate?: Yes
    based on sCr and age, every 8 hours is appropriate

Calculation:
IBW (kg) = 45kg + (2.3*4) = 54.2 kg
DBW (kg) = IBW + 0.4*(66.3-54.2) = 59.04kg
ABW is 22% greater (<25%) than IBW → use IBW to calculate dose (if >25%, use DBW)

5mg/kg/day * 54.2kg = 271mg/day → ~90mg IV Q8H

  • Gentamicin is available as 40 mg/mL solution (80 mg/2 mL vial) and premixed minibag (60 mg/50 mL NS, 80 mg/50 mL NS, 100 mg/100 mL NS, 120 mg/100 mL NS)
    ∴ ↑ to 100mg IV Q8H

100mg IV Q8H

  • Falls within 1-2mg/kg IV Q8H conventional dose (54.2-108.4mg IV)

P: As discussed with MD,

  1. Gentamicin 100mg IV Q8H x 5 days (1st dose given at 1715)
    ∴ dosing times – 1715, 0115, 0915
  2. Gentamicin Peak Concentration  (Target: 8-10 mg/L for meningitis)
    – 30 mins post 30 min infusion of 0915 dose (3rd dose)
  3. Gentamicin Trough Concentration (Target: 1-1.2mg/L for synergy)
    – 30 mins prior to 1715 dose (4th dose)

Dosing times slightly changed and 2nd, 3rd doses wer given at 0030 and 700

Orders:

  1. Please change gentamicin dosing times to 700, 1500, 2300
  2. Gentamicin peak concentration at 1600 today (30 mins after the 30 min infusion ends)
  3. Gentamicin trough concentration at 2300 today (30 mins before the 2300 dose)

Sept 8:

Vitals: Temp 36.4, BP 101/65, HR 69, RR 18, O2Sats: 97% RA (stable)

Labs:
WBC (Sept 7: 9.5 → Sept 8: 9.1)
↑ sCr (Sept 7: 42 → Sept 8: 56)
Calculated CrCl (CG): 135.91 mL/min

Micro:

  • 07/09: Lumbar Puncture – Preliminary: No Growth
    CSF WBC: 293 (H) ↓, Appearance Clear/Colourless (on all tubes), CSF Glucose 4.7 (H), Total Protein: 213 (N)

Levels:

  • Gentamicin Peak: 4.9 mg/L
  • Gentamicin Trough: < 0.5 mg/L

A/Checklist:

  1. Is this drug indicated?: Yes
    See above.
  2. Is the dose appropriate?: Yes
    See above.
  3. Is the dosing interval appropriate?: Yes
    Stable renal function, Q8H still appropriate
  4. Are all the doses given on time?: Yes
  5. Was the level drawn at steady state?: Yes
  6. How is the patient doing?:
    Overall, patient is clinically improving on his antibiotic therapy.
  7. Any side effects?: Renal function is stable. No changes in hearing.

P:
As her lumbar puncture has significantly improved, her gentamicin therapy will only be continued until discharge (likely only 3 days therapy total). Another serum drug concentration is not required.


Resources for AG:

 

C3.1 R4(e): Perform & document a vancomycin or aminoglycoside pharmacokinetic interpretation

ID: 42 yo female admitted for query septic arthritis/deep tissue infection/myositis

s/o:
Current Abx Therapy:

  1. Pip/Taz 3.375mg IV Q6H
  2. Vancomycin 2g IV Loading Dose x 1 dose on August 31 1530
    Currently on 1g IV Q12H (at 330, 1530)

Vital Signs (Sept 2/16): Temp 37.4, BP 119/79, HR 99, RR 18, O2 sats 95% RA
(receives APAP PRN for pain)

Labs:
↓ WBC (Aug 31: 22.2 –> Sept 2: 10.5)
↓ sCr (Aug 31: 98 –> Sept 2: 45)
↑ eGFR (Aug 31: 62 –> Sept 2: 118)

Micro: MRSA screen pending. Blood Cxs on Aug 31/16 are negative.
Urine Cxs + For E. Coli 90 mega CFU/L

Vanco trough level: 6.2 mg/L (target 15-20mg/L)
– drawn 30 mins prior to Sept 2 330 dose (4th dose, including LD)

A/Checklist:

  1. Is the drug indicated?: Although patient is improving (decreased WBC, afebrile, improving overall) and is tolerating vancomycin (urinating well, no compliants, sCr stable), cultures are still pending.
  2. Were all the doses given on time?: All doses were given on time
  3. Was the level drawn at steady state?: Trough level was at steady state (pre-4th dose)
  4. Was the level drawn appropriately?: Level was drawn appropriately 30 mins prior to the 4th dose
  5. Assess the level: Vanco trough level = 6.2, which is below target

P: As discussed with MD:

  1. Discontinue previous vancomycin IV orders.
  2. Increase vancomycin to 1.25g IV Q8H – next dose due at 1530 today
  3. Vancomycin level on Sept 3 at 1500 (30 mins prior to 1530 dose)
  4. Will continue to monitor: renal function, temperature, pain/swelling, WBC, CRP
  5. Pharmacy will continue to follow and adjust dose accordingly. MD to reassess need for vancomycin.

Rationale for vancomycin 1.25g IV Q8H:

  • Improving renal function requires increased frequency (Q8H) to ensure concentrations stay above vancomycin’s MIC
  • Following linear pharmacokinetics:
    • Would expect that we would need to target a daily dose of ~5500mg
      (~1800g IV Q8H)
  • Although we want to ideally target 15-20mg/L, the benefits of ~doubling the dose to target 15-20mg/L likely won’t outweigh the risks (e.g. risk of accumulation
    → increased risk of nephrotoxicity and ototoxicity) when the patient is already improving at a significantly sub-therapeutic level.
  • Therefore: ↑ dosing frequency and ↑ the dose by 250mg (minimum dosing increment)
  • Keeping in mind: patient improving at sub-therapeutic level may indicate that patient is improving on other antibiotic therapy and that coverage against MRSA may not be warranted. Pharmacy should follow up with MRSA screen.

Reflection – Pharmacokinetics

For the past week, Dr. Ensom went over pharmacokinetics for vancomycin, aminoglycosides, phenytoin and digoxin, as well as, gave us a brief overview of other drugs that have TDM. On our last day, we also had clinical pharmacists share real-life cases and how to apply pharmacokinetics in real life. The sessions were incredibly useful, especially since I didn’t take the pharmacokinetics electives. During my general medicine rotation, I hope to get more experience with interpreting levels, applying my pharmacokinetic knowledge and writing concise and comprehensive chart-notes/documentations.

Some things I took away from the sessions:

  • For future chart notes on TDM, I will document if possible on: individual pharmacokinetic parameters, population estimates (if clinically useful)
    – check if this is the first or follow-up note
    – write chart notes in bullet points
    – check infusion times, timing of level relative to dose, previous doses and their timing
    – keep in mind that my audience is the health care team and other pharmacists
  • Patient can only be toxic if they are alive!
  • Population estimates are like clothes off the clothing rack. Whenever possible, want to get individual PK parameters

C3.1 R4(e): Perform & document a vancomycin or aminoglycoside pharmacokinetic interpretation

Patient’s Vancomycin Doses:

Dose # of Doses Prior to Level Level
1g IV Q12H 5 24.3 (High)
750mg IV Q24H 2 15.3
  • Aspirate from L shoulder: MRSA +
  • Challenging to obtain information from patient (e.g. wasn’t able to ask about side effects like sxs of ototoxicity). Patient is mostly in bed, but appears to be improving.

————————————————————————–

Clinical Pharmacy Note: Re: Vancomycin

s/0 77 yo male with MRSA septic arthritis L shoulder. Target vanco should be: 15-20mg/L.

vanco to 750mg Q24H since Jun 19. Vanco level at 2147 on Jun 21: 15.3 mg/L

eGFR~ 89, stable for last few days.
Jun 21 – WBC: 10.3, CRPH 57.7 ↑
Jun 22 – 36.8oC T, BP 130/87, HR 87

Pain was worse last night (pt crying), as per nurse. Settled with PRN hydromorphone dose. No complaints of pain today. Swelling same as yesterday, as per nurse.

A

  1. Septic arthritis appropriately treated with vancomycin for MRSA.
  2. Level is drawn appropriately at steady state and is within target.
  3. Renal function stable
  4. All doses charted as given.

P

  1. Continue vancomycin 750mg IV Q24H
  2. Awaiting ID consult to determine duration of tx.
  3. If prolonged duration, weekly vanco level
  4. Monitor renal function 3 times a week.
  5. Monitor s/s of septic arthritis (pain, swelling, mobility), WBC, CRPH, vital signs. If clinically worsening, increase vanco monitoring and R/A.

Order:

  • Continue vancomycin IV with no stop date. Awaiting ID consult RE: duration of treatment.