PK Carbamazepine, Lithium, and Valproic acid

Drug that is an antiepileptic and auto-inducer

Carbamazepine

Carbamazepine metabolite

10, 11 epoxide

Carbamazepine half life

35 hours single dose

12 hours multidose monotherapy

When does Carbamazepine reach steady state

21-28 days

why is Carbamazepine XL preferred

Lower peaks (less AEs)

Higher troughs

Which Carbamazepine Formulation causes its casings excreted in feces

Tegretol XR

Factors of auto-inducers

Half life decreases with chronic therapy

No first-pass effect

Starts within 3-5 days

What is Carbamazepine‘s major substrate enzyme

CYP3A4

Carbamazepine Target serum concentration range

4-12 mg/L

Monitoring schedule for Carbamazepine Troughs after autoinduction is complete

Q 6-12 months adults

Q 4-6 months children

Random when side effects occur

Steps in Carbamazepine Adjustments

Check range

When are labs drawn

Are they in steady state

Double vision

Diplopia

Can’t see far

Presbyopia

Hearing loss or deafness

Presbycusis

Mood stabilizer for bipolar disorder that does not bind to protein

Lithium

Lithium elimination factors

Renal

T1/2: 16-30 hours

— Longer with poor renal functions

— shorter with increase renal clearance in pregnancy

Lithium monitoring schedule

12 hours post evening dose

Can hold AM dose if needed

Why are Lithium levels 3 - 3.5 mEq/L considered life-threatening

Mania

suicidal ideations

Lithium drug interactions

Diuretics

NSAIDs

ACEi

Lithium steady state

5-7 days

Anticonvulsant drug

Valproic acid

Why are Depakote ER (valproic acid) not bioequivalent to non-ER tabs

Requires 15% increase in dose

Drug that has high

(90-95%) protein binding to albumin

Valproic acid

Valproic acid elimination

Hepatic

No first pass effect

What happens cellularly when Valproic acid dose is increased

Increased unbound level but not in total concentration

Morning Valproic acid monitoring target range

50-100 mcg/mL

After dose change, wait at least 5 days before checking for steady state