DDIs: Inducers Decrease Substrate Drugs

Question 1

Risk

Antiepyleptic CYP inducers (phenytoin, phenobarbital, primidone, carbamazepime, oxcarbazepine)
+
CYP substrates (oral contraceptives, other AEDs, carbamazepine [autoinducer] )

Answer 1

Increased substrate drug metabolism -> decreased levels -> decreased efficacy (with AEDs = loss of seizure control)

Question 2

Solution

Antiepyleptic CYP inducers (phenytoin, phenobarbital, primidone, carbamazepime, oxcarbazepine)
+
CYP substrates (oral contraceptives, other AEDs, carbamazepine [autoinducer] )

Answer 2

Monitor drug levels (induction takes up to 4 weeks)

if substrate is lamotrigine use the starter kit that begins with higher lamotrigine doses

Question 3

Risks

Rifampin + CYP and P-gp substrates

Answer 3

concentration of substrate drugs will greatly decrease

Monitor closely (ex INR with warfarin)

Increase dose of substrate as necessary

Question 4

Risk

CYP3A4 inducers + Opioids that are CYP3A4 substrates (fentanyl, hydrocodone, oxycodone, methadone)

Answer 4

decreased pain relief

Question 5

Solution

CYP3A4 inducers + Opioids that are CYP3A4 substrates (fentanyl, hydrocodone, oxycodone, methadone)

Answer 5

assess patients use of breakthrough pain meds and determine if dose increase is necessary

caution against pre-emptive dose increase due to induction lag time and risk of CNS depression

Question 6

Risk

CYP2D6 Ultrametabolizers + CYP2D6 Metabolized Prodrugs (Codeine or Tramadol)

Answer 6

increased active drug concentration -> toxicity

Question 7

Solution

CYP2D6 Ultrametabolizers + CYP2D6 Metabolized Prodrugs (Codeine or Tramadol)

Answer 7

Do not use codeine or tramadol in children < 12 yo or < 18 after tonsillectomy or adenoidectomy

note: do not use an opioid prodrug metabolized by CYP2D6 in a breast-feeding patient unless it is known that they are not a UM

Question 8

Risk

CYP3A4 / P-gp inducers
+
Calcinurin inhibitors (tacrolimus, cyclosporine)
OR
mTOR kinase inhibitors (sirolimus, everolimus)

Answer 8

decreased transplant drug level -> risk of organ rejection

Question 9

Solution

CYP3A4 / P-gp inducers
+
Calcinurin inhibitors (tacrolimus, cyclosporine)
OR
mTOR kinase inhibitors (sirolimus, everolimus)

Answer 9

avoid using together or increase dose of CNI or mTOR kinase inhibitor carefully

monitor drug levels for efficacy

Question 10

Risk

Smoking (induces CYP1A2, includes tobacco and cannabis)
+
CYP1A2 substrates (some APS, antidepressants, hypnotics, anxiolytics, cafffeine, theophylline, warfarin R-isomer)

Answer 10

decreased drug levels -> decreased efficacy

Question 11

Solution

Smoking (induces CYP1A2, includes tobacco and cannabis)
+
CYP1A2 substrates (some APS, antidepressants, hypnotics, anxiolytics, cafffeine, theophylline, warfarin R-isomer)

Answer 11

higher doses may be required for current smokers