DDI: Inhibitors Increase Substrate Drugs

Question 1

Risk

CYP3A4 inhibitors + Opioids

Answer 1

decreased opioid metabolism -> toxicity

Question 2

Risk

Valproate + Lamotrigine

Answer 2

Valproate decreses lamotrigine metabolism -> increased lamotrigine levels -> inc risk of SJS/TENS

Question 3

Solution

Valproate + Lamotrigine

Answer 3

Titrate lamotrigine slowly
Counsel patient to monitor for rash & seek emergency help if one develops

Question 4

Risk

MAOIs (isocarboxazid, phenelzine, tranylcypromine, rasagiline, selegiline, linezolid, methylene blue)
+
Drugs/foods that increase Epi, NE, or DA (SNRIs, TCAs, bupropion, levodopa, stimulants)
+
Drugs that increase serotonin 5-HT (Antidepressants, opioids, buspirone, dextromethorphan (at high doses), lithium, St. John’s Wort)

Answer 4

high Epi, NE, & DA -> hypertensive crisis

High 5-HT -> serotonin syndrome

Question 5

Solution

MAOIs (isocarboxazid, phenelzine, tranylcypromine, rasagiline, selegiline, linezolid, methylene blue)
+
Drugs/foods that increase Epi, NE, or DA (SNRIs, TCAs, bupropion, levodopa, stimulants)
+
Drugs that increase serotonin 5-HT (Antidepressants, opioids, buspirone, dextromethorphan (at high doses), lithium, St. John’s Wort)

Answer 5

Do not use together!
2 week washout between MAOIs and serotonergic drugs (except fluoxetine -> 5 weeks)

Counsel to limit tyramine rich foods

Question 6

Risk

CYP2D6 inhibitors (amiodarone, fluoxetine, paroxetine, fluvoxamine)
+
CYP2D6 substrates (codeine, meperidine, tramadol, tamoxifen)

Answer 6

Decreased substrate metabolism
increased toxicity
decreased efficacy if prodrug

Avoid using together

Question 7

Risk

CYP3A4 or P-gp inhibitors
+
Calcineurin inhibitors (tacrolimus, cyclosporine)
or
mTOR kinase inhibitors (sirolimus, everolimus)

Answer 7

decreased substrate metabolism
increased ADR/toxicity
* hypertension
* nephrotoxicity
* metabolic syndrome

Question 8

Solution

CYP3A4 or P-gp inhibitors
+
Calcineurin inhibitors (tacrolimus, cyclosporine)
or
mTOR kinase inhibitors (sirolimus, everolimus)

Answer 8

Avoid using together or lower dose CNI or mTOR kinase inhibitor

Monitor transplant drug levels