Pharmacology -Drug/Drug Interactions

NTI Drugs

Warfarin

Digoxin

Phenytoin

Tacrolimus/Cyclosporine

Lithium

Theophylline

Methotrexate

Warfarin

Multiple CYP pathways plus PD bleeding risk, monitor with INR

Digoxin

P-gp substrate, renal clearance, low therapeutic index

monitor concentration, K+, heart rate

Phenytoin

Saturable metabolism, CYP2C9/2C19

monitor free concentration, albumin

Tacrolimus/cyclosporine

CYP3A4 + P-gp, graft loss vs nephrotoxicity

monitor trough concentration, SCr

Lithium

Renal handling tied to sodium and volume

monitor concentration and renal function

Theophylline

CYP1A2, smoking status changes clearance

monitor concentrations and symptoms

Methotrexate

renal secretion, folate antagonism

Monitor CBC, SCr, LFTs

grapefruit juice

inhibits CYP3A4

CYP3A4/5

50%, statins, CCBs, Tacrolimus, midalozam, many TKIs

CYP2D6

20%, highly polymorphic, codeine, tamoxifen, metoprolol, many antidepressants/antipsychotics

CYP2C9

15%, S-Warfarin, phenytoin, NSAIDs, sulfonylureas

CYP2C19

10%, polymorphic, Clopidogrel, PPIs, voriconazole, citalopram

CYP1A2

5%, Theophylline, clozapine, olanzapine, caffeine

CYP2E1

Small, ethanol, acetaminophen (to NAPQ1), volatile anesthetics

Ritonavir

inhibits CYP3A4 and P-gp

Rifampin

induces: CYP -3A4, 2C9, 2C19, Pgp, UGT

inhibits: OATP1B1

St. John’s Wort

induces CYP3A4, Pgp

Gemfibrozil

inhibits OATP1B1, CYP2C8

Cyclosporine

inhibits OATP1B1/P1B3 and BCRP

Amiodarone

inhibits Pgp and CYP2C9