Many adverse drug effects are caused by one drug inhibiting or inducing the metabolism or excretion of a second drug. By recognizing drugs that have these effects many drug interactions can be reduced.
Cytochrome P450 enzymes important in drug metabolism:
(1) CYP1A2
(2) CYP2C9
(3) CYP2C19
(4) CYP2D6
(5) CYP3A4
The P-glycoprotein (P-gp) transport system is important for the excretion of many drugs.
Effect on Target Drug |
Inhibitor |
Inducer |
---|---|---|
dose requirement |
reduces |
increases |
toxic effect from accumulation |
possible |
unlikely |
subtherapeutic |
unlikely |
possible |
|
Inhibit P450 |
Induce P450 |
Inhibit P-gp |
Induce P-gp |
---|---|---|---|---|
amiodarone |
CYP2D6, CYP3A4 |
|
Yes |
|
amprenavir |
|
|
|
Yes |
barbiturates |
|
CYP3A4 |
|
|
carbamazepine |
|
CYP3A4 |
|
|
carvedilol |
|
|
Yes |
|
cimetidine |
CYP1A2, CYP2C19, CYP2D6 |
|
|
|
ciprofloxacin |
CYP1A2 |
|
|
|
clarithromycin |
CYP3A4 |
|
Yes |
|
clotrimazole |
|
|
|
Yes |
cyclosporine |
|
|
Yes |
|
efavirenz |
|
CYP3A4 |
|
|
erythromycin |
CYP3A4 |
|
Yes |
|
fluconazole |
CYP2C9, CYP3A4 |
|
|
|
fluoxetine |
CYP2D6 |
|
|
|
fluvastatin |
CYP2C9 |
|
|
|
fluvoxamine |
CYP1A2, CYP2C19 |
|
|
|
grapefruit juice |
CYP3A4 |
|
|
|
haloperidol |
CYP2D6 |
|
|
|
imatinib |
CYP2C9, CYP2D6, CYP3A4 |
|
|
|
indinavir |
CYP3A4 |
|
|
|
isoniazid |
CYP2C19, CYP3A4 |
|
|
|
itraconazole |
CYP3A4 |
|
Yes |
|
ketoconazole |
CYP3A4 |
|
Yes |
|
nefazodone |
CYP3A4 |
|
|
|
nevirapine |
|
CYP3A4 |
|
|
omeprazole |
|
CYP1A2 |
|
|
paroxetine |
CYP2D6 |
|
|
|
phenothiazine |
|
|
|
Yes |
phenytoin |
|
CYP3A4 |
|
|
quinidine |
CYP2D6 |
|
Yes |
|
rifampin |
|
CYP2C9, CYP2C19, CYP3A4 |
|
Yes |
ritonavir |
CYP2D6, CYP3A4 |
CYP3A4 |
Yes |
Yes |
St John's wort |
|
CYP3A4 |
|
Yes |
tamoxifen |
|
|
Yes |
|
ticlopidine |
CYP1A2 |
|
|
|
tobacco |
|
CYP1A2 |
|
|
troleandomycin |
CYP3A4 |
|
|
|
verapamil |
|
|
Yes |
|
zafirlukast |
CYP2C9 |
|
|
|
Specialty: Toxicology, Emergency Medicine, Critical Care
ICD-10: ,