Pharm Foundations: Inducers/Inhibitors/General Info

Question 1

Concurrent Opioid/Benzo Use Risk

Answer 1

• FDA box warnings on all drugs in each class due to increased fatality risk
• Concomitant use results in profound sedation, respiratory depression, coma, and death
• Limit concomitant prescribing to those who have expended other options
• Restrict doses/durations and monitor for signs/symptoms of respiratory depression/sedation

Question 2

Capecitabine Active Metabolite

Answer 2

Fluorouracil

Question 3

Codeine Active Metabolite

Answer 3

Morphine

Question 4

Colistimethate Active Metabolite

Answer 4

Colistin

Question 5

Cortisone Active Metabolite

Answer 5

Cortisol

Question 6

Famiciclovir Active Metabolite

Answer 6

Penciclovir

Question 7

Fosphenytoin Active Metabolite

Answer 7

Phenytoin

Question 8

Isavuconazonium sulfate Active Metabolite

Answer 8

Isavuconazole

Question 9

Levodopa Active Metabolite

Answer 9

Dopamine

Question 10

Lisdexamfetamine Active Metabolite

Answer 10

Dextroamphetamine

Question 11

Prednisone Active Metabolite

Answer 11

Prednisolone

Question 12

Primidone Active Metabolite

Answer 12

Phenobarbital

Question 13

Valacyclovir Active Metabolite

Answer 13

Acyclovir

Question 14

Valganciclovir Active Metabolite

Answer 14

Ganciclovir

Question 15

Other Prodrug to know

Answer 15

• Tramadol
• Clopidogrel
• Metabolize to “active metabolite”

Question 16

Codeine Safety Considerations

Answer 16

• Risk of toxicity with UM (ultra metabolizers) of CYP2D6, more rapid conversion to morphine (avoid use in these patients)
• Risk of poor analgesia in PMs (poor metabolizers) of CYP2D6 (use alternative analgesic)

Question 17

Clopidogrel Safety Considerations

Answer 17

• Risk with CYP2C19 inhibitors: blocks conversion to active form
• Don’t use with CYP2C19 inhibitors like PPIs (decreases antiplatelet effects)
• Risk with PMs of CYP2C19 (low conversion to active form, reduced activity) - use alternative P2Y12 inhibitor

Question 18

G PACMAN

Answer 18

Common CYP Inhibitors involved in DDI
G - Grapefruit
P - Protease inhibitors (PIs), especially ritonavir
A - Azole antifungals (fluconazole, itraconazole, ketoconazole, etc.)
C - Cyclosporine and cobicistat
M - Macrolides (clarithromycin and erythromycin, NOT azithromycin)
A - Amiodarone (and dronedarone)
N - Non-DHP CCBs (diltiazem, verapamil)

Question 19

PS PORCS

Answer 19

Common CYP Inducers involved in DDI
P - Phenytoin
S - Smoking
P - Phenobarbital
O - Oxcarbazepine (and eslicarbazepine)
R - Rifampin (also rifabutin, rifapentine)
C - Carbamazepine (auto-inducer as well)
S - St. John's wort

Question 20

P-gp Substrates

Answer 20

• Anticoagulants - apixaban, rivaroxaban
• Cardiovascular drugs - digoxin, diltiazem, verapamil
• Immunosuppressants - cyclosporine, tacrolimus
• HCV drugs
• Others: colchicine

Question 21

P-gp Inducers

Answer 21

• Carbamazepine
• Phenobarbital
• Phenytoin
• Rifampin
• St. John’s Wort

Question 22

P-gp Inhibitors

Answer 22

• Anti-infectives (clarithromycin)
• CV drugs: amiodarone, diltiazem, verapamil
• HIV drugs: cobicistat, ritonavir
• HCV drugs
• Other: cyclosporine