Article
Common Oral Chemotherapy Interactions
Although these interactions pose a threat to patients, pharmacists can play a large role in minimizing them.
Oral chemotherapy medications are widely used among cancer patients, but they have a narrow therapeutic index, and their pharmacokinetics and pharmacodynamics can easily be altered by various foods and medications. Although these interactions pose a threat to patients, pharmacists can play a large role in minimizing them.
It’s important to read the package insert before taking oral chemotherapy medications. Some of them should be taken with food or on an empty stomach. Many of them can interact with calcium-containing products, grapefruits, or even high-fat meals, resulting in increased systemic exposure and toxicity.
Oral chemotherapy medications commonly interact with anticoagulants, acid suppressors, and antibiotics/antifungals. Most of these interactions occur because they inhibit or induce a variety of enzymes like the CYP450s and pathways like P-glycoprotein.
Anticoagulant Interactions
Oral chemotherapy medications can affect certain anticoagulants’ absorption or prolong a patient’s QTc interval. The anticoagulant most notorious for exhibiting a variety of drug interactions is warfarin. One way to properly manage this interaction is to closely monitor a patient’s PT/INR or ECG and adjust the dose if necessary.
Acid Suppressor Interactions
Proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), and antacids can affect bioavailability or delay elimination of certain chemotherapy medications because some have pH-dependent absorption and require an acidic environment to work. Common PPIs include esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), and pantoprazole (Protonix), while common H2RAs include cimetidine (Tagamet), famotidine (Pepcid), and ranitidine (Zantac). To avoid potential interactions, a PPI should be switched to a H2RA, or H2RAs/antacids should be taken 2 hours before or after the chemotherapy medication. However, these recommendations are drug-specific.
Antibiotic/Antifungal Interactions
Any medications that are CYP450 inhibitors or inducers will most likely interact with oral chemotherapy medications. Erythromycin, clarithromycin, and the azole antifungals, including fluconazole and ketoconazole, are all potent CYP3A4 inhibitors. To avoid this interaction, avoid concomitant administration or adjust the chemotherapy medication’s dose, which should be increased if given with a CYP450 inducer and decreased if given with a CYP450 inhibitor.
There are many other medications that cause drug interactions, and no chemotherapy medication is the same, so it’s important to clarify concomitant drugs before taking any of these medications.
Here’s a helpful overview of oral chemotherapy medications’ interactions:
Drug
Substrate
Competitive
Inhibitor
Competitive
Inducer
Warfarin effects
QTc prolongation
Effect of Acid Suppression on Absorption
Take with food
Take on empty stomach
Grapefruit Interaction
Abiraterone
(Zytiga)
3A4*
2D6+++, 1A2+++, 2C19++,
2C9++, 3A4 ++, 2C8+++
No
No
None
Yes
Afatinib (Gilotrif)
BCRP, P-gp
BCRP, P-gp
No
No
Not studied
Yes
Altretamine (Hexalen)
No
No
None
Yes
Anastrozole (Arimidex)
1A2+
2C8+, 2C9+, 3A4+
None
Axitinib (Inlyta)
3A4*, 3A5*, 1A2-, 2C19-, UGT1A1
No
Not studied
No
Yes
Bexarotene (Targretin)
3A4-
3A4+
Not studied
Not studied
Not studied
Yes
Moderate
Bicalutamide (Casodex)
3A4++
Yes
No
None
Bosutinib (Bosulif)
3A4*, P-gp
P-gp
No
Yes
Yes
Yes
Busulfan (Myleran)
3A4*
Not studied
Not studied
Not studied
Cabozantinib (Cometriq)
2C9-, 3A4*
P-gp
Not studied
Possible
Not studied
Yes
Yes
Capecitabine (Xeloda)
2C9+++
Yes
Not studied
No
Yes
Chlorambucil (Leukeran)
Not studied
Not studied
Not studied
Yes
Crizotinib (Xalkori)
3A4*, P-gp
3A4++, P-gp, 2B6+++
Not studied
Yes
Possible
Yes
Cyclophosphamide (Cytoxan)
2A6-, 2B6*, 2C19-, 2C9-, 3A4-
3A4+
2B6++, 2C9++
Not studied
Not studied
Not studied
Yes
Dabrafenib (Tafinlar)
3A4, 2C8, P-gp, BCRP
3A4++, 2B6, 2C8, 2C19, UDP
Yes
Not studied
Possible
Yes
Yes
Dasatinib (Sprycel)
3A4*
3A4+
Possible
Yes
yes
Yes
Deferasirox (Exjade)
UGT1A1*
1A2++, 2C8++
3A4++
Yes
No
No
Yes
Eltrombopag (Promacta)
1A2-, 2C8-, UGT1A1-, UGT1A3, BCRP*
2C8++, OATP1B+++, BCRP++, UGT1A1, UGT1A3, UGT1A4, UGT1A6
No
No
No
Yes
Enzalutamide (Xtandi)
2C8*, 3A4*
P-gp
2C19++, 2C9++, 3A4+++
Yes
Possible
No
Erlotinib (Tarceva)
3A4*, 1A2-
Yes
Not studied
Yes
Yes
Moderate
Estramustine (Emcyt)
Not studied
Not studied
No
Yes
Etoposide (VePesid)
P-gp-, 1A2-, 2E1-, 3A4*
3A4+, 2C9+
Not studied
Not studied
Not studied
Moderate
Exemestane (Aromasin)
3A4*
3A4++
Not studied
Not studied
Not studied
Yes
Everolimus (Afinitor)
P-gp-, 3A4*
Not studied
No
Not studied
Yes
Flutamide (Eulexin)
1A2*, 3A4*
1A2+
Yes
Not studied
Not studied
Gefitinib (Iressa)
2D6*, 3A4*
BCRP, 2C19+, 2D6+
Yes
Not studied
Yes
Yes
Hydroxyurea (Hydrea)
Not studied
Not studied
Not studied
Ibrutinib (Imbruivica)
3A4*
P-gp
Not studied
Not studied
Not studied
Yes
Imatinib (Gleevec)
Pg-p-, 3A4*, 1A2-, 2C9-, 2D6- , 2C19-
3A4++, 2C9+, 2D6++, BCRP++, P-gp
Yes
Not studied
Not studied
Yes
Yes
Lapatinib (Tykerb)
P-gp, 3A4*
P-gp, 3A4+ , 2C8++ , BCRP
Yes
Yes
Not studied
Yes
Yes
Lenalidomide (Revlimid)
P-gp
No
No
Not studied
Letrozole (Femara)
3A4-, 2A6-
2A6+++, 2C19+
No
Not studied
No
Lomustine (CeeNU)
2D6-
3A4+, 2D6+
Not studied
Not studied
Not studied
Yes
Melphalan (Alkeran)
Not studied
Not studied
Not studied
Yes
Mercaptopurine (Purinethol)
Not studied
Not studied
Not studied
Yes
Methotrexate (Trexall)
P-gp, SLCO1B1
Not studied
Not studied
Not studied
Mitotane (Lysodren)
Yes
Not studied
Not studied
Nilotinib (Tasigna)
3A4*, P-gp
3A4+, 2C9++ , 2D6++, 2C8++, P- gp, UGT1A1
2B6++, 2C8++, 2C9++
No
Yes
yes
Yes
Yes
Nilutamide (Nilandron)
2C19*
2C19+
No
No
No
Pazopanib (Votrient)
AA4*, 1A2-, 2C8-, P-gp
2C8+, 2D6+, 3A4+, SLCO1B, UGT1A1
No
Yes
No
Yes
Yes
Pomalidomide (Pomalyst)
1A2*, 3A4*, 26-, 2C19-, P-gp
Not studied
Not studied
Not studied
Yes
Ponatinib (Iclusig)
2C8-, 2D6-, 3A4-, P-gp, BCRP
P-gp, BCRP
Not studied
No
Possible
Yes
Procarbazine (Matulane)
MAOI
Not studied
Not studied
no
Regorafenib (Stivarga)
3A4*, UGT1A9
2C8, 2C9, 2B6, 3A4, 2C19, UGT1A9, UGT1A1, BRCP, P-gp
Yes
No
Not studied
Yes
Yes
Ruxolitinib (Jakafi)
3A4*
Not studied
Yes
No
Yes
Sorafenib (Nexavar)
3A4*, UGAT1A9
2B6++, 2C9++, 2C8+++, UGT1A1, UGT1A9
Yes
Yes
No
Yes
Sunitinib (Sutent)
3A4*
BCRP, P-gp
Not studied
Yes
Not studied
Moderate
Tamoxifen (Nolvadex)
2C9*, 2D6*, 3A4*, 2A6-, 2B6-, 2E1-
2B6+, 2C9+, 3A4+, 2C8++, P-gp
Yes
Not studied
Not studied
Temozolomide (Temodar)
Not studied
Not studied
Not studied
Yes
Thalidomide (Thalomid)
Not studied
Not studied
Not studied
Yes
Thioguanine (Tabloid)
Not studied
Not studied
No
Topotecan (Hycamtin)
P-gp, BCRP
Not studied
No
No
Trametinib (Mekinist)
Not studied
Not studied
Not studied
Yes
Not studied
Tretinoin (Vesanoid)
2A6-, 2B6-, 2C9-, 2C8*
2C9+
2E1
Not studied
Not studied
Not studied
Vandetanib (Caprelsa)
3A4*
P-gp, BCRP
Not studied
Yes
No
Vemurafenib (Zelboraf)
3A4-, P-gp
1A2++, 2D6+, P-gp
3A4++
Yes
Yes
Not studied
Vismodegib (Erivedge)
2C9-, 3A4-,
P-gp
2C8+, 2C9+, 2C19+, BCRP+
No
No
Possible
Vorinostat (Zolinza)
Yes
Yes
Not studied
Yes
Empty stomach: medication should be taken 1 hour before or 2 hours after last meal; Major substrate: *; Minor substrate: - ; Weak inducer/inhibitor: +; Moderate inducer/inhibitor: ++; Strong inducer/inhibitor:+++
Reference
Segal EM, et al. Oral chemotherapy food and drug interactions: a comprehensive review of the literature. J Oncol Pract. 2014;10:e255-68.
