World Cancer Day: Exploring Oral Chemotherapy Medication Interactions

Oral chemotherapy medications are frequently used to treat and manage many types of cancer. The ability to self-administer oral medications provides benefits such as more independence for administration and fewer trips to the doctor’s office or cancer center. One disadvantage to oral medications is the potential for more drug-drug interactions. On this World Cancer Day, let’s explore interactions associated with oral chemotherapy medications and how we can manage them.

Oral Chemotherapy Medications

Every year, more oral chemotherapy medications are receiving FDA approval. Many of these medications require monitoring for interactions. Some common interactions include inhibition or induction of CYP3A4, stomach acid suppression affecting absorption, risk of QTc prolongation, interactions with blood-thinning medications, and interactions with food and herbal supplements.¹

Oral chemotherapy can be used alone or in combination with other therapies, such as IV chemotherapy and/or immunotherapy.  In general, oral chemotherapy medications have a higher risk of drug interactions due to the route of administration. The use of oral chemotherapy may contribute to the risk of polypharmacy, especially in older adults who maybe treating multiple chronic conditions with oral medications.¹

CYP3A4 Drug-Drug Interactions

Many oral chemotherapy medications utilize the CYP3A4 pathway for metabolism. Therefore, there is a risk of drug-drug interactions with other medications which utilize the same metabolic pathways.

In general, inhibitors or strong substrates of CYP3A4 may increase the levels of certain oral chemotherapy medications. Depending on the strength of inhibition, the levels may be increased from 2 to 5 fold.² These increased levels may lead to increase toxicity of the chemotherapy medications. These increased levels may reduce tolerability of the chemotherapy and therefore disruption of therapy and in severe cases, hospitalizations and poor outcomes.

Inducers of CYP3A4 have the opposite effect. These medications may lead to increased clearance of these oral chemotherapy medications. This means that patients may be at risk of therapy failure if the standard dose is used.

Specific recommendations exist to mitigate these interactions. These interventions may include dose adjustments, alternative therapy, and discontinuation of the inhibitor or inducer. These interventions are necessary to reduce the risk of side effects and ensure efficacy of the oral chemotherapy agents.

Stomach Acid Suppression

Many oral chemotherapy medications require stomach acid at a certain pH for the best absorption of the medication.³ Therefore, taking certain medications which reduce stomach acid may reduce the ability of the chemotherapy agent to be absorbed into the body. Common medications that suppress stomach acid may include proton pump inhibitors as well as histamine-2 receptor antagonists.

Mitigation of these interactions include changes to the times of administration or avoidance of the acid suppressing medications. Following the guidance for timing of administration is imperative to maintain efficacy of the oral chemotherapy medication.

QTc Prolongation

Certain medications may contribute to the risk of a rare but serious change to the heart rhythm known as QTc prolongation.¹ QTc prolongation left untreated may lead to a fatal heart arrhythmia known as torsades de pointes. Monitoring of the EKG and for concomitant medications which may increase the risk of QTc prolongation is vital to ensuring the safety of patients’ medication regimens.

Anticoagulant Medication Interactions

Patients with cancer tend to be at higher risk of blood clots and therefore are often prescribed an anticoagulant.⁴ Many oral chemotherapy agents increase the risk of bleeding. Some medications increase the bleed risk in general and others increase the risk specifically due to the lowering of platelets. Selection of the best anticoagulant based on these risks is important for maintaining the safety of a medication regimen.

Drug-Food and Drug-Herb Interactions

When discussing drug-food interactions there are multiple aspects and mechanisms of interaction.^5,6 The first consideration is the composition of the food itself. In general, eating raises the pH of the stomach as digestion occurs. This may affect the absorption of medications that require a lower pH. In addition, high fat meals may affect absorption of certain medications. Specifically, lipophilic medications are more soluble when taken with a high fat meal. Therefore, there are specific recommendations for medications to be taken with or without food as well as some that are recommended to be taken with a high fat meal.

The second thing to consider with drug-food interactions is that some foods can affect the CYP3A4 metabolism of oral chemotherapy medications. Specifically, grapefruit, garlic, and red wine may inhibit the activity of CYP3A4. Herbal supplements also primarily interact through the CYP3A4 pathway. Turmeric, echinacea, and green tree extract may inhibit CYP3A4 activity while St. John’s wort may induce CYP3A4 activity.

Mitigating the Risks of Interactions

Based on the multiple ways interactions may occur with oral chemotherapy medications, it is important to consider the entire medication regimen when deciding the best treatment options. When performing medication reconciliations, the GalenusCare Precision Pharmacist collects all prescription, over-the-counter, and herbal supplements to create a full picture of a patient’s medication history.

Using the most up-to-date analytics assists the pharmacist in identifying drug-drug, drug-food, and drug-herbal interactions. This review can be done prospectively so that at the time an oral chemotherapy medication is being considered, a Precision Pharmacist will run the analytics and make recommendations for therapy to ensure the best outcomes for patients.

Navigating chemotherapy can be a stressful process for patients and their caregivers, therefore helping to avoid side effects and promote better outcomes is pivotal for overall patient care.

References

¹Lohr LK, Blake KT, Chan CM, Sturm S, Walsh GT. Managingdrug interactions with oral anticancer treatments. J Adv Pract Oncol.2023;14(5):419–438. doi:10.6004/jadpro.2023.14.5.7. PMID:37576366; PMCID:PMC10414528

²U.S. Food and Drug Administration. Drug Developmentand Drug Interactions | Table of Substrates, Inhibitors and Inducers. FDA.Published online. <ahref="https:>https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers#table2-2.Accessed February 4, 2026</ahref="https:>

³Lam LH, Capparelli EV, Kurzrock R. Association ofConcurrent Acid-Suppression Therapy With Survival Outcomes and Adverse EventIncidence in Oncology Patients Receiving Erlotinib. Cancer ChemotherPharmacol. 2016;78(2):427-432. doi:10.1007/s00280-016-3087-6. PMID:27372908; PMCID: PMC4967016.

⁴Mosarla RC, Vaduganathan M, Qamar A, Moslehi J, PiazzaG, Giugliano RP. Anticoagulation strategies in patients with cancer: JACCreview topic of the week. J Am Coll Cardiol. 2019;73(11):1336-1349.doi:10.1016/j.jacc.2019.01.017. PMID:30898209; PMCID: PMC7957366

⁵Veerman GDM, Hussaarts KGAM, Jansman FGA, Koolen SWL,van Leeuwen RWF, Mathijssen RHJ. Clinical implications of food-druginteractions with small-molecule kinase inhibitors. Lancet Oncology.2020;21(5):E265-E279. doi:10.1016/S1470-2045(20)30069-3.

⁶Singh BN, Malhotra BK. Effects of food onthe clinical pharmacokinetics of anticancer agents: underlying mechanisms andimplications for oral chemotherapy. Clin Pharmacokinet.2004;43(15):1127-1156. doi:10.2165/00003088-200443150-00005