Smart Pills and Oral Chemotherapy: Fasted or Fed? A Drug-Food Interaction Table

Empty Stomach, With Food or Either: A Guide to Food, Acid Reducers and Grapefruit With Oral Cancer Drugs

There is no single rule for oral targeted pills (targeted therapies) and oral chemotherapies: some are taken on an empty stomach, some with food, and for others food makes no difference, because food can increase a drug's absorption, decrease it or leave it unchanged. This updated guide brings together the US label instructions for 31 drugs in one place. At our team's request, fruquintinib (Fruzaqla), trifluridine-tipiracil (Lonsurf), daraxonrasib (Rasonque), lorlatinib, sotorasib, capmatinib, encorafenib and binimetinib have also been added. Medicines that reduce stomach acid, grapefruit and herbal products such as St John's wort can also change the levels of some drugs considerably. This article does not make decisions for you: instructions can vary by drug, formulation and brand. Follow your drug's own patient information leaflet and what your oncology team or pharmacist tells you. We have covered the basics of food and drug interactions in cancer treatment, access to new cancer drugs in Turkey and cancer drugs imported from abroad in separate articles.

Why does this matter?

A growing share of cancer treatment now happens at home, with drugs taken by mouth. With intravenous chemotherapy, the dose, timing and conditions of administration are under the hospital team's control; with oral drugs, much of this responsibility shifts to the patient and family. Details that seem small, such as the food rule, the timing of an acid reducer or a glass of grapefruit juice, can change a drug's blood level several-fold.

These effects are not theoretical: food can raise the blood level of abiraterone up to 10-fold; an acid reducer can cut the sotorasib level by more than half; and an enzyme-inducing drug or herbal product can almost cancel out the effect of lorlatinib. That is why, whenever a new oral cancer drug is started, a written, personalized plan covering the food schedule, acid reducers and herbal products is part of successful treatment (supplements taken without evidence).

Should cancer pills be taken on an empty stomach or with food?

There is no single rule for oral cancer drugs. According to the labels, drugs such as abiraterone, erlotinib, lapatinib, nilotinib and pazopanib are taken on an empty stomach; drugs such as imatinib, capecitabine, Lonsurf, regorafenib and alectinib are taken with food; and drugs such as osimertinib, olaparib, lorlatinib, sotorasib, fruquintinib, encorafenib and daraxonrasib are taken with or without food. Follow your drug's own instructions and what your care team tells you.

How does food change a drug's effect?

As a drug passes from the stomach and intestine into the blood, food can change that passage. A fatty meal can help some poorly water-soluble drugs dissolve and raise their blood levels; with other drugs, food lowers the level by slowing stomach emptying or binding to the drug. For some, it makes no important difference. The food instructions on a label reflect the conditions under which the drug was tested in clinical trials and how a safe, effective level can be maintained.

The instructions in this article are taken from drug labels published on DailyMed in the US; the brand and patient information leaflet may differ in Turkey.

Drug–food interaction table

The three tables below show the food instructions on the labels, along with notes on food, stomach acid and grapefruit. Newly added drugs are marked new. A "—" means that this information could not be found in the relevant label text or was not verified for this article; it does not mean that the information does not exist.

Taken on an empty stomach

Oral cancer drugs taken on an empty stomach (label summary).

Taken with food

Oral cancer drugs taken with food (label summary).

Taken with or without food

Oral cancer drugs with a limited relationship to food (label summary). Even in the "either way" group, acid reducers and enzyme interactions can matter.

What do "on an empty stomach" and "with food" mean in practice?

Labels often describe "on an empty stomach" as a time window. Two wordings describe the same rule: "at least 1 hour before or 2 hours after a meal" and "do not eat for at least 2 hours before and at least 1 hour after the dose" mean the same thing.

• Most drugs taken on an empty stomach: Take them at least 2 hours after your last meal, and do not eat for at least 1 hour after the drug (abiraterone, erlotinib, afatinib, pazopanib, sorafenib, cabozantinib, dabrafenib, trametinib, nilotinib).
• Lapatinib is different: It is taken at least 1 hour before or 1 hour after a meal.
• Drugs taken with food: "With food" follows the description on the label: a low-fat meal for regorafenib, within 30 minutes after the end of a meal for capecitabine, and the morning and evening meals for Lonsurf.
• Consistency: Even in the either-way group, keep the same routine every day; the fruquintinib, sotorasib and daraxonrasib labels say to take them at about the same time every day.
• Swallow whole: Lorlatinib, capmatinib and daraxonrasib tablets should not be crushed, chewed or split. Sotorasib is one of the exceptions: it can be dispersed in water for patients who cannot swallow.

The eight newly added drugs: detailed cards

How much does food change drug levels?

Medicines that reduce stomach acid, and antacids

Medicines that suppress stomach acid (proton pump inhibitors, PPIs; H2 receptor blockers) and antacids change the acidity of the stomach. Some targeted pills dissolve well only in an acidic environment; when stomach acid is reduced, absorption of these drugs can fall. Because heartburn and reflux are common in people with cancer, this interaction comes up often in practice.

• Sotorasib: Avoid PPIs and H2 blockers; if needed, take it 4 hours before or 10 hours after a local antacid.
• Erlotinib: Avoid PPIs if possible; because PPIs act for a long time, separating the doses may not prevent the interaction.
• Dasatinib: Do not take it at the same time as an antacid; avoid using it with H2 blockers and PPIs.
• Gefitinib: With a PPI, take it 12 hours after the last or 12 hours before the next PPI dose; with an H2 blocker or antacid, take it 6 hours after or 6 hours before.
• Neratinib: Do not use it with PPIs; take it at least 2 hours before or 10 hours after the next H2 blocker dose, and 3 hours after an antacid.
• Pazopanib: Avoid medicines that reduce stomach acid; if this is not possible, take a short-acting antacid several hours apart.
• Nilotinib and bosutinib: A short-acting antacid or an H2 blocker can be used instead of a PPI.
• Palbociclib capsules: When taken with food, acid reducers have no meaningful effect; when taken on an empty stomach, rabeprazole lowered the level (CDK4/6 inhibitors).

Do not start or stop an acid reducer on your own; work out with your care team and pharmacist which medicine to take at what time. Also talk to your care team about safe options for treatment-related nausea and heartburn (nausea and vomiting can be prevented).

Grapefruit, St John's wort and other herbal products

The CYP3A4 enzyme, found in the intestinal wall and the liver, breaks down a large share of targeted pills. Grapefruit and grapefruit juice can slow this enzyme and raise the blood levels of some drugs, which increases the risk of side effects. Some herbal products, such as St John's wort, can instead speed up the enzyme, lowering drug levels and reducing the effect of treatment.

Among the labels reviewed, explicit warnings about grapefruit were found for dasatinib, lapatinib, regorafenib and palbociclib. The labels of drugs broken down by CYP3A, such as lorlatinib, encorafenib, capmatinib and daraxonrasib, contain detailed rules for strong CYP3A inhibitors and inducers; grapefruit and St John's wort are food and herbal examples of these groups. Not seeing a grapefruit warning on a label does not mean it is safe. Do not use supplements such as turmeric, green tea extract or black seed oil without asking your care team (black seed oil and cancer).

Abiraterone: the low-dose, low-fat meal approach

Abiraterone is a drug whose level food raises considerably; that is why its label asks for it to be taken on an empty stomach. In a 2012 interview, Mark Ratain noted that bioavailability can rise up to 10-fold with a high-fat meal. An approach that uses this property in reverse has been studied: taking 250 mg with a low-fat meal instead of the labeled 1000 mg on an empty stomach (abiraterone and olaparib).

In the 72-patient randomized phase 2 trial by Szmulewitz and colleagues, no difference from the standard dose was found in PSA response, progression-free survival or androgen levels; there was also no meaningful difference in safety. Critics have questioned the choice of the log change in PSA as the endpoint and the lower abiraterone trough levels in the low-dose group. The NCODA document reports that this approach is listed in the NCCN guidelines for patients who cannot take or afford the standard dose. In a small series, three patients whose liver enzymes rose were found to have unknowingly eaten meals containing more than 10 g of fat.

Practical tips and common misconceptions

• Read the food instructions in your drug's patient information leaflet once more with your care team, and ask for a written plan.
• Take it at the same time every day; use a phone alarm or a medication diary.
• Leave a food-free window before and after drugs taken on an empty stomach; pair drugs taken with food with a meal.
• Do not crush, chew or split tablets unless the label allows it; if you have trouble swallowing, ask your pharmacist (there are exceptions, such as sotorasib, that can be dispersed in water).
• Ask your oncology team or pharmacist before adding a new medicine, stomach protector, supplement or herbal product.
• When handling chemotherapy pills such as capecitabine and Lonsurf, wearing gloves or washing your hands afterward is recommended (what is capecitabine, DPD deficiency).

Frequently asked questions

Are all oral cancer drugs taken on an empty stomach?

No. According to the labels, of the 31 drugs, 10 are taken on an empty stomach, 9 with food and 12 with or without food. For example, abiraterone and lapatinib are taken on an empty stomach; capecitabine and Lonsurf with food; and lorlatinib, sotorasib and daraxonrasib with or without food.

How many hours does "on an empty stomach" mean?

It depends on the drug. For most drugs, at least 1 hour before or 2 hours after a meal; for lapatinib, 1 hour before or 1 hour after; for abiraterone and nilotinib, no food for 2 hours before and 1 hour after the dose.

I take an acid reducer (PPI); will my cancer drug be affected?

With some drugs, yes. The sotorasib level falls by 57% with omeprazole; the erlotinib, dasatinib, gefitinib, neratinib and pazopanib labels also give special instructions. No meaningful effect was seen with lorlatinib, fruquintinib, binimetinib or daraxonrasib. Do not stop your acid reducer on your own; make a plan with your care team.

Can I have grapefruit or use herbal products?

Grapefruit can raise the levels of some drugs; herbal products such as St John's wort can lower them. The dasatinib, lapatinib, regorafenib and palbociclib labels say to avoid grapefruit. Ask your oncology team or pharmacist about every supplement you use.

Glossary

Targeted (smart) pill (targeted oral drug)

A drug taken by mouth that targets a specific protein or pathway in cancer cells.

Oral chemotherapy

A chemotherapy drug taken by mouth rather than into a vein (e.g., capecitabine, trifluridine-tipiracil, temozolomide).

Bioavailability

How much of a drug taken by mouth reaches the bloodstream.

AUC (area under the curve)

Area under the curve; shows a drug's total exposure in the blood over a given period.

Cmax

The highest level of a drug in the blood.

Proton pump inhibitor (PPI)

A group of drugs that suppress stomach acid production for a long time (e.g., omeprazole, esomeprazole).

H2 receptor blocker

Another group of drugs that reduce stomach acid production (e.g., famotidine).

CYP3A4

An intestinal and liver enzyme that breaks down certain drugs; grapefruit slows it, while St John's wort and rifampin speed it up.

P-gp (P-glycoprotein)

A transporter protein that pumps drugs out of cells; it plays a role in some drug interactions.