Lomustine Drug Interactions: What to Avoid and What to Tell Your Doctor

Lomustine (Gleostine) is a powerful chemotherapy drug with a well-documented set of drug interactions. Some interactions can be life-threatening — particularly those that add to its bone marrow suppression effects. Before starting lomustine, and throughout your treatment, it's essential to give your oncologist a complete list of every medication, supplement, and vaccine you take or plan to take.

Why Drug Interactions Matter Especially with Lomustine

Lomustine's toxicity profile is characterized by delayed, cumulative bone marrow suppression that occurs 28–42 days after each dose. Any medication that also suppresses bone marrow, increases myelotoxicity, or weakens immunity will compound these effects — sometimes dangerously. Additionally, lomustine is metabolized by hepatic cytochrome P450 enzymes, meaning drugs that affect these enzymes can alter lomustine's blood levels and toxicity.

Major Interactions — Avoid These Combinations

Live Vaccines (BCG, Varivax, FluMist, etc.)

Severity: Contraindicated. Lomustine suppresses the immune system. Live vaccines (including BCG, varicella/shingles live vaccine, intranasal flu vaccine, and other live-attenuated vaccines) are contraindicated during lomustine treatment and for at least 3 months after the final dose. Administration of live vaccines to an immunosuppressed patient can cause severe, potentially fatal infection from the vaccine strain itself. Always use killed/inactivated vaccine alternatives where available.

CAR-T Cell Therapies (e.g., Ciltacabtagene Autoleucel/Carvykti)

Severity: Avoid or use alternative. Combining lomustine with CAR-T therapies dramatically increases immunosuppressive effects and the risk of severe infections. These combinations should be avoided or carefully managed by the oncology team.

Moderate Interactions — Use With Caution and Monitor Closely

Cimetidine (Tagamet)

Severity: Moderate — Monitor closely. Cimetidine inhibits hepatic CYP enzymes that metabolize lomustine. This decreases the breakdown of lomustine, leading to higher lomustine blood levels and enhanced myelotoxicity. Cimetidine is an older over-the-counter heartburn/H2 blocker that patients may not think to mention. Tell your doctor if you use cimetidine (Tagamet) for heartburn. Alternative heartburn medications (e.g., famotidine/Pepcid, omeprazole/Prilosec) do not have this interaction.

Cisplatin and Other Myelosuppressive Chemotherapy Agents

Severity: Moderate — Monitor closely. Cisplatin and lomustine have additive myelosuppressive effects. When used in combination (which may be clinically appropriate in some regimens), doses must be carefully adjusted and blood counts monitored vigilantly. The same principle applies to other myelosuppressive chemotherapy agents like cyclophosphamide.

Clozapine (Clozaril)

Severity: Moderate. Clozapine is an antipsychotic that on its own carries a risk of agranulocytosis (severe reduction in white blood cells). Combined with lomustine's myelosuppression, the risk of dangerous neutropenia is significantly increased. Monitor closely and inform your psychiatrist that you are taking lomustine.

Adalimumab (Humira) and Other Biologics/Immunosuppressants

Severity: Moderate. Biologic medications for autoimmune conditions (TNF inhibitors like adalimumab/Humira, etanercept/Enbrel) add to lomustine's immunosuppressive effects, increasing the risk of serious infections. Discuss all biologic medications with your oncologist before starting lomustine.

Minor Interactions — Be Aware

Vitamin A and Vitamin E supplements have been noted in drug interaction databases as potentially interacting with lomustine — antioxidants may enhance lomustine's anti-cancer activity and reduce some side effects according to some reports, but this effect is not well-characterized. Do not self-supplement without discussing with your oncologist; high-dose antioxidants may potentially interfere with treatment.

Vaccines: Flu Shot vs. FluMist

On lomustine, you should avoid live vaccines but inactivated vaccines may still be given (though immune response may be blunted due to immunosuppression). For flu protection:

OK on lomustine (with doctor approval): Injectable flu vaccine (inactivated)

Avoid: FluMist nasal spray (live attenuated influenza vaccine)

What to Tell Your Doctors Before Starting Lomustine

Bring a complete medication list to every oncology appointment, including:

All prescription medications (including medications from other doctors)

All over-the-counter medications — especially antacids like cimetidine (Tagamet)

All vitamins, supplements, and herbal products

Any recent or planned vaccines

Any biologic or immunosuppressant medications (for conditions like rheumatoid arthritis, psoriasis, IBD)

For a full overview of lomustine side effects, see Lomustine Side Effects: What to Expect. If you need help finding lomustine at a pharmacy, medfinder can help locate it near you.