What medications cause mucositis?: A comprehensive overview

October 12, 2025 •

4 min read

Affecting up to 40% of patients receiving standard chemotherapy and up to 80% of those undergoing high-dose chemotherapy, mucositis is a common and painful side effect of many medications. Knowing what medications cause mucositis is crucial for both patients and healthcare providers to implement prophylactic measures and manage symptoms effectively. This condition involves the inflammation and ulceration of the mucous membranes lining the gastrointestinal tract, from the mouth to the anus.

Quick Summary

This article details the medications most frequently associated with mucositis, including chemotherapy agents, targeted therapies, and other drug classes. It explores the mechanisms by which these medications damage mucosal cells and discusses risk factors that influence the incidence and severity of the condition.

Key Points

Chemotherapy is the primary cause: Cytotoxic drugs, particularly antimetabolites and alkylating agents, frequently induce mucositis by damaging rapidly dividing mucosal cells.
Targeted therapies have distinct mechanisms: Newer drugs like mTOR inhibitors (e.g., everolimus) and EGFR inhibitors (e.g., cetuximab) cause specific types of mucosal inflammation or stomatitis.
High-risk drugs include: Common chemotherapy agents like 5-fluorouracil, methotrexate, melphalan, and irinotecan are strongly associated with mucositis.
Location depends on the drug: While many agents cause oral mucositis, some, like irinotecan, are particularly associated with gastrointestinal mucositis.
Several risk factors contribute: Individual susceptibility, including age, nutritional status, and oral hygiene, significantly impacts the development and severity of mucositis.
Management focuses on prevention and palliation: Strategies include maintaining good oral hygiene, dietary modifications, and using topical or systemic pain medications.

Mucositis is a distressing and often debilitating side effect for many patients, primarily those undergoing cancer treatment. It can be categorized as either oral mucositis (OM), affecting the mouth, or gastrointestinal mucositis (GIM), affecting the rest of the digestive tract. Understanding the specific medications responsible is the first step toward effective management and prevention.

Chemotherapy Drugs Causing Mucositis

Chemotherapeutic agents are the most well-known class of drugs to cause mucositis due to their cytotoxic nature. They target and damage rapidly dividing cells throughout the body, including the fast-replicating epithelial cells lining the mucosal surfaces. The severity and incidence of mucositis vary significantly depending on the specific agent, dose, and administration schedule.

Antimetabolites: These drugs interfere with DNA synthesis and are particularly potent inducers of mucositis. High-risk agents include:

Fluorouracil (5-FU) and its oral prodrug, capecitabine
Methotrexate
Cytarabine
Gemcitabine

Alkylating Agents: These drugs damage DNA by adding an alkyl group, leading to cell death. High-dose regimens, especially those used in hematopoietic stem cell transplantation, carry a high risk. Common culprits include:

Melphalan
Busulfan
Cyclophosphamide
Cisplatin

Anthracyclines: These agents interfere with DNA replication and are known to cause mucositis. Examples include doxorubicin and daunorubicin.

Topoisomerase I Inhibitors: Drugs like irinotecan inhibit the enzyme topoisomerase I, crucial for DNA replication, and are particularly associated with gastrointestinal mucositis.

Taxanes: While generally causing milder mucositis, taxanes like docetaxel can still induce this side effect.

Targeted Therapies and Immunotherapy

Beyond conventional chemotherapy, modern targeted cancer therapies and immunotherapies can also trigger mucosal injury through different mechanisms. These toxicities can sometimes present differently than classic mucositis.

mTOR Inhibitors: Medications like everolimus and temsirolimus, which inhibit the mammalian target of rapamycin (mTOR), are associated with a specific type of oral ulceration called mTOR inhibitor-associated stomatitis (mIAS). These lesions often appear as aphthous-like ulcers.

Epidermal Growth Factor Receptor (EGFR) Inhibitors: Cetuximab and other EGFR inhibitors can cause stomatitis, sometimes manifesting as aphthous-like lesions or general erythema. The risk of mucositis increases when these are used in combination with other cytotoxic agents.

Immunotherapy Agents (Checkpoint Inhibitors): Drugs like nivolumab and pembrolizumab can cause a range of immune-related side effects, including inflammatory colitis and stomatitis, though these are less frequent than with older chemotherapy regimens.

Other Medications Associated with Mucositis

While less common, other drug classes can also be linked to mucositis or related oral lesions. These effects are often due to immune-mediated reactions or other systemic effects rather than direct cytotoxicity to mucosal cells.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Certain NSAIDs, such as ibuprofen and naproxen, have been associated with oral ulcers.
Immunosuppressants: Methotrexate is also used at lower doses to treat autoimmune diseases, where it can still cause mucositis. Other immunosuppressants, like cyclosporine, are more known for causing gum overgrowth but can contribute to oral complications.
Antibiotics: Some antibiotics, including amoxicillin and tetracyclines, can rarely cause oral ulcers or discoloration. Prolonged use can also disrupt the normal oral flora, potentially leading to fungal infections like thrush, which can exacerbate existing mucosal damage.
Other Agents: Isolated cases or specific immune reactions have linked drugs like captopril, penicillamine, gold compounds, and some antidepressants to oral lesions.

Factors Influencing Mucositis Risk and Severity

Several factors can increase a patient's risk and the potential severity of mucositis:

Treatment-Specific Factors: The type, dose, and schedule of medication, as well as concurrent radiation therapy, are major determinants. High-dose chemotherapy and combination treatments significantly increase risk.
Patient-Specific Factors: Younger patients have faster cell turnover rates, which makes their mucosa more vulnerable. Poor oral hygiene, malnutrition, age, and pre-existing conditions like diabetes can also heighten the risk and severity.
Genetic Factors: Individual genetic variations can influence how a person metabolizes and responds to certain drugs, affecting mucositis risk. For example, variations in the DPD enzyme can lead to higher-than-normal 5-FU levels.

Comparison Table: Common Medication Classes Causing Mucositis


Medication Class	Example Drugs	Mucositis Risk Level	Primary Mechanism	Location Affected
Antimetabolites	5-FU, Methotrexate, Cytarabine	High	Interfere with DNA synthesis in rapidly dividing cells	Oral and Gastrointestinal
Alkylating Agents	Melphalan, Busulfan, Cyclophosphamide	High (especially with high doses)	Damage DNA by adding alkyl groups	Oral and Gastrointestinal
Anthracyclines	Doxorubicin, Daunorubicin	Moderate-High	Inhibit DNA replication and transcription	Oral and Gastrointestinal
Topoisomerase Inhibitors	Irinotecan	Moderate-High	Inhibit topoisomerase I, essential for DNA replication	Mainly Gastrointestinal
mTOR Inhibitors	Everolimus, Temsirolimus	Moderate	Inhibit mTOR pathway, affecting cell growth	Oral (aphthous-like)
EGFR Inhibitors	Cetuximab	Low-Moderate	Interfere with cell signaling pathways	Oral (aphthous-like)
NSAIDs	Ibuprofen, Naproxen	Low	Immune-mediated reaction (less common)	Oral

Conclusion

Mucositis is a significant and often expected side effect of several medication classes, with cytotoxic chemotherapies being the most prominent cause. As cancer treatment evolves, newer targeted therapies and immunotherapies have also been identified as potential triggers, though their mechanisms and presentation can differ. Awareness of what medications cause mucositis is critical for early detection, prophylactic care, and symptom management. For patients, maintaining excellent oral hygiene and discussing any symptoms with their healthcare team is vital. The management of mucositis is an ongoing focus in supportive cancer care to improve quality of life and ensure that patients can complete their intended treatment regimens.

Frequently Asked Questions

Chemotherapy drugs that interfere with DNA synthesis, such as the antimetabolites fluorouracil (5-FU) and methotrexate, are among the most common causes. Other high-risk agents include alkylating agents like melphalan and topoisomerase inhibitors like irinotecan.

Yes, other drug classes can cause mucositis or related oral lesions. These include targeted therapies like mTOR inhibitors (e.g., everolimus), some immunosuppressants, certain antibiotics, and NSAIDs, though the incidence and mechanism can differ from chemotherapy.

Stomatitis is a general term for inflammation of the mouth and lips, while mucositis specifically refers to the inflammation and ulceration of the mucous membranes throughout the gastrointestinal tract. Therefore, oral mucositis is a form of stomatitis caused by certain medical treatments.

mIAS is a type of oral mucositis caused by mTOR inhibitors, a class of targeted therapy. It presents as distinct, aphthous-like ulcers on the non-keratinized tissues of the mouth and typically has a rapid onset during the first cycle of treatment.

Yes, concurrent radiation therapy, especially to the head and neck region, significantly increases the risk and severity of mucositis when combined with chemotherapy. The two treatments have synergistic toxic effects on the mucosa.

Early signs of mucositis typically include oral soreness, a burning sensation, and redness (erythema). These can progress to the formation of painful ulcers and can make eating, drinking, and swallowing difficult.

Immunotherapy agents, particularly checkpoint inhibitors, can cause immune-related adverse events that include colitis and stomatitis. The incidence of severe mucositis is lower compared to traditional chemotherapy, but it can still occur due to the systemic activation of the immune system.