Understanding What Medication Can Cause Blisters in Your Mouth: A Comprehensive Guide

October 12, 2025 •

5 min read

According to the National Institutes of Health, severe blistering drug reactions like Stevens-Johnson Syndrome (SJS) often result from medications like certain anticonvulsants, antibiotics, and allopurinol. This guide explores what medication can cause blisters in your mouth, from life-threatening conditions to less severe but still painful drug-induced oral lesions.

Quick Summary

Several medications can trigger oral blistering or ulceration, ranging from severe and potentially fatal conditions like Stevens-Johnson syndrome and toxic epidermal necrolysis to less dangerous but painful reactions like oral mucositis and drug-induced lichenoid eruptions. The mechanisms vary, but prompt identification and treatment are crucial.

Key Points

Stevens-Johnson Syndrome (SJS): A severe drug-induced hypersensitivity reaction causing painful oral blisters and skin peeling, triggered by drugs like anticonvulsants, allopurinol, and sulfa antibiotics.
Oral Mucositis: Painful ulcers or sores in the mouth are a common side effect of chemotherapy and radiation therapy due to damage to rapidly dividing mucosal cells.
Oral Lichenoid Drug Eruptions: These delayed, inflammatory reactions can cause oral blisters or ulcers and are linked to medications such as ACE inhibitors, beta-blockers, and NSAIDs.
Immune-Mediated Blistering: Other immune-driven reactions like Erythema Multiforme can cause blisters that rupture into erosions, often triggered by antibiotics, NSAIDs, and anticonvulsants.
Localized Ulcers: Less severe oral ulcers can be caused by drugs like methotrexate, certain NSAIDs, and phenytoin, as well as localized contact irritation from medications.
Angioedema: Though less common, ACE inhibitors can cause angioedema, a serious swelling of the lips, face, and mouth that can become life-threatening.
Immediate Consultation: Promptly consulting a healthcare provider for any unexplained oral blisters or ulcers is crucial for determining the cause and safe management, especially since some reactions are severe.

Severe and Life-Threatening Reactions

One of the most serious and potentially fatal causes of drug-induced oral blisters is a severe hypersensitivity reaction known as Stevens-Johnson Syndrome (SJS) or its more severe variant, Toxic Epidermal Necrolysis (TEN). These conditions are considered medical emergencies and require immediate medical attention, often in a burn unit.

Symptoms of SJS and TEN often begin with flu-like symptoms, followed by a painful, spreading rash that develops into large areas of blisters and peeling skin. The mucous membranes of the mouth, eyes, and genitals are typically severely affected, leading to painful blisters and hemorrhagic crusting of the lips.

Medications frequently implicated in SJS/TEN include:

Anticonvulsants: Lamotrigine, carbamazepine, phenytoin, and phenobarbital.
Sulfonamide Antibiotics: Cotrimoxazole, sulfasalazine, and other sulfa drugs.
Other Antibiotics: Penicillins, cephalosporins, and fluoroquinolones.
Pain Relievers: Certain NSAIDs (especially the oxicam type) and acetaminophen.
Anti-gout Medications: Allopurinol.
HIV medications: Nevirapine.

Hypersensitivity and Immunological Reactions

Beyond the most severe reactions, several other immunological responses to drugs can cause oral blisters or ulcerations.

Drug-Induced Erythema Multiforme (EM)

This is an inflammatory hypersensitivity reaction that can be triggered by medications or infections.

Oral Manifestations: Rapidly rupturing vesicles (small blisters) that lead to erosions and encrusted lip lesions.
Common culprits: NSAIDs, antibiotics (like cephalexin and diclofenac), and anticonvulsants.

Oral Lichenoid Drug Eruptions (OLE)

OLE is an uncommon, chronic reaction that clinically resembles oral lichen planus, a common inflammatory condition.

Oral Manifestations: It can appear as white, lacy patches, red and swollen tissues, or erosive/ulcerated lesions, including blisters. A key diagnostic feature is that the lesions tend to resolve after the causative drug is discontinued.
Associated Medications: Antihypertensives (ACE inhibitors, beta-blockers, diuretics), NSAIDs, oral hypoglycemic agents, and gold salts.

Chemotherapy-Related Oral Lesions

Cancer treatments, particularly chemotherapy and radiation to the head and neck, can cause a condition known as oral mucositis.

Oral Manifestations: Oral mucositis involves the breakdown of the mucosal lining of the mouth, leading to redness, swelling, and painful ulcerations that may look like blisters. It typically develops a few days after starting treatment.
Associated Drugs: Antimetabolites like 5-fluorouracil, methotrexate, and cytarabine. Newer targeted therapies like everolimus can also cause oral sores that resemble aphthous ulcers.

Other Drug-Induced Oral Lesions

Some medications can cause non-specific oral ulcerations, sometimes referred to as stomatitis.

List of drugs that can cause oral ulcers and stomatitis:

NSAIDs: Chronic use of NSAIDs like ibuprofen, naproxen, and aspirin can lead to oral ulcerations.
Anticonvulsants: Besides the risk of SJS/TEN, some anticonvulsants, such as phenytoin, can cause general oral ulcers.
Immunosuppressants: Medications like methotrexate, used for autoimmune diseases, are well-known to cause oral sores.
ACE Inhibitors: Captopril and other ACE inhibitors can cause oral ulceration and angioedema, a serious form of swelling involving the lips, tongue, and mouth.

How Medications Cause Blisters in the Mouth

Drug-induced oral lesions can occur through several different mechanisms. Understanding these pathways helps to differentiate between conditions and manage them appropriately.

Direct Cellular Toxicity: This is the primary mechanism for oral mucositis caused by chemotherapy. Cancer treatments target rapidly dividing cells, and unfortunately, the epithelial cells of the oral mucosa are also fast-proliferating and thus become collateral damage.
Hypersensitivity Reactions: SJS/TEN and erythema multiforme are immune-mediated. In these cases, the drug or its metabolite triggers an inappropriate and severe immune response, leading to widespread inflammation, blistering, and destruction of skin and mucosal tissue.
Immune Dysregulation: Oral lichenoid drug eruptions involve a delayed, immune-mediated inflammatory response where the drug interferes with the body's immune regulation, causing lesions that mimic lichen planus.
Localized Irritation: Some medications, especially when held in the mouth or taken over-the-counter for dental pain, can cause a chemical burn or contact allergy, leading to localized erosion or ulceration.
Angioedema: The mechanism behind ACE inhibitor-induced angioedema is different. It involves the accumulation of bradykinin, a substance that increases vascular permeability and leads to swelling.

Comparison of Drug-Induced Oral Reactions


Condition	Typical Onset	Oral Appearance	Associated Medications	Severity	Management
SJS/TEN	Acute (weeks)	Widespread blisters, erosions, hemorrhagic crusting	Anticonvulsants, Sulfa drugs, Allopurinol, NSAIDs	Life-threatening	Immediate drug cessation, supportive care, hospitalization
Erythema Multiforme	Acute (days)	Rapidly rupturing blisters, ulcerations	Antibiotics, NSAIDs, Anticonvulsants	Moderate to severe	Drug discontinuation, topical/systemic steroids
Oral Mucositis	Acute (days to weeks)	Redness, swelling, painful ulcers	Chemotherapy, Radiation	Moderate to severe	Supportive care, oral hygiene, pain relief
Lichenoid Drug Eruption	Delayed (months)	White lacy patches, erosions, ulcers	ACE inhibitors, Beta-blockers, NSAIDs	Mild to moderate	Drug discontinuation, topical steroids
Aphthous-like Ulcers	Variable	Small, round or oval ulcers with a red halo	NSAIDs, Immunosuppressants (e.g., Methotrexate)	Mild to moderate	Drug discontinuation, topical steroids
Angioedema	Acute (minutes to hours)	Rapid, significant swelling of lips, tongue, mouth	ACE Inhibitors	Potentially life-threatening	Immediate medical attention, drug cessation

Identifying and Managing Drug-Induced Oral Blisters

If you develop unexplained oral blisters or ulcers after starting a new medication, it is crucial to consult your healthcare provider. Do not stop taking a prescribed medication without first speaking to your doctor. They can evaluate the severity, identify the potential cause, and determine the safest course of action, which may include switching to an alternative medication or managing the side effects.

Important steps for managing these conditions often include:

Comprehensive Drug History: Provide your doctor with a complete list of all prescription, over-the-counter, and herbal supplements you are taking.
Symptom Management: Topical anesthetics, such as viscous lidocaine, can provide pain relief.
Oral Hygiene: Maintaining good oral hygiene with a soft toothbrush and gentle, alcohol-free mouthwashes is important to prevent secondary infections.
Dietary Adjustments: Avoiding spicy, hot, crunchy, or acidic foods can help minimize irritation and pain.

Conclusion

While many people experience no adverse oral reactions to medication, certain drugs can cause significant discomfort and, in some cases, severe, life-threatening conditions involving blisters in the mouth and on the skin. SJS/TEN, Drug-Induced Erythema Multiforme, Oral Lichenoid Drug Eruptions, and Oral Mucositis are all known drug-induced oral lesions, each with its own set of potential culprits. Promptly reporting any unusual oral symptoms to a healthcare professional is essential for accurate diagnosis and safe management. For more information on Stevens-Johnson Syndrome, consult authoritative sources like the National Institutes of Health.

Frequently Asked Questions

The most dangerous drug-induced oral reactions are Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). These are medical emergencies involving severe, widespread blistering and peeling of the skin and mucous membranes, including the mouth.

Yes, some common pain relievers, particularly NSAIDs like ibuprofen, naproxen, and aspirin, can cause oral ulcers. They are also known triggers for more severe conditions like Erythema Multiforme and, in some cases, SJS/TEN.

Chemotherapy can cause oral mucositis, a condition characterized by painful ulcers, redness, and swelling of the oral mucosa. These sores are a result of the chemotherapy targeting rapidly dividing cells in the mouth.

If you notice new or worsening oral sores after starting a new medication or changing a dosage, you should suspect a drug-induced reaction. Keeping a list of all medications and a timeline of symptom onset can help your doctor determine the cause.

Oral lichenoid drug eruptions, which can cause sores and blisters, are commonly associated with antihypertensive drugs (ACE inhibitors, beta-blockers, diuretics), NSAIDs, and some antimalarials.

Yes. A serious side effect of ACE inhibitors, used for high blood pressure, is angioedema, which causes rapid and potentially life-threatening swelling of the lips, tongue, and throat.

No. You should never stop taking a prescribed medication without first consulting your doctor. They can evaluate the severity of the reaction, recommend alternative treatments, and ensure your underlying medical condition is managed safely.