What is the most severe adverse effect of acetazolamide?

October 10, 2025 •

4 min read

Though relatively rare, the use of acetazolamide has been associated with severe and life-threatening adverse effects. Understanding what is the most severe adverse effect of acetazolamide is crucial for patient safety and requires awareness of conditions such as Stevens-Johnson syndrome, aplastic anemia, and liver injury.

Quick Summary

Several rare but severe adverse effects of acetazolamide exist, including life-threatening skin reactions (Stevens-Johnson syndrome/toxic epidermal necrolysis), severe blood disorders like aplastic anemia, significant metabolic acidosis, and liver damage. Prompt recognition of symptoms is critical for patient management.

Key Points

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): These are rare but potentially fatal skin reactions that can lead to widespread skin peeling and blistering.
Aplastic Anemia and Blood Dyscrasias: Acetazolamide can cause severe blood disorders, including aplastic anemia, which involves the failure of bone marrow to produce blood cells.
Severe Metabolic Acidosis: Inhibition of carbonic anhydrase can lead to excess acid in the blood, which can be life-threatening in patients with pre-existing kidney or liver problems.
Significant Liver Damage (Hepatotoxicity): In rare instances, acetazolamide can cause severe liver injury, and is contraindicated in patients with significant liver disease.
High-Dose Aspirin Interaction: Combining acetazolamide with high doses of aspirin can lead to fatal side effects, including coma.
Immediate Medical Attention is Required: If any severe symptoms appear, immediately stop taking the medication and seek emergency medical care.

Introduction to Acetazolamide

Acetazolamide, a carbonic anhydrase inhibitor, is a medication prescribed for a range of conditions, including glaucoma, epilepsy, edema, and acute mountain sickness. While it is generally considered safe and effective when used appropriately, it is not without risks. Most adverse effects are mild, such as tingling in the extremities, taste alteration, or gastrointestinal issues. However, a small percentage of patients may experience severe, life-threatening complications that require immediate medical attention. This article details the most severe adverse effects to help patients and caregivers recognize and respond to potential drug-induced emergencies.

Severe Adverse Effects of Acetazolamide

The most concerning adverse effects associated with acetazolamide are typically rare and often involve systemic reactions due to its sulfonamide-related chemical structure. The most critical of these include severe skin reactions, blood disorders, and metabolic disturbances.

Life-Threatening Skin Reactions: SJS and TEN

Among the most severe and potentially fatal adverse effects of acetazolamide are Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These are severe mucocutaneous hypersensitivity reactions that can lead to extensive blistering, skin peeling, and necrosis, often starting with flu-like symptoms.

Symptoms of SJS/TEN: Key indicators include a painful red or purple rash that spreads and blisters, fever, flu-like symptoms, and involvement of mucous membranes in the mouth, nose, eyes, and genitals.
Timeline: These reactions can manifest weeks to months after starting the medication, emphasizing the need for ongoing vigilance.
Management: Immediate discontinuation of acetazolamide is required, along with supportive care in a hospital setting, often in a burn unit.

Serious Blood Disorders: Aplastic Anemia

Aplastic anemia, a rare but life-threatening blood disorder, is another severe adverse effect linked to acetazolamide. This condition occurs when the bone marrow fails to produce sufficient new blood cells (red, white, and platelets). This leads to severe weakness, increased risk of infection, and uncontrolled bleeding. Other associated blood problems can include agranulocytosis and thrombocytopenia.

Symptoms of aplastic anemia: Patients may experience unusual fatigue, headache, dizziness, increased bleeding or bruising, frequent infections, shortness of breath, and pale skin.
Detection: Routine blood counts can help detect these issues early, although not always considered necessary in standard practice.
Genetic Susceptibility: Certain genetic predispositions, such as HLA-B59, have been linked to increased risk of SJS-TEN, particularly in Japanese and Korean populations.

Severe Metabolic Acidosis

Acetazolamide's mechanism of action involves inhibiting carbonic anhydrase, which can lead to metabolic acidosis, where too much acid accumulates in the blood. While typically mild and self-limiting, severe cases can occur, especially in patients with pre-existing kidney or liver conditions, or in elderly individuals. Severe acidosis can lead to kidney stones, slowed growth in children, and may be exacerbated by other medications.

Symptoms of severe metabolic acidosis: Fast or irregular heartbeat, rapid breathing, confusion, nausea, and unusual weakness or fatigue are potential signs.
Risk Factors: Patients with severe kidney or liver disease, adrenal gland failure, or pre-existing metabolic acidosis are at higher risk.

Liver Damage (Hepatotoxicity)

Acetazolamide can, in rare cases, cause significant liver damage, or hepatotoxicity. Symptoms may include nausea, abdominal pain, fever, jaundice (yellowing of the skin or eyes), and dark urine. Patients with existing liver problems or cirrhosis should not take acetazolamide, as it can decrease ammonia clearance and increase the risk of hepatic encephalopathy.

High-Dose Aspirin Interaction

It is critical to avoid combining acetazolamide with high doses of aspirin. This combination can lead to severe side effects, including loss of appetite, lethargy, coma, and even death. Patients taking this combination should be monitored closely for symptoms of toxicity.

Comparison of Adverse Effects


Feature	Common Adverse Effects	Severe Adverse Effects
Incidence	Fairly common	Rare (often very rare)
Examples	Tingling in extremities (paresthesia), taste alteration, nausea, fatigue, increased urination, dizziness	Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Aplastic Anemia, Metabolic Acidosis
Urgency	Typically does not require immediate medical attention	Requires immediate medical attention
Onset	Often occurs early in treatment	Can occur weeks to months after starting the medication
Reversibility	Often reversible upon discontinuation of the drug	Can be life-threatening and lead to permanent damage

What to Do If You Suspect a Severe Reaction

If you or someone you know is taking acetazolamide and develops symptoms of a severe adverse effect, it is essential to act quickly.

Stop the medication: Do not take any further doses of acetazolamide.
Seek immediate medical help: Contact your doctor or go to an emergency room immediately. Severe reactions like SJS/TEN or blood disorders are medical emergencies.
Inform healthcare providers: Clearly state that you are taking acetazolamide and describe the symptoms you are experiencing.
Monitor symptoms: Be prepared to provide details on when symptoms started, their progression, and any other medications you are taking.

Conclusion

While acetazolamide is a valuable medication for many conditions, the potential for severe adverse effects, though rare, should not be underestimated. The most severe complications include life-threatening skin reactions like Stevens-Johnson syndrome, blood disorders such as aplastic anemia, and dangerous metabolic imbalances. Awareness of these risks, along with prompt medical action if symptoms arise, is paramount to ensure patient safety while undergoing treatment. It is crucial for patients to discuss any pre-existing conditions and other medications with their healthcare provider to mitigate risks. Early detection and intervention are key to managing these rare but serious adverse effects effectively.

For more detailed medical information, the EyeWiki article on Acetazolamide Complications in Ophthalmology provides comprehensive data and references.

Frequently Asked Questions

The most severe adverse effects, such as Stevens-Johnson syndrome and aplastic anemia, are considered very rare but are life-threatening when they do occur. Metabolic acidosis is more common but typically mild, though it can become severe under certain conditions.

Early signs often mimic the flu and can include fever and general ill feeling, followed by a red or purple rash that spreads and forms blisters. It's crucial to seek immediate medical help if these symptoms appear.

Patients with pre-existing kidney or liver disease, adrenal gland problems, or certain untreated mineral imbalances (like low sodium or potassium) are at higher risk. The risk for SJS/TEN may also vary by ethnicity.

Yes. Severe skin reactions like SJS/TEN can happen weeks to months after starting the medication, which highlights the importance of continued monitoring.

Yes. Your doctor can prescribe alternative treatments depending on the condition being treated. For example, some non-sulfonamide medications can be used for glaucoma, and dexamethasone may be an option for acute mountain sickness.

Treatment involves discontinuing acetazolamide. In severe cases, supportive care is provided, which may include administering bicarbonate to correct the acid-base imbalance.

The combination of these two medications can lead to severe toxicity, with symptoms including confusion, rapid breathing, and coma. This interaction can be fatal, and patients should always inform their doctor of all medications they are taking.