From the Guidelines
Topamax (topiramate) can cause elevated liver function tests (LFTs), though this is an uncommon side effect, and the most recent evidence does not specifically address Topamax, but rather tolvaptan, which also has liver-related side effects 1.
Clinical Considerations
When considering the use of Topamax, it is essential to prioritize the patient's liver health, given the potential for elevated LFTs.
- Baseline LFTs should be checked before starting treatment with Topamax.
- Periodic monitoring of LFTs is recommended, especially during the first 6-12 months of therapy.
- Risk factors for developing elevated LFTs while on Topamax include pre-existing liver disease, concomitant use of other hepatotoxic medications, and higher dosages.
Monitoring and Management
If a patient on Topamax develops symptoms such as jaundice, right upper quadrant pain, fatigue, or nausea, prompt evaluation of liver function is warranted.
- In cases of significant LFT elevations (greater than 3 times the upper limit of normal), dose reduction or discontinuation may be necessary, as seen with tolvaptan 1.
- The mechanism behind Topamax's effect on the liver is not fully understood but may involve metabolic stress or an idiosyncratic immune-mediated reaction.
Recent Evidence
The most recent evidence from the KDIGO 2025 clinical practice guideline for the evaluation, management, and treatment of autosomal dominant polycystic kidney disease (ADPKD) provides guidance on monitoring and managing liver injury associated with tolvaptan, which may be applicable to other medications like Topamax 1.
- Frequent monitoring (monthly for the first 18 months, and then every 3 months until drug discontinuation) of LFTs is mandatory in people treated with tolvaptan for ADPKD.
- Tolvaptan use is associated with an increased risk for idiosyncratic drug-induced liver injury, with approximately 5% of people with ADPKD treated with tolvaptan displaying an increase in transaminase levels that was above 3-fold the upper limit of normal 1.
From the Research
Topamax (Topiramate) and Liver Function Tests (LFTs)
- There is no direct evidence to suggest that Topamax (topiramate) causes elevated Liver Function Tests (LFTs) 2, 3.
- Topiramate is considered to be one of the newer antiepileptic drugs without, or with minimal, hepatic metabolism, making it a safer option for patients with liver disease 2.
- In one case report, a patient with Lennox-Gastaut syndrome was successfully treated with valproate, phenobarbital, lamotrigine, and topiramate after a liver transplant, with no mention of topiramate causing elevated LFTs 3.
- Elevated LFTs can be caused by various factors, including drug-induced liver injury, acute hepatitis, acute liver failure, and exacerbations of pre-existing liver diseases 4.
- Other antiepileptic drugs, such as levetiracetam, have been reported to cause asymptomatic elevation of liver enzymes in some cases 5, 6, but there is no similar evidence for topiramate.