Flupirtine Should Not Be Prescribed Due to Withdrawal from Market and Severe Hepatotoxicity Risk
Flupirtine has been withdrawn from the European market due to serious hepatotoxicity concerns, including cases of acute liver failure, and should not be prescribed. 1
Critical Safety Information
Market Withdrawal and Hepatotoxicity
- Flupirtine was withdrawn from European markets following reports of severe drug-induced liver injury (DILI), including cases progressing to acute liver failure requiring liver transplantation 1
- Even with risk minimization measures implemented in 2013 (restricting use to 2 weeks maximum, requiring weekly liver function tests), the hepatotoxicity risk remained unacceptable 2
- DILI is one of the major causes of acute liver failure and can be life-threatening 1
Historical Context (When Drug Was Available)
- Flupirtine was a non-opioid analgesic that worked through selective neuronal potassium channel opening, providing indirect NMDA receptor antagonism 3
- The recommended dosing was 100-200 mg orally three to four times daily, with a maximum daily dose of 600 mg 4
- It was indicated for moderate acute pain of musculoskeletal origin 3, 4
Why This Drug Is No Longer Appropriate
Compliance Issues with Safety Measures
- When risk minimization measures were implemented, physicians showed poor compliance with weekly liver function testing requirements 2
- While prescription duration improved (91.3% of patients received ≤14 days treatment post-implementation), liver monitoring remained inadequate 2
- The number of flupirtine users decreased by 34.4% following safety measure implementation, reflecting growing safety concerns 2
Severity of Hepatotoxicity
- Cases of flupirtine-induced liver injury progressed rapidly to acute liver failure with encephalopathy 1
- The hepatotoxic potential was significant enough to warrant complete market withdrawal, not just additional restrictions 1
Alternative Analgesic Approaches
For Acute Moderate Pain
- First-line: Acetaminophen 1000 mg every 4-6 hours (maximum 4000 mg/day) for mild to moderate pain 5
- NSAIDs: Ibuprofen 600 mg up to four times daily or diclofenac 75 mg twice daily for inflammatory pain 5
- Weak opioids: Tramadol 50-100 mg (maximum 400 mg/day) or codeine for moderate pain when NSAIDs are insufficient 5
Monitoring for Alternative Agents
- NSAIDs require gastroprotection when used long-term and caution with renal function 5
- Tramadol should not be combined with monoamine oxidase inhibitors and requires caution with seizure risk 5
- Acetaminophen can cause hepatotoxicity if maximum daily dose is exceeded 5
The question of prescribing flupirtine is moot—this medication is no longer available due to unacceptable hepatotoxicity risk, and safer alternatives exist for managing acute moderate pain.