Why Darvocet Was Discontinued
Darvocet (propoxyphene/acetaminophen) was withdrawn from the U.S. market in 2010 due to fatal cardiac arrhythmias and cardiotoxicity that far outweighed any therapeutic benefit, particularly since its analgesic efficacy was no better than acetaminophen alone. 1, 2
Primary Safety Concerns Leading to Withdrawal
Fatal Cardiac Toxicity
- Propoxyphene causes QTc prolongation and life-threatening arrhythmias, with the FDA package insert explicitly warning of fatalities associated with its use 1, 2
- The cardiotoxicity is partially mediated by norpropoxyphene, a non-opioid cardiotoxic metabolite that accumulates with repeated dosing 2
- These cardiac risks were deemed unacceptable given the drug's minimal analgesic benefit 2
Additional Serious Adverse Events
- Propoxyphene causes seizures, particularly in overdose situations 2
- The drug has been implicated in numerous drug-related deaths, making it a significant public safety concern 3
- Subacute painful myopathy can occur following chronic propoxyphene overdosage 1
Lack of Therapeutic Advantage
Equivalent to Acetaminophen Alone
- Multiple studies demonstrated that propoxyphene provides no more analgesia than acetaminophen (APAP) alone, yet adds opioid side effects and mortality risk 2, 3
- In postoperative pain studies, propoxyphene/acetaminophen combinations showed inferior efficacy compared to alternative weak opioid combinations like tramadol/acetaminophen 4
- Even early studies comparing propoxyphene to plain acetaminophen showed minimal additional benefit that did not justify the added risks 5
Risk-Benefit Analysis Unfavorable
- The drug's iatrogenic events (cardiotoxicity, seizures, deaths) far outweighed any perceived therapeutic benefit 2
- Propoxyphene was excluded from modern pain management guidelines even before its withdrawal, with recommendations favoring NSAIDs, acetaminophen, or stronger opioids when needed 6
Prescribing Problems and Misuse
Inappropriate Dosing Patterns
- Studies showed that 49.2% of propoxyphene/acetaminophen prescriptions exceeded maximum daily acetaminophen doses, creating additional hepatotoxicity risk 3
- The combination of propoxyphene's euphorigenic properties created prescription abuse potential without corresponding analgesic benefit 2
Particular Danger in Elderly Patients
- Propoxyphene use in elderly patients should have been avoided due to complex pharmacokinetics and pharmacodynamics that increased adverse event risk 2
- Despite these concerns, propoxyphene had 7.1% prevalence among South Dakota Medicare beneficiaries, demonstrating widespread inappropriate use in vulnerable populations 3
Safer Alternatives Available
When propoxyphene was withdrawn, multiple superior alternatives existed:
- For mild-to-moderate pain: acetaminophen alone (up to 3000-4000 mg/day) provides equivalent analgesia without cardiac or seizure risk 7, 8, 3
- For moderate pain requiring weak opioids: tramadol/acetaminophen combinations demonstrate superior efficacy and safety profiles 4
- For severe pain: stronger opioids (morphine, hydrocodone) with appropriate monitoring provide better pain control when weak opioids are insufficient 6, 7
Common Pitfall to Avoid
- Never assume that older, long-marketed medications are "proven safe"—propoxyphene remained on the market for over 50 years (1957-2010) despite accumulating evidence of harm exceeding benefit 2, 3
- The mere presence of fatality warnings in a package insert should alert prescribers to reconsider whether any analgesic benefit justifies such risks 2