But let's look a little closer as to why this happened. The FDA cites the increasing cardiotoxicity and risk of heart arrythmias in a post-market study conducted by Xanodyne. It is a little difficult to find out more exact information since the study is not published but lets do a little Scooby Doo-like sleuthing.
- Propoxyphene is a synthetic derivative of methadone.
- Methadone causes QT prolongation of questionable clinical significance in palliative care patients.
- QT prolongation is a risk factor for ventricular arrhythmias.
Searching beyond just the press releases and news articles I found this FDA memo from Dr. Sharon Hertz *(Deputy Division Director Division of Anesthesia and Analgesia Products) noting that Xanodyne was asked to do a Thorough QT study. Never heard of that before? Well all new drugs since 2005 have had to pass through one before being approved. Given this increased risk of QT prolongation and the fear of resulting ventricular arrhythmias, the risk of the drug started to overwhelm the very minimal benefit it offered.
Interestingly the FDA has no evidence of QT Prolongation Adverse Event related deaths with Propoxyphene. Here is a quote from the memo: (emphasis mine)
At the 2009 advisory committee meeting, FDA staff shared postmarket data that have been suggestive, but inconclusive, about the risk for propoxyphene-related cardiac toxicity when used at therapeutic doses. No cases of torsades de pointes (TdP) causally associated with propoxyphene have been reported despite extensive use for many years. In an analysis of serious adverse events reported to the Adverse Event Reporting System (AERS) covering the period from marketing to February 2, 2005 (approximately 33 years), there were 91 U.S. deaths associated with Darvocet, the most commonly dispensed formulation of propoxyphene. Most of the reports identified opioid drug overdoses in individuals with profiles of drug dependency, in which there was coingestion of multiple medications, or in those attempting suicide.What is really interesting about this memo is section 1.2.1.1 on page 20, where they discuss QT studies of other opiate agonists. 6 lines of the report are redacted and in the whole 20 pages there is not one mention of methadone despite nearly all other opioids being mentioned. Redaction? Should we call Wikileaks founder Julian Assange?
So in the end I am not sure if propoxyphene being removed is really about cardiotoxicity and QT, minimal effectiveness, abuse and overdose potential or a combination of all of the above.
Well all this may be a whole lot of nothing but my real concern is that methadone may be a drug in the crosshairs of the FDA soon. It already has four strikes against it:
1) documented QT prolongation
2) stigma of heroin treatment programs
3) accelerating percent of all deaths related to opioids
4) methadone could be considered an orphan drug
And evidence of methadone being a very useful medication is possibly not strong enough to overcome these issues. So while we can cheer propoxyphene disappearing we should also be cautious and gather better evidence for the medications we wish to keep in our arsenal to ensure good pain control for years to come.
Beaver, W. (1984). Analgesic Efficacy of Dextropropoxyphene and Dextropropoxyphene-containing Combinations: a Review Human and Experimental Toxicology, 3 (1 suppl), 191-220 DOI: 10.1177/096032718400300118Collins, S., Edwards, J., Moore, R., McQuay, H. (1998). Single-dose dextropropoxyphene in post-operative pain: a quantitative systematic review European Journal of Clinical Pharmacology, 54 (2), 107-112 DOI: 10.1007/s002280050430
Ripamonti, C., Bianchi, M., Bruera, E. (2004). Methadone: An Orphan Drug? Journal of Palliative Medicine, 7 (1), 73-74 DOI: 10.1089/109662104322737278
** Yes the Deputy Direcotr in charge of pain medicine at the FDA is Dr. Hertz. Ha!
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Sign in nowGrrrrr...
So, I'm glad actually. On consults, I have recommended that geriatric patients, and patients on hemodialysis, or with CKD, ARF and/or hepatic dysfunction be switched off of propoxyphene (Darvon) and/or propoxyphene-acetaminphen (Darvocet) to usually oxycodone-containing preparations.
That is a good point about seeing who is aligned with who.. i do not believe the AAHPM had anything to do with the darvocet recall and so i am not sure if they would make a statement on this.
I dont think there was a strong push from pharmaceuticals to push Darvocet out because even amongst clinicians there was only a small minority prescribing it (in my community at least) with a growing majority calling for its withdrawal.
Anon2,
This is not a blog for medical advice so can;t comment on what might work for you and must leave you with the standard, talk with your own doctor about it. Thanks for bringing up the issue of cost. And yo umay want to look at the references showing that Darvocet was statistically no better than tylenol alone.
John Bohlen, MD
I inherited an 87 yr old lady in a nursing home, doing well on q 5 hr ( yes, q 5 is what works for her) darvocet for severe
neuropathic pain. She is intolerant of numerous other drugs , and she
has had a reasonable quality of life on thus regimen. She is very
apprehensive about having to change meds . I wish the FDA would say
"no new starts" but grandfather in folks like my patient.