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Swim recently found out that the US is withdrawing propoxyphene (Darvon, Darvocet, Wygesic, etc) altogether.
Consider someone stabilized on chronic propoxyphene/apap. For the sake of argument, let Swim say it is to be taken 3 times a day PRN. Let's also assume aside from olgeneral old-person pain issues, the 75yr old is otherwise healthy.
Swim would like some opinions. What would Swiy switch their "patient" to, who is completely hypothetical? Swim's ideas currently floating around....
something comprable like 30mg codeine tid
perhaps a little stronger, 7.5mh hydrocodone bid
there's always a chance of jumping to 5mg oxycodone bid
or perhaps a COX-3 inh. like celecoxib
Swim's just lookin for ideas and what would happen. "What would SWIY do?"
Actually I believe it was all propoxyphene containing compounds because the dextro isomer cased QT prolongation....although, interestingly, this is not a cumulative effect. It'll go back once you stop.
Last edited by Politicalchalk; 22-11-2010 at 13:44.
Oh, thank goodness! Propoxyphene can be *SUCH* a dangerous drug! Pretty much the rest of the world has already taken the stuff off the market, it's about time the USA caught up!
To answer the question, codeine would be an acceptable substitute for (dextro)propoxyphene. Tramadol would also be acceptable if the patient didn't tolerate codeine for whatever reason; however tramadol also acts as an SSRI to some extent, and that should be taken into account, particularly if the patient will be coming off the painkillers at some point in the future (withdrawals/"discontinuation syndrome" from tramadol tends to not only have the typical opioid symptoms, but SSRI symptoms as well).
Fair play to anyone who has taken propoxyphene long-term without having to up the dose! In addition to it's own dangers in larger doses, they put so much damn APAP in those pills (650mg per tablet! *sheesh*) that it's liver failure waiting to happen! And CWE is impossible with the formulation they generally prescribe.
Anyway, as I said, codeine or tramadol is generally the replacement for propoxyphene.
Dont quote my Panda just yet, but he seems to recall a number of factors playing into the total U.S. market ban (+ W.H.O. recommendation to remove it from its approved formulary).
1. Propoxyphene HCL (DARVON, Darvocet when -w- paracetamol) has been repeatedly proven in clinical trials to have negligible physical pain relief properties when compared to safer, more redily available analgesics.
2. It is favored as a a means of suiciding-self among proponents of right to die groups.
3. It's been long advocated as carrying a black-box warning -- the strongest most strenuous warning advisory in the U.S. for years.
Many of this info may be referenced on the 'W' site not to be named on DF.
My personal feelings, good riddance to such a sh!tty drug -- never did anything for me besides made W/D's at a center which would only dispense this piss poor 'drug' / opioid-substitute absufukinlutely unbearable to the point of having to bail from the program early, and an unplanned nerve-racking emergency room trip in my early 20's when it interacted in a really f'd up way with another med I was on at the time.
Please note this is only the opinion of a psychotic Panda having spent way too much time at the zoo scoring various vet drugs of higher caliber in his twisted opinion.
My chimp is indifferent about this. The only time he's taken it is when he runs out of him regular pain meds too soon and can't get them filled for a couple more days. He's told me that it does absolutely nothing for his pain but does help to stave off the WD (if he takes 2 or 3 of the 100/650 dosage every 4 hours) which was liver failure waiting to happen. He supposes it doesn't matter to him any more because he has no more and has no desire to get any, he just better manages his regular meds now.
Burnz, you're quite correct. I know the QT prolongation was the straw that broke the camel's back.
And chimps don't really have to worry, in all honesty, about 2 or 3 100/650 --- I mean, yeah it'll mess with your liver, but not significantly enough to if the chimps body had morphologically changed to accommodate not just the propoxyphene, but also the APAP ("paracetamol" as our friends across the pond prefer.) -- given enough time and at the correct rate, a pretty decent degree of acetaminophen metabolic changes occur such that a similar "tolerance" happens. Note: THIS IS NOT AN ENDORSEMENT OF DOSE ESCELATION!!!
*bump* cmon people, let's get creative! let us allow the following conditions: assume all opioid substances are available. Consider the age and general condition of patient.
Just to play devil's advocate and see if I can't generate some response.... I'm going ketobimidone. What the hell, with a meprobamate chaser (yes, I know it's not an opiate. but let's just say ALL substances are available.)
Ketobemidone (the corect spelling of what you are speaking of) is sched. I in the US, meaning it is not available on prescritpion. Look, you said darvocet worked. Tramadol or Tylenol 3/4 is stronger than darovcet. What else can we tell you?
You want a suggestion since propoxphen is off the market. Tramadol is the next step, then codeine/acet, imo.
What else do you want to hear?
Ketobemidone isnt available in the US.
Assuming it is an elderly patient who Darvo worked for, tram or T3/4 is the best pain med. No one with any knowledge of pain meds will tell you otherwise.
Moving Pictures...Swim is now more interested in a thought experiment rather than literal prescribing information. Hence, Swim has amended the question to include any and all substances. So, one supposes, the refined question at heart:
What is SWIM's personal analgesic advice, given pharmaceutical omnipotence? Swim's always been interested in Ketobemidone, and long acting meds in general. SWIM's grandma's cat was offered fentanyl patches as substitute! So it seems that the equianalgesic thing is off the table. A group I work for, called NYPIRG, does this thing called "Question of the day" -- i'm looking for more esoterica or interesting combos rather than...ya know, "sound medical advice."
Incidentally, Swim's gram's cat is elderly and polish. Swim advised her against the Duragesic because she cooks over hot stoves a lot and sleeps due to her age quite a bit, which as swim recalls, are two big factors that screw with the transdermal release system.
And what the hell, to make things interesting again, let's say the meprobamate is done iontophoretically.
Swim hopes this clears up the nature of kittie's question
What is her actual condition? Besides "old person pain issues"? I mean, I knew an old man in his mid-80s who had the general old person pain issues and a thing with his toe that is like the nerve pain caused from diabetes though he wasn't diabetic. He was given everything "good". 10mg oxymorphone IR, 10 mg hydrocodone, darvocet, and fentanyl (I don’t know what strength) but that was because the doctors knew he was going to be dead soon. As a matter of fact, when I first met him, he was only on Lyrica (pregabablin) and hydrocodone 7.5 bid for pain and he died about 8 months later. He was given those other stronger drugs during his end stages, probably the last 5 months of his life. He was a tough motherfucker though. He was up and walking around, albeit with a walker, and even driving a week before he died. His mind never went even though his body did. He came down with an infection in his chest and spent a few day in the hospital before he died. The doctors knew it was coming soon, so they didn't worry about giving him strong pain meds. He actually got a citation for DUI because of how strong the meds were. He fell asleep at the wheel and smashed into a telephone poll. The case got dismissed though and he never went to jail because the cops knew him. They did take him to the hospital to get him checked out and do a blood draw. After they found out it was just the meds the doc gave him, they decided to throw it out but that’s because this is a small town and everyone has known him forever. They wouldn’t do that for most people. Geez, I miss him now that I’m thinking about it. He had had a stroke a few years back and had problems on his right side but his memory was better than mine!
Not to suggest anything that is too mean but is your gram in the end stages of her life? That is my guess as to why the offered fentanyl but if it is one of the lower dose patches, very little "high" (less sedation) would be felt and she would have pain relief for 3 days without having to worry about taking pills. Personally, I think fent is a great option for elderly people who are on a lot of drugs already and may forget to take their pain meds. They are people who take it for pain because the doctor gives it to them, they aren't looking to get high, so they sometimes forget to take the pills, unlike a drug abuser who‘s going to be sure to take ‘em. That's why I think the patch is a good idea. They should start her off at 12mcg/hour though.
Meprobromate (Miltown) is an old school sedative, very old school. It's been replaced by the benzos, though it is sometime still given. I just asked my mom about it and she said it was the first drug she ever stole from her mom, lol. That was back in the late '60s. She said it was sedating but different from valium and the like. She said she really can't remember that well how it effected her. She said maybe it's like Phenobarbital but not pentobarbital or amobarbital or any of the strong barbs. Why would grandma need a sedative? Why would she go with something as old as milltown? It's also much more dangerous overdose wise than benzos. It has some muscle relaxant properties but valium or carisopradol would be far more effective. Even flexeril. In fact, for a muscle relaxant for an elderly person, I'd go with 5 mg valium or 10 mg flexeril. One soma makes me tired as hell so it might be too much for your gram.
So maybe 12 mcg/hr fentanyl every 72 hrs and 5 mg diazepam or 10 mg cyclobenzaprine prn or bid as I don‘t know her conditions so I can‘t speculate on how often she should take the muscle relaxants. See how that is tolerated because we don't want her too sedated. Does she ever drink? Does she smoke? Breathing problems? Those all come into play when deciding what to prescribe.
Look, I'm not a doctor and don't even want to be one. I have a somewhat halfway decent knowledge of prescription meds from reading the PDR cover to cover several times and internet searches and such. So I'm just throwing things out there.
The reason I suggest fentanyl is only because it can be hard for elderly patients to remember to take their meds. I mean if she was on a pain med bid or tid or qid, she could forget to take one of the pills. I know this could be resolved by a pill box but it could still be an issues. That's why I think a continuous 72 hour patch is great but something low like the 12 mcg so she isn't fucked up. I don't have any evidence, just educated guess, that 12 mcg/hr would be equal to 5 or 7.5 mg hydro bid or maybe even tid.
Or is she is she taking pain meds prn? If so, no fentanyl. Oxy or hydrocodone or tramadol or codeine would be the way to go.
Oh yeah, for a muscle relaxant instead of flexeril, meprobromate, carisopradol, or diazepam, why not Robaxin (methocarbamol)? It's is not very sedating at all and helps a lot for minor muscle pain. Maybe 500 mg to start off with and if it’s not enough 1000 mg? If for chronic pain it would probably be need qid, at least bid. To the issues of sedation from it, my friend had a large prescription for muscle pain/spasms for his heroin withdrawals and took up to 7 or 8 at a time to feel sleepy enough to get a nap in.
If we want to go real crazy and talk about anything possible, poppy pod tea or oral opium would be my suggestion. It is sedating but it is also great for pain, imo, even in low doses. Of course it would be impossible to measure the exact dose making this a hard option. Not to mention it is illegal. Do to all the alkaloids in it, I think it is stronger than a lot of other pain meds (codeine, hydrocodone, tramadol, propoxyphene to be particular). But it is far more sedating. Also constipation is very real with it. More so than a moderate strength opioid/opiate, imo.
Constipation is an issues with all opiates and can become a very serious problem in elderly people so that would have to be taken into account with what ever she is given. She will need a good diet, fiber supplements, and perhaps a daily laxative/stool softener.
So those are my thoughts. A little jumbled but my friend is on Ritalin right now his thoughts aren't so clear. I'm typing for him of course.
Oh another option besides fentanyl could be Opana (oxymorphone) ER 5 or 10 mg once or bid. Or a equal dose of Oxycontin (oxycodone), 20 or 40 mg would be my guess, once or bid.
Good luck and I hope this helps.
Edit- you totally lost me on iontophoretically administration meprobromate. I didn't know what that word meant so I looked it up and got this definition
the introduction of an ionized substance (as a drug) through intact skin by the application of a direct electric current
I have no idea how that would be possible but that's just me. I don't know that much...
You clearly know a LOT more about pharmacology than I do.
Last edited by Moving Pictures; 15-12-2010 at 19:55.
Swim advised her against the Duragesic because she cooks over hot stoves a lot and sleeps due to her age quite a bit, which as swim recalls, are two big factors that screw with the transdermal release system.
And what the hell, to make things interesting again, let's say the meprobamate is done iontophoretically.
Panda asks two things regarding the above:
1) It seems to Panda that cooking over a hot stove a lot might, possibly increase the rate of absorption (and therein potency) of the Duragesic / Fentanyl patch if it truly managed to have enough heat transfer to the patch to affect the delivery rate -- and it seems that the amount of heat required to attain / affect a raised level of fentanyl release is not really all that much as Panda seems to recall an information leaflet/insert with the fentanyl patches to specifially mention that patients with fevers (heightened body temp) may require closer monitoring as this would be enough to cause a higher 'drug dump' than a regular patient... The question: is the patient emaciated and/or have a lower body fat level? This has definitely been established as a causal factor in several hospital-based unintentional OD deaths in this demographic group.
2) It was Panda's understanding that "passive transdermal administration of drugs, as with a skin patch, is suitable for non-ionized drugs requiring a relatively small dosage. Ionized drugs, however, do not easily penetrate the skin and are therefore not generally suitable for routine transdermal dosage".Seeing as how Meprobamate is standardized in the 200 or 400 mg range vs. the 12.5 to 100 mcg -- isn't a microgram a thousandth? or was it a ten-thousandth? of a milligram? 1 microgram (mcg) = 0.001 milligrams. 1 milligram = 1000 micrograms (mcg) -- range for transdermal fentanyl delivery systems and Panda is unsure as to the ionization potential of Meprobamate, would iontophoretic drug delivery be a feasible ROA for Meprobamate?
Just two silly thoughts with question marks from a silly Panda with remedial maths/science capacities
P.S. to Politicalchalk: Nice job mentioning the QT prolongation effect inherent to propoxyphene! As it is most closely chemically related to methadone which reportedly has a QT prolongation potential as well, albeit not purpotedly as severe and (according to a pharmacist/'chemist' Panda consulted once upon a time in a dream, far, far away ) mainly begining to manifest at dosages above 200 mg. True? False? 'the world may never know'
Now that propoxyphene is unavailable, what are other options for analgesia?
Response from Scott Lothian, RPh
Clinical Pharmacist, Oncology & Pain Management; Epic Beacon Analyst, Pharmacy Department, Northwestern Memorial Hospital, Chicago, Illinois Recently, Xanodyne Pharmaceuticals, Inc. agreed to withdraw propoxyphene from the market at the request of the US Food and Drug Administration (FDA). New research found that propoxyphene, which was sold under the brand names Darvon®and Darvocet®, was associated with cardiac toxicity (prolonged QT interval, prolonged PR interval, and widened QRS complex) even at therapeutic dosing. This article serves as a general overview of analgesics for clinicians now faced with finding alternative pain medications for their patients. Strong opioids (eg, morphine, hydromorphone, oxycodone, methadone) are not be discussed. Acetaminophen
Acetaminophen (APAP) alone is as effective as the combination of propoxyphene and APAP for arthritis, postsurgical, or musculoskeletal pain. Acetaminophen is well tolerated at recommended doses with relatively few side effects. However, long-term maximum daily dosing can lead to toxicities (hepatic and renal), especially if taken with excessive alcohol. APAP now carries a black box warning in regard to the possibility of increased risk for severe liver injury.
Patients should be advised not to exceed the maximum daily dose of APAP and to avoid taking other sources of APAP concomitantly. The American Geriatrics Society (AGS) recommends that the maximum dose of APAP be reduced 50%-75% in patients with hepatic insufficiency or a history of alcohol abuse.
In addition, the maximum daily dose of APAP may interfere with warfarin, causing an increased risk for anticoagulation and an increased international normalized ratio (INR). Patients on warfarin therapy should contact their healthcare professional if they start taking doses exceeding 2 g/day; close INR monitoring is required when starting or stopping high-dose APAP therapy.
The FDA recently posted a safety announcement recommending that the content of APAP in all prescription combination products be limited to a maximum of 325 mg. This does not pertain to over-the-counter products. NSAIDs
Available nonsteroidal anti-inflammatory drugs (NSAIDs) include nonselective agents, such as ibuprofen and naproxen, and selective agents, such as the cyclooxygenase (COX)-2 inhibitor celecoxib. NSAIDs have proven to be more effective than propoxyphene plus APAP for inflammatory or musculoskeletal pain.
Many clinicians consider NSAIDs as the initial agent in most patients if there are no contraindications, whereas others believe that use should be limited to short-term treatment and will not recommend them for patients over 65 years of age.
If NSAIDs are used and one agent is not effective, it is often worth trying another agent before giving up on NSAID-based pain therapy. According to an evidence-based review, ibuprofen should be considered first because it has the lowest risk for gastrointestinal adverse effects. Naproxen can be considered if other nonselective NSAIDs are required because it has an intermediate risk for adverse events. If single-agent analgesia is inadequate, NSAIDs may be combined with APAP or opioids.
The FDA has provided guidance on the use of NSAIDs:
The lowest effective dose of NSAIDs should be used for the shortest duration.
NSAIDs should be avoided in high-risk patients (eg, history of ischemic heart disease, stroke, congestive heart failure, or those having recently undergone a coronary artery bypass graft).
Nonselective NSAID use in patients < 65 years of age without gastrointestinal risk factors is generally appropriate.
Nonselective NSAID use alone is inappropriate in patients with a history of a previous gastrointestinal event and in those receiving aspirin, steroids, or warfarin. These patients should receive concomitant proton-pump inhibitor (PPI) therapy or therapy with a COX-2 inhibitor.
Therapy with a COX-2 inhibitor and a PPI is appropriate only in patients at very high risk for a gastrointestinal event.
In addition, the AGS recommends that older persons taking nonselective NSAIDs should receive mucoprotective agents, and patients taking any NSAIDs should be routinely assessed for gastrointestinal and renal toxicity, hypertension, heart failure, drug-drug interactions, and drug-disease interactions.
All NSAIDs carry a black box warning in regard to the possibilities of increased risk for serious cardiovascular thrombotic events, stroke, and myocardial infarction as well as serious gastrointestinal events such as bleeding, ulceration, and perforation. Opioid-like Agents
Tramadol is a centrally acting analgesic indicated for moderate to moderately severe pain. One study found that tramadol demonstrated comparative efficacy to propoxyphene with APAP. Tapentadol (Schedule II), another centrally acting analgesic, is indicated for moderate-to-severe acute pain. Both tramadol and tapentadol are thought to work by mu-opioid agonist activity and inhibition of norepinephrine reuptake; tramadol also inhibits serotonin reuptake. (Tapentadol may increase serotonin levels, but this is not considered a mechanism of its analgesic effect.[9,10]) These agents are especially suited for pain with a neuropathic component; they may not be as effective for moderate pain that is usually well treated by traditional opioid combinations or other agents if a neuropathic component is absent.
Drug interactions may limit use of these agents. Because both can potentially increase serotonin levels, they should not be given concurrently with serotonergic drugs such as monoamine oxidase inhibitors (MAOIs), triptans, selective serotonin reuptake inhibitors, or serotonin-norepinephrine reuptake inhibitors due to the increased risk for seizures and serotonin syndrome.[9,10] Tapentadol is contraindicated with concomitant use or use within 14 days of MAOIs. Side effects of both include dizziness, nausea, vomiting, and constipation.[9,10] Because tapentadol is a newer analgesic, its role has yet to be proven in wider clinical use. Opioid Combination Products
Combination opioids such as APAP with codeine or APAP with hydrocodone are effective for the short-term treatment of most types of moderate pain. Long-acting agents should be considered for baseline pain control of well-established chronic pain to avoid chronic short-acting opioid use. Constipation, even with limited use, is almost always an issue and should be treated prophylactically with a stimulant/softener laxative. Due to concerns of addiction, opioids are often underused. Full assessment of the patient's pain and history may help to better define their proper use in most patients, but in the end, good pain control should be the defining factor. Other Agents
When selecting an analgesic, one should evaluate the pain fully to determine the most appropriate agent(s); prescribe an agent that will not be needed at its maximum dosage for a prolonged period of time; and consider the patient's age, history, and comorbidities. Guidelines[3,11] and algorithms are available that can assist clinicians in choosing appropriate analgesic and mucoprotective therapy.