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#105222 - 07/19/04 06:16 AM
Buprenorphine - Temgesic
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Melody
Moderator
Pooh-Bah
Registered: 03/20/03
Posts: 1498
Loc: DrugBuyers.Com
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Buprenorphine, a derivative of thebaine, is an opioid that has been marketed in the United States as the Schedule V parenteral analgesic Buprenex®. In 2002, based on a reevaluation of available evidence regarding the potential for abuse, diversion, addiction, and side effects, the DEA reclassified buprenorphine from a Schedule V to a Schedule III narcotic.
In October 2002, Reckitt Benckiser received FDA approval to market a buprenorphine monotherapy product, Subutex®, and a buprenorphine/naloxone combination product, Suboxone®, for use in opioid addiction treatment. The combination product is designed to decrease the potential for abuse by injection. Subutex® and Suboxone® are currently the only Schedule III, IV, or V medications to have received FDA approval for this indication. In January 2003, Reckitt Benckiser began shipments of Suboxone® to pharmacies in the United States.
The FDA approval of these buprenorphine formulations does not affect the status of other medication-assisted opioid addiction treatments, such as methadone and LAAM (levo-alpha-acetyl-methadol). As indicated in Title 42 Code of Federal Regulations Part 8 (42 CFR Part 8), these treatments can only be dispensed, and only in the context of an Opioid Treatment Program. Also, neither the approval of Subutex® and Suboxone®, nor the provisions of DATA 2000, affect the use of other Schedule III, IV, or V medications, such as codeine, that are not approved for the treatment of addiction. Lastly, note that aside from Subutex® and Suboxone®, other forms of buprenorphine, e.g., Buprenex®, are not approved for treatment of opioid addiction.
Buprenorphine is an opioid partial agonist. This means that, although buprenorphine is an opioid, and thus can produce typical opioid agonist effects and side effects such as euphoria and respiratory depression, its maximal effects are less than those of full agonists like heroin and methadone. At low doses buprenorphine produces sufficient agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. The agonist effects of buprenorphine increase linearly with increasing doses of the drug until at moderate doses they reach a plateau and no longer continue to increase with further increases in dose-the "ceiling effect." Thus, buprenorphine carries a lower risk of abuse, addiction, and side effects compared to full opioid agonists. In fact, in high doses and under certain circumstances, buprenorphine can actually block the effects of full opioid agonists and can precipitate withdrawal symptoms if administered to an opioid-addicted individual while a full agonist is in the bloodstream.
Buprenorphine has poor oral bioavailability and moderate sublingual bioavailability. Formulations for opioid addiction treatment are in the form of sublingual tablets.
Buprenorphine is highly bound to plasma proteins. It is metabolized by the liver via the cytochrome P4503A4 enzyme system into norbuprenorphine and other metabolites. The half-life of buprenorphine is 24–60 hours.
Because of its ceiling effect and poor bioavailability, buprenorphine is safer in overdose than opioid full agonists. The maximal effects of buprenorphine appear to occur in the 16–32 mg dose range for sublingual tablets. Higher doses are unlikely to produce greater effects.
Respiratory depression from buprenorphine (or buprenorphine/naloxone) overdose is less likely than from other opioids. There is no evidence of organ damage with chronic use of buprenorphine, although increases in liver enzymes are sometimes seen. Likewise, there is no evidence of significant disruption of cognitive or psychomotor performance with buprenorphine maintenance dosing.
Information about the use of buprenorphine in pregnant, opioid-addicted women is limited; the few available case reports have not demonstrated any significant problems due to buprenorphine use during pregnancy. Suboxone® and Subutex® are classified by the FDA as Pregnancy Category C medications.
See the Buprenorphine Clinical Practice Guidelines (available soon on this Web site) for more information about the use of buprenorphine in pregnancy. Currently, methadone remains the standard of care for the medication-assisted treatment of opioid-addicted women in the United States.
Side Effects
Side effects of buprenorphine are similar to those of other opioids and include nausea, vomiting, and constipation. Buprenorphine and buprenorphine/naloxone can precipitate the opioid withdrawal syndrome. Additionally, the withdrawal syndrome can be precipitated in individuals maintained on buprenorphine. Signs and symptoms of opioid withdrawal include:
Dysphoric mood
Nausea or vomiting
Muscle aches/cramps
Lacrimation
Rhinorrhea
Pupillary dilation
Sweating
Piloerection
Diarrhea
Yawning
Mild fever
Insomnia
Craving
Distress/irritability
Drug Interactions, Cautions and Contraindications
Refer to the Subutex® and Suboxone® package inserts (http://www.fda.gov/cder/drug/infopage/subutex_suboxone/default.htm) for a complete listing of drug interactions, contraindications, warnings, and precautions.
Abuse Potential
Because of its opioid agonist effects, buprenorphine is abusable, particularly by individuals who are not physically addicted to opioids. Naloxone is added to buprenorphine to decrease the likelihood of diversion and abuse of the combination product. Sublingual buprenorphine has moderate bioavailability, while sublingual naloxone has poor bioavailability. Thus, when the buprenorphine/naloxone tablet is taken in sublingual form, the buprenorphine opioid agonist effect predominates, and the naloxone does not precipitate opioid withdrawal in the opioid-addicted user.
Naloxone via the parenteral route, however, has good bioavailability. If the sublingual buprenorphine/naloxone tablets are crushed and injected by an opioid-addicted individual, the naloxone effect predominates and can precipitate the opioid withdrawal syndrome.
Under certain circumstances buprenorphine by itself can also precipitate withdrawal in opioid-addicted individuals. This is more likely to occur with higher levels of physical addiction, with short time intervals (e.g., less than 2 hours) between a dose of opioid agonist (e.g., methadone) and a dose of buprenorphine, and with higher doses of buprenorphine.
Evidence of Effectiveness
Studies have shown that buprenorphine is more effective than placebo and is equally as effective as moderate doses of methadone and LAAM in opioid maintenance therapy. Buprenorphine is unlikely to be as effective as more optimal-dose methadone, and therefore may not be the treatment of choice for patients with higher levels of physical dependence.
Few studies have been reported on the efficacy of buprenorphine for completely withdrawing patients from opioids. In general, the results of studies of medically assisted withdrawal using opioids (e.g., methadone) have shown poor outcomes. Buprenorphine, however, is known to cause a milder withdrawal syndrome compared to methadone and for this reason may be the better choice if opioid withdrawal therapy is elected.
Non-pharmacological Therapies
Effective treatment of drug addiction requires comprehensive attention to all of an individual’s medical and psychosocial co-morbidities. Pharmacological therapy alone rarely achieves long-term success. Thus Suboxone® and Subutex® treatment should be combined with concurrent behavioral therapies and with the provision of needed social services. This point is of such importance that physicians must attest to their capacity to refer patients for counseling when they submit their Notification of Intent to SAMHSA to begin prescribing Suboxone® and Subutex®.
The choice of treatment setting in which to provide non-pharmacological therapies should be determined based on the intensity of intervention required for a patient. The continuum of treatment setting intensities ranges from episodic office-based therapy to intensive inpatient therapy. For more information on this topic refer to the American Society of Addiction Medicine’s Patient Placement Criteria (ASAM PPC-2R, (www.asam.org), the most widely used and comprehensive national guidelines for placement, continued stay, and discharge of patients with alcohol and other drug problems.
Many different types of behavioral therapies (e.g., Motivational Enhancement Therapy, self-help programs) have been used successfully for substance abuse disorders. The SAMHSA Treatment Improvement Protocol (TIP) series (http://www.treatment.org/Externals/tips.html) includes a number of documents that contain best practice guidelines for the provision of interventions and therapies for individuals with substance abuse disorders.
Opioid Addiction Therapy with Buprenorphine
This section provides a brief overview of the clinical use of buprenorphine (Suboxone® and Subutex®) for opioid addiction therapy. For detailed information on this topic see the Buprenorphine Clinical Practice Guidelines (available soon).
Ideal candidates for opioid addiction treatment with buprenorphine are individuals who have been objectively diagnosed with opioid addiction, are willing to follow safety precautions for treatment, can be expected to comply with the treatment, have no contraindications to buprenorphine therapy, and who agree to buprenorphine treatment after a review of treatment options. There are three phases of buprenorphine maintenance therapy: induction, stabilization, and maintenance.
The induction phase is the medically monitored startup of buprenorphine therapy. Buprenorphine for induction therapy is administered when an opioid-addicted individual has abstained from using opioids for 12–24 hours and is in the early stages of opioid withdrawal. If the patient is not in the early stages of withdrawal, i.e., if he or she has other opioids in the bloodstream, then the buprenorphine dose could precipitate acute withdrawal.
Induction is typically initiated as observed therapy in the physician’s office and may be carried out using either Suboxone® or Subutex®, dependent upon the physician’s judgment. As noted above, Buprenex®, the parenteral analgesic form of buprenorphine, is not FDA-approved for use in opioid addiction treatment.
The stabilization phase has begun when a patient has discontinued or greatly reduced the use of his or her drug of abuse, no longer has cravings, and is experiencing few or no side effects. The buprenorphine dose may need to be adjusted during the stabilization phase. Because of the long half-life of buprenorphine it is sometimes possible to switch patients to alternate-day dosing once stabilization has been achieved.
The maintenance phase is reached when the patient is doing well on a steady dose of buprenorphine (or buprenorphine/naloxone). The length of time of the maintenance phase is individualized for each patient and may be indefinite. The alternative to going into (or continuing) a maintenance phase, once stabilization has been achieved, is medically supervised withdrawal. This takes the place of what was formerly called “detoxification.”
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#105228 - 01/21/05 10:09 PM
Re: Buprenorphine - Temgesic
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virola
Journeyman
Registered: 01/08/02
Posts: 63
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Interestingly, buprenorphine is supposedly remotely used "off label" as an anti-depressant and that perks my curiosity as any other opiate would over time very likely cause a depressed person many additional problems, even if it did initially ameliorate their depression. So this makes me wonder, how long would it take for a person on bup to need to up the dose to retain the same effect? I am sure it varies depending on whether one is on the micro dose Temgesic .2 mg type or the full-on suboxone multi milligram type. Opiates generally don't take long before they fizz out and dosage needs to be upped. I guess many ofthe SSRIs poop out too, but not nearly as quickly and not with everyone.
Ona side note, I have seen lists of drugs that are used "off label" and some drugs companies make extraordinary claims, a few meds seem to be good for practically every illness, and I can only guess that the drug companies are either very hopeful or outright deceitful when they suggest such a wide array of uses for their new products. Gabapentin for example is supposed to be good for so many things it is doubtful that the company making it is honest. There are even lawsuits against the makers of gabapentin claiming the company is excessive with their off label suggestions.
On a side note on a side note, I read (sorry link lost) that small amounts of Tramadol (Click here for TramadolX180tabs for only 99.95 dollars) (Ultram) will be added to some well known antidepressants to augment the supply of serotonin in the brain synapse, creating a new line of more pOwerful, quicker acting antidepressants. It seems that there is no consistency in the latest research in drug development and my guess is that they really do not know what they are doing, sometimes they just dump the drugs on people and see what happens. Yikes!
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#105229 - 03/16/05 04:07 AM
Re: Buprenorphine - Temgesic
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jeremypaka
Banned: silly, off topic, jokes about drug abuse
Registered: 02/08/05
Posts: 94
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What would be a reasonable price to charge/pay for the
8mg Suboxone.
On an international site they were selling Temgesic; 100 .2mg tabs for $200, so a
.2mg Temgesic costs $2.00 per pill.
Using that price as a guide
Suboxone 2mg would cost $20.00 per pill and the
Suboxone 8mg would cost $80.00 per pill
That sounds ridiculous but if you mess with the math at the International site and change the 100 .2mg tabs to 1 20mg tab (100 X .2= 20), that's paying $200 for 2 1/2 8mg tabs.
I'd be willing to put up with the withdrawal symptoms if I could get that kind of money for my meds. 
JP
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#105231 - 03/16/05 05:52 AM
Re: Buprenorphine - Temgesic
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bcousin222
Stranger
Registered: 06/04/04
Posts: 14
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Why dont you go to a certified bupe doctor and get a script? There have been posts here about temgesic vs suboxone. I have a lot of experience with both and here is my advice: The doctors who prescribe buprenorphine (suboxone) are only required to take an 8 hour course to be certified. I took the course and it is amazingly weak. The doctors are, for the most part, uneducated in the proper dosing. The rule with bupe is that LESS IS MORE (DONT go chasing a buzz with this!! it actually is an agonist at small doses and more of an antagonist at larger doses. SO, your best chance for feeling good from bupe is to take SMALL doses). In other words, those .2 mg temgesics DO work. When you go to a bupe doctor they will put you on anywhere from 8mg-32mg's per day for up to a year! this is WAY overdosing. If you go to a sub doctor and get the 8 mg pills, try breaking off a small piece and letting it dissolve under your tongue for [censored] long as possible. wait an hour and see how you feel. if you are still in withdrawals, take another small piece and wait. (I forgot to mention, you must be in mild withdrawals before you start or the bupe will put you into withdrawals and it wont be pretty. Also, the naloxone mixed in with the bupe in Suboxone will have ZERO effect on you sublingally or orally, if you happen to swallow some. it only has antagonistic effects if administered IV)).
Anyway, I think the cheapest, best route is to find a bupe doc if you can and get the script for the 8mg's and make them last. The final piece of the puzzle is to get off of them ASAP. As in 2 weeks MAX. If you stay on over a month, you will need to do a 6 month taper to get off of it and it WILL BE DIFFICULT. Bupe withdrawals (if you take it too long) will be MUCH worse that regular opiate withdrawals and can last months, instead of days. So, this drug is a miracle drug for getting off opiates if you take small doses for a short period of time.
It's hard to give this kind of info when it goes against what your doc may tell you. I'm not a doc, but have reviewed over 1500 case studies and taken the same course they take. People wonder why the .2 temgesics work while epople are prescribed 8mg-32mgs a day by a bupe doc and it's because they are being overdosed and this will lead to bupe dependence and, ultimately, a bupe withdrawal nightmare.
When I used bupe to get off a SERIOUS hydro habit (started with legit pain, but got way out of control as in 60+ norcos a day, I made an 8 mg suboxone pill last 5 days. at the end of my detox, I was taking pieces of suboxone the size of a crumb, and they worked!!, then, it was easy to step off the drug and get on with the real battle - staying clean!.
Sorry to ramble, but tis drug is HIGHLY misunderstood and misused. Please PM me if you are interested in going this route and I will help you out the best I can. My first piece of advise - get the drug from a certified doctor and not from an IOP if you can. In the long run it will be cheaper and healthier (you should have your vitals monitored and have a doc make sure you're not mixing bupe with counterindicated drugs ie: benzos).....
enough rambling. PM me if you want and if you're sick of opiates and feel you need to get off, please reach out to me and I'll help..
-bcousin
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#105235 - 03/16/05 09:23 AM
Re: Buprenorphine - Temgesic
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jeremypaka
Banned: silly, off topic, jokes about drug abuse
Registered: 02/08/05
Posts: 94
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I was actually prescribed Suboxone to get off of Tramadol (Click here for TramadolX180tabs for only 99.95 dollars).
I had an enormous Daily intake of Tramadol (Click here for TramadolX180tabs for only 99.95 dollars).
Through a health care worker friend I found my Bupe doctor.
I went to the ER and the doctor met me there and admitted me for 5 days.
I was put on 2mg every 4 hours for the first 48 hours.
I kept insisting that the withdrawal I was experiencing was just as nasty as usual. I didn't seem to feel any lessening of W/D symptoms.
After about a day and a half of this misery the doctor upped me to an 8 mg tab every 8 hours.
The doctor happened to be in the room when the nurse brought me the 8mg bupe which I promptly swallowed.
The doctor was quite upset that the nurses didn't know that I was supposed to dissolve the tab under my tongue.
He immediately had me dissolve another tab the proper way.
I began to feel better almost immediately. He didn't reduce my dosage back to the 2mgs even though they might have worked had I not been swallowing them for the last 36 hours so I really don't know if the 2mgs would have been enough to ease the discomfort of w/d.
Unfortunately the Suboxones are crappy pain killers so after about a month of the Sub., my Sub doctor put me on Methadone until after my pending back surgery.
I would definitely say that Suboxone is a wonder drug when they are taken properly.
JP
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#105244 - 01/03/06 03:28 PM
Re: Buprenorphine - Temgesic
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JasonBourne
Member
Registered: 07/11/05
Posts: 105
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Just one of the clinical studies which I have personally witnessed these results, I have many more but must dig through my archives a little deeper.
At the receptors: (Per my research) In a clinical setting a few years ago (2001/02.
Bupe has a high affinity at all 4 major opioid receptors (mu, delta, kappa,
and ORL1) (Miller,Bourne.el 2001, (1))
Order of affinity (How much attraction to and how tightly it binds to each
receptor):
mu > kappa > delta > ORL1
(delta has about 30 fold less affinity than mu)
Bupe is a partial agonist at mu, delta, and ORL1. It is a full and potent
antagonist at kappa*. (J.Bourne,Miller 2001) It's efficacy at the receptors
is related to dose. The higher the dose, the less efficacious it works, (1)
until it reaches a dose (~32mg SL) where increasing it any more would make
it work less efficacious, although more data is necessary. (See Bupe and
Dose)
Order of efficacy (how strong it works as an agonist):
ORL1 (34%) > mu > delta (Miller,Bourne., 2001,)
The fact that it is efficient at ORL1 is very significant; as I don't think
any other traditional opioids can stimulate ORL1 (this definitely includes
morphine and heroin.) Unfortunately it has a very low affinity for it, which
would require large doses to create a significant effect there. Fairly large
doses have been attempted in limited studies with no interesting results,
other than the apparent reversal of agonist effects. (Bourne) I Believe ORL1 has
been shown to have similar effects to mu. Describing ORL1 is beyond the
scope of this document and my knowledge.
* There is a lot of conflicting studies in regards to kappa. Some say that it
does indeed produce kappa agonism. This isn't the case, I'm fairly positive
of it, but I'd like to know why this is. It possibly has something to do
with in vitro testing, however the in vitro testing summary (Miller,Bourne et al.,
2001) has determined bupe to be a kappa antagonist. I look forward to
finding further information on this, as always, for the next version...
Bupe has an extremely long half-life at the receptors. It takes about a
month for the drug to be completely removed from your system.
Finally, Buprenorphine has a major active metabolite, norbuprenorphine,
which has activity at the receptors,See metabolism for more information(J.Bourne)P.2232 LLMA Subjective analysis)
General Pharmacological Information:
Bupe has a slow onset of action, with peak effects taking place in
approximately 100 minutes. (Suboxone full prescribing information.) The peak
effects for methadone take place in approximately 120 minutes (VERIFY.)
Bupe readily crosses the blood brain barrier, and is highly lipophilic.
Bupe is about 10x more potent IM than PO (oral), which is about the same
ratio as morphine. You CAN eat bupe, although there is no reason. Nor should it be done in this manner..Sublingual absorption varies greatly, and can be anywhere from 25%-75%.~ The same percentages can be applied to an IM/SL potency comparison. However,
in most people, their personal variation from one dose to another is low.
(Subutex full prescribing information)
A comparison of bupe to 'done for respiratory effects found that bupe had a
much higher incidence of respiratory depression *not* requiring medical
intervention. Bupe can cause respiratory depression, but *very* rarely
anything resembling life threatening. Both drugs decreased 02 saturation to
the same degree. The chances of severe respiratory depression are increased
via the injection route. (Suboxone full prescribing information)
Bupe is a very safe drug for an opioid. Overdose is very difficult, even for
opiate naive individuals. (Subutex full prescribing information)
Buprenorphine is approximately 96% plasma bound, primary to alpha and beta
globulin (Subutex full prescribing information)
Bupe has a mean half-life plasma elimination of 37 hours.
I can take 2mg suboxone at 6am and at 2pm I can take a CII (morphine, oxycodone,fentanyl,etc) and the CII’s will clear the receptors within 30 minutes.
But if I use a CIII as hydro it makes me feel worse.
This is per my research, others may vary.
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