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Proudly announcing the birth of an alternative medication to methadone:

Drug Treatment Act Of 2000

Title XXXV, Section 3502 of the Children's Health Act of 2000 - Waiver Authority for Physicians Who Dispense or Prescribe Certain Narcotic Drugs for Maintenance Treatment or Detoxification Treatment.

DATA 2000 permits qualified physicians to obtain a waiver from the separate registration requirements of the Narcotic Addict Treatment Act to treat opioid addiction with Schedule III, IV, and V opioid medications or combinations of such medications that have been specifically approved by the Food and Drug Administration (FDA) for that indication. Such medications may be prescribed and dispensed.

In order to qualify for a waiver under DATA 2000, physicians must hold a current State medical license, a valid DEA registration number, and must meet one or more of the following conditions:

The physician holds a subspecialty board certification in addiction psychiatry from the American Board of Medical Specialties.

The physician holds an addiction certification from the American Society of Addiction Medicine.

The physician holds a subspecialty board certification in addiction medicine from the American Osteopathic Association.

1.  The physician has completed not less than eight hours of training with respect to the treatment and management of opioid-addicted patients. This training can be provided through classroom situations, seminars at professional society meetings, electronic communications, or otherwise. The training must be sponsored by one of five organizations authorized in the DATA 2000 legislation to sponsor such training, or by any other organization that the Secretary of the Department of Health and Human Services (the Secretary) determines to be appropriate.

2.  The physician has participated as an investigator in one or more clinical trials leading to the approval of a narcotic drug in Schedule III, IV, or V for maintenance or detoxification treatment, as demonstrated by a statement submitted to the Secretary by the sponsor of such approved drug.

3.  The physician has other training or experience, considered by the State Medical Licensing Board (of the State in which the physician will provide maintenance or detoxification treatment) to demonstrate the ability of the physician to treat and manage opioid-addicted patients.

4.  The physician has other training or experience the Secretary considers demonstrates the ability of the physician to treat and manage opioid-addicted patients. In addition, physicians must attest that they have the capacity to refer addiction treatment patients for appropriate counseling and other nonpharma--cologic therapies, and that they will not have more than 30 patients on such addiction treatment at any one time.    (Note: The patient limit applies to both physicians in solo practice and to entire group practices, and is not affected by the number of physician or group practice locations.)

For the 3-year period after the passage of DATA 2000, States may not preclude practitioners from dispensing or prescribing eligible medications for opioid maintenance or detoxification treatment. The effect of the three-year provision in DATA 2000 is to put into abeyance current State law or Regulations prohibiting physicians from prescribing Subutex® or Suboxone® for the treatment of opioid addiction, and to prevent State regulatory agencies from prohibiting prescribing by regulation. The FDA approved Subutex® and Suboxone® on October 8, 2002. A 2002 appropriations bill amended the DATA 2000 three-year State preemption provision to start on the date that the FDA approved Subutex® and Suboxone®. Thus, until October 8, 2005 States may not preclude practitioners from dispensing or prescribing eligible medications for opioid maintenance or detoxification treatment unless the State passes legislation to that effect.

The Secretary and the Attorney General are authorized to evaluate the effectiveness and impact of the program and to discontinue it with 60 days notice.


 
    

In October 2002, the FDA approved 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. Note that aside from Subutex® and Suboxone®, other forms of buprenorphine, such as  Buprenex®, are not approved for treatment of opioid addiction.

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®, no other forms of buprenorphine have been approved for use.


Suboxone®, a sublingual tablet, comes in two dosage forms: 2 mg buprenorphine/0.5 mg naloxone and 8 mg buprenorphine/2 mg naloxone. Subutex®, also a sublingual tablet, is available in 2 mg and 8 mg strengths. The Subutex® and Suboxone® drug labels are available on the FDA Web site at: http://www.fda.gov/cder/drug/infopage/subutex_suboxone/default.htm


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 act-ually 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 bioavail-ability. 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 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:

1.Dysphoric mood
2.Nausea and vomiting
3 Muscle Aches/Cramps
4. Lacrimation
5  Rhinorrhea
6. Pupillary dilation
7. Sweating
8. Pilorection
9. Diarrhea
10.Yawning
11.Mild Fever
12 Insomnia 
13.Craving/distress
14. Irritability

Drug Interactions, Cautions and Contraindications

Refer to the Subutex® and Suboxone® package insert for a complete listing of drug interactions, contraindications, warnings, and precautions.

What is the most important information I should know about Suboxone® and Subutex®?

*Suboxone® and Subutex® can cause death from overdose, especially if you inject them with tranquilizers. Use Suboxone® and Subutex® the way your Doctor tells you to with medicines used to treat depression or anxiety.

*Use Suboxone snd Subutex only for the condition for which it was prescribed."

*Suboxone® and Subutex® can cause Drug Dependence.  This means that you can get withdrawal symptoms if you stop using the medicine too quickly. Suboxone and Subutex are not for occasional (as needed) use. 

*Prevent theft and misuse.  Suboxone® and Subutex® contain a narcotic painkiller that can be a target for people who abuse prescription medications or street drugs.  Therefore, keep your tablets in a safe place, to protect then from theft.  Never give them to anyone else.  Selling or giving away medicine is against the law!

In an emergency,  have family members tell emergency room staff that you are dependent on opioids (narcotic painkillers) and are being treated with Suboxone® or Subutex®. 

 Benzodiazepines and Other Sedative Drugs

 *  Can cause death when             
mixed with benzodiazepines,
tranquilizers and/
 or alcohol! 
Can precipitate withdrawal!
     

There have been case reports of deaths apparently associated with injections of buprenorphine combined with benzodiazepines and/or other central nervous system (CNS) depressants (e.g., alcohol) ( Reynaud et al. 1998a ,b). Gaulier et al. (2000) reported a case of  fatal  overdose in  which  buprenorphine  and  its metabolites, as well as the metabolites of flunitrazepam, were very high at the time of death. Although it is not known if this is a pharmacodynamic interaction, Ibrahim et al. (2000) and Kilicarslan and Sellers (2000) suggest that, because of buprenorphine's weak ability to inhibit the cytochrome P450 3A4 system, the effect is more likely pharmacodynamic. This interaction, however, underscores the importance for physicians to be cautious in prescribing buprenorphine in conjunction with benzodiazepines, as well as in prescribing buprenorphine to patients who are addicted to opioids and also are abusing or are addicted to benzodiazepines.  It is prudent to assume that these cautions also should be applied to buprenorphine combined with other CNS depressants, including alcohol and barbiturates.

Opioid Antagonists

Buprenorphine treatment should not be combined with opioid antagonists, for example, naltrexone. It is common for individuals who are addicted to opioids to be concurrently dependent on alcohol.  Although naltrexone may decrease the likelihood of relapse to drinking, patients maintained on opioids should not be given naltrexone to prevent alcohol relapse since the naltrexone can precipitate an opioid withdrawal syndrome in buprenorphine -maintained patients.  

Thus, physicians should not prescribe naltrexone for patients being treated with buprenorphine for opioid addiction.

 Medications Metabolized by Cytochrome P450 3A4.

Buprenorphine is metabolized by the cytochrome P450 3A4 enzyme system. Other medications that interact with this enzyme system should be used with caution in patients taking buprenorphine. No controlled studies, however, have examined these pharmacokinetic interactions. Figure 2-3 lists some of the drugs known to be metabolized by cytochrome P450 3A4. In some cases, these drugs may either enhance or decrease buprenorphine's effects through actions on the cytochrome P450 3A4 system.*

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 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 with-drawing patients from opioids. In general, the results of studies of medically assisted withdrawal using opioids  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®.

Many different types of behavioral therapies (such as  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.

Method Of Administration


Buprenorphine sublingual tablets should be placed under the tongue until they are dissolved. -  For doses requiring the use of more than two tablets, patients should either place all the tablets at once or alternatively, if they cannot fit in more than two tablets comfortably, place two tablets at a time under the tongue. Either way, the tablets should be held under the tongue until they dissolve; swallowing the tablets reduces the bioavailability of the drug.  - - - To ensure consistency in bioavailability, patients should follow the same manner of dosing with continued use of the medication.  Dissolution rates vary, but, on average, the sublingual tablets should dissolve in approximately 5-10 minutes.

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.

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 “detoxiifica-tion .”


Notice: The Drug Addiction Treatment Act of 2000 limits physicians or physician group practices to prescribing buprenorphine for opioid addiction to a maximum of 30 patients at   one  time.   Because of this, some physicians listed on  the Locator  may not  be accepting new patients at this time.  -- If you are unable to find a physician within your area who is accepting new patients, please check later, as new physicians are being added weekly.

To locate the physician(s) authorized to prescribe Buprenorphine nearest you, find your State on the map below and click on it. Please click on the link below to take you to the physician locator --- along with more valuable information if desired.

CLICK HERE

Pharmacists:

Click here for information on how to verify whether a prescribing physician has a valid DATA waiver.

The National Alliance of Advocates For Buprenorphine Treatment System allows paients to register anonymously for treatment in a given geographic area...  This alerts participating physicians in that area that they are seeking treatment. Once an area can treat an additional patient, this system allowts the physician to email that patient to discuss treatment.

If you are thinking seriously about trying Suboxone® then please click on the link below:

http://www.naabt.org/patient_doctor/splash.cfm



1. What are Suboxone and Subutex?

Subutex and Suboxone are medications approved for the treatment of opiate dependence. Both medicines contain the active ingredient, buprenorphine hydrochloride, which works to reduce the symptoms of opiate dependence.

2. Why did the FDA approve two medications? 

Subutex contains only buprenorphine hydrochloride. This formulation was developed as the initial product. The second medication, Suboxone contains an additional ingredient called naloxone to guard against misuse.

Subutex is given during the first few days of treatment, while Suboxone is used during the maintenance phase of treatment.

.3. Will most prescriptions be for the Suboxone formulation?

Yes, Suboxone is the formulation used in the majority of patients.

4. How are Subutex and Suboxone different from the current treatment options for opiate dependence such as methadone?

Currently opiate dependence treatments like methadone can be dispensed only in a limited number of clinics that specialize in addiction treatment. There are not enough addiction treatment centers to help all patients seeking treatment. Subutex and Suboxone are the first narcotic drugs available under the Drug Abuse Treatment Act (DATA) of 2000 for the treatment of opiate dependence that can be prescribed in a doctor’s office. This change will provide more patients the opportunity to access treatment.

5. What are some possible side effects of Subutex and Suboxone?  (This is NOT a complete list of side effects reported with Suboxone and Subutex. Refer to the package insert for a more complete list of side effects.)

The most common reported side effect of Subutex and Suboxone include:cold or flu-like symptoms, headaches, sweating, sleeping diffulties, nausea, and mood swings..

Like other opioids Subutex and Suboxone have been associated with respiratory depression (difficulty breathing) especially when combined with other depressants.

6. Are patients able to take home supplies of these medicines? 

Yes. Subutex and Suboxone are less tightly controlled than methadone because they have a lower potential for abuse and are less dangerous in an overdose.   As patients progress on therapy, their doctor may write a prescription for a take-home supply of the medication.

7. How will FDA know if these drugs are being misused, and what can be done if they are? 

 FDA has worked with the manufacturer, Reckitt - Benckiser, and other agencies to develop an in-depth risk-management plan. FDA will receive quarterly reports from the comprehensive surveillance program. This should permit early detection of any problems. Regulations can be enacted for tighter control of buprenorphine treatment if it is clear that it is being widely diverted and misused.

8. What are the key components of the risk management plan?

The main components of the risk-management plan are preventive measures and surveillance.
Preventive Measures include:

*Education.
*Tailored distribution.
*Schedule III control under the Controlled Substances Act (CSA) child resistant   packaging.
*Supervised dose induction.

The risk management plan uses many different surveillance approaches. Some active methods include plans to:

*Conduct interviews with drug abusers entering treatment programs.
* Monitor local drug markets and drug using network areas where these medicines are most likely to be used and possibly abused.
*Examine web sites.

Additionally data collection sources can indicate whether Subutex and/or Suboxone are implicated in abuse or fatalities. These include:

DAWN—The Drug Abuse Warning Network. This is run by the Substance Abuse and Mental Health Services Administration

(SAMHSA)- which publishes a collection of data on emergency department episodes related to the use of illegal drugs or non-medical use of a legal drug.

CEWG—Community Epidemiology Working Group. This working group has agreed to monitor buprenorphine use.

NIDA—National Institute of Drug Abuse. NIDA will send a letter to their doctors telling them to be aware of the potential for abuse and to report it if necessary

 9. Who can prescribe Subutex and Suboxone?

Only qualified doctors with the necessary Dea (Drug Enforcement Agency) Identification Number are able to start In-office Treatment and provide the prescriptions for ongoing medication CSAT (Center For Substance Abuse Treatment) will maintain a database to help patients locate qualified doctors. 

10. How will Subutex and Suboxone be supplied?

Both medications come in 2 mg and 8 mg strengths as sublingual (placed under the tongue to dissolve) tablets.

11.  Where can patients get Subutex and Suboxone?

These medications will be available in most commercial pharmacies. Qualified doctors with the necessary DEA Identification Numbers will be encouraged to help patients locate pharmacies that can fill prescriptions for Subutex and Suboxone.

12.  Where can I go for more information?

Go To:      

http://www.SuboxoneAssistedTreatment.org                                                     

http://www.fda.gov/cder/drug/infopage/subutex_suboxone/default.htm

Contact::

770.428.0871 (Phone)        770.527-9119  (Cellular)       770.428.0864 (Facsimile)      

CSAT Buprenorphine Information Center at 866-BUP-CSAT, or via email at info@buprenorphine.samhsa.gov or http://buprenorphine.samhsa.gov/ 

  Deborah Shrira, Editor  August 2008 Copyrighted

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