Chronic opioid use is a precursor to the brain changes characteristic of opioid dependence, but it is only one of the etiologic factors in the development of the disease.^2,3 Chronic opioid use alone does not cause opioid dependence.

According to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), the hallmark of drug dependence is continued use "despite [the patient's] knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance."⁴

The standard of "continued use despite harm" is important because patients may become tolerant or even physically dependent on opioids, without it being cause for concern.^3-5 In fact, most patients who are appropriately using opioids to treat a chronic condition report improvements to their overall quality of life, regardless of how their bodies may have adapted to the continued use of opioids over time.⁶

The DSM-IV criteria for opioid dependence are listed under How do physicians diagnose opioid dependence?

Under DATA 2000, qualified physicians may obtain a waiver allowing them to prescribe and/or dispense approved Schedule III-V medications for the treatment of opioid dependence outside a hospital or opioid treatment program (ie, methadone clinic). This means that for the first time in almost 30 years, qualified physicians have the legal right to use opioids to treat opioid dependence in an office setting.

The significance of office-based treatment lies in its potential to enhance both treatment privacy and overall access to care in this undertreated population. The prospect of a more confidential treatment option is expected to encourage many opioid-dependent patients to finally seek medical attention. The prospect of a more confidential treatment option is expected to encourage many opioid-dependent patients to finally seek medical attention.

SUBOXONE is also the first opioid approved under DATA 2000 for the office-based treatment of opioid dependence. Office-based treatment is important because of its potential to enhance the privacy of treatment as well as patients' access to care.

NOTE: SUBUTEX® (buprenorphine HCl sublingual tablets) is also approved for office-based treatment of opioid dependence (see How is SUBOXONE different from SUBUTEX?).

This means that with respect to tasks like inventory, record-keeping, etc. SUBOXONE is handled just like any other Schedule III medication dispensed by your pharmacy.

• Because a special waiver is required to prescribe SUBOXONE, your pharmacy will need to check that the prescribing physician's DEA number is valid (verifying a DEA number)

Physicians must write their "X" DEA number on all SUBOXONE and SUBUTEX prescriptions to treat opioid dependence.

As a pharmacist, the scope of your contribution—covering everything from the general (eg, stocking SUBOXONE) to the individual (eg, counseling patients about possible side effects)—allows you the opportunity to reinforce both patients' and physicians' efforts.

• Learning about opioid dependence and its treatment
• Helping opioid-dependent patients to feel at ease
• Counseling patients about potential drug-drug interactions
• Advising patients on the safe and appropriate use of their medications
• Ordering SUBOXONE and keeping it in stock
• Protecting patient confidentiality
• Verifying that physicians are certified to prescribe SUBOXONE
• Referring patients with opioid dependence to physicians certified to prescribe SUBOXONE
• Maintaining appropriate records

You may also be interested to read some of the more recent demographic and trend data for this patient population.

Also see How can I contribute to patients' success with SUBOXONE for more on how pharmacists can help support SUBOXONE patients.

• Complete an approved 8-hour CME course
• Notify the government of their intent to use SUBOXONE for treatment of opioid-dependent patients
• In addition, physicians must meet BOTH of the following criteria:
• Have the capacity to provide or to refer patients for necessary ancillary services, such as psychosocial therapy
• Agree to treat no more than 30 patients at any one time in their individual or group practice

Under DATA 2000, some physicians are exempt from the 8-hour CME requirement on the basis of their specialty or other professional experience (see Qualifications), but the other conditions listed above still apply.

Physicians interested in becoming certified to prescribe SUBOXONE are encouraged to visit www.buprenorphine.samhsa.gov, OpioidDependence.com, or DocOptIn.com.

See the full text of DATA 2000 for more information about certification requirements.

• Check that the physician's prescribing number begins with "X" (when a DATA 2000 waiver is granted, DEA issues the physician a unique identifier that always starts with "X"
• Physicians are required to include their "X" identifying number and their DEA registration number on all prescriptions for SUBOXONE and SUBUTEX written for treatment of opioid dependence
• Check the Substance Abuse and Mental Health Services (SAMHSA) physician locator at www.buprenorphine.samhsa.gov. This website lists some of the physicians in each state that have DATA 2000 waivers
• Some physicians elect not to be listed on this site
• Call SAMHSA at (866)287-2728 (866-BUP-CSAT) to verify a physician has a valid DATA 2000 waiver
• Call the physician directly and ask to have the DEA registration certificate containing the "X" identifier faxed to you

When verifying a physician's waiver, it may be a violation of federal regulations to disclose the name of the patient for whom the prescription was written—even if you are speaking with people who already know the patient is being treated for opioid dependence (eg, the prescribing physician). This subject is addressed in more detail in Are there confidentiality issues I should be aware of related to substance abuse treatment?

• Tolerance (defined as a need for substantially greater amounts of an opioid to achieve the desired effect or a substantially reduced effect with continued use of the same amount of the opioid)
• Withdrawal (which, for opioid dependence, is characterized by certain symptoms that appear when heavy or prolonged use of the opioid ceases or when an opioid antagonist is taken after a period of opioid use)
• Frequent use of larger amounts of the opioid than planned or use of it over a longer period of time than planned
• Persistent desire to cut down or control use of the opioid or trying unsuccessfully to do so
• Devotion of a great deal of time toward obtaining the opioid, using it, or recovering from its effects
• Surrendering of or reduction of important social, occupational, or recreational activities because of use of the opioid
• Continued use of the opioid despite knowing that one has a persistent or recurrent physical or psychological problem probably caused or made worse by the opioid

However, SUBOXONE also contains naloxone, an opioid antagonist, to help deter diversion and misuse (the ratio of buprenorphine to naloxone in SUBOXONE is 4:1).

When SUBOXONE is taken sublingually as prescribed, the naloxone is not absorbed into the bloodstream sufficiently to have any effect. However, if the tablet is crushed and injected by someone who either has recently used or is dependent on a full opioid agonist (eg, morphine, methadone, or heroin), the naloxone will cause that person to experience opioid withdrawal symptoms.

• Induction phase
• Treating pregnant women who prefer not to switch to methadone and for whom the potential benefit justifies the potential risk to the fetus
• Treating patients who cannot tolerate naloxone

See the SUBOXONE Dosing Guide for specific information about dosing during treatment.

Induction: The goal of induction is to safely suppress opioid withdrawal as rapidly as possible with adequate doses of SUBOXONE. Patients cannot begin their induction to SUBOXONE (and off of their previous opioid) until they are experiencing mild-to-moderate withdrawal symptoms.

Induction is complete when the patient experiences no withdrawal symptoms, no uncontrollable opioid cravings, and minimal to no side effects. The induction phase usually averages about 2 to 5 days.

Stabilization: During stabilization, the patient's SUBOXONE dose is "fine-tuned." The objective is to find the minimum dose necessary to keep the patient in treatment. After each dose adjustment, 3 to 7 days should be allowed for steady-state blood levels to be achieved. Stabilization can last anywhere from a week to several weeks.

Maintenance: The goals of the maintenance phase are to prevent opioid withdrawal symptoms, suppress opioid cravings, and greatly attenuate the use of self-administered opioids. The maintenance phase can last from months to years, depending on the individual.

Medically supervised withdrawal: In this phase, the SUBOXONE dose is slowly tapered. Patients may proceed directly to this phase from stabilization; however, maintenance is usually encouraged, because it is associated with a higher likelihood of treatment success.⁵ Mild withdrawal symptoms are possible as the SUBOXONE dose declines. Patients may elect to discontinue their taper and return to a previous (higher) dose at any time.

For more information on the different phases of treatment see Treatment Walk-through.

Other physicians write prescriptions for induction doses to be picked up at local pharmacies by the patients themselves

• Patients may be in the early stages of withdrawal when they pick up their induction prescription
• Some physicians may send patients' family members or close friends to pick up the induction doses

A prescribing physician may call or fax in the induction prescription, either to request delivery (if your pharmacy provides this service) or to ensure that the prescription is ready in advance of the patient's arrival. The physician cannot call in or fax a SUBOXONE prescription to your pharmacy without first obtaining the patient's signed consent. When the physician directly transmits SUBOXONE prescriptions to your pharmacy, further redisclosure of patient-identifying information by your pharmacy is prohibited, unless you also obtain signed consent from the patient.¹

Having the induction prescription filled before the patient arrives will make the process easier for the patient (again, she or he may be experiencing mild withdrawal symptoms).

During the induction phase, it is common for SUBOXONE prescriptions to be written for 1- to 3-day quantities as opposed to typical 30-day supplies. You should expect patients to come in frequently at the beginning of their SUBOXONE treatment.

For this reason, federal regulations protect the privacy of patients' medical information, namely Title 42 Part 2 of the Code of Federal Regulations (42 CFR Part 2) and the Health Insurance Portability and Accountability Act (HIPAA).

As a pharmacist, you are most likely already well acquainted with HIPAA, as well as HIPAA compliant.

You may not be as familiar with 42 CFR Part 2. In short, this regulation states that any patient-identifying information pertaining to treatment for substance abuse must be handled with a greater degree of confidentiality than patients' general medical information.

Under 42 CFR Part 2, before a physician can disclose any information to a third party about a patient's treatment for substance abuse, that physician must first obtain the patient's signed consent. Consequently, if a physician were to call in a patient's SUBOXONE prescription without first receiving the patient's signed consent to do so, that physician would be in violation of 42 CFR Part 2.

When a physician directly transmits a SUBOXONE prescription to your pharmacy, any redisclosure of that patient-identifying information by the pharmacy is prohibited without the patient's signed consent.

• Patient's name, physician's name, pharmacist's name
• Purpose of the disclosure; recipient of the disclosure
• What information will be released
• An indication that the patient understands he/she can revoke this consent at any time and that this revocation can be verbal
• The date and terms under which the consent expires
• Patient's dated signature

For more information, visit www.hipaa.samhsa.gov.

Please review the Important Safety Information that appears at the bottom of the screen. The full Prescribing Information may be accessed by clicking on the icon with that same name that appears at the top of this screen.

Despite of buprenorphine's favorable safety profile, caution is advised regarding its concomitant use with other sedatives, such as benzodiazepines, due to the additive effects exerted by buprenorphine.⁹ Inappropriate concomitant use (eg, higher doses than prescribed, parenteral administration) of psychotropics (especially benzodiazepines) and buprenorphine appears to be one of the risk factors for buprenorphine-related fatalities.^10,11

SUBOXONE patients may require a dose reduction if CYP 3A4 inhibitors such as azole antifungal agents (eg, ketoconazole), macrolide antibiotics (eg, erythromycin), or HIV protease inhibitors (eg, ritonavir) are coadministered.

• Buprenorphine is a partial mu-opioid agonist, so its maximal effect is less than that of a full mu-opioid agonist (eg, morphine, methadone, heroin)
• Buprenorphine dissociates slowly from the opioid receptors, thereby decreasing the intensity and delaying the onset of withdrawal symptoms

When SUBOXONE is taken sublingually by patients who have recently discontinued use of an opioid but are not yet experiencing mild-to-moderate withdrawal symptoms, SUBOXONE may cause the onset of withdrawal symptoms. "Precipitated withdrawal" occurs because buprenorphine has a higher affinity for the opioid receptors and will displace any full opioid agonist from the receptor. SUBOXONE's lower intrinsic activity results in a reduction of opioid activity which is experienced by patients as symptoms of withdrawal.

More information about buprenorphine is available under Treatment Advantages of a Partial Opioid Agonist.

One of the most valuable functions that you provide is counseling patients.

• Understand the importance of maintaining patient confidentiality
• Special federal regulations apply to how you verify prescriptions for SUBOXONE. These regulations deal with confidentiality of substance abuse treatment records (42 CFR Part 2) and the privacy of health records (HIPAA)
• Enhance patient confidentiality by providing a private area for patient counseling
• Counsel patients on the appropriate dosing instructions for SUBOXONE (see Dosing Instructions Tear Pad)
• Take into consideration that:
• These patients may be experiencing uncomfortable symptoms
• An accepting, positive attitude on your part is critically important to patients

• Order SUBOXONE through a pharmaceutical wholesaler.
• Follow the federal and state requirements that you use for stocking and dispensing other Schedule III medications. Pharmacists and pharmacies are not required to have any special credentials for dispensing these medications above or beyond those for other Schedule III medications.
• Verify if a physician has a waiver to prescribe SUBOXONE. You can do this in a number of ways, for example:
• Determine if a physician has prescribing rights. The DEA registration certificate should contain an "X" to prove the physician has prescribing rights
• Check the Substance Abuse and Mental Health Services Administration (SAMHSA) Physician Locator at www.buprenorphine.samhsa.gov. This website lists the physicians in each state that have DATA 2000 waivers
• Call SAMHSA at (866) 287-2728 (866-BUP-CSAT) to verify a physician has prescribing rights
• Or, call the physician directly and ask the physician to fax the DEA registration certificate to you
• Provide the names of physicians qualified to prescribe buprenorphine to customers who inquire about SUBOXONE treatment and to physicians whose practices serve people who may have developed opioid dependence. Qualified physicians can be found through:
• www.suboxone.com
• www.buprenorphine.samhsa.gov
• As with many prescription opioid medications that you dispense, take steps to avoid diversion by:
• Maintain open communication with physicians who prescribe SUBOXONE
• Being alert to patients presenting simultaneous prescriptions for SUBOXONE or other opioids from more than one physician
• Bearing in mind that the DATA 2000 allows each physician or group practice to treat no more than 30 patients with SUBOXONE at one time, and contacting the physician or group for verification should you receive a large number of prescriptions from any of these sources

The US Food and Drug Administration buprenorphine pages
(www.fda.gov/cder/drug/infopage/subutex_suboxone/default.htm) feature information for pharmacists, physicians, and patients, questions and answers about SUBOXONE and SUBUTEX, and a range of other information.

Detailed information about DATA 2000 and the physician waiver process can be found at www.buprenorphine.samhsa.gov or by contacting SAMHSA directly:

SAMHSA Buprenorphine Information Center
Phone: (866) 287-2728 (866-BUP-CSAT)
E-mail: info@buprenorphine.samhsa.gov