Suboxone (Buprenorphine HCl and naloxone HCl)
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Suboxone (Buprenorphine HCl and naloxone HCl)

SUBOXONE
(buprenorphine and naloxone)

DRUG DESCRIPTION

SUBOXONE (buprenorphine and naloxone) sublingual film is an orange film, imprinted with a logo identifying the product and strength in white ink. It contains buprenorphine HCl, a mu-opioid receptor partial agonist and a kappa-opioid receptor antagonist, and naloxone HCl dihydrate, an opioid receptor antagonist, at a ratio of 4:1 (ratio of free bases). It is intended for sublingual administration and is available in four dosage strengths, 2 mg buprenorphine with 0.5 mg naloxone, 4 mg buprenorphine with 1 mg naloxone, 8 mg buprenorphine with 2 mg naloxone, and 12 mg buprenorphine with 3 mg naloxone . Each sublingual film also contains polyethylene oxide, hydroxypropyl methylcellulose, maltitol, acesulfame potassium, lime flavor, citric acid, sodium citrate, FD&C yellow #6, and white ink.

Chemically, buprenorphine HCl is (2S)-2-[17-Cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6-methoxy-6α,14-ethano14α-morphinan-7α-yl]-3,3-dimethylbutan-2-ol hydrochloride. It has the following chemical structure:

Buprenorphine Structural Formula Illustration

Buprenorphine HCl has the molecular formula C29H41NO4 • HCl and the molecular weight is 504.10. It is a white or off-white crystalline powder, sparingly soluble in water, freely soluble in methanol, soluble in alcohol, and practically insoluble in cyclohexane.

Chemically, naloxone HCl dihydrate is 17-Allyl-4,5 α -epoxy-3, 14-dihydroxymorphinan-6-one hydrochloride dihydrate. It has the following chemical structure:

Naloxone Structural Formula Illustration

Naloxone hydrochloride dihydrate has the molecular formula C19H21NO4 • HCl • 2H 20 and the molecular weight is 399.87. It is a white to slightly off-white powder and is freely soluble in water, soluble in alcohol, and practically insoluble in toluene and ether.

What are the possible side effects of buprenorphine and naloxone (Suboxone)?

Buprenorphine and naloxone can cause drug dependence. This means that withdrawal symptoms may occur if you stop using the medicine too quickly. Withdrawal symptoms may also occur at the start of treatment due to dependence on another drug. Buprenorphine and naloxone is not for occasional ("as needed") use. Do not stop taking buprenorphine and naloxone without first talking to your doctor. Your doctor may want to gradually reduce the dose to avoid or minimize withdrawal symptoms.

Seek emergency medical attention or contact your doctor immediately if you experience any of...

Read All Potential Side Effects and See Pictures of Suboxone »

What are the precautions when taking buprenorphine hcl and naloxone hcl (Suboxone)?

Before taking this medication, tell your doctor or pharmacist if you are allergic to buprenorphine or naloxone; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: brain disorders (such as head injury, tumor, seizures), breathing problems (such as asthma, sleep apnea, chronic obstructive pulmonary disease-COPD), liver disease, mental/mood disorders (such as confusion, depression, thoughts of suicide), stomach/intestinal problems (such as blockage, constipation, diarrhea due to infection, paralytic ileus), difficulty urinating (such as due to enlarged...

Read All Potential Precautions of Suboxone »

Last reviewed on RxList: 8/29/2012
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

SUBOXONE sublingual film is indicated for maintenance treatment of opioid dependence and should be used as part of a complete treatment plan to include counseling and psychosocial support.

Under the Drug Addiction Treatment Act (DATA) codified at 21 U.S.C. 823(g), prescription use of this product in the treatment of opioid dependence is limited to physicians who meet certain qualifying requirements, and who have notified the Secretary of Health and Human Services (HHS) of their intent to prescribe this product for the treatment of opioid dependence and have been assigned a unique identification number that must be included on every prescription.

DOSAGE AND ADMINISTRATION

SUBOXONE sublingual film is administered sublingually as a single daily dose. SUBOXONE sublingual film should be used in patients who have been initially inducted using SUBUTEX® (buprenorphine) sublingual tablets.

Maintenance

  • SUBOXONE sublingual film is indicated for maintenance treatment. The recommended target dosage of SUBOXONE sublingual film is 16 mg/4 mg buprenorphine/nal oxone/day as a single daily dose.
  • The dosage of SUBOXONE sublingual film should be progressively adjusted in increments/decrements of 2 mg/0.5 mg or 4 mg/1 mg buprenorphine/naloxone to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms.
  • The maintenance dose of SUBOXONE sublingual film is generally in the range of 4 mg/1 mg buprenorphine/naloxone to 24 mg/6 mg buprenorphine/naloxone per day depending on the individual patient. Dosages higher than this have not been demonstrated to provide any clinical advantage.

Method of Administration

Do not cut, chew, or swallow SUBOXONE sublingual film. Place a sublingual film under the tongue. If an additional sublingual film is necessary to achieve the prescribed dose, place an additional sublingual film sublingually on the opposite side from the first film. Place the sublingual film in a manner to minimize overlapping as much as possible. The sublingual film must be kept under the tongue until the film is completely dissolved.

SUBOXONE sublingual film should NOT be moved after placement. Proper administration technique should be demonstrated to the patient.

Clinical Supervision

Treatment should be initiated with supervised administration, progressing to unsupervised administration as the patient's clinical stability permits. SUBOXONE sublingual film is subject to diversion and abuse. When determining the prescription quantity for unsupervised administration, consider the patient's level of stability, the security of his or her home situation, and other factors likely to affect the ability to manage supplies of take-home medication.

Ideally patients should be seen at reasonable intervals (e.g., at least weekly during the first month of treatment) based upon the individual circumstances of the patient. Medication should be prescribed in consideration of the frequency of visits. Provision of multiple refills is not advised early in treatment or without appropriate patient follow-up visits. Periodic assessment is necessary to determine compliance with the dosing regimen, effectiveness of the treatment plan, and overall patient progress.

Once a stable dosage has been achieved and patient assessment (e.g., urine drug screening) does not indicate illicit drug use, less frequent follow-up visits may be appropriate. A once-monthly visit schedule may be reasonable for patients on a stable dosage of medication who are making progress toward their treatment objectives. Continuation or modification of pharmacotherapy should be based on the physician's evaluation of treatment outcomes and objectives such as:

  1. Absence of medication toxicity.
  2. Absence of medical or behavioral adverse effects.
  3. Responsible handling of medications by the patient.
  4. Patient's compliance with all elements of the treatment plan (including recovery-oriented activities, psychotherapy, and/or other psychosocial modalities).
  5. Abstinence from illicit drug use (including problematic alcohol and/or benzodiazepine use).

If treatment goals are not being achieved, the physician should re-evaluate the appropriateness of continuing the current treatment.

Unstable Patients

Physicians will need to decide when they cannot appropriately provide further management for particular patients. For example, some patients may be abusing or dependent on various drugs, or unresponsive to psychosocial intervention such that the physician does not feel that he/she has the expertise to manage the patient. In such cases, the physician may want to assess whether to refer the patient to a specialist or more intensive behavioral treatment environment. Decisions should be based on a treatment plan established and agreed upon with the patient at the beginning of treatment.

Patients who continue to misuse, abuse, or divert buprenorphine products or other opioids should be provided with, or referred to, more intensive and structured treatment.

Stopping Treatment

The decision to discontinue therapy with SUBOXONE sublingual film after a period of maintenance should be made as part of a comprehensive treatment plan. Both gradual and abrupt discontinuation of buprenorphine has been used, but the data are insufficient to determine the best method of dose taper at the end of treatment.

Switching between SUBOXONE Sublingual Tablets and SUBOXONE Sublingual Film

Patients being switched between SUBOXONE sublingual tablets and SUBOXONE sublingual film should be started on the same dosage as the previously administered product. However, dosage adjustments may be necessary when switching between products. Not all strengths and combinations of the SUBOXONE sublingual films are bioequivalent to the SUBOXONE sublingual tablets as observed in pharmacokinetic studies [see CLINICAL PHARMACOLOGY]. Therefore, systemic exposures of buprenorphine and naloxone may be different when patients are switched from tablets to strips or vice-versa. Patients should be monitored for symptoms related to over-dosing or under-dosing.

Switching between SUBOXONE Sublingual Film strengths

As indicated in Table 1, the sizes and the compositions of the four units of SUBOXONE sublingual films, i.e., 2 mg/0.5 mg, 4 mg/2 mg, 8 mg/2 mg and the 12 mg/3 mg units, are different from one another. If patients switch between various combinations of lower and higher strength units of SUBOXONE sublingual films to obtain the same total dose, (e.g., from three 4 mg/1 mg units to a single 12 mg/3 mg unit, or vice-versa), systemic exposures of buprenorphine and naloxone may be different and patients should be monitored for over-dosing or under-dosing. For this reason, pharmacist should not substitute one or more film strengths for another without approval of the prescriber.

Table 1: Comparison of available Suboxone film strengths by dimensions and drug concentrations.

Suboxone film unit strength (buprenorphine/ naloxone) Suboxone film unit dimensions Buprenorphine Concentration % (w/w) Naloxone Concentration % (w/w)
2 mg/0.5 mg 22.0 mm x 12.8 mm 5.4 1.53
4 mg/1 mg (2 times the length of the 2 mg/0.5 mg unit) 22.0 mm x 25.6 mm 5.4 1.53
8 mg/2 mg 22.0 mm x 12.8 mm 17.2 4.88
12 mg/3 mg (1.5 times the length of the 8 mg/2 mg unit) 22 mm X 19.2 mm 17.2 4.88

HOW SUPPLIED

Dosage Forms And Strengths

SUBOXONE sublingual film is supplied as an orange rectangular sublingual film with a white printed logo in four dosage strengths:

  • buprenorphine/naloxone 2 mg/0.5 mg,
  • buprenorphine/naloxone 4 mg/1 mg,
  • buprenorphine/naloxone 8 mg/2 mg, and
  • buprenorphine/naloxone 12 mg/3 mg

Storage And Handling

SUBOXONE sublingual film is supplied as an orange rectangular sublingual film with a white printed logo in child-resistant polyester/foil laminated pouches:

NDC 12496-1202-3 (buprenorphine/naloxone 2 mg/0.5 mg/film; content expressed in terms of free base) - 30 films per carton

NDC 12496-1204-3 (buprenorphine/naloxone 4 mg/1 mg/film; content expressed in terms of free base) - 30 films per carton

NDC 12496-1208-3 (buprenorphine/naloxone 8 mg/2 mg/film; content expressed in terms of free base) 30 films per carton

NDC 12496-1212-3 (buprenorphine/naloxone 12 mg/3 mg/film; content expressed in terms of free base) - 30 films per carton

Store at 25°C (77°F), excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]

Patients should be advised to store buprenorphine-containing medications safely and out of sight and reach of children.

Manufactured for Reckitt Benckiser Pharmaceuticals Inc., Richmond, VA 23235 by: MonoSol Rx, LLC, Warren, NJ 07059. Distributed by: Reckitt Benckiser Pharmaceuticals Inc. Richmond, VA 23235. Revised August 2012

Last reviewed on RxList: 8/29/2012
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse Events in Clinical Trials - SUBOXONE sublingual film

The safety of SUBOXONE sublingual film is supported by clinical trials using SUBUTEX (buprenorphine) sublingual tablets and SUBOXONE (buprenorphine and naloxone) sublingual tablets, and other trials using buprenorphine sublingual solutions, as well as an open-label study in 194 patients treated with SUBOXONE sublingual film. In total, safety data from clinical studies are available from over 3000 opioid-dependent subjects exposed to buprenorphine at doses in the range used in the treatment of opioid dependence. Few differences in the adverse event profile were noted among SUBOXONE sublingual film, SUBOXONE (buprenorphine and naloxone) sublingual tablets, SUBUTEX (buprenorphine) sublingual tablets and a buprenorphine ethanolic sublingual solution.

The most common adverse event ( > 1%) associated with the sublingual administration of the SUBOXONE sublingual film was oral hypoesthesia. Other adverse events were constipation, glossodynia, oral mucosal erythema, vomiting, intoxication, disturbance in attention, palpitations, insomnia, withdrawal syndrome, hyperhidrosis, and blurred vision.

Other adverse event data were derived from larger, controlled studies of SUBOXONE (buprenorphine and naloxone) and SUBUTEX (buprenorphine) tablets and of buprenorphine sublingual solution. In a comparative study of SUBOXONE (buprenorphine and naloxone) and SUBUTEX (buprenorphine) sublingual tablets, adverse event profiles were similar for subjects treated with 16 mg/4 mg SUBOXONE (buprenorphine and naloxone) sublingual tablets or 16 mg SUBUTEX (buprenorphine) sublingual tablets. The following adverse events were reported to occur by at least 5% of patients in a 4-week study of SUBOXONE (buprenorphine and naloxone) sublingual tablets and SUBUTEX (buprenorphine) sublingual tablets.

Table 2: Adverse Events ( ≥ 5%) by Body System and Treatment Group in a 4-week Study

Body System/Adverse Event (COSTART Terminology) SUBOXONE (buprenorphine and naloxone) sublingual tablets 16 mg/4 mg/day
N=107
n (%)
SUBUTEX (buprenorphine) sublingual tablets 16 mg/day
N=103
n (%)

Placebo
N=107
n (%)

Body as a Whole
Asthenia 7 (6.5%) 5 (4.9%) 7 (6.5%)
Chills 8 (7.5%) 8 (7.8%) 8 (7.5%)
Headache 39 (36.4%) 30 (29.1%) 24 (22.4%)
Infection 6 (5.6%) 12 (11.7%) 7 (6.5%)
Pain 24 (22.4%) 19 (18.4%) 20 (18.7%)
Pain abdomen 12 (11.2%) 12 (11.7%) 7 (6.5%)
Pain back 4 (3.7%) 8 (7.8%) 12 (11.2%)
Withdrawal syndrome 27 (25.2%) 19 (18.4%) 40 (37.4%)
Cardiovascular System
Vasodilation 10 (9.3%) 4 (3.9%) 7 (6.5%)
Digestive System
Constipation 13 (12.1%) 8 (7.8%) 3 (2.8%)
Diarrhea 4 (3.7%) 5 (4.9%) 16 (15.0%)
Nausea 16 (15.0%) 14 (13.6%) 12 (11.2%)
Vomiting 8 (7.5%) 8 (7.8%) 5 (4.7%)
Nervous System
Insomnia 15 (14.0%) 22 (21.4%) 17 (15.9%)
Respiratory System
Rhinitis 5 (4.7%) 10 (9.7%) 14 (13.1%)
Skin And Appendages
Sweating 15 (14.0%) 13 (12.6%) 11 (10.3%)
Abbreviations: COSTART = Coding Symbols for Thesaurus of Adverse Reaction Terms.

The adverse event profile of buprenorphine was also characterized in the dose-controlled study of a buprenorphine ethanolic solution, over a range of doses in four months of treatment. Table 3 shows adverse events reported by at least 5% of subjects in any dose group in the dose-controlled trial.

Table 3: Adverse Events ( ≥ 5%) by Body System and Treatment Group in a 16-week Study

Body System/Adverse Event (COSTART Terminology) Buphrenorphine Dose
Very Low*
N=184
n (%)
Low*
N=180
n (%)
Moderate*
N=186
n (%)
High*
N=181
n (%)
Total*
N=731 n (%)
Body as a Whole
Abscess 9 (5%) 2 (1%) 3 (2%) 2 (1%) 16 (2%)
Asthenia 26 (14%) 28 (16%) 26 (14%) 24 (13%) 104 (14%)
Chills 11 (6%) 12 (7%) 9 (5%) 10 (6%) 42 (6%)
Fever 7 (4%) 2 (1%) 2 (1%) 10 (6%) 21 (3%)
Flu syndrome 4 (2%) 13 (7%) 19 (10%) 8 (4%) 44 (6%)
Headache 51 (28%) 62 (34%) 54 (29%) 53 (29%) 220 (30%)
Infection 32 (17%) 39 (22%) 38 (20%) 40 (22%) 149 (20%)
Injury accidental 5 (3%) 10 (6%) 5 (3%) 5 (3%) 25 (3%)
Pain 47 (26%) 37 (21%) 49 (26%) 44 (24%) 177 (24%)
Pain back 18 (10%) 29 (16%) 28 (15%) 27 (15%) 102 (14%)
Withdrawal syndrome 45 (24%) 40 (22%) 41 (22%) 36 (20%) 162 (22%)
Digestive System
Constipation 10 (5%) 23 (13%) 23 (12%) 26 (14%) 82 (11%)
Diarrhea 19 (10%) 8 (4%) 9 (5%) 4 (2%) 40 (5%)
Dyspepsia 6 (3%) 10 (6%) 4 (2%) 4 (2%) 24 (3%)
Nausea 12 (7%) 22 (12%) 23 (12%) 18 (10%) 75 (10%)
Vomiting 8 (4%) 6 (3%) 10 (5%) 14 (8%) 38 (5%)
Nervous System
Anxiety 22 (12%) 24 (13%) 20 (11%) 25 (14%) 91 (12%)
Depression 24 (13%) 16 (9%) 25 (13%) 18 (10%) 83 (11%)
Dizziness 4 (2%) 9 (5%) 7 (4%) 11 (6%) 31 (4%)
Insomnia 42 (23%) 50 (28%) 43 (23%) 51 (28%) 186 (25%)
Nervousness 12 (7%) 11 (6%) 10 (5%) 13 (7%) 46 (6%)
Somnolence 5 (3%) 13 (7%) 9 (5%) 11 (6%) 38 (5%)
Respiratory System
Cough increase 5 (3%) 11 (6%) 6 (3%) 4 (2%) 26 (4%)
Pharyngitis 6 (3%) 7 (4%) 6 (3%) 9 (5%) 28 (4%)
Rhinitis 27 (15%) 16 (9%) 15 (8%) 21 (12%) 79 (11%)
Skin and Appendages
Sweat 23 (13%) 21 (12%) 20 (11%) 23 (13%) 87 (12%)
Special Senses
Runny eyes 13 (7%) 9 (5%) 6 (3%) 6 (3%) 34 (5%)
*Sublingual solution. Doses in this table cannot necessarily be delivered in tablet form, but for comparison purposes:
1 mg solution would be less than a tablet dose of 2 mg
4 mg solution approximates a 6 mg tablet dose
8 mg solution approximates a 12 mg tablet dose
16 mg solution approximates a 24 mg tablet dose

Adverse Events – Post-marketing Experience with Suboxone Sublingual Tablets

The most frequently reported post-marketing adverse event not observed in clinical trials was peripheral edema.

Read the Suboxone (buprenorphine hcl and naloxone hcl) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

Cytochrome P-450 3A4 (CYP3A4) Inhibitors and Inducers

Buprenorphine is metabolized to norbuprenorphine primarily by cytochrome CYP3A4; therefore, potential interactions may occur when SUBOXONE sublingual film is given concurrently with agents that affect CYP3A4 activity. The concomitant use of SUBOXONE sublingual film with CYP3A4 inhibitors (e.g., azole antifungals such as ketoconazole, macrolide antibiotics such as erythromycin, and HIV protease inhibitors) should be monitored and may require dose-reduction of one or both agents.

The interaction of buprenorphine with CYP3A4 inducers has not been studied; therefore, it is recommended that patients receiving SUBOXONE sublingual film be monitored for signs and symptoms of opioid withdrawal if inducers of CYP3A4 (e.g., efavirenz, phenobarbital, carbamazepine, phenytoin, rifampicin) are co-administered [see CLINICAL PHARMACOLOGY].

Antiretrovirals

Three classes of antiretroviral agents have been evaluated for CYP3A4 interactions with buprenorphine. Nucleoside reverse transcriptase inhibitors (NRTIs) do not appear to induce or inhibit the P450 enzyme pathway, thus no interactions with buprenorphine are expected. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are metabolized principally by CYP3A4. Efavirenz, nevirapine and etravirine are known CYP3A inducers whereas delaviridine is a CYP3A inhibitor. Significant pharmacokinetic interactions between NNRTIs (e.g., efavirenz and delavirdine) and buprenorphine have been shown in clinical studies, but these pharmacokinetic interactions did not result in any significant pharmacodynamic effects. It is recommended that patients who are on chronic buprenorphine treatment have their dose monitored if NNRTIs are added to their treatment regimen. Studies have shown some antiretroviral protease inhibitors (PIs) with CYP3A4 inhibitory activity (nelfinavir, lopinavir/ritonavir, ritonavir) have little effect on buprenorphine pharmacokinetic and no significant pharmacodynamic effects. Other PIs with CYP3A4 inhibitory activity (atazanavir and atazanavir/ritonavir) resulted in elevated levels of buprenorphine and norbuprenorphine and patients in one study reported increased sedation. Symptoms of opioid excess have been found in post-marketing reports of patients receiving buprenorphine and atazanavir with and without ritonavir concomitantly. Monitoring of patients taking buprenorphine and atazanavir with and without ritonavir is recommended, and dose reduction of buprenorphine may be warranted.

Benzodiazepines

There have been a number of post-marketing reports regarding coma and death associated with the concomitant use of buprenorphine and benzodiazepines. In many, but not all, of these cases, buprenorphine was misused by self-injection. Preclinical studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. SUBOXONE sublingual film should be prescribed with caution to patients taking benzodiazepines or other drugs that act on the CNS, regardless of whether these drugs are taken on the advice of a physician or are being abused/misused. Patients should be warned that it is extremely dangerous to self-administer non-prescribed benzodiazepines while taking SUBOXONE sublingual film, and should also be cautioned to use benzodiazepines concurrently with SUBOXONE sublingual film only as directed by their physician.

Drug Abuse And Dependence

Controlled Substance

Buprenorphine is a Schedule III narcotic under the Controlled Substances Act.

Under the Drug Addiction Treatment Act (DATA) codified at 21 U.S.C. 823(g), prescription use of this product in the treatment of opioid dependence is limited to physicians who meet certain qualifying requirements, and who have notified the Secretary of Health and Human Services (HHS) of their intent to prescribe this product for the treatment of opioid dependence and have been assigned a unique identification number that must be included on every prescription.

Abuse

Buprenorphine, like morphine and other opioids, has the potential for being abused and is subject to criminal diversion. This should be considered when prescribing or dispensing buprenorphine in situations when the clinician is concerned about an increased risk of misuse, abuse, or diversion. Healthcare professionals should contact their state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

Patients who continue to misuse, abuse, or divert buprenorphine products or other opioids should be provided with or referred for more intensive and structured treatment.

Abuse of buprenorphine poses a risk of overdose and death. This risk is increased with the abuse of buprenorphine and alcohol and other substances, especially benzodiazepines.

The physician may be able to more easily detect misuse or diversion by maintaining records of medication prescribed including date, dose, quantity, frequency of refills, and renewal requests of medication prescribed. Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper handling and storage of the medication are appropriate measures that help to limit abuse of opioid drugs.

Dependence

Buprenorphine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid type, characterized by moderate withdrawal signs and symptoms upon abrupt discontinuation or rapid taper. The withdrawal syndrome is typically milder than seen with full agonists and may be delayed in onset [see WARNINGS AND PRECAUTIONS].

A neonatal withdrawal syndrome has been reported in the infants of women treated with buprenorphine during pregnancy [see WARNINGS AND PRECAUTIONS].

Last reviewed on RxList: 8/29/2012
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Abuse Potential

Buprenorphine can be abused in a manner similar to other opioids, legal or illicit. Prescribe and dispense buprenorphine with appropriate precautions to minimize risk of misuse, abuse, or diversion, and ensure appropriate protection from theft, including in the home. Clinical monitoring appropriate to the patient's level of stability is essential. Multiple refills should not be prescribed early in treatment or without appropriate patient follow-up visits. [see Drug Abuse and Dependence].

Respiratory Depression

Buprenorphine, particularly when taken by the IV route, in combination with benzodiazepines or other CNS depressants (including alcohol), has been associated with significant respiratory depression and death. Many, but not all, post-marketing reports regarding coma and death associated with the concomitant use of buprenorphine and benzodiazepines involved misuse by self-injection. Deaths have also been reported in association with concomitant administration of buprenorphine with other depressants such as alcohol or other CNS depressant drugs. Patients should be warned of the potential danger of self-administration of benzodiazepines or other depressants while under treatment with SUBOXONE sublingual film. [see DRUG INTERACTIONS].

In the case of overdose, the primary management should be the re-establishment of adequate ventilation with mechanical assistance of respiration, if required. Naloxone may be of value for the management of buprenorphine overdose. Higher than normal doses and repeated administration may be necessary.

SUBOXONE sublingual film should be used with caution in patients with compromised respiratory function (e.g., chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression).

CNS Depression

Patients receiving buprenorphine in the presence of opioid analgesics, general anesthetics, benzodiazepines, phenothiazines, other tranquilizers, sedative/hypnotics, or other CNS depressants (including alcohol) may exhibit increased CNS depression. Consider dose reduction of CNS depressants, SUBOXONE sublingual film, or both in situations of concomitant prescription. [see DRUG INTERACTIONS].

Unintentional Pediatric Exposure

Buprenorphine can cause severe, possibly fatal, respiratory depression in children who are accidentally exposed to it. Store buprenorphine-containing medications safely out of the sight and reach of children.

Dependence

Buprenorphine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid type, characterized by withdrawal signs and symptoms upon abrupt discontinuation or rapid taper. The withdrawal syndrome is typically milder than seen with full agonists and may be delayed in onset. Buprenorphine can be abused in a manner similar to other opioids. This should be considered when prescribing or dispensing buprenorphine in situations when the clinician is concerned about an increased risk of misuse, abuse, or diversion. [see Drug Abuse and Dependence]

Hepatitis, Hepatic Events

Cases of cytolytic hepatitis and hepatitis with jaundice have been observed in individuals receiving buprenorphine in clinical trials and through post-marketing adverse event reports. The spectrum of abnormalities ranges from transient asymptomatic elevations in hepatic transaminases to case reports of death, hepatic failure, hepatic necrosis, hepatorenal syndrome, and hepatic encephalopathy. In many cases, the presence of pre-existing liver enzyme abnormalities, infection with hepatitis B or hepatitis C virus, concomitant usage of other potentially hepatotoxic drugs, and ongoing injecting drug use may have played a causative or contributory role. In other cases, insufficient data were available to determine the etiology of the abnormality. Withdrawal of buprenorphine has resulted in amelioration of acute hepatitis in some cases; however, in other cases no dose reduction was necessary. The possibility exists that buprenorphine had a causative or contributory role in the development of the hepatic abnormality in some cases. Liver function tests, prior to initiation of treatment is recommended to establish a baseline. Periodic monitoring of liver function during treatment is also recommended. A biological and etiological evaluation is recommended when a hepatic event is suspected. Depending on the case, SUBOXONE sublingual film may need to be carefully discontinued to prevent withdrawal signs and symptoms and a return by the patient to illicit drug use, and strict monitoring of the patient should be initiated.

Allergic Reactions

Cases of hypersensitivity to buprenorphine and naloxone containing products have been reported both in clinical trials and in the post-marketing experience. Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported. The most common signs and symptoms include rashes, hives, and pruritus. A history of hypersensitivity to buprenorphine or naloxone is a contraindication to the use of SUBOXONE sublingual film.

Precipitation of Opioid Withdrawal Signs and Symptoms

Because it contains naloxone, SUBOXONE sublingual film is highly likely to produce marked and intense withdrawal signs and symptoms if misused parenterally by individuals dependent on full opioid agonists such as heroin, morphine, or methadone. Because of the partial agonist properties of buprenorphine, SUBOXONE sublingual film may precipitate opioid withdrawal signs and symptoms in such persons if administered sublingually before the agonist effects of the opioid have subsided.

Neonatal Withdrawal

Neonatal withdrawal has been reported in the infants of women treated with buprenorphine during pregnancy. From post-marketing reports, the time to onset of neonatal withdrawal signs ranged from Day 1 to Day 8 of life with most cases occurring on Day 1. Adverse events associated with the neonatal withdrawal syndrome included hypertonia, neonatal tremor, neonatal agitation, and myoclonus, and there have been reports of convulsions, apnea, respiratory depression, and bradycardia.

Use in Opioid Naïve Patients

There have been reported deaths of opioid naive individuals who received a 2 mg dose of buprenorphine as a sublingual tablet for analgesia. SUBOXONE sublingual film is not appropriate as an analgesic.

Impairment of Ability to Drive or Operate Machinery

SUBOXONE sublingual film may impair the mental or physical abilities required for the performance of potentially dangerous tasks such as driving a car or operating machinery, especially during treatment induction and dose adjustment. Patients should be cautioned about driving or operating hazardous machinery until they are reasonably certain that SUBOXONE sublingual film therapy does not adversely affect his or her ability to engage in such activities.

Orthostatic Hypotension

Like other opioids, SUBOXONE sublingual film may produce orthostatic hypotension in ambulatory patients.

Elevation of Cerebrospinal Fluid Pressure

Buprenorphine, like other opioids, may elevate cerebrospinal fluid pressure and should be used with caution in patients with head injury, intracranial lesions, and other circumstances when cerebrospinal pressure may be increased. Buprenorphine can produce miosis and changes in the level of consciousness that may interfere with patient evaluation.

Elevation of Intracholedochal Pressure

Buprenorphine has been shown to increase intracholedochal pressure, as do other opioids, and thus should be administered with caution to patients with dysfunction of the biliary tract.

Effects in Acute Abdominal Conditions

As with other opioids, buprenorphine may obscure the diagnosis or clinical course of patients with acute abdominal conditions.

General Precautions

SUBOXONE sublingual film should be administered with caution in debilitated patients and those with myxedema or hypothyroidism, adrenal cortical insufficiency (e.g., Addison's disease); CNS depression or coma; toxic psychoses; prostatic hypertrophy or urethral stricture; acute alcoholism; delirium tremens; or kyphoscoliosis.

Patient Counseling Information

See FDA-approved patient labeling (Medication Guide)

Patients should be advised NOT to cut, chew or swallow SUBOXONE sublingual film.

Safe Use

Before initiating treatment with Suboxone, explain the points listed below to caregivers and patients. Instruct patients to read the Medication Guide each time Suboxone is dispensed because new information may be available.

  • Patients should be warned that it is extremely dangerous to self-administer non-prescribed benzodiazepines or other CNS depressants (including alcohol) while taking SUBOXONE sublingual film. Patients prescribed benzodiazepines or other CNS depressants should be cautioned to use them only as directed by their physician. [see WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS]
  • Patients should be advised that SUBOXONE sublingual film contains an opioid that can be a target for people who abuse prescription medications or street drugs. Patients should be cautioned to keep their films in a safe place, and to protect them from theft.
  • Patients should be instructed to keep SUBOXONE sublingual film in a secure place, out of the sight and reach of children. Accidental or deliberate ingestion by a child may cause respiratory depression that can result in death. Patients should be advised that if a child is exposed to SUBOXONE sublingual film, medical attention should be sought immediately.
  • Patients should be advised never to give SUBOXONE sublingual film to anyone else, even if he or she has the same signs and symptoms. It may cause harm or death.
  • Patients should be advised that selling or giving away this medication is against the law.
  • Patients should be cautioned that SUBOXONE sublingual film may impair the mental or physical abilities required for the performance of potentially dangerous tasks such as driving or operating machinery. Caution should be taken especially during drug induction and dose adjustment and until individuals are reasonably certain that buprenorphine therapy does not adversely affect their ability to engage in such activities. [see WARNINGS AND PRECAUTIONS]
  • Patients should be advised not to change the dosage of SUBOXONE sublingual film without consulting their physician.
  • Patients should be advised to take SUBOXONE sublingual film once a day.
  • Patients should be informed that SUBOXONE sublingual film can cause drug dependence and that withdrawal signs and symptoms may occur when the medication is discontinued.
  • Patients seeking to discontinue treatment with buprenorphine for opioid dependence should be advised to work closely with their physician on a tapering schedule and should be apprised of the potential to relapse to illicit drug use associated with discontinuation of opioid agonist/partial agonist medication-assisted treatment.
  • Patients should be cautioned that, like other opioids, SUBOXONE sublingual film may produce orthostatic hypotension in ambulatory individuals. [see WARNINGS AND PRECAUTIONS]
  • Patients should inform their physician if any other prescription medications, over-the-counter medications, or herbal preparations are prescribed or currently being used. [see DRUG INTERACTIONS]
  • Women of childbearing potential who become pregnant or are planning to become pregnant, should be advised to consult their physician regarding the possible effects of using SUBOXONE sublingual film during pregnancy. [see Use In Specific Populations]
  • Patients should be warned that buprenorphine passes into breast milk. Breast-feeding is not advised in mothers treated with buprenorphine products. [see Use In Specific Populations].
  • Patients should inform their family members that, in the event of emergency, the treating physician or emergency room staff should be informed that the patient is physically dependent on an opioid and that the patient is being treated with SUBOXONE sublingual film.
  • Refer to the Medication Guide for additional information regarding the counseling information.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity

Carcinogenicity data on SUBOXONE sublingual film are not available.

A carcinogenicity study of buprenorphine/naloxone (4:1 ratio of the free bases) was performed in Alderley Park rats. Buprenorphine/naloxone was administered in the diet at doses of approximately 7, 31, and 123 mg/kg/day for 104 weeks (estimated exposure was approximately 4, 18, and 44 times the recommended human sublingual dose of 16 mg/4 mg buprenorphine/naloxone based on buprenorphine AUC comparisons). A statistically significant increase in Leydig cell adenomas was observed in all dose groups. No other drug-related tumors were noted.

Carcinogenicity studies of buprenorphine were conducted in Sprague-Dawley rats and CD-1 mice. Buprenorphine was administered in the diet to rats at doses of 0.6, 5.5, and 56 mg/kg/day (estimated exposure was approximately 0.4, 3, and 35 times the recommended human daily sublingual dose of 16 mg on a mg/m² basis) for 27 months. As in the buprenorphine/naloxone carcinogenicity study in rat, statistically significant dose-related increases in Leydig cell tumors occurred. In an 86-week study in CD-1 mice, buprenorphine was not carcinogenic at dietary doses up to 100 mg/kg/day (estimated exposure was approximately 30 times the recommended human daily sublingual dose of 16 mg on a mg/m² basis).

Mutagenicity

The 4:1 combination of buprenorphine and naloxone was not mutagenic in a bacterial mutation assay (Ames test) using four strains of S. typhimurium and two strains of E. coli. The combination was not clastogenic in an in vitro cytogenetic assay in human lymphocytes or in an IV micronucleus test in the rat.

Buprenorphine was studied in a series of tests utilizing gene, chromosome, and DNA interactions in both prokaryotic and eukaryotic systems. Results were negative in yeast (S. cerevisiae) for recombinant, gene convertant, or forward mutations; negative in Bacillus subtilis “rec” assay, negative for clastogenicity in CHO cells, Chinese hamster bone marrow and spermatogonia cells, and negative in the mouse lymphoma L5178Y assay.

Results were equivocal in the Ames test: negative in studies in two laboratories, but positive for frame shift mutation at a high dose (5mg/plate) in a third study. Results were positive in the Green-Tweets (E. coli) survival test, positive in a DNA synthesis inhibition (DSI) test with testicular tissue from mice, for both in vivo and in vitro incorporation of [3H]thymidine, and positive in unscheduled DNA synthesis (UDS) test using testicular cells from mice.

Impairment of Fertility

Dietary administration of buprenorphine in the rat at dose levels of 500 ppm or greater (equivalent to approximately 47 mg/kg/day or greater; estimated exposure approximately 28 times the recommended human daily sublingual dose of 16 mg on a mg/m² basis) produced a reduction in fertility demonstrated by reduced female conception rates. A dietary dose of 100 ppm (equivalent to approximately 10 mg/kg/day; estimated exposure approximately 6 times the recommended human daily sublingual dose of 16 mg on a mg/m² basis) had no adverse effect on fertility.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies of SUBOXONE sublingual film or buprenorphine/naloxone in pregnant women. SUBOXONE sublingual film should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Teratogenic Effects

Effects on embryo-fetal development were studied in Sprague-Dawley rats and Russian white rabbits following oral (1:1) and intramuscular (IM) (3:2) administration of mixtures of buprenorphine and naloxone. Following oral administration to rats and rabbits, no teratogenic effects were observed at buprenorphine doses up to 250 mg/kg/day and 40 mg/kg/day, respectively (estimated exposure approximately 150 times and 50 times, respectively, the recommended human daily sublingual dose of 16 mg on a mg/m² basis). No definitive drug-related teratogenic effects were observed in rats and rabbits at IM doses up to 30 mg/kg/day (estimated exposure approximately 20 times and 35 times, respectively, the recommended human daily dose of 16 mg on a mg/m² basis). Acephalus was observed in one rabbit fetus from the low-dose group and omphalocele was observed in two rabbit fetuses from the same litter in the mid-dose group; no findings were observed in fetuses from the high-dose group. Following oral administration of buprenorphine to rats, dose-related post-implantation losses, evidenced by increases in the numbers of early resorptions with consequent reductions in the numbers of fetuses, were observed at doses of 10 mg/kg/day or greater (estimated exposure approximately 6 times the recommended human daily sublingual dose of 16 mg on a mg/m² basis). In the rabbit, increased post-implantation losses occurred at an oral dose of 40 mg/kg/day. Following IM administration in the rat and the rabbit, post-implantation losses, as evidenced by decreases in live fetuses and increases in resorptions, occurred at 30 mg/kg/day.

Buprenorphine was not teratogenic in rats or rabbits after IM or subcutaneous (SC) doses up to 5 mg/kg/day (estimated exposure was approximately 3 and 6 times, respectively, the recommended human daily sublingual dose of 16 mg on a mg/m² basis), after IV doses up to 0.8 mg/kg/day (estimated exposure was approximately 0.5 times and equal to, respectively, the recommended human daily sublingual dose of 16 mg on a mg/m² basis), or after oral doses up to 160 mg/kg/day in rats (estimated exposure was approximately 95 times the recommended human daily sublingual dose of 16 mg on a mg/m² basis) and 25 mg/kg/day in rabbits (estimated exposure was approximately 30 times the recommended human daily sublingual dose of 16 mg on a mg/m² basis). Significant increases in skeletal abnormalities (e.g., extra thoracic vertebra or thoraco-lumbar ribs) were noted in rats after SC administration of 1 mg/kg/day and up (estimated exposure was approximately 0.6 times the recommended human daily sublingual dose of 16 mg on a mg/m² basis), but were not observed at oral doses up to 160 mg/kg/day. Increases in skeletal abnormalities in rabbits after IM administration of 5 mg/kg/day (estimated exposure was approximately 6 times the recommended human daily sublingual dose of 16 mg on a mg/m² basis) or oral administration of 1 mg/kg/day or greater (estimated exposure was approximately equal to the recommended human daily sublingual dose of 16 mg on a mg/m² basis) were not statistically significant.

In rabbits, buprenorphine produced statistically significant pre-implantation losses at oral doses of 1 mg/kg/day or greater and post-implantation losses that were statistically significant at IV doses of 0.2 mg/kg/day or greater (estimated exposure approximately 0.3 times the recommended human daily sublingual dose of 16 mg on a mg/m² basis).

Non-teratogenic Effects

Dystocia was noted in pregnant rats treated intramuscularly with buprenorphine 5 mg/kg/day (approximately 3 times the recommended human daily sublingual dose of 16 mg on a mg/m² basis). Fertility, peri-, and post-natal development studies with buprenorphine in rats indicated increases in neonatal mortality after oral doses of 0.8 mg/kg/day and up (approximately 0.5 times the recommended human daily sublingual dose of 16 mg on a mg/m² basis), after IM doses of 0.5 mg/kg/day and up (approximately 0.3 times the recommended human daily sublingual dose of 16 mg on a mg/m² basis), and after SC doses of 0.1 mg/kg/day and up (approximately 0.06 times the recommended human daily sublingual dose of 16 mg on a mg/m² basis). Delays in the occurrence of righting reflex and startle response were noted in rat pups at an oral dose of 80 mg/kg/day (approximately 50 times the recommended human daily sublingual dose of 16 mg on a mg/m² basis).

Nursing Mothers

Buprenorphine passes into breast milk. Breast-feeding is not advised in mothers treated with buprenorphine products. An apparent lack of milk production during general reproduction studies with buprenorphine in rats caused decreased viability and lactation indices.

Pediatric Use

The safety and effectiveness of SUBOXONE sublingual film have not been established in pediatric patients.

Geriatric Use

Clinical studies of SUBOXONE sublingual film, SUBOXONE (buprenorphine and naloxone) sublingual tablets, or SUBUTEX (buprenorphine) sublingual tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Hepatic Impairment

The effect of hepatic impairment on the pharmacokinetics of buprenorphine and naloxone is unknown. Since both drugs are extensively metabolized, the plasma levels will be expected to be higher in patients with moderate and severe hepatic impairment. However, it is not known whether both drugs are affected to the same degree. Therefore, dosage should be adjusted and patients should be watched for signs and symptoms of precipitated opioid withdrawal.

Renal Impairment

No differences in buprenorphine pharmacokinetics were observed between 9 dialysis-dependent and 6 normal patients following IV administration of 0.3 mg buprenorphine. The effects of renal failure on naloxone pharmacokinetics are unknown.

Last reviewed on RxList: 8/29/2012
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

The manifestations of acute overdose include pinpoint pupils, sedation, hypotension, respiratory depression, and death.

In the event of overdose, the respiratory and cardiac status of the patient should be monitored carefully. When respiratory or cardiac functions are depressed, primary attention should be given to the re-establishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. Oxygen, IV fluids, vasopressors, and other supportive measures should be employed as indicated.

In the case of overdose, the primary management should be the re-establishment of adequate ventilation with mechanical assistance of respiration, if required. Naloxone may be of value for the management of buprenorphine overdose. Higher than normal doses and repeated administration may be necessary.

CONTRAINDICATIONS

SUBOXONE sublingual film should not be administered to patients who have been shown to be hypersensitive to buprenorphine or naloxone as serious adverse reactions, including anaphylactic shock, have been reported [see WARNINGS AND PRECAUTIONS].

Last reviewed on RxList: 8/29/2012
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

SUBOXONE sublingual film contains buprenorphine and naloxone. Buprenorphine is a partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor. Naloxone is a potent antagonist at mu-opioid receptors and produces opioid withdrawal signs and symptoms in individuals physically dependent on full opioid agonists when administered parenterally.

Pharmacodynamics

Subjective Effects

Comparisons of buprenorphine to full opioid agonists such as methadone and hydromorphone suggest that sublingual buprenorphine produces typical opioid agonist effects which are limited by a ceiling effect. In opioid-experienced subjects who were not physically dependent, acute sublingual doses of buprenorphine/naloxone tablets produced opioid agonist effects which reached a maximum between doses of 8 mg/2 mg and 16 mg/4 mg buprenorphine/naloxone.

Opioid agonist ceiling-effects were also observed in a double-blind, parallel group, dose-ranging comparison of single doses of buprenorphine sublingual solution (1, 2, 4, 8, 16, or 32 mg), placebo and a full agonist control at various doses. The treatments were given in ascending dose order at intervals of at least one week to 16 opioid-experienced subjects who were not physically dependent. Both active drugs produced typical opioid agonist effects. For all measures for which the drugs produced an effect, buprenorphine produced a dose-related response. However, in each case, there was a dose that produced no further effect. In contrast, the highest dose of the full agonist control always produced the greatest effects. Agonist objective rating scores remained elevated for the higher doses of buprenorphine (8-32 mg) longer than for the lower doses and did not return to baseline until 48 hours after drug administration. The onset of effects appeared more rapidly with buprenorphine than with the full agonist control, with most doses nearing peak effect after 100 minutes for buprenorphine compared to 150 minutes for the full agonist control.

Physiologic Effects

Buprenorphine in IV (2, 4, 8, 12 and 16 mg) and sublingual (12 mg) doses has been administered to opioid-experienced subjects who were not physically dependent to examine cardiovascular, respiratory, and subjective effects at doses comparable to those used for treatment of opioid dependence. Compared to placebo, there were no statistically significant differences among any of the treatment conditions for blood pressure, heart rate, respiratory rate, O2 saturation, or skin temperature across time. Systolic BP was higher in the 8 mg group than placebo (3-hour AUC values). Minimum and maximum effects were similar across all treatments. Subjects remained responsive to low voice and responded to computer prompts. Some subjects showed irritability, but no other changes were observed.

The respiratory effects of sublingual buprenorphine were compared with the effects of methadone in a double-blind, parallel group, dose ranging comparison of single doses of buprenorphine sublingual solution (1, 2, 4, 8, 16, or 32 mg) and oral methadone (15, 30, 45, or 60 mg) in non-dependent, opioid-experienced volunteers. In this study, hypoventilation not requiring medical intervention was reported more frequently after buprenorphine doses of 4 mg and higher than after methadone. Both drugs decreased O2 saturation to the same degree.

Effect of Naloxone

Physiologic and subjective effects following acute sublingual administration of buprenorphine tablets and buprenorphine/naloxone tablets were similar at equivalent dose levels of buprenorphine. Naloxone had no clinically significant effect when administered by the sublingual route, although blood levels of the drug were measurable. Buprenorphine/naloxone, when administered sublingually to an opioid-dependent cohort, was recognized as an opioid agonist, whereas when administered intramuscularly, combinations of buprenorphine with naloxone produced opioid antagonist actions similar to naloxone. This finding suggests that the naloxone in buprenorphine/naloxone tablets may deter injection of buprenorphine/naloxone tablets by persons with active substantial heroin or other full mu-opioid dependence. However, clinicians should be aware that some opioid-dependent persons, particularly those with a low level of full mu-opioid physical dependence or those whose opioid physical dependence is predominantly to buprenorphine, abuse buprenorphine/naloxone combinations by the intravenous or intranasal route. In methadone-maintained patients and heroin-dependent subjects, IV administration of buprenorphine/naloxone combinations precipitated opioid withdrawal signs and symptoms and was perceived as unpleasant and dysphoric. In morphine-stabilized subjects, intravenously administered combinations of buprenorphine with naloxone produced opioid antagonist and withdrawal signs and symptoms that were ratio-dependent; the most intense withdrawal signs and symptoms were produced by 2:1 and 4:1 ratios, less intense by an 8:1 ratio.

Pharmacokinetics

Absorption

In pharmacokinetic studies, the 2 mg/0.5 mg and 4 mg/1 mg doses administered as SUBOXONE sublingual films showed comparable relative bioavailability to the same total dose of SUBOXONE sublingual tablets. whereas the 8 mg/2 mg and 12 mg/3 mg doses administered as SUBOXONE sublingual films showed higher relative bioavailability for both buprenorphine and naloxone compared to the same total dose of SUBOXONE sublingual tablets. A combination of one 8 mg/2 mg and two 2 mg/0.5 mg SUBOXONE sublingual films (total dose of 12 mg/ 3 mg) showed comparable relative bioavailability to the same total dose of SUBOXONE sublingual tablets [See DOSAGE AND ADMINISTRATION].

Distribution

Buprenorphine is approximately 96% protein bound, primarily to alpha and beta globulin. Naloxone is approximately 45% protein bound, primarily to albumin.

Metabolism

Buprenorphine undergoes both N-dealkylation to norbuprenorphine and glucuronidation. The N-dealkylation pathway is mediated primarily by the CYP3A4. Norbuprenorphine, the major metabolite, can further undergo glucuronidation. Norbuprenorphine has been found to bind opioid receptors in-vitro; however, it has not been studied clinically for opioid-like activity. Naloxone undergoes direct glucuronidation to naloxone-3-glucuronide as well as N-dealkylation, and reduction of the 6-oxo group.

Elimination

A mass balance study of buprenorphine showed complete recovery of radiolabel in urine (30%) and feces (69%) collected up to 11 days after dosing. Almost all of the dose was accounted for in terms of buprenorphine, norbuprenorphine, and two unidentified buprenorphine metabolites. In urine, most of buprenorphine and norbuprenorphine was conjugated (buprenorphine, 1% free and 9.4% conjugated; norbuprenorphine, 2.7% free and 11% conjugated). In feces, almost all of the buprenorphine and norbuprenorphine were free (buprenorphine, 33% free and 5% conjugated; norbuprenorphine, 21% free and 2% conjugated). Based on all studies performed with SUBOXONE sublingual film, buprenorphine has a mean elimination half-life from plasma ranging from 24 to 42 hours and naloxone has a mean elimination half-life from plasma ranging from 2 to 12 hours.

Drug-drug Interactions

CYP3A4 Inhibitors and Inducers: Subjects receiving SUBOXONE sublingual film should be monitored if inhibitors of CYP3A4 such as azole antifungal agents (e.g., ketoconazole), macrolide antibiotics (e.g., erythromycin) or HIV protease inhibitors and may require dose-reduction of one or both agents. The interaction of buprenorphine with all CYP3A4 inducers has not been studied, therefore it is recommended that patients receiving SUBOXONE sublingual film be monitored for signs and symptoms of opioid withdrawal if inducers of CYP3A4 (e.g., phenobarbital, carbamazepine, phenytoin, rifampicin) are co-administered [See DRUG INTERACTIONS].

Buprenorphine has been found to be a CYP2D6 and CYP3A4 inhibitor and its major metabolite, norbuprenorphine, has been found to be a moderate CYP2D6 inhibitor in in-vitro studies employing human liver microsomes. However, the relatively low plasma concentrations of buprenorphine and norbuprenorphine resulting from therapeutic doses are not expected to raise significant drug-drug interaction concerns.

Last reviewed on RxList: 8/29/2012
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

SUBOXONE®
(Sub-OX-own)
(buprenorphine and naloxone) Sublingual Film

IMPORTANT:

Keep SUBOXONE in a secure place away from children. Accidental use by a child is a medical emergency and can result in death. If a child accidentally uses SUBOXONE, get emergency help right away.

Read this Medication Guide that comes with SUBOXONE before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor. Talk to your doctor or pharmacist if you have questions about SUBOXONE.

Share the important information in this Medication Guide with members of your household.

What is the most important information I should know about SUBOXONE?

  • SUBOXONE can cause serious and life-threatening breathing problems. Call your doctor right away or get emergency help if:
    • You feel faint, dizzy, or confused
    • Your breathing gets much slower than is normal for you

These can be signs of an overdose or other serious problems.

  • SUBOXONE contains an opioid that can cause physical dependence.
    • Do not stop taking SUBOXONE without talking to your doctor. You could become sick with uncomfortable withdrawal signs and symptoms because your body has become used to this medicine.
    • Physical dependence is not the same as drug addiction.
    • SUBOXONE is not for occasional or “as needed” use.
  • An overdose and even death can happen if you take benzodiazepines, sedatives, tranquilizers, antidepressants, or alcohol while using SUBOXONE. Ask your doctor what you should do if you are taking one of these.
  • Call a doctor or get emergency help right away if you:
    • Feel sleepy and uncoordinated
    • Have blurred vision
    • Have slurred speech
    • Cannot think well or clearly
    • Have slowed reflexes and breathing
  • Do not inject (“shoot-up”) SUBOXONE
    • Injecting this medicine may cause life-threatening infections and other serious health problems.
    • Injecting SUBOXONE may cause serious withdrawal symptoms such as pain, cramps, vomiting, diarrhea, anxiety, sleep problems, and cravings.
  • In an emergency, have family members tell emergency department staff that you are physically dependent on an opioid and are being treated with SUBOXONE.

What is SUBOXONE?

  • SUBOXONE is a prescription medicine used to treat adults who are addicted to (dependent on) opioid drugs (either prescription or illegal) as part of a complete treatment program that also includes counseling and behavioral therapy.

SUBOXONE is a controlled substance (CIII) because it contains buprenorphine, which can be a target for people who abuse prescription medicines or street drugs. Keep your SUBOXONE in a safe place to protect it from theft. Never give your SUBOXONE to anyone else; it can cause death or otherwise harm them. Selling or giving away this medicine is against the law.

  • It is not known if SUBOXONE is safe or effective in children.

Who should not take SUBOXONE?

Do not take SUBOXONE if you are allergic to buprenorphine or naloxone.

What should I tell my doctor before taking SUBOXONE?

SUBOXONE may not be right for you. Before taking SUBOXONE, tell your doctor if you:

  • Have trouble breathing or lung problems
  • Have an enlarged prostate gland (men)
  • Have a head injury or brain problem
  • Have problems urinating
  • Have a curve in your spine that affects your breathing
  • Have liver or kidney problems
  • Have gallbladder problems
  • Have adrenal gland problems
  • Have Addison's disease
  • Have low thyroid (hypothyroidism)
  • Have a history of alcoholism
  • Have mental problems such as hallucinations (seeing or hearing things that are not there)
  • Have any other medical condition
  • Are pregnant or plan to become pregnant. It is not known if SUBOXONE will harm your unborn baby. If you take SUBOXONE while pregnant, your baby may have symptoms of withdrawal at birth. Talk to your doctor if you are pregnant or plan to become pregnant.
  • Are breast feeding or plan to breast feed. SUBOXONE can pass into your milk and may harm the baby. Talk to your doctor about the best way to feed your baby if you take SUBOXONE. Breast feeding is not recommended while taking SUBOXONE.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. SUBOXONE may affect the way other medicines work, and other medicines may affect how SUBOXONE works. Some medicines may cause serious or life-threatening medical problems when taken with SUBOXONE.

Sometimes the doses of certain medicines and SUBOXONE may need to be changed if used together. Do not take any medicine while using SUBOXONE until you have talked with your doctor. Your doctor will tell you if it is safe to take other medicines while you are using SUBOXONE.

Be especially careful about taking other medicines that may make you sleepy, such as pain medicines, tranquilizers, antidepressant medicines, sleeping pills, anxiety medicines or antihistamines. Know the medicines you take. Keep a list of them to show your doctor or pharmacist each time you get a new medicine.

How should I take SUBOXONE sublingual film?

  • Always take SUBOXONE exactly as your doctor tells you. Your doctor may change your dose after seeing how it affects you. Do not change your dose unless your doctor tells you to change it.
  • Do not take SUBOXONE more often than prescribed by your doctor.
  • Each SUBOXONE sublingual film comes in a sealed child-resistant foil pouch. Wait to open SUBOXONE until right before you use it.
  • To open your SUBOXONE sublingual film foil pouch, fold along the dotted line and tear down at slit (see Figure 1) or cut with scissors along the arrow.

Figure 1

To open, fold along the dotted line and tear down - Illustration

  • Before taking SUBOXONE, drink water to moisten your mouth. This helps the film dissolve more easily.
  • Hold the film between two fingers by the outside edges.
  • Place SUBOXONE sublingual film under your tongue, close to the base either to the left or right of the center (see Figure 2).

Figure 2

Place SUBOXONE sublingual film under your tongue - Illustration

    • If your doctor tells you to take 2 films at a time, place the second film under your tongue on the opposite side. Try to avoid having the films touch as much as possible.
    • Keep the films in place until they have completely dissolved.
    • If you are directed to take a third film, place it under your tongue on either side after the first 2 films have dissolved.
  • While SUBOXONE is dissolving, do not chew or swallow the film because the medicine will not work as well.
  • Talking while the film is dissolving can affect how well the medicine in SUBOXONE is absorbed.
  • If you miss a dose of SUBOXONE, take your medicine when you remember. If it is almost time for your next dose, skip the missed dose and take the next dose at your regular time. Do not take 2 doses at the same time unless your doctor tells you to. If you are not sure about your dosing, call your doctor.
  • Do not stop taking SUBOXONE suddenly. You could become sick and have withdrawal symptoms because your body has become used to the medicine. Physical dependence is not the same as drug addiction. Your doctor can tell you more about the differences between physical dependence and drug addiction. To have fewer withdrawal symptoms, ask your doctor how to stop using SUBOXONE the right way.
  • If you take too much SUBOXONE or overdose, call Poison Control or get emergency medical help right away.

What should I avoid while taking SUBOXONE?

  • Do not drive, operate heavy machinery, or perform any other dangerous activities until you know how this medication affects you. Buprenorphine can cause drowsiness and slow reaction times. This may happen more often in the first few weeks of treatment when your dose is being changed, but can also happen if you drink alcohol or take other sedative drugs when you take SUBOXONE.
  • You should not drink alcohol while using SUBOXONE, as this can lead to loss of consciousness or even death.

What are the possible side effects of SUBOXONE?

SUBOXONE can cause serious side effects, including:

  • See “What is the most important information I should know about SUBOXONE?”
  • Respiratory problems. You have a higher risk of death and coma if you take SUBOXONE with other medicines, such as benzodiazepines.
  • Sleepiness, dizziness, and problems with coordination
  • Dependency or abuse
  • Liver problems. Call your doctor right away if you notice any of these signs of liver problems: Your skin or the white part of your eyes turning yellow (jaundice), urine turning dark, stools turning light in color, you have less of an appetite, or you have stomach (abdominal) pain or nausea. Your doctor should do tests before you start taking and while you take SUBOXONE.
  • Allergic reaction. You may have a rash, hives, swelling of the face, wheezing, or a loss of blood pressure and consciousness. Call a doctor or get emergency help right away.
  • Opioid withdrawal. This can include: shaking, sweating more than normal, feeling hot or cold more than normal, runny nose, watery eyes, goose bumps, diarrhea, vomiting, and muscle aches. Tell your doctor if you develop any of these symptoms.
  • Decrease in blood pressure. You may feel dizzy if you get up too fast from sitting or lying down.

Common side effects of SUBOXONE sublingual film include:

  • Nausea
  • Vomiting
  • Drug withdrawal syndrome
  • Headache
  • Sweating
  • Numb mouth
  • Constipation
  • Painful tongue
  • The inside of your mouth is more red than normal
  • Intoxication (feeling lightheaded or drunk)
  • Disturbance in attention
  • Irregular heart beat (palpitations)
  • Decrease in sleep (insomnia)
  • Blurred vision
  • Back pain
  • Fainting
  • Dizziness
  • Sleepiness

Tell your doctor about any side effect that bothers you or that does not go away.

These are not all the possible side effects of SUBOXONE sublingual film. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store SUBOXONE?

  • Store at 25°C (77°F), excursions permitted to 15-30°C (59-86°F).
  • Keep SUBOXONE in a safe place, out of the sight and reach of children.

General information about the safe and effective use of SUBOXONE

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not take SUBOXONE for a condition for which it was not prescribed. Do not give SUBOXONE to other people, even if they have the same symptoms you have. It may harm them and it is against the law.

This Medication Guide summarizes the most important information about SUBOXONE sublingual film. If you would like more information, talk to your doctor or pharmacist. You can ask your doctor or pharmacist for information that is written for healthcare professionals. For more information call 1-877-782-6966.

What are the ingredients in SUBOXONE sublingual film?

Active Ingredients: buprenorphine and naloxone.

Inactive Ingredients: polyethylene oxide, hydroxypropyl methylcellulose, maltitol, acesulfame potassium, lime flavor, citric acid, sodium citrate, FD&C yellow #6, and white ink.

Last reviewed on RxList: 8/29/2012
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

SUBOXONE®
(Sub-OX-own)
(buprenorphine and naloxone) Sublingual Film

IMPORTANT:

Keep SUBOXONE in a secure place away from children. Accidental use by a child is a medical emergency and can result in death. If a child accidentally uses SUBOXONE, get emergency help right away.

Read this Medication Guide that comes with SUBOXONE before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor. Talk to your doctor or pharmacist if you have questions about SUBOXONE.

Share the important information in this Medication Guide with members of your household.

What is the most important information I should know about SUBOXONE?

  • SUBOXONE can cause serious and life-threatening breathing problems. Call your doctor right away or get emergency help if:
    • You feel faint, dizzy, or confused
    • Your breathing gets much slower than is normal for you

These can be signs of an overdose or other serious problems.

  • SUBOXONE contains an opioid that can cause physical dependence.
    • Do not stop taking SUBOXONE without talking to your doctor. You could become sick with uncomfortable withdrawal signs and symptoms because your body has become used to this medicine.
    • Physical dependence is not the same as drug addiction.
    • SUBOXONE is not for occasional or “as needed” use.
  • An overdose and even death can happen if you take benzodiazepines, sedatives, tranquilizers, antidepressants, or alcohol while using SUBOXONE. Ask your doctor what you should do if you are taking one of these.
  • Call a doctor or get emergency help right away if you:
    • Feel sleepy and uncoordinated
    • Have blurred vision
    • Have slurred speech
    • Cannot think well or clearly
    • Have slowed reflexes and breathing
  • Do not inject (“shoot-up”) SUBOXONE
    • Injecting this medicine may cause life-threatening infections and other serious health problems.
    • Injecting SUBOXONE may cause serious withdrawal symptoms such as pain, cramps, vomiting, diarrhea, anxiety, sleep problems, and cravings.
  • In an emergency, have family members tell emergency department staff that you are physically dependent on an opioid and are being treated with SUBOXONE.

What is SUBOXONE?

  • SUBOXONE is a prescription medicine used to treat adults who are addicted to (dependent on) opioid drugs (either prescription or illegal) as part of a complete treatment program that also includes counseling and behavioral therapy.

SUBOXONE is a controlled substance (CIII) because it contains buprenorphine, which can be a target for people who abuse prescription medicines or street drugs. Keep your SUBOXONE in a safe place to protect it from theft. Never give your SUBOXONE to anyone else; it can cause death or otherwise harm them. Selling or giving away this medicine is against the law.

  • It is not known if SUBOXONE is safe or effective in children.

Who should not take SUBOXONE?

Do not take SUBOXONE if you are allergic to buprenorphine or naloxone.

What should I tell my doctor before taking SUBOXONE?

SUBOXONE may not be right for you. Before taking SUBOXONE, tell your doctor if you:

  • Have trouble breathing or lung problems
  • Have an enlarged prostate gland (men)
  • Have a head injury or brain problem
  • Have problems urinating
  • Have a curve in your spine that affects your breathing
  • Have liver or kidney problems
  • Have gallbladder problems
  • Have adrenal gland problems
  • Have Addison's disease
  • Have low thyroid (hypothyroidism)
  • Have a history of alcoholism
  • Have mental problems such as hallucinations (seeing or hearing things that are not there)
  • Have any other medical condition
  • Are pregnant or plan to become pregnant. It is not known if SUBOXONE will harm your unborn baby. If you take SUBOXONE while pregnant, your baby may have symptoms of withdrawal at birth. Talk to your doctor if you are pregnant or plan to become pregnant.
  • Are breast feeding or plan to breast feed. SUBOXONE can pass into your milk and may harm the baby. Talk to your doctor about the best way to feed your baby if you take SUBOXONE. Breast feeding is not recommended while taking SUBOXONE.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. SUBOXONE may affect the way other medicines work, and other medicines may affect how SUBOXONE works. Some medicines may cause serious or life-threatening medical problems when taken with SUBOXONE.

Sometimes the doses of certain medicines and SUBOXONE may need to be changed if used together. Do not take any medicine while using SUBOXONE until you have talked with your doctor. Your doctor will tell you if it is safe to take other medicines while you are using SUBOXONE.

Be especially careful about taking other medicines that may make you sleepy, such as pain medicines, tranquilizers, antidepressant medicines, sleeping pills, anxiety medicines or antihistamines. Know the medicines you take. Keep a list of them to show your doctor or pharmacist each time you get a new medicine.

How should I take SUBOXONE sublingual film?

  • Always take SUBOXONE exactly as your doctor tells you. Your doctor may change your dose after seeing how it affects you. Do not change your dose unless your doctor tells you to change it.
  • Do not take SUBOXONE more often than prescribed by your doctor.
  • Each SUBOXONE sublingual film comes in a sealed child-resistant foil pouch. Wait to open SUBOXONE until right before you use it.
  • To open your SUBOXONE sublingual film foil pouch, fold along the dotted line and tear down at slit (see Figure 1) or cut with scissors along the arrow.

Figure 1

To open, fold along the dotted line and tear down - Illustration

  • Before taking SUBOXONE, drink water to moisten your mouth. This helps the film dissolve more easily.
  • Hold the film between two fingers by the outside edges.
  • Place SUBOXONE sublingual film under your tongue, close to the base either to the left or right of the center (see Figure 2).

Figure 2

Place SUBOXONE sublingual film under your tongue - Illustration

    • If your doctor tells you to take 2 films at a time, place the second film under your tongue on the opposite side. Try to avoid having the films touch as much as possible.
    • Keep the films in place until they have completely dissolved.
    • If you are directed to take a third film, place it under your tongue on either side after the first 2 films have dissolved.
  • While SUBOXONE is dissolving, do not chew or swallow the film because the medicine will not work as well.
  • Talking while the film is dissolving can affect how well the medicine in SUBOXONE is absorbed.
  • If you miss a dose of SUBOXONE, take your medicine when you remember. If it is almost time for your next dose, skip the missed dose and take the next dose at your regular time. Do not take 2 doses at the same time unless your doctor tells you to. If you are not sure about your dosing, call your doctor.
  • Do not stop taking SUBOXONE suddenly. You could become sick and have withdrawal symptoms because your body has become used to the medicine. Physical dependence is not the same as drug addiction. Your doctor can tell you more about the differences between physical dependence and drug addiction. To have fewer withdrawal symptoms, ask your doctor how to stop using SUBOXONE the right way.
  • If you take too much SUBOXONE or overdose, call Poison Control or get emergency medical help right away.

What should I avoid while taking SUBOXONE?

  • Do not drive, operate heavy machinery, or perform any other dangerous activities until you know how this medication affects you. Buprenorphine can cause drowsiness and slow reaction times. This may happen more often in the first few weeks of treatment when your dose is being changed, but can also happen if you drink alcohol or take other sedative drugs when you take SUBOXONE.
  • You should not drink alcohol while using SUBOXONE, as this can lead to loss of consciousness or even death.

What are the possible side effects of SUBOXONE?

SUBOXONE can cause serious side effects, including:

  • See “What is the most important information I should know about SUBOXONE?”
  • Respiratory problems. You have a higher risk of death and coma if you take SUBOXONE with other medicines, such as benzodiazepines.
  • Sleepiness, dizziness, and problems with coordination
  • Dependency or abuse
  • Liver problems. Call your doctor right away if you notice any of these signs of liver problems: Your skin or the white part of your eyes turning yellow (jaundice), urine turning dark, stools turning light in color, you have less of an appetite, or you have stomach (abdominal) pain or nausea. Your doctor should do tests before you start taking and while you take SUBOXONE.
  • Allergic reaction. You may have a rash, hives, swelling of the face, wheezing, or a loss of blood pressure and consciousness. Call a doctor or get emergency help right away.
  • Opioid withdrawal. This can include: shaking, sweating more than normal, feeling hot or cold more than normal, runny nose, watery eyes, goose bumps, diarrhea, vomiting, and muscle aches. Tell your doctor if you develop any of these symptoms.
  • Decrease in blood pressure. You may feel dizzy if you get up too fast from sitting or lying down.

Common side effects of SUBOXONE sublingual film include:

  • Nausea
  • Vomiting
  • Drug withdrawal syndrome
  • Headache
  • Sweating
  • Numb mouth
  • Constipation
  • Painful tongue
  • The inside of your mouth is more red than normal
  • Intoxication (feeling lightheaded or drunk)
  • Disturbance in attention
  • Irregular heart beat (palpitations)
  • Decrease in sleep (insomnia)
  • Blurred vision
  • Back pain
  • Fainting
  • Dizziness
  • Sleepiness

Tell your doctor about any side effect that bothers you or that does not go away.

These are not all the possible side effects of SUBOXONE sublingual film. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store SUBOXONE?

  • Store at 25°C (77°F), excursions permitted to 15-30°C (59-86°F).
  • Keep SUBOXONE in a safe place, out of the sight and reach of children.

General information about the safe and effective use of SUBOXONE

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not take SUBOXONE for a condition for which it was not prescribed. Do not give SUBOXONE to other people, even if they have the same symptoms you have. It may harm them and it is against the law.

This Medication Guide summarizes the most important information about SUBOXONE sublingual film. If you would like more information, talk to your doctor or pharmacist. You can ask your doctor or pharmacist for information that is written for healthcare professionals. For more information call 1-877-782-6966.

What are the ingredients in SUBOXONE sublingual film?

Active Ingredients: buprenorphine and naloxone.

Inactive Ingredients: polyethylene oxide, hydroxypropyl methylcellulose, maltitol, acesulfame potassium, lime flavor, citric acid, sodium citrate, FD&C yellow #6, and white ink.

Last reviewed on RxList: 8/29/2012
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Suboxone Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

BUPRENORPHINE/NALOXONE FILM - SUBLINGUAL

(BUE-pre-NOR-feen/nal-OX-one)

COMMON BRAND NAME(S): Suboxone

USES: This medication contains 2 medicines: buprenorphine and naloxone. It is used to treat narcotic (opioid) dependence/addiction. Buprenorphine belongs to a class of drugs called mixed narcotic agonist-antagonists. Buprenorphine helps prevent withdrawal symptoms caused by stopping other opiate-type narcotics.

Naloxone is a narcotic antagonist that blocks the effect of narcotics and can cause severe narcotic withdrawal when injected. Withdrawal is less likely when naloxone is taken by mouth or dissolved under the tongue. It is combined with buprenorphine to prevent abuse and misuse (injection) of this medication. This combination medication is used as part of a complete treatment program for drug abuse (such as compliance monitoring, counseling, behavioral contract, lifestyle changes).

This medication should not be used for pain relief. Serious, possibly fatal, breathing problems may occur.

HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using this medication and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Use this medication during your treatment maintenance period as directed by your doctor, usually once daily. Drink some water to moisten your mouth before use. This helps the film dissolve. Open the foil packet with dry hands immediately before use and place the medication film under your tongue. Keep the film under the tongue until it dissolves completely. Do not talk, swallow, chew, or move the film after placing under the tongue. It will not work as well.

If you are prescribed more than one film each day, place the second film under your tongue at the same time but on the opposite side of the mouth. Try not to place films on top of each other. If your doctor has ordered a 3rd film, place it under your tongue after the first 2 films have completely dissolved.

Buprenorphine alone is usually used for the first 2 days after you have stopped all other narcotics. It is usually given in your doctor's office. Your doctor will then switch you to this combination buprenorphine/naloxone medication for maintenance treatment.

The dosage is based on your medical condition and response to treatment. Your doctor will adjust the dose until there are no symptoms of withdrawal. Do not switch between sublingual tablets and film, because you may need a different dose if you switch. Do not increase your dose, use the medication more frequently, or use it for a longer time than prescribed. Properly stop the medication when so directed.

Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same time each day.

Do not inject ("shoot up") buprenorphine/naloxone. Injecting it is dangerous, and will likely cause severe withdrawal symptoms due to the naloxone in this medication, especially if you have been using narcotics such as heroin, morphine or methadone.

This medication may cause withdrawal reactions if it has been used regularly for a long time or in high doses. In such cases, withdrawal symptoms (such as diarrhea, restlessness, watering eyes, runny nose, nausea, sweating, muscle aches) may occur if you suddenly stop using this medication. To prevent withdrawal reactions, your doctor may reduce your dose gradually. Consult your doctor or pharmacist for more details, and report any withdrawal reactions immediately. (See also Side Effects section.)

Keep this medicine in a safe place to prevent theft, misuse, or abuse. If a child accidentally swallows this drug, get medical help right away.

Tell your doctor immediately if you experience any withdrawal reactions.

Disclaimer

Suboxone Consumer (continued)

SIDE EFFECTS: Nausea, vomiting, drowsiness, dizziness, constipation, or headache may occur. If any of these effects persist or worsen, tell your doctor or pharmacist immediately.

To prevent constipation, eat a diet adequate in fiber, drink plenty of water, and exercise. Consult your pharmacist for help in selecting a laxative (such as a stimulant type with stool softener).

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Although this medication is used to prevent withdrawal reactions, it may rarely cause narcotic withdrawal symptoms. This is more likely when you first start treatment or if you have been using long-acting narcotics such as methadone. If such symptoms occur, tell your doctor or pharmacist immediately.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Severe (possibly fatal) breathing problems can occur, especially if this medication is abused, injected, or mixed with other depressants (such as alcohol, benzodiazepines including diazepam, other narcotics). Get medical help right away if any of these serious side effects occur: slow/shallow breathing, fainting, mental/mood changes (such as agitation, confusion, hallucinations), unusual drowsiness/difficulty waking up.

This drug may rarely cause serious liver disease. Get medical help right away if you have any symptoms of liver damage, including: dark urine, persistent nausea/vomiting, yellowing eyes/skin, severe stomach/abdominal pain.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Suboxone (buprenorphine hcl and naloxone hcl) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking this medication, tell your doctor or pharmacist if you are allergic to buprenorphine or naloxone; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: brain disorders (such as head injury, tumor, seizures), breathing problems (such as asthma, sleep apnea, chronic obstructive pulmonary disease-COPD), liver disease, mental/mood disorders (such as confusion, depression, thoughts of suicide), stomach/intestinal problems (such as blockage, constipation, diarrhea due to infection, paralytic ileus), difficulty urinating (such as due to enlarged prostate).

This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Avoid alcoholic beverages. Alcohol increases your risk for serious, possibly fatal, breathing problems.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Older adults may be more sensitive to the effects of this drug, especially dizziness and drowsiness.

Before using this medication, women of childbearing age should talk with their doctor(s) about the risks and benefits. Tell your doctor if you are pregnant or if you plan to become pregnant. During pregnancy, this medication should be used only when clearly needed. It may slightly increase the risk of birth defects if used during the first two months of pregnancy. Also, using it for a long time or in high doses near the expected delivery date may harm the unborn baby. To lessen the risk, use the smallest effective dose for the shortest possible time. Tell the doctor right away if you notice any symptoms in your newborn baby such as slow/shallow breathing, irritability, abnormal/persistent crying, vomiting, or diarrhea.

This drug passes into breast milk and may rarely have undesirable effects on a nursing infant. Tell the doctor immediately if your baby develops unusual sleepiness, difficulty feeding, or trouble breathing. Breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

Disclaimer

Suboxone Consumer (continued)

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this medication include: narcotic antagonists (such as naltrexone), certain narcotic pain medications (mixed narcotic agonist-antagonists such as butorphanol, nalbuphine, pentazocine).

Other medications can affect the removal of buprenorphine from your body, which may affect how buprenorphine works. Examples include azole antifungals (such as ketoconazole), HIV medications (such as atazanavir), macrolide antibiotics (such as erythromycin), rifamycins (such as rifabutin), St. John's wort, drugs used to treat seizures (such as carbamazepine, phenytoin), among others.

The risk of serious side effects (such as slow/shallow breathing, severe drowsiness, dizziness) may be increased if this medication is taken with other products that may also affect breathing or cause drowsiness. Therefore, tell your doctor or pharmacist if you are taking other products such as alcohol, allergy or cough-and-cold products, anti-seizure drugs (such as phenobarbital), medicine for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants, other narcotics (such as hydrocodone, oxycodone), and psychiatric medicines (such as risperidone, amitriptyline, trazodone). Your medications or doses of your medications may need to be changed.

Deaths have occurred when this medication has been misused by injecting it ("shooting up"), especially when used in combination with benzodiazepines (such as diazepam) or other depressants such as alcohol or additional narcotics.

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: slow breathing, slow heartbeat, loss of consciousness.

NOTES: Do not share this medication with others. It is against the law.

Tell all of your doctors that you use this medication and have regularly used narcotics, especially in cases of emergency treatment.

Laboratory and/or medical tests (such as liver function tests, urine drug screening) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store in a secure place at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Properly discard this product when it is expired or no longer needed. Remove the film from the foil pouch and flush the films down the toilet. Do not flush the foil packet or carton down the toilet. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. Make sure close friends and family members know you are taking this medication and can tell emergency personnel. For enrollment information call MedicAlert at 1-800-854- 1166 (US) or 1-800-668-1507 (Canada).

Information last revised September 2011. Copyright(c) 2011 First Databank, Inc.

Suboxone Patient Information Including Side Effects

Brand Names: Suboxone

Generic Name: buprenorphine and naloxone (Pronunciation: byoo PREH nor feen and NAH lox own)

What is buprenorphine and naloxone (Suboxone)?

Buprenorphine is an opioid medication. Buprenorphine is similar to other opioids such as morphine, codeine, and heroin however, it produces less euphoric ("high") effects and therefore may be easier to stop taking.

Naloxone blocks the effects of opioids such as morphine, codeine, and heroin. If buprenorphine and naloxone is injected, naloxone will block the effects of buprenorphine and lead to withdrawal symptoms in a person with an opioid addiction. When administered under the tongue as directed, naloxone will not affect the actions of buprenorphine.

Buprenorphine and naloxone is used to treat opiate addiction.

Buprenorphine and naloxone may also be used for purposes other than those listed in this medication guide.

Suboxone 8 mg-2 mg

hexagonal, orange, imprinted with N8, LOGO

What are the possible side effects of buprenorphine and naloxone (Suboxone)?

Buprenorphine and naloxone can cause drug dependence. This means that withdrawal symptoms may occur if you stop using the medicine too quickly. Withdrawal symptoms may also occur at the start of treatment due to dependence on another drug. Buprenorphine and naloxone is not for occasional ("as needed") use. Do not stop taking buprenorphine and naloxone without first talking to your doctor. Your doctor may want to gradually reduce the dose to avoid or minimize withdrawal symptoms.

Seek emergency medical attention or contact your doctor immediately if you experience any of the following serious side effects:

  • an allergic reaction (difficulty breathing; closing of the throat, swelling of the lips, tongue, or face; or hives);
  • slow breathing;
  • dizziness or confusion; or
  • liver problems such as yellowing of the skin or eyes, dark colored urine, light colored stools (bowel movements), decreased appetite for several days or longer, nausea, or lower stomach pain.

Other less serious side effects may be more likely to occur. Continue to take buprenorphine and naloxone and talk to your doctor if you experience

  • headache;
  • pain;
  • problems sleeping;
  • nausea;
  • sweating;
  • stomach pain; or
  • constipation.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

Read the Suboxone (buprenorphine hcl and naloxone hcl) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about buprenorphine and naloxone (Suboxone)?

Buprenorphine and naloxone can cause death from overdose, especially if it is injected with a tranquilizer. Use buprenorphine and naloxone exactly as directed by your doctor.

Buprenorphine and naloxone can cause drug dependence. This means that withdrawal symptoms may occur if you stop using the medicine too quickly. Withdrawal symptoms may also occur at the start of treatment due to dependence on another drug. Buprenorphine and naloxone is not for occasional ("as needed") use. Do not stop taking buprenorphine and naloxone without first talking to your doctor. Your doctor may want to gradually reduce the dose to avoid or minimize withdrawal symptoms.

In an emergency, have family members tell emergency room staff that you are taking buprenorphine and naloxone and that you are dependent on opioids.

Use caution when driving, operating machinery, or performing other hazardous activities. Buprenorphine and naloxone may cause drowsiness, dizziness, or impaired thinking. If you experience drowsiness, dizziness, or impaired thinking, avoid these activities.

Avoid alcohol while taking buprenorphine and naloxone. Alcohol may dangerously increase drowsiness and dizziness caused by the medication.

Buprenorphine and naloxone may dangerously increase the effects of other drugs that cause drowsiness, including antidepressants, alcohol, antihistamines, sedatives (used to treat insomnia), other pain relievers, anxiety medicines, and muscle relaxants. Tell your doctor about all medicines that you are taking, and do not take any other prescription or over-the-counter medicine, including herbal products, without first talking to your doctor.

Side Effects Centers

Suboxone Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking buprenorphine and naloxone (Suboxone)?

Do not take buprenorphine and naloxone if:

  • the medication was not prescribed for you; or
  • you are allergic to buprenorphine, naloxone, or any components of the tablets.

Before taking buprenorphine and naloxone, tell your doctor if you have:

  • lung problems or difficulty breathing;
  • a head injury or brain problem;
  • liver problems;
  • kidney problems;
  • gallbladder problems;
  • adrenal gland problems, such as Addison's disease;
  • low thyroid (hypothyroidism);
  • enlarged prostate gland;
  • problems urinating;
  • a curve in the spine that affects breathing;
  • severe mental problems or hallucinations (seeing or hearing thing that are not really there); or
  • alcoholism.

You may not be able to take buprenorphine and naloxone, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.

Buprenorphine and naloxone is in the FDA pregnancy category C. This means that it is not known whether buprenorphine and naloxone will be harmful to an unborn baby. Use of buprenorphine and naloxone during pregnancy may cause withdrawal symptoms in a newborn baby. Do not take buprenorphine and naloxone if you are pregnant or could become pregnant during treatment.

Buprenorphine and naloxone passes into breast milk and may be harmful to a nursing baby. Do not take buprenorphine and naloxone if you are breast-feeding a baby.

How should I take buprenorphine and naloxone (Suboxone)?

Take buprenorphine and naloxone exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

The buprenorphine and naloxone tablets should be placed under the tongue and allowed to dissolve. This will take 2 to 10 minutes. If more than one tablet is prescribed per dose, your doctor may tell you to put all of the tablets under your tongue at the same time, or put 2 tablets under your tongue and allow them to dissolve completely, then put the next tablet or tablets under the tongue right away.

Do not chew or swallow the tablets. The medicine will not work this way and you may get withdrawal symptoms.

Do not change the dose of buprenorphine and naloxone or take it more often than prescribed without first talking to your doctor.

Do not inject ("shoot-up") buprenorphine and naloxone. Shooting-up is dangerous and may cause bad withdrawal symptoms.

Buprenorphine and naloxone may cause withdrawal symptoms if taken too soon after a dose of heroin, morphine, or methadone.

Buprenorphine and naloxone can cause drug dependence. This means that withdrawal symptoms may occur if you stop using the medicine too quickly. Withdrawal symptoms may also occur at the start of treatment due to dependence on another drug. Buprenorphine and naloxone is not for occasional ("as needed") use. Do not stop taking buprenorphine and naloxone without first talking to your doctor. Your doctor may want to gradually reduce the dose to avoid or minimize withdrawal symptoms.

When treatment with buprenorphine and naloxone is completed, flush any unused tablets down the toilet.

Buprenorphine and naloxone can cause constipation. Drink plenty of water (six to eight full glasses a day) to lessen this side effect. Increasing the amount of fiber in your diet can also help to alleviate constipation.

Your doctor may want to perform blood tests or other forms of monitoring during treatment with buprenorphine and naloxone.

Store buprenorphine and naloxone at room temperature away from moisture and heat. Buprenorphine and naloxone may be a target for people who abuse prescription or street drugs. Therefore, keep the tablets in a safe place to protect them from theft. Never give them to anyone else. Sell or giving away this medicine is against the law.

Side Effects Centers

Suboxone Patient Information including If I Miss a Dose

What happens if I miss a dose (Suboxone)?

Take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take only the next regularly scheduled dose. Do not take a double dose of this medication.

What happens if I overdose (Suboxone)?

Seek emergency medical attention.

Symptoms of a buprenorphine and naloxone overdose may include slow breathing, seizures, dizziness, weakness, loss of consciousness, coma, confusion, tiredness, cold and clammy skin, and small pupils.

What should I avoid while taking buprenorphine and naloxone (Suboxone)?

In an emergency, have family members tell emergency room staff that you are taking buprenorphine and naloxone and that you are dependent on opioids.

Use caution when driving, operating machinery, or performing other hazardous activities. Buprenorphine and naloxone may cause drowsiness, dizziness, or impaired thinking. If you experience drowsiness, dizziness, or impaired thinking, avoid these activities.

Dizziness may be more likely to occur when rising from a sitting or lying position. Rise slowly to minimize dizziness and prevent a fall.

Avoid alcohol while taking buprenorphine and naloxone. Alcohol may dangerously increase drowsiness and dizziness caused by the medication.

Buprenorphine and naloxone may dangerously increase the effects of other drugs that cause drowsiness, including antidepressants, alcohol, antihistamines, sedatives (used to treat insomnia), other pain relievers, anxiety medicines, and muscle relaxants. Tell your doctor about all medicines that you are taking, and do not take any other prescription or over-the-counter medicine, including herbal products, without first talking to your doctor.

What other drugs will affect buprenorphine and naloxone (Suboxone)?

Buprenorphine and naloxone can cause death from overdose, especially if it is injected with a tranquilizer. Use buprenorphine and naloxone exactly as directed by your doctor.

Do not take buprenorphine and naloxone without first talking to your doctor if you are taking:

  • a benzodiazepine such as alprazolam (Xanax), diazepam (Valium), clonazepam (Klonopin), clorazepate (Tranxene), lorazepam (Ativan), chlordiazepoxide (Librium), oxazepam (Serax), triazolam (Halcion), temazepam (Restoril), estazolam (Prosom), quazepam (Doral), or flurazepam (Dalmane);
  • erythromycin (Ery-Tab, E.E.S., E-Mycin, others) or clarithromycin (Biaxin);
  • itraconazole (Sporanox) or ketoconazole (Nizoral);
  • an HIV protease inhibitor such as indinavir (Crixivan), ritonavir (Norvir) or saquinavir (Fortovase, Invirase);
  • rifampin (Rifadin, Rimactane), rifapentine (Priftin), or rifabutin (Mycobutin);
  • phenytoin (Dilantin);
  • carbamazepine (Tegretol);
  • a barbiturate such as phenobarbital, mephobarbital (Mebaral), and others.

You may not be able to take buprenorphine and naloxone, or you may require a dosage adjustment or special monitoring during treatment if you are taking any of the medications listed above.

Buprenorphine and naloxone may dangerously increase the effects of other drugs that cause drowsiness, including antidepressants, alcohol, antihistamines, sedatives (used to treat insomnia), other pain relievers, anxiety medicines, and muscle relaxants. Tell your doctor about all medicines that you are taking, and do not take any other prescription or over-the-counter medicine, including herbal products, without first talking to your doctor.

Drugs other than those listed here may also interact with buprenorphine and naloxone. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including herbal products.

Where can I get more information?

Your pharmacist may have additional information about buprenorphine and naloxone written for health professionals that you may read.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 1.05. Revision date: 12/15/2010.

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Side Effects Centers

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