Buprenorphine and Naloxone 8 mg; 2 mg Film, Soluble — NDC 43598-582-30 (Billing 43598-0582-30)
This is a package of Buprenorphine and Naloxone 8 mg; 2 mg Film, Soluble from Dr.Reddys Laboratories Inc, marketed since Jun 2018 and currently FDA-listed; retail pharmacies pay about $1.98 per unit (NADAC). It is this product's only package size.
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 066636
- GCN: 28959
- GPI-14 (Medi-Span): 65200010208240
- HICL (First Databank): 024846
- AHFS class code: 28:08.12.00
- RxCUI (RxNorm): 1010600
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Partial Opioid Agonist class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Buprenorphine and the combination of buprenorphine and naloxone are used to treat opioid dependence (addiction to opioid drugs, including heroin and narcotic painkillers). Buprenorphine is in a class of medications called opioid partial agonist-antagonists and naloxone is in a class of medications called opioid antagonists. Buprenorphine alone and the combination of buprenorphine and naloxone work to prevent withdrawal symptoms when someone stops taking opioid drugs by producing similar effects to these drugs.
Read the full MedlinePlus article ↗- It treats opioid dependence. It works best as part of a full plan that includes counseling and support.
- You take it once a day, letting it dissolve under your tongue. The film may also be placed inside the cheek. Don't chew or swallow it unless your pharmacist or prescriber says othe...
- Please don't without talking to your prescriber. Alcohol, benzodiazepines and other sedating drugs can slow your breathing dangerously. Tell every provider you see that you take th...
- Can I drink alcohol or take my anxiety or sleep medicine with it?
Patient education
Supplement & herbal interactions
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $1.982 | $59.47 / 30 film |
| Medicaid paysCMS SDUD · 12 mo | $2.35 | $70.58 / 30 film |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 43598-0582-30 You're viewing this Main listing | 30 POUCH in 1 CARTON / 1 FILM, SOLUBLE in 1 POUCH | 2018-06-14 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Buprenorphine and Naloxone 8 mg/1; 2 mg 00378-8767-93 | Mylan | 30 films | $1.982 | AB | Availability likely | — |
| Buprenorphine and Naloxone 8 mg/1; 2 mgthis 43598-0582-30 | Dr.Reddys | 1 film | $1.982 | AB | Availability likely | — |
| Buprenorphine and Naloxone Sublingual Film 8 mg/1; 2 mg 47781-0357-03 | Alvogen | 30 films | $1.982 | AB | Availability likely | — |
| Buprenorphine and Naloxone 8 mg/1; 2 mg 50742-0364-30 | INGENUS | 30 films | $1.982 | AB | Availability likely | — |
| Suboxone 8 mg/1; 2 mg 12496-1208-03 | INDIVIOR | 1 film | $8.592 | AB | Availability likely | +333% |
| Buprenorphine and Naloxone 8 mg/1; 2 mg 03215-6523-30 | Aveva | 30 films | — | AB | FDA listed | — |
| Buprenorphine and Naloxone 8 mg/1; 2 mg 31722-0481-30 | Camber | 1 film | — | AB | FDA listed | — |
| Buprenorphine and Naloxone Sublingual Film 8 mg/1; 2 mg 67296-1933-01 | Redpharm | 1 film | — | AB | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Oct 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 23OV73Q5G9
Acesulfame potassium is an artificial sweetener that tastes about 200 times sweeter than sugar. It's added to medicines to improve taste without adding calories or affecting blood sugar.
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UNII 5138Q19F1X
Ammonia is a colorless gas made from nitrogen and hydrogen. It's used in medicines as a pH buffer to maintain the correct acidity level and help keep the product stable.
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UNII XF417D3PSL
Anhydrous citric acid is a sour, crystalline powder derived from citric acid with water removed. In medicines, it acts as a buffer to control pH, adds tartness to improve taste, and helps tablets disintegrate.
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UNII REK4960K2U
Butylated hydroxyanisole is a synthetic preservative that prevents oils and fats in medicines from spoiling or becoming rancid. It keeps the medicine stable and extends its shelf life.
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UNII 1P9D0Z171K
BHT is a synthetic antioxidant that prevents fats and oils in medicines from breaking down and becoming rancid. It helps keep the product stable and effective during storage.
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UNII H3R47K3TBD
FD&C Blue No. 1 is a synthetic blue dye approved for use in foods and medicines. It serves as a colorant to give the medication its distinctive appearance and help with product identification.
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UNII H77VEI93A8
A synthetic yellow dye used to color medications. It helps identify the drug and make it visually distinctive, with no effect on how the medicine works.
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UNII D65DG142WK
Maltitol is a sugar alcohol made by hydrogenating maltose. It's used as a sweetener and filler in medicines to improve taste and add bulk to tablets and capsules.
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UNII 3WJQ0SDW1A
Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
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UNII 390RMW2PEQ
Povidone K29/32 is a synthetic polymer made from vinyl pyrrolidone. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break down in the stomach for drug release.
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UNII U725QWY32X
Povidone K30 is a synthetic polymer made from petroleum. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the stomach so the medicine can be absorbed.
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UNII 46N107B71O
Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
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UNII 22ADO53M6F
A mineral salt derived from phosphoric acid, used as a buffer to maintain the pH balance of the medication and help stabilize the active ingredients.
13 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
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Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Buprenorphine and naloxone sublingual film is indicated for treatment of opioid dependence. Buprenorphine and naloxone sublingual film should be used as part of a complete treatment plan that includes counseling and psychosocial support. Buprenorphine and naloxone sublingual film contains buprenorphine, a partial-opioid agonist and naloxone, an opioid antagonist, and is indicated for treatment of opioid dependence.
( 1 ) Buprenorphine and naloxone sublingual film should be used as part of a complete treatment plan that includes counseling and psychosocial support. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Administer buprenorphine and naloxone sublingual film as a single daily dose. ( 2.1 ) Strongly consider recommending or prescribing an opioid overdose reversal agent (e.g., naloxone, nalmefene) at the time buprenorphine and naloxone sublingual film is initiated or renewed because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose. ( 2.2 ) To avoid precipitating withdrawal, induction with buprenorphine and naloxone sublingual film should be undertaken when objective and clear signs of withdrawal are evident and buprenorphine and naloxone sublingual film should be administered in divided doses when used as initial treatment.
( 2.3 ) For patients dependent on short-acting opioid products who are in opioid withdrawal; on Day 1, administer up to 8 mg/2 mg buprenorphine and naloxone sublingual film (in divided doses). On Day 2, administer up to 16 mg/4 mg of buprenorphine and naloxone sublingual film as a single dose. (2.3) For patients dependent on methadone or long-acting opioid products, induction onto sublingual buprenorphine monotherapy is recommended on Days 1 and 2 of treatment.
(2.3) The maintenance dose of buprenorphine and naloxone sublingual film is generally in the range of 4 mg/1 mg to 24 mg/6 mg per day and should be based on clinical response. (2.4) Sublingual Administration: Place one film under the tongue, close to the base on the left or right side, and allow to completely dissolve. Buccal Administration: Place one film on the inside of the left or right cheek and allow to completely dissolve.
( 2.5 ) Buprenorphine and naloxone sublingual film must be administered whole. Do not cut, chew, or swallow buprenorphine and naloxone sublingual film (2.5) When discontinuing treatment, gradually taper to avoid signs and symptoms of withdrawal. (2.8)
2.1Important Dosage and Administration Information Buprenorphine and naloxone sublingual film is administered sublingually or buccally as a single daily dose. 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.
2.2Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene) and discuss the importance of having access to an opioid overdose reversal agent. Because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose, strongly consider recommending or prescribing an overdose reversal agent for the emergency treatment of opioid overdose, both when initiating and renewing treatment with buprenorphine and naloxone sublingual film.
Also consider recommending or prescribing such an agent if the patient has household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose [see Warnings and Precautions ( 5.2 )]. Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program) [see Warnings and Precautions ( 5.2 )]. There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics.
Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent. Advise patients and caregivers that opioid overdose reversal agents, such as naloxone or nalmefene, may also be administered for a known or suspected overdose with buprenorphine itself. Higher than normal doses and repeated administration of an opioid overdose reversal agent may be necessary due to the long duration of action of buprenorphineand its affinity for the mu-opioid receptor [see Overdosage (… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Buprenorphine and naloxone sublingual film, 2 mg/0.5 mg or 8 mg/2 mg is available as orange rectangular film, imprinted with "2" or "8" in blue ink as a strength identifier ("2" or "8" may appear to be green in color), in dosage strengths: Buprenorphine 2 mg/naloxone 0.5 mg and Buprenorphine 8 mg/naloxone 2 mg Sublingual film: buprenorphine 2 mg / naloxone 0.5 mg and buprenorphine 8 mg / naloxone 2 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Buprenorphine and naloxone sublingual film is contraindicated in patients with a history of hypersensitivity to buprenorphine or naloxone as serious adverse reactions, including anaphylactic shock, have been reported [ see Warnings and Precautions ( 5.9 )]. Hypersensitivity to buprenorphine or naloxone. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Addiction, Abuse, and Misuse: Buprenorphine can be abused in a similar manner to other opioids. Monitor patients for conditions indicative of diversion or progression of opioid dependence and addictive behaviors. Multiple refills should not be prescribed early in treatment or without appropriate patient follow-up visits.
( 5.1 ) Respiratory Depression: Life-threatening respiratory depression and death have occurred in association with buprenorphine use. Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with buprenorphine and naloxone sublingual film. ( 5.2 , 5.3 ) Unintentional Pediatric Exposure: Store buprenorphine and naloxone sublingual film safely out of the sight and reach of children.
Buprenorphine can cause severe, possibly fatal, respiratory depression in children. ( 5.4 ) Neonatal Opioid Withdrawal Syndrome : Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy ( 5.5 ) Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.6 ) Risk of Opioid Withdrawal with Abrupt Discontinuation : If treatment is temporarily interrupted or discontinued, monitor patients for withdrawal and treat appropriately.
( 5.7 ) Risk of Hepatitis, Hepatic Events: Monitor liver function tests prior to initiation and during treatment and evaluate suspected hepatic events. ( 5.8 ) Precipitation of Opioid Withdrawal Signs and Symptoms: An opioid withdrawal syndrome is likely to occur with parenteral misuse of buprenorphine and naloxone sublingual film by individuals physically dependent on full opioid agonists, or by sublingual or buccal administration before the agonist effects of other opioids have subsided. ( 5.10 ) Risk of Overdose in Opioid-Naïve Patients: Buprenorphine and naloxone sublingual film is not appropriate as an analgesic.
There have been reported deaths of opioid naïve individuals who received a 2 mg sublingual dose. ( 5.11 )
5.1Addiction, Abuse, and Misuse Buprenorphine and naloxone sublingual film contains buprenorphine, a schedule III controlled substance that 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 ( 9.2 )].
5.2Risk of Life-Threatening Respiratory and Central Nervous System (CNS) Depression Buprenorphine has been associated with life-threatening respiratory depression and death. Many, but not all, post-marketing reports regarding coma and death involved misuse by self-injection or were associated with the concomitant use of buprenorphine and benzodiazepines or other CNS depressants, including alcohol. Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with buprenorphine and naloxone sublingual film [ see Warnings and Precautions ( 5.3 ), Drug Interactions ( 7 ) ].
Use buprenorphine and naloxone sublingual film with caution in patients with compromised respiratory function (e.g., chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression). Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Patient Counseling Information ( 17 )]. Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-relate… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.1 )] Respiratory and CNS Depression [see Warnings and Precautions ( 5.2 ), ( 5.3 )] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.5 )] Adrenal Insufficiency [see Warnings and Precautions ( 5.6 )] Opioid Withdrawal [see Warnings and Precautions ( 5.7 , 5.10 )] Hepatitis, Hepatic Events [see Warnings and Precautions ( 5.8 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.9 )] Orthostatic Hypotension [see Warnings and Precautions ( 5.16 )] Elevation of Cerebrospinal Fluid Pressure [see Warnings and Precautions ( 5.17 ) ] Elevation of Intracholedochal Pressure [see Warnings and Precautions ( 5.18 ) Adverse events commonly observed with the sublingual/buccal administration of the buprenorphine and naloxone sublingual film are oral hypoesthesia, glossodynia, oral mucosal erythema, headache, nausea, vomiting, hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia, pain, and peripheral edema.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy’s Laboratories, Inc. at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience 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. The safety of buprenorphine and naloxone sublingual film is supported by clinical trials using buprenorphine sublingual tablets and buprenorphine and naloxone sublingual tablets, and other trials using buprenorphine sublingual solutions, as well as an open-label study in 194 patients treated with buprenorphine and naloxone sublingual film administered sublingually and 188 patients treated with the film administered buccally.
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 with regard to sublingually and bucally administered buprenorphine and naloxone sublingual film, buprenorphine and naloxone sublingual tablets, buprenorphine sublingual tablets and a buprenorphine ethanolic sublingual solution. The most common adverse event (>1%) associated with the sublingual administration of the buprenorphine and naloxone 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. The most common adverse events associated with the buccal administration were similar to those observed with sublingual administration of the film. Other adverse event data were derived from larger, controlled studies of buprenorphine and naloxone sublingual tablets and buprenorphine sublingual tablets and of buprenorphine sublingual solution.
In a comparative study of buprenorphine and naloxone sublingual tablets and buprenorphine sublingual tablets, adverse event profiles were similar for subjects treated with 16 mg/4 mg buprenorphine and naloxone sublingual tablets or 16 mg buprenorphine sublingual tablets. The following adverse events were reported to occur by at least 5% of patients in a 4 week study of buprenorphine and naloxone sublingual tablets and 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) Buprenorphine and naloxone sublingual tablets 16 mg/4 mg/day N = 107 n (%) 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%… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Table 4 Includes clinically significant drug interactions with buprenorphine and naloxone Table 4 Clinically Significant Drug Interactions Benzodiazepines and Other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effects, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, increases the risk of respiratory depression, profound sedation, coma, and death. Intervention: Cessation of benzodiazepines or other CNS depressants is preferred in most cases of concomitant use.
In some cases, monitoring in a higher level of care for taper may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate. Before co-prescribing benzodiazepines for anxiety or insomnia, ensure that patients are appropriately diagnosed and consider alternative medications and non-pharmacologic treatments [see Warnings and Precautions ( 5.2 , 5.3)] .If concomitant use is warranted, strongly consider recommending or prescribing an opioid overdose reversal agent, as is recommended for all patients on buprenorphine treatment for opioid use disorder [ see Warnings and Precautions (5.2) ] .
Examples: Alcohol, benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), and other opioids. Inhibitors of CYP3A4 Clinical Impact: The concomitant use of buprenorphine and CYP3A4 inhibitors can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when an inhibitor is added after a stable dose of buprenorphine and naloxone sublingual film is achieved.
After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the buprenorphine plasma concentration will decrease [see Clinical Pharmacology ( 12.3) ] , potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to buprenorphine. Intervention: If concomitant use is necessary, consider dosage reduction of buprenorphine and naloxone sublingual film until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals.
If a CYP3A4 inhibitor is discontinued, consider increasing the buprenorphine and naloxone sublingual film dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 Inducers Clinical Impact: The concomitant use of buprenorphine and CYP3A4 inducers can decrease the plasma concentration of buprenorphine [see Clinical Pharmacology (12.3)] , potentially resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine.
After stopping a CYP3A4 inducer, as the effects of the inducer decline, the buprenorphine plasma concentration will increase [see Clinical Pharmacology (12.3) ] , which could increase or prolong both therapeutic effects and adverse reactions and may cause serious respiratory depression. Intervention: If concomitant use is necessary, consider increasing the buprenorphine and naloxone sublingual film dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.
If a CYP3A4 inducer is discontinued, consider buprenorphine and naloxone sublingual film dosage reduction and monitor for signs of respiratory depression. Examples: Rifampin, carbamazepine, phenytoin Antiretrovirals: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Clinical Impact: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are metabolized principally by CYP3A4. Efavirenz, nevirapine, and etravirine are known CYP3A inducers, whereas delavirdine is a CYP3A inhibitor… [Excerpted — this section continues on DailyMed.]
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Buprenorphine passes into mother’s milk. ( 8.2 ) Geriatric Patients: Monitor for sedation and respiratory depression. ( 8.5 ) Moderate or Severe Hepatic Impairment: Buprenorphine/naloxone products are not recommended in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment. ( 8.6 )
8.1Pregnancy Risk Summary The data on use of buprenorphine, one of the active ingredients in buprenorphine and naloxone sublingual film, in pregnancy, are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure. There are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations [see Data] . Observational studies have reported on congenital malformations among buprenorphine‐exposed pregnancies, but were also not designed appropriately to assess the risk of congenital malformations specifically due to buprenorphine exposure [see Data] .
The extremely limited data on sublingual naloxone exposure in pregnancy are not sufficient to evaluate a drug‐associated risk. Reproductive and developmental studies in rats and rabbits identified adverse events at clinically relevant and higher doses. Embryofetal death was observed in both rats and rabbits administered buprenorphine during the period of organogenesis at doses approximately 6 and 0.3 times, respectively, the human sublingual dose of 16 mg/day of buprenorphine.
Pre-and postnatal development studies in rats demonstrated increased neonatal deaths at 0.3 times and above and dystocia at approximately 3 times the human sublingual dose of 16 mg/day of buprenorphine. No clear teratogenic effects were seen when buprenorphine was administered during organogenesis with a range of doses equivalent to or greater than the human sublingual dose of 16 mg/day of buprenorphine. However, increases in skeletal abnormalities were noted in rats and rabbits administered buprenorphine daily during organogenesis at doses approximately 0.6 and approximately equal to the human sublingual dose of 16 mg/day of buprenorphine, respectively.
In a few studies, some events such as acephalus and omphalocele were also observed but these findings were not clearly treatment-related [ see Data ]. Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population are unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo-fetal risk Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death.
In addition, untreated opioid addiction often results in continued or relapsing illicit opioid use. Dose Adjustment during Pregnancy and the Postpartum Period Dosage adjustments of buprenorphine, such as higher doses, may be required during pregnancy, even if the patient was maintained on a stable dose prior to pregnancy.Dosing should based on individual response, and withdrawal signs and symptoms should be monitored closely and the dose adjusted as necessary. Fetal/neonatal adverse reactions Neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment with buprenorphine and naloxone sublingual film.
Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight. Signs of neonatal withdrawal usually occur in the first days after birth. The duration and sev… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary The data on use of buprenorphine, one of the active ingredients in buprenorphine and naloxone sublingual film, in pregnancy, are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure. There are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations [see Data] . Observational studies have reported on congenital malformations among buprenorphine‐exposed pregnancies, but were also not designed appropriately to assess the risk of congenital malformations specifically due to buprenorphine exposure [see Data] .
The extremely limited data on sublingual naloxone exposure in pregnancy are not sufficient to evaluate a drug‐associated risk. Reproductive and developmental studies in rats and rabbits identified adverse events at clinically relevant and higher doses. Embryofetal death was observed in both rats and rabbits administered buprenorphine during the period of organogenesis at doses approximately 6 and 0.3 times, respectively, the human sublingual dose of 16 mg/day of buprenorphine.
Pre-and postnatal development studies in rats demonstrated increased neonatal deaths at 0.3 times and above and dystocia at approximately 3 times the human sublingual dose of 16 mg/day of buprenorphine. No clear teratogenic effects were seen when buprenorphine was administered during organogenesis with a range of doses equivalent to or greater than the human sublingual dose of 16 mg/day of buprenorphine. However, increases in skeletal abnormalities were noted in rats and rabbits administered buprenorphine daily during organogenesis at doses approximately 0.6 and approximately equal to the human sublingual dose of 16 mg/day of buprenorphine, respectively.
In a few studies, some events such as acephalus and omphalocele were also observed but these findings were not clearly treatment-related [ see Data ]. Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population are unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo-fetal risk Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death.
In addition, untreated opioid addiction often results in continued or relapsing illicit opioid use. Dose Adjustment during Pregnancy and the Postpartum Period Dosage adjustments of buprenorphine, such as higher doses, may be required during pregnancy, even if the patient was maintained on a stable dose prior to pregnancy.Dosing should based on individual response, and withdrawal signs and symptoms should be monitored closely and the dose adjusted as necessary. Fetal/neonatal adverse reactions Neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment with buprenorphine and naloxone sublingual film.
Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight. Signs of neonatal withdrawal usually occur in the first days after birth. The duration and severity of neonatal opioid withdrawal syndrome may vary.
Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions ( 5.5 )]. Labor or Delivery Opioid‐dependent women on buprenorphine maintenance therapy may require additional analgesia during labor. Data Human Data Studies have been conducted to evaluate neonatal outcomes… [Excerpted — this section continues on DailyMed.]
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of buprenorphine and naloxone sublingual film have not been established in pediatric patients. This product is not appropriate for the treatment of neonatal abstinence syndrome in neonates, because it contains naloxone, an opioid antagonist.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of buprenorphine and naloxone sublingual film, buprenorphine and naloxone sublingual tablets, or 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. Due to possible decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in geriatric patients, the decision to prescribe buprenorphine and naloxone sublingual film should be made cautiously in individuals 65 years of age or older and these patients should be monitored for signs and symptoms of toxicity or overdose.
🆘 Overdosage ▾
10 OVERDOSAGE Clinical Presentation The manifestations of acute buprenorphine overdose include pinpoint pupils, sedation, hypotension,hypoglycemia, respiratory depression, and death. Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication. Treatment of Overdose 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.
An opioid overdose reversal agent may be of value for the management of buprenorphine overdose. Higher than normal doses and repeated administration may be necessary. The long duration of action of buprenorphine and naloxone sublingual film should be taken into consideration when determining the length of treatment and medical surveillance needed to reverse the effects of an overdose.
Insufficient duration of monitoring may put patients at risk.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Buprenorphine and naloxone 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.
12.2Pharmacodynamics 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 mg to 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, O 2 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 O 2 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 na… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Buprenorphine and naloxone 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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Buprenorphine 2 mg and naloxone 0.5 mg sublingual film, (content expressed in terms of free base) is supplied as an orange rectangular film with imprint "2" in blue ink ("2" may appear to be green in color), in child-resistant polyester/foil laminated pouches. NDC 43598-579-30 30 films per carton Buprenorphine 8 mg and naloxone 2 mg sublingual film, (content expressed in terms of free base) is supplied as an orange rectangular film with imprint "8" in blue ink ("8" may appear to be green in color), in child-resistant polyester/foil laminated pouches.
NDC 43598-582-30 30 films per carton Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Store buprenorphine and naloxone sublingual film securely and dispose of properly [see Patient Counseling Information ( 17 )].
📋 Description ▾
11 DESCRIPTION Buprenorphine and naloxone sublingual film, 2 mg/0.5 mg or 8 mg/2 mg are orange rectangular films, imprinted with "2" or "8" in blue ink as a strength identifier ("2" or "8" may appear to be green in color). It contains buprenorphine HCl, a mu-opioid receptor partial agonist, and a kappa-opioid receptor antagonist, and naloxone HCl dihydrate, an opioid antagonist, at a ratio of 4:1 (ratio of free bases). It is intended for sublingual or buccal administration and is available as 2 mg buprenorphine with 0.5 mg naloxone and 8 mg buprenorphine with 2 mg naloxone.
Each film also contains acesulfame potassium salt, ammonium hydroxide, anhydrous citric acid, butylated hydroxyanisole, butylated hydroxytoluene, FD&C Blue No. 1, FD&C Yellow #6, lemon-lime flavor, maltitol, polyethylene oxide, povidone, shellac, and sodium phosphate dibasic anhydrous. Chemically, buprenorphine HCl is (2 S )-2-[17-Cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6-methoxy-6α,14-ethano-14α-morphinan-7α-yl]-3,3-dimethylbutan-2-ol hydrochloride.
It has the following chemical structure: Buprenorphine HCl is a white or almost 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 hydrochloride dihydrate is a white or almost white powder and is soluble in water, slightly soluble in alcohol, and practically insoluble in toluene and ether.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise patients to read the FDA-approved patient labeling (Medication Guide). Storage and Disposal Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store buprenorphine and naloxone sublingual film securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home [ see Warnings and Precautions ( 5.1 , 5.4 ), Drug Abuse and Dependence ( 9.2) ]. Inform patients that leaving buprenorphine and naloxone sublingual film unsecured can pose a deadly risk to others in the home.
Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Expired, unwanted, or unused buprenorphine and naloxone sublingual film should be disposed of by removing the buprenorphine and naloxone sublingual film from the foil packaging, and flushing the unused medication down the toilet (if a drug take-back option is not readily available). Inform patients that they can visit www.fda.gov/drugdisposal for a complete list of medicines recommended for disposal by flushing, as well as additional information on disposal of unused medicines.
Safe Use Before initiating treatment with buprenorphine and naloxone sublingual film, explain the points listed below to caregivers and patients. Instruct patients to read the Medication Guide each time buprenorphine and naloxone sublingual film is dispensed because new information may be available. Buprenorphine and naloxone sublingual film must be administered whole.
Advise patients not to cut, chew, or swallow buprenorphine and naloxone sublingual film. Inform patients and caregivers that potentially fatal additive effects may occur if buprenorphine and naloxone sublingual film is used with benzodiazepines or other CNS depressants, (e.g., alcohol, non-benzodiazepine sedative/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids) and not to use these concomitantly unless supervised by a healthcare provider [see Warnings and Precautions ( 5.2 , 5.3 ), Drug Interactions ( 7 )].
Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [ see Warnings and Precautions ( 5.2 )]. Patient Access to an Opioid overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene) and discuss the importance of having access to an opioid overdose reversal agent.
Because patients being treated for opioid use disorder are at risk for relapse, discuss the importance of having access to an opioid overdose reversal agent. Also discuss the importance of having access to an opioid overdose reversal agent if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. Discuss with the patient the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter (some products), or as part of a community-based program) [see Dosage and Administration ( 2.2 ), Warnings and Precautions (5.2)].
There are important differences among the opioid overdose reversal agents. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent. Educate patients and caregivers on how to recognize the signs and symptoms of an opioid overdose.
Explain to patients and caregivers that effects of opioid overdose reversal agents like naloxone and nalmefene are temporary, and that they must call 911 or get emergency medical help right away in all cases of known or suspected opioid overdose, even if an opioid overdose reversal agent is administered. Repeat administration may be… [Excerpted — this section continues on DailyMed.]
💬 Medication Guide ▾
MEDICATION GUIDE Buprenorphine and Naloxone (bue” pre nor’ feen) and (nal ox’ one) Sublingual Film, CIII IMPORTANT: Keep buprenorphine and naloxone sublingual film 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 takes buprenorphine and naloxone sublingual film, get emergency help or call 911 right away.
Tell your healthcare provider if you are living in a household where there are small children. What is the most important information I should know about buprenorphine and naloxone sublingual film? Buprenorphine and naloxone contains a medicine called buprenorphine.
Buprenorphine is an opioid that can cause serious and life‐threatening breathing problems, especially if you take or use certain other medicines or drugs. Ask your healthcare provider about medicines like naloxone or nalmefene that can be used in an emergency to reverse opioid overdose, including accidental use of buprenorphine and naloxone sublingual film by a child. If naloxone or nalmefene is given, you must call 911 or get emergency medical help right away to treat an overdose or accidental use of an opioid.
Buprenorphine and naloxone may cause serious and life‐threatening breathing problems. Get emergency help right away if you: feel faint feel dizzy are confused feel sleepy or uncoordinated have blurred vision have slurred speech are breathing slower than normal cannot think well or clearly Do not take buprenorphine and naloxone with certain medicines. Taking buprenorphine and naloxone with other opioid medicines, benzodiazepines, gabapentinoids (gabapentin or pregabalin), alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma, and death.
Do not inject (“shoot‐up”) buprenorphine and naloxone. Injecting buprenorphine and naloxone may cause life‐threatening infections and other serious health problems. Injecting buprenorphine and naloxone may cause sudden serious withdrawal symptoms such as pain, cramps, vomiting, diarrhea, anxiety, sleep problems, and cravings.
Do not switch from buprenorphine and naloxone sublingual film to other medicines that contain buprenorphine without talking with your healthcare provider. The amount of buprenorphine in a dose of buprenorphine and naloxone sublingual film is not the same as in other medicines that contain buprenorphine. Your healthcare provider will prescribe a starting dose of buprenorphine and naloxone sublingual film that may be different than other buprenorphine containing medicines you may have been taking.
Do not stop taking buprenorphine and naloxone suddenly. You could become sick and have withdrawal symptoms because your body has become used to the medicine (physical dependence). Physical dependence is not the same as drug addiction.
In an emergency, have family members tell emergency department staff that you are physically dependent on an opioid and are being treated with buprenorphine and naloxone sublingual film. Never give anyone else your buprenorphine and naloxone sublingual film. They could die from taking it.
Selling or giving away buprenorphine and naloxone sublingual film is against the law. Store buprenorphine and naloxone sublingual film securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. What is buprenorphine and naloxone sublingual film?
Buprenorphine and naloxone sublingual film is a prescription medicine used to treat opioid addiction in adults and is part of a complete treatment program that also includes counseling and behavioral therapy. Who should not take buprenorphine and naloxone sublingual film? Do not take buprenorphine and naloxone sublingual film if you are allergic to buprenorphine or naloxone.
Before taking buprenorphine and naloxone, tell your healthcare provider about all your medical conditions, including if you have trouble bre… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Absorption In several pharmacokinetic studies following the administration of different dosages, a dose of one or two of the 2 mg/0.5 mg buprenorphine and naloxone sublingual films administered sublingually or buccally showed comparable relative bioavailability to the same total dose of buprenorphine and naloxone sublingual tablets. In contrast, one 8 mg/2 mg and one 12 mg/3 mg buprenorphine and naloxone sublingual films administered sublingually or buccally showed higher relative bioavailability for both buprenorphine and naloxone compared to the same total dose of buprenorphine and naloxone sublingual tablets.
A combination of one 8 mg/2 mg and two 2 mg/0.5 mg buprenorphine and naloxone sublingual films (total dose of 12 mg/ 3 mg) administered sublingually showed comparable relative bioavailability to the same total dose of buprenorphine and naloxone sublingual tablets, while buccally administered buprenorphine and naloxone sublingual films showed higher relative bioavailability. Table 5, below, illustrates the relative increase in exposure to buprenorphine and naloxone associated with buprenorphine and naloxone sublingual films compared to buprenorphine and naloxone sublingual tablets, and shows the effect of route of administration [see Dosage and Administration ( 2.9 , 2.10 ) ].
Across relevant pharmacokinetic studies, the pharmacokinetic parameters and exposures derived from the buccal and sublingual administrations of buprenorphine and naloxone sublingual film were comparable to one another. Table 5. Changes in Pharmacokinetic Parameters for Buprenorphine and Naloxone Sublingual Film Administered Sublingually or Buccally in Comparison to Buprenorphine and Naloxone Sublingual Tablet Dosage PK Parameter Increase in Buprenorphine PK Parameter Increase in Naloxone Film Sublingual Compared to Tablet Sublingual Film Buccal Compared to Tablet Sublingual Film Buccal Compared to Film Sublingual Film Sublingual Compared to Tablet Sublingual Film Buccal Compared to Tablet Sublingual Film Buccal Compared to Film Sublingual 1 x 2 mg/0.5 mg C max 22% 25% - C max - - - AUC 0-last - 19% - AUC 0-last - - - 2 x 2 mg/0.5 mg C max - 21% 21% C max - 17% 21% AUC 0-last - 23% 16% AUC 0-last - 22% 24% 1 x 8 mg/2 mg C max 28% 34% - C max 41% 54% - AUC 0-last 20% 25% - AUC 0-last 30% 43% - 1 x 12 mg/3 mg C max 37% 47% - C max 57% 72% 9% AUC 0-last 21% 29% - AUC0-last 45% 57% - 1 x 8 mg/2 mg plus 2 x 2 mg/0.5 mg C max - 27% 13% C max 17% 38% 19% AUC 0-last - 23% - AUC 0-last - 30% 19% 1 x 16 mg/4 mg film C max 34% 29% 7% C max 44% 46% 9% AUC 0-last 32% - - AUC 0-last 49% 36% 3% Note: 1. the 16 mg/4 mg strength film is not marketed; it is compositionally proportional to the 8 mg/2 mg strength film and has the same size of 2 x 8 mg/2 mg film.
2. – represents no change when the 90% confidence intervals for the geometric mean ratios of the C max and AUC 0-last values are within the 80% to 125% limit. 3. There are no data for the 4 mg/1 mg strength film; it is compositionally proportional to 2 mg/0.5 mg strength film and has the same size of 2 x 2 mg/0.5 mg film strength.
Distribution Buprenorphine is approximately 96% protein bound, primarily to alpha and beta globulin. Naloxone is approximately 45% protein bound, primarily to albumin. Elimination Buprenorphine is metabolized and eliminated in urine and feces.
Naloxone undergoes metabolism as well. When buprenorphine and naloxone sublingual film is administered sublingually or buccally, buprenorphine has a mean elimination half-life ranging from 24 to 42 hours and naloxone has a mean elimination half-life ranging from 2 to 12 hours. 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… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics 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 mg to 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, O 2 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 O 2 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… [Excerpted — this section continues on DailyMed.]
🔒 Drug Abuse and Dependence ▾
9 DRUG ABUSE AND DEPENDENCE
9.1Controlled Substance Buprenorphine and naloxone sublingual film contains buprenorphine, a Schedule III controlled substance under the Controlled Substances Act.
9.2Abuse 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 healthcare provider 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.
9.3Dependence 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 ( 5.7 ) ]. Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy [ see Warnings and Precautions ( 5.5 ) ].
🔒 Controlled Substance ▾
9.1Controlled Substance Buprenorphine and naloxone sublingual film contains buprenorphine, a Schedule III controlled substance under the Controlled Substances Act.
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity Carcinogenicity data on buprenorphine and naloxone 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/m 2 basis) for 27 months. As in the buprenorphine/naloxone carcinogenicity study in rats, 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/m 2 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 (5 mg/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 [ 3 H]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/m 2 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/m 2 basis) had no adverse effect on fertility.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity Carcinogenicity data on buprenorphine and naloxone 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/m 2 basis) for 27 months. As in the buprenorphine/naloxone carcinogenicity study in rats, 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/m 2 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 (5 mg/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 [ 3 H]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/m 2 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/m 2 basis) had no adverse effect on fertility.
📄 Recent Major Changes ▾
RECENT MAJOR CHANGES SECTION Dosage and Administration ( 2.2 ) 01/2026 Dosage and Administration ( 2.4 ) 05/2025 Warnings and precautions ( 5.2 ; 5.3 ) 01/2026
📄 Package Label / Principal Display Panel ▾
PACKAGE LABEL PRINCIPAL DISPLAY PANEL SECTION Buprenorphine and Naloxone Sublingual Film, 2 mg/0.5 mg - Pouch Label
Buprenorphine and Naloxone Sublingual Film, 2 mg/0.5 mg - Carton Label
Buprenorphine and Naloxone Sublingual Film, 8 mg/2 mg - Pouch Label
Buprenorphine and Naloxone Sublingual Film, 8 mg/2 mg - Carton Label