buprenorphine (Suboxone)

no boxed warning, and what the label warns about instead

the suboxone film label has no boxed warning [label]. the warnings that matter most, in plain words:

• breathing and overdose: "buprenorphine has been associated with life-threatening respiratory depression and death." the label says many, but not all, of the reported comas and deaths "involved misuse by self-injection or were associated with the concomitant use of buprenorphine and benzodiazepines or other cns depressants, including alcohol" [label 5.2]. it asks prescribers to strongly consider an overdose reversal medicine such as naloxone for every patient, both when starting and when renewing, because relapse puts people at risk of opioid overdose [label 2.2, 5.2].
• children: "buprenorphine can cause severe, possibly fatal, respiratory depression in children who are accidentally exposed to it." the instruction is to store it out of sight and reach and destroy unused medicine [label 5.4].
• newborns: neonatal opioid withdrawal syndrome "is an expected and treatable outcome of prolonged use of opioids during pregnancy", and the label weighs it against the risk of untreated opioid addiction, which "often results in continued or relapsing illicit opioid use and is associated with poor pregnancy outcomes" [label 5.5].
• withdrawal at the start: taken too soon after another opioid, it can bring on withdrawal, so the first dose is given "when objective signs of moderate opioid withdrawal appear, not less than six hours after the patient last used opioids". people coming off methadone or other long-acting opioids "may be more susceptible to precipitated and prolonged withdrawal" [label 2.3, 5.10].
• liver: cases of hepatitis, from silent rises in liver enzymes to "case reports of death, hepatic failure", have been reported, often alongside hepatitis b or c, other liver-toxic drugs or injecting. the label recommends liver tests before starting and periodically after [label 5.8]. it is not recommended in severe liver impairment [label 5.12].
• teeth, set out in the next block [label 5.13].
• also on the label: adrenal insufficiency, a qt effect of up to 15 milliseconds in formal studies, dizziness on standing, impaired driving at the start and after dose changes, and allergic reactions [label 5.6, 5.9, 5.14 to 5.16].

does suboxone cause tooth decay? what the fda found

on january 12, 2022 the fda warned that "dental problems have been reported with medicines containing buprenorphine that are dissolved in the mouth", including "tooth decay, cavities, oral infections, and loss of teeth", and that they "can be serious and have been reported even in patients with no history of dental issues" [fda-2022]. it counted 305 cases reported to its adverse event system or published, 131 of them serious. the average age was 42; 26 people had no prior dental history; 113 cases involved two or more teeth; the commonest treatment was tooth extraction, in 71 cases. some problems appeared as soon as 2 weeks after starting, and the median time to diagnosis was about 2 years [fda-2022]. the fda says these are only the cases it knows about and that "we cannot determine how likely it is that someone will experience these side effects". the concern is limited to tablets and films dissolved under the tongue or against the cheek; the fda "has not identified a concern for dental health" with the patch or the injection [fda-2022].

the fda required a dental warning on every such product. the suboxone label now says cases of dental caries, "some severe (i.e., tooth fracture, tooth loss)", have been reported, "multiple cases were reported in individuals without any prior history of dental problems", and lists what helps: refer patients to dental care and regular checkups, gently rinse the teeth and gums with water and swallow once the film has completely dissolved, and "wait for at least one hour after taking suboxone before brushing teeth" [label 5.13]. in the same notice the fda says "the benefits of these medicines clearly outweigh the risks" and that patients should keep taking it as prescribed [fda-2022]. a case count of this kind has no comparison group, so it shows that the problem is real and can be severe, not how often it happens.

benzodiazepines and other sedatives: the warning that tells prescribers not to refuse treatment

the label says taking buprenorphine with benzodiazepines or other sedatives, a list that runs from alcohol and sleeping pills to antipsychotics, gabapentin, pregabalin and other opioids, "increases the risk of adverse reactions including overdose, respiratory depression, and death" [label 5.3; label-row]. then it says something most interaction warnings do not: treatment "should not be categorically denied to patients taking these drugs. prohibiting or creating barriers to treatment can pose an even greater risk of morbidity and mortality due to the opioid use disorder alone" [label 5.3]. it adds that "there is no evidence to support dose limitations or arbitrary caps of buprenorphine" as a way to manage benzodiazepine use, that benzodiazepines "are not the treatment of choice for anxiety or insomnia" for people in buprenorphine treatment, and that stopping or tapering the sedative is preferred in most cases [label 5.3].

the size of the combination risk comes from studies of opioids in general, not of buprenorphine treatment, and is labelled here as class evidence. the benzodiazepine labels have carried a boxed warning on the opioid combination, rewritten for the whole class in 2020 [fda-2020]. among 315,428 insured adults filling an opioid prescription, those also filling a benzodiazepine had about twice the odds (adjusted odds ratio 2.14) of an emergency visit or admission for opioid overdose [sun-2017]; a benzodiazepine was present in 33.1% of prescription-opioid deaths in 2017 [tori-2020]; and in 25 states in early 2018, 62.6% of opioid deaths also involved cocaine, methamphetamine or a benzodiazepine [gladden-2019]. none of these studies is about people on buprenorphine for opioid dependence.

what the label says about stopping

buprenorphine causes physical dependence, with withdrawal on abrupt stopping or a rapid taper that is "typically milder than seen with full agonists and may be delayed in onset" [label 5.7, 9.3]. the label’s instruction: "the decision to discontinue therapy with suboxone sublingual film after a period of maintenance should be made as part of a comprehensive treatment plan. advise patients of the potential to relapse to illicit drug use following discontinuation", and taper to reduce withdrawal [label 2.8]. it gives no taper schedule. the fda’s dental notice repeats the point for anyone worried about their teeth: do not stop suddenly without talking to a health care professional [fda-2022].

what the trials measured, in whom, and for how long

the film was not tested for efficacy on its own. its label says its safety "is supported by clinical trials using" the earlier tablets and a sublingual solution, plus an open-label study of 194 people taking the film under the tongue and 188 against the cheek, and an induction study of 34 [label 6.1]. the efficacy trials sit on the tablet labels [tablet-label 14]. all of them gave buprenorphine with counseling; "there were no clinical studies conducted to assess the efficacy of buprenorphine as the only component of treatment" [tablet-label 14].

three trials carry the dosing. in a 4-week trial, 326 people addicted to heroin took buprenorphine with naloxone (16 mg/4 mg), buprenorphine alone (16 mg) or placebo; the share of thrice-weekly urine samples free of other opioids "was statistically higher" on both active tablets than on placebo [tablet-label 14]. in a 16-week trial, 162 people took buprenorphine solution (8 mg) or one of two low doses of a full-agonist comparator; buprenorphine kept more people in treatment and reduced opioid use more than the lower comparator dose, and was similar to the moderate dose, "but equivalence was not demonstrated" [tablet-label 14]. in a 16-week dose trial of 731 people given 1, 4, 8 or 16 mg of solution, the three higher doses beat 1 mg on retention and clean urine samples [tablet-label 14]. the label prints none of these results as percentages, only as better or not.

in pregnancy, the label reports a randomised trial (mother) of 175 women: newborns exposed to buprenorphine needed less morphine (mean 1.1 mg against 10.4 mg), left hospital sooner (10.0 against 17.5 days) and were treated for withdrawal for fewer days (4.1 against 9.9) than those exposed to methadone, with no difference in how many needed treatment. but 33% of the women on buprenorphine left treatment before delivery against 18% on methadone, and the label says that imbalance makes the findings "difficult to interpret" [label 8.1].

side effects, with the label’s numbers

in the 4-week trial (107 on buprenorphine with naloxone, 103 on buprenorphine, 107 on placebo), headache was 36.4% and 29.1% against 22.4% on placebo, constipation 12.1% and 7.8% against 2.8%, nausea 15.0% and 13.6% against 11.2%, abdominal pain 11.2% and 11.7% against 6.5%, and sweating 14.0% and 12.6% against 10.3%. withdrawal symptoms ran the other way, 25.2% and 18.4% against 37.4% on placebo, as did diarrhea (3.7% and 4.9% against 15.0%) [label table 2]. in the 16-week dose trial of 731 people, with no placebo arm, the commonest events were headache (30%), insomnia (25%), pain (24%), withdrawal (22%) and infection (20%) [label table 3].

with the film itself, the commonest event was numbness in the mouth, and others included constipation, a sore or burning tongue, redness inside the mouth, vomiting, trouble concentrating, palpitations, insomnia, withdrawal, sweating and blurred vision [label 6.1]. after approval, the most frequent reports were swelling of the legs and inflammation, blistering and ulcers of the mouth and tongue; dental decay, including tooth fracture and loss, is on the same post-approval list [label 6.2]. the film must be dissolved whole under the tongue or against the cheek, not cut, chewed or swallowed [label 2.5].

what the research says, in both directions

a limit to state first: this site’s library holds one row tagged buprenorphine: The buprenorphine label says the benzodiazepine interaction is a reason to manage, not to refuse treatment. when this section was checked on 2026-10-13 that one row was the label’s own benzodiazepine warning [label-row], and the library held no buprenorphine trial. the evidence below is the label’s trials, the fda’s notice and class evidence on sedative combinations, each marked as such.

in favour. in every placebo- or dose-controlled trial on the label, buprenorphine kept more people in treatment or produced more opioid-free urine samples than placebo or a near-placebo dose [tablet-label 14]. the fda, in the same notice that announced the dental warning, states that the benefits "clearly outweigh the risks", that regular use "reduces withdrawal symptoms and the desire to use opioids", and, citing samhsa, that medication with counseling "has been shown to be effective in improving patient survival, decreasing opioid use" [fda-2022]. the label itself says the risks of untreated opioid addiction, in pregnancy and with sedatives, can outweigh the drug’s own [label 5.3, 5.5].

against, or smaller than it sounds. the label’s trials ran 4 to 16 weeks, measured retention and urine tests rather than overdose or death, and print no effect sizes [tablet-label 14]. equivalence with the full-agonist comparator was not shown [tablet-label 14]. the film’s own data are open-label [label 6.1]. the dental harm can be severe and has been seen in people with healthy teeth, and how often it happens is unknown [fda-2022; label 5.13]. reported deaths include people who had never used opioids given a 2 mg dose for pain, which is why the label says the film "is not appropriate as an analgesic" [label 5.11]. and the survival claim the fda quotes is samhsa’s; no mortality trial sits on this label or in this library.

questions people ask

does suboxone have a black box warning?

no. the suboxone sublingual film label has no boxed warning. its main warnings are life-threatening breathing problems, especially with benzodiazepines, alcohol or other sedatives; accidental exposure in children, which can be fatal; withdrawal in newborns after use in pregnancy; withdrawal if the first dose is taken too soon after another opioid; liver injury; and dental problems. it is a schedule iii controlled substance.

does suboxone cause tooth decay?

the fda says dental problems, including tooth decay, cavities, infections and tooth loss, have been reported with buprenorphine medicines dissolved in the mouth, suboxone among them, and can be serious even in people with no dental history. in january 2022 it counted 305 cases, 131 serious, with extraction the commonest treatment, and required a dental warning on the label. it says it cannot estimate how likely the problem is, that the benefits clearly outweigh the risks, and that patients should not stop suddenly. the label advises rinsing with water after the film dissolves, waiting an hour before brushing, and regular dental checkups.

can you take suboxone with a benzodiazepine?

the label says the combination raises the risk of overdose, breathing problems and death, and asks prescribers to educate patients and manage the sedative, with stopping or tapering it preferred in most cases. it also says treatment should not be categorically denied to people taking these drugs, because the untreated opioid disorder can be the greater risk, and that capping the buprenorphine dose is not supported. this is a question for the prescriber.

what happens if you stop suboxone suddenly?

the label says buprenorphine causes physical dependence and abrupt stopping or a rapid taper brings withdrawal, typically milder and slower to start than with full opioids. it says the decision to stop should be part of a treatment plan, that patients should be told about the risk of relapse, and that the dose should be tapered. the fda adds that stopping suddenly can lead to relapse that could result in overdose and death.

how well does suboxone work?

in the trials on the tablet labels, buprenorphine given with counseling produced more opioid-free urine samples than placebo over 4 weeks, kept more people in treatment than a low dose of a full-agonist comparator over 16 weeks, and doses of about 6 mg and up beat a very low dose. the label prints no effect sizes, and the trials ran 4 to 16 weeks. the fda says the benefits clearly outweigh the risks and cites samhsa that medication with counseling improves survival.

what are the most common side effects of suboxone?

in the 4-week tablet trial, headache (36% against 22% on placebo), nausea, constipation (12% against 3%), abdominal pain and sweating; withdrawal symptoms were less common than on placebo. with the film, numbness in the mouth was the commonest event. after approval, swelling of the legs and mouth and tongue inflammation were the most reported, and dental decay is on the same post-approval list.

sources for this section

the library rows link to our one-page summary of each study, with the original paper, its funding and our evidence grade on that page.

1. suboxone (buprenorphine and naloxone) sublingual film prescribing information, fda label on dailymed (set id 8a5edcf9-828c-4f97-b671-268ab13a8ecd, version 37, effective december 22, 2025): sections 1, 2.2, 2.3, 2.5, 2.8, 5.2 to 5.16, 6.1, 6.2, 8.1, 9.1, 9.3 and tables 2 and 3; no boxed warning and no clinical studies section
2. drugs@fda, nda 022410 (suboxone sublingual film), approved august 30, 2010; the tablet form, nda 020733, was approved october 8, 2002
3. buprenorphine hcl and naloxone hcl sublingual tablets prescribing information, fda label on dailymed (set id 17b63f10-c9df-44be-80fa-6f1c305583b8, version 55, effective february 2, 2026; a generic of the suboxone tablet): section 14, clinical studies
4. us food and drug administration. fda warns about dental problems with buprenorphine medicines dissolved in the mouth to treat opioid use disorder and pain (drug safety communication, january 12, 2022); read on the verification date
5. the suboxone film label’s benzodiazepine and sedative warning, read for the library: sections 5.2 and 5.3, including "should not be categorically denied" (dailymed, february 2026) (library row)
6. cms medicare part d prescribers by geography and drug, national rows, 2024: 378,699 beneficiaries summed across buprenorphine label rows, including pain products, an upper bound on distinct people; against 54,375,198 part d enrollees (cms medicare monthly enrollment, 2024)
7. ahrq medical expenditure panel survey, 2024 prescribed medicines public-use file (hc-254a): buprenorphine is masked in the public file, so no all-payer count is published; checked by veisund
8. fda drug safety communication, september 2020: fda requiring boxed warning updated to improve safe use of benzodiazepine drug class (class evidence, not buprenorphine) (library row)
9. sun ec, et al. association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. bmj 2017 (opioid prescriptions in general, not buprenorphine treatment) (library row)
10. tori me, larochelle mr, naimi ts. alcohol or benzodiazepine co-involvement with opioid overdose deaths in the united states, 1999 to 2017. jama network open 2020 (library row)
11. gladden rm, et al. changes in opioid-involved overdose deaths by opioid type and presence of benzodiazepines, cocaine, and methamphetamine, 25 states, 2017 to 2018. mmwr 2019 (library row)

Withdrawal symptoms on the buprenorphine label

The buprenorphine FDA label names withdrawal symptoms in its Adverse Reactions section, in the list below.

Most-reported reactions

• Drug dependence16,380
• Death14,201
• Overdose14,042
• Toxicity to various agents11,449
• Pain10,907
• Drug withdrawal syndrome10,188
• Drug ineffective7,557
• Emotional distress6,722
• Nausea6,718
• Drug abuse4,985