Buprenorphine

Is buprenorphine safe?

Buprenorphine carries fewer risks than full opioids such as methadone or oxycodone, but safe is relative here. It is a partial opioid: its effects rise with the dose and then level off, so a large dose taken alone by a tolerant adult is much less likely to stop breathing than the same mistake with methadone or oxycodone. The risk returns when it is mixed with benzodiazepines or alcohol, injected, or taken by a child or someone with no tolerance. We score it 42, well above full opioids such as oxycodone (26) and methadone (22).

For people with opioid addiction, the more important number is how much it lowers the risk of dying. That is large, and the score should not be read as a reason to avoid or stop treatment.

Treatment saves lives

In a 2017 BMJ meta-analysis of cohort studies, people in buprenorphine treatment died of an overdose at 1.4 per 1,000 person-years against 4.6 after leaving treatment, and all-cause deaths were 4.3 against 9.5. Among 17,568 Massachusetts adults who survived an overdose, buprenorphine treatment was linked to a 38% lower risk of opioid-related death. The weeks after stopping were among the riskiest periods, because tolerance falls quickly.

Access has widened. The US ended its special prescriber waiver in January 2023; in health records covering more than a million US adults with opioid use disorder, people newly diagnosed afterwards had 14% higher odds of starting buprenorphine.

The ceiling effect and its limits

The Suboxone label reports that in opioid-experienced volunteers, opioid effects reached their maximum between 8 mg/2 mg and 16 mg/4 mg and rose little after that. That is part of why maintenance doses of up to 24 mg a day can be used in people already tolerant.

The ceiling does not protect everyone. The label reports deaths in opioid-naive adults given a single 2 mg dose, and buprenorphine can cause severe, possibly fatal, breathing problems in children who find a film or tablet. Of 74,474 opioid overdose deaths reported to the CDC’s SUDORS system by 32 US jurisdictions between July 2019 and June 2021, 2.6% involved buprenorphine, and 92.7% of those also involved at least one other drug; about half involved illicit fentanyl.

The real danger: mixing

The label says many of the reports of coma and death involved injection misuse or benzodiazepines and other sedatives, including alcohol, sleeping pills, gabapentin and pregabalin. It also says treatment should not be categorically denied to people who use these drugs, because barriers to treatment can be more dangerous than the combination; the safer path is honest discussion and closer monitoring.

CYP3A4CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary inhibitors, such as some antifungals, macrolide antibiotics and HIV medicines, can raise buprenorphine levels, and inducers can lower them, so mention every new medicine to your pharmacist.

Forms and what each is for

Butrans is limited to people who need up to the equivalent of 80 mg of oral morphine a day. The pain products carry the same addiction and breathing warnings as other strong painkillers.

Other side effects

In a 4-week trial, headache affected 36.4% of people on Suboxone tablets against 22.4% on placebo, and constipation 12.1% against 2.8%; nausea and sweating are also common. The label warns of hepatitis, so liver tests are advised before and during treatment, and of dental problems from products dissolved in the mouth, including cavities and tooth loss. Starting too soon after a full opioid can bring on precipitated withdrawal. Newborn withdrawal is expected after use in pregnancy and is treatable.

Staying safe

• Keep naloxone at home; for a buprenorphine overdose, higher or repeated doses may be needed.
• Store films and tablets locked away from children and visitors.
• Avoid alcohol and do not add sleeping pills or benzodiazepines without talking to your prescriber.
• Do not stop suddenly; withdrawal is milder than with full opioids, but relapse after stopping carries a high overdose risk.

How we scored it

Track record (85) is strong after 45 years of use. Dependence (25), interactions (30) and regulatory warnings (35) are low, reflecting a Schedule IIIControlled substanceA medicine or drug that the law restricts because it can be misused or cause dependence. Countries group them into schedules or classes.More in the glossary opioid with boxed warningsBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary on several forms. Overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (40) and serious side effects (45) score better than any full opioid because of the ceiling effect, but stay below 50 because mixing with sedatives can still be fatal.