Will a patient taking Brixadi (buprenorphine) 128mg subcutaneously (subcut) experience withdrawal symptoms when stopping the medication?

Brixadi Discontinuation and Withdrawal Risk

A patient stopping Brixadi (buprenorphine) 128mg subcutaneous will likely experience withdrawal symptoms, as buprenorphine does not "taper itself" despite its long-acting formulation—the extended-release depot formulation provides gradual decline in plasma levels but this does not eliminate withdrawal risk, and physical dependence develops with chronic opioid exposure including buprenorphine. 1

Understanding Buprenorphine Physical Dependence

• Physical dependence develops with repeated buprenorphine exposure, manifesting as withdrawal symptoms upon discontinuation including restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, mydriasis, irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. 1

• The FDA label explicitly warns that buprenorphine should not be abruptly discontinued in physically-dependent patients, as an abstinence/withdrawal syndrome may occur. 1

• While buprenorphine produces less physical dependence than full opioid agonists and patients may be more easily detoxified compared to methadone, withdrawal symptoms still occur. 2

Brixadi-Specific Pharmacokinetics

• Brixadi's extended-release formulation provides sustained buprenorphine levels over weeks (weekly or monthly dosing depending on formulation), but once the depot is exhausted, plasma concentrations decline and withdrawal can emerge. 1

• The gradual pharmacokinetic decline from depot formulations does not constitute therapeutic tapering—it simply reflects slower drug elimination, not a planned dose reduction strategy designed to minimize withdrawal. 1

• When CYP3A4 inhibitors are discontinued (causing buprenorphine levels to decrease), the FDA warns of potential withdrawal syndrome in physically-dependent patients, demonstrating that even gradual declines in buprenorphine levels can trigger withdrawal. 1

Withdrawal Timeline and Severity

• Withdrawal symptoms from buprenorphine typically resolve within 3-7 days but can be uncomfortable, with severity varying based on dose and treatment duration. 3

• Opioid withdrawal symptoms generally resolve relatively rapidly after discontinuation depending on the specific opioid, dose, and treatment duration. 3

• "Protracted withdrawal" may occur months after elimination, with symptoms including dysphoria, irritability, insomnia, anhedonia, or vague sense of being unwell—these must be anticipated and addressed. 3

Critical Clinical Considerations

• Abrupt discontinuation without support carries significant risks: Very low-certainty evidence suggests abrupt discontinuation increases relapse risk (HR 2.09,95% CI 1.59-2.74) compared to continuation. 4

• Fear of withdrawal is a major reason patients continue opioid therapy and contributes to treatment dropout when tapering is attempted. 3

• Drugs acting on the central nervous system, including opioids, are known to cause severe withdrawal symptoms when stopped abruptly, necessitating gradual tapering. 5

Recommended Approach to Discontinuation

• Gradual tapering is essential: Withdrawal symptoms can be averted by tapering the drug slowly rather than abrupt cessation. 3

• For patients on Brixadi 128mg (high dose), consider transitioning to sublingual buprenorphine to allow more controlled tapering with dose reductions typically starting at 10% decrements. 3

• Withdrawal management should include adjuvant medications: α2-adrenergic agonists (clonidine, lofexidine), antiemetics for nausea, benzodiazepines for anxiety/muscle cramps, and loperamide for diarrhea. 3

• Psychological support during discontinuation may improve outcomes: Preventive cognitive therapy or mindfulness-based cognitive therapy combined with tapering resulted in 40-75% successful discontinuation rates in some studies. 4

Common Pitfalls to Avoid

• Do not assume the depot formulation eliminates withdrawal risk—physical dependence persists regardless of delivery method. 1

• Do not confuse pain exacerbation with withdrawal—increased pain during discontinuation may represent a withdrawal symptom (hyperalgesia) rather than return of original pain, as descending pain facilitatory tracts show increased firing during early abstinence. 3

• Avoid equating physical dependence with addiction—physical dependence is an expected physiological response to chronic opioid exposure that occurs even in appropriate medical use, while addiction is a separate behavioral disorder. 3