Can You Take Opioids with Sublocade?
Yes, you can take opioid analgesics together with Sublocade (extended-release buprenorphine injection), but higher-than-usual opioid doses will be required and careful monitoring is essential. 1, 2
Why This Combination Is Challenging
Buprenorphine (the active ingredient in Sublocade) is a partial mu-opioid receptor agonist with extremely high receptor binding affinity, meaning it occupies opioid receptors very tightly and can block or compete with full opioid agonists like morphine, oxycodone, or hydromorphone. 2, 3 This pharmacologic property makes pain management more complex but not impossible.
Evidence-Based Management Strategies
The 2021 Mayo Clinic/SPAQI consensus statement recommends continuing buprenorphine therapy (including extended-release formulations like Sublocade) and adding full mu-opioid agonists at higher doses when analgesia is inadequate after optimizing non-opioid therapies. 1 This approach is supported by the 2006 Annals of Internal Medicine guidelines, which state that full opioid agonists can be titrated alongside buprenorphine maintenance therapy. 1
Recommended Approach for Acute Pain
Continue your Sublocade injections without interruption. Discontinuing buprenorphine precipitates withdrawal and dramatically increases relapse risk to illicit opioids. 1
Add short-acting full opioid agonists (morphine, oxycodone, hydromorphone, or fentanyl) at higher doses and shorter intervals than used in opioid-naïve patients—typically every 3–4 hours rather than every 4–6 hours. 1, 4, 2
Use scheduled (around-the-clock) dosing rather than as-needed dosing to maintain consistent analgesia and prevent breakthrough pain. 1, 4
Avoid mixed agonist-antagonist opioids (pentazocine, nalbuphine, butorphanol) because they can precipitate acute withdrawal syndrome. 1, 4, 2
Why Higher Opioid Doses Are Needed
Patients on buprenorphine maintenance develop cross-tolerance to other opioids and may have increased pain sensitivity (opioid-induced hyperalgesia), requiring substantially higher analgesic doses to achieve adequate pain relief. 1, 4 Animal studies confirm that combining buprenorphine with full mu-agonists in the therapeutic dose range produces additive or synergistic analgesic effects rather than antagonism. 3
Alternative Strategies for Severe Pain
If standard doses of added opioids fail to control pain, three additional options exist:
Divide the Sublocade-equivalent dose into every 6–8 hour sublingual buprenorphine dosing to leverage buprenorphine's own analgesic properties (which last 6–8 hours rather than the 24+ hours needed for opioid-dependence treatment), then add supplemental full agonists as needed. 1, 2
For hospitalized patients with severe acute pain, temporarily discontinue buprenorphine and convert to methadone 20–40 mg daily plus short-acting opioid analgesics, then convert back to buprenorphine before discharge. This requires inpatient monitoring with naloxone at bedside. 1
Discontinue buprenorphine entirely and use full opioid agonists alone, converting back to buprenorphine once acute pain resolves. This approach carries the highest relapse risk and should be reserved for situations where other strategies have failed. 1, 2
Critical Safety Precautions
Have naloxone immediately available when administering full opioid agonists to patients on buprenorphine, and monitor respiratory rate and level of consciousness frequently. 1, 2
The FDA black-box warning states that combining opioids with benzodiazepines or other CNS depressants (alcohol, sedatives, muscle relaxants, general anesthetics) markedly increases the risk of respiratory depression and death. If you are taking benzodiazepines, this risk is substantially amplified. 5
Screen for QT-prolonging medications before adding opioids, as buprenorphine can prolong the QT interval by up to 15 msec. 5
Notify your Sublocade prescriber or opioid-treatment program about any additional opioids prescribed, as they will appear on routine urine drug screening. 1, 4
Multimodal Analgesia Is Essential
Maximize non-opioid analgesics first: scheduled acetaminophen, NSAIDs (if no contraindications), and adjuvant medications (gabapentin, pregabalin, tricyclic antidepressants) before escalating opioid doses. 4, 2, 6
Consider regional anesthesia or nerve blocks for surgical or procedural pain when feasible. 6
Common Pitfalls to Avoid
Under-treating pain due to fear that buprenorphine will block opioid effects. While higher doses are needed, adequate analgesia is achievable. 1, 4
Using as-needed dosing instead of scheduled dosing, which allows pain to recur and increases patient distress. 1, 4
Abruptly discontinuing Sublocade to "make room" for other opioids, which precipitates withdrawal and increases overdose risk if the patient relapses to illicit opioids. 1
What to Expect
Recent case series demonstrate that patients on extended-release buprenorphine formulations (including Sublocade) can achieve adequate pain control through continuation of buprenorphine combined with full opioid agonists and non-opioid adjuncts, with no cases of respiratory depression or toxicity reported when properly monitored. 6 A 2024 trial of 100 patients receiving extended-release buprenorphine found the formulation to be acceptable, well-tolerated, and safe. 7
The key principle is that your addiction treatment should never be interrupted to manage pain—both can be addressed simultaneously with appropriate dosing and monitoring. 1, 4