Common Side Effects of Suboxone
The most common side effects of Suboxone (buprenorphine/naloxone) include constipation, headache, nausea, sedation, and dizziness, with constipation being particularly persistent as tolerance does not develop to this effect. 1
Gastrointestinal Effects
Constipation is the most clinically significant side effect because unlike other opioid-related adverse effects, tolerance does not develop to constipation and it requires active therapeutic management with scheduled bowel regimens including stimulant laxatives and stool softeners. 1, 2
Nausea occurs commonly, particularly during treatment initiation, and is generally well tolerated as a transient effect. 3, 4
The mechanism behind constipation may relate to exposure to norbuprenorphine, an active metabolite that is a potent full agonist at mu-opioid receptors; sublingual formulations may expose patients to higher concentrations of norbuprenorphine compared to buccal formulations, potentially explaining higher constipation rates with sublingual administration. 5
Central Nervous System Effects
Headache is extremely common and typically resolves with continued therapy, though acetaminophen or NSAIDs may be considered if symptoms persist. 1, 2
Sedation and drowsiness occur frequently, particularly at higher doses (above 8-16 mg daily), and patients should be monitored during analgesic administration and dose titration. 1, 4
Dizziness is a common complaint that generally improves with continued treatment. 4
Anxiety may emerge as a side effect, particularly during dose adjustments. 4
Dose-Related Considerations
Side effects including headache, constipation, and sedation may be more pronounced at higher doses (above 16 mg daily), which is an important consideration when titrating buprenorphine for optimal therapeutic effect. 1, 6
The FDA label confirms that buprenorphine produces typical opioid agonist effects which are limited by a ceiling effect, meaning that increasing doses beyond a certain point do not produce proportionally greater effects but may increase side effect burden. 7
Respiratory Effects
Respiratory depression can occur but has a ceiling effect, making buprenorphine safer than full opioid agonists; this ceiling effect on respiratory depression has been verified at doses up to 70 times normal analgesic doses. 1, 2
Hypoventilation not requiring medical intervention has been reported more frequently after buprenorphine doses of 4 mg and higher in opioid-experienced volunteers. 7
Rare but Serious Adverse Effects
Serotonin syndrome is a rare but potentially serious complication when buprenorphine is combined with serotonergic medications such as tricyclic antidepressants, SSRIs, or SNRIs; emergency physicians should maintain awareness of this interaction. 8
Acute intoxication may present with mild mental status changes, minimal respiratory depression, small (but not pinpoint) pupils, and relatively normal vital signs; symptoms may persist for 12-24 hours due to buprenorphine's long duration of action. 9
Important Clinical Pitfalls
Do not discontinue buprenorphine if edema develops, as edema is not a recognized adverse effect of buprenorphine therapy; instead, evaluate for cardiac, renal, hepatic, venous, or endocrine causes, and review concurrent medications (particularly NSAIDs and calcium channel blockers) as more likely culprits. 2
Patients on tricyclic antidepressants or other serotonergic agents require careful monitoring when initiating buprenorphine due to serotonin syndrome risk. 8
The combination of buprenorphine with other sedating medications (particularly benzodiazepines) carries an FDA black box warning for possible serious effects including slowed or difficult breathing and death. 1