Suboxone (Buprenorphine/Naloxone)

Suboxone (Buprenorphine/Naloxone) is a combination medication used in opioid replacement therapy in opioid use disorder, and chronic pain management. Buprenorphine is a partial opioid agonist, while naloxone is a competitive opioid antagonist added to prevent misuse.

Suboxone contains both buprenorphine and naloxone in a 4:1 ratio (the lowest possible prescribed ratio is 2mg/0.5mg). Buprenorphine is the active opioid partial agonist, while naloxone is an opioid antagonist added to reduce abuse potential. Naloxone has poor oral bioavailability and will precipitate withdrawal in opioid-dependent patients if injected intravenously.

Buprenorphine is a partial µ-receptor agonist with a low intrinsic activity at the receptor site. Clinically, this gives it a “ceiling effect”: the opioid agonist effects plateau at higher doses. As a result, there is a much lower risk of overdose (including respiratory depression) compared to methadone and other opioids. Buprenorphine also attaches tightly to opioid receptors and dissociates slowly, giving it up to 72 hours duration of action. Suboxone must be taken sublingually, since it has poor oral bioavailability.

  • Rapid absorption by buccal mucosa, then slowly released into bloodstream, 45 to 90 minutes
  • Peak plasma concentration in 1 to 4 hours
  • Very low oral bioavailability due to first pass metabolism, hence it is delivered either sublingual or intradermal (via a patch)

Ensure the patient has waited the appropriate amount of time prior to induction (see Table). Buprenorphine/naloxone is a safe medication, but will displace any opioids attached to the opioid receptors. Always remind the patient to keep the sublingual tablet in their mouth until the tablet is dissolved, which can take several minutes.

Waiting Period Prior to Induction

Short-Acting Opioid Intermediate-Acting Opioid Long-Acting Opioid
Example Heroin, morphine, hydrocodone, immediate-release oxycodone Slow-release oral morphine, controlled-release
hydromorphone, sustained-release oxycodone
Methadone
Tapering Schedule Stop at midnight Stop at midnight Reduce methadone by up to 30mg per day over a period of 1 week
Onset of Moderate Withdrawal Symptoms (i.e. - COWS > 12) 12–16 hours after last
dose
17–24 hours after last
dose
30–48 hours (or more) after last dose
When to Start Induction As soon as COWS > 12 As soon as COWS > 12 Wait at least 24 hours, but preferably 48–72 hours after last methadone dose if patient can tolerate withdrawal symptoms, before beginning induction
Ambulatory (Office) Induction
  • Patient waits in ambulatory care office until the report withdrawal symptoms and have a COWS score of 12+
  • First dose: 4 mg SL
  • Reassess in 2 hours. If patient improved but still in withdrawal, give another 4 mg to take in office or at home
  • Maximum dose is 12mg in 24 hours
Home Induction
  • Prescribe 2mg SL q4H PRN, up to 6 tabs over 24 hours, x 1–3 days (e.g. - 18 tabs all as take-home or 6 tabs daily dispensed for 3 days)
  • Patient must wait at least 12 hours after last opioid, or longer if using a long-acting.
  • First dose: 4mg SL
  • If still in withdrawal after 2 hours, take another 4mg SL
  • Maximum dose is 12mg in 24 hours

After induction, reassess the daily dosing in within 3 days. It is appropriate to increase the dose by 2–4 mg at each visit if patient continues to report withdrawal symptoms or cravings towards the end of a dosing interval. Each dose increase should increase duration of relief from withdrawal and cravings. The typical maintenance dose is usually 8 to 16 mg daily, with a maximum dose of 24 mg daily. Higher doses have been noted in case reports. An optimal dose will relieve withdrawal symptoms and cravings for 24 hours; prescribers should also ask for common side effects such as sedation.

The Burnese Method is an induction method of using microdoses of buprenorphine in patients with concomitant full opioid agonist use.[1] The theory behind this method is that repetitive administration of very small doses of buprenorphine in regular intervals will not precipitate opioid withdrawal. Since there is a long receptor binding time, buprenorphine will continue to accumulate at the opioid receptor and an increasing amount of a full μ-agonist will be replaced by buprenorphine at the opioid receptor. It is important to note that this is not yet considered an evidence-based method. This method may be helpful for patients fearful of precipitated withdrawal, or if they experience severe withdrawal symptoms during conventional induction.

A common starting dose for induction is buprenorphine 0.5mg, which involves splitting Suboxone 2mg/0.5mg tablet into quarters. Here are is a sample micro-induction schedule for individuals on short-acting opioids:

Burnese Method: Short-Acting Opioid

Day Buprenorphine / Naloxone Opioid
1 0.5 mg daily Maintain dose
2 1.0 mg daily Maintain dose
3 1.5 mg daily Maintain dose
4 2.0 mg daily Maintain dose
5 2.5 mg daily Maintain dose
6 3.0 mg daily Maintain dose
7 4.0 mg daily Stop short-acting opioid
  • To transition from sublingual Suboxone to intradermal (patch):
    • Stop all opioid medications at midnight (no opioids x 8-12 hours)
    • To prevent the patient from going into precipitated withdrawal, the COWS must be > 12. Allow patient to enter into withdrawal for at least 8 hours if they are on a short-acting opioid
    • Start buprenorphine patch 20mcg/hr patch x 7 days

Suggestions for Managing Missed Doses

Buprenorphine Dose Number of Consecutive Days Missed Missed New Starting Dose
> 8mg > 7 days 4mg
> 8mg 6-7 days 8mg
6-8mg 6 or more days 4mg
2-4mg 6 or more days 2-4mg

In patients with concomitant alcohol and opioid withdrawal, the alcohol withdrawal should always be treated first. While opioid withdrawal can be extremely uncomfortable, it does not result in mortality. On the other hand, untreated alcohol withdrawal can result in high mortality. When treating concomitant withdrawal symptoms, consider using lorazepam instead of diazepam, to reduce the length of respiratory depression. Once the alcohol withdrawal has resolved, then the patient can start on a suboxone induction. While the patient is on alcohol withdrawal treatment, they can be treated symptomatically with clonidine 0.05mg PO q1h.

  • Remind your patients: do not swallow the foam, the sublingual tablet must sit under the tongue and be absorbed by the buccal mucosa. If the foam is swallowed, the medication will not have any effect due to its poor oral bioavailability!
  • Avoid prescribing benzodiazepines with Suboxone! The combined use of opioids with benzodiazepines can result in serious side effects, including respiratory depression and death. If prescribed together, limit the dosages and duration of each drug to a minimum. Warn patients and caregivers about the risks of slowed or difficult breathing and/or sedation. The vast majority of deaths involving buprenorphine also had the presence of other sedating drugs, especially benzodiazepines.[2]
  • Buprenorphine has side effects similar to other opioids, including sedation, constipation, and nausea.
  • Liver dysfunction 3-5x the upper limit of normal, due to the naloxone's effect on the liver

Naloxone poses a theoretical risk of elevating maternofetal cortisol levels. Though previously considered a contraindication, more recent studies have not validated these concerns, and as a result pregnancy is no longer considered a contraindication to Suboxone.[3]

For Providers