Dosing & Uses
Dosage Forms & Strengths
film, sublingual (Suboxone): Schedule III
tablet, sublingual (Zubsolv): Schedule III
buccal film (Bunavail): Schedule III
tablet, sublingual (generic): Schedule III
Induction (buprenorphine SL)
- Day 1: 4 mg SL initially; may be repeated after 2 hours if withdrawal symptoms are not relieved; not to exceed 8 mg
- Day 2: If no withdrawal symptoms are present, 4 mg SL; if withdrawal symptoms are present, dose is increased by 4 mg; if symptoms are not relieved after >2 hr, 4 mg is administered; not to exceed 16 mg SL
- Switch to buprenorphine/naloxone for unsupervised maintenance
Induction (buprenorphine/naloxone [Suboxone])
- Caution: buprenorphine/naloxone (Suboxone) induction is only for patients dependent on short-acting opioids (eg, heroin) and not for those dependent on long-acting opioids (eg, methadone); buprenorphine monotherapy is recommended for induction for long-acting opioids
- Day 1: 2 mg/0.5 mg or 4 mg/1 mg SL initially; may titrate upwards in 2-4 mg increments at 2 hr intervals, under supervision; not to exceed 8 mg/2 mg
- Day 2: Up to 16 mg/4 mg SL as a single daily dose
Induction (buprenorphine/naloxone [Zubsolv])
- Caution: buprenorphine/naloxone (Zubsolv) induction is only for patients dependent on short-acting opioids (eg, heroin) and not for those dependent on long-acting opioids (eg, methadone); buprenorphine monotherapy is recommended for induction for long-acting opioids
- Day 1
- An induction dose of up to 5.7 mg/1.4 mg is recommended, given in divided doses; initiate with 1.4 mg/0.36 mg SL; give remainder of Day 1 dose of up to 4.2 mg/1.08 mg should be divided into doses of 1 to 2 tablets of 1.4 mg/0.36 mg at 1.5 to 2 hr intervals
- Some patients (eg, those with recent exposure to buprenorphine) may tolerate up to 3 x 1.4 mg/0.36 mg SL as a single, second dose
- Day 2
- A single daily dose up to 11.4 mg/2.9 mg SL is recommended
Maintenance (buprenorphine/naloxone combo [Suboxone, generic])
- Target dose: 12-16 mg/4 mg buprenorphine/naloxone SL as a single daily dose
- Range: 16-24 mg buprenorphine component; not to exceed 32 mg/day
- Progressively adjust buprenorphine/naloxone dose in increments or decrements of 2 mg/0.5 mg or 4 mg/1 mg to level that holds patient in treatment and suppresses opioid withdrawal signs and symptoms
Maintenance (buprenorphine/naloxone combo [Zubsolv])
- Target dose: 11.4/2.9 mg as a single daily dose
- Range: 2.9/0.71 mg to 17.2/4.2 mg
- Progressively adjust buprenorphine/naloxone dose in increments or decrements of 1.4/0.36 mg or 2.9/0.71 mg to level that holds patient in treatment and suppresses opioid withdrawal signs and symptoms
Maintenance (buprenorphine/naloxone combo [Bunavail])
- Target dose: 8.4/1.4 mg as a single daily dose
- Range: 2.1/0.3 mg to 12.6/2.1 mg
- Progressively adjust dose in increments or decrements of 2.1/0.3 mg to a level that holds patient in treatment and suppresses opioid withdrawal signs and symptoms
Prior to induction, consideration should be given to the type of opioid dependence (ie, long- or short-acting opioid products, the time since last opioid use, and the degree or level of opioid dependence
To avoid precipitating an opioid withdrawal syndrome, the first dose of buprenorphine/naloxone should be administered only when objective and clear signs of moderate withdrawal are evident, and divided doses should be used
It is recommended that an adequate treatment dose, titrated to clinical effectiveness, be achieved as rapidly as possible
Patients dependent on methadone or long-acting opioid products may be more susceptible to precipitated and prolonged withdrawal during induction than those on short-acting opioid products; buprenorphine monotherapy is recommended in patients taking long-acting opioids instead of buprenorphine/naloxone, which may worsen withdrawal symptoms
Patients dependent on heroin or other short-acting opioid products may be induced with buprenorphine/naloxone or with SL buprenorphine monotherapy
- Zubsolv 5.7/1.4 mg SL provides equivalent buprenorphine exposure to Suboxone 8/2 mg SL
- Bunavail 2.1/0.3 mg buccal provides equivalent buprenorphine exposure to Suboxone 4/1 mg SL
- Bunavail 4.2/0.7 mg buccal provides equivalent buprenorphine exposure to Suboxone 8/2 mg SL
- Bunavail 6.3/1 mg buccal provides equivalent buprenorphine exposure to Suboxone 12/3 mg SL
Safety and efficacy not established
Serious - Use Alternative
Significant - Monitor Closely
Withdrawal syndrome (24-25.2%)
Abdominal pain (11.2%)
Vasodilation or peripheral edema (9.3%)
Significant respiratory depression may occur with therapeutic doses
Use with caution in hypothyroidism, preexisting respiratory compromise, obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve and kyphoscoliosis, myxedema, adrenocortical insufficiency, alcohol intoxication, alcohol withdrawal syndrome, coma, severe renal impairment, geriatric or debilitated patients, delirium tremens, toxic psychoses, kyphoscoliosis, prostatic hypertrophy, urethral stricture, comatose patients, central nervous system (CNS) depression, biliary tract dysfunction, severe hepatic impairment, head injury, intracranial lesions, and intracranial hypertension or conditions in which intracranial pressure (ICP) may be increased
Use caution with concurrent use of other CNS depressants
Respiratory sedation is dose-dependent; usual doses may depress respiration to same degree as 10 mg of parenteral morphine
Use caution in patients with history of ileus or bowel obstruction
May cause orthostatic hypotension; use caution in patients with hypovolemia, cardiovascular disease, or drugs that may worsen hypertension
Effects in CNS depression may impair ability to perform tasks that require mental alertness
Life-threatening neonatal syndrome may occur in newborns following maternal exposure to opioids; treat according to protocols developed by neonatology experts
Use caution when switching between formulations; certain sublingual film strengths may have greater bioavailability compared to the same strength of sublingual tablet; monitor for overdosing or underdosing when switching formulations
Buprenorphine may precipitate acute narcotic withdrawal in opioid-dependent patients upon rapid discontinuation or rapid taper; taper dose gradually when discontinuing therapy
May obscure diagnosis or clinical course of patients with acute abdominal conditions
Pregnancy & Lactation
Pregnancy category: C
Lactation: Buprenorphine is excreted in breast milk; breastfeeding is not advised
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Mechanism of Action
Buprenorphine: Semisynthetic narcotic mixed agonist-antagonist analgesic; exerts agonistic effects at mu and delta opioid receptors in CNS, as well as antagonistic effects at kappa opioid receptor
Naloxone: Potent antagonist at mu opioid receptors and produces opioid withdrawal signs and symptoms in individuals physically dependent on full opioid agonists when administered parenterally
- Peak plasma time: Buprenorphine, 1.53-1.72 hr; naloxone, 0.77-0.81 hr
- Peak plasma concentration: Buprenorphine, 0.947-3.37 ng/mL; naloxone, 54.1-193 pg/mL
- Bioavailability differs from that of Suboxone
- Compared with Suboxone 8/2 mg, Zubsolv 5.7/1.4 mg provides equivalent buprenorphine exposure and 12% lower naloxone exposure
- Bioavailability differs from that of Suboxone
- Compared with Suboxone 8/2 mg, Bunavail 4.2/0.7 mg provides equivalent buprenorphine exposure and 33% lower naloxone exposure
- Coadministration of liquids reduced the systemic exposure up to 59% for buprenorphine and up to 76% for naloxone (depending on the pH of the liquid)
Protein bound: Buprenorphine, 96% (primarily alpha and beta globulin); naloxone, 45% (primarily albumin)
Buprenorphine: Metabolized by N-dealkylation via CYP3A4 to norbuprenorphine (active metabolite) and by glucuronidation
Naloxone: Metabolized by direct glucuronidation to naloxone-3-glucuronide, as well as by N-dealkylation and reduction of 6-oxo group
Half-life: Buprenorphine, 24-42 hr; naloxone, 2-12 hr
Excretion: Buprenorphine, urine (30%) and feces (69%)
Switching between SL tablet and SL film: Potential for greater bioavailability with SL film than with generic SL tablets (monitor for over- or underdosing)
Use entire tablet/film; do not chew, cut, or swallow SL or buccal preparations
Bunavail Buccal Film Application
Use the tongue to wet the inside of the cheek or rinse mouth with water to moisten the area immediately before placement
Open package immediately prior to use
Hold the buccal film with clean, dry fingers with the text (BN2, BN4, or BN6) facing up, THEN
Place the side of the film with the text (BN2, BN4, or BN6) against the inside of the cheek
Press and hold the film in place for 5 seconds
Buccal film completely dissolves after applicationInstruct the patient to avoid manipulating the film(s) with the tongue or finger(s) and avoid drinking or eating food until the film(s) dissolve
Multiple Bunavail films
- If multiple films are needed, the patient should immediately apply the next film according to the steps above
- When 2 films are required for one dose, the patient should place one film on the inside of one cheek and the other film on the inside of the other cheek
- For doses requiring multiple films, no more than 2 films should be applied to the inside of one cheek at a time
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