Buprenorphine/Naloxone

Reviewed on 1/26/2022

What Is Buprenorphine/Naloxone and How Does It Work?

Buprenorphine/Naloxone is a prescription medication used for reversing opioid dependence.

What Are Dosages of Buprenorphine/Naloxone?

 Adult dosage

Film, sublingual: Schedule III

  • 2mg/0.5mg (Suboxone, generic)
  • 4mg/1mg (Suboxone, generic)
  • 8mg/2mg (Suboxone, generic)
  • 12mg/3mg (Suboxone, generic)
  • 16mg/4mg (Cassipa)

Tablet, sublingual (Zubsolv): Schedule III

  • 0.7mg/0.18mg
  • 1.4mg/0.36mg
  • 2.9mg/0.71mg
  • 5.7mg/1.4mg
  • 8.6mg/2.1mg
  • 11.4mg/2.9mg

Buccal film (Bunavail): Schedule III

  • 2.1mg/0.3mg
  • 4.2mg/0.7mg
  • 6.3mg/1mg

Tablet, sublingual (generic): Schedule III

  • 2mg/0.5mg
  • 8mg/2mg

Opioid dependence

  • Adult dosage
  • Induction (buprenorphine SL)
  • Day 1: 4 mg sublingual 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 sublingual; if withdrawal symptoms are present, the dose is increased by 4 mg; if symptoms are not relieved after more than 2 hr, 4 mg is administered; not to exceed 16 mg sublingual

Induction (buprenorphine/naloxone [Suboxone])

  • Day 1: 2 mg/0.5 mg or 4 mg/1 mg sublingual 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 sublingual as a single daily dose

Induction (buprenorphine/naloxone [Zubsolv])

  • 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 sublingual; give the 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 (e.g., those with recent exposure to buprenorphine) may tolerate up to 3 x 1.4 mg/0.36 mg sublingual as a single, second dose
  • Day 2: A single daily dose up to 11.4 mg/2.9 mg sublingual is recommended

Induction (buprenorphine/naloxone [Bunavail])

  • Day 1: The first dose should not be administered before 6 hr after the patient last used an opioid
  • An induction dose of up to 4.2 mg/0.7 mg is recommended; initiate with 2.1 mg/0.3 mg and repeat at ~2-hr, under supervision, to a total dose of 4.2 mg/0.7 mg based on control of acute withdrawal symptoms
  • Day 2: A single daily dose of up to 8.4 mg/1.4 mg buccal is recommended

Maintenance

  • Suboxone
    • Target dose: 12-16 mg/4 mg buprenorphine/naloxone sublingual 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 a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms
  • 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 a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms
  • 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 the dose in increments or decrements of 2.1/0.3 mg to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms
  • Cassipa
    • Sublingual film available only as 16 mg buprenorphine/4 mg naloxone

Dosage Considerations – Should be Given as Follows

  • See “Dosages”

SLIDESHOW

Prescription Drug Abuse: Addiction, Health Risks, and Treatments See Slideshow

What Are Side Effects Associated with Using Buprenorphine/Naloxone?

Common side effects of Buprenorphine/Naloxone include:

  • dizziness,
  • drowsiness,
  • blurred vision,
  • feeling drunk,
  • trouble concentrating,
  • withdrawal symptoms,
  • tongue pain,
  • redness or numbness inside the mouth,
  • nausea,
  • vomiting,
  • constipation,
  • headache,
  • back pain,
  • fast or pounding heartbeats,
  • increased sweating, and
  • sleep problems (insomnia)

Serious side effects of Buprenorphine/Naloxone include:

  • weak or shallow breathing,
  • breathing that stops during sleep,
  • confusion,
  • loss of coordination,
  • extreme weakness,
  • blurred vision,
  • slurred speech,
  • upper stomach pain,
  • loss of appetite,
  • dark urine,
  • clay-colored stools,
  • yellowing of the skin or eyes (jaundice),
  • nausea,
  • dizziness,
  • worsening tiredness or weakness,
  • shivering,
  • goosebumps,
  • increased sweating,
  • feeling hot or cold,
  • runny nose,
  • watery eyes,
  • diarrhea, and
  • muscle pain

Rare side effects of Buprenorphine/Naloxone include:

  • none 
This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

What Other Drugs Interact with Buprenorphine/Naloxone?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first

  • Buprenorphine/Naloxone has severe interactions with the following drugs:
    • alvimopan
    • lefamulin
  • Buprenorphine/Naloxone has serious interactions with at least 72 drugs:
  • Buprenorphine/Naloxone has moderate interactions with at least 211 other drugs
  • Buprenorphine/Naloxone has minor interactions with the following drugs:

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

What Are Warnings and Precautions for Buprenorphine/Naloxone?

Contraindications

  • Hypersensitivity

Effects of drug abuse

  • None

Short-Term Effects

  • See “What Are Side Effects Associated with Using Buprenorphine/Naloxone?”

Long-Term Effects

  • See “What Are Side Effects Associated with Using Buprenorphine/Naloxone?”

Cautions

  • 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 the same degree as 10 mg of parenteral morphine
  • Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia; opioid use increases the risk of CSA in a dose-dependent fashion; in patients who present with CSA, consider decreasing opioid dosage using best practices for opioid taper
  • Use caution in patients with a 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 the ability to perform tasks that require mental alertness
  • The life-threatening neonatal syndrome may occur in newborns following maternal exposure to opioids; treat according to protocols developed by neonatology experts; prescribers should discuss with patients, the importance and benefits of management of opioid addiction throughout pregnancy
  • Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; unknown whether effects on fertility are reversible
  • 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
  • Because it contains naloxone, the drug is highly likely to produce marked and intense withdrawal signs and symptoms if misused parenterally by individuals dependent on full opioid agonists such as heroin, morphine, or methadone
  • May obscure diagnosis or clinical course of patients with acute abdominal conditions
  • Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers; other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency
  • Advise pregnant women receiving opioid addiction treatment with a sublingual film of risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available
  • Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose
  • The drug can be abused in a manner similar to other opioids; consider this when prescribing or dispensing buprenorphine in situations when the clinician is concerned about the increased risk of misuse, abuse, or diversion

Increased risk of dental problems

  • On January 12, 2022, FDA warned of potential dental problems associated with transmucosal buprenorphine-containing products (e.g., buccal, sublingual)
  • Dental problems (i.e., tooth decay, cavities, oral infections, loss of teeth), can be serious and have been reported even in patients with no history of dental issues
  • Despite these risks, buprenorphine is an important treatment option for opioid use disorder and pain, and the benefits of these medicines clearly outweigh the risks
  • Review patient’s health before initiating transmucosal buprenorphine
  • Counsel patients regarding the potential for dental problems and the importance of taking extra steps after the medicine have completely dissolved, including gently rinsing teeth and gums with water and then swallowing; advice to wait at least 1 hour before brushing their teeth
  • Dentists treating patients taking transmucosal buprenorphine should perform a baseline dental evaluation and caries risk assessment, establish a dental caries preventive plan, and encourage regular dental checkups
  • Coadministration with benzodiazepines
  • Life-threatening respiratory depression and death may occur; many, but not all, postmarketing reports regarding coma and death involved misused by self-injection or were associated with concomitant use of benzodiazepines or other CNS depressants, including alcohol; warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment
  • Concomitant use of buprenorphine and benzodiazepines or other CNS depressants increases the risk of adverse reactions including overdose and death; medication-assisted treatment of opioid use disorder, however, should not be categorically denied to patients taking these drugs; prohibiting or creating barriers to treatment can pose an even greater risk of morbidity and mortality due to the opioid use disorder alone
  • If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response; follow patients closely for signs and symptoms of respiratory depression and sedation
  • Develop strategies to manage the use of prescribed or illicit benzodiazepines or other CNS depressants at the initiation of buprenorphine treatment, or if it emerges as a concern during treatment; adjustments to induction procedures and additional monitoring may be required; there is no evidence to support dose limitations or arbitrary caps of buprenorphine as a strategy to address benzodiazepine use in buprenorphine-treated patients; however, if a patient is sedated at the time of buprenorphine dosing, delay or omit the buprenorphine dose if appropriate
  • Cessation of benzodiazepines or other CNS depressants is preferred in most cases of concomitant use. In some cases, monitoring in a higher level of care for taper may be appropriate. In others, gradually tapering a patient off a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate
  • Ensure that other healthcare providers prescribing benzodiazepines or other CNS depressants are aware of the patient’s buprenorphine treatment and coordinate care to minimize the risks associated with concomitant use
  • If concomitant use with a benzodiazepine is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose
  • Confirm patients are taking their medications as prescribed and are not diverting or supplementing with illicit drugs; toxicology screening should test for prescribed and illicit benzodiazepines
  • Patient access to naloxone for emergency treatment of opioid overdose
  • Assess potential need for naloxone; consider prescribing for emergency treatment of opioid overdose
  • Consult on availability and ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines
  • Educate patients regarding the signs and symptoms of respiratory depression and to call 911 or seek immediate emergency medical help in the event of a known or suspected overdose
  • Pregnancy and Lactation
  • Data on the use of buprenorphine, one of the active ingredients are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure; there are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations; the extremely limited data on sublingual naloxone exposure in pregnancy are not sufficient to evaluate a drug-associated risk; dosage adjustments of buprenorphine may be required during pregnancy, even if the patient was maintained on stable dose prior to pregnancy; withdrawal signs and symptoms should be monitored closely and the dose adjusted as necessary
  • Neonates whose mothers have been taking opioids long term may exhibit withdrawal signs, either at birth and/or in the nursery because they have developed physical dependence; neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening and should be treated according to protocols developed by neonatology experts
  • Caution should be exercised when therapy is administered to nursing women; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition; advice breastfeeding women taking buprenorphine products to monitor the infant for increased drowsiness and breathing difficulties
References
https://reference.medscape.com/drug/suboxone-zubsolv-buprenorphine-naloxone-343334#6

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