Dosage & Administration
Dosing to clinical effectiveness
The National Institute on Drug Abuse recommends that opioid dependence treatment be individualized to meet the needs of each patient.1 ZUBSOLV allows healthcare providers the flexibility to dose up or down to clinical effectiveness at any time, for any reason.2 Compared to other buprenorphine/naloxone medications,2-4 ZUBSOLV offers patients2:
- Widest dosage range with 6 dosage strengths
- Lowest available dosage (0.7 mg/0.18 mg)
1.4 mg/0.36 mg
2.9 mg/0.71 mg
5.7 mg/1.4 mg
8.6 mg/2.1 mg
11.4 mg/2.9 mg
When prescribing ZUBSOLV2:
- Prior to induction, consideration should be given to the type of opioid dependence, i.e., long- or short-acting opioid products, the time since last opioid use, and the degree or level of opioid dependence. Induction with ZUBSOLV is not appropriate for all patients
- The recommended target maintenance dose of ZUBSOLV is 11.4 mg/2.9 mg (buprenorphine/naloxone) administered as a single daily dose
- For patients being switched between ZUBSOLV sublingual tablets and other buprenorphine/naloxone products dosage adjustments may be necessary. Patients should be monitored for over-medication as well as withdrawal or other signs of under-dosing
- The dosage of ZUBSOLV from Day 3 onwards should be progressively adjusted in increments/decrements of 2.9 mg/0.71 mg or lower of buprenorphine/naloxone to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms
- The maintenance dose of ZUBSOLV is generally in the range of 2.9 mg/0.71 mg to 17.2 mg/4.2 mg per day depending on the individual patient and clinical response
- Dosages higher than 17.2 mg/4.2 mg per day have not been demonstrated to provide any clinical advantage
- When determining the prescription quantity for unsupervised administration, consider the patient’s level of stability, the security of his or her home situation, and other factors likely to affect the ability to manage supplies of take-home medication
- There is no maximum recommended duration of maintenance treatment. Patient may require treatment indefinitely and should continue for as long as patients are benefiting and the use of ZUBSOLV contributes to the intended treatment goals
1. National Institute on Drug Abuse. Principles of drug addiction treatment: a research-based guide. 3rd ed. https://d14rmgtrwzf5a.cloudfront.net/sites/default/files/podat_1.pdf. NIH publication no. 12-4180. December 2012. Accessed March 20, 2018.
2. ZUBSOLV [prescribing information]. Morristown, NJ: Orexo US, Inc.; 2018.
3. Bunavail [prescribing information]. Raleigh, NC: BioDelivery Sciences International, Inc.; 2018.
4. Suboxone [prescribing information]. North Chesterfield, VA: Indivior Inc.; 2018.
5. ZUBSOLV [medication guide]. Morristown, NJ: Orexo US, Inc.; 2016.
ZUBSOLV offers easy administration
As soon as patients remove their prescribed dose of ZUBSOLV from the blister pack, they should be instructed to5:
- Place the tablet under the tongue. If more than 1 tablet is required, tablets should be placed in different places under the tongue at the same time
- Allow the tablet to dissolve completely. If patients have dry mouth, instruct them to take a sip of water to moisten it. Water should be spit out or swallowed and hands must be dry before the tablet can be placed under the tongue
Important patient counseling information5
- Distribute the ZUBSOLV Medication Guide to your patient
- Chewing or swallowing the tablet while it is dissolving will prevent the medication from working as it should
- Instruct patients to not eat, drink, or talk while the tablet is dissolving as this can affect how well the medicine in ZUBSOLV is absorbed
- If patients miss a dose of ZUBSOLV, they should take their medicine when they remember. If it is almost time for their next dose, advise patients to skip the missed dose and take the next dose at their regular time. Patients should not take 2 doses at the same time unless advised by a healthcare provider
- Patients should not stop taking ZUBSOLV suddenly. They could become sick and have withdrawal symptoms because their body has become used to the medicine
- If too much ZUBSOLV is taken, advise patients to go to the nearest hospital emergency room right away
ZUBSOLV® (buprenorphine and naloxone) sublingual tablet (CIII) is indicated for the treatment of opioid dependence. ZUBSOLV should be used as part of a complete treatment plan that includes counseling and psychosocial support.
Treatment should be initiated under the direction of healthcare providers who meet certain qualifying requirements under the Drug Addiction Treatment Act of 2000, and who have been assigned a unique identification number (“X” number).
IMPORTANT SAFETY INFORMATION
ZUBSOLV is contraindicated in patients with a history of hypersensitivity to buprenorphine or naloxone, as serious adverse reactions, including anaphylactic shock, have been reported.
Warnings and Precautions
Addiction, Abuse, and Misuse: Buprenorphine can be abused in a similar manner to other opioids. Monitor patients for conditions indicative of diversion or progression of opioid dependence and addictive behaviors. Multiple refills should not be prescribed early in treatment or without appropriate patient follow-up visits.
Respiratory Depression: Life-threatening respiratory depression and death have occurred in association with buprenorphine use. Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with ZUBSOLV.
Unintentional Pediatric Exposure: Store ZUBSOLV safely out of the sight and reach of children. Buprenorphine can cause severe, possibly fatal respiratory depression in children.
Neonatal Opioid Withdrawal Syndrome (NOWS): Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy.
Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patients off of the opioid.
Risk of Opioid Withdrawal with Abrupt Discontinuation: If treatment is temporarily interrupted or discontinued, monitor patients for withdrawal and treat appropriately.
Risk of Hepatitis; Hepatic Events: Monitor liver function tests prior to initiation and during treatment and evaluate suspected hepatic events.
Precipitation of Opioid Withdrawal Signs and Symptoms: An opioid withdrawal syndrome is likely to occur with parenteral misuse of ZUBSOLV by individuals physically dependent on full opioid agonists or by sublingual administration before the agonist effects of other opioids have subsided.
Risk of Overdose in Opioid-Naïve Patients: ZUBSOLV is not appropriate as an analgesic. There have been reported deaths of opioid-naïve individuals who received a 2-mg sublingual dose of buprenorphine.
Use in Specific Populations
Lactation: Buprenorphine passes into mother’s milk.
Geriatric Patients: Monitor for sedation and respiratory depression.
Moderate and Severe Hepatic Impairment: Buprenorphine/naloxone products are not recommended in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment.
Adverse Reactions & Drug Interactions
Adverse events commonly observed with the sublingual administration of ZUBSOLV are headache, nausea, vomiting, hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia, pain, and peripheral edema.
Benzodiazepines: Use caution in prescribing ZUBSOLV for patients receiving benzodiazepines or other CNS depressants and warn patients against concomitant self-administration/misuse.
CYP3A4 Inhibitors and Inducers: Monitor patients starting or ending CYP3A4 inhibitors or inducers for potential over or under dosing.
Antiretrovirals: Patients who are on chronic buprenorphine treatment should have their dose monitored if NNRTIs are added to their treatment regimen. Monitor patients taking buprenorphine and atazanavir with and without ritonavir, and reduce dose of buprenorphine if warranted.
Serotonergic Drugs: Concomitant use may result in serotonin syndrome. Discontinue ZUBSOLV if serotonin syndrome is suspected.
This is not a complete list of potential adverse events associated with buprenorphine/naloxone sublingual tablets. Please see full Prescribing Information for a complete list.
To report an adverse event associated with taking ZUBSOLV sublingual tablet, please call 1-888-ZUBSOLV (1-888-982-7658). You are encouraged to report adverse events of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.