|
Zubsolv(buprenorphine and naloxone) sublingual tablets
Generic Name: buprenorphine hydrochloride and naloxone hydrochloride
Dosage Form: tablet, orally disintegrating
Indications and Usage for Zubsolv
Zubsolv sublingual tablet is indicated for the maintenance treatment of opioid dependence and should be used as part of a complete treatment plan to include counseling and psychosocial support.
Under the Drug Addiction Treatment Act (DATA) codified at 21 U.S.C. 823(g), prescription use of this product in the treatment of opioid dependence is limited to physicians who meet certain qualifying requirements, and who have notified the Secretary of Health and Human Services (HHS) of their intent to prescribe this product for the treatment of opioid dependence and have been assigned a unique identification number that must be included on every prescription.
Zubsolv Dosage and Administration
Zubsolv sublingual tablet is administered sublingually as a single daily dose. Zubsolv sublingual tablets should be used in patients who have been initially inducted using buprenorphine sublingual tablets.
The difference in bioavailability of Zubsolv compared to SUBOXONE tablet requires a different tablet strength to be given to the patient. One Zubsolv 5.7/1.4 mg sublingual tablet provides equivalent buprenorphine exposure to one SUBOXONE 8/2 mg sublingual tablet.
The corresponding doses going from induction to maintenance treatment are:
|
Induction phase: Final sublingual buprenorphine dose |
Maintenance phase: Corresponding sublingual Zubsolv dose |
|
8 mg buprenorphine, taken as: |
5.7 mg/1.4 mg Zubsolv, taken as: |
-
One 8 mg buprenorphine tablet
|
-
One 5.7 mg/1.4 mg Zubsolv tablet
|
|
12 mg buprenorphine, taken as: |
8.5 mg/2.12 mg Zubsolv, taken as: |
-
One 8 mg buprenorphine tablet AND
-
Two 2 mg buprenorphine tablets
|
-
One 5.7 mg/1.4 mg Zubsolv tablet AND
-
Two 1.4 mg/0.36 mg Zubsolv tablets
|
|
16 mg buprenorphine, taken as: |
11.4 mg/2.8 mg Zubsolv, taken as: |
-
Two 8 mg buprenorphine tablets
|
-
Two 5.7 mg/1.4 mg Zubsolv tablets
|
Maintenance
Zubsolv sublingual tablet is indicated for maintenance treatment. The recommended target dosage of Zubsolv sublingual tablet is 11.4 mg/2.8 mg buprenorphine/naloxone/day (two 5.7/1.4 mg tablets) as a single daily dose
The dosage of Zubsolv sublingual tablet should be progressively adjusted in increments/decrements of 1.4 mg/0.36 mg or 2.8 mg/0.72 mg buprenorphine/naloxone to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms
The maintenance dose of Zubsolv sublingual tablet is generally in the range of 2.8 mg/0.72 mg buprenorphine/naloxone to 17.1 mg/4.2 mg buprenorphine/naloxone per day depending on the individual patient. Dosages higher than this 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.
Method of Administration
Do not cut, chew, or swallow Zubsolv sublingual tablets. Zubsolv sublingual tablet should be placed under the tongue until dissolved. The dissolve time for Zubsolv varies between individuals, and the median dissolve time observed was 5 minutes. For dosages requiring more than one sublingual tablet, place all tablets in different places under the tongue at the same time. Patients should keep the tablets under the tongue until dissolved; swallowing the tablets reduces the bioavailability of the drug. Advise patients not to eat or drink anything until the tablet is completely dissolved. To ensure consistency in bioavailability, patients should follow the same manner of dosing with continued use of the product.
If a sequential mode of administration is preferred, patients should follow the same manner of dosing with continued use of the product, to ensure consistency in bioavailability.
Proper administration technique should be demonstrated to the patient.
Clinical Supervision
Treatment should be initiated with supervised administration, progressing to unsupervised administration as the patient's clinical stability permits. Zubsolv sublingual tablet is subject to diversion and abuse. 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.
Ideally patients should be seen at reasonable intervals (e.g., at least weekly during the first month of treatment) based upon the individual circumstances of the patient. Medication should be prescribed in consideration of the frequency of visits. Provision of multiple refills is not advised early in treatment or without appropriate patient follow-up visits. Periodic assessment is necessary to determine compliance with the dosing regimen, effectiveness of the treatment plan, and overall patient progress.
Once a stable dosage has been achieved and patient assessment (e.g., urine drug screening) does not indicate illicit drug use, less frequent follow-up visits may be appropriate. A once-monthly visit schedule may be reasonable for patients on a stable dosage of medication who are making progress toward their treatment objectives. Continuation or modification of pharmacotherapy should be based on the physician's eva luation of treatment outcomes and objectives such as:
-
Absence of medication toxicity
-
Absence of medical or behavioral adverse effects
-
Responsible handling of medications by the patient
-
Patient's compliance with all elements of the treatment plan (including recovery-oriented activities, psychotherapy, and/or other psychosocial modalities)
-
Abstinence from illicit drug use (including problematic alcohol and/or benzodiazepine use)
If treatment goals are not being achieved, the physician should re-eva luate the appropriateness of continuing the current treatment.
Unstable Patients
Physicians will need to decide when they cannot appropriately provide further management for particular patients. For example, some patients may be abusing or dependent on various drugs, or unresponsive to psychosocial intervention such that the physician does not feel that he/she has the expertise to manage the patient. In such cases, the physician may want to assess whether to refer the patient to a specialist or more intensive behavioral treatment environment. Decisions should be based on a treatment plan established and agreed upon with the patient at the beginning of treatment.
Patients who continue to misuse, abuse, or divert buprenorphine products or other opioids should be provided with, or referred to, more intensive and structured treatment
Stopping Treatment
The decision to discontinue therapy with Zubsolv sublingual tablets after a period of maintenance should be made as part of a comprehensive treatment plan. Both gradual and abrupt discontinuation of buprenorphine has been used, but the data are insufficient to determine the best method of dose taper at the end of treatment.
Switching between Zubsolv sublingual Tablets and other buprenorphine/naloxone combination products
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 differences in bioavailability of Zubsolv compared to SUBOXONE tablet requires that different tablet strengths be given to the patient. One Zubsolv 5.7/1.4 mg sublingual tablet provides equivalent buprenorphine exposure to one SUBOXONE 8/2 mg sublingual tablet.
When switching between SUBOXONE dosage strengths and Zubsolv dosage strengths the corresponding dosage strengths are:
|
SUBOXONE sublingual tablets dosage strength |
Corresponding Zubsolv dosage strength |
|
One 2 mg/0.5 mg buprenorphine/naloxone sublingual tablet |
One 1.4 mg/0.36 mg Zubsolv sublingual tablet |
|
One 8 mg/2 mg buprenorphine/naloxone sublingual tablet |
One 5.7 mg/1.4 mg Zubsolv sublingual tablet |
Dosage Forms and Strengths
Zubsolv sublingual tablet is supplied in two dosage strengths:
-
buprenorphine/naloxone 1.4 mg/0.36 mg, white, triangular shape, tablets and
-
buprenorphine/naloxone 5.7 mg/1.4 mg, white, round shape tablets
Contraindications
Zubsolv sublingual tablet should not be administered to patients who have been shown to be hypersensitive to buprenorphine or naloxone as serious adverse reactions, including anaphylactic shock, have been reported [see Warnings and Precautions (5.7)].
Warnings and Precautions
Abuse Potential
Buprenorphine can be abused in a manner similar to other opioids, legal or illicit. Prescribe and dispense buprenorphine with appropriate precautions to minimize risk of misuse, abuse, or diversion, and ensure appropriate protection from theft, including in the home. Clinical monitoring appropriate to the patient's level of stability is essential. Multiple refills should not be prescribed early in treatment or without appropriate patient follow-up visits. [see Drug Abuse and Dependence (9.2)].
Respiratory Depression
Buprenorphine, particularly when taken by the IV route, in combination with benzodiazepines or other CNS depressants (including alcohol), has been associated with significant respiratory depression and death. Many, but not all, post-marketing reports regarding coma and death associated with the concomitant use of buprenorphine and benzodiazepines involved misuse by self-injection. Deaths have also been reported in association with concomitant administration of buprenorphine with other depressants such as alcohol or other CNS depressant drugs. Patients should be warned of the potential danger of self-administration of benzodiazepines or other depressants while under treatment with Zubsolv sublingual tablets. [see Drug Interactions (7.3)]
In the case of overdose, the primary management should be the re-establishment of adequate ventilation with mechanical assistance of respiration, if required. Naloxone may be of value for the management of buprenorphine overdose. Higher than normal doses and repeated administration may be necessary.
Zubsolv sublingual tablets should be used with caution in patients with compromised respiratory function (e.g., chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression).
CNS Depression
Patients receiving buprenorphine in the presence of opioid analgesics, general anesthetics, benzodiazepines, phenothiazines, other tranquilizers, sedative/hypnotics, or other CNS depressants (including alcohol) may exhibit increased CNS depression. Consider dose reduction of CNS depressants, Zubsolv sublingual tablets, or both in situations of concomitant prescription. [see Drug Interactions (7.3)]
Unintentional Pediatric Exposure
Buprenorphine can cause fatal respiratory depression in children who are accidentally exposed to it. Store buprenorphine containing medications safely out of the sight and reach of children and destroy any unused medication appropriately. [see Patient Counseling Information (17.2)]
Dependence
Buprenorphine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid type, characterized by withdrawal signs and symptoms upon abrupt discontinuation or rapid taper. The withdrawal syndrome is typically milder than seen with full agonists and may be delayed in onset. Buprenorphine can be abused in a manner similar to other opioids. This should be considered when prescribing or dispensing buprenorphine in situations when the clinician is concerned about an increased risk of misuse, abuse, or diversion. [see Drug Abuse and Dependence (9.3)]
Hepatitis, Hepatic Events
Cases of cytolytic hepatitis and hepatitis with jaundice have been observed in individuals receiving buprenorphine in clinical trials and through post-marketing adverse event reports. The spectrum of abnormalities ranges from transient asymptomatic elevations in hepatic transaminases to case reports of death, hepatic failure, hepatic necrosis, hepatorenal syndrome, and hepatic encephalopathy. In many cases, the presence of pre-existing liver enzyme abnormalities, infection with hepatitis B or hepatitis C virus, concomitant usage of other potentially hepatotoxic drugs, and ongoing injecting drug use may have played a causative or contributory role. In other cases, insufficient data were available to determine the etiology of the abnormality. Withdrawal of buprenorphine has resulted in amelioration of acute hepatitis in some cases; however, in other cases no dose reduction was necessary. The possibility exists that buprenorphine had a causative or contributory role in the development of the hepatic abnormality in some cases. Liver function tests, prior to initiation of treatment is recommended to establish a baseline. Periodic monitoring of liver function during treatment is also recommended. A biological and etiological eva luation is recommended when a hepatic event is suspected. Depending on the case, Zubsolv sublingual tablet may need to be carefully discontinued to prevent withdrawal signs and symptoms and a return by the patient to illicit drug use, and strict monitoring of the patient should be initiated.
Allergic Reactions
Cases of hypersensitivity to buprenorphine and naloxone containing products have been reported both in clinical trials and in the post-marketing experience. Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported. The most common signs and symptoms include rashes, hives, and pruritus. A history of hypersensitivity to buprenorphine or naloxone is a contraindication to the use of Zubsolv sublingual tablet.
Precipitation of Opioid Withdrawal Signs and Symptoms
Because it contains naloxone, Zubsolv sublingual tablet is likely to produce withdrawal signs and symptoms if misused parenterally by individuals dependent on full opioid agonists such as heroin, morphine, or methadone. Because of the partial agonist properties of buprenorphine, Zubsolv sublingual tablet may precipitate opioid withdrawal signs and symptoms in such persons if administered sublingually before the agonist effects of the opioid have subsided.
Neonatal Abstinence Syndrome
Neonatal abstinence syndrome has been reported in the infants of women treated with buprenorphine during pregnancy. From post-marketing reports, the time to onset of neonatal withdrawal signs ranged from Day 1 to Day 8 of life with most cases occurring on Day 1. Adverse events associated with the neonatal abstinence syndrome included hypertonia, neonatal tremor, neonatal agitation, and myoclonus, and there have been reports of convulsions, apnea, respiratory depression, and bradycardia.
Use in Opioid Naïve Patients
There have been reported deaths of opioid naive individuals who received a 2 mg dose of buprenorphine as a sublingual tablet for analgesia. Zubsolv sublingual tablet is not appropriate as an analgesic.
|
|
