Zubsolv buprenorphine hydrochloride and naloxone .7 mg; .18 mg Tablet, Orally Disintegrating

1 INDICATIONS AND USAGE ZUBSOLV is indicated for treatment of opioid dependence. ZUBSOLV should be used as part of a complete treatment plan that includes counseling and psychosocial support. ZUBSOLV contains buprenorphine, a partial opioid agonist, and naloxone, an opioid antagonist, and is indicated for treatment of opioid dependence.

( 1 ) ZUBSOLV should be used as part of a complete treatment plan that includes counseling and psychosocial support. ( 1 )

2 DOSAGE AND ADMINISTRATION Following induction, ZUBSOLV is administered sublingually as a single daily dose. ( 2.1 ) Strongly consider recommending or prescribing an opioid overdose reversal agent (e.g., naloxone, nalmefene) at the time ZUBSOLV is initiated or renewed because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose.( 2.2 ) To avoid precipitating withdrawal, induction with ZUBSOLV should be undertaken when objective and clear signs of withdrawal are evident and Zubsolv should be administered in divided doses when used as initial treatment.

( 2.3 ) For patients dependent on short-acting opioid products who are in opioid withdrawal; on Day 1, administer up to 5.7 mg/1.4 mg of Zubsolv (in divided doses). On Day 2, administer up to a total dose of 11.4 mg/2.9 mg of Zubsolv as a single dose. ( 2.3 ) For patients dependent on methadone or long-acting opioid products, induction onto sublingual buprenorphine monotherapy is recommended on Days 1 and 2 of treatment.

( 2.3 ) 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 and should be based on clinical response. ( 2.4 ) Administer Zubsolv as directed in the Full Prescribing Information. ( 2.5 ) When discontinuing treatment, gradually taper to avoid signs and symptoms of withdrawal.

( 2.8 )

2.1Important Dosage and Administration Information The difference in bioavailability of ZUBSOLV compared to Suboxone® sublingual tablet requires a different tablet strength to be given to the patient. One ZUBSOLV 5.7 mg/1.4 mg sublingual tablet provides equivalent buprenorphine exposure to one Suboxone 8 mg/2 mg sublingual tablet. 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.

2.2Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene) and discuss the importance of having access to an opioid overdose reversal agent. Because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose, strongly consider recommending or prescribing an overdose reversal agent for the emergency treatment of opioid overdose, both when initiating and renewing treatment with ZUBSOLV.

Also consider recommending or prescribing such an agent if the patient has household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose [see Warnings and Precautions (5.2) ] . Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program) [ see Warnings and Precautions (5.2) ]. There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics.

Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent. Advise patients and caregivers that opioid overdose reversal agents, such as naloxone or nalmefene, may also be administered for a known or suspected overdose with ZUBSOLV itself. Higher than normal doses and repeated administration of an opioid overdose reversal agent may be necessary due to the long duration of action of ZUBSOLV and its affinity for the mu receptor [see Overdosage (10) ] .

2.3Induction 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. Patients dependent on heroin or other short-acting opioid products Patients dependent on heroin or other short-acting opioid products may be induced…

3 DOSAGE FORMS AND STRENGTHS ZUBSOLV sublingual tablet is supplied in six dosage strengths: Buprenorphine 0.7 mg /naloxone 0.18 mg, white, oval shape tablets imprinted with “.7” Buprenorphine 1.4 mg /naloxone 0.36 mg, white, triangular shape tablets imprinted with “1.4” Buprenorphine 2.9 mg /naloxone 0.71 mg, white, D shape tablets imprinted with “2.9” Buprenorphine 5.7 mg /naloxone 1.4 mg, white, round shape tablets imprinted with “5.7” Buprenorphine 8.6 mg /naloxone 2.1 mg, white, diamond shape tablets imprinted with “8.6” Buprenorphine 11.4 mg /naloxone 2.9 mg, white, capsule shape tablets imprinted with “11.4” Sublingual tablet: Buprenorphine 0.7 mg /naloxone 0.18 mg, Buprenorphine 1.4 mg /naloxone 0.36 mg, Buprenorphine 2.9 mg /naloxone 0.71 mg, Buprenorphine 5.7 mg /naloxone 1.4 mg, Buprenorphine 8.6 mg /naloxone 2.1 mg and Buprenorphine 11.4 mg /naloxone 2.9 mg.

( 3 )

17 PATIENT COUNSELING INFORMATION Storage and Disposal Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store ZUBSOLV securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home [see Warnings and Precautions (5.1 , 5.2 , 5.4 , 5.11 ), Drug Abuse and Dependence (9.2) ]. Inform patients that leaving ZUBSOLV unsecured can pose a deadly risk to others in the home. Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly.

Expired, unwanted, or unused ZUBSOLV should be disposed of by flushing the unused medication down the toilet if a drug take-back option is not readily available. Inform patients that they can visit www.fda.gov/drugdisposal for a complete list of medicines recommended for disposal by flushing, as well as additional information on disposal of unused medicines. Advise patients to read the FDA-approved patient labeling.

( Medication Guide ) Safe Use Before initiating treatment with ZUBSOLV, explain the points listed below to caregivers and patients. Instruct patients to read the Medication Guide each time ZUBSOLV is dispensed because new information may be available. ZUBSOLV must be administered whole.

Advise patients not to cut, chew, or swallow ZUBSOLV. Inform patients and caregivers that potentially fatal additive effects may occur if ZUBSOLV is used with benzodiazepines or other CNS depressants (e.g., alcohol, non-benzodiazepines, sedative/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids) and not to use these concomitantly unless supervised by a healthcare provider [ see Warnings and Precautions (5.2 , 5.3) , Drug Interactions (7) ].

Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Warnings and Precautions (5.2) ] . Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene) and discuss the importance of having access to an opioid overdose reversal agent.

Because patients being treated for opioid use disorder are at risk for relapse, discuss the importance of having access to an opioid overdose reversal agent. Also discuss the importance of having access to an opioid overdose reversal agent if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. Discuss with the patient the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter (some products), or as part of a community-based program) [ see Dosage and Administration (2.2) , Warnings and Precautions (5.2) ].

There are important differences among the opioid overdose reversal agents. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent. Educate patients and caregivers on how to recognize the signs and symptoms of an opioid overdose.

Explain to patients and caregivers that effects of opioid overdose reversal agents like naloxone and nalmefene are temporary, and that they must call 911 or get emergency medical help right away in all cases of known or suspected opioid overdose, even if an opioid overdose reversal agent is administered. Repeat administration may be necessary, particularly for overdose involving buprenorphine [ Dosage and Administration ( 2.2) , Warnings and Precautions (5.2) , Overdosage (10) ]. Advise patients and caregivers: how to treat with an opioid overdose reversal agent in the event of an opioid overdose to tell family and friends about their opioid overdose reversal agent, and to keep it…

Medication Guide Medication Guide ZUBSOLV ® (Zub-solve) (buprenorphine and naloxone) Sublingual Tablet, CIII IMPORTANT: Keep ZUBSOLV in a secure place away from children. Accidental use by a child is a medical emergency and can result in death. If a child accidentally uses ZUBSOLV, get emergency help or call 911 right away.

Tell your healthcare provider if you are living in a household where there are small children. What is the most important information I should know about ZUBSOLV ? ZUBSOLV contains a medicine called buprenorphine.

Buprenorphine is an opioid that can cause serious and life-threatening breathing problems, especially if you take or use certain other medicines or drugs. Ask your healthcare provider about medications like naloxone or nalmefene that can be used in an emergency to reverse opioid overdose including accidental use of ZUBSOLV sublingual tablet by a child. If naloxone or nalmefene is given, you must call 911 or get emergency medical help right away to treat an overdose or accidental use of an opioid.

ZUBSOLV may cause serious and life-threatening breathing problems. Get emergency help right away if: ◦ feel faint ◦ feel dizzy ◦ are confused ◦ feel sleepy or uncoordinated ◦ have blurred vision ◦ have slurred speech ◦ are breathing slower than normal ◦ cannot think well or clearly Do not take ZUBSOLV with certain medicines. Taking ZUBSOLV with other opioid medicines, benzodiazepines, gabapentinoids (gabapentin or pregabalin), alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma, and death.

Do not inject (“shoot-up”) ZUBSOLV . Injecting ZUBSOLV may cause life-threatening infections and other serious health problems, Injecting ZUBSOLV may cause sudden serious withdrawal symptoms such as pain, cramps, vomiting, diarrhea, anxiety, sleep problems, and cravings. Do not switch from ZUBSOLV to other medicines that contain buprenorphine without talking with your doctor.

The amount of buprenorphine in a dose of ZUBSOLV is not the same as in other medicines that contain buprenorphine. Your healthcare provider will prescribe a starting dose of buprenorphine that may be different than other buprenorphine containing medicines you may have been taking. Do not stop taking ZUBSOLV suddenly.

You could become sick and have withdrawal symptoms because your body has become used to the medicine (physical dependence). Physical dependence is not the same as drug addiction. In an emergency, have family members tell the emergency department staff that you are physically dependent on an opioid and are being treated with ZUBSOLV.

Never give anyone else your ZUBSOLV. They could die from taking it. Selling or giving away ZUBSOLV is against the law.

Store ZUBSOLV securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. What is ZUBSOLV? ZUBSOLV is a prescription medicine used to treat opioid addiction in adults and is part of a complete treatment program that also includes counseling and behavioral therapy.

Who should not take ZUBSOLV? Do not take ZUBSOLV if you are allergic to buprenorphine or naloxone. What should I tell my doctor before taking ZUBSOLV?

Before taking ZUBSOLV, tell your healthcare provider about all of your medical conditions, including if you have: trouble breathing or lung problems a curve in your spine that affects your breathing Addison’s disease an enlarged prostate (men) problems urinating liver, kidney, or gallbladder problems alcoholism a head injury or brain problem mental health problems adrenal gland or thyroid gland problems tooth problems, including a history of cavities Tell your healthcare provider if you are: pregnant or plan to become pregnant.

If you take ZUBSOLV while pregnant, your baby may have symptoms of opioid withdrawal at birth that could be life-threatening if not recognized and treated. Talk to your healthcare provider if you ar…