Buprenorphine Sublingual and Buccal (opioid dependence)

Buprenorphine and the combination of buprenorphine and naloxone are used to treat opioid dependence (addiction to opioid drugs, including heroin and narcotic painkillers). Buprenorphine is in a class of medications called opioid partial agonist-antagonists and naloxone is in a class of medications called opioid antagonists. Buprenorphine alone and the combination of buprenorphine and naloxone work to prevent withdrawal symptoms when someone stops taking opioid drugs by producing similar effects to these drugs.

Buprenorphine comes as a sublingual tablet. The combination of buprenorphine and naloxone comes as a sublingual tablet (Zubsolv) and as a sublingual film (Suboxone) to take under the tongue or to apply between the gum and cheek. After your doctor determines an appropriate dose, these products are usually taken once a day. To help you remember to take or apply buprenorphine or buprenorphine and naloxone, take or apply it around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take or apply buprenorphine or buprenorphine and naloxone exactly as directed. Do not take or apply more or less of it or take or apply it more often than prescribed by your doctor.

Your doctor may decide to start your treatment for opioid dependence with buprenorphine, which you will take in the doctor's office. You will start on a low dose of buprenorphine and your doctor may increase your dose for 1 or 2 days before switching you to buprenorphine and naloxone. Depending on the type of opioid that you were taking, a different option that your doctor may choose is to start you on treatment with buprenorphine and naloxone right away. Your doctor may increase or decrease your buprenorphine and naloxone dose depending on your response.

If you are taking the sublingual tablets, place the tablets under your tongue until they completely melt. If you are taking more than two tablets, either place them all under your tongue at the same time or place them under your tongue up to two at a time. Do not chew the tablets or swallow them whole. Do not eat, drink, or talk until the tablet dissolves completely.

If you are using the buccal film, rinse your mouth with water before you apply the film. Apply the film with a dry finger against the inside of the cheek. Then remove your finger and the film will stick to the inside of your cheek. If you are to use two films, place another film on the inside of your other cheek at the same time. Do not apply films on top of each other and do not apply more than two films to the inside of the mouth at one time. Leave the film(s) in the mouth until they dissolve. Do not cut, tear, chew, swallow, touch or move the film while it dissolves. Do not eat or drink anything until the film dissolves completely.

If you are using the sublingual film, rinse your mouth with water before you place the film. Place the film with a dry finger under your tongue to the right or left of the center and hold the film in place for 5 seconds. If you are using two films, place the other one on the opposite side under the tongue. Do not put the films on top of or near each other or let them touch each other. Do not use more than two films at one time. Do not cut, tear, chew, swallow, touch or move the film while it dissolves. Do not eat or drink anything until the film dissolves completely.

After the sublingual tablets or sublingual or buccal film have dissolved, take a sip of water, swish it around your teeth and gums, and then swallow. Do not brush your teeth for at least one hour after the tablets or film have dissolved.

If you need to switch from one buprenorphine or buprenorphine and naloxone product to another, your doctor may need to adjust your dose. Each time you receive your medication, check to be sure that you have received the buprenorphine product that was prescribed for you. Ask your pharmacist if you have are not sure that you received the right medication.

Do not stop taking buprenorphine or buprenorphine and naloxone without talking to your doctor. Stopping buprenorphine or buprenorphine and naloxone too quickly can cause withdrawal symptoms. Your doctor will tell you when and how to stop taking buprenorphine or buprenorphine and naloxone. If you suddenly stop taking buprenorphine or buprenorphine and naloxone, you may experience withdrawal symptoms such as hot or cold flushes, restlessness, teary eyes, runny nose, sweating, chills, muscle pain, vomiting, or diarrhea.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Before taking buprenorphine or buprenorphine and naloxone,

• tell your doctor and pharmacist if you are allergic to buprenorphine, naloxone, any other medications, or any of the other ingredients in buprenorphine or buprenorphine and naloxone sublingual tablets or film. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor or pharmacist if you are taking the following medications or have stopped taking them within the past two weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Emsam, Zelapar), or tranylcypromine (Parnate).
• The following nonprescription or herbal products may interact with buprenorphine: St. John's wort and tryptophan. Be sure to let your doctor and pharmacist know that you are taking these medications before you start taking buprenorphine or buprenorphine and naloxone. Do not start these medications while taking buprenorphine or buprenorphine and naloxone without discussing it with your healthcare provider.
• tell your doctor if you drink or have ever drunk large amounts of alcohol or have or have ever had prolonged QT syndrome (condition that increases the risk of developing an irregular heartbeat that may cause loss of consciousness or sudden death). Also, tell your doctor if you have or have ever had low levels of potassium or magnesium in the blood; heart failure; a slow or irregular heartbeat; adrenal problems such as Addison's disease (condition in which the adrenal gland produces less hormone than normal); benign prostatic hypertrophy (BPH, enlargement of the prostate gland); difficulty urinating; a head injury; depression or other mental illness; a curve in the spine that makes it hard to breathe; gallbladder disease; liver disease, including hepatitis B or C; chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways); or thyroid, kidney, or lung disease.
• tell your doctor if you are pregnant or plan to become pregnant. If you become pregnant while taking buprenorphine or buprenorphine and naloxone, call your doctor. If you take buprenorphine or buprenorphine and naloxone tablets or film regularly during your pregnancy, your baby may experience life-threatening withdrawal symptoms after birth. Tell your baby's doctor right away if your baby experiences any of the following symptoms: irritability, seizures, uncontrollable shaking of a part of the body, vomiting, diarrhea, or failure to gain weight.
• tell your doctor if you are breastfeeding. Tell your baby's doctor right away if your baby is sleepier than usual or has trouble breathing while you are taking this medication.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking buprenorphine or buprenorphine and naloxone.
• you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking buprenorphine or buprenorphine and naloxone.
• you should know that buprenorphine or buprenorphine and naloxone may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
• you should not drink alcohol or take prescription or nonprescription medications that contain alcohol while taking this medication.
• you should know that buprenorphine or buprenorphine and naloxone may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start taking buprenorphine or buprenorphine and naloxone. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• you should know that buprenorphine may cause serious problems with your teeth, including dental cavities, dental infections, tooth fracture, and tooth loss. Be sure to have regular dental checkups during your treatment with buprenorphine and call your dentist immediately if you have a toothache, mouth pain, or any other problems with your teeth or gums.

Unless your doctor tells you otherwise, continue your normal diet.

Take or apply the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take or apply a double dose to make up for a missed one.

Buprenorphine or buprenorphine and naloxone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• headache
• stomach pain
• constipation
• difficulty falling asleep or staying asleep
• mouth numbness or redness
• tongue pain
• blurred vision
• back pain

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNINGS or SPECIAL PRECAUTIONS sections, call your doctor immediately:

• hives; rash; itching; difficulty breathing or swallowing; or swelling of your face, throat, tongue, lips, or eyes
• swelling of the hands, feet, ankles, or lower legs
• agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, or diarrhea
• nausea, vomiting, loss of appetite, weakness, or dizziness
• inability to get or keep an erection
• irregular menstruation
• decreased sexual desire
• slowed breathing
• upset stomach
• extreme tiredness
• confusion
• blurred vision
• slurred speech
• lack of energy
• yellowing of the skin or eyes, dark-colored urine, light-colored stools, loss of appetite, nausea, or pain in the upper right part of the stomach

Buprenorphine or buprenorphine and naloxone may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the packaging it came in, tightly closed, and out of reach of children. Buprenorphine or buprenorphine and naloxone can be a target for people who abuse prescription medications or street drugs. Store it in a safe place so that no one else can use it accidentally or on purpose. Store buprenorphine or buprenorphine and naloxone at room temperature and away from excess heat and moisture (not in the bathroom). Do not freeze buprenorphine or buprenorphine and naloxone.

You must immediately dispose of any medication that is outdated or no longer needed through a medicine take-back program. If you do not have a take-back program nearby or one that you can access promptly, then dispose of unneeded tablets or films by removing them from the packaging and flushing them down the toilet. Do not flush buprenorphine or buprenorphine and naloxone down the toilet in the foil packages. Call your pharmacist or the manufacturer if you have questions or need help disposing of unneeded medication.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

While taking buprenorphine or buprenorphine and naloxone, you should talk to your doctor about having a rescue medication called naloxone readily available (e.g., home, office). Naloxone is used to reverse the life-threatening effects of an overdose. It works by blocking the effects of opiates to relieve dangerous symptoms caused by high levels of opiates in the blood. Your doctor may also prescribe you naloxone if you are living in a household where there are small children or someone who has abused street or prescription drugs. Ask your doctor about other ways that you can obtain naloxone (directly from a pharmacy or as part of a community based program). You should make sure that you and your family members, caregivers, or the people who spend time with you know how to recognize an overdose, how to use naloxone, and what to do until emergency medical help arrives. Your doctor or pharmacist will show you and your family members how to use the medication. Ask your pharmacist for the instructions or visit the manufacturer's website to get the instructions. If symptoms of an overdose occur, a friend or family member should give the first dose of naloxone, call 911 immediately, and stay with you and watch you closely until emergency medical help arrives. Your symptoms may return within a few minutes after you receive naloxone. If your symptoms return, the person should give you another dose of naloxone. Additional doses may be given every 2 to 3 minutes, if symptoms return before medical help arrives.

Symptoms of overdose may include the following:

• narrowing of the pupils (black circles in the center of the eye)
• sleepiness or extreme drowsiness
• slow or shallow breathing
• difficulty breathing
• unable to respond or wake up

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body's response to buprenorphine and naloxone.

Before having any laboratory test (especially those that involve methylene blue), tell your doctor and the laboratory personnel that you are taking buprenorphine or buprenorphine and naloxone.

In case of an emergency, you or a family member should tell the treating doctor or emergency room staff that you are taking buprenorphine or buprenorphine and naloxone.

Do not inject buprenorphine or buprenorphine and naloxone sublingual film or tablets. Severe reactions may happen, including withdrawal symptoms.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

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• Bunavail^® (containing Buprenorphine, Naloxone)^¶
• Suboxone^® (containing Buprenorphine, Naloxone)^¶
• Zubsolv^® (containing Buprenorphine, Naloxone)