FDA Drug Safety Communication:
- As part of its ongoing efforts to address the nation's opioid crisis, FDA is requiring several updates to the prescribing information of opioid pain medicines. The changes are being made to provide additional guidance for safe use of these drugs while also recognizing the important benefits when used appropriately. The changes apply to both immediate-release (IR) and extended-release/long-acting preparations (ER/LA).
- Updates to the IR opioids state that these drugs should not be used for an extended period unless the pain remains severe enough to require an opioid pain medicine and alternative treatment options are insufficient, and that many acute pain conditions treated in the outpatient setting require no more than a few days of an opioid pain medicine.
- Updates to the ER/LA opioids recommend that these drugs be reserved for severe and persistent pain requiring an extended period of treatment with a daily opioid pain medicine and for which alternative treatment options are inadequate.
- A new warning is being added about opioid-induced hyperalgesia (OIH) for both IR and ER/LA opioid pain medicines. This includes information describing the symptoms that differentiate OIH from opioid tolerance and withdrawal.
- Information in the boxed warning for all IR and ER/LA opioid pain medicines will be updated and reordered to elevate the importance of warnings concerning life-threatening respiratory depression, and risks associated with using opioid pain medicines in conjunction with benzodiazepines or other medicines that depress the central nervous system (CNS).
- Other changes will also be required in various other sections of the prescribing information to educate clinicians, patients, and caregivers about the risks of these drugs.
AUDIENCE: Dentistry, Anesthesiology, Patient, Health Professional, Pharmacy
ISSUE: The FDA is warning that dental problems have been reported with medicines containing buprenorphine that are dissolved in the mouth. The dental problems, including tooth decay, cavities, oral infections, and 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 (OUD) and pain, and the benefits of these medicines clearly outweigh the risks. The FDA is requiring a new warning about the risk of dental problems be added to the prescribing information and the patient Medication Guide (https://bit.ly/3FYER1g for all buprenorphine-containing medicines dissolved in the mouth.
BACKGROUND: Buprenorphine was approved in 2002 as a tablet to be administered under the tongue to treat OUD. In 2015, buprenorphine was approved as a film to be placed inside the cheek to treat pain. The buprenorphine medicines that are associated with dental problems are tablets and films dissolved under the tongue or placed against the inside of the cheek.
- Continue taking your buprenorphine medicine as prescribed; do not suddenly stop taking it without first talking to your health care professional as it could lead to serious consequences. Suddenly stopping these medicines could cause you to become sick with withdrawal symptoms because your body has become used to the buprenorphine medicine, or to relapse to opioid misuse that could result in overdose and death.
- Patients using buprenorphine medicines dissolved in the mouth should take extra steps to help lessen the risk of serious dental problems. After the medicine is completely dissolved, take a large sip of water, swish it gently around your teeth and gums, and swallow. You should wait at least 1 hour before brushing your teeth to avoid damage to your teeth and give your mouth a chance to return to its natural state.
- Inform your health care professional if you have a history of tooth problems, including cavities. Schedule a dentist visit soon after starting this medicine and inform your dentist that you are taking buprenorphine, and schedule regular dental checkups while taking this medicine. Your dentist can customize a tooth decay prevention plan for you. Notify both your health care professional and your dentist immediately if you experience any problems with your teeth or gums.
- Health Professionals
- Health care professionals should be aware the benefits of buprenorphine medicines clearly outweigh the risks and are an important tool to treat OUD. When combined with counseling and other behavioral therapies, this comprehensive https://www.samhsa.gov/medication-assisted-treatment approach is often the most effective way for treating OUD, and can help sustain recovery and prevent or reduce opioid overdose.
- Ask patients about their oral health history prior to prescribing treatment with a transmucosal buprenorphine medicine. These serious dental problems have been reported even in patients with no history of dental issues, so refer them to a dentist as soon as possible after starting transmucosal buprenorphine. Counsel patients about the potential for dental problems and the importance of taking extra steps after the medicine has completely dissolved, including to gently rinse their teeth and gums with water and then swallow. Patients should be advised to wait at least 1 hour before brushing their teeth. Dentists treating someone taking a transmucosal buprenorphine product should perform a baseline dental evaluation and caries risk assessment, establish a dental caries preventive plan, and encourage regular dental checkups.
Buprenorphine (Belbuca) may be habit forming, especially with prolonged use. Apply buprenorphine exactly as directed. Do not apply more buprenorphine buccal films, use the buccal films more often, or use the buccal films in a different way than prescribed by your doctor. While using buprenorphine, discuss with your health care provider your pain treatment goals, length of treatment, and other ways to manage your pain. Tell your doctor if you or anyone in your family drinks or has ever drunk large amounts of alcohol, uses or has ever used street drugs, or has overused prescription medications, or has had an overdose, or if you have or have ever had depression or another mental illness. There is a greater risk that you will overuse buprenorphine if you have or have ever had any of these conditions. Talk to your health care provider immediately and ask for guidance if you think that you have an opioid addiction or call the U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) National Helpline at 1-800-662-HELP.
Buprenorphine (Belbuca) may cause serious or life-threatening breathing problems, especially during the first 24 to 72 hours and any time that your dose is increased. Your doctor will monitor you carefully during your treatment. Your doctor will adjust your dose carefully to control your pain and decrease the risk that you will experience serious breathing problems. Tell your doctor if you have breathing difficulties and if you have or have ever had asthma. Your doctor may tell you not to use buprenorphine (Belbuca.) Also tell your doctor if you have or have ever had chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways), other lung diseases, a head injury, a brain tumor, or any condition that increases the amount of pressure in your brain. The risk that you will develop breathing problems may also be higher if you are an older adult or are weakened or malnourished due to disease. If you have any of the following symptoms, call your doctor immediately: difficulty breathing, shortness of breath, extreme drowsiness, fainting, or loss of consciousness.
Taking certain medications with buprenorphine (Belbuca) may increase the risk of serious or life-threatening breathing problems, sedation, or coma. Tell your doctor and pharmacist if you are taking or plan to take any of the following medications: benzodiazepines such as such as alprazolam (Xanax), chlordiazepoxide (Librium), clonazepam (Klonopin), diazepam (Diastat, Valium), estazolam, flurazepam, lorazepam (Ativan), oxazepam, temazepam (Restoril), and triazolam (Halcion); medications for mental illness and nausea; other medications for pain; muscle relaxants; sedatives; sleeping pills; or tranquilizers. Your doctor may need to change the dosages of your medications and will monitor you carefully. If you use buprenorphine with any of these medications and develop any of the following symptoms, call your doctor immediately or seek emergency medical care: unusual dizziness, lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness. Be sure that your caregiver or family members know which symptoms may be serious so they can call the doctor or emergency medical care if you are unable to seek treatment on your own.
Drinking alcohol, taking prescription or nonprescription medications that contain alcohol, or using street drugs during your treatment with buprenorphine increases the risk that you will experience these serious, life-threatening side effects. Do not drink alcohol or use street drugs during your treatment.
Buprenorphine (Belbuca) may cause serious harm or death if used accidentally by a child or by an adult who has not been prescribed the medication. Do not allow anyone else to use your medication. Store buprenorphine (Belbuca) in a safe place so that no one else can use it accidentally or on purpose. Keep track of how many buccal films are left so you will know if any are missing.
Tell your doctor if you are pregnant or plan to become pregnant. If you use buprenorphine 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, hyperactivity, abnormal sleep, high-pitched cry, uncontrollable shaking of a part of the body, vomiting, diarrhea, or failure to gain weight.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with buprenorphine (Belbuca) and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide.
Talk to your doctor about the risks of using buprenorphine (Belbuca).
Why is this medication prescribed?
Buprenorphine (Belbuca) is used to relieve severe pain in people who are expected to need pain medication around the clock for a long time and who cannot be treated with other medications. Buprenorphine (Belbuca) should not be used to treat pain that can be controlled by medication that is taken as needed. Buprenorphine (Belbuca) in a class of medications called opiate partial agonists. It works by changing the way the brain and nervous system respond to pain.
How should this medicine be used?
Buprenorphine (Belbuca) comes as a buccal film to apply inside the cheek. It is usually applied twice a day. Apply buprenorphine (Belbuca) at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use buprenorphine (Belbuca) exactly as directed.
Your doctor will probably start you on a low dose of buprenorphine (Belbuca), either once daily or every 12 hours, and gradually increase your dose, not more than once every 4 days. Your doctor may decrease your dose if you experience side effects. Tell your doctor if you feel that your pain is not controlled or if you experience side effects during your treatment with buprenorphine (Belbuca). Do not change the dose of your medication without talking to your doctor.
Do not stop using buprenorphine (Belbuca) without talking to your doctor. Your doctor will probably decrease your dose gradually. If you suddenly stop using buprenorphine (Belbuca), you may have symptoms of withdrawal. Call your doctor if you experience any of these symptoms of withdrawal: restlessness, teary eyes, runny nose, yawning, sweating, chills, muscle and back aches, large pupils (black circles in the center of the eyes), irritability, anxiety, difficulty falling asleep or staying asleep, diarrhea, nausea, vomiting, decreased appetite, stomach cramps, pain in the joints, weakness, fast heartbeat, or rapid breathing.
Buprenorphine (Belbuca) is sealed in a foil package. Do not open the package until ready to use. Do not apply buprenorphine (Belbuca) if the package seal is broken or the buccal film is cut, damaged, or changed in any way.
To apply the buccal film, follow these steps:
- Fold along the dotted line at the top of the foil package. Keep folded and tear down or cut with scissors at the notch in the direction of the scissors on the dotted line. Tear all the way to the bottom. Be careful to avoid cutting and damaging the buccal film when using scissors.
- Use your tongue to wet the inside of your cheek or rinse your mouth with water to moisten the area in your mouth where you will apply the buccal film. Avoid placing the buccal film in areas with open sores.
- Remove the buccal film from the package and hold it with clean, dry fingers with the yellow side facing up.
- Immediately place the yellow side of the buccal film against the inside of your moistened cheek. Press and hold the buccal film in place for 5 seconds and then take your finger away.
- The buccal film should stick against your cheek. Leave the buccal film in place until it has completely dissolved, usually within 30 minutes after you apply it. Avoid touching or moving the buccal film with your tongue or fingers after you apply it. Do not eat or drink anything until the buccal film has dissolved completely. Do not chew or swallow the buccal film.
Other uses for this medicine
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before using buprenorphine (Belbuca),
- tell your doctor and pharmacist if you are allergic to buprenorphine, any other medications, or any of the ingredients in buprenorphine buccal films. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: amiodarone (Nexterone, Pacerone); anticholinergics (atropine, belladonna, benztropine, dicyclomine, diphenhydramine, isopropamide, procyclidine, and scopolamine); butorphanol; carbamazepine (Carbatrol, Tegretol, Teril, others); clarithromycin (Biaxin, in Prevpac); cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; in Nuedexta); disopyramide (Norpace); diuretics ('water pills'); dofetilide (Tikosyn); enzalutamide (Xtandi); human immunodeficiency virus (HIV) medications such as atazanavir (Reyataz, in Evotaz), delavirdine (Rescriptor), efavirenz (Sustiva, in Atripla), etravirine (Intelence), indinavir (Crixivan), nelfinavir (Viracept), nevirapine (Viramune), ritonavir (Norvir, in Kaletra), and saquinavir (Invirase); itraconazole (Onmel, Sporanox); ketoconazole (Nizoral); lithium (Lithobid); medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); nalbuphine; nefazodone; pentazocine (Talwin); phenobarbital; phenytoin (Dilantin, Phenytek); pioglitazone (Actos); procainamide; quinidine (in Nuedexta); rifabutin (Mycobutin); rifampin (Rifadin, Rimactane); 5HT3 serotonin blockers such as alosetron (Lotronex), dolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran, Zuplenz), or palonosetron (Aloxi); selective serotonin-reuptake inhibitors such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Prozac, Pexeva), and sertraline (Zoloft); serotonin and norepinephrine reuptake inhibitors such as duloxetine (Cymbalta), desvenlafaxine (Khedezla, Pristiq), milnacipran (Savella), and venlafaxine (Effexor); tramadol (Conzip, Ultram, in Ultracet); trazodone ; sotalol (Betapace, Sotylize, others); or tricyclic antidepressants ('mood elevators') such as amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Also tell your doctor or pharmacist if you are taking or receiving the following monoamine oxidase (MAO) inhibitors or if you have stopped taking them within the past two weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with buprenorphine, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
- tell your doctor what herbal products you are taking, especially St. John's wort and tryptophan.
- tell your doctor if you have any of the conditions listed in the IMPORTANT WARNING section or paralytic ileus (condition in which food does not move through the intestines) or a blockage in the stomach or intestines. Your doctor may tell you not to use buprenorphine (Belbuca).
- tell your doctor if you or an immediate family member 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); if you have low levels of potassium or magnesium in the blood; and if you have or have ever had a slow or irregular heartbeat; heart failure; low blood pressure; any condition that causes difficulty urinating; seizures; mouth sores; or gallbladder, pancreas, kidney, thyroid, or liver disease.
- tell your doctor if you are breastfeeding.
- you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of using buprenorphine.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are using buprenorphine (Belbuca).
- you should know that buprenorphine (Belbuca) may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
- you should know that buprenorphine (Belbuca) may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. 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 (Belbuca) may cause constipation. Talk to your doctor about changing your diet or using other medications to prevent or treat constipation while you are using buprenorphine (Belbuca).
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What should I do if I forget a dose?
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 apply a double dose to make up for a missed one.
What side effects can this medication cause?
Buprenorphine (Belbuca) may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- dry mouth
Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment:
- changes in heartbeat
- 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
- chest pain
- swelling of your face, tongue or throat
Buprenorphine (Belbuca) may cause other side effects. Call your doctor if you have any unusual problems while using 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).
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).
Dispose of any medication as soon as it becomes outdated or is no longer needed. 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 remove any unused films from their foil packages and flush them down the toilet. Throw away the foil packaging in the trash. Do not flush buprenorphine (Belbuca) down the toilet in the foil packages or cartons.
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 emergency/overdose
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 using buprenorphine (Belbuca), 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. 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:
- slow or shallow breathing or difficulty breathing
- extreme sleepiness or drowsiness
- unable to respond or wake up
- slow heartbeat
- cold, clammy skin
- muscle weakness
- narrowing or widening of the pupils (black circles in the center of the eye)
- unusual snoring
What other information should I know?
Keep all appointments with your doctor and laboratory. Your doctor may order certain lab tests to check your body's response to buprenorphine.
Before having any laboratory test (especially those that involve methylene blue), tell your doctor and the laboratory personnel that you are using buprenorphine.
Do not let anyone else use your medication. Buprenorphine (Belbuca) is a controlled substance. Prescriptions may be refilled only a limited number of times; ask your pharmacist if you have any questions.
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.