TOPIC: Opioid Pain Relievers or Medicines to Treat Opioid Use Disorder: MedWatch Safety Alert - FDA Recommends Health Care Professionals Discuss Naloxone with All Patients when Prescribing.
AUDIENCE: Patient, Health Professional, Pharmacy
ISSUE: FDA is requiring drug manufacturers for all opioid pain relievers and medicines to treat opioid use disorder (OUD) to add new recommendations about naloxone to the prescribing information. This will help ensure that health care professionals discuss the availability of naloxone and assess each patient's need for a naloxone prescription when opioid pain relievers or medicines to treat OUD are being prescribed or renewed. The patient Medication Guides, available at: https://bit.ly/3hzDavc, will also be updated.
BACKGROUND: Opioid pain relievers are medicines that can help manage pain when other treatments and medicines are not able to provide enough pain relief. Certain opioids are also used to treat OUD. Opioids have serious risks, including misuse and abuse, addiction, overdose, and death. Naloxone can help reverse opioid overdose to prevent death.
The misuse and abuse of illicit and prescription opioids and the risks of addiction, overdose, and death are a public health crisis in the United States. As a result, FDA is committed to encouraging health care professionals to raise awareness of the availability of naloxone when they are prescribing and dispensing opioid pain relievers or medicines to treat OUD. FDA held discussions about naloxone availability with the Anesthetic and Analgesic Drug Products and the Drug Safety and Risk Management Advisory Committees, available at: https://bit.ly/3hx8tXG, which recommended that all patients being prescribed opioids for use in the outpatient setting would benefit from a conversation with their health care professional about the availability of naloxone.
- Talk to your health care professionals about the benefits of naloxone and how to obtain it.
- Recognize the signs and symptoms of a possible opioid overdose. These include slowed, shallow, or difficult breathing, severe sleepiness, or not being able to respond or wake up. If you know or think someone is overdosing, give the person naloxone if you have access to it, and always call 911 or go to an emergency room right away. Naloxone is a temporary treatment, so repeat doses may be required. Even if you give naloxone, you still need to get emergency medical help right away.
- If you have naloxone, make sure to tell your caregivers, household members, and other close contacts that you have it, where it is stored, and how to properly use it in the event of an overdose. When using opioid medicines away from home, carry naloxone with you and let those you are with know you have it, where it is, and how to use it. Read the Patient Information leaflet or other educational material and Instructions for Use that comes with your naloxone because it explains important information, including how to use the medicine.
Health Care Professionals:
- Discuss the availability of naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat OUD.
- Consider prescribing naloxone to patients prescribed medicines to treat OUD and patients prescribed opioid analgesics who are at increased risk of opioid overdose.
- Consider prescribing naloxone when a patient has household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose.
- Additionally, even if the patients are not receiving a prescription for an opioid analgesic or medicine to treat OUD, consider prescribing naloxone to them if they are at increased risk of opioid overdose.
- Educate patients and caregivers on how to recognize respiratory depression and how to administer naloxone. Inform them about their options for obtaining naloxone as permitted by their individual state, available at: https://www.usa.gov/state-health, dispensing and prescribing requirements or guidelines for naloxone. Emphasize the importance of calling 911 or getting emergency medical help right away, even if naloxone is administered.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
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 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 you are using buprenorphine (Belbuca), you may be told to always have a rescue medication called naloxone 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. You will probably be unable to treat yourself if you experience an opiate overdose. You should make sure that your family members, caregivers, or the people who spend time with you know how to tell if you are experiencing 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 someone sees that you are experiencing symptoms of an overdose, he or she should give you your 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:
- slowed or difficulty breathing
- extreme sleepiness or drowsiness
- coma (loss of consciousness for a period of time)
- 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.