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.
Fentanyl may be habit forming, especially with prolonged use. Use fentanyl exactly as directed. Do not use a larger dose of fentanyl, use the medication more often, or use it for a longer period of time than prescribed by your doctor. While using fentanyl, 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 fentanyl 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.
Fentanyl should only be prescribed by doctors who are experienced in treating pain in cancer patients. It should be used only to treat breakthrough cancer pain (sudden episodes of pain that occur despite around-the-clock treatment with pain medication) in cancer patients at least 18 years of age (or at least 16 years of age if using Actiq brand lozenges) who are taking regularly scheduled doses of another narcotic (opiate) pain medication, and who are tolerant (used to the effects of the medication) to narcotic pain medications. This medication should not be used to treat pain other than chronic cancer pain, especially short-term pain such as migraines or other headaches, pain from an injury, or pain after a medical or dental procedure. Fentanyl may cause serious breathing problems or death if it is used by people who are not being treated with other narcotic medications or who are not tolerant to narcotic medications.
Fentanyl may cause serious harm or death if used accidentally by a child or by an adult who has not been prescribed the medication. Even partially used fentanyl may contain enough medication to cause serious harm or death to children or other adults. Keep fentanyl out of reach of children, and if you are using the lozenges, ask your doctor how to obtain a kit from the manufacturer containing child safety locks and other supplies to prevent children from getting the medication. Dispose of partially used lozenges according to the manufacturer's directions immediately after you remove them from your mouth. If fentanyl is used by a child or an adult who has not been prescribed the medication, try to remove the medication from the person's mouth and get emergency medical help.
Fentanyl should be used along with your other pain medication(s). Do not stop taking your other pain medication(s) when you begin your treatment with fentanyl. If you stop taking your other pain medication(s) you will need to stop using fentanyl.
If you still have pain after using one lozenge or tablet, your doctor may tell you to use a second lozenge or tablet. You may use the second lozenge (Actiq) 15 minutes after you finish the first lozenge, or use the second tablet (Abstral, Fentora) 30 minutes after you started using the first tablet. Do not use a second lozenge or tablet to treat the same episode of pain unless your doctor tells you that you should. If you are using fentanyl film (Onsolis), you should not use a second dose to treat the same episode of pain. After you treat an episode of pain using 1 or 2 doses of fentanyl as directed, you must wait at least 2 hours after using fentanyl (Abstral or Onsolis) or 4 hours after using fentanyl (Actiq or Fentora) before treating another episode of breakthrough cancer pain.
Taking certain medications with fentanyl may increase the risk that you will develop serious or life-threatening breathing problems, sedation, or coma. Tell your doctor if you are taking any of the following medications: amiodarone (Nexterone, Pacerone); certain antibiotics such as clarithromycin (Biaxin, in PrevPac), erythromycin (Erythocin), telithromycin (Ketek), and troleandomycin (TAO) (not available in the US); certain antifungals such as fluconazole (Diflucan), itraconazole (Onmel, Sporanox), and ketoconazole (Nizoral); aprepitant (Emend); benzodiazepines such as alprazolam (Xanax), chlordiazepoxide (Librium), clonazepam (Klonopin), diazepam (Diastat, Valium), estazolam, flurazepam, lorazepam (Ativan), oxazepam, temazepam (Restoril), and triazolam (Halcion); cimetidine (Tagamet); diltiazem (Cardizem, Taztia, Tiazac, others); certain medications for human immunodeficiency virus (HIV) such as amprenavir (Agenerase), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), and saquinavir (Invirase); medications for mental illness and nausea; muscle relaxants; nefazodone; sedatives; sleeping pills; tranquilizers; or verapamil (Calan, Covera, Verelan). Your doctor may need to change the dosages of your medications and will monitor you carefully. If you use fentanyl with any of these medications and you 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.
Fentanyl comes as four different transmucosal products and several other types of products. The medication in each product is absorbed differently by the body, so one product cannot be substituted for any other fentanyl product. If you are switching from one product to another, your doctor will prescribe a dose that is best for you.
A program has been set up for each fentanyl product to decrease the risk of using the medication. Your doctor will need to enroll in the program in order to prescribe fentanyl and you will need to have your prescription filled at a pharmacy that is enrolled in the program. As part of the program, your doctor will talk with you about the risks and benefits of using fentanyl and about how to safely use, store, and dispose of the medication. After you talk with your doctor, you will sign a form acknowledging that you understand the risks of using fentanyl and that you will follow your doctor's instructions to use the medication safely. Your doctor will give you more information about the program and how to get your medication and will answer any questions you have about the program and your treatment with fentanyl.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with fentanyl and each time you get more medication. 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 this medication.
Why is this medication prescribed?
Fentanyl is used to treat breakthrough pain (sudden episodes of pain that occur despite round the clock treatment with pain medication) in cancer patients at least 18 years of age (or at least 16 years of age if using Actiq brand lozenges) who are taking regularly scheduled doses of another narcotic (opiate) pain medication, and who are tolerant (used to the effects of the medication) to narcotic pain medications. Fentanyl is in a class of medications called narcotic (opiate) analgesics. It works by changing the way the brain and nervous system respond to pain.
How should this medicine be used?
Fentanyl comes as a lozenge on a handle (Actiq), a sublingual (underneath the tongue) tablet (Abstral), a film (Onsolis), and a buccal (between the gum and cheek) tablet (Fentora) to dissolve in the mouth. Fentanyl is used as needed to treat breakthrough pain but not more often than four times a day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand.
Your doctor will probably start you on a low dose of fentanyl and gradually increase your dose until you find the dose that will relieve your breakthrough pain. If you still have pain 30 minutes after using fentanyl films (Onsolis), your doctor may tell you to use another pain medication to relieve that pain, and may increase your dose of fentanyl films (Onsolis) to treat your next episode of pain . Talk to your doctor about how well the medication is working and whether you are experiencing any side effects so that your doctor can decide whether your dose should be adjusted.
Do not use fentanyl more than four times a day. Call your doctor if you experience more than four episodes of breakthrough pain per day. Your doctor may need to adjust the dose of your other pain medication(s) to better control your pain.
Swallow the buccal tablet whole; do not split, chew, or crush. Also do not chew or bite the lozenge on a handle; only suck on this medication as directed.
Do not stop using fentanyl without talking to your doctor. Your doctor may decrease your dose gradually. If you suddenly stop using fentanyl, you may experience unpleasant withdrawal symptoms.
To use fentanyl lozenges (Actiq), follow these steps:
- Check the blister package and the handle of the lozenge to make sure the lozenge contains the dose of medication you have been prescribed.
- Use scissors to cut open the blister package and remove the lozenge. Do not open the blister package until you are ready to use the medication.
- Place the lozenge in your mouth, between your cheek and gum. Actively suck on the lozenge, but do not chew, crush, or bite it. Move the lozenge around in your mouth, from one side to the other, using the handle. Twirl the handle often.
- Do not eat or drink anything while the lozenge is in your mouth.
- Finish the lozenge in about 15 minutes.
- If you begin to feel dizzy, very sleepy, or nauseated before you have finished the lozenge, remove it from your mouth. Dispose of it immediately as described below or put it in the temporary storage bottle for later disposal.
- If you finish the entire lozenge, throw the handle away in a garbage can that is out of the reach of children. If you did not finish the entire lozenge, hold the handle under hot running water to dissolve all the medication, and then throw the handle away in a garbage can that is out of the reach of children and pets.
To use fentanyl buccal tablets (Fentora), follow these steps:
- Separate one blister unit from the blister card by tearing along the perforations. Peel back the foil to open the blister unit. Do not try to push the tablet through the foil. Do not open the blister unit until you are ready to use the tablet.
- Place the tablet in your mouth above one of your upper back teeth between your cheek and your gum.
- Leave the tablet in place until it dissolves completely. You may notice a gentle bubbling feeling between your cheek and gum as the tablet dissolves. It may take 14 to 25 minutes for the tablet to dissolve. Do not split, chew, bite, or suck the tablet.
- If any of the tablet is left in your mouth after 30 minutes, swallow it with a drink of water.
- If you begin to feel dizzy, very sleepy, or nauseated before the tablet dissolves, rinse your mouth with water and spit the remaining pieces of tablet into the sink or toilet. Flush the toilet or rinse the sink to wash away the tablet pieces.
To use fentanyl sublingual tablets (Abstral), follow these steps:
- Take a sip of water to moisten your mouth if it is dry. Spit out or swallow the water. Make sure your hands are dry before handling the tablet.
- Separate one blister unit from the blister card by tearing along the perforations. Peel back the foil to open the blister unit. Do not try to push the tablet through the foil. Do not open the blister unit until you are ready to use the tablet.
- Place the tablet under your tongue as far back as you can. If more than 1 tablet is needed for your dose, spread them around on the floor of your mouth under your tongue.
- Leave the tablet in place until it dissolves completely. Do not suck, chew, or swallow the tablet.
- Do not eat or drink anything until the tablet is completely dissolved and you no longer feel it in your mouth.
To use fentanyl films (Onsolis), follow these steps:
- Use scissors to cut along the arrows of the foil package to open it. Separate the layers of the foil package and remove the film. Do not open the foil package until you are ready to use the medication. Do not cut or tear the film.
- Use your tongue to wet the inside of your cheek, or if needed, rinse your mouth with water to wet the area where you will place the film.
- Hold the film on a clean, dry finger, with the pink side facing up. Place the film in your mouth, with the pink side against the inside of your moistened cheek. With your finger, press the film against your cheek for 5 seconds. Then remove your finger and the film will stick to the inside of your cheek. If more than one film is needed for your dose, do not put the films on top of each other. You may place the films on either side of your mouth.
- Leave the film in place until it dissolves completely. The film will release a minty flavor as it dissolves. It may take 15 to 30 minutes for the film to dissolve. Do not chew or swallow the film. Do not touch or move the film while it dissolves.
- You may drink liquids after 5 minutes, but do not eat anything until the film dissolves completely.
Other uses for this medicine
This medication should not be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before using fentanyl,
- tell your doctor and pharmacist if you are allergic to fentanyl patches, injection, nasal spray, tablets, lozenges, or films; any other medications; or any of the ingredients in fentanyl tablets, lozenges, or 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 medications: antihistamines; barbiturates such as phenobarbital; buprenorphine (Buprenex, Subutex, in Suboxone); butorphanol (Stadol); carbamazepine (Carbatrol, Epitol, Tegretol); efavirenz (Sustiva, in Atripla); modafinil (Provigil); nalbuphine (Nubain); naloxone (Evzio, Narcan); nevirapine (Viramune); oral steroids such as dexamethasone, methylprednisolone (Medrol), and prednisone (Rayos); oxcarbazepine (Trileptal); pentazocine (Talwin); phenytoin (Dilantin, Phenytek); pioglitazone (Actos, in Actoplus Met, in Duetact); rifabutin (Mycobutin); and rifampin (Rifadin, Rimactane, in Rifamate, in Rifater). Also tell your doctor or pharmacist if you are taking any of the following medications or if you have stopped taking them within the past two weeks: monoamine oxidase (MAO) inhibitors including isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor what herbal products you are taking, especially St. John's wort.
- tell your doctor if you or anyone in your family drinks or has ever drunk large amounts of alcohol or uses or has ever used street drugs or excessive amounts of prescription medications. Also tell your doctor if you have or have ever had a head injury, a brain tumor, a stroke, or any other condition that caused high pressure inside your skull; seizures; slowed heartbeat or other heart problems; low blood pressure; mental problems such as depression, schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions), or hallucinations (seeing things or hearing voices that do not exist); breathing problems such as asthma and chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema); or kidney or liver disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while using fentanyl, call your doctor.
- you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of using fentanyl.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are using fentanyl.
- you should know that fentanyl may make you drowsy or dizzy. Do not drive a car or operate machinery until you know how this medication affects you.
- you should know that fentanyl may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start using fentanyl. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
- if you have diabetes, you should know that each fentanyl lozenge (Actiq) contains about 2 grams of sugar.
- if you will be using the lozenges (Actiq), talk to your dentist about the best way to care for your teeth during your treatment. The lozenges contain sugar and may cause tooth decay and other dental problems.
- you should know that fentanyl may cause constipation. Talk to your doctor about changing your diet and using other medications to treat or prevent constipation.
What special dietary instructions should I follow?
Do not eat grapefruit or drink grapefruit juice while using this medication.
What should I do if I forget a dose?
This medication is usually used as needed according to directions.
What side effects can this medication cause?
Fentanyl may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- stomach pain
- weight loss
- difficulty urinating
- changes in vision
- unusual thinking
- unusual dreams
- difficulty falling asleep or staying asleep
- dry mouth
- sudden reddening of the face, neck, or upper chest
- uncontrollable shaking of a part of the body
- back pain
- chest pain
- pain, sores, or irritation in the mouth in the area where you placed the medication
- swelling of the hands, arms, feet, ankles, or lower legs
Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:
- 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
If you experience any of these symptoms, stop using fentanyl and call your doctor immediately or get emergency medical treatment:
- slow, shallow breathing
- decreased urge to breathe
- difficulty breathing or swallowing
- extreme drowsiness
Fentanyl 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 packaging it came in, tightly closed, and out of reach of children. Store fentanyl in a safe place so that no one else can use it accidentally or on purpose. Use the child-resistant locks and other supplies provided by the manufacturer to keep children away from the lozenges. Keep track of how much fentanyl is left so you will know if any is missing. Store fentanyl at room temperature and away from excess heat and moisture (not in the bathroom). Do not freeze fentanyl.
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 flush the fentanyl down the toilet so that others will not take it. Dispose of unneeded lozenges by removing each lozenge from the blister package, holding the lozenge over the toilet, and cutting off the medicine end with wire cutters so that it falls into the toilet. Throw away the remaining handles in a place that is out of the reach of children and pets, and flush the toilet twice when it contains up to five lozenges. Dispose of unneeded tablets or films by removing them from the packaging and flushing them down the toilet. Throw the remaining fentanyl packaging or cartons into a trash container; do not flush these items down the toilet. 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 emergency/overdose
In case of overdose, remove the fentanyl from the victim's mouth and call local emergency services at 911.
While using fentanyl, 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:
- slow, shallow breathing or stopped breathing
- smaller pupils (black circles in the middle of the eyes)
What other information should I know?
Keep all appointments with your doctor.
Do not let anyone else use your medication, even if he or she has the same symptoms that you have. Selling or giving away this medication may cause severe harm or death to others and is against the law.
This prescription is not refillable. Be sure to schedule appointments with your doctor on a regular basis so that you do not run out of medication.
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.
¶ This branded product is no longer on the market. Generic alternatives may be available.