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 nasal spray may be habit forming, especially with prolonged use. Use fentanyl nasal spray exactly as directed. Do not use a larger dose of fentanyl nasal spray, use the medication more often, or use it for a longer period of time than prescribed by your doctor. While using fentanyl nasal spray, discuss with your healthcare 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 nasal spray if you have or have ever had any of these conditions. Talk to your healthcare 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 nasal spray may cause serious breathing problems or death, especially if it is used by people who have not been treated with other narcotic medications or who are not tolerant (used to the effects of the medication) to narcotic medications. Fentanyl nasal spray 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 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 nasal spray may cause serious harm or death if used accidentally by a child or by an adult who has not been prescribed the medication. Partially used fentanyl nasal spray bottles contain enough medication to cause serious harm or death to children or other adults. Always keep fentanyl nasal spray in its child-resistant container and out of the reach of children. If fentanyl nasal spray is used by a child or an adult who has not been prescribed the medication, get emergency medical help.
Fentanyl nasal spray should be used along with your other pain medication(s). If you stop taking your other pain medication(s) you will need to stop using fentanyl nasal spray.
You must wait at least 2 hours after using fentanyl nasal spray before using another dose, even if you still have pain. Tell your doctor if you still have pain 30 minutes after using fentanyl nasal spray.
Taking certain medications during your treatment with fentanyl nasal spray 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), benzodiazepines such as alprazolam (Xanax), chlordiazepoxide (Librium), clonazepam (Klonopin), diazepam (Diastat, Valium), estazolam, flurazepam, lorazepam (Ativan), oxazepam, temazepam (Restoril), and triazolam (Halcion); erythromycin (Erythocin, Eryc, Erythrocin, others), and telithromycin (Ketek); certain antifungals such as fluconazole (Diflucan), itraconazole (Onmel, Sporanox), and ketoconazole (Nizoral); aprepitant (Emend); cimetidine (Tagamet); diltiazem (Cardizem, Taztia, Tiazac, others); certain medications for human immunodeficiency virus (HIV) such as amprenavir (no longer available in the U.S.; 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, in Tarka). 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.
Drinking alcohol, taking prescription or nonprescription medications that contain alcohol, or using street drugs during your treatment with fentanyl increases the risk that you will experience these serious, life-threatening side effects. Do not drink alcohol, take prescription or nonprescription medications that contain alcohol, or use street drugs during your treatment.
Fentanyl comes as several different 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 to decrease the risk of using fentanyl nasal spray. Your doctor will need to enroll in the program in order to prescribe fentanyl nasal spray 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 nasal spray 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 nasal spray 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 nasal spray.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with fentanyl nasal spray 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 nasal spray is used to treat breakthrough pain (sudden episodes of pain that occur despite round the clock treatment with pain medication) in cancer patients 18 years of age or older 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 nasal spray comes as a solution (liquid) to spray in the nose. It is used as needed to treat breakthrough pain but not more often than four times per 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 start you on a low dose of fentanyl nasal spray and gradually increase your dose until you find the dose that will relieve your breakthrough 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. If you still have pain 30 minutes after using fentanyl nasal spray, your doctor may tell you to use another pain medication to relieve that pain, and may increase your dose of fentanyl nasal spray to treat your next episode of pain. Do not increase your dose of fentanyl nasal spray unless your doctor tells you that you should.
Do not use fentanyl nasal spray 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.
Do not stop using fentanyl nasal spray without talking to your doctor. If you suddenly stop using fentanyl nasal spray, you may experience unpleasant withdrawal symptoms.
To use fentanyl nasal spray, follow these steps:
- Blow your nose, if you have a runny nose.
- Remove the cap from the child-resistant container and take the bottle of fentanyl nasal spray out. Remove the protective cap from the bottle tip. Hold the bottle so that the nozzle is between your first and second fingers and your thumb is on the bottom.
- If you are using a new bottle, you must prime the bottle before use. Prime the bottle by spraying 4 sprays into the pouch following the manufacturer's instructions in the Medication Guide.
- Sit upright and insert the tip of the bottle approximately 1/2 inch (1 cm) into one nostril, pointing the tip toward the bridge of your nose. Close your other nostril with your finger.
- Press down firmly on the finger grips until you hear a ''click'' sound. You may not feel the spray go into your nose, but as long as the number in the counting window increases by 1, the spray has been given.
- Breathe in gently through your nose and out through your mouth one time after spraying. Do not sniff after spraying the medication into your nose.
- If your doctor wants you to use two sprays, repeat steps 4 through 6, using your other nostril.
- When the number in the counting window is an ''8'', do not try to use any more sprays from the bottle. There will still be some liquid in the bottle that will need to be sprayed in the pouch following the manufacturer's instructions in the Medication Guide.
- Stay sitting down for at least 1 minute after using fentanyl nasal spray.
- Do not blow your nose for at least 30 minutes after using fentanyl nasal spray.
- Replace the protective cap on the bottle and put the bottle back in the child-resistant container, out of reach of children.
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 nasal spray,
- 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 nasal spray. 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; carbamazepine (Carbatrol, Epitol, Tegretol, Teril); cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; in Nuedexta); efavirenz (in Atripla, Sustiva); lithium (Lithobid); medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Alsuma, Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); modafinil (Provigil); nalbuphine; naloxone (Evzio, Narcan); nasal decongestants such as oxymetazoline (Afrin, Neo-Synephrine, Vicks Sinex, others); nevirapine (Viramune); oxcarbazepine (Trileptal); pentazocine (Talwin); phenytoin (Dilantin, Phenytek); pioglitazone (Actos, in Actoplus Met, in Duetact, others); rifabutin (Mycobutin); rifampin (Rifadin, Rimactane, in Rifamate, in Rifater); 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 desvenlafaxine (Khedezla, Pristiq), duloxetine (Cymbalta), milnacipran (Savella), and venlafaxine (Effexor); oral steroids such as dexamethasone, methylprednisolone (Medrol), and prednisone (Rayos); trazodone (Oleptro); and 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 any of the following medications or if you have stopped taking them within the past two weeks: monoamine oxidase (MAO) inhibitors including isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate). Many other medications may also interact with fentanyl, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. 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 and tryptophan.
- 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 a runny nose or have or have ever had a head injury, a stroke, or any other condition that caused high pressure inside your skull; seizures; slowed heartbeat or other heart problems; low blood pressure; difficulty urinating; 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 nasal spray, 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 nasal spray.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are using fentanyl nasal spray.
- you should know that fentanyl nasal spray 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 nasal spray 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 fentanyl nasal spray 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 nasal spray may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
Some side effects can be serious. If you experience this symptom, call your doctor immediately:
- slow 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 nasal spray and call your doctor immediately or get emergency medical treatment:
- slow, shallow breathing
- decreased urge to breathe
- difficulty breathing or swallowing
- extreme drowsiness
Fentanyl nasal spray 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?
Store fentanyl nasal spray in its child-resistant container, tightly closed, and out of reach of children. Store the child-resistant container and pouch in the cardboard box it came in when not in use. Store fentanyl nasal spray in a safe place so that no one else can use it accidentally or on purpose. Keep track of how many sprays in each bottle are left so you will know if any are missing. Store it at room temperature and away from light, excess heat and moisture (not in the bathroom). Do not freeze fentanyl nasal spray.
Dispose of fentanyl nasal spray as soon as it becomes outdated or is no longer needed. Dispose of any bottle of fentanyl nasal spray if 5 days have passed since you last used it or if 14 days have passed since you prepared the bottle for its first use. You can safely dispose of fentanyl nasal spray by spraying remaining liquid into the pouch provided with the medication, as described in the Medication Guide. The sealed pouch and empty bottle should then be placed in the child-resistant container before putting it in the trash. Wash your hands with soap and water right away after handling the pouch. Call your pharmacist or the manufacturer if you have questions, need help disposing of unneeded medication, or do not have a pouch available.
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 fentanyl nasal spray, 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 and laboratory. Your doctor will order certain lab tests to check your body's response to fentanyl.
Before having any laboratory test (especially those that involve methylene blue), tell your doctor and the laboratory personnel that you are using fentanyl.
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.