Fentanyl Sublingual Spray

FDA Drug Safety Communication:

[Posted 4/13/2023]

• 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.

Fentanyl sublingual spray may be habit forming, especially with prolonged use. Use fentanyl sublingual spray 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 sublingual spray, 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 fentanyl sublingual spray 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 sublingual 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 sublingual spray should 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 sublingual spray may cause serious harm or death if used accidentally by a child or by an adult who has not been prescribed the medication. Even used fentanyl sublingual spray containers may contain enough medication to cause serious harm or death to children or other adults. Keep fentanyl sublingual spray out of reach of children. 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 unused doses of fentanyl according to the manufacturer's directions. If fentanyl sublingual spray is used by a child or an adult who has not been prescribed the medication, get emergency medical help.

Fentanyl sublingual spray 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 sublingual spray. If you stop taking your other pain medication(s) you will need to stop using fentanyl sublingual spray.

Taking certain medications with fentanyl sublingual 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: certain antibiotics such as clarithromycin (Biaxin, in PrevPac), erythromycin (Erythocin, Eryc, Erythrocin, others), telithromycin (Ketek), and troleandomycin (TAO) (not available in the United States); certain antifungals such as fluconazole (Diflucan), itraconazole (Onmel, Sporanox) and ketoconazole; aprepitant (Emend); benzodiazepines such as alprazolam (Xanax), chlordiazepoxide (Librium), clonazepam (Klonopin), diazepam (Diastat, Valium), estazolam, flurazepam, lorazepam (Ativan), oxazepam, temazepam (Restoril), and triazolam (Halcion); 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, 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 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 to decrease the risk of using this 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 (https://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.

Fentanyl sublingual 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 and 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.

Fentanyl comes as a solution (liquid) to spray sublingually (under the tongue). It is used as needed to treat breakthrough pain but not more often than directed by your doctor. 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 sublingual spray and gradually increase your dose until you find the dose that will relieve your breakthrough pain. Use one dose of fentanyl sublingual spray for breakthrough pain. If you are still in pain after your first dose, use a second dose 30 minutes after your first dose. Do not use more than two doses per breakthrough pain episode. After you treat an episode of pain using one or two doses of fentanyl sublingual spray, wait at least 4 hours after using fentanyl sublingual spray before treating a new episode of breakthrough pain. If you have more than four episodes of breakthrough cancer pain in a day, call your doctor.

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. Take fentanyl exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Do not stop using fentanyl sublingual spray without talking to your doctor. Your doctor may decrease your dose gradually. If you suddenly stop using fentanyl sublingual spray, you may experience unpleasant withdrawal symptoms.

To use the oral spray, follow these directions and those that appear in the package label:

1. Remove the fentanyl sublingual spray unit from the blister package by cutting along the dashed line with a pair of scissors.
2. Swallow any saliva in your mouth.
3. Hold the fentanyl sublingual spray unit upright using your index and middle fingers and thumb.
4. Point the nozzle into your mouth and under your tongue.
5. Squeeze your fingers and thumb together to spray the medication under your tongue.
6. Hold the medication under your tongue for 30 to 60 seconds. Do not spit out the medication or rinse your mouth. The fentanyl sublingual spray is a one-time use unit and will remain locked after use.
7. Place the used fentanyl sublingual spray unit in one of the provided disposal bags. Remove the backing from the adhesive strip and fold the flap to seal the bag.
8. Discard the sealed bag into the trash out of the reach of children.

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

Before taking 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 sublingual 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; 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); medications for seizures such as carbamazepine (Tegretol, Teril), oxcarbazepine (Trileptal), and phenytoin (Dilantin, Phenytek); modafinil (Provigil); nalbuphine; naloxone (Evzio, Narcan); nevirapine (Viramune); oral steroids such as dexamethasone, methylprednisolone (Medrol), and prednisone (Rayos); pioglitazone (Actos); rifampin (Rifadin, Rimactane, in Rifamate, in Rifater); rifabutin (Mycobutin); 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); trazodone (Oleptro); tricyclic antidepressants ('mood elevators') such as amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); or troglitazone (Rezulin). 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), and 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 or have ever had sores, ulcers, or swelling in your mouth, a head injury, a brain tumor, a stroke, or any other condition that caused high pressure inside your skull; slowed heartbeat or other heart problems; difficulty urinating; 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 sublingual spray.
• 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.
• you should know that fentanyl sublingual spray may cause constipation. Talk to your doctor about changing your diet and using other medications to treat or prevent constipation.

Talk to your doctor about eating grapefruit and drinking grapefruit juice while taking this medication.

This medication is usually used as needed according to directions.

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

• itching
• drowsiness
• pain on the right side of your stomach
• dry mouth
• headache
• uncontrollable shaking of a part of the body
• difficulty falling asleep or staying asleep
• anxiety
• back pain
• itching
• cough

Some side effects can be serious. If you experience any of the following symptoms or those listed in the IMPORTANT WARNING or SPECIAL PRECAUTIONS section, 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:

• drowsiness with slowed breathing
• slow, shallow breathing
• decreased urge to breathe
• difficulty breathing or swallowing
• fainting

Fentanyl may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

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

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 (https://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the sealed blister package, 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 medication. Keep track of how much fentanyl is left so you will know if any is missing. Store it at room temperature and away from light, excess heat and moisture (not in the bathroom).

Dispose of fentanyl sublingual spray as soon as it is used or is no longer needed. Place the used spray unit into a disposable bag. Seal the bag and discard into a trash container out of the reach of children. If you have unused spray units, open the packaging according to directions. Spray the content of the unit into the disposal bottle provided in the packaging. Repeat with each unused container. Close the disposal container and shake. Place the disposal container into a disposable bag and discard into a trash container. Talk to your pharmacist about the proper disposal of your 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. https://www.upandaway.org

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

While using fentanyl sublingual spray, 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, shallow, or stopped breathing
• difficulty breathing
• sleepiness
• unable to respond or wake up
• confusion
• smaller pupils (black circles in the middle of the eyes)

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 taking 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.

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.

• Subsys^®