What is Subsys?

Warning: Life-Threatening Respiratory Depression, Accidental Ingestion; Cytochrome P450 3A4 Interaction; Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants; Risk of Medication Errors; Addiction, Abuse, and Misuse; REMS; and Neonatal Opioid Withdrawal SyndromeSerious, life-threatening, and/or fatal respiratory depression has occurred. Monitor closely, especially upon initiation or following a dose increase. Due to the risk of fatal respiratory depression, fentanyl sublingual spray is contraindicated in opioid non-tolerant patients and in management of acute or postoperative pain, including headache/migraines.Accidental ingestion of fentanyl sublingual spray, especially by children, can result in a fatal overdose of fentanyl. Keep out of reach of children. Ensure proper storage and disposal.Concomitant use with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of fentanyl.Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation.When prescribing, do not convert patients on a mcg per mcg basis from any other oral transmucosal fentanyl product to fentanyl sublingual spray.When dispensing, do not substitute with any other fentanyl products.Fentanyl sublingual spray exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient's risk before prescribing and monitor regularly for these behaviors and conditions.Fentanyl sublingual spray is available only through a restricted program called the TIRF REMS Access program. Outpatients, healthcare professionals who prescribe to outpatients, pharmacies, and distributors are required to enroll in the program.Prolonged use of fentanyl sublingual spray during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If prolonged opioid use is required in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available..

Due to the risk of fatal respiratory depression, transmucosal fentanyl citrate is contraindicated in opioid non-tolerant patients and in management of acute or postoperative pain, including headache/migraines. Monitor for respiratory depression during treatment. Accidental ingestion of fentanyl can result in a fatal overdose, especially in children; keep out of reach of children. Use with CYP3A4 inhibitors or inducers may change fentanyl plasma levels resulting in a fatal overdose of fentanyl and monitoring is recommended. Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients with inadequate alternative treatment options, limit dosage and duration to the minimum required, and monitor for respiratory depression and sedation. When prescribing, do not convert patients on a mcg per mcg basis from any other fentanyl products. When dispensing, do not substitute with any other fentanyl products. Fentanyl is a Schedule II controlled substance with abuse liability similar to other opioid analgesics. Assess risk prior to initiation and monitor for signs of misuse, abuse, and addiction during treatment. Only available through a restricted program called the Transmucosal Immediate Release Fentanyl Risk Evaluation and Mitigation Strategy (TIRF REMS) Access program. Outpatients, healthcare professionals who prescribe to outpatients, pharmacies, and distributors are required to enroll in the program. Prolonged use during pregnancy may result in neonatal opioid withdrawal syndrome. If prolonged use is required in a pregnant woman, advise patient of potential fetal risk and ensure appropriate treatment will be available .

Due to the risk of fatal respiratory depression, sublingual fentanyl citrate is contraindicated in opioid non-tolerant patients and in management of acute or postoperative pain, including headache/migraines. Monitor for respiratory depression during treatment. Accidental ingestion of fentanyl can result in a fatal overdose, especially in children; keep out of reach of children. Use with CYP3A4 inhibitors or inducers may change fentanyl plasma levels resulting in fatal overdose and monitoring is recommended. Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients with inadequate alternative treatment options, limit dosage and duration to the minimum required, and monitor for respiratory depression and sedation. When prescribing, do not convert patients on a mcg per mcg basis from any other fentanyl products. When dispensing, do not substitute with any other fentanyl products. Fentanyl is a Schedule II controlled substance with abuse liability similar to other opioid analgesics. Assess risk prior to initiation and monitor for signs of misuse, abuse, and addiction during treatment. Only available through a restricted program called the Transmucosal Immediate Release Fentanyl Risk Evaluation and Mitigation Strategy (TIRF REMS) Access program. Outpatients, healthcare professionals who prescribe to outpatients, pharmacies, and distributors are required to enroll in the program. Prolonged use during pregnancy may result in neonatal opioid withdrawal syndrome. If prolonged use is required in a pregnant woman, advise patient of potential fetal risk and ensure appropriate treatment will be available .

Fentanyl is used to treat severe pain in cancer patients. It is used for breakthrough cancer pain, which are flares of pain that “break through” after a routine pain medicine has been used. Fentanyl belongs to the group of medicines called narcotic analgesics. It is only used in patients who are already taking narcotic analgesics.

Fentanyl acts in the central nervous system (CNS) to relieve pain. Some of its side effects are also caused by actions in the CNS. When a narcotic is used for a long time, it may become habit-forming or cause mental or physical dependence. However, people who have continuous pain should not let the fear of dependence keep them from using narcotics to relieve pain. Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly. Withdrawal side effects can usually be prevented by gradually reducing the dose over a period of time before the medicine is stopped completely. Talk to your doctor about the benefits of this medicine and how to prevent withdrawal side effects.

This medicine is available only with your doctor's prescription. The Abstral®, Actiq®, Fentora®, Onsolis®, and Subsys® products are only available under a restricted distribution program. You will have to read and sign papers that explain how the medicine is used when you pick up your prescription.

Use this medicine only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered.

The Abstral®, Actiq®, Fentora®, Onsolis®, and Subsys® products are only available under a restricted distribution program. You will have to read and sign papers that explain how the medicine is used when you pick up your prescription.

This medicine should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions. Ask your pharmacist for the Medication Guide if you do not have one.

Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

Keep the medicine in the original blister package. Open the package right before use.

Abstral® tablets:

• Place the tablet under the tongue until it dissolves. Do not chew, suck, or swallow the tablet.
• Do not eat or drink anything until the tablet has dissolved. If your mouth is dry, use water to rinse the mouth before you place the tablet under the tongue.

Actiq® lozenges:

• Place the lozenge in the mouth between the cheek and lower gum. Using the handle, move the lozenge from one side to the other every now and then.
• Suck the medicine for 15 minutes and do not chew it.

Fentora® buccal tablets:

• Peel the blister back to remove the tablet. Do not push the tablet through the blister as this may damage the tablet.
• Place the tablet between the upper cheek and gum, above a back molar, until it dissolves. Do not chew, suck, or swallow the tablet.
• If the tablet does not dissolve completely after 30 minutes, you may swallow it with a glass of water.

Onsolis® buccal film:

• Use your tongue to wet the side of your cheek or rinse your mouth with water in the area where you will place the film.
• Do not cut or tear the film. Hold the film on a clean, dry finger with the pink side facing up.
• Press the film against your cheek and hold it there for 5 seconds.
• Leave the film in place until it dissolves and do not touch or move the film. Do not chew or swallow the film.
• If you must use more than one film, place the second film on the other side of your mouth.
• Do not eat any food until the film dissolves. You may drink water or other liquids after 5 minutes.

Subsys® sublingual spray:

• Carefully spray the medicine under your tongue.
• Hold the medicine under your tongue for 30 to 60 seconds. Do not rinse your mouth and do not spit out any medicine.

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For cancer pain:
  • For buccal dosage form (film):
    • Adults—At first, one 200 microgram (mcg) film for each pain episode. Your doctor may adjust your dose as needed. However, the maximum number of pain episodes that can be treated each day is 4.
    • Children—Use and dose must be determined by your doctor.
  • For buccal dosage form (tablets):
    • Adults—At first, 100 micrograms (mcg) for each pain episode. If instructed by your doctor, this dose may be repeated after waiting 30 minutes between doses. Your doctor may adjust your dose as needed. However, the maximum number of pain episodes that can be treated each day is 4.
    • Children—Use and dose must be determined by your doctor.
  • For transmucosal dosage form (lozenges):
    • Adults and children 16 years of age and older—At first, 200 micrograms (mcg) for each pain episode. If instructed by your doctor, this dose may be repeated after waiting 15 minutes between doses. Your doctor may adjust your dose as needed. However, the maximum number of units that can be used each day is 4.
    • Children younger than 16 years of age—Use and dose must be determined by your doctor.
  • For sublingual dosage form (spray):
    • Adults—At first, 100 micrograms (mcg) or 1 spray for each pain episode. If instructed by your doctor, this dose may be repeated once after waiting 30 minutes. Additional pain episodes may be treated after a minimum of 4 hours.
    • Children—Use and dose must be determined by your doctor.
  • For sublingual dosage form (tablets):
    • Adults—At first, 100 micrograms (mcg) for each pain episode. If instructed by your doctor, this dose may be repeated after waiting 30 minutes between doses. Your doctor may adjust your dose as needed. However, the maximum number of pain episodes that can be treated each day is 4.
    • Children—Use and dose must be determined by your doctor.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Abstral® tablets: If you have questions about the best way to dispose of the tablets you do not use, ask your pharmacist or call 1-888-227-8725.

Actiq® lozenges: If you have questions about the best way to dispose of the lozenges you do not use, ask your pharmacist or call 1-800-896-5855.

Fentora® tablets: If you have questions about the best way to dispose of the tablets you do not use, ask your pharmacist or call 1-800-896-5855.

Onsolis® film: If you have questions about the best way to dispose of the films you do not use, ask your pharmacist or call 1-800-526-3840.

Subsys® spray: Place the used spray unit into a disposal bag. Seal the disposal bag and throw it into a trash container that is out of the reach of children. For the unopened spray units, use the disposal bottle to empty the liquid from each unit. Place the disposal bottle in a bag and seal it. Throw the bag into a trash container that is out of the reach of children. If you have questions, call 1-877-978-2797.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Appropriate studies have not been performed on the relationship of age to the effects of fentanyl in children younger than 18 years of age for the Abstral®, Fentora®, Onsolis®, and Subsys® brands, and in children younger than 16 years of age for the Actiq® brand. Safety and efficacy have not been established in these age groups.

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of fentanyl in the elderly. However, elderly patients may be more sensitive to the effects of narcotic analgesics than younger adults and are more likely to have age-related lung or kidney problems, which may require caution and an adjustment in the dose for patients receiving fentanyl in order to avoid serious side effects.

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Mifepristone
• Nalmefene
• Naltrexone
• Safinamide

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acepromazine
• Alefacept
• Alfentanil
• Almotriptan
• Alprazolam
• Amineptine
• Amiodarone
• Amisulpride
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Amprenavir
• Anileridine
• Aprepitant
• Aripiprazole
• Armodafinil
• Asenapine
• Atazanavir
• Baclofen
• Benperidol
• Benzhydrocodone
• Benzphetamine
• Boceprevir
• Bosentan
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Buspirone
• Butabarbital
• Butorphanol
• Carbamazepine
• Carbinoxamine
• Cariprazine
• Carisoprodol
• Carphenazine
• Ceritinib
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clobazam
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Cyclosporine
• Darunavir
• Delavirdine
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexamethasone
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diltiazem
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Doxepin
• Dronedarone
• Droperidol
• Duloxetine
• Efavirenz
• Eletriptan
• Eluxadoline
• Enflurane
• Enzalutamide
• Erythromycin
• Escitalopram
• Eslicarbazepine Acetate
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Etravirine
• Flibanserin
• Fluconazole
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fosamprenavir
• Fosaprepitant
• Fosnetupitant
• Fosphenytoin
• Fospropofol
• Frovatriptan
• Furazolidone
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Idelalisib
• Imatinib
• Imipramine
• Indinavir
• Iproniazid
• Isocarboxazid
• Isoflurane
• Itraconazole
• Ivacaftor
• Ketamine
• Ketobemidone
• Ketoconazole
• Lanreotide
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lomitapide
• Lopinavir
• Lorazepam
• Lorcaserin
• Loxapine
• Lumacaftor
• Meclizine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methylene Blue
• Metoclopramide
• Mibefradil
• Midazolam
• Milnacipran
• Mirtazapine
• Mitotane
• Moclobemide
• Modafinil
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nafcillin
• Nalbuphine
• Naratriptan
• Nefazodone
• Nelfinavir
• Netupitant
• Nevirapine
• Nialamide
• Nicardipine
• Nicomorphine
• Nifedipine
• Nilotinib
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxcarbazepine
• Oxycodone
• Oxymorphone
• Palbociclib
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Pazopanib
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenelzine
• Phenobarbital
• Phenytoin
• Pimozide
• Piperacetazine
• Pipotiazine
• Piritramide
• Pitolisant
• Posaconazole
• Prazepam
• Prednisone
• Primidone
• Procarbazine
• Prochlorperazine
• Promazine
• Promethazine
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Ramelteon
• Ranitidine
• Ranolazine
• Rasagiline
• Remifentanil
• Remoxipride
• Ribociclib
• Rifabutin
• Rifampin
• Rifapentine
• Ritonavir
• Rizatriptan
• Saquinavir
• Secobarbital
• Selegiline
• Sertindole
• Sertraline
• Sibutramine
• Sodium Oxybate
• St John's Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Suvorexant
• Tapentadol
• Telaprevir
• Telithromycin
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Topiramate
• Tramadol
• Tranylcypromine
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Venlafaxine
• Verapamil
• Vilazodone
• Voriconazole
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol
• Grapefruit Juice

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse, or history of or
• Brain tumor, history of or
• Breathing problems (eg, asthma, apnea) or
• Chronic obstructive pulmonary disease (COPD) or
• Cor pulmonale (serious heart condition) or
• Depression, history of or
• Drug dependence, especially narcotic abuse, history of or
• Head injury, history of or
• Mental health problems, history of—Use with caution. May cause side effects to become worse.

• Bradyarrhythmia (slow heart rhythm) or
• Hypotension (low blood pressure) or
• Pancreatitis (inflammation of the pancreas)—Use with caution. May make these conditions worse.

• Diabetes—Use the Actiq® brand with caution. There are 2 grams of sugar in each unit.

• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Stomach or bowel blockage (including paralytic ileus), known or suspected—Should not be used in patients with these conditions.

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it.

Do not use this medicine for minor aches and pains (eg, headaches, migraines) or after surgery or injuries.

Do not use this medicine if you have taken a monoamine oxidase (MAOI) inhibitor (eg, isocarboxazid phenelzine, selegiline, tranylcypromine, Eldepryl®, Marplan®, Nardil®, or Parnate®) in the past 2 weeks.

Using this medicine while you are pregnant may cause serious unwanted effects in your newborn baby. Tell your doctor right away if you think you are pregnant or if you plan to become pregnant while using this medicine.

Fentanyl is a medicine that can harm or cause death to a child. Patients and caregivers should keep this medicine out of the reach of children. Carefully dispose of any partially used units or unused medicine properly.

This medicine may be habit-forming. If you feel that the medicine is not working as well, do not use more than your prescribed dose. Call your doctor for instructions.

This medicine will add to the effects of alcohol and other central nervous system (CNS) depressants. CNS depressants are medicines that slow down the nervous system, which may cause drowsiness or make you less alert. This effect may last for a few days after you stop using this medicine. Some examples of CNS depressants are antihistamines or medicine for hay fever, allergies, or colds, sedatives, tranquilizers, benzodiazepines, other prescription pain medicine or narcotics, barbiturates or seizure medicines, muscle relaxants, or anesthetics (numbing medicines), including some dental anesthetics. Check with your doctor before taking any of the medicines listed above while you are using this medicine.

Fentanyl may cause some people to become drowsy, confused, or dizzy. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert. Check with your doctor if you have confusion or drowsiness that is severe enough to interfere with your daily activities.

Using narcotics for a long time can cause severe constipation. To prevent this, your doctor may tell you to take laxatives, drink fluids, or increase the amount of fiber in your diet. Follow the directions carefully. Constipation that continues can lead to more serious problems.

If you have been using this medicine regularly for several weeks or more, do not suddenly stop using it without checking with your doctor. You may be directed to gradually reduce the amount you are using before stopping it completely to lessen the chance of withdrawal side effects.

Using too much fentanyl, or taking too much of another narcotic with fentanyl, may cause an overdose. If this occurs, get emergency help right away. An overdose can cause severe breathing problems (breathing may even stop), unconsciousness, and death. Serious signs of an overdose include very slow breathing (fewer than 8 breaths each minute) and drowsiness that is so severe you are not able to answer when spoken to, or if asleep, cannot be awakened.

The Actiq® product contains sugar and may increase your chance for tooth decay. Schedule regular dentist visits if you are using Actiq®.

Check with your doctor right away if you have anxiety, restlessness, a fast heartbeat, fever, sweating, muscle spasms, twitching, nausea, vomiting, diarrhea, or see or hear things that are not there. These may be symptoms of a serious condition called serotonin syndrome. Your risk may be higher if you also take certain other medicines that affect serotonin levels in your body.

Using too much of this medicine may cause reduced infertility (unable to have children). Talk with your doctor before using this medicine if you plan to have children.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.