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SUBSYS is used for the management of breakthrough pain in cancer patients 18 years of age and older who are already receiving and are tolerant to opioid therapy for their underlying constant cancer pain.
SUBSYS is the first and only breakthrough pain medication for patients with cancer offered as a sublingual spray. SUBSYS may provide pain relief in as little as 5 minutes. SUBSYS is a unique fentanyl sublingual spray that delivers a fine mist of medication underneath the tongue to provide pain relief. It is the first and only sublingual spray for breakthrough cancer pain.
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SUBSYS® is indicated for the management of breakthrough pain in cancer patients 18 years of age and older who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain.
Patients considered opioid tolerant are those who are taking for one week or longer, around-the-clock medicine consisting of at least 60 mg of oral morphine per day, at least 25 mcg of transdermal fentanyl per hour, at least 30 mg of oral oxycodone per day, at least 8 mg of oral hydromorphone per day, or at least 25 mg oral oxymorphone per day, or at least 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid daily for a week or longer. Patients must remain on around-the-clock opioids when taking SUBSYS.
This product must not be used in opioid non-tolerant patients because life-threatening respiratory depression and death could occur at any dose in patients not on a chronic regimen of opioids. For this reason, SUBSYS is contraindicated in the management of acute or postoperative pain.
Limitations of Use
Not for use in opioid non-tolerant patients.
Not for use in the management of acute or postoperative pain, including headache/migraine, dental pain, or in the emergency room.
Because of the risk for misuse, abuse, addiction, and overdose, SUBSYS is available only as part of the Transmucosal Immediate-Release Fentanyl (TIRF) REMS Access Program. SUBSYS may be dispensed only to outpatients enrolled in the program. For inpatient administration (e.g., hospitals, hospices, and long-term care facilities that prescribe for inpatient use) of SUBSYS, patient enrollment is not required.
IMPORTANT SAFETY INFORMATION
- Opioid non-tolerant patients: Life-threatening respiratory depression and death could occur at any dose in opioid non-tolerant patients
- Acute or postoperative pain including headache/migraine and dental pain, or in the emergency department
- Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment.
- Known or suspected gastrointestinal obstruction, including paralytic ileus.
- Known hypersensitivity (e.g., anaphylaxis) to fentanyl or components of SUBSYS
Warnings and Precautions
- Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of SUBSYS, the risk is greatest during the initiation of therapy or following a dosage increase.
- In cancer patients with mucositis, exposure to SUBSYS was greater than in patients without mucositis. For patients with Grade 1 mucositis, the increased maximum serum concentration and overall exposure requires closer monitoring for respiratory depression and central nervous system depression, particularly during initiation of therapy with SUBSYS
- For patients with Grade 2 mucositis or higher, avoid the use of SUBSYS unless the benefits outweigh the potential risk of respiratory depression from increased exposure
- Patients and their caregivers must be instructed that SUBSYS contains a medicine in an amount that can be fatal to a child. Death has been reported in children who have accidentally ingested transmucosal immediate–release fentanyl products. While all units should be disposed of immediately after use, partially consumed units represent a special risk to children. In the event that a unit is not completely consumed it must be properly disposed of as soon as possible
- Concomitant use of SUBSYS with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythmycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of fentanyl and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression [see Warnings and Precautions (5.5)], particularly when an inhibitor is added after a stable dose of SUBSYS is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in SUBSYS-treated patients may increase fentanyl plasma concentrations and prolong opioid adverse reactions. When using SUBSYS with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in SUBSYS-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of SUBSYS until stable drug effects are achieved [see Drug Interactions (7)].
- Profound sedation, respiratory depression, coma, and death may result from the concomitant use of SUBSYS with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
- When prescribing, DO NOT convert a patient to SUBSYS from any other fentanyl product on a mcg per mcg basis as SUBSYS and other fentanyl products are not equivalent on a microgram per microgram basis. SUBSYS is NOT a generic version of other transmucosal immediate-release fentanyl (TIRF) formulations. When dispensing, DO NOT substitute a SUBSYS prescription for any other TIRF formulation under any circumstances. Other TIRF formulations and SUBSYS are not equivalent. Substantial differences exist in the pharmacokinetic profile of SUBSYS compared to other fentanyl products including other TIRF formulations that result in clinically important differences in the rate and extent of absorption of fentanyl. As a result of these differences, the substitution of SUBSYS for any other fentanyl product may result in a fatal overdose.
- SUBSYS contains fentanyl, a Schedule II controlled substance. As an opioid, SUBSYS exposes users to the risks of addiction, abuse, and misuse. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed SUBSYS. Addiction can occur at recommended dosages and if the drug is misused or abused. The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as SUBSYS, but use in such patients necessitates intensive counseling about the risks and proper use of SUBSYS along with intensive monitoring for signs of addiction, abuse, and misuse.
- Because of the risk of misuse, abuse, addiction, and overdose [see Warnings and Precautions (5.1)], SUBSYS is available only through a restricted program called the TIRF REMS Access program. Under the TIRF REMS Access program, outpatients, healthcare professionals who prescribe to outpatients, pharmacies, and distributors must enroll in the program. For inpatient administration (e.g. hospitals, hospices, and long-term care facilities that prescribe for inpatient use) of SUBSYS, patient and prescriber enrollment is not required.
- Prolonged use of SUBSYS during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts.
- The use of SUBSYS in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.
- Patients treated with SUBSYS who have significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of SUBSYS.
- Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients.
- Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of SUBSYS with serotonergic drugs. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
- Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.
- SUBSYS may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs.
- Administer SUBSYS with extreme caution in patients who may be particularly susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors) as SUBSYS may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure.
- SUBSYS is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus. The fentanyl in SUBSYS may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms.
- The fentanyl in SUBSYS may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures.
- Patients taking SUBSYS must be warned that opioid analgesics impair the mental and/or physical ability required for the performance of potentially dangerous tasks (e.g., driving a car or operating machinery). Warn patients taking SUBSYS of these dangers and counsel them accordingly.
- Intravenous fentanyl may produce bradycardia. Therefore, use SUBSYS with caution in patients with bradyarrhythmias.
- Monitor patients for opioid toxicity who begin therapy with, or increase the dose of, inhibitors of CYP450 3A4, or stop therapy with, or decrease the dose of, inducers of CYP450 3A4.
- Due to the additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants including alcohol, increases the risk of respiratory depression, profound sedation, coma, and death.
- The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
- MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma).
- Mixed agonist/antagonist and partial agonist opioid analgesics may reduce the analgesic effect of SUBSYS and/or precipitate withdrawal symptoms.
- Fentanyl may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
- The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
- The most serious adverse reactions associated with all opioids including SUBSYS are respiratory depression (potentially leading to apnea or respiratory arrest), circulatory depression, hypotension, and shock. Follow all patients for symptoms of respiratory depression.
- The most common adverse events subsequent to titration (frequency ? 5%): nausea, vomiting, constipation, asthenia, dyspnea, and anxiety.
- The most common adverse events during titration (frequency ? 5%): nausea, vomiting, constipation, somnolence, and dizziness.
- The most common adverse reaction leading to discontinuation of SUBSYS was nausea.
SYNDROS is a prescription medicine used in adults to treat:
- Loss of appetite (anorexia) in people with AIDS (Acquired Immune Deficiency Syndrome) who have lost weight
- Nausea and vomiting caused by anti-cancer medicine (chemotherapy) in people whose nausea and vomiting have not improved with usual anti-nausea and vomiting medicines
SYNDROS is the first and only FDA-approved liquid dronabinol, which allows for fast absorption, flexible dosing and a potential solution for patients who may prefer a liquid medication.
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What is SYNDROS?
SYNDROS is a prescription medicine used in adults to treat:
- loss of appetite (anorexia) in people with AIDS (Acquired Immune Deficiency Syndrome) who have lost weight.
- nausea and vomiting caused by anti-cancer medicine (chemotherapy) in people whose nausea and vomiting have not improved with usual anti-nausea medicines.
SYNDROS is a controlled substance (CII) because it contains dronabinol which can be a target for people who abuse prescription medicines or street drugs. Keep your SYNDROS in a safe place to protect it from theft. Never give your SYNDROS to anyone else because it may cause death or harm them. Selling or giving away this medicine is against the law.
It is not known if SYNDROS is safe and effective in children.
Do not take SYNDROS if you:
- had an allergic reaction to dronabinol. Signs and symptoms of an allergic reaction to dronabinol include: swelling of the lips, hives, a rash over your whole body, mouth sores, skin burning, flushing, and throat tightness.
- had an allergic reaction to alcohol.
- are using a medicine that contains disulfiram (Antabuse) or metronidazole (Pylera, Flagyl, Flagyl ER, Nuvessa, Vandazole) or have taken or received a medicine that contains disulfiram or metronidazole in the last 14 days.
Before taking SYNDROS, tell your doctor about all of your medical conditions, including if you:
- have or had heart problems.
- have or had problems with drug abuse or dependence.
- have or had problems with alcohol abuse or dependence.
- have or had mental health problems including mania, depression or schizophrenia.
- have had a seizure or have a medical condition that may increase your risk of having a seizure.
- are pregnant or plan to become pregnant. SYNDROS may harm your unborn baby. Avoid the use of SYNDROS if you are pregnant.
- are breastfeeding or plan to breastfeed. The Centers for Disease Control and Prevention recommends that mothers with HIV not breastfeed because they can pass the HIV through their breast milk to the baby. It is not known if SYNDROS passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take SYNDROS. Do not breastfeed while taking SYNDROS and for 9 days after your last dose of SYNDROS if you are being treated for nausea and vomiting caused by anti-cancer medicine.
Tell your doctor about all the medicines you take or have taken in the last 14 days, including prescription and over-the-counter medicines, vitamins, and herbal supplements. SYNDROS and certain other medicines can affect each other, causing serious side effects.
How should I take SYNDROS?
- See the "Instructions for Use" at the end of the Patient Information for detailed instructions about the right way to take SYNDROS.
- Always use the oral syringe that comes with your SYNDROS oral solution to measure your prescribed dose. Ask your doctor or pharmacist to show you how to measure your prescribed dose.
- Take SYNDROS exactly as your doctor tells you to. Your doctor may change your dose after seeing how it affects you. Do not change your dose unless your doctor tells you to change it.
- Drink a full glass of water (6 to 8 ounces) right after you take your prescribed dose of SYNDROS oral solution.
- If you are an adult with AIDS with loss of appetite and weight loss:
- SYNDROS is usually taken 2 times each day, 1 hour before lunch and 1 hour before dinner. If you are elderly, or unable to tolerate this dose of SYNDROS, your doctor may prescribe SYNDROS to be taken 1 time each day, 1 hour before dinner or bedtime.
- If you are an adult with nausea and vomiting caused by anti-cancer medicine:
- SYNDROS is usually taken 1 to 3 hours before your chemotherapy treatment and then every 2 to 4 hours after chemotherapy for up to 4 to 6 doses each day. If you are elderly, your doctor may prescribe SYNDROS to be taken 1 to 3 hours before your chemotherapy, 1 time each day.
- Take your first dose of SYNDROS on an empty stomach at least 30 minutes before eating. After your first dose of SYNDROS, you can take SYNDROS with or without food.
- After your doctor has decided the dose of SYNDROS that is right for you, take SYNDROS exactly at the same time before or after meals during future chemotherapy treatment.
- If you take too much SYNDROS, call your Poison Control Center at 1-800-222-1222 right away or go to the nearest emergency room.
What should I avoid while taking SYNDROS?
- Do not drive, operate machinery, or do other dangerous activities until you know how SYNDROS affects you. SYNDROS taken with medicines that cause dizziness, confusion, and sleepiness may make these symptoms worse.
What is the most important information I should know about SYNDROS?
SYNDROS can cause serious side effects, including:
- Worsening mental (psychiatric) symptoms. Psychiatric symptoms can worsen in people who have mania, depression, or schizophrenia and who take SYNDROS. SYNDROS taken with medicines that cause psychiatric symptoms can worsen psychiatric symptoms. Elderly people who take SYNDROS may have a greater risk of having psychiatric symptoms. Tell your doctor if you have new or worsening mood symptoms, including symptoms of mania, depression, or schizophrenia.
- Problems thinking clearly. Tell your doctor if you have trouble remembering things, concentrating, have increased sleepiness, or confusion. Elderly people may have a greater risk of having problems thinking clearly.
- Changes in your blood pressure. SYNDROS may increase or decrease your blood pressure, especially when you start taking SYNDROS or when your dose is changed. Tell your doctor if you have signs or symptoms of changes in your blood pressure including: headaches, vision problems, dizziness, feeling lightheaded, fainting, or a fast heartbeat. Elderly people, especially those with dementia, and people with heart problems may have an increased risk of changes in blood pressure and an increased risk of falls.
- Interactions with disulfiram or metronidazole. SYNDROS contains alcohol, which can cause you to have a reaction to medicines that contain disulfiram or metronidazole. You should not use any medicine that contains disulfiram (Antabuse) or metronidazole (Pylera, Flagyl, Flagyl ER, Nuvessa, Vandazole) if you take SYNDROS. You should not use a medicine that contains disulfiram or metronidazole for at least 14 days before you start taking SYNDROS and within 7 days after your last dose of SYNDROS. Tell your doctor if you have signs or symptoms of a reaction to disulfiram or metronidazole including: stomach-area (abdominal) cramping, nausea, vomiting, headache, and flushing.
What are the possible side effects of SYNDROS?
SYNDROS may cause serious side effects, including:
- See "What is the most important information I should know about SYNDROS?"
- Seizures. SYNDROS may increase your risk of seizures. Stop taking SYNDROS and call your doctor and get medical care right away if you have a seizure during treatment with SYNDROS.
- Drug and alcohol abuse. You may have an increased risk of abusing SYNDROS if you have a history of drug or alcohol abuse or dependence, including marijuana. Tell your doctor if you develop abuse behaviors such as increased irritability, nervousness, restlessness or want more or higher doses of SYNDROS during your treatment.
- Nausea, vomiting, or stomach-area (abdominal) pain. Tell your doctor if you have nausea, vomiting, or abdominal pain or if your nausea, vomiting, or abdominal pain gets worse during treatment with SYNDROS.
The most common side effects of SYNDROS include:
- stomach-area (abdominal) pain
- feeling extremely happy (euphoria)
- overly suspicious or feeling people want to harm you (paranoid reaction)
- abnormal thoughts
These are not all the possible side effects of SYNDROS. Tell your doctor if you have any side effect that bothers you or does not go away. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about the safe and effective use of SYNDROS
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use SYNDROS for a condition for which it was not prescribed. Do not give SYNDROS to other people, even if they have the same symptoms that you have. It may harm them. You can ask your doctor or pharmacist for information about SYNDROS that is written for health professionals.
What are the ingredients in SYNDROS?
Active ingredient: dronabinol
Inactive ingredients: dehydrated alcohol, polyethylene glycol 400, propylene glycol, sucralose, methyl paraben, propyl paraben, butylated hydroxyanisole, and water