Indications for SUBSYS:
Management of breakthrough pain in opioid-tolerant cancer patients who are already receiving and are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain. Opioid-tolerant patients are those taking oral morphine ≥60mg/day, transdermal fentanyl ≥25mcg/hr, oral oxycodone ≥30mg/day, oral hydromorphone ≥8mg/day, oral oxymorphone ≥25mg/day, oral hydrocodone ≥60mg/day, or equianalgesic dose of another opioid for ≥1 week.
Limitations of Use:
May be dispensed only to outpatients enrolled in the TIRF REMS ACCESS program; not required for inpatient use.
Do not substitute with other fentanyl products; not equivalent to other fentanyl products on a mcg per mcg basis. Use lowest effective dose for shortest duration. Spray contents into the mouth under the tongue. Individualize. ≥18yrs: Initially 100mcg; monitor and titrate to a tolerable dosage level until adequate analgesia achieved using a single Subsys dose per episode. For each episode, if pain not relieved after 30 mins, may take 1 additional dose at same strength for that episode; max 2 doses per episode. Wait at least 4hrs before treating another episode. If adequate analgesia obtained within 30 mins, treat subsequent episodes with this dose. Titration steps: 100mcg using 1 x 100mcg unit; 200mcg using 1 x 200mcg unit; 400mcg using 1 x 400mcg unit; 600mcg using 1 x 600mcg unit; 800mcg using 1 x 800mcg; 1200mcg using 2 x 600mcg unit; 1600mcg using 2 x 800mcg unit. Maintenance: once an appropriate dose has been established, use that dose for subsequent breakthrough episodes. Limit to ≤4 doses per day. Reevaluate if >4 episodes per day occur. Conversion from Actiq: see full labeling. Cancer patients with oral mucositis: Grade 1: monitor for respiratory and CNS depression (esp. during initiation); Grade ≥2: avoid. Concomitant use or discontinuation of CYP3A4 inhibitors or inducers: monitor closely and consider dose adjustments (see full labeling).
<18yrs: not established.
Opioid non-tolerant patients. Acute or post-op pain (including headache/migraine, dental pain, or ER). Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment. Known or suspected GI obstruction, including paralytic ileus.
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 access program. Neonatal opioid withdrawal syndrome.
Assess the potential need for access to naloxone when initiating and renewing therapy. Consider prescribing naloxone based on risk factors for overdose (eg, history of opioid use disorder, prior opioid overdose, household members or other close contacts at risk for accidental ingestion or overdose). Life-threatening respiratory depression; monitor within first 24–72hrs of initiating therapy and following dose increases. Accidental ingestion may cause fatal overdose (esp. in children). Sleep-related breathing disorders (including central sleep apnea (CSA), sleep-related hypoxemia); consider dose reduction if CSA develops. COPD, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression; monitor and consider non-opioid analgesics. Abuse potential (monitor). Adrenal insufficiency. Head injury. Increased intracranial pressure, brain tumors; monitor. Seizure disorders. CNS depression. Impaired consciousness, coma, shock; avoid. Biliary tract disease. Acute pancreatitis. Bradyarrhythmias. Drug abusers. Renal or hepatic impairment. Reevaluate periodically. Avoid abrupt cessation. Elderly. Cachectic. Debilitated. Pregnancy; potential neonatal opioid withdrawal syndrome during prolonged use. Labor & delivery, nursing mothers: not recommended.
Increased risk of hypotension, respiratory depression, sedation with benzodiazepines or other CNS depressants (eg, non-benzodiazepine sedatives/hypnotics, anxiolytics, general anesthetics, phenothiazines, tranquilizers, muscle relaxants, antipsychotics, alcohol, other opioids); reserve concomitant use in those for whom alternative options are inadequate; limit dosages/durations to minimum required; monitor closely; consider prescribing naloxone if concomitant use is warranted. During or within 14 days of MAOIs: not recommended. Risk of serotonin syndrome with serotonergic drugs (eg, SSRIs, SNRIs, TCAs, triptans, 5-HT3 antagonists, mirtazapine, trazodone, tramadol, cyclobenzaprine, metaxalone, MAOIs, linezolid, IV methylene blue); monitor and discontinue if suspected. Avoid concomitant mixed agonist/antagonist opioids (eg, butorphanol, nalbuphine, pentazocine) or partial agonist (eg, buprenorphine); may reduce effects and/or precipitate withdrawal symptoms. Potentiated by CYP3A4 inhibitors (eg, macrolides, azole antifungals, protease inhibitors). Antagonized by CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin). May antagonize diuretics; monitor. Paralytic ileus may occur with anticholinergics.
Vomiting, nausea, constipation, dyspnea, somnolence; respiratory depression, severe hypotension, syncope.
Available by restricted distribution program. Call (866) 822-1483 or visit www.tirfremsaccess.com to enroll. Caution patients and caregivers in proper handling and disposal; may be fatal to children.
Generic Drug Availability:
Blister pack (spray units)—10, 30