Indications for: ULTRACET
Short-term (≤5 days) management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.
Limitations of Use:
Reserve for use in patients for whom alternative treatment options (eg, non-opioid analgesics): have not been tolerated, or are not expected to be tolerated; have not provided adequate analgesia, or are not expected to provide adequate analgesia.
Single-Dose Studies for Treatment of Acute Pain
In single-dose studies in acute pain, 2 tablets of Ultracet administered to patients with pain following oral surgical procedures provided greater relief than placebo or either of the individual components given at the same dose. The onset of pain relief after Ultracet was faster than tramadol alone. Onset of analgesia occurred in less than one hour. The duration of pain relief after Ultracet was longer than acetaminophen alone. Analgesia was generally comparable to that of the comparator, ibuprofen.
Use lowest effective dose for shortest duration. Individualize. ≥18yrs: initially 2 tabs every 4–6hrs as needed; max 8 tabs/day. Renal impairment (CrCl <30mL/min): max 2 tabs every 12hrs. Concomitant use or discontinuation of CYP2D6 inhibitors, CYP3A4 inhibitors or inducers: monitor closely and consider dose adjustments (see full labeling). Withdraw gradually (esp. if opioid-dependent), taper by ≤10–25%.
<18yrs: not recommended.
Children <12yrs. Post-op management in children <18yrs following tonsillectomy and/or adenoidectomy. Significant respiratory depression. Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment. Known or suspected GI obstruction, including paralytic ileus. During or within 14 days of MAOIs.
Addiction, abuse, and misuse. Risk evaluation and mitigation strategy (REMS). Life-threatening respiratory depression. Accidental ingestion. Ultra-rapid metabolism of tramadol and other risk factors for life-threatening respiratory depression in children. Neonatal opioid withdrawal syndrome. Interactions with drugs affecting CYP450 isoenzymes. Hepatotoxicity. Risks from concomitant use with benzodiazepines or other CNS depressants.
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). Abuse potential (monitor). History of substance abuse. Life-threatening respiratory depression; monitor within first 24–72hrs of initiating therapy and following dose increases. Accidental exposure 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. Risk of life-threatening respiratory depression and death related to ultra-rapid metabolizers of tramadol (esp. in children for post-tonsillectomy and/or adenoidectomy pain). Avoid in adolescents 12–18yrs with conditions associated with hypoventilation (eg, post-op status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, concomitant drugs that cause respiratory depression). COPD, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression; monitor and consider non-opioid analgesics. Adrenal insufficiency. Head injury. Increased intracranial pressure, brain tumors; monitor. Seizure disorders. Avoid in depressed, suicidal, or addiction-prone patients; consider non-narcotic analgesics. Emotional disturbance. CNS depression. Impaired consciousness, coma, shock; avoid. Biliary tract disease. Acute pancreatitis. Hyponatremia. Hypoglycemia. Diabetes. Drug or alcohol abusers. Hepatic impairment: not recommended. Renal impairment. Ultra-rapid metabolizers (due to CYP2D6 polymorphism): avoid. Reevaluate periodically. Avoid abrupt cessation. Elderly. Cachectic. Debilitated. Pregnancy; potential neonatal opioid withdrawal syndrome during prolonged use. Labor & delivery, nursing mothers: not recommended.
Opioid + analgesic.
Concomitant other forms of tramadol, acetaminophen or carbamazepine: 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. 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. Increased risk of seizures with SSRIs, SNRIs, anorectics, TCAs, cyclobenzaprine, promethazine, other opioids, MAOIs, naloxone, neuroleptics, and others that lower seizure threshold. Avoid concomitant mixed agonist/antagonist opioids (eg, butorphanol, nalbuphine, pentazocine) or partial agonist (eg, buprenorphine); may reduce effects and/or precipitate withdrawal symptoms. May be affected by CYP2D6 inhibitors (eg, amiodarone, quinidine, fluoxetine, paroxetine, bupropion). Potentiated by CYP3A4 inhibitors (eg, macrolides, azole antifungals, protease inhibitors). May potentiate serum amylase. Antagonized by CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin). May antagonize diuretics; monitor. Paralytic ileus may occur with anticholinergics. Monitor digoxin, warfarin.
Constipation, somnolence, increased sweating, diarrhea, nausea, anorexia, dizziness; respiratory depression, severe hypotension, syncope, hepatotoxicity (acetaminophen >4g/day); rare: serious skin reactions or other hypersensitivity; discontinue if occur.
Tramadol is eliminated primarily through metabolism by the liver and the metabolites are eliminated primarily by the kidneys. Acetaminophen is eliminated primarily by formation of glucuronide and sulfate conjugates in a dose dependent manner. Both tramadol and acetaminophen are excreted in the urine.
Half-life: 5 to 7 hours (tramadol); 2 to 3 hours (acetaminophen).
Clearance to bioavailability: 588 to 736 mL/min (tramadol); 365 mL/min (acetaminophen).
Generic Drug Availability: