Tramadol Extended-Release Dosage & Rx Info

Tramadol Extended-release Generic Name & Formulations

Legal Class

CIV

General Description

Tramadol HCl 100mg, 200mg, 300mg; ext-rel tabs.

Pharmacological Class

Opioid agonist.

How Supplied

Contact supplier

Manufacturer

Various generic manufacturers

Mechanism of Action

Tramadol is an opioid agonist and inhibitor of norepinephrine and serotonin reuptake. Although the mode of action is not completely understood, the analgesic effect of tramadol is believed to be due to both binding to µ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin.

Tramadol Extended-release Indications

Indications

Management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatments are inadequate.

Limitations of Use

Not for use as an as-needed (prn) analgesic. Use only if alternative treatment options (eg, non-opioid analgesics) are ineffective, not tolerated, or otherwise inadequate to provide sufficient management of pain.

Tramadol Extended-release Dosage and Administration

Adult

Use lowest effective dose for shortest duration. Swallow whole. Individualize. ≥18yrs: initially 100mg once daily; may increase by 100mg every 5 days; max 300mg/day. Severe renal (CrCl <30mL/min) or hepatic (Child-Pugh Class C) impairment: not recommended. 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% every 2–4 weeks.

Children

<18yrs: not recommended.

Tramadol Extended-release Contraindications

Contraindications

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.

Tramadol Extended-release Boxed Warnings

Boxed Warning

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. Risks from concomitant use with benzodiazepines or other CNS depressants.

Tramadol Extended-release Warnings/Precautions

Warnings/Precautions

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. Severe hepatic (Child-Pugh Class C) or renal impairment (CrCl<30mL/min): not recommended. Ultra-rapid metabolizers (due to CYP2D6 polymorphism): avoid. Reevaluate periodically. Avoid abrupt cessation. Elderly (esp. >75yrs). Cachectic. Debilitated. Pregnancy; potential neonatal opioid withdrawal syndrome during prolonged use. Labor & delivery, nursing mothers: not recommended.

REMS

YES

Tramadol Extended-release Pharmacokinetics

Metabolism

Primarily CYP2D6, CYP3A4.

Elimination

Renal.

Tramadol Extended-release Interactions

Interactions

Concomitant other forms of tramadol 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.

Tramadol Extended-release Adverse Reactions

Adverse Reactions

Dizziness, nausea, constipation, headache, somnolence, flushing, pruritus, vomiting, insomnia, dry mouth; respiratory depression, severe hypotension, syncope; rare: serious skin reactions or other hypersensitivity; discontinue if occur.

Tramadol Extended-release Clinical Trials

See Literature

Tramadol Extended-release Note

Notes

Formerly known under the brand name Ultram ER.

Tramadol Extended-release Patient Counseling