Usual Adult Dose for Pain

Adults (17 years or older): 50 to 100 mg orally every 4 to 6 hours as needed for pain

• For patients not requiring rapid onset of analgesic effect: Initial dose: 25 mg orally once a day; titrate in 25 mg increments every 3 days to reach a dose of 25 mg four times a day; thereafter increase by 50 mg as tolerated every 3 days

Maximum dose: 400 mg per day

Comments:

• Doses should be individualized; for patients not requiring rapid analgesia, tolerability may be increased by a slow dose titration.
• The US FDA warns against use of tramadol in pediatric patients; product labeling for immediate-release tramadol describes adult patients as 17 years or older.
• Tramadol should not be used postoperatively in patients up to 18 years after tonsillectomy and/or adenoidectomy or in adolescents up to 18 years who are obese or have conditions that may increase the risk of breathing problems.

Use: For the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Usual Adult Dose for Chronic Pain

Extended-Release (ER):
18 years or older (tramadol-naive): 100 mg orally once a day

• Individually titrate in 100 mg increments every 5 days to an effective dose that minimizes adverse reactions
• Maximum Dose: 300 mg/day

For patients CURRENTLY receiving Immediate-Release (IR) Tramadol:
Initial Dose: Calculate 24-hour IR requirement and initiate with a total daily ER dose rounded down to the next lowest 100 mg increment orally once a day

Conversion from OTHER Opioids: Discontinue all other around the clock opioid drugs prior to initiating therapy

• Initial dose: 100 mg ER orally once a day
• Individually titrate in 100 mg increments every 5 days to an effective dose that minimizes adverse reactions
• Maximum Dose: 300 mg/day

Comments:

• Due to limitations of dose selection with ER formulations, some patients may not be able to convert from the IR to ER.
• The ER products should not be used with other tramadol products and should not be taken more often than once a day.
• Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of therapy and following dose increases.
• For patients with moderate to moderately severe chronic pain not requiring rapid onset of analgesic effect, tolerability can be improved by initiating slowly, possibly with the immediate-release product.
• This drug is not recommended for patients less than 18 years old.

Use: For the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

Usual Geriatric Dose for Pain

Dose selection should be cautious generally starting at the low end of the dose range

Over 75 years:
Maximum dose of Immediate-release: 300 mg per day

Comments:

• Respiratory depression is the chief risk for elderly patients treated with opioids; titrate dose slowly and monitor closely for signs of central nervous system and respiratory depression.
• Because this drug is substantially excreted by the kidney, consider monitoring renal function.

Usual Geriatric Dose for Chronic Pain

Dose selection should be cautious generally starting at the low end of the dose range

Over 75 years:
Maximum dose of Immediate-release: 300 mg per day

Comments:

• Respiratory depression is the chief risk for elderly patients treated with opioids; titrate dose slowly and monitor closely for signs of central nervous system and respiratory depression.
• Because this drug is substantially excreted by the kidney, consider monitoring renal function.

Usual Pediatric Dose for Pain

Tramadol is not recommended for use in pediatric patients

17 years or older: See Adult Dose

Renal Dose Adjustments

Immediate-release:

• CrCl less than 30 mL/min: Increase dosing interval to every 12 hours; Maximum dose should not exceed 200 mg per day

Extended-release:

• CrCl less than 30 mL/min: Use is not recommended

Liver Dose Adjustments

Immediate-release:

• Patients with cirrhosis: 50 mg orally every 12 hours

Extended-release:

• Severe hepatic impairment (Child-Pugh Class C): Use is not recommended

Dose Adjustments

Concomitant use of Drugs affecting CYP450 Isoenzymes:

• CYP450 3A4 inhibitors/inducers and CYP450 2D6 inhibitors: Interactions are complex, consult drug interaction monographs

Safe Reduction or Discontinuation of Therapy in Patients who may be Physically Dependent:

• Discontinuation/reduction plans should be individualized and take into consideration multiple factors such as type of pain, dose and duration of treatment, and patient specific physical and psychological attributes; patients should receive ongoing care and follow-up that addresses agreed upon and realistic goals.
• While there are no standard opioid tapering schedules suitable for all patients, good clinical practice dictates tapering in small increments (e.g., no greater than 10% to 25% of the total daily dose) at 2 to 4-week intervals; patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.
• When an opioid analgesic is being discontinued due to a suspected substance use disorder, patients should be evaluated and treated, or referred for evaluation and treatment of a substance use disorder; treatment should include evidence-based approaches, such as medication assisted treatment.
• When discontinuing or reducing opioid doses in patients who have been receiving therapy for an extended period and/or at higher doses for chronic pain, a multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic.

Precautions

US BOXED WARNINGS: 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; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS:

• Addiction, Abuse, and Misuse: Use of this drug exposes patients and other users to the risks of opioid addiction and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions.
• Opioid Analgesic REMS: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to complete a REMS-compliant education program; counsel patients and/or their caregivers, with every prescription on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and consider other tools to improve patient, household, and community safety.
• Life-Threatening Respiratory Depression: Serious life-threatening or fatal respiratory depression may occur. Monitor for respiratory depression, especially during initiation or following a dose increase.
• Accidental Ingestion of/exposure to even one dose, especially by children, can result in a fatal overdose.
• Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-Threatening Respiratory Depression in Children: Life-threatening respiratory depression and death have occurred in children who received tramadol. Some of the reported cases occurred following tonsillectomy and/or adenoidectomy, and in at least 1 case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP450 2D6 polymorphism. This drug is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid use in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol.
• Neonatal Opioid Withdrawal Syndrome may result from prolonged maternal opioid use during pregnancy; it may be life-threatening if not recognized and treated; management according to protocols developed by neonatology experts will be required. If opioid use is needed for a prolonged period in a pregnant woman, she should be advised of the risk of neonatal opioid withdrawal syndrome and ensure appropriate treatment be available.
• Concomitant use or discontinuation of CYP450 isoenzymes including CYP450 3A4 inducers, CYP450 3A4 inhibitors, or CYP450 2D6 inhibitors are complex; concomitant use requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1.
• Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for 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.

CONTRAINDICATIONS:

• Children less than 12 years of age
• Postoperative pain management in pediatric patients undergoing tonsillectomy and/or adenoidectomy
• Hypersensitivity (e.g., anaphylaxis) to the active substance
• Significant respiratory depression
• Acute or severe bronchial asthma, in an unmonitored setting or in the absence of resuscitative equipment
• Known or suspected gastrointestinal obstruction, including paralytic ileus
• Concomitant use or within 2 weeks of monoamine oxidase inhibitors (MAOIs)

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule IV

Dialysis

Hemodialysis patients can receive their regular dose on dialysis days since only 7% of dose is removed
Peritoneal dialysis: No data available

Other Comments

OTHER COMMENTS:
Administration advice:

• Take orally with or without food

Extended release (ER) capsules and tablets:

• Swallow whole; do not crush, chew, split, or dissolve
• ER capsules should be taken with liquid
• May take with or without food, but should be taken in a consistent manner once a day

General:

• During periods of changing analgesic requirements, including initial dose titration, frequent communication among members of the healthcare team, patients, and caregivers, is important; patients who experience breakthrough pain may require dose adjustments or if receiving the extended-release (ER) product, may need rescue medication with an immediate-release analgesic.
• Seizures and/serotonin syndrome may occur when used concomitantly with serotonergic agents (SSRIs, SNRIs, and triptans) or with drugs that significantly reduce the metabolic clearance of tramadol.
• Taking this drug in excessive doses, either alone or in combination with other CNS depressants, including alcohol, is a major cause of drug-related deaths.
• Extended-release products should be prescribed by healthcare professionals knowledgeable in the use of potent opioids for the management of chronic pain; this drug should not be used for longer than therapeutically necessary; evaluate continued use at regular intervals.

Monitoring:

• Monitor closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and with each dose increase.
• Monitor regularly for the development of addiction, abuse, and misuse.
• Consider monitoring renal function in elderly patients.

Patient advice:

• Patients should be instructed to read the US FDA-approved Medication Guide each time this drug is dispensed; they should understand the safe use, serious risks, and proper storage and disposal of this drug.
• Patients should understand that taking this medication exposes them to the risk of addiction.
• Patients should understand the risks of life-threatening respiratory depression, and be informed as to when this risk is greatest.
• This drug may cause drowsiness, dizziness, or impair thinking or motor skills; patients should avoid driving or operating machinery until adverse effects are determined.
• Patients should be instructed to avoid alcohol, not to exceed the recommended dose, and to speak with their healthcare provider regarding all concomitant medications including starting or stopping any products while taking this drug.
• Patients should be instructed to report bowel problems and signs and symptoms of adrenal insufficiency.
• Advise patient to speak to physician or health care professional if pregnant, intend to become pregnant, or are breastfeeding.
• Women of child bearing potential should understand that prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome and that prompt recognition and treatment will be necessary.

Frequently asked questions

• Is tramadol stronger than codeine?
• Can you take tramadol with acetaminophen, ibuprofen, or aspirin?
• How long does withdrawal last?
• How long does it take to start working?
• How much tramadol should I give my dog?
• How long does it stay in your system?
• Can you take 800mg ibuprofen with 50mg tramadol?
• Which drugs cause opioid-induced constipation?
• Is it an anti-inflammatory drug?