What is the maximum recommended dose of tramadol (opioid analgesic) per day?

Maximum Tramadol Dose

The maximum daily dose of tramadol is 400 mg per day for immediate-release formulations and 300 mg per day for extended-release formulations, with important reductions required for elderly patients over 75 years (300 mg/day maximum) and those with renal or hepatic impairment. 1

Standard Dosing Limits

Immediate-Release Formulations

• Maximum daily dose: 400 mg/day for adults under 75 years with normal organ function 1, 2
• Administered as 50-100 mg every 4-6 hours as needed 1, 3
• Duration of analgesic effect is approximately 6 hours per dose 4

Extended-Release Formulations

• Maximum daily dose: 300 mg/day for once-daily sustained-release preparations 2
• This lower maximum reflects the pharmacokinetic profile of sustained-release formulations 5

Dose Reductions for Special Populations

Elderly Patients

• Patients over 75 years: maximum 300 mg/day regardless of formulation 1, 2
• Start at the low end of the dosing range (50 mg once or twice daily) due to decreased hepatic, renal, and cardiac function 1

Renal Impairment

• Creatinine clearance <30 mL/min: maximum 200 mg/day with dosing interval increased to every 12 hours 1, 2
• Hemodialysis patients can receive regular doses on dialysis days since only 7% is removed by dialysis 1

Hepatic Impairment

• Cirrhosis: 50 mg every 12 hours (maximum 100 mg/day) 1

Titration Strategy to Minimize Adverse Effects

Recommended Approach

• Start at 50 mg once or twice daily, then increase by 50-100 mg every 3 days as tolerated 2, 1
• Gradual titration significantly reduces discontinuation rates due to adverse effects, particularly nausea 1, 4
• Nausea is dose-dependent and occurs early in treatment; slow titration is the key strategy to improve tolerability 4, 6

Rapid Onset Option

• For patients requiring immediate pain relief where benefits outweigh risks, 50-100 mg every 4-6 hours can be initiated without titration, not exceeding 400 mg/day 1
• This approach carries higher risk of adverse effects and discontinuation 1

Clinical Context and Potency

Relative Effectiveness

• Tramadol has 0.1-0.2 times the potency of oral morphine, classifying it as a WHO Level II (weak) opioid 3, 2
• This low potency ceiling explains why there is a defined maximum dose beyond which additional analgesia is unlikely 3

When Maximum Dose Is Inadequate

• If pain remains uncontrolled after 4 weeks at 400 mg/day, transition to a stronger opioid (WHO Level III) such as morphine sulfate 20-40 mg daily or oxycodone 20 mg daily 2
• The 400 mg ceiling reflects both efficacy limitations and increased seizure risk at higher doses 2

Critical Safety Considerations

Seizure Risk

• Risk of seizures increases with high doses or in predisposed patients 2
• This is a key reason the 400 mg/day maximum should never be exceeded 2

Serotonin Syndrome Risk

• Use caution or avoid tramadol in patients taking SSRIs or other serotonergic medications due to tramadol's serotonin reuptake inhibition properties 2, 3
• This dual mechanism (weak opioid + monoamine reuptake inhibition) distinguishes tramadol from pure opioids 4

Accumulation with Repeated Dosing

• Tramadol and its active M1 metabolite accumulate approximately 2-fold during multiple-dose treatment 4
• Half-life is 5.1 hours for tramadol and 9 hours for M1 metabolite, explaining the need for dosing intervals of at least 4-6 hours 4