What is the recommended dose and frequency of Tramadol (Ultram)?

From the Guidelines

Tramadol should be prescribed at a starting dose of 50-100 mg every 4-6 hours as needed for pain, with a maximum daily dose of 400 mg for immediate-release formulations and 300 mg for extended-release formulations, as recommended by the NCCN panel 1. The medication works as both a weak opioid agonist and by inhibiting the reuptake of serotonin and norepinephrine, providing pain relief through multiple mechanisms. Some key points to consider when prescribing tramadol include:

• Starting at lower doses in elderly patients, those with renal or hepatic impairment, and gradually increasing to minimize side effects
• Being aware of the risks of dependence and withdrawal symptoms, and not stopping the medication abruptly after prolonged use
• Avoiding combination with alcohol, other opioids, or certain antidepressants due to potential serious interactions
• Monitoring for common side effects such as nausea, dizziness, constipation, and drowsiness Tramadol is typically prescribed for moderate to moderately severe pain when non-opioid options are insufficient, and its efficacy and safety have been compared to other opioids such as hydrocodone and codeine in patients with cancer 1. However, the NCCN panel recommends using tramadol with caution or avoiding it in patients taking other serotonergic or monoamine oxidase inhibitors (MAOI)-like medications due to the risk of serotonin syndrome 1. In terms of dosing, the NCCN panel recommends a maximum daily dose of 400 mg for immediate-release formulations (100 mg 4 times a day) and 300 mg/day for extended-release formulations for adults with normal hepatic and renal function 1. Lower doses are recommended for older adults (75 years and older) and those with hepatic and/or renal dysfunction to reduce the risk of seizures. Overall, tramadol can be an effective option for managing moderate to moderately severe pain, but its use should be carefully considered and monitored in clinical practice.

From the FDA Drug Label

DOSAGE & ADMINISTRATION Adults (17 years of age and over) For patients with moderate to moderately severe chronic pain not requiring rapid onset of analgesic effect, the tolerability of tramadol hydrochloride tablets, USP can be improved by initiating therapy with a titration regimen: The total daily dose may be increased by 50 mg as tolerated every 3 days to reach 200 mg/day (50 mg q.i.d.) After titration, tramadol hydrochloride tablets, USP 50 to 100 mg can be administered as needed for pain relief every 4 to 6 hours not to exceed 400 mg/day For the subset of patients for whom rapid onset of analgesic effect is required and for whom the benefits outweigh the risk of discontinuation due to adverse events associated with higher initial doses, tramadol hydrochloride tablets, USP 50 mg to 100 mg can be administered as needed for pain relief every four to six hours, not to exceed 400 mg per day In all patients with creatinine clearance less than 30 mL/min, it is recommended that the dosing interval of tramadol hydrochloride tablets be increased to 12 hours, with a maximum daily dose of 200 mg. The recommended dose for adult patients with cirrhosis is 50 mg every 12 hours. In general, dose selection for an elderly patient over 65 years old should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. For elderly patients over 75 years old, total dose should not exceed 300 mg/day.

The recommended tramadol dose is:

• 50 to 100 mg every 4 to 6 hours as needed for pain relief, not to exceed 400 mg/day for adults with moderate to moderately severe chronic pain
• For patients with creatinine clearance less than 30 mL/min, the dosing interval should be increased to 12 hours, with a maximum daily dose of 200 mg
• For adult patients with cirrhosis, the recommended dose is 50 mg every 12 hours
• For elderly patients over 65 years old, dose selection should be cautious, usually starting at the low end of the dosing range, and for those over 75 years old, total dose should not exceed 300 mg/day 2

From the Research

Tramadol Dose and Frequency

• The recommended dose of tramadol is 50-100 mg immediate-release (IR) tablets every 4-6 hours 3
• Tramadol hydrochloride is available as 50 mg immediate-release (IR) and 100 mg, 200 mg, and 300 mg sustained-release (SR) tablets 3
• The tramadol SR 200 mg tablet is a better therapeutic option, with a reduced frequency of dosing, and improved patient compliance and quality of life 3

Factors Affecting Tramadol Dose and Frequency

• Medical comorbidities, use or abuse of supratherapeutic doses of tramadol, and concomitant administration of proconvulsant serotonergic cytochrome P-450 inhibitors can increase the risk of serotonin syndrome and seizures 4
• Long-term utilization of tramadol is associated with various neurological disorders like seizures, serotonin syndrome, Alzheimer's disease, and Parkinson's disease 5
• Tramadol produces seizures through inhibition of nitric oxide, serotonin reuptake, and inhibitory effects on GABA receptors 5

Interactions with Other Medications

• Selective serotonin reuptake inhibitors (SSRIs) can inhibit the analgesic activity of tramadol and codeine through inhibition of their metabolic activation 6
• SSRIs can also induce serotonin syndrome when used chronically in the presence of high doses of tramadol through synergistic serotonergic action 6
• The use of ibuprofen according to OTC guidelines in patients taking cardioprotective doses of aspirin does not appear to interfere with aspirin's antiplatelet activity 6