Ultracet Dosing for Moderate to Moderately Severe Pain
For adults with moderate to moderately severe pain, start Ultracet (tramadol 37.5 mg/acetaminophen 325 mg) at 2 tablets every 4-6 hours as needed, not exceeding 8 tablets (300 mg tramadol/2600 mg acetaminophen) per 24 hours. 1
Standard Adult Dosing Protocol
The FDA-approved regimen is 2 tablets (tramadol 37.5 mg/acetaminophen 325 mg per tablet) every 4-6 hours as needed for pain, with a maximum of 8 tablets in 24 hours. 1 This provides 75 mg tramadol and 650 mg acetaminophen per dose, totaling a maximum daily exposure of 300 mg tramadol and 2600 mg acetaminophen. 1
Clinical Context and Evidence Base
The fixed-dose combination of tramadol 37.5 mg/acetaminophen 325 mg provides faster onset of analgesia (17 minutes) compared to tramadol alone (51 minutes), with longer duration of action than either component as monotherapy. 2
This combination demonstrates superior efficacy to either agent alone in dental pain, postoperative pain, and musculoskeletal pain, with the precise dose ratio optimized for additive analgesic effect. 3, 4, 5
Two tablets of tramadol/acetaminophen 37.5/325 mg provide similar analgesia to hydrocodone/acetaminophen 10/650 mg over 8 hours in postoperative dental pain. 4
Dose Adjustments for Special Populations
Elderly Patients (Over 75 Years)
Reduce maximum daily dose to 6 tablets (225 mg tramadol/1950 mg acetaminophen) per 24 hours in patients over 75 years old. 1 Start at the low end of the dosing range and titrate cautiously. 1
Renal Impairment
For creatinine clearance <30 mL/min, increase dosing interval to every 12 hours with a maximum of 4 tablets (150 mg tramadol/1300 mg acetaminophen) per 24 hours. 1 Dialysis patients can receive their regular dose on dialysis days since only 7% is removed by hemodialysis. 1
Hepatic Impairment (Cirrhosis)
For patients with cirrhosis, administer 1 tablet every 12 hours only (maximum 2 tablets/day). 1 Tramadol bioavailability increases 2-3 fold in liver cirrhosis, making standard dosing dangerous and potentially precipitating hepatic encephalopathy. 6
Clinical Positioning in Pain Management
Ultracet is appropriate for moderate to moderately severe pain when acetaminophen alone is inadequate. 3, 5
The combination is classified as WHO Step II (weak opioid) analgesia and should not be used for severe pain requiring strong opioids like morphine. 6
For osteoarthritis pain, tramadol/acetaminophen taken for up to 3 months may decrease pain and improve stiffness, function, and overall well-being, with typical dosing ranging from 1 tablet once daily to maximum recommended doses. 7
Critical Safety Considerations
Absolute Maximum Limits
Never exceed 8 tablets per day (300 mg tramadol/2600 mg acetaminophen) to avoid both tramadol-related adverse effects and acetaminophen hepatotoxicity. 1 The tramadol component has an absolute maximum of 400 mg/day for all formulations, but the combination product limits this to 300 mg due to acetaminophen content. 6, 1
Serotonin Syndrome Risk
Avoid concurrent use with SSRIs, SNRIs, tricyclic antidepressants, or MAO inhibitors due to high risk of serotonin syndrome from tramadol's serotonergic effects. 7, 6
Seizure Risk
Use with extreme caution in patients with seizure history or those taking medications that lower seizure threshold, as tramadol increases seizure risk, particularly at higher doses. 7
Hidden Acetaminophen Sources
Explicitly counsel patients to avoid all other acetaminophen-containing products including over-the-counter cold remedies and other opioid combinations to prevent unintentional overdose. 8 This is the most common cause of inadvertent acetaminophen toxicity in clinical practice.
Common Pitfalls to Avoid
Failing to adjust dosing in elderly, renal, or hepatic patients: Standard dosing can cause significant toxicity in these populations. 6 Always calculate creatinine clearance and assess liver function before prescribing.
Using Ultracet for severe pain: This delays appropriate strong opioid therapy and provides inadequate analgesia. 6 Tramadol is only 0.1-0.2 times as potent as oral morphine.
Prescribing without checking medication reconciliation: Missing concurrent serotonergic medications or other acetaminophen sources leads to dangerous drug interactions and overdose. 7, 8
Exceeding dosing frequency: Taking doses closer than every 4 hours rapidly approaches toxic thresholds for both components. 8, 1