What is the recommended regimen for managing moderate to severe pain using Tramadol (tramadol hydrochloride) and Paracetamol (acetaminophen)?

From the Guidelines

For moderate to severe pain, the recommended regimen typically involves Tramadol 50-100 mg combined with Paracetamol 325-650 mg taken every 4-6 hours as needed, not exceeding 400 mg of Tramadol and 4000 mg of Paracetamol daily. This recommendation is based on the most recent and highest quality study available, which suggests that Tramadol and Paracetamol can be used effectively for managing moderate to severe pain 1.

Key Considerations

• The combination of Tramadol and Paracetamol works effectively due to their dual mechanism of action, with Tramadol acting as a weak opioid that binds to μ-opioid receptors and inhibits serotonin and norepinephrine reuptake, while Paracetamol blocks pain signals through central prostaglandin inhibition.
• Patients should be monitored for common side effects including nausea, dizziness, constipation, and drowsiness.
• This regimen should be used for the shortest duration necessary to control pain, typically reassessing after 3-7 days for acute pain conditions.
• Those with liver or kidney disease, elderly patients, or those taking other medications may require dose adjustments, as recommended by the NCCN panel, which suggests a maximum daily dose of 400 mg for IR formulations of Tramadol and 300 mg/day for ER formulations for adults with normal hepatic and renal function 1.

Important Safety Information

• Tramadol and Paracetamol should be used with caution in patients taking other serotonergic or monoamine oxidase inhibitors (MAOI)-like medications due to the risk of serotonin syndrome 1.
• The use of Tramadol is less potent than other opioids and is considered to be approximately one tenth as potent as morphine, with a Cochrane review concluding that limited evidence supports the use of Tramadol for treatment of cancer pain and that Tramadol is likely not as effective as morphine in this setting 1.

Additional Recommendations

• Treatment should begin with the lowest effective dose and be adjusted based on pain severity and individual response.
• The recommended regimen is supported by the PROSPECT recommendations, which suggest the use of weak opioids in combination with paracetamol for moderate to low-intensity pain, and COX-2 selective inhibitors or conventional NSAIDs for high-intensity pain 1.

From the FDA Drug Label

DOSAGE AND 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 can be improved by initiating therapy with the following 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 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 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 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

The recommended regimen for managing moderate to severe pain using Tramadol is to administer 50 mg to 100 mg as needed for pain relief every four to six hours, not to exceed 400 mg per day. However, the label does not provide information on the use of Inj Tramadol + Inj PCM in NS.

• Key points:
  • The dose should be individualized according to patient need using the lowest beneficial dose.
  • Elderly patients should be cautious, usually starting at the low end of the dosing range.
  • The label does not provide information on the combination of Tramadol and Paracetamol for pain management 2

From the Research

Recommended Regimen for Managing Moderate to Severe Pain

• The recommended regimen for managing moderate to severe pain using Tramadol and Paracetamol is a fixed-dose combination of Tramadol 37.5 mg and Paracetamol 325 mg, which is effective and generally well tolerated in patients with moderate to severe pain 3.
• This combination is indicated for the symptomatic treatment of moderate to severe pain and has been shown to be effective in providing pain relief in adult patients with postoperative pain, musculoskeletal pain, and other types of pain 3.
• The analgesic efficacy of Tramadol/Paracetamol is better than that of Paracetamol alone and is generally similar to or better than that of Tramadol alone or other analgesic combinations 3.
• The combination of Tramadol and Paracetamol has a favorable tolerability profile, with no additional tolerability issues relative to its components, and the incidence of adverse events is generally similar to or lower than that of other active comparators 3.

Alternative Combinations

• Other combinations, such as Tramadol/Paracetamol/Caffeine/Taurine, have also been shown to be effective in managing moderate to moderately severe acute low back pain, with a superior analgesic effect and fewer adverse reactions compared to Tramadol/Paracetamol alone 4.
• Dexketoprofen/Tramadol is another fixed-dose combination that offers a comprehensive multimodal approach to moderate-to-severe acute pain, with a good tolerability profile and a favorable pharmacokinetic and pharmacodynamic profile 5.

Tramadol Usage in Pain Management

• Tramadol is a centrally acting weak μ-opioid receptor analgesic that is used worldwide for pain management and is listed in many medical guidelines for pain management 6.
• Tramadol is prescribed to relieve moderate to severe pain management in patients and has a lower potential for dependency and serious adverse effects compared to other opioids 6.