Tramadol

After titration, tramadol hydrochloride, tablets 50 mg to 100 mg can be administered as needed for pain relief every 4 to 6 hours not to exceed 400 mg/day ( 2.3 , 2.4 ). Severe Renal Impairment: increase the tramadol hydrochloride tablets, dosing interval to 12 hours, and limit maximum daily dose to 200 mg. Severe hepatic impairment : Recommended dose is 50 mg every 12 hours.

Dosage Modification in Patients with Renal Impairment 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. Since only 7% of an administered dose is removed by hemodialysis, dialysis patients can receive their regular dose on the day of dialysis.

Renal and Hepatic Impairment Impaired renal function results in a decreased rate and extent of excretion of tramadol and its active metabolite, M1. In patients with creatinine clearances of less than 30 mL/min, dosing reduction is recommended [see Dosage and Administration] . Metabolism of tramadol and M1 is reduced in patients with severe hepatic impairment based on a study in patients with advanced cirrhosis of the liver.

In patients with severe hepatic impairment, dosing reduction is recommended [see Dosage and Administration] . With the prolonged half-life in these conditions, achievement of steady-state is delayed, so that it may take several days for elevated plasma concentrations to develop.

Important Dosage and Administration Instructions Do not use tramadol hydrochloride tablets concomitantly with other tramadol-containing products. Do not administer tramadol hydrochloride tablets at a dose exceeding 400 mg per day. Tramadol hydrochloride tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks.

Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see Warnings and Precautions] . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of tramadol hydrochloride tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks.

Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors.

Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions] . Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with tramadol hydrochloride tablets.

Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings and Precautions] .