Does tramadol (tramadol hydrochloride) affect renal function?

From the Guidelines

Tramadol is not recommended in patients with renal insufficiency (GFR <30 mL/min/1.73 m2) and ESRD due to the potential for accumulation and increased risk of toxicity. According to the Society for Perioperative Assessment and Quality Improvement (SPAQI) consensus statement published in the Mayo Clinic Proceedings in 2021 1, tramadol and tapentadol are not recommended in renal insufficiency and ESRD. This is because these medications can increase the likelihood of toxicity when combined with other medications that increase serotonergic and/or noradrenergic activity.

Key Considerations

• Tramadol is a prodrug that requires metabolism by CYP2D6 to active metabolites, and the addition of medications that inhibit CYP2D6 can reduce the amount of prodrug converted to active drug, resulting in inadequate analgesia 1.
• Patients with renal insufficiency or ESRD should use opioids with no active metabolites, such as fentanyl, sufentanil, and methadone, which are preferred due to their lower risk of accumulation and toxicity 1.
• Regular kidney function monitoring is advisable for long-term tramadol users with renal impairment, and patients should be cautious of side effects like nausea, dizziness, and constipation, which may be more pronounced due to decreased drug clearance.

Clinical Implications

• In patients with normal renal health, tramadol can be used with caution, but it is essential to monitor for potential side effects and adjust the dosage as needed.
• For patients with moderate to severe kidney impairment, dosage adjustments are typically recommended, such as extending the time between doses to 12 hours and reducing the maximum daily dose.
• Patients with end-stage renal disease on dialysis should not exceed 100-200mg of tramadol daily, and alternative analgesics should be considered to minimize the risk of toxicity and accumulation.

From the FDA Drug Label

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, adjustment of the dosing regimen is recommended The total amount of tramadol and M1 removed during a 4-hour dialysis period is less than 7% of the administered dose

Tramadol may affect kidney function in patients with impaired renal function, as it can lead to a decreased rate and extent of excretion of tramadol and its active metabolite, M1.

• Dosing reduction is recommended in patients with creatinine clearances of less than 30 mL/min.
• The total amount of tramadol and M1 removed during dialysis is less than 7% of the administered dose 2.
• Renal impairment can delay the achievement of steady-state tramadol concentrations, which may take several days to develop 2.

From the Research

Tramadol and Kidney Function

• Tramadol is primarily eliminated by the hepatic route, but it is also partly eliminated by the renal route, with up to 30% of the dose being excreted through the kidneys 3.
• In patients with severely impaired kidney function (creatinine clearance below 30 ml/min), some dosage reduction or extension of the dosage interval should be considered when taking tramadol 3.
• A case study reported a 16-year-old female who developed transient acute renal impairment after an intentional tramadol ingestion, with peak serum creatinine levels of 4.04 mg/dL, which improved over 6 days with minimal intervention 4.
• Another study found that new tramadol and opioid prescription rates decreased significantly after the 2016 Centers for Disease Control and Prevention (CDC) Guideline for Prescribing Opioids for Chronic Pain, and that among patients discharged with a new tramadol prescription, 72.3% were dosed correctly based on kidney function 5.

Opioids and Kidney Disease

• Opioid use has been associated with adverse outcomes in patients with chronic kidney disease (CKD), including a increased risk of kidney disease progression, hospitalization, and death 6.
• A study found that time-updated opioid use was associated with a higher risk of kidney disease progression and hospitalization compared to non-opioid users, while NSAID use was associated with a lower risk of kidney disease progression in certain subgroups 6.
• In patients with CKD or end-stage renal disease (ESRD), opioids should be used with caution and under close monitoring, with dosage adjustments made as necessary to minimize the risk of adverse effects 7.
• Certain opioids, such as morphine and codeine, are not recommended in patients with CKD or ESRD due to the risk of neurotoxic symptoms, while others, such as buprenorphine and fentanyl, may be considered first-line agents in the management of pain in CKD patients 7.