Suzetrigine: Is It A Safer Pain Medication For Patients With Kidney Disease?

Pain management in patients with chronic kidney disease (CKD) is complex. Widely used analgesics like opioids, NSAIDs and gabapentinoids may directly or indirectly result in acute or chronic kidney disease. Many opioids (e.g. morphine) accumulate in the body due to reduced clearance, resulting in neurotoxic symptoms. NSAIDs are associated with acute interstitial nephritis, minimal change disease, and pre-renal acute kidney injury (AKI). These drugs may result in fluid retention and increased blood pressure. Gabapentinoids are exclusively eliminated by the kidney and require dose adjustment in CKD to avoid excess sedation, falls, and other issues.

Suzetrigine (Journavx) is a non-opioid analgesic, approved by the FDA in January 2025. It is the first medication in the selective NaV1.8 voltage-gated channel inhibitors class. These receptors are expressed in the peripheral sensory neurons; hence, this medication inhibits the transmission of pain signals to the spinal cord and brain. Unlike opioids, Suzetrigine does not interact with opioid receptors, sparing the patient from respiratory depression, sedation, or dependence. 

Phase 3 trials, primarily those studying post-surgical pain following a bunionectomy or abdominoplasty showed that Suzetrigine significantly reduced pain and opioid use, positioning the drug as a promising opioid-sparing alternative.

This is where Suzetrigine could be a game-changer—offering pain relief without risking nephrotoxicity. But does it live up to its potential? Let’s take a closer look.

Suzetrigine And Monitoring Kidney Function

For patients with an eGFR >15 mL/min, no dosage adjustment of suzetrigine is required. The medication is taken by mouth on an empty stomach, at least 1 hour before food. The 50 or 100-mg tablet may be taken every 12 hours and does not interact with other drugs. It has not been studied in patients with CKD stage 5 (eGFR < 15 ml/min) or patients receiving dialysis. Since the drug is 99% protein-bound, the free drug concentration is reduced and time to elimination is increased. This makes the medication very difficult to remove via dialysis, in the event of toxicity. There is no available antidote in the event of an overdose. Commonly reported side effects include itching, rash, and nausea. Compared to placebo, nearly twice as many patients on suzetrigine (1 to 1.3% compared to 0.5%) developed muscle spasms and/or an increase in creatine phosphokinase. An elevated creatine phosphokinase (a.k.a creatine kinase) with clinical muscle injury may result in rhabdomyolysis, a condition that is associated with kidney impairment. However, this was not explicitly reported in the trials.

So, while Suzetrigine looks promising, it may be prudent to monitor kidney function in those with eGFR < 15 ml/min. 

A Look At The Trials: Promising But Cautious

Suzetrigine’s clinical trials, though exciting, included patients without substantial kidney impairment. In these studies, the drug performed well in reducing pain and opioid use, with no major safety concerns. However, the data for patients with CKD, particularly those with severe impairment or on dialysis, is still limited. This leaves us asking: How will Suzetrigine behave in patients with CKD Stage 5 or in those receiving dialysis? Should the dose be adjusted in post-operative patients who develop AKI?

Research And Clinical Considerations

Given these unanswered questions, more research is needed, before broadly using this medication in vulnerable patients with advanced CKD. Areas that require closer attention include:

• Monitoring serum creatine levels or dipstick-positive hematuria to assess for nephrotoxicity or clinically relevant rhabdomyolysis.
• Tracking long-term kidney function in patients with eGFR > 15 ml/min to determine if there is a subsequent decline in eGFR

Conclusion: A Safer Option For CKD?

Suzetrigine shows promise as a non-opioid alternative for pain relief in patients with diminished kidney function (CKD Stage 1- 4), potentially reducing opioid dependence and avoiding the nephrotoxic effects of NSAIDs. Ongoing research will determine its safety profile in patients with advanced CKD (eGFR < 15 ml/min). We recommend caution in patients with CKD stage 5 or receiving dialysis based on lack of data. 

Written by: Ankita Ojha, MD

Edited by: Arrsh Bajaj, MD

Reviewed by: Matthew Sparks