Can ramelteon (rozerem) cause acute renal failure (Impaired renal function)?

Ramelteon and Acute Renal Failure

Ramelteon (Rozerem) does not cause acute renal failure and can be safely used in patients with renal impairment without dose adjustment.

Pharmacokinetics and Renal Safety

Ramelteon is primarily metabolized by the liver through CYP1A2, with minor involvement of CYP2C and CYP3A4 enzymes 1. The drug's elimination pathway is predominantly hepatic with minimal renal clearance:

• Less than 0.1% of ramelteon is excreted unchanged in urine 1
• Ramelteon is principally eliminated via hepatic metabolism 1
• No adjustment of ramelteon dosage is required in patients with renal impairment, including those with severe renal impairment (creatinine clearance ≤30 mL/min/1.73 m²) 1
• Patients requiring chronic hemodialysis can take ramelteon without dose adjustment 1

Evidence from Clinical Studies

The FDA drug label for ramelteon specifically addresses renal impairment:

• "The pharmacokinetic characteristics of ramelteon were studied after administering a 16 mg dose to subjects with mild, moderate, or severe renal impairment... No effects on Cmax or AUC of parent drug or M-II were seen in any of the treatment groups" 1

• "No adjustment of ramelteon dosage is required in patients with renal impairment, including patients with severe renal impairment and patients who require chronic hemodialysis" 1

In a comprehensive 1-year safety study of ramelteon in adults and older adults with chronic insomnia, there were "no noteworthy changes in vital signs, physical examinations, clinical chemistry, hematology, or urinalysis values" 2. This long-term study did not identify any renal safety concerns with ramelteon use.

Contrast with Known Nephrotoxic Agents

Unlike some medications that are known to cause acute renal failure, ramelteon has not been associated with:

• Direct nephrotoxicity
• Prerenal injury through volume depletion
• Interstitial nephritis
• Tubular damage

For comparison, certain medications are well-documented to cause acute kidney injury:

• Aliskiren can cause acute renal failure in patients with severe bilateral renal artery stenosis 3
• NSAIDs can cause significant reduction in GFR, RPF, and sodium clearance in patients with various conditions 4

Clinical Implications

When considering medications for patients with renal impairment:

1. Ramelteon is a safe option for treating insomnia in patients with any degree of renal impairment
2. No renal function monitoring is specifically required when using ramelteon
3. No dose adjustment is needed for patients with renal dysfunction, including those on hemodialysis

Recent Research

Interestingly, recent research suggests ramelteon may actually have renoprotective effects. A 2023 study found that ramelteon attenuated renal ischemia-reperfusion injury in an experimental model by:

• Reducing mitochondrial damage
• Decreasing inflammatory markers (IL-6, TNF-α, IL-1β)
• Inhibiting cell apoptosis 5

While this protective effect requires further clinical validation, it suggests ramelteon may potentially benefit rather than harm renal function in certain contexts.

Conclusion

Based on the FDA drug label and available clinical evidence, ramelteon does not cause acute renal failure and can be safely used in patients with renal impairment without dose adjustment.