What is the appropriate renal dosing of Norco (hydrocodone 5 mg/acetaminophen 325 mg) for an 88‑year‑old woman, 5 ft 5 in, 167 lb, with serum creatinine 0.88 mg/dL (creatinine clearance ≈50‑55 mL/min)?

Renal Dosing for Norco 5/325 in Moderate Renal Impairment

For this 88-year-old woman with a calculated creatinine clearance of approximately 50–55 mL/min (Stage 3A CKD), start with Norco 5/325 at a reduced frequency—one tablet every 6–8 hours as needed instead of every 4–6 hours—and monitor closely for sedation and respiratory depression, because both hydrocodone and acetaminophen are renally excreted and accumulate in renal impairment. 1

Step 1: Calculate Creatinine Clearance Using Cockcroft-Gault

• Apply the Cockcroft-Gault formula for medication dosing: CrCl (mL/min) = [(140 − age) × weight kg] / [72 × serum creatinine mg/dL] × 0.85 for females. 2, 3
• For this patient: [(140 − 88) × 75.9 kg] / [72 × 0.88 mg/dL] × 0.85 ≈ 53 mL/min. 2
• This value classifies her as Stage 3A chronic kidney disease (CrCl 45–59 mL/min), requiring dose adjustment for all renally cleared medications. 2

Step 2: Recognize the Limitations of "Normal" Serum Creatinine in the Elderly

• A serum creatinine of 0.88 mg/dL appears normal but represents significant renal impairment in an 88-year-old due to age-related muscle mass loss. 2
• Serum creatinine alone markedly underestimates renal insufficiency in elderly patients; the same creatinine value can correspond to CrCl ~110 mL/min in a young adult but only ~40 mL/min in an older adult. 2
• The Cockcroft-Gault formula systematically underestimates true GFR in the oldest patients, yet at CrCl ~53 mL/min it may overestimate true GFR because tubular secretion of creatinine increases as kidney function declines. 2

Step 3: Apply FDA Label Guidance for Hydrocodone/Acetaminophen in Renal Impairment

• The FDA label explicitly states: "Patients with renal impairment may have higher plasma hydrocodone concentrations than those with normal function. Use a low initial dose of Hydrocodone Bitartrate and Acetaminophen Tablets in patients with renal impairment and follow closely for adverse events such as respiratory depression and sedation." 1
• Both hydrocodone and acetaminophen are substantially excreted by the kidney, and the risk of adverse reactions is greater in patients with impaired renal function. 1
• Elderly patients (≥65 years) have increased sensitivity to hydrocodone, and respiratory depression is the chief risk when opioids are initiated at high doses or combined with other CNS depressants. 1

Step 4: Implement Conservative Dosing Strategy

• Start at the low end of the dosing range: one tablet (hydrocodone 5 mg/acetaminophen 325 mg) every 6–8 hours as needed rather than the standard every 4–6 hours. 1
• Titrate slowly based on pain control and tolerance, monitoring for signs of CNS depression (sedation, confusion) and respiratory depression. 1
• Avoid exceeding 4 grams of acetaminophen per day from all sources to minimize hepatotoxicity risk, which is compounded by renal impairment. 1

Step 5: Monitor Renal Function and Drug Response

• Follow serum creatinine levels during the first week of therapy, as acetaminophen overdose can cause acute tubular necrosis even at therapeutic doses in vulnerable patients. 4
• Creatinine may exacerbate acetaminophen-induced liver injury by increasing oxidative stress through ROS/JNK signaling, particularly when creatinine levels are elevated. 5
• Reassess renal function if clinical status changes (dehydration, infection, addition of nephrotoxic drugs), because measured CrCl can vary significantly from Cockcroft-Gault estimates in hospitalized elderly patients. 6

Step 6: Recognize Common Pitfalls

• Do not rely on serum creatinine alone; always calculate CrCl before dosing renally cleared medications in elderly patients. 2, 3
• Avoid co-administration with other CNS depressants (benzodiazepines, sedatives, alcohol) or nephrotoxic agents (NSAIDs, ACE inhibitors) that can worsen renal function or increase opioid toxicity. 2, 1
• Recognize that "normal" creatinine is misleading in the elderly; this patient's CrCl of ~53 mL/min mandates dose reduction despite a creatinine of 0.88 mg/dL. 2
• Measured CrCl may be needed if clinical response is inconsistent with calculated values, as Cockcroft-Gault estimates show large limits of agreement (−75.5 to 57.7 mL/min) in hospitalized elderly patients. 6

Step 7: Alternative Considerations

• If pain control is inadequate with reduced-frequency Norco, consider non-opioid analgesics (acetaminophen alone at renal-adjusted doses, topical agents) or consult pain management for multimodal strategies. 1
• For patients requiring chronic opioid therapy with CrCl <60 mL/min, therapeutic drug monitoring and direct GFR measurement may improve dosing precision and safety. 2, 3