What is the relationship between Norco (Hydrocodone and Acetaminophen) and Acute Kidney Injury (AKI)?

From the Guidelines

Norco 5 (hydrocodone/acetaminophen) should be used with caution in patients with acute kidney injury (AKI), and alternative pain medications with less nephrotoxicity should be considered. For patients with AKI, I recommend reducing the dose or frequency of Norco 5. The hydrocodone component of Norco is metabolized primarily by the liver and is generally safe in kidney injury, but the acetaminophen component (325mg per tablet) can potentially worsen kidney function in patients with AKI, as drugs can affect the kidney by multiple mechanisms, including systemic or renal/glomerular hemodynamic effects and tubular or structural damage 1. If Norco must be used, limit the total daily acetaminophen dose to less than 3000mg and monitor kidney function closely, as the use of drugs associated with kidney injury or dysfunction is common both in the hospital setting and in the community for patients with chronic illnesses 1. Consider extending the dosing interval to every 6-8 hours instead of every 4-6 hours in moderate to severe AKI. Hydration status should be optimized while using this medication, as recommended by the KDIGO clinical practice guideline for acute kidney injury, which suggests using isotonic crystalloids rather than colloids for expansion of intravascular volume in patients at risk for AKI or with AKI 1. The concern with acetaminophen in AKI relates to its metabolites which can cause additional oxidative stress to already compromised kidneys. In cases of severe AKI, pure opioid formulations without acetaminophen may be safer alternatives for pain management until kidney function improves. It is essential to consider the mechanisms of drug-induced kidney injury or dysfunction and to classify drugs that affect kidney function or are nephrotoxic in a clinically useful way, as suggested by the KDIGO conference 1. Additionally, the KDIGO guideline recommends not using diuretics to prevent AKI and suggests not using diuretics to treat AKI, except in the management of volume overload 1. Overall, the management of AKI requires careful consideration of the potential nephrotoxic effects of medications and the implementation of strategies to prevent or mitigate kidney injury.

From the FDA Drug Label

Hydrocodone and acetaminophen are known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Patients with renal impairment may have higher plasma hydrocodone concentrations than those with normal function Use a low initial dose Hydrocodone Bitartrate and Acetaminophen Tablets in patients with renal impairment and follow closely for adverse events such as respiratory depression and sedation.

The use of Norco 5 (hydrocodone and acetaminophen) may be associated with a higher risk of adverse reactions in patients with impaired renal function, including those with Acute Kidney Injury (AKI).

• Key considerations for patients with AKI include:
  • Dose selection: Use a low initial dose of Hydrocodone Bitartrate and Acetaminophen Tablets.
  • Monitoring: Follow closely for adverse events such as respiratory depression and sedation.
  • Renal function monitoring: It may be useful to monitor renal function in patients with AKI. 2

From the Research

Norco 5 and AKI

• Norco 5, a combination of acetaminophen and hydrocodone, can be a potential risk factor for acute kidney injury (AKI) due to its acetaminophen component 3, 4.
• Acetaminophen overdose is known to cause severe liver and kidney failure, but therapeutic doses can also lead to AKI in healthy individuals, especially when combined with other nephrotoxic agents or in cases of volume depletion 3, 4.
• The management of AKI involves prompt workup of the underlying cause, optimization of volume status, and avoidance of nephrotoxic medications, including acetaminophen 5, 6.
• Fluid management is crucial in AKI, with crystalloids preferred over colloids, and attention should be paid to overall fluid balance to avoid volume overload 5, 6.
• There are no targeted pharmacotherapies approved for the treatment of AKI, and the optimal timing of renal replacement therapy in critically ill patients with AKI is unclear 5.

Risk Factors for AKI

• Infections and hypovolaemic shock are the predominant causes of AKI in low-income and middle-income countries, while in high-income countries, AKI mostly occurs in elderly patients who are in hospital, and is related to sepsis, drugs, or invasive procedures 7.
• The use of nephrotoxic medications, such as acetaminophen, can increase the risk of AKI, especially in patients with pre-existing kidney disease or volume depletion 3, 4.
• Awareness campaigns and education for health-care professionals on diagnosis and management of AKI can improve outcomes, and electronic early warning systems can help with early detection 6.

Prevention and Early Detection

• Prevention and early detection of AKI are essential, as AKI can have long-term consequences, including chronic kidney disease and cardiovascular morbidity 7, 6.
• Biomarker-based strategies have not shown improvements in outcome, and fluid management should aim for early, rapid restoration of circulatory volume, but should be more limited after the first 24-48 h to avoid volume overload 6.