What are the contraindications to starting fenofibrate (Fibric acid derivative)?

Contraindications to Starting Fenofibrate

Fenofibrate is contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²), active liver disease, preexisting gallbladder disease, nursing mothers, and known hypersensitivity to fenofibrate or fenofibric acid. 1

Absolute Contraindications

1. Severe Renal Impairment

   • eGFR <30 mL/min/1.73 m² 2, 1
   • Patients receiving dialysis 1

2. Hepatic Disease

   • Active liver disease 1
   • Primary biliary cirrhosis 1
   • Unexplained persistent liver function abnormalities 1

3. Gallbladder Disease

   • Preexisting gallbladder disease 1
   • Fenofibrate increases the biliary lithogenic index, which may exacerbate gallstone formation 3

4. Nursing Mothers

   • Contraindicated during breastfeeding 1

5. Hypersensitivity

   • Known hypersensitivity to fenofibrate or fenofibric acid 1

Relative Contraindications and Cautions

1. Moderate Renal Impairment

   • For patients with eGFR 30-59 mL/min/1.73 m², dose should be reduced to ≤54 mg/day 2
   • Regular monitoring of renal function is required 2

2. Concurrent Statin Use

   • Increased risk of myopathy and rhabdomyolysis when combined with statins 4
   • If combination therapy is necessary, fenofibrate is preferred over gemfibrozil due to lower risk of myopathy 2

3. Advanced Hepatic Fibrosis

   • Traditionally contraindicated in advanced hepatic fibrosis due to limited clinical data 5
   • Recent evidence suggests fenofibrate may be used with caution in patients with mild hepatic impairment or advanced fibrosis due to metabolic-associated fatty liver disease 5

4. Elderly Patients

   • Dose selection should be based on renal function 1
   • Increased risk of adverse effects due to age-related decline in renal function 1

Monitoring Requirements When Starting Fenofibrate

When initiating fenofibrate in eligible patients, the following monitoring is essential:

1. Baseline Assessment

   • Renal function (eGFR, serum creatinine)
   • Liver function tests
   • Complete blood count
   • Creatine phosphokinase (CPK) levels

2. Follow-up Monitoring

   • Lipid profiles at 4-8 week intervals to assess efficacy 1
   • Renal function, particularly in patients with baseline impairment
   • Liver function tests to detect potential hepatotoxicity
   • CPK levels if muscle symptoms develop

Special Considerations

1. Dosing in Renal Impairment

   • Normal or mild-moderate CKD (stages 1-2): 96 mg/day
   • Moderate CKD (stage 3): 48 mg/day
   • Severe CKD (stages 4-5): Avoid use 2

2. Treatment Duration

   • Therapy should be withdrawn in patients who do not have an adequate response after two months of treatment with the maximum recommended dose 1

3. Combination with Statins

   • The concurrent use of statins and fibrates increases the risk of rhabdomyolysis, and this combination should be used with caution, especially in patients with CKD 4

4. Pregnancy

   • Safety during pregnancy has not been established, and potential risks should be carefully considered

By adhering to these contraindications and monitoring guidelines, the risk of adverse events associated with fenofibrate therapy can be minimized while maximizing therapeutic benefits for appropriate patients.