ANTARA (MICRONIZED)
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ANTARA (MICRONIZED) (ANTARA (MICRONIZED)).
Fenofibrate, a fibric acid derivative, activates peroxisome proliferator-activated receptor alpha (PPARα). This leads to increased lipolysis and elimination of triglyceride-rich particles from plasma by inducing lipoprotein lipase activity and reducing production of apolipoprotein C-III.
| Metabolism | Primarily hepatic via glucuronidation and oxidation; CYP450 isoenzymes are not significantly involved. Fenofibrate is excreted as fenofibric acid and glucuronide conjugates, mainly in urine. |
| Excretion | Renal (approximately 70% of a dose is excreted in the urine, primarily as the glucuronide conjugate; less than 10% is excreted as unchanged drug in urine); fecal/biliary elimination accounts for about 20% (mainly as unchanged drug and metabolites via bile). |
| Half-life | Terminal elimination half-life is approximately 15–17 hours (range 13–22 hours) in normolipidemic subjects; in hypertriglyceridemic patients, half-life may be prolonged up to 24–33 hours due to increased volume of distribution. Repeated dosing leads to steady state by about 4–5 days. |
| Protein binding | Approximately 99% bound to plasma proteins, mainly albumin (90–95%), with some binding to lipoproteins. Fenofibric acid has high affinity for albumin; saturation occurs at concentrations >300 µg/mL. |
| Volume of Distribution | Apparent volume of distribution (Vd/F) is 0.9–1.0 L/kg (range 60–70 L for a 70 kg individual), indicating distribution into total body water; extensive tissue binding occurs (especially liver, kidney, and adipose tissue). |
| Bioavailability | Oral bioavailability of the micronized capsule is approximately 80–90% relative to the non-micronized formulation; food increases the rate and extent of absorption (AUC increases by 30–50%). Absorption is enhanced when taken with meals; absolute bioavailability compared to i.v. is not determined, but relative bioavailability is high. |
| Onset of Action | Oral: Reductions in serum triglycerides are observed within 2–5 days; maximal effects on triglycerides and VLDL may require 3–4 weeks of continuous therapy. |
| Duration of Action | Duration of lipid-lowering effect persists for up to 6–8 weeks after discontinuation, with gradual return to baseline. Clinical monitoring should occur after 4–8 weeks of therapy. Immediate effects on triglyceride levels begin within days but the therapeutic duration is continuous with daily dosing. |
Oral: 130 mg once daily with or without food. Capsules should be swallowed whole; do not crush or chew.
| Dosage form | CAPSULE |
| Renal impairment | Severe renal impairment (eGFR <30 mL/min/1.73 m²): Use is not recommended. For patients with eGFR 30-60 mL/min/1.73 m², no dose adjustment is needed, but monitor renal function closely. |
| Liver impairment | Contraindicated in active liver disease or unexplained persistent liver function abnormalities. For Child-Pugh Class A or B: Use with caution; no specific dose adjustment guidelines available; monitor hepatic enzymes. Child-Pugh Class C: Contraindicated. |
| Pediatric use | Safety and efficacy in pediatric patients (<18 years) have not been established; not recommended. |
| Geriatric use | No specific dose adjustments are required based on age alone; however, elderly patients may have reduced renal function; consider renal function monitoring and adjust as per renal guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ANTARA (MICRONIZED) (ANTARA (MICRONIZED)).
| Breastfeeding | Excretion into human milk unknown; M/P ratio not established. Discontinue nursing or drug due to potential for serious adverse reactions in nursing infants. |
| Teratogenic Risk | Fenofibrate is Pregnancy Category C. First trimester: No adequate human studies; animal studies show embryotoxicity at high doses. Second and third trimesters: Potential fetal harm due to lipid metabolism disruption; use only if benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
Severe renal impairment (eGFR <30 mL/min/1.73 m²), active liver disease including primary biliary cirrhosis, preexisting gallbladder disease, breastfeeding, known hypersensitivity to fenofibrate or fenofibric acid.
| Precautions | Should not be used in patients with preexisting gallbladder disease; may increase risk of cholelithiasis. Elevations in serum transaminases have occurred; monitor liver function tests. May increase serum creatinine; monitor renal function. Myopathy/rhabdomyolysis risk increased when used with statins or in patients with renal impairment. Avoid in severe renal impairment (eGFR <30 mL/min/1.73 m²). |
| Food/Dietary | Take with a meal containing some fat to enhance absorption. Avoid high-fat meals if also taking a statin to reduce additive muscle risk. No specific food restrictions but maintain a low-fat diet per lipid management. |
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| Monitor maternal lipid profiles, hepatic function (AST/ALT), renal function (serum creatinine), and gallbladder studies if symptomatic. Fetal monitoring per standard obstetric care. |
| Fertility Effects | Animal studies show reversible impairment of fertility at high doses. Human data insufficient to determine effects on female or male fertility. |
| Clinical Pearls | Fenofibrate (micronized) is preferred over gemfibrozil when used with statins due to lower risk of myopathy. Monitor renal function (Cr) and hepatic enzymes (ALT/AST) at baseline and periodically. Avoid use in severe renal impairment (eGFR <30 mL/min) and active liver disease. May increase serum creatinine due to reduced creatinine secretion; stable elevations up to 0.2 mg/dL are common. Co-administration with bile acid sequestrants (e.g., cholestyramine) should be staggered by at least 2 hours. For patients with gallbladder disease, weigh risks due to increased biliary cholesterol saturation. |
| Patient Advice | Take with food to reduce gastrointestinal upset. · Do not crush or chew capsules; swallow whole. · Avoid alcohol while on this medication. · Report unexplained muscle pain, tenderness, or weakness to your doctor immediately. · You will need periodic blood tests to monitor liver and kidney function. · Inform your doctor if you have a history of gallstones, kidney disease, or liver disease. |