Side Effects of Antara (fenofibrate)

Antara (fenofibrate) is a derivative of fibric acid used with dietary modifications to treat lipid disorders. It helps reduce levels of LDL-C, total cholesterol, triglycerides, and apolipoprotein B, and increase HDL-C. Antara is prescribed to patients with primary hypercholesterolemia or mixed dyslipidemia, and hypertriglyceridemia.

Common side effects of Antara include

• abnormal liver tests including
  • AST and ALT, and
  • headache.

Less common side effects of Antara include

• high blood pressure (hypertension),
• dizziness,
• itching,
• nausea,
• upset stomach,
• constipation,
• diarrhea,
• urinary tract infections (UTIs),
• influenza,
• muscle pain,
• kidney problems, and
• respiratory tract infections.

Drug interactions of Antara include bile acid sequestrants which may decrease the absorption of Antara and reduce their effectiveness.

• Antara may increase the adverse effects of colchicine on muscle tissue.
• Cyclosporine may increase the toxic effects of Antara on the kidney while Antara may decrease blood levels of cyclosporine.
• Antara may increase the adverse effects associated with ezetimibe, HMG-CoA reductase inhibitors (statins), and sulfonylureas.
• Antara may increase the anticoagulation (blood-thinning) benefits of warfarin.

Use of Antara in pregnant females has not been adequately evaluated. Antara should be avoided during pregnancy unless the benefits justify the potential risk to the fetus.

Antara should not be used in breastfeeding mothers; however, it is unknown whether Antara is excreted into breast milk.

Common adverse effects of fenofibrate are abnormal liver tests including AST and ALT, and headache.

Less common side effects are:

• high blood pressure,
• dizziness,
• itching,
• nausea,
• upset stomach (dyspepsia),
• constipation,
• diarrhea,
• urinary tract infections,
• flu (influenza),
• muscle pain,
• kidney problems, and
• respiratory tract infections.

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect rates observed in clinical practice.

• Adverse events reported by 2% or more of patients treated with fenofibrate and greater than placebo during double-blind, placebo-controlled trials, regardless of causality, are listed in Table 1.
• Adverse reactions led to discontinuation of treatment in 5.0% of patients treated with fenofibrate and in 3.0% treated with placebo.
• Increases in liver function tests were the most frequent events, causing discontinuation of fenofibrate treatment in 1.6% of patients in double-blind trials.

Table 1 : Adverse Reactions Reported by 2% or More of Patients Treated with Fenofibrate and Greater than Placebo During the Double-Blind, Placebo-Controlled Trials

Urticaria was seen in 1.1 vs. 0%, and rash in 1.4 vs. 0.8% of fenofibrate and placebo patients, respectively, in controlled trials.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of fenofibrate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

• myalgia,
• rhabdomyolysis,
• pancreatitis,
• renal failure,
• muscle spasms,
• acute renal failure,
• hepatitis,
• cirrhosis,
•  anemia,
•  arthralgia,
•  asthenia, and
•  severely depressed HDL-cholesterol levels.

Photosensitivity reactions have occurred days to months after initiation; in some of these cases, patients reported a prior photosensitivity reaction to ketoprofen.

Coumarin Anticoagulants

• Potentiation of coumarin-type anticoagulant effects has been observed with prolongation of the PT/INR.
• Caution should be exercised when coumarin anticoagulants are given in conjunction with Antara.
• The dosage of the anticoagulants should be reduced to maintain the PT/INR at the desired level to prevent bleeding complications.
• Frequent PT/INR determinations are advisable until it has been definitely determined that the PT/INR has stabilized.

Immunosuppressants

• Immunosuppressants such as cyclosporine and tacrolimus can produce nephrotoxicity with decrease in creatinine clearance and because renal excretion is the primary elimination route of fibrate drugs including Antara, there is a risk that an interaction will lead to deterioration of renal function.
• The benefits and risks of using Antara with immunosuppressants and other potentially nephrotoxic agents should be carefully considered, and the lowest effective dose employed.

Bile-Acid Binding Resins

• Since bile acid binding resins may bind other drugs given concurrently, patients should take Antara at least 1 hour before or 4 to 6 hours after a bile acid binding resin to avoid impeding its absorption.

Colchicine

• Cases of myopathy, including rhabdomyolysis, have been reported with fenofibrates co-administered with colchicine, and caution should be exercised when prescribing fenofibrate with colchicine.