Fenofibrate (Tricor) belongs to the class of medicines called fibrates. It is used along with a diet that contains low fats and low calories and exercise to treat high triglycerides levels. It is less preferred to statins, however, in patients with very high triglyceride levels and LDL levels, it may be used in conjunction with a statin.

Fenofibrate (Tricor) Uses:

• Hypercholesterolemia or mixed dyslipidemia:

  • It is used as Adjunctive therapy to diet for the reduction of cholesterol. it reduces LDL-cholesterol, total cholesterol, triglycerides, and apolipoprotein B, and increases HDL-cholesterol. It is used when the response to diet and non-pharmacological interventions alone has been inadequate.

FDA-approved fenofibrate for hypercholesterolemia. Other agents may be more suitable. Fenofibrate is not a first- or second-line choice. if there is no hypertriglyceridemia, its use is not recommended to lower LDL-Cholesterol or raise HDL-Cholesterol.

• Hypertriglyceridemia:

  • It is indicated in severe hypertriglyceridemia as adjunctive therapy to diet

• Off Label Use of Fenofibrate in Adults:

  • Primary biliary cholangitis

Note: At least 2 to 3 months of therapy is required to determine efficacy.

Fenofibrate use in patients with COVID-19 infection:

It has been hypothesized that fenofibrate may negatively regulate the fusion proteins that aid the viral entry into human cells. It acts as an agonist of PPAr alfa and increases the levels of sulfatide in the body that is primarily involved in inhibiting the viral entry into human cells. Children and non-hypertensive patients have high levels of sulfatides and that could be the reason for fewer symptoms and low mortality rates in these groups. However, studies are being conducted and the results are still awaited.

Fenofibrate (Tricor) Dose in Adults

Fenofibrate (Tricor) Dose in the treatment of Hypertriglyceridemia: Oral: Initial:

• Antara (micronized):
  • 30 to 90 mg once a day;
  • maximum dose: 90 mg/day
• Fenofibrate (micronized):
  • 43 to 130 mg once a day;
  • maximum dose: 130 mg/day
• Fenoglide:
  • 40 to 120 mg once a day;
  • maximum dose: 120 mg/day
• Fibricor:
  • 35 to 105 mg once a day;
  • maximum dose: 105 mg/day
• Lipidil EZ:
  • 145 mg once a day;
  • maximum dose: 145 mg/day
• Lipidil Supra:
  • 160 mg once a day;
  • maximum dose: 200 mg/day
• Lipofen:
  • 50 to 150 mg once a day;
  • maximum dose: 150 mg/day
• Lofibra (micronized):
  • 67 to 200 mg once a day;
  • maximum dose: 200 mg/day
• Lofibra (tablets):
  • 54 to 160 mg once a day;
  • maximum dose: 160 mg/day
• TriCor:
  • 48 to 145 mg once a day;
  • maximum dose: 145 mg/day
• Triglide:
  • 160 mg once a day
• Trilipix:
  • 45 to 135 mg once a day;
  • maximum dose: 135 mg/day

Fenofibrate (Tricor) Dose in the treatment of Hypercholesterolemia or mixed hyperlipidemia: Oral: Initial:

• Antara (micronized):
  • 90 mg once a day;
  • maximum dose: 90 mg/day
• Fenofibrate (micronized):
  • 130 mg once a day;
  • maximum dose: 130 mg/day
• Fenoglide:
  • 120 mg once a day
• Fibricor:
  • 105 mg once a day
• Lipidil EZ [Canadian product]:
  • 145 mg once a day;
  • maximum dose: 145 mg/day
• Lipidil Supra [Canadian product]:
  • 160 mg once a day;
  • maximum dose: 200 mg/day
• Lipofen:
  • 150 mg once a day
• Lofibra (micronized):
  • 200 mg once a day
• Lofibra (tablets):
  • 160 mg once a day
• TriCor:
  • 145 mg once a day
• Triglide:
  • 160 mg once a day
• Trilipix:
  • 135 mg once a day

Fenofibrate (Tricor) Dose in the treatment of patients with primary biliary cholangitis (off-label): Oral:

Note: It is indicated for patients in which biochemical response is inadequate to ursodiol monotherapy. It is not recommended for patients with decompensated liver disease (Child-Pugh B or C).

• 145 to 160 mg once a day in combination with ursodiol

Use in Children:

Not indicated.

Fenofibrate Pregnancy Risk Category: N (FDA), B3 (AU)

• During pregnancy, lipid and triglyceride levels increase. These are essential for normal fetal development.
• If the increase is greater than anticipated, supervision of dietary intervention should begin.
• Fenofibrate may be used in the second trimester in cases of severe hypertriglyceridemia, particularly in pregnant women who are at high risk of developing pancreatitis.
• Agents other than fibrates should be used to treat hypercholesterolemia

Fenofibrate use during breastfeeding:

• It is unknown whether breast milk contains fenofibrate.
• Breast milk contains lipids as a normal part, and the fatty acids component is necessary for normal infant neurologic development.
• The composition of fatty acids may be affected by factors such as maternal diet and other factors.
• Fenofibrate is known to disrupt lipid metabolism and can cause serious side effects in breastfeeding infants. 
• The manufacturer has declared it to be contraindicated. You should not breastfeed for five days after your last dose.
• If necessary, fenofibrate therapy can be used to treat very severe hypertriglyceridemia among breastfeeding women who are at high risk of developing pancreatitis.
• Agents other than fenofibrate should be used when treatment is required for other indications.

Fenofibrate (Tricor) Dose in Kidney Disease:

Monitor renal function and lipid panel before adjusting.

• Antara (micronized):

  • CrCl >80 mL/minute or eGFR ≥60 mL/minute/1.73 m²:
    • No dosage adjustment is necessary.
  • CrCl >30 to 80 mL/minute or eGFR 30 to 59 mL/minute/1.73 m²:
    • Initiate at 30 mg once a day
  • CrCl ≤30 mL/minute or eGFR <30 mL/minute/1.73 m²:
    • contraindicated.
  • Dialysis:
    • contraindicated.

• Fenofibrate (micronized):

  • CrCl >80 mL/minute or eGFR ≥60 mL/minute/1.73 m²:
    • No dosage adjustment is necessary.
  • CrCl >30 to 80 mL/minute or eGFR 30 to 59 mL/minute/1.73 m²:
    • Initiate at 43 mg once a day
  • CrCl ≤30 mL/minute or eGFR <30 mL/minute/1.73 m²:
    • contraindicated.
  • Dialysis:
    • contraindicated.

• Fenoglide:

  • CrCl >80 mL/minute or eGFR ≥60 mL/minute/1.73 m²:
    • No dosage adjustment is necessary.
  • CrCl >30 to 80 mL/minute or eGFR 30 to 59 mL/minute/1.73 m²:
    • Initiate at 40 mg once a day
  • CrCl ≤30 mL/minute or eGFR <30 mL/minute/1.73 m²:
    • contraindicated.
  • Dialysis:
    • contraindicated.

• Fibricor:

  • eGFR ≥60 mL/minute/1.73 m²:
    • No dosage adjustment is necessary.
  • eGFR 30 to 59 mL/minute/1.73 m²:
    • Initiate at 35 mg once a day
  • eGFR <30 mL/minute/1.73 m²:
    • contraindicated.
  • Dialysis:
    • contraindicated.

• Lipidil EZ [Canadian product]:

Note: If CrCl >50% the upper limit of normal, discontinue therapy

• • CrCl >60 mL/minute:
    • No dosage adjustment is necessary.
  • CrCl 30 to 60 mL/minute:
    • 48 mg once a day
  • CrCl <30 mL/minute:
    • contraindicated.

• Lipidil Supra [Canadian product]:

Note: Discontinue treatment in patients with an increase in CrCl >50% the upper limit of normal.

• • CrCl >60 mL/minute:
    • No dosage adjustment is necessary.
  • CrCl 30 to 60 mL/minute:
    • Initial: 100 mg once a day; titrate cautiously.
  • CrCl <30 mL/minute:
    • contraindicated.

• Lipofen:

  • eGFR ≥90 mL/minute/1.73 m²:
    • No dosage adjustment is necessary.
  • eGFR 30 to 89 mL/minute/1.73 m²:
    • Initiate at 50 mg once a day
  • eGFR <30 mL/minute/1.73 m²:
    • contraindicated.
  • Dialysis:
    • contraindicated.

• Lofibra (micronized):

  • CrCl >80 mL/minute:
    • No dosage adjustment is necessary.
  • CrCl >30 to 80 mL/minute:
    • Initiate at 67 mg once a day
  • CrCl ≤30 mL/minute:
    • contraindicated.
  • Dialysis:
    • contraindicated.

• Lofibra tablets:

  • eGFR ≥60 mL/minute/1.73 m²:
    • No dosage adjustment is necessary.
  • eGFR 30 to 59 mL/minute/1.73 m²:
    • Initiate at 54 mg once a day
  • eGFR <30 mL/minute/1.73 m²:
    • contraindicated.
  • Dialysis:
    • contraindicated.

• TriCor:

  • eGFR ≥60 mL/minute/1.73 m²:
    • No dosage adjustment is necessary.
  • eGFR 30 to 59 mL/minute/1.73 m²:
    • Initiate at 48 mg once a day
  • eGFR <30 mL/minute/1.73 m²:
    • contraindicated.
  • Dialysis:
    • contraindicated.

• Triglide:

  • CrCl >80 mL/minute or eGFR ≥60 mL/minute/1.73 m²:
    • No dosage adjustment is necessary.
  • CrCl >30 to 80 mL/minute or eGFR 30 to 59 mL/minute/1.73 m²:
    • Avoid use.
  • CrCl ≤30 mL/minute or eGFR <30 mL/minute/1.73 m²:
    • contraindicated.
  • Dialysis:
    • contraindicated.

• Trilipix:

  • eGFR ≥60 mL/minute/1.73 m²:
    • No dosage adjustment required.
  • eGFR 30 to 59 mL/minute/1.73 m² :
    • Initiate at 45 mg once a day.
  • eGFR <30 mL/minute/1.73 m²:
    • contraindicated.
  • Dialysis:
    • contraindicated.

Fenofibrate (Tricor) Dose in Liver disease:

It is contraindicated in liver disease. Regular monitoring of liver function tests required: If the level of transaminases above 3 times upper limit of normal and persistently raised  discontinue therapy

Common Side Effects of Fenofibrate (Tricor):

• Hepatic:

  • Increased serum transaminases

Less Common Side Effects of Fenofibrate (Tricor):

• Cardiovascular:

  • Pulmonary Embolism
  • Thrombophlebitis

• Central Nervous System:

  • Dizziness
  • Pain

• Dermatologic:

  • Skin Rash
  • Urticaria

• Gastrointestinal:

  • Abdominal Pain
  • Diarrhea
  • Dyspepsia
  • Constipation

• Hepatic:

  • Abnormal Hepatic Function Tests
  • Increased Serum Alanine Aminotransferase

• Neuromuscular & Skeletal:

  • Arthralgia
  • Limb Pain
  • Myalgia
  • Increased Creatine Phosphokinase In Blood Specimen

• Respiratory:

  • Nasopharyngitis
  • Sinusitis
  • Upper Respiratory Tract Infection
  • Rhinitis

Contraindications to Fenofibrate (Tricor):

• Hypersensitivity to any ingredient of the formulation
• Liver disease active, which includes primary biliary dysfunction and unexplained, deranged functions
• A persistent abnormality in liver function testing
• Dialysis patients with severe renal impairment
• Gallbladder disease that is already present
• Breastfeeding

There is not much evidence of cross-reactivity between fibrates and allergens. This means that cross-sensitivity cannot be excluded.

Canadian labeling:

• Pregnancy;
• Photoallergy known

Lipidil EZ, Lipidil Supra - Additional contraindications are:

• Allergy or intolerance to peanut, Arachis, soya or other related products
• Chronic or acute pancreatitis
• Patients 18 years old
• Patients with myopathy predisposition may co-administer HMG-CoA reductase inhibits.

Warnings and precautions

• Cholelithiasis

  • If the patient has gallstones, discontinue use. Cholelithiasis can be caused by its use.

• HDL cholesterol

  • Reports have shown a paradoxical, but reversible drop in HDL cholesterol (as low at 2 mg/dL). 
  • It is possible that there may be a simultaneous drop in apolipoproteinA1.
  • Within a few months after initiation of therapy, monitoring of HDL cholesterol is recommended. 
  • Stop taking the drug if HDL cholesterol is very low. Do not restart the therapy. use alternate drug

• Hematologic effects

  • Reports of mild-to-moderate hemoglobin (HB) and hematocrit(HCT) drops have been made. 
  • These changes will return to normal after long-term therapy.
  • There have been reports of thrombocytopenia and granulocytosis. 
  • It is important to monitor blood cells count frequently during the first year after therapy has been initiated.

• Hepatic effects

  • Dose-related significant elevations in hepatic transaminases can occur.
  • Hepatic impairment forms of hepatocellular active, chronic active and cholestatic liver disease have been reported after weeks or years of treatment.
  • Regular monitoring and baseline screening of LFTs are required. If transaminases levels rise above the upper limit of normal or persistently, discontinue therapy

• Hypersensitivity reactions

  • Reports of angioedema and anaphylaxis, which are both acute hypersensitivity reactions, were made.
  • Delay hypersensitivity reactions: Stevens Johnson syndrome (SJS), toxic Epidermal Necrolysis (TEN) and drug reaction with Eosinophilia (DRESS), have been reported.
  • These delayed reactions can appear up to weeks after fenofibrate is initiated.
  • If hypersensitivity occurs, stop immediately

• Myopathy/Rhabdomyolysis:

  • Rare myositis, myopathy or rhabdomyolysis can occur. It is recommended that patients be monitored.
  • Risk factors: Elderly, concomitant HMG-CoA reducer inhibitors or colchicine use, Diabetes mellitus or renal insufficiency.
  • Patients should report any unexplained pain, tenderness or weakness, particularly if it is accompanied by malaise or fever; and/or brown urine.
  • If you notice a markedly elevated CPK level or if myopathy/myositis has been diagnosed or suspected, discontinue use.

• Pancreatitis

  • it has been reported fenofibrate may cause pancreatitis; possible mechanism includes due to a failure of efficacy in patients with severe hypertriglyceridemia, medication side effect, or formation of biliary tract stone or sludge from bile duct obstruction.

• Photosensitivity

  • After therapy is initiated, there may be photosensitivity reactions that last from days to months.

• Effects on the renal system:

  • Use of Fenofibrate may increase serum creatinine levels by up to >2 mg/dL. Its clinical significance remains unknown.
  • The return to baseline creatinine levels is possible by stopping fenofibrate.
  • Fenofibrate does not reduce creatinine clearance. Fenofibrate increases creatinine production, which results in an equal rise of creatinuria.
  • Patients with kidney impairment, or at greater risk of developing it (eg elderly patients and diabetics) should be monitored for their renal function.

• Venous thromboembolism

  • It is associated with DVT and PE. Patients at high risk of developing DVT should be cautious

• Cardiovascular disease

  • Major clinical trials have shown that Fibric acid derivatives used as monotherapy or fenofibrate in combination with simvastatin have not reduced mortality and morbidity from cardiovascular disease.

• Hepatic impairment

  • Patients with active liver disease are advised to avoid this medication

• Renal impairment

  • Mild to moderate renal impairment. Dosage adjustment and caution are required. Triglide should not be used
  • Contraindicated for severe renal impairment

Fenofibrate: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Blood counts: periodically, during the first year of initiation of therapy
• Lipid profile: periodically
• LFTs: regularly and discontinue therapy if levels remain >3 times normal limits.
• RFTs: In patients with renal impairment or in those at increased risk of developing renal impairment. Evaluate renal status at baseline, within 3 months after initiation, and every 6 months thereafter.

How to administer Fenofibrate (Tricor)?

Oral:

• Antara, fenofibrate (micronized), Fibricor, Lipidil EZ [Canadian product], Lofibra tablets, TriCor, Triglide, Trilipix:
  • can be taken with or without food.
  • Swallow whole;
  • Do not open the capsules, crush, dissolve, or chew.
• Lofibra (micronized) capsules:
  • Administer with meals.
• Fenoglide, Lipofen, Lipidil Supra [Canadian product]:
  • Administer with meals.
  • Swallow whole;
  • Do not open (capsules), crush, dissolve, or chew.

Mechanism of action of Fenofibrate (Tricor):

Fenofibric acid is an agonist for the nuclear transcription factor peroxisome proliferator-activated receptor-alpha (PPAR-alpha) which causes:

• Apopprotein C-III, an inhibitor of lipoprotein lipase, is downregulated
• Increases the synthesis of Apolipoprotein I-I
• Lipoprotein lipase and Fatty Acid Transport Protein are the results

These actions lead to an increase in VLDL catabolism and fatty acid oxidation as well as the elimination of triglyceride rich particles. The desired effect can be seen in the form of a drop in VLDL levels, a reduction in total plasma cholesterol by 30% to 60%, and a slight increase in HDL in hypertriglycemic patients.

Absorption:

• Increased when taken with meals

Distribution:

• Widely to most tissues

Protein binding:

• ~99%

Metabolism:

• Fenofibrate is metabolized in the tissue and plasma. Its active form is fenofibric acid. Esterases in tissue and plasma convert fenofibrate to its active form Fenofibric acid then undergoes inactivation by glucuronidation hepatically or renally

Bioavailability:

• Fenofibric acid: ~81%

Half-life elimination:

• Fenofibric acid: Mean: 20 hours (range: 10 to 35 hours);
• half-life prolonged in patients with renal impairment

Time to peak:

• 2 to 8 hours

Excretion:

• Urine (~60% as metabolites)
• Feces (25%)
• Hemodialysis has no effect on the removal of fenofibric acid from plasma

International Brand Names of Fenofibrate:

• Antara
• Fenoglide
• Fibricor
• Lipofen
• Lofibra
• Tricor
• Triglide
• Trilipix
• APO-Feno Micro
• APO-Feno-Micro
• APO-Feno-Super
• APO-Fenofibrate
• DOM-Fenofibrate Micro
• Feno-Micro-200
• Fenofibrate Micro
• Fenomax
• Lipidil EZ
• Lipidil Micro
• Lipidil Supra
• MINT-Fenofibrate E
• MYLAN-Fenofibrate Micro
• NOVO-Fenofibrate
• Micronized
• NU-Feno-Micro
• PHL-Fenofibrate Micro
• PMS-Fenofibrate
• PMS-Fenofibrate Micro
• PRO-Feno-Super-100
• PRO-Feno-Super-160
• Q-Fenofibrate Micro
• RATIO-Fenofibrate MC
• RIVA-Fenofibrate Micro
• SANDOZ Fenofibrate E
• SANDOZ Fenofibrate S
• TEVA-Fenofibrate-S
• Apo-Feno
• Apo-Feno-Micro
• Biofibrat
• Catalip
• Cholecaps
• CIL
• Controlip
• Cordialibrel
• Craveril
• Daunlip
• Durafenat
• Eticer
• Evothyl
• Exlip
• Febira
• Febira 200
• Febrate
• Fegenor
• Fenacor
• Fenardin
• Fenatrol
• Fenobrat
• Fenobrate
• Fenobraty
• Fenocap
• Fenocor
• Fenofast
• Fenofix
• Fenoflex
• Fenogal
• Fenoget
• Fenogetz
• Fenolip
• Fenopidil
• Fenosup
• Fenosup Lidose
• Fenoswiss
• Fenox
• Fiba
• Fibra
• Fibrafen
• Fibral
• Fibranor
• Fibrate
• Fibronil
• Fulcro
• Fulcrosupra
• Grofibrat
• Hafenthyl
• Hicholfen
• Hyperchol
• Kemifib
• Lexemin
• Lifen
• Lipanon
• Lipanthyl
• Lipanthyl NT
• Lipanthyl Supra
• Lipantil
• Lipantil Supra
• Lipcor
• Liperial
• Lipicard
• Lipidil
• Lipidil Supra
• Lipidof
• Lipiduce
• Lipifen T.U.
• Lipilfen
• Lipilo
• Lipired
• Lipirex
• Lipivim
• Lipofen
• Lipofib
• Lipsin
• Lipway
• Lofat
• Lofibra
• Lofibrate
• Lolipid
• Lowpirol S
• Minuslip
• Nanofib
• Nofibra
• Nopid
• Normalip
• Normolip
• Notricol
• Nubrex
• Qi Shu
• Qualipantyl
• Redose
• Reducofen
• Sclerofin
• Sclerofin UD
• Secalip
• Secalip Retard
• Secalip Supra
• Stanlip
• Sulnit
• Sulnit CD
• Supralip
• Suprelip
• Tilene
• Tizabate
• Trichek
• Tricor
• Trilipix
• Trolip
• Ziglip
• Zigotrig
• Zinof
• Zumafib

Fenofibrate Brand Names in Pakistan: