Proctofene - General Information
An antilipemic agent which reduces both cholesterol and triglycerides in the blood. [PubChem]
Pharmacology of Proctofene
Proctofene is a lipid regulating agent indicated as adjunctive therapy to diet to reduce elevated LDL-C, Total-C,Triglycerides and Apo B, and to increase HDL-C in adult patients with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson Types IIa and IIb). Proctofene is also indicated as adjunctive therapy to diet for treatment of adult patients with hypertriglyceridemia (Fredrickson Types IV and V hyperlipidemia). Fenofibric acid, the active metabolite of Proctofene, produces reductions in total cholesterol, LDL cholesterol, apolipoprotein B, total triglycerides and triglyceride rich lipoprotein (VLDL) in treated patients. In addition, treatment with fenofibrate results in increases in high density lipoprotein (HDL) and apoproteins apoAI and apoAII.
Proctofene for patients
CAUTION SHOULD BE EXERCISED WHEN COUMARIN ANTICOAGULANTS ARE GIVEN IN CONJUNCTION WITH TRICOR. THE DOSAGE OF THE ANTICOAGULANTS SHOULD BE REDUCED TO MAINTAIN THE PROTHROMBIN TIME/INR AT THE DESIRED LEVEL TO PREVENT BLEEDING COMPLICATIONS. FREQUENT PROTHROMBIN TIME/INR DETERMINATIONS ARE ADVISABLE UNTIL IT HAS BEEN DEFINITELY DETERMINED THAT THE PROTHROMBIN TIME/INR HAS STABILIZED.
HMG-CoA reductase inhibitors
The combined use of TRICOR and HMG-CoA reductase inhibitors should be avoided unless the benefit of further alterations in lipid levels is likely to outweigh the increased risk of this drug combination.
Since bile acid sequestrants may bind other drugs given concurrently, patients should take TRICOR at least 1 hour before or 4-6 hours after a bile acid binding resin to avoid impeding its absorption.
Because cyclosporine can produce nephrotoxicity with decreases in creatinine clearance and rises in serum creatinine, and because renal excretion is the primary elimination route of fibrate drugs including TRICOR, there is a risk that an interaction will lead to deterioration. The benefits and risks of using TRICOR with immunosuppressants and other potentially nephrotoxic agents should be carefully considered, and the lowest effective dose employed.
In vitro studies using human liver microsomes indicate that fenofibrate and fenofibric acid are not inhibitors of cytochrome (CYP) P450 isoforms CYP3A4, CYP2D6, CYP2E1, or CYP1A2. They are weak inhibitors of CYP2C19 and CYP2A6, and mild-to-moderate inhibitors of CYP2C9 at therapeutic concentrations.
Potentiation of coumarin-type anticoagulants has been observed with prolongation of the prothrombin time/INR.
Bile acid sequestrants have been shown to bind other drugs given concurrently. Therefore, fenofibrate should be taken at least 1 hour before or 4-6 hours after a bile acid binding resin to avoid impeding its absorption.
Concomitant administration of fenofibrate (equivalent to 145mg TRICOR) with pravastatin (40 mg) once daily for 10 days has been shown to increase the mean Cmax and AUC values for pravastatin by 36% (range from 69% decrease to 321% increase) and 28% (range from 54% decrease to 128% increase), respectively, and for 3α-hydroxy-iso-pravastatin by 55% (range from 32% decrease to 314% increase) and 39% (range from 24% decrease to 261% increase), respectively in 23 healthy adults.
A single dose of pravastatin had no clinically important effect on the pharmacokinetics of fenofibric acid.
Concomitant administration of fenofibrate (equivalent to 145 mg TRICOR) with atorvastatin (20 mg) once daily for 10 days resulted in approximately 17% decrease (range from 67% decrease to 44% increase) in atorvastatin AUC values in 22 healthy males. The atorvastatin Cmax values were not significantly affected by fenofibrate. The pharmacokinetics of fenofibric acid were not significantly affected by atorvastatin.
TRICOR is contraindicated in patients who exhibit hypersensitivity to fenofibrate.
TRICOR is contraindicated in patients with hepatic or severe renal dysfunction, including primary biliary cirrhosis, and patients with unexplained persistent liver function abnormality.
TRICOR is contraindicated in patients with preexisting gallbladder disease.
Additional information about Proctofene
Proctofene Indication: For use as adjunctive therapy to diet to reduce elevated LDL-C, Total-C,Triglycerides and Apo B, and to increase HDL-C in adult patients with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson Types IIa and IIb)
Mechanism Of Action: Proctofene exerts its therapeutic effects through activation of peroxisome proliferator activated receptor a (PPARa). This increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein C-III. The resulting fall in triglycerides produces an alteration in the size and composition of LDL from small, dense particles, to large buoyant particles. These larger particles have a greater affinity for cholesterol receptors and are catabolized rapidly.
Drug Interactions: Anisindione The fibrate increases the anticoagulant effect
Dicumarol The fibrate increases the anticoagulant effect
Acenocoumarol The fibrate increases the anticoagulant effect
Warfarin The fibrate increases the anticoagulant effect
Atorvastatin Increased risk of myopathy/rhabdomyolysis
Cerivastatin Increased risk of myopathy/rhabdomyolysis
Fluvastatin Increased risk of myopathy/rhabdomyolysis
Lovastatin Increased risk of myopathy/rhabdomyolysis
Pravastatin Increased risk of myopathy/rhabdomyolysis
Simvastatin Increased risk of myopathy/rhabdomyolysis
Rosuvastatin Rosuvastatin possibly increases the effect of the fibrate
Ursodeoxycholic acid The fibric acid derivative decreases the effect of ursodiol
Food Interactions: Increased absorption- take with meals.
Generic Name: Fenofibrate
Synonyms: Fenofibrato [Inn-Spanish]; Fenofibratum [Inn-Latin]; FNF; Finofibrate
Drug Category: Antilipemic Agents; Fribic Acid Derivatives
Drug Type: Small Molecule; Approved
Absorption: Fenofibrate is well absorbed from the gastrointestinal tract. After absorption, fenofibrate is mainly excreted in the urine in the form of metabolites, primarily fenofibric acid and fenofibric acid glucuronide
Toxicity (Overdose): LD50=1600 mg/kg (Oral, in mice); Investigated as a teratogen and reproductive hazard.
Protein Binding: ~99% (Serum protein binding)
Biotransformation: Not Available
Half Life: 20 hours
Dosage Forms of Proctofene: Tablet Oral
Chemical IUPAC Name: propan-2-yl 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoate
Chemical Formula: C20H21ClO4
Fenofibrate on Wikipedia: https://en.wikipedia.org/wiki/Fenofibrate
Organisms Affected: Humans and other mammals