Clofar - General Information:A fibric acid derivative used in the treatment of hyperlipoproteinemia type III and severe hypertriglyceridemia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p986)
Pharmacology:Clofar is an antilipidemic agent similar to gemfibrozil. It acts to lower elevated serum lipids by reducing the very low-density lipoprotein fraction (Sf 20-400) rich in triglycerides. Serum cholesterol may be decreased, particularly in those patients whose cholesterol elevation is due to the presence of IDL as a result of Type III hyperlipoproteinemia. Several investigators have observed in their studies that clofibrate may produce a decrease in cholesterol linoleate but an increase in palmitoleate and oleate, the latter being considered atherogenic in experimental animals. The significance of this finding is unknown at this time. Reduction of triglycerides in some patients treated with clofibrate or certain of its chemically and clinically similar analogs may be associated with an increase in LDL cholesterol. Increase in LDL cholesterol has been observed in patients whose cholesterol is initially normal. Animal studies suggest that clofibrate interrupts cholesterol biosynthesis prior to mevalonate formation.
Clofar for patients
Caution should be exercised when anticoagulants are given in conjunction with Atromid-S. Usually, the dosage of the anticoagulant should be reduced by one-half (depending on the individual case) to maintain the prothrombin time at the desired level to prevent bleeding complications. Frequent prothrombin determinations are advisable until it has been determined definitely that the prothrombin level has been stabilized.
Atromid-S may displace acidic drugs such as phenytoin or tolbutamide from their binding sites. Caution should be exercised when treating patients with either of these drugs or other highly protein-bound drugs and Atromid-S. The hypoglycemic effect of tolbutamide has been reported to increase when Atromid-S is given concurrently.
Fulminant rhabdomyolysis has been seen as early as three weeks after initiation of combined therapy with another fibrate and lovastatin but may be seen after several months. For these reasons, it is felt that, in most subjects who have had an unsatisfactory lipid response to either drug alone, the possible benefits of combined therapy with lovastatin and a fibrate do not outweigh the risks of severe myopathy, rhabdomyolysis, and acute renal failure. While it is not known whether this interaction occurs with fibrates other than gemfibrozil, myopathy and rhabdomyolysis have occasionally been associated with the use of fibrates alone, including clofibrate. Therefore, the combined use of lovastatin with fibrates should generally be avoided.
Clofibrate is contraindicated in pregnant women. While teratogenic studies have not demonstrated any effect attributable to clofibrate, it is known that serum of the rabbit fetus accumulates a higher concentration of clofibrate than that found in maternal serum, and it is possible that the fetus may not have developed the enzyme system required for the excretion of clofibrate.
It is contraindicated in patients with clinically significant hepatic or renal dysfunction. Rhabdomyolysis and severe hyperkalemia have been reported in association with pre-existing renal insufficiency.
It is contraindicated in patients with primary biliary cirrhosis, since it may raise the already elevated cholesterol in these cases.
It is contraindicated in patients with a known hypersensitivity to clofibrate.
It is contraindicated in nursing women.
Additional information about ClofarClofar Indication: For Primary Dysbetalipoproteinemia (Type III hyperlipidemia) that does not respond adequately to diet.
Mechanism Of Action: Clofar increases the activity of extrahepatic lipoprotein lipase (LL), thereby increasing lipoprotein triglyceride lipolysis. Chylomicrons are degraded, VLDLs are converted to LDLs, and LDLs are converted to HDL. This is accompanied by a slight increase in secretion of lipids into the bile and ultimately the intestine. Clofar also inhibits the synthesis and increases the clearance of apolipoprotein B, a carrier molecule for VLDL.
Drug Interactions: Acetohexamide The agent increases the effect of sulfonylurea
Anisindione The fibrate increases the anticoagulant effect
Chlorpropamide The agent increases the effect of sulfonylurea
Dicumarol The fibrate increases the anticoagulant effect
Gliclazide The agent increases the effect of sulfonylurea
Glipizide The agent increases the effect of sulfonylurea
Glisoxepide The agent increases the effect of sulfonylurea
Glycodiazine The agent increases the effect of sulfonylurea
Tolazamide The agent increases the effect of sulfonylurea
Tolbutamide The agent increases the effect of sulfonylurea
Insulin Increases the effect of insulin
Insulin-aspart Increases the effect of insulin
Insulin-detemir Increases the effect of insulin
Insulin-glargine Increases the effect of insulin
Insulin-glulisine Increases the effect of insulin
Insulin-lispro Increases the effect of insulin
Acenocoumarol The fibrate increases the anticoagulant effect
Warfarin The fibrate increases the anticoagulant effect
Ursodeoxycholic acid The fibric acid derivative decreases the effect of ursodiol
Glibenclamide The agent increases the effect of sulfonylurea
Food Interactions: Take with food, since it may reduce gastric irritation.
Generic Name: Clofibrate
Synonyms: Chlorfenisate; Chlorphenisate; Clofibate; Clofibrato; Clofibratum; Ethyl chlorophenoxyisobutyrate; Ethyl clofibrate; EPIB; Ethyl p-chlorophenoxyisobutyrate; Ethyl para-chlorophenoxyisobutyrate; CPIB
Drug Category: Anticholesteremic Agents; Antilipemic Agents
Drug Type: Small Molecule; Approved
Other Brand Names containing Clofibrate: Amotril; Amotril S; Angiokapsul; Anparton; Antilipid; Antilipide; Apolan; Arterioflexin; Arterosol; Artes; Artevil; Ateculon; Ateriosan; Athebrate; Atheromide; Atheropront; Athranid-Wirkstoff; Atrolen; Atromid; Atromid S; Atromid-S; Atromida; Atromidin; Atrovis; Azionyl; Bioscleran; Bresit; Cartagyl; Citiflus; Claripex; Claripex CPIB; Cloberat; Clobrat; Clobren-5F; Clobren-SF; Clofar; Clofibram; Clofibrat; Clofinit; Clofipront; Delipid; Deliva; Dura clofibrat; ELPI; Fibralem; Gerastop; Hyclorate; Klofibrat; Klofiran; Levatrom; Lipamid; Lipavil; Lipavlon; Lipide 500; Lipidsenker; Lipofacton; Lipomid; Liponorm; Liporeduct; Liporil; Liposid; Liprin; Liprinal; Lobetrin; Miscleron; Negalip; Neo-Atromid; Normalip; Normat; Normolipol; Novofibrate; Oxan 600; Persantinat; Regardin; Regelan; Regelan N; Robigram; Scrobin; Serofinex; Serotinex; Skerolip; Sklerepmexe; Sklero; Sklero-Tablinen; Sklero-tablinene; Sklero-tabuls; Sklerolip; Skleromex; Skleromexe; Tetrasipton; Thillate; Thiosan; Ticlobran; Vincamin compositum; Xyduril; Yoclo; neo-Atomid;
Absorption: Completely but slowly absorbed from the intestine. Between 95% and 99% of an oral dose of clofibrate is excreted in the urine as free and conjugated clofibric acid; thus, the absorption of clofibrate is virtually complete.
Toxicity (Overdose): Oral, mouse: LD50 = 1220 mg/kg; Oral, rabbit: LD50 = 1370 mg/kg; Oral, rat: LD50 = 940 mg/kg. No reported case of overdosage in humans.
Protein Binding: Highly protein-bound (95% to 97%).
Biotransformation: Hepatic and gastrointestinal: rapid de-esterification occurs in the gastrointestinal tract and/or on first-pass metabolism to produce the active form, clofibric acid (chlorophenoxy isobutyric acid [CPIB]).
Half Life: Half-life in normal volunteers averages 18 to 22 hours (range 14 to 35 hours) but can vary by up to 7 hours in the same subject at different times.
Dosage Forms of Clofar: Capsule Oral
Chemical IUPAC Name: ethyl 2-(4-chlorophenoxy)-2-methylpropanoate
Chemical Formula: C12H15ClO3
Clofibrate on Wikipedia: http://en.wikipedia.org/wiki/Clofibrate
Organisms Affected: Humans and other mammals
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