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Rx
FENORATE
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COMPOSITION:
Each tablet contains
Fenofibrate
160 mg ( non-micronized).
DESCRIPTION:
Fenofibrate
is chemically designated as (propan-2-yl 2-{4-[(4-chlorophenyl) carbonyl]phenoxy}-2-methylpropanoate).
Its molecular formula is C20H21ClO4, and its molecular mass is 360.831.
Fenofibrate
is a drug of the fibrate class, ie a fibric acid derivative, used as an oral
antilipemic agent. Fenofibrate is a prodrug that is hydrolyzed to
fenofibric acid.
It is mainly used to reduce cholesterol
levels in patients at risk of cardiovascular diseases. Fenofibrate is most
effective in treating lipid disorders associated with very high elevations of
serum triglycerides and both LDL (Low Density Lipoproteins) & VLDL (Very
Low Density Lipoproteins), as well as increasing HDL (High Density
Lipoproteins).
It also appears to have a beneficial
effect on the insulin resistance featured by the metabolic
syndrome.
It works by
increasing the production of an enzyme (lipoprotein lipase) that breaks down triglyceride-rich
particles (VLDL) and increases their removal from the body. The medication
can also decrease the amount of these particles that are made and released from
the liver.
In clinical research studies, people taking fenofibrate daily were able
to:
· Reduce triglyceride levels by 20 to 55 percent
· Reduce LDL cholesterol by 20 to 35 percent
· Reduce total cholesterol by 20 to 30 percent
· Raise HDL cholesterol by 10
to 20 percent.
PHARMACODYNAMICS:
Fenofibrate
induces lipid modification activity by mediation of PPAR alpha (Peroxisome
Proliferator Activated Receptor). Through activation of PPAR, fenofibrate
increases the lipolysis and elimination of atherogenic triglyceride rich
particle from plasma by activating lipoprotein lipase and reducing production
of apoproteins.
PPAR
controls transcription of genes that regulate fatty acid and cholesterol
metabolism, thus hepatic synthesis of triglyceride is reduced by increased
hepatic fatty acid oxidation. It also reduces postprandial lipema and serum
fibrinogen levels. It also increases urinary excretion of serum uric acid, thus
preventing cardiac risk in patients with hyperlipoproteinemia.
PHARMACOKINETICS:
Absorption:
Maximum
plasma concentration occurs within 4 to 5 hours after oral administration. The
absorption of fenofibrate is increased when administered with food. Half Life
(t1/2): 19-27 hrs.
Distribution:
Fenofibrate
is highly bound to plasma protein (more than 99%), mostly distributed to liver,
kidney and GI tract.
Metabolism:
It is
not metabolized by cytochrome P450 enzyme, but is primarily conjugated with
Glucuronic acid. Absorbed fenofibrate is completely hydrolysed to active form
fenofibric acid.
Elimination:
Mainly renal (60-88% in urine as the active metabolite and
glucuronidated forms, 5-25% in feces as unchanged fenofibrate).
The elimination half-life of
fenofibrate is 20 hours in patients with normal renal function.
INDICATION:
It is
mainly indicated for hypercholesterolemia,
hypertriglyceridaemia and mixed dyslipidemia.
CONTRAINDICATION:
Fenorate
is contraindicated in patients who are hypersensitive to any of the component
in this product, in severe hepatic and renal impairment, gall bladder diseases,
during pregnancy & lactation.
WARNING & PRECAUTION:
Proper
liver function test is to be done before initiation of the treatment with
Fenofibrate. Special care is to be taken if the patient is alcoholic or have
thyroid problems. Fenofibrate is not recommended for pregnant women and
lactating mother as its extracts is seen in milk that can harm the fetus.
Special
precaution is to be taken when taking this drug with other medications.
ADVERSE EFFECTS:
Cardiovascular: pulmonary embolism, deep vein thrombosis
Dermatologic: rashes, Steven-Jhonson syndrome (rare), toxic epidermal
necrolysis, photosensitive reaction.
Gastrointestinal: constipation, diarrhea, dyspepsia, flatulence
(3-5%).
Hematologic: Decreased
hemoglobin, hematocrit, white blood cells (early onset, stabilizes with time).
Musculoskeletal: myopathy, rhabdomysis.
DRUG INTERACTION:
Statins and other fibrates: increased chance of muscular disorders, ie
myopathy, rhabdomysis.
Cyclosporions: can encounter reversible kidney problem.
Contraceptives: oestrogen containing contraceptives may interfere with
effects of fenofibrate.
Anticoagulants: increased risk of bleeding may occur.
Daptomycin: increased risk of myopathy when fibrates given with
daptomycin (preferably avoid concomitant use)
Sulfonylureas: fibrates may
improve glucose tolerance and have an additive effect with sulfonylureas
Ezetimibe: increased risk
of cholelithiasis and gallbladder disaese when fibrates given with
ezetimibe—discontinue if suspected
DOSAGE & ADMINISTRATION:
The
effective dose range of fenofibrate is usually 45-200 mg per day, and should be
adjusted following repeat lipid determinations at 4-8 weeks.
Adults: The recommended dose is 160 mg taken once daily.
Elderly: the usual adult dose is recommended.
Renal Impairment: Initial dose is to be reduced, uausally 100 mg
per day, (for creatinine clearance between 20 to 100 ml/min).
Children: 5mg/kg dose has been recommended to children above 10 years.
Administration: the tablet should be swallowed whole during a meal.
PRESENTATION;
