FIBRIC ACID DERIVATIVES
acid derivatives, including clofibrate, fenofibrate, bezafi-brate,
ciprofibrate, and simfibrate, are antilipidaemic agents which decrease serum
lipids by reducing the very-low-density lipoprotein fraction (Sf 20 to 400)
rich in triglycerides. These drugs reduce triglycerides (TG) and VLDL, while
increasing HDL levels. They act by increasing the activity of lipoprotein
lipase and other enzymes. Clofibrate also decreases serum cholesterol levels,
primarily the low-density lipoprotein frac-tion (Sf 0 to 20).
Clofibrate is indicated as
adjunctive therapy to diet for the treatment of type III hyperlipidaemia. It
may also be helpful in some patients with severe hypertriglyceridaemia due to
Type IIb, Type IV, and Type V hyperlipidaemias.
Fenofibrate is indicated as
adjunctive therapy to diet for the treatment of Type IV and V hyperlipidaemia
in patients who are at risk for pancreatitis.
Ciprofibrate is being investigated
as a lipid regulating drug with actions on plasma lipids similar to those of
Myalgia, GI upset, rash, alopecia
(rare). Muscular syndrome may be dose-dependant; the most frequent effect is
myalgia, with the most commonly affected muscles being those of the lower
extremities. Arthralgia and flu-like symptoms have also been reported.
Nausea, vomiting, constipation,
dyspepsia, diarrhoea, and flatulence occur transiently in approximately 10% of
patients. Epigastric pain has been reported as a frequent side effect, and
cholelithiasis is increased.
Impotence and decreased libido have
Clofibrate therapy has been
associated with multiple cardiovascular side effects (peripheral vascular
disease, pulmonary embolism, thrombophlebitis, angina pectoris, cardiac
arrhythmias, cardiomegaly) of varying severity, fever, hepatotoxicity,
myopathies, and gastrointestinal irritation. Fatigue, weakness, drowsiness,
dizziness, and headache have also been reported. Renal effects of clofi-brate
have included dysuria, haematuria, proteinuria and oliguria. Hepatomegaly,
jaundice, hepatitis, and transient increases in serum transaminase levels have
Increases of serum transaminase
levels greater than 3 times the upper limit of normal were reported following
Concomitant administration of
clofibrate with antico-agulants may cause hypoprothrombinaemia. When
anti-coagulants are given concurrently with clofibrate, the dosage of the
anticoagulant should usually be reduced by one-half (depending on the
individual case) to maintain the prothrombin time at the desired level in order
to prevent bleeding complications.
Co-administration of clofibrate with
phenytoin may cause an increase in phenytoin serum levels due to displacement
of phenytoin from its protein binding site.
An increased hypoglycaemic effect
has been reported following concurrent administration of clofibrate and
· Patients should be observed for
potential CNS depres-sion, musculoskeletal, cardiovascular, and hepatic or
renal damage, as these are the primary manifestations of toxicity due to
· Periodic examinations for muscle
tenderness and dysfunc-tion are mandatory to detect the muscular syndrome, and
determinations of CPK and AST should be performed during therapy.
· Parameters that may increase—serum
aldolase, BSP reten-tion, thymol turbidity, glutamic-oxaloacetic transaminase.
· Parameters that may
decrease—fibrinogen, gamma-glutamyl transpeptidase, serum alkaline phosphatase.
· Therapeutic plasma levels of
p-chlorophenoxyisobutyric acid (CPIB) have been reported to be 80 to 150
mcg/ml. The average maximum plasma level after a 500 mg oral dose was 44.0
Gastric decontamination is probably usually not necessary
and should be considered only if several times the daily therapeutic dose was