Fenofibrate 200 mg capsules are indicated as an adjunct to diet and other nonpharmacological
treatment (e.g. exercise, weight reduction) for the following:
- Treatment of severe hypertriglyceridaemia with or without low HDL cholesterol.
- Mixed hyperlipidaemia when a statin is contraindicated or not tolerated.
- Mixed hyperlipidaemia in patients at high cardiovascular risk in addition to a statin
when triglycerides and HDL cholesterol are not adequately controlled.

Dietary measures initiated before therapy should be continued. Response to therapy
should be monitored by determination of serum lipid values. If an adequate response
has not been achieved after several months (e.g. 3 months), complementary or
different therapeutic measures should be considered. Posology
Adults
The recommended dose is 200 mg daily administered as one capsule of Fenofibrate
200mg capsules.
The dose can be titrated up to 267 mg daily administered as 4 capsules of
Fenofibrate 67 mg capsules, if required. This maximum dose is not recommended in
addition to a statin.
Special populations
Elderly patients (≥ 65 years old)
No dose adjustment is necessary. The usual dose is recommended, except for
decreased renal function with estimated glomerular filtration rate < 60 mL/min/1.73
(see Patients with renal impairment).
Patients with renal impairment
Fenofibrate should not be used if severe renal impairment, defined as eGFR <30
mL/min per 1.73 m2, is present.
If eGFR is between 30 and 59 mL/min per 1.73 m2, the dose of fenofibrate should
not exceed 100 mg standard or 67 mg micronized once daily.
If, during follow-up, the eGFR decreases persistently to <30 mL/min per 1.73 m2,
fenofibrate should be discontinued.
Hepatic impairment
Fenofibrate 200mg capsules are is not recommended for use in patients with hepatic
impairment due to the lack of data.
Paediatric population
The safety and efficacy of fenofibrate in children and adolescents younger than 18
years has not been established. No data are available.
Therefore, the use of fenofibrate is not recommended in paediatric subjects under 18
years
Method of administration
Capsules should be swallowed whole during a meal.

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. • Hepatic insufficiency (including biliary cirrhosis and unexplained persistent liver function abnormality). • Known gallbladder disease. • Severe renal insufficiency (estimated glomerular filtration rate < 30 mL/min/1.73m2) Chronic or acute pancreatitis with the exception of acute pancreatitis due to severe hypertriglyceridemia. • Known photoallergy or phototoxic reaction during treatment with fibrates or ketoprofen

Secondary causes of hyperlipidaemia:
Secondary causes of hyperlipidaemia, such as uncontrolled type 2 diabetes mellitus,
hypothyroidism, nephrotic syndrome, dysproteinemia, obstructive liver disease,
pharmacological treatment, alcoholism, should be adequately treated before
fenofibrate therapy is considered. Secondary cause of hypercholesterolemia related
to pharmacological treatment can be seen with diuretics, β-blocking agents,
oestrogens, progestogens, combined oral contraceptives, immunosuppressive
agents and protease inhibitors. In these cases it should be ascertained whether the
hyperlipidaemia is of primary or secondary nature (possible elevation of lipid values
caused by these therapeutic agents).
Liver function:
As with other lipid lowering agents, increases have been reported in transaminase
levels in some patients. In the majority of cases these elevations were transient,
minor and asymptomatic. It is recommended that transaminase levels are monitored
every 3 months during the first 12 months of treatment and thereafter periodically.
Attention should be paid to patients who develop increase in transaminase levels
and therapy should be discontinued if AST (SGOT) and ALT (SGPT) levels increase
to more than 3 times the upper limit of the normal range. When symptoms indicative
of hepatitis occur (e.g. jaundice, pruritus), and diagnosis is confirmed by laboratory
testing, fenofibrate therapy should be discontinued. Pancreas:
Pancreatitis has been reported in patients taking fenofibrate (see sections 4.3 and
4.8). This occurrence may represent a failure of efficacy in patients with severe
hypertriglyceridaemia, a direct drug effect, or a secondary phenomenon mediated
through biliary tract stone or sludge formation with obstruction of the common bile
duct.
Muscle:
Muscle toxicity, including rare cases of rhabdomyolysis, with or without renal failure
has been reported with administration of fibrates and other lipid-lowering agents. The
incidence of this disorder increases in cases of hypoalbuminaemia and previous
renal insufficiency. Patients with pre-disposing factors for myopathy and/or
rhabdomyolysis, including age above 70 years, personal or familial history of
hereditary muscular disorders, renal impairment, hypothyroidism and high alcohol
intake, may be at an increased risk of developing rhabdomyolysis. For these
patients, the putative benefits and risks of fenofibrate therapy should be carefully
weighed up.
Muscle toxicity should be suspected in patients presenting diffuse myalgia, myositis,
muscular cramps and weakness and/or marked increases in CPK (levels exceeding
5 times the normal range). In such cases treatment with fenofibrate should be
stopped.
The risk of muscle toxicity may be increased if the drug is administered with another
fibrate or an HMG-CoA reductase inhibitor, especially in cases of pre-existing
muscular disease. Consequently, the co-prescription of fenofibrate with a HMG-CoA
reductase inhibitor or another fibrate should be reserved to patients with severe
combined dyslipidaemia and high cardiovascular risk without any history of muscular
disease and a close monitoring of potential muscle toxicity.
Renal function:
Fenofibrate 200 mg capsules are contraindicated in severe renal impairment (see
section 4.3).
Fenofibrate 200 mg capsules should be used with caution in patients with mild to
moderate renal insufficiency. Dose should be adjusted in patients whose estimated
glomerular filtration rate is 30 to 59 mL/min/1.73 m2 (see section 4.2).
Reversible elevations in serum creatinine have been reported in patients receiving
fenofibrate monotherapy or co-administered with statins. Elevations in serum
creatinine were generally stable over time with no evidence for continued increases
in serum creatinine with long term therapy and tended to return to baseline following
discontinuation of treatment.
During clinical trials, 10% of patients had a creatinine increase from baseline greater
than 30 μmol/L with co-administered fenofibrate and simvastatin versus 4.4% with statin monotherapy. 0.3% of patients receiving co-administration had clinically
relevant increases in creatinine to values > 200 μmol/L.
Treatment should be interrupted when creatinine level is 50% above the upper limit
of normal. It is recommended that creatinine is measured during the first 3 months
after initiation of treatment and periodically thereafter.
Excipients:
Lactose
This medicine contains lactose. Patients with rare hereditary problems of galactose
intolerance, total lactase deficiency or glucose-galactose malabsorption should not
take this medicine.

Oral anti-coagulants
Fenofibrate enhances oral anti-coagulant effect and may increase risk of bleeding. In
patients receiving oral anti-coagulant therapy, the dose of anti-coagulant should be
reduced by about one-third at the commencement of treatment and then gradually
adjusted if necessary according to INR (International Normalised Ratio) monitoring.
Ciclosporin
Some severe cases of reversible renal function impairment have been reported
during concomitant administration of fenofibrate and ciclosporin. The renal function
of these patients must therefore be closely monitored and the treatment with
fenofibrate stopped in the case of severe alteration of laboratory parameters.
HMG-CoA reductase inhibitors or Other Fibrates
The risk of serious muscle toxicity is increased if a fibrate is used concomitantly with
HMG-CoA reductase inhibitors or other fibrates. Such combination therapy should be
used with caution and patients monitored closely for signs of muscle toxicity (see
Section 4.4).
There is currently no evidence to suggest that fenofibrate affects the
pharmacokinetics of simvastatin.
Glitazones
Some cases of reversible paradoxical reduction of HDL-cholesterol have been
reported during concomitant administration of fenofibrate and glitazones. Therefore it
is recommended to monitor HDL-cholesterol if one of these components is added to
the other and stopping of either therapy if HDL-cholesterol is too low. Cytochrome P450 enzymes
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 mildto-
moderate of CYP2C9 at therapeutic concentrations.
Patients co-administered fenofibrate and CYP2C19, CYP2A6, and especially
CYP2C9 metabolised drugs with a narrow therapeutic index should be carefully
monitored and, if necessary, dose adjustment of these drugs is recommended.
Other
In common with other fibrates, fenofibrate induces microsomal mixed-function
oxidases involved in fatty acid metabolism in rodents and may interact with drugs
metabolised by these enzymes.

Pregnancy
There are no adequate data from the use of fenofibrate in pregnant women. Animal
studies have not demonstrated any teratogenic effects. Embryotoxic effects have
been shown at doses in the range of maternal toxicity (see section 5.3). The
potential risk for humans is unknown. Therefore, Fenofibrate 200mg capsules should
only be used during pregnancy after a careful benefit/risk assessment.
Breast-feeding
It is unknown whether fenofibrate and/or its metabolites are excreted in human milk.
A risk to the suckling child cannot be excluded. Therefore fenofibrate should not be
used during breast-feeding.
Fertility
Reversible effects on fertility have been observed in animals (see section 5.3). There
are no clinical data on fertility from the use of Fenofibrate 200mg capsules.

Fenofibrate 200mg capsules has no or negligible influence on the ability to drive and use machines.

The most commonly reported ADRs during fenofibrate therapy are digestive, gastric
or intestinal disorders.
The following undesirable effects have been observed during placebo-controlled
clinical trials (n=2344) with the below indicated frequencies:
The adverse drug reactions are stated in the table below using the following
convention:
Very common (>1/10); common (>1/100; <1/10); uncommon (>1/1,000; <1/100); rare
(>1/10,000; <1/1,000); very rare (<1/10,000) including isolated reports.

* In the FIELD-study, a randomized placebo-controlled trial performed in 9795
patients with type 2 diabetes mellitus, a statistically significant increase in
pancreatitis cases was observed in patients receiving fenofibrate versus patients
receiving placebo (0.8% versus 0.5%; p = 0.031). In the same study, a statistically
significant increase was reported in the incidence of pulmonary embolism (0.7% in
the placebo group versus 1.1% in the fenofibrate group; p = 0.022) and a statistically
non-significant increase in deep vein thromboses (placebo: 1.0 % [48/4900 patients]
versus fenofibrate 1.4% [67/4895 patients]; p = 0.074).
** In the FIELD study the average increase in blood homocysteine level in patients
treated with fenofibrate was 6.5 μmol/L, and was reversible on discontinuation of
fenofibrate treatment. The increased risk of venous thrombotic events may be
related to the increased homocysteine level. The clinical significance of this is not
clear.
In addition to those events reported during clinical trials, the following side effects
have been reported spontaneously during postmarketing use of fenofibrate. A
precise frequency cannot be estimated from the available data and is therefore
classified as “not known”.
- Respiratory, thoracic and mediastinal disorders: Interstitial lung disease.
- Musculoskeletal, connective tissue and bone disorders: Rhabdomyolysis.
- Hepatobiliary disorders: jaundice, complications of cholelithiasis (e.g. cholecystitis,
cholangitis, biliary colic)
- Skin and Subcutaneous Tissue Disorders: severe cutaneous reactions (e.g
erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis)
- General disorders and administration site conditions: Fatigue 

Reporting of suspected adverse reactions
To Report Any Side Effects
• Saudi Arabia
The National Pharmacovigilance Centre (NPC):
• Fax: +966-11-205-7662
• Call NPC at +966-11-2038222, Ext 2317-2356-2340
• SFDA Call Center: 19999
• E-mail: npc.drug@sfda.gov.sa
• Website: www.sfda.gov.sa/npc
• Other GCC States:
• Please contact the relevant competent authority. 

Only anecdotal cases of fenofibrate overdosage have been received. In the majority
of cases no overdose symptoms were reported.
No specific antidote is known. If overdose is suspected, treat symptomatically and
institute appropriate supportive measures as required. Fenofibrate cannot be
eliminated by haemodialysis.

5.1 Pharmacodynamic properties
Serum Lipid Reducing Agents/Cholesterol and Triglyceride Reducers/Fibrates. ATC
code: C10 AB 05.
Fenofibrate 200 mg capsule is a formulation containing 200 mg of micronised
fenofibrate: the administration of this product results in effective plasma
concentrations identical to those obtained with 3 capsules of Fenofibrate 67 mg
capsules containing 67 mg of micronised fenofibrate. Fenofibrate is a fibric acid derivative whose lipid modifying effects reported in
humans are mediated via activation of Peroxisome Proliferator Activated Receptor
type α (PPARα). Through activation of PPARα, fenofibrate increases lipolysis and
elimination of atherogenic triglyceride rich particles from plasma by activating
lipoprotein lipase and reducing production of Apoprotein C-III. Activation of PPARα
also induces an increase in the synthesis of Apoproteins A-I, and A-II.
There is evidence that treatment with fibrates may reduce coronary heart disease
events but they have not been shown to decrease all-cause mortality in the primary
or secondary prevention of cardiovascular disease.
The Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial was a
randomized placebo-controlled study of 5518 patients with type 2 diabetes mellitus
treated with fenofibrate in addition to simvastatin. Fenofibrate plus simvastatin
therapy did not show any significant differences compared to simvastatin
monotherapy in the composite primary outcome of non-fatal myocardial infarction,
non-fatal stroke, and cardiovascular death (hazard ratio [HR] 0.92, 95% CI 0.79-
1.08, p = 0.32 ; absolute risk reduction: 0.74%). In the pre-specified subgroup of
dyslipidaemic patients, defined as those in the lowest tertile of HDL-C (≤34 mg/dl or
0.88 mmol/L) and highest tertile of TG (≥204 mg/dl or 2.3 mmol/L) at baseline,
fenofibrate plus simvastatin therapy demonstrated a 31% relative reduction
compared to simvastatin monotherapy for the composite primary outcome (hazard
ratio [HR] 0.69, 95% CI 0.49-0.97, p = 0.03 ; absolute risk reduction: 4.95%). Another
prespecified subgroup analysis identified a statistically significant treatment-bygender
interaction (p = 0.01) indicating a possible treatment benefit of combination
therapy in men (p=0.037) but a potentially higher risk for the primary outcome in
women treated with combination therapy compared to simvastatin monotherapy
(p=0.069). This was not observed in the aforementioned subgroup of patients with
dyslipidaemia but there was also no clear evidence of benefit in dyslipidaemic
women treated with fenofibrate plus simvastatin, and a possible harmful effect in this
subgroup could not be excluded.
Studies with fenofibrate on lipoprotein fractions show decreases in levels of LDL and
VLDL cholesterol. HDLcholesterol levels are frequently increased. LDL and VLDL
triglycerides are reduced. The overall effect is a decrease in the ratio of low and very
low density lipoproteins to high density lipoproteins, which epidemiological studies
have correlated with a decrease in atherogenic risk. Apolipoprotein-A and
apolipoprotein-B levels are altered in parallel with HDL and LDL and VLDL levels
respectively.
Extravascular deposits of cholesterol (tendinous and tuberous xanthoma) may be
markedly reduced or even entirely eliminated during fenofibrate therapy.
Plasma uric acid levels are increased in approximately 20 % of hyperlipidaemic
patients, particularly in those with type IV disease. Patients with raised levels of fibrinogen treated with fenofibrate have shown
significant reductions in this parameter, as have those with raised levels of Lp(a).
Other inflammatory markers such as C Reactive Protein are reduced with fenofibrate
treatment.
The uricosuric effect of fenofibrate leading to reduction in uric acid levels of
approximately 25% should be of additional benefit in those dyslipidaemic patients
with hyperuricaemia.
Fenofibrate has been shown to possess an anti-aggregatory effect on platelets in
animals and in a clinical study, which showed a reduction in platelet aggregation
induced by ADP, arachidonic acid and epinephrine.

Absorption:
Maximum plasma concentrations (Cmax) occur within 4 to 5 hours after oral
administration. Plasma concentrations are stable during continuous treatment in any
given individual.
The absorption of fenofibrate is increased when administered with food.
Distribution:
Fenofibric acid is strongly bound to plasma albumin (more than 99%).
Metabolism and excretion:
After oral administration, fenofibrate is rapidly hydrolised by esterases to the active
metabolite fenofibric acid.
No unchanged fenofibrate can be detected in the plasma. Fenofibrate is not a
substrate for CYP 3A4. No hepatic microsomal metabolism is involved.
The drug is excreted mainly in the urine. Practically all the drug is eliminated within 6
days. Fenofibrate is mainly excreted in the form of fenofibric acid and its
glucuronoconjugate.
In elderly patients, the fenofibric acid apparent total plasma clearance is not
modified.
Kinetic studies following the administration of a single dose and continuous
treatment have demonstrated that the drug does not accumulate.
Fenofibric acid is not eliminated during haemodialysis.
The plasma elimination half-life of fenofibric acid is approximately 20 hours. 

In a three-month oral nonclinical study in the rat species with fenofibric acid, the
active metabolite of fenofibrate, toxicity for the skeletal muscles (particularly those
rich in type I -slow oxidative- myofibres) and cardiac degeneration, anaemia and
decreased body weight were seen. No skeletal toxicity was noted at doses up to 30
mg/kg (approximately 17-time the exposure at the human maximum recommended
dose (MRHD). No signs of cardiomyotoxicity were noted at an exposure about 3
times the exposure at MRHD. Reversible ulcers and erosions in the gastro-intestinal
tract occurred in dogs treated for 3 months. No gastro-intestinal lesions were noted
in that study at an exposure approximately 5 times the exposure at the MRHD.
Studies on the mutagenicity of fenofibrate have been negative. In rats and mice, liver
tumours have been found at high dosages, which are attributable to peroxisome
proliferation. These changes are specific to small rodents and have not been
observed in other animal species. This is of no relevance to therapeutic use in man.
Studies in mice, rats and rabbits did not reveal any teratogenic effect. Embryotoxic
effects were observed at doses in the range of maternal toxicity. Prolongation of the
gestation period and difficulties during delivery were observed at high doses.
Reversible hypospermia and testicular vacuolation and immaturity of the ovaries
were observed in a repeat-dose toxicity study with fenofibric acid in young dogs.
However no effects on fertility were detected in non-clinical reproductive toxicity
studies conducted with fenofibrate.

Composition of LYPFEN 200 mg capsules
LACTOSE MONOHYDRATE
PARTIALLY PREGELATINIZED MAIZE STARCH
CROSPOVIDONE
SODIUM LAURYL SULPHATE
POVIDONE
PURIFIED WATER
COLLOIDAL SILICON DIOXIDE
MAGNESIUM STEARATE
HARD GELATIN CAPSULE

Not applicable.

2 years (24 Months).

Store below 30 ºC

LYPFEN 200 mg capsules available in pack sizes of 30 capsules.

Any unused medicinal product or waste material should be disposed of in
accordance with local requirements, Keep out of the reach & sight of children