Lipanthyl 200 Micronised is indicated as an adjunct to diet and other non-pharmacological 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 Lipanthyl 200 Micronised.
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:
Lipanthyl 200 Micronised 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.

- Hepatic insufficiency (including biliary cirrhosis and unexplained persistent liver function abnormality), - Known gallbladder disease, - Severe renal insufficiency (estimated glomerular filtration rate < 30 mL/min/1.73 m2), - 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, - Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Secondary causes of hyperlipidemia:
Secondary causes of hyperlipidemia, 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, estrogens, 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:
Lipanthyl 200 Micronised is contraindicated in severe renal impairment (see section 4.3).
Lipanthyl 200 Micronised 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 coadministered
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 coadministered
fenofibrate and simvastatin versus 4.4% with statin monotherapy. 0.3% of patients receiving coadministration
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:
As this medicinal product contains Lactose, patients with rare hereditary problems of galactose intolerance, the Lapp
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 anticoagulant
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.
Cyclosporin
Some severe cases of reversible renal function impairment have been reported during concomitant administration of
fenofibrate and cyclosporin. 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 mild-to-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, Lipanthyl 200 Micronised should only be used during pregnancy after a careful benefit/risk assessment.

Lactation: 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 Lipanthyl 200 Micronised.

Lipanthyl 200 Micronised has no or negligible influence on the ability to drive and use machines.

The most commonly reported ADRs during Lipanthyl 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:

MedDRA system organ class	Common ≥1/100, <1/10	Uncommon ≥1/1,000, <1/100	Rare ≥1/10,000, <1/1,000	Very rare <1/10,000 incl. isolated reports
Blood and lymphatic system disorders			Haemoglobin decreased White blood cell count decreased
Immune system disorders			Hypersensitivity
Nervous system disorders		Headache
Vascular disorders		Thromboembolism (pulmonary embolism, deep vein thrombosis)*
Gastrointestinal disorders	Gastrointestinal signs and symptoms (abdominal pain, nausea, vomiting, diarrhoea, flatulence)	Pancreatitis*
Hepatobiliary disorders	Transaminases increased (see section 4.4)	Cholelithiasis (see section 4.4)	Hepatitis
Skin and subcutaneous tissue disorders		Cutaneous hypersensitivity (e.g. Rashes, pruritus, urticaria)	Alopecia  Photosensitivity reactions
Musculoskeletal, connective tissue and bone disorders		Muscle disorder (e.g. myalgia, myositis, muscular spasms and weakness)
Reproductive system and breast disorders		Sexual dysfunction
Investigations	Blood homocysteine level increased**	Blood creatinine increased	Blood urea increased

* 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 Lipanthyl. 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
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued
monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any
suspected adverse reactions directly.

To report any side effect(s):

-National Pharmacovigilance Center (NPC)

o Fax: +966-11-205-7662

o SFDA Call Center: 19999

o E-mail: npc.drug@sfda.gov.sa

o Website: https://ade.sfda.gov.sa

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.

Serum Lipid Reducing Agents/Cholesterol and Triglyceride Reducers/Fibrates. ATC code:C10 AB 05.
Lipanthyl 200 Micronised is a formulation containing 200mg 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-

by-gender 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. HDL
cholesterol 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.

Excipients: lactose monohydrate, pregelatinised starch, sodium laurilsulfate, crospovidone and magnesium stearate.
Composition of the capsule shell: gelatin, titanium dioxide (E171), red iron oxide (E172) and yellow iron oxide (E172).

No effect noted to date.

3 years.

Keep in dry place. Store below 30°C.

Pack of 10, 28, 30 capsules in blisters (PVC/Aluminium).
*Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.