Information about MINULIPID
Composition& excipients:
Each delayed release capsule contains cholinefenofibrate, equivalent to 45 mg or 135 mg of fenofibric acid.
Excipients: pellets ready for filling.
CLINICALPHARMACOLOGY
Mechanism of Action
The lipid-modifying effects of fenofibric acidseen in clinical practice have been explained by the activation of peroxisomeproliferator activated receptor α (PPARα). Through this mechanism, fenofibricacid increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of Apo CIII (aninhibitor of lipoprotein lipase activity).
Activation of PPARα also induces an increase in the synthesis of HDL-C and Apo AI and AII.
Pharmacokinetics
Minulipid contains fenofibric acid, which is the only circulating pharmacologically active moiety in plasma after oral administration of Minulipid. Fenofibric acid is also the circulating pharmacologically active moiety in plasma after oral administration offenofibrate, the ester of fenofibric acid.
Plasma concentrations of fenofibric acid after administration of one 135 mg Minulipid delayed release capsule are equivalent to those after one 200 mg capsule of micronized fenofibrate administered underfed conditions.
Absorption Fenofibric acid is well absorbed throughout the gastrointestinal tract. The absolute bio availability of fenofibric acid is approximately 81%.
Peak plasma levels of fenofibric acid occur within 4 to 5 hours after a single dose administration of Minulipid capsule under fasting conditions.
Fenofibric acid exposure in plasma, as measured by Cmax and AUC, is not significantly different when a single 135 mg dose of Minulipid is administered under fasting or non fasting conditions.
Distribution Upon multiple dosing of Minulipid, fenofibric acid levels reach steady state within 8 days. Plasma concentrations of fenofibric acid at steady state are approximately slightly more than double those following a single dose. Serumprotein binding is approximately 99% in normal and dyslipidemic subjects.
Metabolism Fenofibric acid is primarily conjugated with glucuronic acid and then excreted in urine.
Excretion Minulipidis primarily excreted in the urine in the form of fenofibric acid and fenofibric acid glucuronide.
Fenofibric acid is eliminated with a half-life of approximately 20 hours, allowing once daily administration of Minulipid.
INDICATIONSAND USAGE
v Co-administration Therapy with Statins for theTreatment of Mixed Dyslipidemia
Trlipi is indicated as an adjunct to diet in combination with a stain to reduce TG and increase HDL-Cin patients with mixed dyslipidemia and CHD or a CHD risk equivalent who are on optimal stain therapy to achieve their LDL-C goal.
CHD risk equivalents comprise:
Other clinical forms of atherosclerotic disease (peripheral arterial disease,abdominal aortic aneurysm, and symptomatic carotid artery disease);
Diabetes;
Multiplerisk factors that confer a 10-year risk for CHD > 20%.
v Treatment of Severe Hypertriglyceridemia
Trlipiis indicated as adjunctive therapy to diet to reduce TG in patients with severe hyperglycemia. Improving glycemic control in diabetic patients showing fasting chylomicronemia will usually obviate the need for pharmacological intervention. Markedly elevated levels of serum triglycerides (e.g. > 2,000mg/dL) may increase the risk of developing pancreatitis. The effect of Trlipi the rapy on reducing this risk has not been adequately studied.
v Treatment of Primary Hyperlipidemia or MixedDyslipidemia
Trlipiis indicated as adjunctive therapy to diet to reduce elevated LDL-C, Total-C,TG, and Apo B, and to increase HDL-C in patients with primary hyperlipidemia ormixed dyslipidemia.
v General Considerations for Treatment
Fenofibrateat a dose equivalent to 135 mg of Trlipi was not shown to reduce coronary heart disease morbidity in a large, randomized controlled trial of patients with type 2 diabetes mellitus.
Laboratorystudies should be performed to establish that lipid levels are abnormal before instituting Trlipi the rapy.
Every reasonable attempt should be made to control serum lipids with non-drug methods including appropriate diet, exercise, weight loss in obese patients, and control of any medical problems such as diabetes mellitus and hypothyroidism that may be contributing to the lipid abnormalities. Medications known to exacerbate hyperglycemia(beta-blockers, thiazides, estrogens) should be discontinued or changed if possible, and excessive alcohol intake should be addressed before triglyceride-lowering drug therapy is considered. If the decision is made to use lipid-altering drugs, the patient should be instructed that this does not reduce the importance of adhering to diet.
Drug therapy is not indicated for patients who have elevations of chylomicrons and plasma triglycerides, but who have normal levels of VLDL.
DOSAGEAND ADMINISTRATION
General Considerations
Patients should be placed on an appropriate lipid-lowering diet before receiving minulipid as mono therapy or co-administered with a statin and should continue this diet during treatment. Trlipi delayed release capsules can be taken without regard to meals. Serumlipids should be monitored periodically. The maximum dose is 135 mg once daily.
Co-administration Therapy with Statins for the Treatment of Mixed Dyslipidemia
Trlipi 135 mg may be co-administered with anHMG-CoA reductase inhibitor (statin) in patients with mixed dyslipidemia. For convenience, the daily dose of Trlipi may be taken at the same time as astatin, according to the dosing recommendations for each medication.Co-administration with the maximum dose of a statin has not been evaluated in clinical studies and should be avoided unless the benefits are expected to outweigh the risks.
Severe Hypertriglyceridemia
The initial dose of Trlipi is 45 to 135 mg once daily. Dosage should be individualized according to patient response, and should be adjusted if necessary following repeat lipid determinations at 4 to 8 week intervals. The maximum dose is 135 mg once daily.
Primary Hyperlipidemia or Mixed Dyslipidemia
The dose of Minulipid is 135 mg once daily.
Impaired Renal Function
Treatment with Minulipid should be initiated ata dose of 45 mg once daily in patients with mild to moderate renal impairment and should only be increased after evaluation of the effects on renal function and lipid levels at this dose. The use of Trlipi should be avoided in patients with severely impaired renal function.
Elderly Patients
Dose selection for the elderly should be madeon the basis of renal function
CONTRAINDICATIONS
Trlipiis contraindicated in:
patients with severe renal impairment, including those receiving dialysis.
patients with active liver disease, including those with primary biliary cirrhosis and unexplained persistent liver function abnormalities.
patients with preexisting gallbladder disease.
nursing mothers.
patients with hypersensitivity to fenofibric acid, choline fenofibrate or fenofibrate [see WARNINGS and PRECAUTIONS ( 5.7)].
WhenTrlipi is co-administered with a statin.
WARNINGSAND PRECAUTIONS
üSkeletal Muscle
Fibrateand statin mono therapy increase the risk of myositis or myopathy, and have been associated with rhabdomyolysis. Data from observational studies suggest that the risk for rhabdomyolysis is increased when fibrates are co-administered with a statin (with a significantly higher rate observed for gemfibrozil).
ü Serum Creatinine
Reversible elevations in serum create nine have been reported in patients receiving Trlipias monotherapy or co-administered with statins as well as patients receiving fenofibrate.
ü Liver Function
Trlipiat a dose of 135 mg once daily administered as mono therapy or co-administered with low to moderate doses of statins has been associated with increases in serum transaminases [AST (SGOT) or ALT (SGPT)].
Regular monitoring of liver function, including serum ALT (SGPT) should be performed for the duration of therapy with Trlipi,and therapy discontinued if enzyme levels persist above 3 times the upper limit of normal.
ü Cholelithiasis
Trlipi, like fenofibrate, clofibrate, and gemfibrozil, may increase cholesterol excretion into the bile, potentially leading to cholelithiasis.
Trlipi therapy should be discontinued if gallstones are found.
ü Concomitant Oral Anticoagulants
Caution should be exercised when Trlipi isgiven in conjunction with oral coumarin anticoagulants.
Trlipi may potentiate the anticoagulant effects of these agents resulting in prolongation of the prothrombin time/INR.
ü Pancreatitis
Pancreatitis has been reported in patient staking drugs of the fibrate class, including Trlipi
ü Hypersensitivity Reactions
Acute hypersensitivity reactions including severe skin rashes requiring patient hospitalization and treatment with steroids have occurred very rarely during treatment with fenofibrate, including rare spontaneous reports of Stevens-Johnson Syndrome and toxic epidermal necrolysis.
ü Hematological Changes
Mild to moderate hemoglobin, hematocrit, and white blood cell decreases have been observed in patients following initiation of Trlipi and fenofibrate therapy.
ADVERSEREACTIONS
Adverse Events Reported in ≥ 3% of Patients Receiving minulipid or Co-Administered with a Statin During Double-Blind Controlled Studies [Number (%)]
Constipation, Diarrhea, Dyspepsia, Nausea, Fatigue, Pain, Nasopharyngitis, Sinusitis, Upper Respiratory Tract, Arthralgia, Back Pain, Muscle Spasms, Myalgia, Pain in Extremity, Dizziness, Headache, Co-Administration Therapy with Statins, Bronchitis,influenza, and urinary tract infection.
AST increased, blood CPK increased, and hepatic enzyme increased.
Musculoskeletalpain.
Psychiatric Disorders :Insomnia.
Coughand pharyngolaryngeal pain.
Hypertension.
Reported by 2% or More of Patients Treated with Fenofibrate and Greater :
Abdominal Pain
Back Pain
Headache
Nausea
Constipation
Abnormal Liver Tests
Increased AST
Increased ALT
Increased Creatine Phosphokinase
Respiratory Disorder
Rhinitis
DRUG INTERACTIONS
8.1 Oral Anticoagulants
Caution should be exercised when oral coumarin anticoagulants are given in conjunction with Trlipi.
8.2 BileAcid Resins
Since bile acid resins may bind other drugs given concurrently, patients should take Trlipi at least 1 hour before or 4-6 hours after a bile acid resin to avoid impeding its absorption.
8.3Cyclosporine
Because cyclosporine can produce nephrotoxicity with decreases in creatinine clearance and rises in serum creatinine, and because renal excretion is the primary elimination route of drugs of the fibrate class including Trlipi, there is a risk that an interaction will lead to decline of renal function.
USE INSPECIFIC POPULATIONS
Pregnancy
Pregnancy Category: C
The safety of Trlipi in pregnant women has not been established. There are no adequate and well controlled studies of Minulipid in pregnant women. Minulipid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
When Minulipid is administered with a statin in a woman of childbearing potential, refer to pregnancy category and product labeling for the statin . All statins are contraindicated in pregnant women.
Nursing Mothers
Minulipid should not be used in nursing mothers. A decision should be made whether to discontinue nursing or to discontinue the drug.
Pediatric Use
The safety and effectiveness of Minulipid monotherapy or co-administration with a statin in pediatric patients have not been established.
Geriatric Use
Since elderly patients have a higher incidence of renal impairment, the dose selection for the elderly should be made on the basis of renal function. Consider monitoring renal function in elderly patients taking Minulipid.
Renal Impairment
The use of Minulipid should be avoided inpatients who have severe renal impairment. Dose reduction is required inpatients with mild to moderate renal impairment. Monitoring renal function inpatients with renal impairment is recommended.
Hepatic Impairment
The use of Minulipid has not been evaluated in subjects with hepatic impairment
OVER DOSAGE
There is no specific treatment for overdose with Minulipid. General supportive care of the patient is indicated, including monitoring of vital signs and observation of clinical status, should an overdose occur. If indicated, elimination of absorbed drug should be achieved by or gastric lavage; usual precautions should be observed to maintain the airway. Because Minulipid is highly bound to plasma proteins, hemodialysis should not be considered.
Storage:
Store at 25°C;
Keep out of the reach of children.
Protect from moisture.
Package:
Minulipid 45mg contains 14 Capsules.
Minulipid 135mg contains 10 Capsules.