Grofibrate
Grofibrate Uses, Dosage, Side Effects, Food Interaction and all others data.
Grofibrate is a fibric acid derivative, a prodrug comprising fenofibric acid linked to an isopropyl ester. Grofibrate is rapidly hydrolyzed after oral ingestion to its pharmacologically active form, fenofibric acid. The effects of fenofibric acid seen in clinical practice have been explained in vivo in transgenic mice and in vitro in human hepatocyte cultures by the activation of peroxisome proliferator activated receptor α (PPARα)
It lowers lipid levels by activating peroxisome proliferator-activated receptor alpha (PPARα). PPARα activates lipoprotein lipase and reduces apoprotein CIII (an inhibitor of lipoprotein lipase activity), which increases lipolysis and elimination of triglyceride-rich particles from plasma. The resulting fall in triglycerides produces an alteration in the size and composition of LDL from small, dense particles (which are thought to be atherogenic due to their susceptibility to oxidation), to large buoyant particles. These larger particles have a greater affinity for cholesterol receptors and are catabolized rapidly
PPARα also increases apoproteins AI and AII, reduces VLDL- and LDL-containing apoprotein B, and increases HDL-containing apoprotein AI and AII. Grofibrate also reduces serum uric acid levels in hyperuricemic and normal individuals by increasing the urinary excretion of uric acid.
Grofibrate is a fibrate that activates peroxisome proliferator activated receptor alpha (PPARα) to alter lipid metabolism and treat primary hypercholesterolemia, mixed dyslipidemia, and severe hypertriglyceridemia. Grofibrate requires once daily dosing and has a half life of 19-27 hours so its duration of action is long. Grofibrate capsules are given at a dose of 50-150mg daily so the therapeutic index is wide. Patients should be counselled about the risk of rhabdomyolysis, myopathy, and cholelithiasis when taking fibrates.
| Trade Name | Grofibrate |
| Availability | Prescription only |
| Generic | Fenofibrate |
| Fenofibrate Other Names | Fenofibrate, Fenofibrato, Fenofibratum, Finofibrate, Procetofen |
| Related Drugs | atorvastatin, simvastatin, rosuvastatin, Lipitor, Crestor, pravastatin, gemfibrozil, Vascepa, niacin, Fish Oil |
| Type | |
| Formula | C20H21ClO4 |
| Weight | Average: 360.831 Monoisotopic: 360.112836867 |
| Protein binding | Fenofibrate is 99% protein bound in serum, primarily to albumin. |
| Groups | Approved |
| Therapeutic Class | Fibrates |
| Manufacturer | |
| Available Country | Russia |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Grofibrate is used for an adjunct to diet and other non pharmacological treatment (e.g. exercise, weight reduction) for the following:
- Treatment of severe hypertriglyceridemia with or without low HDL cholesterol.
- Mixed hyperlipidemia when a statin is contraused or not tolerated.
- Mixed hyperlipidemia in patients at high cardiovascular risk in addition to a statin when triglycerides and HDL cholesterol are not adequately controlled
Grofibrate is also used to associated treatment for these conditions: Mixed Dyslipidemias, Primary Hypercholesterolemia, Severe Hypertriglyceridemia, Severe Fredrickson Type IV Hypertriglyceridemia, Severe Fredrickson Type V Hypertriglyceridemia
How Grofibrate works
Grofibrate activates peroxisome proliferator activated receptor alpha (PPARα), increasing lipolysis, activating lipoprotein lipase, and reducing apoprotein C-III. PPARα is a nuclear receptor and its activation alters lipid, glucose, and amino acid homeostasis. Activation of PPARα activates transcription of gene transcription and translation that generates peroxisomes filled with hydrogen peroxide, reactive oxygen species, and hydroxyl radicals that also participate in lipolysis. This mechanism of increased lipid metabolism is also associated with increased oxidative stress on the liver. In rare cases this stress can lead to cirrhosis and chronic active hepatitis.
Dosage
Grofibrate dosage
The dose is one 200 mg capsule per day. Dosage should be individualized according to patient response, and should be increased sequentially if necessary following repeat serum triglyceride estimations at 4 to 8 week intervals. Patients should be placed on an appropriate triglyceride-lowering diet before receiving fenofibrate, and should continue this diet during treatment with fenofibrate. Grofibrate should be given with meals, thereby optimizing the bioavailability of the medication.
Side Effects
Digestive: hepatitis, cholelithiasis, cholecystitis, hepatomegaly
Musculoskeletal: myalgia, myasthenia, rhabdomyolysis
Skin and appendages: photosensitivity, eczema
Cardiovascular: peripheral edema, angina, palpitations, tachycardia, and migraine
Toxicity
The oral LD50 in rats is >2g/kg and in mice is 1600mg/kg. The oral TDLO in rats is 9mg/kg.
Treat patients with supportive care including monitoring of vital signs and observing clinical status. Recent overdose may be treated with inducing vomiting or gastric lavage. Due to fenofibrate's extensive protein binding, hemodialysis is not expected to be useful.
Precaution
Increased risk of cholelithiasis, pancreatitis, skeletal muscle effects. Patient at risk of rhabdomyolysis. Renal impairment. Pregnancy.
Interaction
Oral Anticoagulants: Caution should be exercised when anticoagulants are given in conjunction with fenofibrate. The dosage of the anticoagulants should be reduced to maintain the prothrombin time at the desired level to prevent bleeding complications.
Resins: Since bile acid sequestrants may bind other drugs given concurrently, patients should take fenofibrate at least 1 hour before or 4-6 hours after a bile acid binding resin to avoid impending its absorption.
Cyclosporine: 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 fibrate drugs including fenofibrate, there is a risk that an interaction will lead to deterioration.
Food Interaction
- Take with food. Bioavailability is increased 2- to 3-fold when taken with food.
Grofibrate Cholesterol interaction
[Major] There have been reports of severe decreases in HDL cholesterol (HDL-C) levels (as low as 2 mg The decrease has been reported to occur within 2 weeks to years after initiation of therapy. It is recommended that HDL-C levels be checked within the first few months after initiation therapy and if a severely depressed HDL-C level is detected, therapy with these agents should be withdrawn. Monitor HDL-C level until it has returned to baseline, and therapy with these agents should not be re-initiated in these patients.
Grofibrate Drug Interaction
Major: rosuvastatin, rosuvastatinUnknown: aspirin, aspirin, aspirin, aspirin, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, pregabalin, pregabalin, metoprolol, metoprolol, metoprolol, metoprolol, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol
Grofibrate Disease Interaction
Major: biliary cirrhosis, cholelithiasis, HDL cholesterol, liver disease, renal dysfunction, rhabdomyolysisModerate: hematological changes
Volume of Distribution
The volume of distribution of fenofibrate is 0.89L/kg, and can be as high as 60L.
Elimination Route
A single 300mg oral dose of fenofibrate reaches a Cmax of 6-9.5mg/L with a Tmax of 4-6h in healthy, fasting volunteers.
Half Life
Fenofibric acid, the active metabolite of fenofibrate, has a half life of 23 hours. Grofibrate has a half life of 19-27 hours in healthy subjects and up to 143 hours in patients with renal failure.
Clearance
The oral clearance of fenofibrate is 1.1L/h in young adults and 1.2L/h in the elderly.
Elimination Route
5-25% of a dose of fenofibrate is eliminated in the feces, while 60-88% is eliminated in the urine. 70-75% of the dose recovered in the urine is in the form of fenofibryl glucuronide and 16% as fenofibric acid.
Pregnancy & Breastfeeding use
Pregnancy Category C. Grofibrate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing mothers: Grofibrate should not be used in nursing mothers. Because of the potential for tumorigenicity seen in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug.
Contraindication
Grofibrate is contraindicated in patients with-
- Hypersensitivity to fenofibrate or any component of this medication.
- Known photoallergy or phototoxic reaction during treatment with fibrates or ketoprofen.
- Severe liver dysfunction, gallbladder disease, biliary cirrhosis, severe renal disorders.
- Chronic or acute pancreatitis with the exception of acute pancreatitis due to severe hypertriglyceridemia.
- Pregnancy and lactation.
Special Warning
Geriatrics: This indicates that a similar dosage regimen can be used in the elderly, without increasing accumulation of the drug or metabolites.
Pediatrics: No data are available. Grofibrate is not indicated for use in the pediatric population.
Gender: No pharmacokinetic difference between male and female has been observed for fenofibrate.
Renal insufficiency: The dosage of fenofibrate should be minimized in patients who have severe renal impairment, while no modification of dosage is required in patients having moderate renal impairment.
Hepatic insufficiency: No pharmacokinetic study has been conducted in patients having hepatic insufficiency.
Storage Condition
Store at cool & dry place. Protect from light and moisture.
Innovators Monograph
You find simplified version here Grofibrate
Grofibrate contains Fenofibrate see full prescribing information from innovator Grofibrate Monograph, Grofibrate MSDS, Grofibrate FDA label
FAQ
What is Grofibrate used for?
Grofibrate is used together with a proper diet to reduce and treat high cholesterol and triglyceride (fat-like substances) levels in the blood. This may help prevent the development of pancreatitis (inflammation or swelling of the pancreas) caused by high levels of triglycerides in the blood. Grofibrate used to treat abnormal blood lipid levels. It is less preferred to statin medications as it does not appear to reduce the risk of heart disease or death. Its use is recommended together with dietary changes.
How safe is Grofibrate?
In general, Grofibrate can be considered a safe and well-tolerated lipid-lowering drug that has been scrutinized extensively for safety in clinical research and during an already long marketing period in Europe.
How does Grofibrate work?
Grofibrate works by increasing the natural substance (enzyme) that breaks down fats in the blood.
What are the common side effects of Grofibrate?
Common side effects of Grofibrate are include:
- stomach pain,
- back pain,
- headache, or.
- runny or stuffy nose.
Is Grofibrate safe during pregnancy?
In this case, no harmful effects on fetal development were observed after exposure to Grofibrate during organogenesis. Use is recommended only if clearly needed and the benefit outweighs the risk.
Is Grofibrate safe during breastfeeding?
Do not breast-feed while using this Grofibrate, and for at least 5 days after your last dose.
Can I drink alcohol with Grofibrate?
Avoid eating foods high in fat or cholesterol, or Grofibrate will not be as effective. Avoid drinking alcohol. It can raise triglyceride levels and may increase your risk of liver damage.
Can I drive after taking Grofibrate?
You may feel dizzy, drowsy or tired while taking Grofibrate. Always take this medicine exactly as your doctor or pharmacist has told you.
When should be best taken of Grofibrate?
You should take Grofibrate with food, so taking your doses during a mealtime is ideal.
How often is Grofibrate taken?
At first, 43 to 130 milligrams (mg) once a day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 130 mg per day: At first, 50 to 150 mg once a day with a meal.
How long does Grofibrate take to work?
Grofibrate is quickly absorbed and converted into its active ingredient Grofibrate acid once inside the body. Takes about a week for levels to stabilize.
What is the half life of Grofibrate?
The plasma elimination half-life of Grofibrate acid is approximately 20 hours.
Can I take Grofibrate for a long time?
Grofibrate oral tablet is used for long-term treatment. It comes with risks if you don't take it as prescribed. If you stop taking the drug suddenly or don't take it at all: Your cholesterol levels may not be controlled. This raises your risk of serious health problems such as heart disease, heart attack, or stroke.
Who should not take Grofibrate?
You should not take Grofibrate if you are allergic to it, or if you have: Do not breast-feed while using this medicine, and for at least 5 days after your last dose.
What happens if I miss a dose?
Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.
What happen If I suddenly stop taking Grofibrate?
If you stop taking the Grofibrate suddenly or don't take it at all: Your cholesterol levels may not be controlled. This raises your risk of serious health problems such as heart disease, heart attack, or stroke.
What happens if I take too much Grofibrate ?
Tiredness and fever, abdominal pain, nausea, or vomiting. These may be signs of inflammation (swelling) of the gallbladder or pancreas.
Can Grofibrate cause liver damage?
Grofibrate can cause abnormal results in tests of liver function. These abnormal results can indicate liver damage. This drug can also cause other liver damage and inflammation after years of use.
Can Grofibrate help me lose weight?
Grofibrate prevents and reduces body weight gain and adiposity in diet-induced obese rats.
Is Grofibrate safe for kidneys?
No adverse effect of Grofibrate on renal function was reported.
Will Grofibrate affect my fertility?
Grofibrate usage was not adversely associated with sperm parameters other than sperm viability. The combination of atorvastatin and Grofibrate significantly reduced the sperm count and viability.
