Grifogemzilo
Grifogemzilo Uses, Dosage, Side Effects, Food Interaction and all others data.
Grifogemzilo is an anti-lipemic agent. Grifogemzilo decreases serum triglycerides in healthy individuals and patients with hyper-triglyceridemia. It decreases very low-density lipoprotein (VLDL)- triglyceride concentration and to a lesser extent, LDL triglyceride concentration. HDL-triglyceride is usually decreased slightly. Grifogemzilo usually increases the HDL-cholesterol fraction in healthy individuals and patients with hyperlipoproteinemia, an action that may be beneficial in slowing the progression of atherosclerosis and in reducing the risk of coronary heart disease.
Grifogemzilo also inhibits synthesis of VLDL carrier apolipoprotein B, leading to a decrease in VLDL production. How gemfibrozil raises HDL concentration is not known. Grifogemzilo inhibits lipolysis of fat in adipose tissue and decreases the hepatic uptake of plasma free fatty acids, thereby reducing hepatic triglyceride production.
Grifogemzilo alters lipid metabolism to treat patients with hyperlipidemia. The duration of action requires twice daily dosing as the mean residence time of gemfibrozil is up to 9.6h in patients with chronic renal failure. Grifogemzilo has a wide therapeutic index as trials with twice the standard dose were not associated with severe side effects. Patients taking gemfibrozil may be at an increased risk of developing cholelithiasis and cholecystitis, as seen in patients taking clofibrate.
Trade Name | Grifogemzilo |
Availability | Prescription only |
Generic | Gemfibrozil |
Gemfibrozil Other Names | Gemfibrozil, Gemfibrozilo, Gemfibrozilum |
Related Drugs | Zetia, Praluent, Repatha, atorvastatin, simvastatin, rosuvastatin, Lipitor, fenofibrate, ezetimibe, Crestor |
Type | |
Formula | C15H22O3 |
Weight | Average: 250.3334 Monoisotopic: 250.15689457 |
Protein binding | Gemfibrozil is 99% protein bound. It is 98.6% bound to serum albumin, 0.8% bound to erythrocytes, and 0.8% unbound. There is negligible binding to alpha-1-acid glycoprotein. |
Groups | Approved |
Therapeutic Class | Dyslipidaemic Agents |
Manufacturer | |
Available Country | Chile, Peru |
Last Updated: | September 19, 2023 at 7:00 am |
Uses
Grifogemzilo is used as a hypolipidemic agent in conjunction with dietary modification. It is recommended in the treatment of type IIa, type IIb, type III, type IV and type V hyperlipoproteinemia.
Grifogemzilo is also used to associated treatment for these conditions: Coronary Heart Disease (CHD), Fredrickson classification type IV Hyperlipidemia, Fredrickson classification type V Hyperlipidemia
How Grifogemzilo works
Grifogemzilo activates peroxisome proliferator-activated receptor-α (PPARα), which alters lipid metabolism. This activation leads to increased HDL, apo AI, apo AII, lipoprotein lipase (LPL), inhibition of apo B synthesis, peripheral lipolysis, decreased removal of free fatty acids by the liver, and increased clearance of apoB.
Upregulated LPL reduces plasma triglyceride levels. Decreased hepatic removal of fatty acids decreases the production of triglycerides. The effects on apoB synthesis and clearance decrease VLDL production which also reduce plasma triglyceride levels.
Grifogemzilo's glucuronide metabolite is also an inhibitor of CYP2C8.
Dosage
Grifogemzilo dosage
The usual dose by mouth is 1.2 gm daily in 2 divided doses given 30 minutes before morning and evening meal. The dosage range may vary between 0.9-1.5 gm daily or as directed by the physician.
Side Effects
The most frequent adverse effect involves the G. I. Tract. Abdominal pain and epigastric pain or dyspepsia is common adverse G. I. effects. Other adverse reaction includes pruritus, rash, headache, dizziness, blurred vision, painful extremities and rarely myalgia.
Toxicity
The oral TDLO of gemfibrozil in humans is 18gm/kg/3Y. The oral LD50 in mice is 2218mg/kg and in rats is 1414mg/kg. The intraperitoneal LD50 in rats is 445mg/kg.
Patients experiencing an overdose may present with abdominal cramps, adnormal liver function tests, diarrhea, increased CPK, joint and muscle pain, nausea, and vomiting. Patients should be treated with symptomatic and supportive measures.
Precaution
Causes of secondary hyperlipidaemia such as hypothyroidism and diabetes must be treated before initiating therapy. Renal impairment; blood disorders. Periodic monitoring of the serum lipids should be done; if no adequate response after 3 mth, treatment should be withdrawn. May increase risk of cholelithiasis.
Interaction
Concomitant anticoagulant dosage may need to be reduced and frequent determinations of prothrombin carried out to confirm that the desired prothrombin level has been re-established. There have been reports of severe myositis with marked elevation of creatinine kinase and myoglobinuria when Grifogemzilo and lovastatin were used concomitantly. In most subjects who have had an unsatisfactory lipid response to either drug alone, the possible benefit of combined therapy with lovastatin and Grifogemzilo does not outweigh the risks of severe myopathy, rhabdomyolysis and acute renal failure.
Food Interaction
- Take before a meal. Take 30 minutes before meals.
Grifogemzilo 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.
Grifogemzilo Drug Interaction
Major: rosuvastatin, rosuvastatinUnknown: aspirin, aspirin, duloxetine, duloxetine, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, pregabalin, pregabalin, metoprolol, metoprolol, metoprolol, metoprolol, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol
Grifogemzilo Disease Interaction
Major: biliary cirrhosis, cholelithiasis, HDL cholesterol, rhabdomyolysis, liver disease, renal dysfunctionModerate: hematological changes
Volume of Distribution
The volume of distribution of gemfibrozil is estimated to be 0.8L/kg.
Elimination Route
Grifogemzilo is absorbed from the gastrointestinal tract.
In healthy volunteers, a 900mg oral dose of gemfibrozil has a Cmax of 46±16µg/mL with a Tmax of 2.2±1.1h. In patients with chronic renal failure, gemfibrozil has a Cmax of 13.8±11.1µg/mL with a Tmax of 2.3±1.0h. In patients with liver disease, gemfibrozil has a Cmax of 23.0±10.3µg/mL with a Tmax of 2.6±1.7h.
Half Life
Grifogemzilo has a plasma half-life of 1.5 hours. In patients with renal failure the half life is 2.4h and in patients with liver disease the half life is 2.1h.
Clearance
The clearance of gemfibrozil is estimated to be 6.0L/h.
Elimination Route
Approximately 70% of a dose of gemfibrozil is eliminated in the urine. The majority of a dose is eliminated as a glucuronide conjugate and 11 6% of a dose is eliminated in the feces.
In healthy volunteers, 0.02-0.15% of a dose was detected in the urine as unmetabolized gemfibrozil, with 7-14% detected as conjugated metabolites. In patients with renal failure, trace amounts of unmetabolized gemfibrozil is present in the urine, with 0.5-9.8% detected as conjugated metabolites. In patients with liver disease, 0.1-0.2% of a dose was detected in the urine as unmetabolized gemfibrozil, with 25-50% detected as conjugated metabolites.
Pregnancy & Breastfeeding use
Safe use in human pregnancy has not been established. It is not known whether gemfibrozil is secreted in human milk. Like most drugs, gemfibrozil should normally be avoided during pregnancy and lactation.
Contraindication
Hypersensitivity. Severe hepatic or renal dysfunction; gall stones; neonates, children, pregnancy, lactation.
Storage Condition
It should be stored in a dry place at room temperature.
Innovators Monograph
You find simplified version here Grifogemzilo
Grifogemzilo contains Gemfibrozil see full prescribing information from innovator Grifogemzilo Monograph, Grifogemzilo MSDS, Grifogemzilo FDA label