Actions of Lipifol-D3 in details
Pharmacology: Lipifol-D3 is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol. In animal models, Lipifol-D3 lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and by increasing the number of hepatic low-density lipoprotein (LDL) receptors on the cell-surface to enhance uptake and catabolism of LDL. Lipifol-D3 also reduces LDL production and the number of LDL particles.
Pharmacokinetics: Lipifol-D3 is rapidly absorbed after oral administration; maximum plasma concentrations occur within 1-2 hrs. The absolute bioavailability of Lipifol-D3 (parent drug) is approximately 14% and the systemic availability of HMG-CoA reductase inhibitory activity is approximately 30%.
Mean volume of distribution of Lipifol-D3 is approximately 381 L. Lipifol-D3 is 98% bound to plasma proteins. Lipifol-D3 is extensively metabolized to ortho- and parahydroxylate derivatives and various β-oxidation products. Approximately 70% of circulative inhibitory activity for HMG-CoA reductase is attributed to active metabolites. Lipifol-D3 and its metabolites are eliminated primarily in bile following hepatic and/or extrahepatic metabolism. Mean plasma elimination half-life (t½) of Lipifol-D3 in humans is approximately 14 hrs, but the t½ of inhibitory activity for HMG-CoA reductase is 20-30 hrs due to the contribution of active metabolites. Less than 2% of a dose of Lipifol-D3 is recovered in urine following oral administration.
How should I take Lipifol-D3?
Take Lipifol-D3 only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it or for a longer time than your doctor ordered.
In addition to Lipifol-D3, your doctor may change your diet to one that is low in fat, sugar, and cholesterol. Carefully follow your doctor's orders about any special diet.
Take Lipifol-D3 at the same time each day.
Swallow the tablet whole. Do not break, crush, or chew it. Take Lipifol-D3 with or without food.
Do not drink large amounts of alcohol with Lipifol-D3. This could cause unwanted effects on the liver.
Tell your doctor if you regularly drink grapefruit juice. Drinking large amounts of grapefruit juice (more than 1.2 liters each day) while you take Lipifol-D3 may increase your risk of muscle injury and could result in kidney problems.
Dosing
The dose of Lipifol-D3 will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Lipifol-D3. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
- For oral dosage form (tablets):
- For high cholesterol:
- Adults—At first, 10 or 20 milligrams (mg) once a day. Some patients may need to start at 40 mg per day. Your doctor may increase your dose as needed. However, the dose is usually not more than 80 mg per day.
- Children 10 to 17 years of age—At first, 10 mg once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 20 mg per day.
- Children younger than 10 years of age)—Use and dose must be determined by your doctor.
- For high cholesterol:
Missed Dose
If you miss a dose of Lipifol-D3, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
However, do not take 2 doses of Lipifol-D3 within 12 hours.
Storage
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
Lipifol-D3 administration
Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Do not break an Lipifol-D3 tablet unless your doctor has told you.
Lipifol-D3 is usually taken once a day, with or without food. Take the medicine at the same time each day. Your doctor may occasionally change your dose to make sure you get the best results.
You may need to stop using Lipifol-D3 for a short time if you have:
- uncontrolled seizures;
- an electrolyte imbalance (such as high or low potassium levels in your blood);
- severely low blood pressure;
- a severe infection or illness; or
- surgery or a medical emergency.
To be sure this medicine is helping your condition, your blood will need to be tested often. Visit your doctor regularly.
Lipifol-D3 is only part of a complete program of treatment that also includes diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely. You may need to take Lipifol-D3 on a long-term basis for the treatment of high cholesterol.
Store at room temperature away from moisture, heat, and light.
Lipifol-D3 pharmacology
Mechanism Of Action
Lipifol-D3 is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol. Cholesterol and triglycerides circulate in the bloodstream as part of lipoprotein complexes. With ultracentrifugation, these complexes separate into HDL (high-density lipoprotein), IDL (intermediate-density lipoprotein), LDL (low-density lipoprotein), and VLDL (very-low-density lipoprotein) fractions. Triglycerides (TG) and cholesterol in the liver are incorporated into VLDL and released into the plasma for delivery to peripheral tissues. LDL is formed from VLDL and is catabolized primarily through the high-affinity LDL receptor. Clinical and pathologic studies show that elevated plasma levels of total cholesterol (total-C), LDL-cholesterol (LDL-C), and apolipoprotein B (apo B) promote human atherosclerosis and are risk factors for developing cardiovascular disease, while increased levels of HDL-C are associated with a decreased cardiovascular risk.
In animal models, Lipifol-D3 lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and by increasing the number of hepatic LDL receptors on the cell surface to enhance uptake and catabolism of LDL; Lipifol-D3 also reduces LDL production and the number of LDL particles. Lipifol-D3 reduces LDL-C in some patients with homozygous familial hypercholesterolemia (FH), a population that rarely responds to other lipid-lowering medication(s).
A variety of clinical studies have demonstrated that elevated levels of total-C, LDL-C, and apo B (a membrane complex for LDL-C) promote human atherosclerosis. Similarly, decreased levels of HDL-C (and its transport complex, apo A) are associated with the development of atherosclerosis. Epidemiologic investigations have established that cardiovascular morbidity and mortality vary directly with the level of total-C and LDL-C, and inversely with the level of HDL-C.
Lipifol-D3 reduces total-C, LDL-C, and apo B in patients with homozygous and heterozygous FH, nonfamilial forms of hypercholesterolemia, and mixed dyslipidemia. Lipifol-D3 also reduces VLDL-C and TG and produces variable increases in HDL-C and apolipoprotein A-1. Lipifol-D3 reduces total-C, LDL-C, VLDL-C, apo B, TG, and non-HDL-C, and increases HDL-C in patients with isolated hypertriglyceridemia. Lipifol-D3 reduces intermediate density lipoprotein cholesterol (IDL-C) in patients with dysbetalipoproteinemia.
Like LDL, cholesterol-enriched triglyceride-rich lipoproteins, including VLDL, intermediate density lipoprotein (IDL), and remnants, can also promote atherosclerosis. Elevated plasma triglycerides are frequently found in a triad with low HDL-C levels and small LDL particles, as well as in association with non-lipid metabolic risk factors for coronary heart disease. As such, total plasma TG has not consistently been shown to be an independent risk factor for CHD. Furthermore, the independent effect of raising HDL or lowering TG on the risk of coronary and cardiovascular morbidity and mortality has not been determined.
Pharmacodynamics
Lipifol-D3, as well as some of its metabolites, are pharmacologically active in humans. The liver is the primary site of action and the principal site of cholesterol synthesis and LDL clearance. Drug dosage, rather than systemic drug concentration, correlates better with LDL-C reduction. Individualization of drug dosage should be based on therapeutic response.
Pharmacokinetics
Absorption
Lipifol-D3 is rapidly absorbed after oral administration; maximum plasma concentrations occur within 1 to 2 hours. Extent of absorption increases in proportion to Lipifol-D3 dose. The absolute bioavailability of Lipifol-D3 (parent drug) is approximately 14% and the systemic availability of HMGCoA reductase inhibitory activity is approximately 30%. The low systemic availability is attributed to presystemic clearance in gastrointestinal mucosa and/or hepatic first-pass metabolism. Although food decreases the rate and extent of drug absorption by approximately 25% and 9%, respectively, as assessed by Cmax and AUC, LDL-C reduction is similar whether Lipifol-D3 is given with or without food. Plasma Lipifol-D3 concentrations are lower (approximately 30% for Cmax and AUC) following evening drug administration compared with morning. However, LDL-C reduction is the same regardless of the time of day of drug administration.
Distribution
Mean volume of distribution of Lipifol-D3 is approximately 381 liters. Lipifol-D3 is ≥98% bound to plasma proteins. A blood/plasma ratio of approximately 0.25 indicates poor drug penetration into red blood cells. Based on observations in rats, Lipifol-D3 is likely to be secreted in human milk.
Metabolism
Lipifol-D3 is extensively metabolized to ortho- and parahydroxylated derivatives and various beta-oxidation products. In vitro inhibition of HMG-CoA reductase by ortho- and parahydroxylated metabolites is equivalent to that of Lipifol-D3. Approximately 70% of circulating inhibitory activity for HMG-CoA reductase is attributed to active metabolites. In vitro studies suggest the importance of Lipifol-D3 metabolism by cytochrome P450 3A4, consistent with increased plasma concentrations of Lipifol-D3 in humans following co-administration with erythromycin, a known inhibitor of this isozyme. In animals, the ortho-hydroxy metabolite undergoes further glucuronidation.
Excretion
Lipifol-D3 and its metabolites are eliminated primarily in bile following hepatic and/or extrahepatic metabolism; however, the drug does not appear to undergo enterohepatic recirculation. Mean plasma elimination half-life of Lipifol-D3 in humans is approximately 14 hours, but the half-life of inhibitory activity for HMG-CoA reductase is 20 to 30 hours due to the contribution of active metabolites. Less than 2% of a dose of Lipifol-D3 is recovered in urine following oral administration.
Specific Populations
Geriatric
Plasma concentrations of Lipifol-D3 are higher (approximately 40% for Cmax and 30% for AUC) in healthy elderly subjects (age ≥65 years) than in young adults. Clinical data suggest a greater degree of LDL-lowering at any dose of drug in the elderly patient population compared to younger adults.
Pediatric
Pharmacokinetic data in the pediatric population are not available.
Gender
Plasma concentrations of Lipifol-D3 in women differ from those in men (approximately 20% higher for Cmax and 10% lower for AUC); however, there is no clinically significant difference in LDL-C reduction with Lipifol-D3 between men and women.
Renal Impairment
Renal disease has no influence on the plasma concentrations or LDL-C reduction of Lipifol-D3; thus, dose adjustment in patients with renal dysfunction is not necessary.
Hemodialysis
While studies have not been conducted in patients with end-stage renal disease, hemodialysis is not expected to significantly enhance clearance of Lipifol-D3 since the drug is extensively bound to plasma proteins.
Hepatic Impairment
In patients with chronic alcoholic liver disease, plasma concentrations of Lipifol-D3 are markedly increased. Cmax and AUC are each 4-fold greater in patients with Childs-Pugh A disease. Cmax and AUC are approximately 16-fold and 11-fold increased, respectively, in patients with Childs-Pugh B disease.
TABLE 3. Effect of Co-administered Drugs on the Pharmacokinetics of Lipifol-D3
| Co-administered drug and dosing regimen | Lipifol-D3 | ||
| Dose (mg) | Change in AUC* | Change in Cmax* | |
| Significantly different from simvastatin, ANCOVA, p ≤0.05 |
The impact on clinical outcomes of the differences in lipid-altering effects between treatments shown in Table 7 is not known. Table 7 does not contain data comparing the effects of Lipifol-D3 10 mg and higher doses of lovastatin, pravastatin, and simvastatin. The drugs compared in the studies summarized in the table are not necessarily interchangeable.
Hypertriglyceridemia (Fredrickson Type IV)
The response to Lipifol-D3 in 64 patients with isolated hypertriglyceridemia treated across several clinical trials is shown in the table below (Table 8). For the Lipifol-D3-treated patients, median (min, max) baseline TG level was 565 (267
References
- DailyMed. "ASCORBIC ACID; BIOTIN; CYANOCOBALAMIN; DEXPANTHENOL; ERGOCALCIFEROL; FOLIC ACID; NIACINAMIDE; PHYTONADIONE; PYRIDOXINE HYDROCHLORIDE; RIBOFLAVIN 5'-PHOSPHATE SODIUM; THIAMINE HYDROCHLORIDE; VITAMIN A; VITAMIN E: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- DailyMed. "ASCORBIC ACID; BIOTIN; CHOLECALCIFEROL; CYANOCOBALAMIN; DEXPANTHENOL; FOLIC ACID; NIACINAMIDE; PYRIDOXINE; RIBOFLAVIN; THIAMINE; TOCOPHEROL ACETATE; VITAMIN A; VITAMIN K: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- DailyMed. "CHOLECALCIFEROL: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Lipifol-D3 are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Lipifol-D3. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
Consumer reported administration
No survey data has been collected yetConsumer reviews
There are no reviews yet. Be the first to write one! |
Information checked by Dr. Sachin Kumar, MD Pharmacology
