Actions of Rosuchen in details
Pharmacology: style="font-style: italic;">Pharmacodynamics: Rosuchen is a selective and competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme that converts HMG-CoA to mevalonate, a precursor of cholesterol. Rosuchen produces its lipid-modifying effects in 2 ways. First, it increases the number of hepatic low-density lipoprotein (LDL) receptors on the cell surface to enhance uptake and catabolism of LDL. Second, Rosuchen inhibits hepatic synthesis of very low-density lipoprotein (VLDL), which reduces the total number of VLDL and LDL particles.
style="font-style: italic;">Pharmacokinetics: Absorption: Peak plasma concentrations (Cmax) of Rosuchen were reached 3-5 hrs following oral dosing. Both Cmax and area under the plasma concentration time curve (AUC) increase in approximate proportion to Rosuchen dose.
Distribution: Mean volume of distribution at steady state of Rosuchen is approximately 134 L. Rosuchen is 88% bound to plasma proteins, mostly albumin.
Metabolism: Rosuchen is not extensively metabolized. The major metabolite of Rosuchen is N-desmethyl Rosuchen which have approximately 1/6-½ the HMG-CoA reductase inhibitory activity of Rosuchen. Overall, >90% of active plasma HMG-CoA reductase inhibitory activity is accounted for by Rosuchen.
Elimination: Following oral administration, Rosuchen and its metabolites are primarily excreted in the faeces (90%). The elimination half-life (t½) of Rosuchen is approximately 19 hrs.
How should I take Rosuchen?
Use Rosuchen only as directed by your doctor. Do not use more of it, do not use it more often, or do not use it for a longer time than your doctor ordered. Also, Rosuchen works best if there is a constant amount in the blood. To help keep this amount constant, do not miss any doses and take the medicine at the same time each day.
In addition to Rosuchen, 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.
Rosuchen comes with a patient information insert. Read and follow the instructions in the insert carefully. Talk to your doctor if you have any questions.
Swallow the tablet whole. Do not break, crush, or chew it. You may take Rosuchen with or without food.
If you need to take an antacid that contains aluminum and magnesium (e.g., Maalox®), take the antacid at least 2 hours after you take Rosuchen.
Do not drink large amounts of alcohol while taking Rosuchen. This could cause side effects on the liver.
Dosing
The dose of Rosuchen 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 Rosuchen. 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 and atherosclerosis:
- Adults—5 to 40 milligrams (mg) once a day.
- Children 10 to 17 years of age—5 to 20 mg per day.
- Children younger than 10 years of age—Use and dose must be determined by your doctor.
- For high cholesterol and atherosclerosis:
Missed Dose
If you miss a dose of Rosuchen, 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 Rosuchen 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.
Rosuchen 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.
Rosuchen 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 Rosuchen 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;
- dehydration; or
- surgery or a medical emergency.
To be sure this medicine is helping your condition and is not causing harmful effects, your blood will need to be tested often. Visit your doctor regularly.
Rosuchen 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 Rosuchen on a long-term basis for the treatment of high cholesterol.
Store at room temperature away from moisture, heat, and light.
Rosuchen pharmacology
Mechanism Of Action
Rosuchen is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy3methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol. In vivo studies in animals, and in vitro studies in cultured animal and human cells have shown Rosuchen to have a high uptake into, and selectivity for, action in the liver, the target organ for cholesterol lowering. In in vivo and in vitro studies, Rosuchen produces its lipid-modifying effects in two ways. First, it increases the number of hepatic LDL receptors on the cell-surface to enhance uptake and catabolism of LDL. Second, Rosuchen inhibits hepatic synthesis of VLDL, which reduces the total number of VLDL and LDL particles.
Pharmacokinetics
Absorption
In clinical pharmacology studies in man, peak plasma concentrations of Rosuchen were reached 3 to 5 hours following oral dosing. Both Cmax and AUC increased in approximate proportion to Rosuchen dose. The absolute bioavailability of Rosuchen is approximately 20%.
Administration of Rosuchen with food did not affect the AUC of Rosuchen.
The AUC of Rosuchen does not differ following evening or morning drug administration.
Distribution
Mean volume of distribution at steady-state of Rosuchen is approximately 134 liters. Rosuchen is 88% bound to plasma proteins, mostly albumin. This binding is reversible and independent of plasma concentrations.
Metabolism
Rosuchen is not extensively metabolized; approximately 10% of a radiolabeled dose is recovered as metabolite. The major metabolite is N-desmethyl Rosuchen, which is formed principally by cytochrome P450 \ 2C9, and in vitro studies have demonstrated that N-desmethyl Rosuchen has approximately one-sixth to one-half the HMGCoA reductase inhibitory activity of the parent compound. Overall, greater than 90% of active plasma HMGCoA reductase inhibitory activity is accounted for by the parent compound.
Excretion
Following oral administration, Rosuchen and its metabolites are primarily excreted in the feces (90%). The elimination half-life (t½) of Rosuchen is approximately 19 hours.
After an intravenous dose, approximately 28% of total body clearance was via the renal route, and 72% by the hepatic route.
Specific Populations
Race
A population pharmacokinetic analysis revealed no clinically relevant differences in pharmacokinetics among Caucasian, Hispanic, and Black or Afro-Caribbean groups. However, pharmacokinetic studies, including one conducted in the US, have demonstrated an approximate 2fold elevation in median exposure (AUC and Cmax) in Asian subjects when compared with a Caucasian control group.
Gender
There were no differences in plasma concentrations of Rosuchen between men and women.
Pediatric
In a population pharmacokinetic analysis of two pediatric trials involving patients with heterozygous familial hypercholesterolemia 10 to 17 years of age and 8 to 17 years of age, respectively, Rosuchen exposure appeared comparable to or lower than Rosuchen exposure in adult patients.
Geriatric
There were no differences in plasma concentrations of Rosuchen between the nonelderly and elderly populations (age ≥ 65 years).
Renal Impairment
Mild to moderate renal impairment (CLcr ≥ 30 mL/min/1.73 m²) had no influence on plasma concentrations of Rosuchen. However, plasma concentrations of Rosuchen increased to a clinically significant extent (about 3fold) in patients with severe renal impairment (CLcr < 30 mL/min/1.73 m²) not receiving hemodialysis compared with healthy subjects (CLcr > 80 mL/min/1.73 m²).
Hemodialysis
Steady-state plasma concentrations of Rosuchen in patients on chronic hemodialysis were approximately 50% greater compared with healthy volunteer subjects with normal renal function.
Hepatic Impairment
In patients with chronic alcohol liver disease, plasma concentrations of Rosuchen were modestly increased.
In patients with ChildPugh A disease, Cmax and AUC were increased by 60% and 5%, respectively, as compared with patients with normal liver function. In patients with ChildPugh B disease, Cmax and AUC were increased 100% and 21%, respectively, compared with patients with normal liver function.
Drug-Drug Interactions
Rosuchen clearance is not dependent on metabolism by cytochrome P450 3A4 to a clinically significant extent.
Rosuchen is a substrate for certain transporter proteins including the hepatic uptake transporter organic anion-transporting polyprotein 1B1 (OATP1B1) and efflux transporter breast cancer resistance protein (BCRP). Concomitant administration of Rosuchen with medications that are inhibitors of these transporter proteins (e.g. cyclosporine, certain HIV protease inhibitors) may result in increased Rosuchen plasma concentrations and an increased risk of myopathy. It is recommended that prescribers consult the relevant product information when considering administration of such products together with Rosuchen.
Table 4: Effect of Coadministered Drugs on Rosuchen Systemic Exposure
Box plots are a representation of the 25th, 50th, and 75th percentile values, with whiskers representing the 10th and 90th percentile values. Mean baseline LDLC: 189 mg/dL
Table 7: Percent Change in LDL-C From Baseline to Week 6 (LS Mean*) by Treatment Group (Sample Sizes Ranging from 156-167 Patients Per Group)
The individual components of the primary end point are presented in Figure 3. Rosuchen significantly reduced the risk of nonfatal myocardial infarction, nonfatal stroke, and arterial revascularization procedures. There were no significant treatment differences between the Rosuchen and placebo groups for death due to cardiovascular causes or hospitalizations for unstable angina.
Rosuchen significantly reduced the risk of myocardial infarction (6 fatal events and 62 nonfatal events in placebo-treated subjects vs. 9 fatal events and 22 nonfatal events in Rosuchen-treated events in placebo-treated subjects vs. 9 fatal events and 22 nonfatal events in Rosuchen-treated subjects) and the risk of stroke (6 fatal events and 58 nonfatal events in placebo-treated subjects vs. 3 fatal events and 30 nonfatal events in Rosuchen-treated subjects).
In a post-hoc subgroup analysis of JUPITER subjects (n=1405; Rosuchen=725, placebo=680) with a hsCRP ≥ 2 mg/L and no other traditional risk factors (smoking, BP ≥ 140/90 or taking antihypertensives, low HDLC) other than age, after adjustment for high HDLC, there was no significant treatment benefit with Rosuchen treatment.
Figure 3: Major CV Events by Treatment Group in JUPITER
At one year, Rosuchen increased HDLC and reduced LDLC, hsCRP, total cholesterol and serum triglyceride levels (p < 0.001 for all versus placebo).
References
- DailyMed. "ROSUVASTATIN CALCIUM: 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).
- NCIt. "Rosuvastatin: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
- EPA DSStox. "Rosuvastatin: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Rosuchen 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 Rosuchen. 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
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Information checked by Dr. Sachin Kumar, MD Pharmacology
