Chemistatin: Medicine to treat high blood cholesterol

2021-07-02 07:22 PM

Chemistatin reduces elevated LDL-cholesterol, total cholesterol and triglycerides and increases HDL-cholesterol. The drug also decreased ApoB, nonHDL-C, VLDL-C, VLDL-TG and increased ApoA-I.

Ingredient

Chemistatin 10mg Each tablet: Rosuvastatin calcium equivalent to rosuvastatin 10mg.

Chemistatin 20mg Each tablet: Rosuvastatin calcium equivalent to rosuvastatin 20mg.

Describe

Chemistatin 10mg: Pink round film-coated tablets, biconvex, one side engraved with the letters ROS and the number 10, one side smooth.

Chemistatin 20mg: Pink round film-coated tablets, biconvex, one side engraved with the letters ROS and the number 20, one side smooth.

Pharmacodynamic

Pharmacotherapeutic group

HMG-CoA reductase inhibitors.

ATC code: C10A A07.

Mechanism of activation

Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the enzyme that catalyzes the conversion of 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a cholesterol precursor. The main site of action of rosuvastatin is the liver, which is the target organ for cholesterol lowering.

Rosuvastatin increases the number of LDL receptors on the cell surface of the liver, thereby increasing the absorption and catabolism of LDL and inhibits the synthesis of VLDL in the liver, thereby reducing the components of VLDL and LDL.

Pharmacodynamic effects

Rosuvastatin reduces elevated LDL-cholesterol, total cholesterol and triglycerides and increases HDL-cholesterol. The drug also decreased ApoB, nonHDL-C, VLDL-C, VLDL-TG and increased ApoA-I. Rosuvastatin also reduced the LDL-C/HDL-C, total C/HDL-C, nonHDL-C/HDL-C and ApoB/ApoA-I ratios.

Pharmacokinetics

Absorb

Rosuvastatin is incompletely absorbed from the gastrointestinal tract, with a bioavailability of about 20%. Peak plasma concentrations are reached approximately 5 hours after oral administration.

Distribution

Rosuvastatin is widely distributed in the liver, which is the major site of cholesterol synthesis and clearance of LDL-C. The volume of distribution of rosuvastatin is approximately 134 L. Approximately 90% of rosuvastatin is bound to plasma proteins, mainly to albumin.

Biotransformation

Rosuvastatin is poorly metabolized (approximately 10%). In vitro metabolism studies using human hepatocytes have determined that rosuvastatin is a weak substrate for cytochrome P450 metabolism. CYP2C9 is the major coenzyme involved in metabolism, CYP2C19, CYP3A4 and CYP2D6 participate to a lesser extent. The major metabolites identified were N-desmethyl and lactone. The N-desmethyl metabolite is approximately 50% less active than rosuvastatin while the lactone form is clinically inactive. Rosuvastatin accounts for more than 90% of circulating HMG-CoA reductase inhibitory activity.

Elimination

The plasma half-life is approximately 19 hours. Approximately 90% of an oral dose of rosuvastatin is excreted in the feces (including absorbed and unabsorbed active substances) and the remainder is excreted in the urine. Approximately 5% of an administered dose is excreted unchanged in the urine.

Special patient groups

Age and gender

The effects of age or sex on the pharmacokinetics of rosuvastatin are not clinically relevant in adults. The pharmacokinetics of rosuvastatin in children and adolescents with heterozygous familial hypercholesterolemia were similar in adult volunteers.

Race

Pharmacokinetic studies have shown an approximately 2-fold increase in AUC and Cmax in Asians (Japan, China, Philippines, Vietnam and Korea) compared with Western Caucasians. A population pharmacokinetic analysis revealed no clinically significant differences in pharmacokinetics between black and white populations.

Patients with renal failure

In a study in subjects with varying degrees of renal impairment, mild to moderate renal disease did not affect plasma concentrations of rosuvastatin or its N-desmethyl metabolite. Patients with severe renal impairment (plasma creatinine clearance < 30 mL/min) had a 3-fold increase in plasma drug concentrations and a 9-fold increase in N-desmethyl metabolite concentrations compared with healthy volunteers. . Steady-state plasma concentrations of rosuvastatin in patients undergoing hemodialysis are approximately 50% higher than in healthy volunteers.

Patients with liver failure

In human studies with varying degrees of hepatic impairment, there was no evidence of increased exposure to rosuvastatin over time and concentration in patients with Child-Pugh scores less than 7. However, The 2 patients with Child-Pugh scores of 8 and 9 had at least 2 times more rosuvastatin exposure by concentration and duration of rise than those with lower Child-Pugh scores. There is no experience in patients with Child-Pugh scores greater than 9.

Children

Two pharmacokinetic studies with rosuvastatin (tablet formulation) in patients 10 to 17 years of age with heterozygous familial hypercholesterolemia or 6 to 17 years of age (214 patients total) demonstrated that exposure Drug exposure in children may be equal to or lower than in adult patients.

Indications and uses

Treatment of high blood cholesterol

Primary hypercholesterolemia (type IIa including heterozygous familial hypercholesterolaemia) or mixed dyslipidemia (type IIb): As an adjunct to diet when the response to diet is inadequate diet and other non-pharmacological therapies (eg exercise, weight loss).

Primary dyslipidemia (type III hyperlipoproteinemia): Chemistatin is indicated as an adjunct to diet in the treatment of patients with primary dyslipidemia (type III hyperlipoproteinemias). ).

Homozygous familial hypercholesterolemia: Used as an adjunct to diet and other lipid-lowering treatments (such as hemodialysis) or when these therapies are not appropriate.

Primary prevention of cardiovascular disease

In individuals without clinical evidence of coronary heart disease but at risk for cardiovascular disease, such as men over 50 years of age, women over 60 years of age, hsCRP above 2 mg/L and at least 1 additional risk factor Cardiovascular disease such as hypertension, low HDL-C, smoking or family history of premature coronary heart disease, rosuvastatin is indicated to: Reduce the risk of stroke, reduce the risk of myocardial infarction and reduce the risk of cardiovascular disease. coronary reperfusion procedures.

Dosage and Administration

Before initiating treatment, patients should follow a standard low-cholesterol diet that should be maintained for the duration of treatment. Dosage should be individualized on a case-by-case basis based on treatment goals and patient response.

Adults

Treatment of high blood cholesterol

The recommended starting dose is 5 mg orally once a day, if necessary the dose can be increased to 20 mg after 4 weeks. The dose should only be increased to 40 mg for patients with severe hypercholesterolemia at high risk for cardiovascular disease (especially patients with familial hypercholesterolemia) who have not achieved the therapeutic goal of 20 mg. In this case, the patient should be closely monitored.

In patients receiving the combination of atazanavir, atazanavir/ritonavir or lopinavir and ritonavir, a dose of rosuvastatin 10 mg orally once daily is recommended.
 
In patients receiving gemfibrozil, a dose of rosuvastatin 10 mg orally once daily is recommended.

Prevention of cardiovascular events

The daily dose is 20 mg.

Children

The use of medicines in children should be carried out by qualified medical personnel.

Children and adolescents 10-17 years of age with heterozygous familial hypercholesterolemia

The usual starting dose is 5 mg/day. The usual dose range is 5-20 mg orally once daily. The dose should be adjusted according to the patient's response and tolerability in pediatric patients. In children and adolescents who should be fed a standard low-cholesterol diet prior to initiating treatment with rosuvastatin, this diet should be continued for the duration of treatment. The safety and effectiveness of doses greater than 20 mg have not been studied in this patient population.

Children under 10 years old

Experience in children under 10 years of age is limited with a small number of patients (ages 8-10) with homozygous familial hypercholesterolemia. Therefore, this drug is not indicated for children under 10 years of age.

Elderly

It is recommended to start with a dose of 5 mg once daily in patients over 70 years of age and no dose adjustment is required for age.

Patients with renal failure

No dose adjustment is required in patients with mild to moderate renal impairment. The recommended starting dose is 5 mg in patients with moderate renal impairment (creatinine clearance less than 60 mL/min). A dose of 40 mg is contraindicated in patients with moderate renal impairment. This drug is contraindicated in patients with severe renal impairment at any dose level.

Patients with liver failure

There was no increase in systemic exposure to rosuvastatin in patients with a Child-Pugh index less than 7. However, systemic exposure was increased in patients with a Child-Pugh index between 8 and 9. In this patient, evaluation of renal function should be considered. There is no experience in patients with a Child-Pugh index greater than 9. This drug is contraindicated in patients with advanced liver disease.

Patients at risk of myopathy

The recommended starting dose is 5 mg. In some patients, doses up to 40 mg are contraindicated.

Patient is Asian

Consider starting with rosuvastatin 5 mg once daily due to increased plasma concentrations of rosuvastatin. Attention should be paid to increased exposure in Asian patients when inadequate control is achieved with doses above 20 mg/day. The 40 mg dose is contraindicated in these patients.

Combination therapy

The risk of myopathy (including paroxysmal globinuria, also known as acute rhabdomyolysis) is increased when rosuvastatin is co-administered with certain drugs that may increase rosuvastatin plasma concentrations (eg, ciclosporin and some protease inhibitors including including the combination of ritonavir with atazanavir, lopinavir, and/or tipranavir). In patients receiving the combination of atazanavir, atazanavir/ritonavir or lopinavir/ritonavir, a dose of rosuvastatin 10 mg orally once daily is recommended.

Co-administration of rosuvastatin with ciclosporin or fibrates such as gemfibrozil is contraindicated.

How to use

The drug is taken orally with water and can be taken with or without food at any time of the day.

Warning

This drug is for a doctor's prescription.

Prior to administration of rosuvastatin, hypercholesterolemia should be controlled with appropriate diet, exercise, weight loss in obese patients, and treatment of other underlying medical conditions.

Care should be taken when administering rosuvastatin to patients with risk factors for muscle damage. Rosuvastatin has the potential to cause adverse reactions in the muscular system such as muscle atrophy, myositis, especially in patients with risk factors such as patients over 65 years of age, patients with hypothyroidism not under control, the patient has kidney disease. It is necessary to closely monitor for adverse reactions during drug administration.

In patients with hypercholesterolemia secondary to hypothyroidism or nephrotic syndrome, these conditions must be treated prior to initiating rosuvastatin.

Liver enzyme abnormalities may occur. Liver enzyme testing should be performed before and at 12 weeks after initiation of therapy and after dose escalation, and then periodically.

Consider creatine kinase (CK) monitoring in cases of:

Before starting statin therapy

CK testing should be performed in the following cases: Impaired renal function, hypothyroidism, personal or family history of hereditary myopathy, history of myopathy due to previous statin or fibrate use, history of liver disease and/or heavy alcohol consumption, elderly patients (over 70 years of age) with risk factors for rhabdomyolysis, the possibility of drug interactions, and some special patient populations. In these cases, the benefits/risks should be weighed and the patient monitored clinically during statin therapy. If CK test results are above 5 times the upper limit of normal, statin therapy should not be initiated.

During statin therapy

Patients should immediately notify when there are muscle symptoms such as muscle pain, stiffness, muscle weakness... When these symptoms are present, the patient needs to do a CK test to have appropriate interventions.

The risk of myopathy and rhabdomyolysis is increased when rosuvastatin is co-administered with high doses of niacin (over 1 g/day), fibric acid derivatives (gemfibrozil and other fibrates).

Concomitant use of statins with lipid-lowering agents of the statin class with HIV drugs as well as hepatitis C virus (HCV) drugs may increase the risk of muscle damage, especially rhabdomyolysis, and kidney failure. Damage leading to renal failure and possibly death: do not exceed 10 mg rosuvastatin once daily with atazanavir, atazanavir + ritonavir, lopinavir + ritonavir.

The incidence of myositis and myopathy is increased in patients receiving other HMG-CoA reductase inhibitors with fibric and derivatives including gemfibrozil, ciclosporin, nicotinic acid, azole antifungals, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when used with certain HMG-CoA reductase inhibitors. Therefore, rosuvastatin should not be combined with gemfibrozil.

Rosuvastatin should not be used in patients with serious acute muscle disease or at risk of renal failure secondary to rhabdomyolysis (eg, infection, hypotension, major surgery, trauma, electrolyte, endocrine disturbances, etc.) and severe metabolism, or uncontrolled seizures).

Tell your doctor right away if during treatment you have signs or symptoms of muscle pain, weakness, fever, dark urine, nausea or vomiting.

Proteinuria and hematuria have been observed in patients receiving high doses of rosuvastatin, particularly at the 40 mg dose. Dosage should be reduced in patients with persistent proteinuria and/or hematuria of unknown cause during routine urinalysis.

Race

Pharmacokinetic studies have shown an increase in exposure over time and concentration in Asian patients compared with Caucasians.

Effects on the endocrine system

Increased HbA1c and increased fasting blood glucose have been reported with HMG-CoA reductase inhibitors, including rosuvastatin. Based on rosuvastatin clinical data, this increase may in some cases exceed the threshold for defining diabetes.

Children

The safety and efficacy of rosuvastatin in 10- to 17-year-old patients with heterozygous familial hypercholesterolemia were evaluated in a 12-week controlled clinical trial, followed by an open-label phase. 40 weeks. Patients treated with rosuvastatin 5 mg, 10 mg, and 20 mg daily had generally similar adverse drug reactions (ADRs) data to those in the placebo group. Although not all of the adverse reactions observed in the adult population have been reported in clinical trials in children and adolescents, cautions and cautions should be considered in children and adolescents. Teenagers should be similar to adults. No effects of rosuvastatin were found on growth, body weight, body mass index or reproductive system maturation in pediatric patients (aged 10 to 17 years). Adolescent female patients should be advised to use appropriate contraception during treatment with rosuvastatin. No studies in controlled clinical trials involving prepubertal patients or patients younger than 10 years of age have received rosuvastatin. Doses of rosuvastatin greater than 20 mg have not been studied in pediatric patients. The study of pediatric and adolescent patients with homozygous familial hypercholesterolemia was limited to 8 patients.

Excipients

The drug contains lactose. Patients with hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Note before using in cases

Renal impairment, hypothyroidism, personal or family history of hereditary myopathy, history of myotoxicity with other HMG-CoA reductase inhibitors or fibrates, alcoholism and/or medical history liver, over 70 years of age, conditions that may cause increased plasma concentrations, concomitant use of fibrates.

Effects of the drug on the ability to drive and use machinery

When driving or operating machinery, be aware that dizziness may occur during treatment.

Overdose

Symptom

Information on overdose is limited.

To solve

There is no specific treatment for drug overdose. If an overdose occurs, symptomatic treatment and supportive measures are essential. Liver function and creatinine kinase levels should be monitored. Hemodialysis may not provide any benefit.

Contraindications

Patients with hypersensitivity to rosuvastatin or any of the excipients.

Patients with advanced liver disease including persistent and unexplained elevations in serum transaminases, and when serum transaminases are elevated more than 3 times the upper limit of normal (ULN).

Patients with severe renal impairment (creatinine clearance less than 30mL/min).

The patient has a muscle disease.

Patient is taking concomitantly with ciclosporin.

Pregnant and lactating women.

Women of childbearing age who are not using appropriate contraception.

Use in excess of 10 mg rosuvastatin once/day in combination with atazanavir, atazanavir + ritonavir, lopinavir + ritonavir.

Patients with risk factors for myopathy/rhabdomyolysis at no 40 mg dose are as follows: Moderate renal impairment (creatinine clearance less than 60 mL/min), hypothyroidism, family history personal or family history of hereditary muscle disorders, previous history of myotoxicity with another HMG-CoA reductase inhibitor or fibrates, alcoholism, conditions in which plasma drug levels are may increase, Asian, take with fibrates.

Use in pregnant and lactating women

Pregnant

Rosuvastatin is contraindicated for pregnant women.

Women of childbearing age should use appropriate contraception. Since cholesterol and other cholesterol biosynthetic products are essential for fetal development, the potential risk of HMG-CoA reductase inhibition outweighs the benefits of rosuvastatin treatment during pregnancy. pregnant. Animal studies have shown little evidence of reproductive toxicity. If a patient becomes pregnant during treatment with rosuvastatin, the drug should be discontinued immediately.

Breastfeeding Women

Rosuvastatin is contraindicated for nursing women. Rosuvastatin is excreted in the milk of test rats. There are no data on excretion into human milk.

Interactive

Contraindicated interactions

Alcohol: Do not drink alcohol while taking rosuvastatin because alcohol can increase triglycerides and damage the liver.

High-dose niacin, fibric acid derivative: The risk of myopathy and rhabdomyolysis is increased when rosuvastatin is co-administered with high doses of niacin (over 1 g/day), fibric acid derivatives (gemfibrozil and other fibrates). A dose of 40 mg rosuvastatin is contraindicated with a fibrate (eg, gemfibrozil).

Ciclosporin: During concomitant treatment with rosuvastatin and ciclosporin, the average rosuvastatin AUC values ​​were 7 times higher than in healthy volunteers. Rosuvastatin is contraindicated in patients receiving ciclosporin. Concomitant administration has no effect on plasma concentrations of ciclosporin.

HIV drugs, hepatitis C drugs: Contraindicated to use more than 10 mg rosuvastatin once/day when combined with atazanavir, atazanavir + ritonavir, lopinavir + ritonavir.

Interact with caution

HIV drugs, hepatitis C drugs: Concomitant use of lipid-lowering statins with HIV drugs as well as hepatitis C virus (HCV) drugs may increase the risk of muscle damage, especially rhabdomyolysis, kidney failure leading to renal failure and possibly death: do not exceed 10 mg rosuvastatin once daily with atazanavir, atazanavir + ritonavir, lopinavir + ritonavir.

Oral Anticoagulants: Rosuvastatin significantly increased INR in patients receiving coumarin anticoagulants. Caution should be exercised when coumarin anticoagulants and rosuvastatin are co-administered. In patients receiving coumarin anticoagulants and rosuvastatin concomitantly, the INR should be determined prior to initiating treatment with rosuvastatin and monitored frequently throughout the early treatment period to ensure that there is no change in the INR. significant happens.

Aluminum and magnesium hydroxide antacids: Co-administration of rosuvastatin with a suspension of antacids containing aluminum and magnesium hydroxide reduces plasma concentrations of rosuvastatin by approximately 50%. Antacids should be taken 2 hours after taking rosuvastatin.

Ezetimibe: Concomitant administration of 10 mg rosuvastatin and 10 mg ezetimibe resulted in a 1.2-fold increase in rosuvastatin AUC in hypercholesterolemic patients. A pharmacodynamic interaction in terms of Adverse Reactions (ADR) between rosuvastatin and ezetimibe cannot be excluded.

Colchicine: Cases of muscle damage, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors, including rosuvastatin, concomitantly with colchicine, and caution should be exercised when rosuvastatin is co-administered with colchicine.

Erythromycin: Co-administration of rosuvastatin and erythromycin resulted in a 20% decrease in the AUC and a 30% decrease in the Cmax of rosuvastatin. The cause of this interaction may be the increased intestinal motility induced by erythromycin.

Drugs metabolized by cytochrome P450 enzymes: Results from in vitro and in vivo studies indicate that rosuvastatin is not an inhibitor or inducer of cytochrome P450 enzymes. In addition, rosuvastatin is a weak substrate for these isoenzymes. Therefore, no drug interactions mediated by cytochrome P450 metabolism are expected. There were also no clinically relevant interactions between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4) or with ketoconazole (an inhibitor of CYP2A6 and CYP3A4).

Hormonal replacement therapy/oral contraceptives (HRT): Concomitant use of rosuvastatin and oral contraceptives resulted in an increase in the AUC of ethinyl estradiol and norgestrel by 26% and 34%, respectively. Increased plasma concentrations should be considered when selecting oral contraceptive doses. There are no pharmacokinetic data in subjects receiving rosuvastatin and HRT concomitantly and a similar effect cannot therefore be excluded. However, the combination has been used extensively in women in clinical trials and has been well tolerated.

Adverse Effects (ADRs)

Adverse effects due to rosuvastatin are usually mild and transient. The adverse reactions listed below are sorted by frequency and organ type. The frequency of adverse reactions is classified according to the following convention: Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1000); Very rare (<1/10,000); Unknown (cannot be estimated from available data).

Blood and lymphatic system disorders

Rare: Thrombocytopenia

Immune system disorder

Rare: Hypersensitivity reactions including angioedema

Endocrine disorders

Common: Diabetes mellitus. Increased HbA1c and increased fasting blood glucose have been reported with HMG-CoA reductase inhibitors, including rosuvastatin. In some cases this increase may exceed the threshold for diabetes.

Psychosis

Unknown: Depression:

Nervous system disorder

Common: Headache, dizziness

Very rare: Polyneuropathy, memory impairment.

Not known: Sleep disturbance (including insomnia and nightmares), cognitive impairment (such as memory loss, confusion, etc.).

Respiratory, thoracic and mediastinal disorders

Unknown: Cough, difficulty breathing

Digestive disorders

Common: Constipation, nausea, abdominal pain

Rare: Pancreatitis

Unknown: Diarrhea

Liver and biliary disorders

Rare: Increased liver transaminases

Very rare: Jaundice, hepatitis

Skin and subcutaneous tissue disorders

Uncommon: Pruritus, rash, urticaria

Unknown: Stevens-Johnson syndrome

Musculoskeletal and connective tissue disorders

Common: Myalgia

Rare: Myopathy (including myositis), rhabdomyolysis

Very rare: Arthralgia

Not known: Immune-mediated necrotizing myopathy

Renal and urinary disorders

Very rare: Hematuria (hematuria)

Breast and reproductive system disorders

Very rare: Gynecomastia in men

Other disorders

Common: Asthenia

Proteinuria has occurred in patients treated with rosuvastatin.

Dose-related increases in creatinine kinase (CK) levels have occurred in patients receiving rosuvastatin; Most cases are mild, asymptomatic and transient.

Preservation

Store at a temperature below 30ºC, protected from light.

Presentation and packaging

Film coated tablets: box of 4 blisters x 7 tablets.