LOWLIP Tablet

Hypercholesterolaemia

As an adjunct to diet for reduction of elevated total cholesterol (total-C), LDL cholesterol (LDL-C), apolipoprotein B, and triglycerides in adults, adolescents and children aged 10 years or older with primary hypercholesterolaemia including familial hypercholesterolaemia (heterozygous variant) or combined (mixed) hyperlipidaemia (Corresponding to Types Ⅱa and Ⅱb of the Fredrickson classification) when response to diet and other nonpharmacological measures is inadequate.

Atorvastatin Tablets is also indicated to reduce total-C and LDL-C in adults with homozygous familial hypercholesterolaemia as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) or if such treatments are unavailable.

Prevention of cardiovascular disease

Prevention of cardiovascular events in adult patients estimated to have a high risk for a first cardiovascular event, as an adjunct to correction of other risk factors.

Dosage and Administration

This drug should be used under physician’s prescription only.

The patients are recommended to start treatment with the minimal effective dosage.

If necessary, the dose can be adjusted according to patient’s requirement and response by increasing the dose at the intervals of ≥4weeks and adverse reactions should be monitored, especially adverse reaction for muscular system.

In patients taking Amiodarone concomitantly with atorvastatin, the maximum recommended dosage is 20mg/day.

General: Before instituting therapy with Atorvastatin, an attempt should be made to control hypercholesterolemia with appropriate diet, exercise and weight reduction in obese patients, ad to treat underlying medical problems. The patient should continue on a standard cholesterol-lowering diet during treatment with Atorvastatin.

The recommended starting dose is 10-20mg once daily.

Patients who require a large reduction in LDL-C (<45%) may be started at 40mg once daily.

The dosage range is 10-80mg once daily.

Atorvastatin can be administered as a single dose at any time of the day, with or without food.

The doses should be individualized according to baseline LDL-C levels, the goal of therapy and patient response. After initiation and/or upon titration of Atorvastatin, lipid levels should be analyzed within 2-4 weeks, and dosage adjusted accordingly.

Prevention of Cardiovascular Disease: Recommended dose: 10mg once daily.

Primary Hypercholesterolemia and Combined (mixed) Hyperlipidemia: The majority of patients are controlled with 10mg Atorvastatin once a day. A therapeutic response is evident within 2 weeks and the maximum response is usually achieved within 4 weeks. The response is maintained during chronic therapy.

Homozygous Familial Hypercholesterolemia: In a study of patients with homozygous familial hypercholesterolemia, most patients responded to 80mg of Atorvastatin with a >15% reduction in LDL-C (18-45%).

Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10-17 years): Recommended Starting Dose: 10mg/day, the maximum recommended dose is 20mg/day (doses > 20mg have not been studied in this patient population). Doses should be individualized according to the goal of therapy. Adjustments should be made at intervals of ≥4weeks.

Children: Treatment experience in pediatric population is limited to doses of Atorvastatin up to 80mg/day for 1 year in 8 patients with homozygous FH. No clinical or biochemical abnormalities were reported in these patients.

Elderly: No differences in safety, efficacy was observed between elderly patients and the overall population.

Patients with Hepatic Insufficiency: See “Contraindications” and “Precautions”.

Patients with Renal Insufficiency: Renal disease has no influence on the plasma concentrations or on the LDL-C reduction of Atorvastatin. Thus, no adjustment of the dose is required.

Patients

- who are hypersensitive to any component of Atorvastatin,

- who have active liver disease or unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit of normal,

- who are pregnant who are breastfeeding, or in women of childbearing potential who are not using adequate contraceptive measures.

Atorvastatin should be administered to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards to the fetus.

The most frequent adverse effects, in patients participating in controlled clinical studies were:

Psychiatric Disorders: Insomnia

Nervous System Disorders: Headache

Gastrointestinal Disorders: Nausea, diarrhoea, abdominal pain, dyspepsia, constipation, flatulence.

Musculoskeletal and Connective Tissue Disorders: Myalgia.

General Disorders: Asthenia.

See the package insert about the details below:

- The inhibitor of CYP34 (cyclosporine, fibric acid derivatives, erythromycin, azole antifungals, niacin)

- Antacids containing magnesium and aluminum hydroxides

- Antipyrine

- Colestipol

- Digoxin

- Erythromycin/Clarithromycin

- Azithromycin

- Terfenadine

- Oral contraceptives containing norethindrone and ethinyl estradiol

- Warfarin

- Cimetidine

- Amlodipine

- Protease inhibitors

- Other Concomitant Therapy: In clinical studies, Atorvastatin was used concomitantly with antihypertensive agents and estrogen replacement therapy without evidence of clinically significant adverse interactions. Interaction studies with specific agents have not been conducted.

See the package insert about the details below:

Pregnancy

Contraindicated.

Lactation

Contraindicated.

Consideration should be taken when using drugs belongs to statin group in patients who have risk factor of muscle injury.

Drugs belong to statin group have risk to cause dangerous reaction for muscle system such as myasthenia, myositis, especially for patients that have risk factor as patients over 65 years old, patents uncontrolled hypothyroidism, patients with impaired renal. Care should be taken for dangerous reactions during treatment with these medications.

See the package insert about the details below:

- Liver Dysfunction

- Skeletal Muscle

Lipid modifying agents, HMG-CoA reductase inhibitors.

Atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme responsible for the conversion of e-hydroxy-e-methyl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol. Triglycerides and cholesterol in the liver are incorporated into very low-density lipoproteins (VLDL) and release into the plasma for delivery to peripheral tissues. Low-density lipoprotein (LDL) is formed from VLDL and is catabolized primarily through the receptor with high affinity to LDL (LDL receptor).

Atorvastatin lowers plasma cholesterol and lipoprotein serum concentrations by inhibiting HMG-CoA reductase and subsequently cholesterol biosynthesis in the liver and increases the number of hepatic LDL receptors on the cell surface for enhanced uptake and catabolism of LDL.

Atorvastatin reduces LDL production and the number of LDL particles. Atorvastatin produces a profound and sustained increase in LDL receptor activity coupled with a beneficial change in the quality of circulating LDL particles. Atorvastatin is effective in reducing LDL-C in patients with homozygous familial hypercholesterolaemia, a population that has not usually responded to lipid-lowering medicinal products.

Atorvastatin has been shown to reduce concentrations of total-C (30-46%), LDL-C (41-61%), apolipoprotein B (34-50%), and triglycerides (14-33%) while producing variable increases in HDL-C and apolipoprotein A1 in a dose response study. These results are consistent in patients with heterozygous familial hypercholesterolaemia, nonfamilial forms of hypercholesterolaemia, and mixed hyperlipidaemia, including patients with noninsulin-dependent diabetes mellitus.

Reductions in total-C, LDL-D, and apolipoprotein B have been proven to reduce risk for cardiovascular events and cardiovascular mortality.