LIPIGET Tablet

See the package insert about the details:

- Hypercholesterolemia

- Prevention of Cardiovascular Disease

Dosage and Administration

The patient should be placed on a standard cholesterol-lowering diet before receiving LIPIGET and should continue on this diet during treatment with LIPIGET. Doses should be individualized according to baseline LDL-C levels, the goal of therapy and patient response. Adjustment of dosage should be made at intervals of 4 weeks or more. The maximum dose is 80mg once a day.

For patients taking interacting drugs that increase plasma exposure to atorvastatin, the starting dose should be 10mg once a day and a maximum dose of less than 80mg may need to be considered. In some cases a dose reduction, or where not practical, a temporary dose suspension may be considered.

Doses above 20mg/day have not been investigated in patients aged <18 years.

Primary Hypercholesterolemia and Combined (Mixed) Hyperlipidemia

Adults:

The majority of patients are controlled with 10mg LIPIGET 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.

Children aged 10-17 years:

Doses above 20mg/day have not been investigated.

Heterozygous Familial Hypercholesterolemia

Adults:

Patients should be started with LIPIGET 10mg daily. Doses should be individualized and adjusted every 4 weeks to 40mg daily. Thereafter, either the dose may be increased to a maximum of 80mg daily or a bile acid sequestrant (e.g. colestipol) may be combined with 40mg LIPIGET.

Children aged 10-17 years:

Doses above 20mg/day and combination therapies have not been investigated.

Homozygous Familial Hypercholesterolemia

Adults:

In a compassionate-use study of patients with homozygous familial hypercholesterolemia, most patients responded to a dose of 80mg of LIPIGET.

Children:

Treatment experience in a pediatric population with doses of LIPIGET up to 80mg/day is limited.

Prevention of Cardiovascular disease

In the primary prevention the dose is 10mg/day. Patients with higher levels with require conventional measurement and dose titration.

Geriatric Use

Adequate treatment experience in adults age 70 or older with doses of LIPIGET up to 80mg/day has been obtained. Efficacy and safety in older patients using recommended doses is similar to that seen in the general population.

The following guidelines may be used to establish treatment goals. (See the package insert.)

- In patients with hypersensitivity to any component of this medication.

- In patients with active liver disease or unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit of normal.

- Safety of atorvastatin in pregnancy has not been established, and is contraindicated for use during pregnancy.

- Use of atorvastatin during breast feeding is not recommended, because of the potential for serious adverse effects in nursing infants.

- In women of child-bearing potential not using appropriate contraceptive measures.

Common: Constipation, flatulence, dyspepsia, nausea, diarrhea, allergic reactions (including anaphylaxis), insomnia, headache, dizziness, paresthesia, hypoesthesia, skin rash, pruritus, myalgia, arthralgia, asthenia, chest pain, back pain, fatigue.

Uncommon: Anorexia, vomiting, pancreatitis, thrombocytopenia, alopecia, hyperglycemia, hypoglycemia, amnesia, peripheral neuropathy, urticaria, alopecia, tinnitus, myopathy, muscle cramps, impotence, malaise, weight gain.

Rare: Hepatitis, cholestatic jaundice, myositis, rhabdomyolysis, peripheral oedema.

Very rare: Dysgeusia, visual disturbance, hepatic failure, angioneurotic oedema, bullous rashes (including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis), hearing loss, tendon rupture, gynecomastia.

The risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concurrent administration of cyclosporin, fibrates, macrolide antibiotics, azole antifungals, HIV-protease inhibitors or niacin and on rare occasions has resulted in rhabdomyolysis with renal dysfunction secondary to myoglobinuria.

Endocrine Function: Caution should be exercised if an HMG-CoA reductase inhibitor is administered concomitantly with other drugs that may decrease the levels of activity of endogenous steroid hormones such as ketoconazole, spironolactone and cimetidine.

See the package insert about the details below:

Clarithromycin

Erythromycin

Itraconazole

Protease inhibitors

Diltiazem hydrochloride

Ezetimibe

Grapefruit juice

Inducers of CYP3A4 (e.g. efavirenz, rifampin, St. John’s Wort)

Oral contraceptives containing norethisterone and ethinyl oestradiol

Colestipol

Warfarin

Antacid suspension containing magnesium and aluminium hydroxides

Digoxin

Pregnancy

Contraindicated.

Lactation

Not recommended.

General

Before instituting therapy with atorvastatin, an attempt should be made to control hypercholesterolemia with appropriate diet, exercise, and weight reduction in obese patients, and to treat other underlying medical problems.

Liver function abnormalities

Liver function tests should be performed before the initiation of treatment and periodically thereafter. Patients who develop any signs or symptoms suggestive of liver injury should have liver function tests performed. Patents who develop increased transaminase levels should be monitored until the abnormality (ies) resolve. Should an increase in ALT or AST of greater than 3 times the upper limit of normal persist, reduction of dose or withdrawal of atorvastatin is recommended. Atorvastatin should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease.

Skeletal Muscle

Atorvastatin therapy should be temporarily withheld or discontinued in any patient with an acute, serious condition suggestive of a myopathy of having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis (e.g. severe acute infection. hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders, and uncontrolled seizures). Patients should be advised to report promptly any unexplained muscle pan, tenderness or weakness, particularly if accompanied by malaise or fever.

Hemorrhagic Stroke

In a post-hoc analysis of stroke subtypes in patients without CHD who had a recent stroke or TIA there was a higher incidence of hemorrhagic stroke in patients initiated on atorvastatin 80mg compared to placebo. For patients with prior hemorrhagic stroke or lacunar infarct, the balance of risks and benefits of atorvastatin 80mg is uncertain and the potential risk of hemorrhagic stroke should be carefully considered before initiating treatment.

Pediatric use

Treatment experience in a pediatric population is limited to doses of atorvastatin upto 80mg daily for 1 year in patients with homozygous FH. No clinical and biochemical abnormalities were reported in these patients.

Atorvastatin is a selective, competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme responsible for the conversion of HMG-CoA to mevalonate, a precursor of sterols, including cholesterol. The primary site of action of HMG-CoA reductase inhibition is the liver. Inhibition of cholesterol synthesis in the liver leads to upregulation of LDL-receptors and an increase in LDL-catabolism. There is also some reduction of LDL-production as a result of inhibition of hepatic synthesis of very low-density lipoprotein (VLDL), the precursor of LDL-cholesterol. Atorvastatin reduces total cholesterol, LDL-cholesterol and apo B in patients with homozygous and heterozygous familial hypercholesterolemia, non-familial forms of hypercholesterolemia and mixed dyslipidemias. Atorvastatin also reduces VLDL-cholesterol and triglycerides and produces variable increases in HLDL-cholesterol and Apolipoprotein A1.