Active Ingredient and Strength	ATORVASTATIN CALCIUM 86.8 MG EQV ATORVASTATIN - 80 MG
Dosage Form	TABLET, FILM COATED
Manufacturer and Country	VIATRIS PHARMACEUTICALS LLC - PUERTO RICO
Registration Number	SIN13301P
Licence Holder	VIATRIS PRIVATE LIMITED
Forensic Classification	PRESCRIPTION ONLY MEDICINES
Anatomical Therapeutic Chemical (ATC) code	NA

4.1. Therapeutic indications

Atorvastatin is indicated as an adjunct to diet for reduction of elevated total cholesterol (total-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo B), and triglycerides (TG) in adults, adolescents and children aged 10 years or older with primary hypercholesterolemia, heterozygous familial hypercholesterolemia, or combined (mixed) hyperlipidemia (Fredrickson Types IIa and IIb), elevated serum TG levels (Fredrickson Type IV), and for patients with dysbetalipoproteinemia (Fredrickson Type III) when response to diet and other non-pharmacological measures is inadequate.

Atorvastatin also raises high density lipoprotein cholesterol (HDL-C) and lowers the LDL/HDL and total-C/HDL ratios.

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

Prevention of Cardiovascular Disease

Eturion is indicated to reduce the risk of myocardial infarction (MI) in adult hypertensive patients without clinically evident coronary heart disease (CHD), but with at least three additional risk factors for CHD such as age ≥55 years, male sex, smoking, left ventricular hypertrophy, other specified abnormalities on electrocardiogram (ECG), microalbuminuria or proteinuria, ratio of plasma total-C to HDL-C ≥6, or premature family history of CHD.

In adults with type 2 diabetes and without clinically evident CHD, but with multiple risk factors for CHD such as retinopathy, albuminuria, smoking or hypertension, Eturion is indicated to:

Reduce the risk of MI.
Reduce the risk of stroke.

In adults with clinically evident CHD, atorvastatin is indicated to:

Reduce the risk of non-fatal MI.
Reduce the risk of fatal and non-fatal stroke.
Reduce the risk for revascularization procedures.
Reduce the risk of hospitalization for congestive heart failure (CHF).
Reduce the risk of angina.

4.2. Posology and method of administration

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 the underlying medical problems. The patient should continue on a standard cholesterol-lowering diet during treatment with atorvastatin. The recommended starting dose of atorvastatin is 10 mg or 20 mg once daily. Patients who require a large reduction in LDL-C (more than 45%) may be started at 40 mg once daily. The dosage range is 10 mg to 80 mg 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 to 4 weeks, and dosage adjusted accordingly.

Prevention of Cardiovascular Disease (CVD)

For primary prevention, the recommended dose is 10 mg once daily. For secondary prevention, optimal dosing may range from 10 mg to 80 mg atorvastatin once daily, to be given at the discretion of the prescriber, taking into account the expected benefit and safety considerations relevant to the patient to be treated (see section 5.1. – Pharmacodynamic properties: Secondary Prevention of Cardiovascular Events – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Primary Hypercholesterolemia and Combined (Mixed) Hyperlipidemia

The majority of patients are controlled with 10 mg atorvastatin once daily. 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 compassionate-use study of patients with homozygous familial hypercholesterolemia, most patients responded to 80 mg atorvastatin with a greater than 15% reduction in LDL-C (18%–45%).

Use in Patients with Hepatic Insufficiency

See section 4.3. – Contraindications and section 4.4. – Special warnings and precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Use in Patients with Renal Insufficiency

Renal disease has no influence on plasma concentrations or on LDL-C reduction with atorvastatin. Thus, no dose adjustment is required (see section 4.4. – Special warnings and precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Pediatric Use, Hypercholesterolemia

Pediatric use should only be carried out by physicians experienced in the treatment of pediatric hyperlipidemia and patients should be re-evaluated on a regular basis to assess progress.

For patients aged 10 years and above, the recommended starting dose of atorvastatin is 10 mg daily with titration up to 20 mg daily. Titration should be conducted according to the individual response and tolerability in pediatric patients. Safety information for pediatric patients treated with doses above 20 mg, corresponding to about 0.5 mg/kg, is limited.

Experience in pediatric patients older than 6 to less than 10 years of age is derived from open-label studies (see section 4.8. – Undesirable effects, section 5.1. – Pharmacodynamic properties, and section 5.2. – Pharmacokinetic properties: Special Populations – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Atorvastatin is not indicated in the treatment of patients below the age of 10 years.

Treatment experience in a pediatric population is limited to doses of atorvastatin up to 80 mg/day for one year in 8 patients with homozygous familial hypercholesterolemia. No clinical or biochemical abnormalities were reported in these patients.

Use in the Elderly

No differences in safety, efficacy or lipid treatment goal attainment were observed between elderly patients and the overall population (see section 5.2. – Pharmacokinetic properties: Special Populations – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Use in Combination with Other Medicinal Compounds

In cases where co-administration of atorvastatin with cyclosporine, telaprevir, or the combination tipranavir/ritonavir is necessary, the dose of atorvastatin should not exceed 10 mg.

Dose of atorvastatin should not exceed 20 mg/day with concomitant use with elbasvir/grazoprevir (see section 4.4. – Special warnings and precautions for use: Skeletal Muscle Effects and section 4.5. – Interaction with other medicinal products and other forms of interaction – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Use of atorvastatin is not recommended in patients taking letermovir co-administered with cyclosporine.

Pharmacokinetic drug interactions that result in increased systemic concentration of atorvastatin have also been noted with other human immunodeficiency virus (HIV) protease inhibitors (lopinavir/ritonavir, saquinavir/ritonavir, darunavir/ritonavir, fosamprenavir, fosamprenavir/ritonavir and nelfinavir), hepatitis C (HCV) protease inhibitors (boceprevir, elbasvir/grazoprevir, simeprevir), clarithromycin, itraconazole, and letermovir. Caution should be used when co-prescribing atorvastatin, and appropriate clinical assessment is recommended to ensure that the lowest dose of atorvastatin necessary is employed (see section 4.4. – Special warnings and precautions for use: Skeletal Muscle Effects and section 4.5. – Interaction with other medicinal products and other forms of interaction – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

THE FOLLOWING TREATMENT GUIDELINES MAY BE USED TO ESTABLISH TREATMENT GOALS

After the LDL-C goal has been achieved, if the TG is still ≥200 mg/dL (2.2 mmol/L), non-HDL-C (total-C minus HDL-C) becomes a secondary target of therapy. Non-HDL-C goals are set 30 mg/dL (0.8 mmol/L) higher than LDL-C goals for each risk category.

4.3. Contraindications

Atorvastatin is contraindicated in patients who have:

Hypersensitivity to any component of this medication

Active liver disease or unexplained persistent elevations of serum transaminases exceeding three times the upper limit of normal (ULN)

or who are:

Pregnant, breast-feeding, or of child-bearing potential who are not using adequate contraceptive measures. Atorvastatin should be administered to women of child-bearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards to the fetus.

Concomitantly treated with glecaprevir/pibrentasvir.