Posology : מינונים

3 DOSAGE AND ADMINISTRATION

General - Before instituting therapy with LIPITOR, an attempt should be made to control hypercholesterolemia with
appropriate diet, exercise and weight reduction in obese patients, and to treat underlying medical problems. The patient
should continue on a standard cholesterol lowering diet during treatment with LIPITOR. (see National Cholesterol
Education Program (NCEP) Guidelines, summarized in Table 1).

The usual starting dose is 10 mg or 20 mg once daily. The dosage range of LIPITOR is 10 to 80 mg once daily. Starting and
maintenance 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 80 mg once a day.
Doses may be given at any time of day with or without food.
After initiation and/or upon titration of LIPITOR, lipid levels should be analyzed within 2 to 4 weeks and dosage adjusted
accordingly.
Therapy with lipid-altering agents should be a component of multiple-risk-factor intervention in individuals at increased risk
for atherosclerotic vascular disease due to hypercholesterolemia.

TABLE 1. NCEP Treatment Guidelines: LDL-C Goals and Cutpoints for Therapeutic Lifestyle Changes
and Drug Therapy in Different Risk Categories

LDL Level at Which to             LDL Level at Which to Consider
LDL Goal              Initiate Therapeutic                        Drug
Risk Category           (mg/dL)          Lifestyle Changes (mg/dL)                Therapy (mg/dL)
CHD a or CHD risk
equivalents             <100                       ≥100                                  ≥130
(10-year risk >20%)                                                                (100-129: drug optional) b


2+ Risk Factors       <130                       ≥130                       10-year risk 10%-20%: ≥130
(10-year risk ≤20%)                                                            10-year risk <10%: ≥ 160


0-1 Risk factor c      <160                       ≥160                                  ≥190
(160-189: LDL-lowering
drug optional)
a
CHD, coronary heart disease
b
Some authorities recommend use of LDL-lowering drugs in this category if an LDL-C level of < 100 mg/dL
cannot be achieved by therapeutic lifestyle changes. Others prefer use of drugs that primarily modify
triglycerides and HDL-C, e.g., nicotinic acid or fibrate. Clinical judgement also may call for deferring drug
therapy in this subcategory.
c
Almost all people with 0-1 risk factor have 10-year risk <10%; thus, 10-year risk assessment in people with 0-1
risk factor is not necessary.

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

Prior to initiating therapy with LIPITOR, secondary causes for hypercholesterolemia (e.g., poorly controlled diabetes
mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, and
alcoholism) should be excluded, and a lipid profile performed to measure total-C, LDL-C, HDL-C, and TG. For patients
with TG <400 mg/dL (<4.5 mmol/L), LDL-C can be estimated using the following equation: LDL-C = total-C - (0.20 x
[TG] + HDL-C). For TG levels >400 mg/dL (<4.5 mmol/L) this equation is less accurate and LDL-C concentrations should
be determined by ultracentrifugation.

LIPITOR has not been studied in conditions where the major lipoprotein abnormality is elevation of chylomicrons
(Fredrickson Types I and V).
NCEP (National Cholesterol Education Program) Pediatric Panel Guidelines
Classification of cholesterol levels in pediatric patients with a familial history of hypercholesterolemia or premature
cardiovascular disease is summarized below:

Category                   Total-C (mg/dL)                    LDL-C (mg/dL)
Acceptable                       <170                             <110
Borderline                     170-199                          110-129
High                             ≥200                             ≥130



Primary Hypercholesterolaemia including familial hypercholesterolaemia (heterozygous variant) or combined (mixed)
hyperlipidaemia (Fredrickson Types IIa and IIb)
Patients should be started with LIPITOR 10 mg daily. A therapeutic response is evident within two weeks, and the
maximum response is usually achieved within four weeks. The response is maintained during chronic therapy.Doses should
be individualized and adjusted every 4 weeks to 40 mg daily. Thereafter, either the dose may be increased to a maximum of
80 mg daily or a bile acid sequestrant may be combined with 40 mg LIPITOR.


Homozygous Familial Hypercholesterolaemia
The dosage of LIPITOR in patients with homozygous FH is 10 to 80 mg daily. LIPITOR should be used as an adjunct to
other lipid-lowering treatment (e.g. LDL apheresis) in these patients or if such treatments are unavailable.
In a compassionate-use study of patients with homozygous familial hyper-cholesterolaemia, most patients responded to
80mg of atorvastatin with a greater than 15% reduction in LDL-C (18%-45%).

Severe dyslipidemias in Pediatric Patients -
Experience in pediatrics is limited to a small number of patients (age 4-17 years) with severe dyslipidemias, such as familial
hypercholesterolemia. The recommended starting dose in this population is 10 mg of LIPITOR per day. The dose may be
increased to 80 mg daily, according to the response and tolerability. Doses should be individualized according to the
recommended goal of therapy (see section 2 Therapeutic indications, and section 9.4 Pediatric Use).
Adjustments should be made at intervals of 4 weeks or more.

Prevention of cardiovascular or cerebrovascular events
In the primary prevention trials the dose was 10 mg/day. Higher dosages may be necessary in order to attain (LDL-)
cholesterol levels according to current guidelines.

Use in Patients with Hepatic Insufficiency
(See sections 5 Contraindications and 6 Warnings and Precautions )

Dosage in Patients with Renal Insufficiency
Renal disease has no influence on the plasma concentrations or on the LDL-C reduction with LIPITOR ; thus, no adjustment
of dose is required. (see section 6 Warnings and Precautions).

Dosage in Patients Taking Cyclosporine, Clarithromycin, Itraconazole, or Certain Protease Inhibitors
In patients taking cyclosporine or the HIV protease inhibitors (tipranavir plus ritonavir) or the hepatitis C protease inhibitor
(telaprevir), therapy with LIPITOR should be avoided. In patients with HIV taking lopinavir plus ritonavir, caution should
be used when prescribing LIPITOR and the lowest dose necessary employed. In patients taking clarithromycin, itraconazole,
or in patients with HIV taking a combination of saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, or
fosamprenavir plus ritonavir, therapy with LIPITOR should be limited to 20 mg, and appropriate clinical assessment is
recommended to ensure that the lowest dose necessary of LIPITOR is employed.In patients taking the HIV protease
inhibitor nelfinavir or the hepatitis C protease inhibitor boceprevir, therapy with LIPITOR should be limited to 40 mg, and
appropriate clinical assessment is recommended to ensure that the lowest dose necessary of LIPITOR is employed (see
section 6.1 Warnings and Precaution -Myopathy and Rhabdomyolysis and section 8 Drug Interactions).

Use in Elderly
Efficacy and safety in patients older than 70 using recommended doses is similar to that seen in the
general population. (see section9.5 Use in Specific Populations- Geriatric Use).


4 DOSAGE FORMS AND STRENGTHS

LIPITOR tablets are white round, film-coated, and are available in four strengths (see Table 1).

Table 1: LIPITOR Tablet Strengths and Identifying Features

Tablet Strength              Identifying Features
10 mg of atorvastatin        “10” on one side and “ATV” on the other
20 mg of atorvastatin                  “20” on one side and “ATV” on the other.
40 mg of atorvastatin                  “40” on one side and “ATV” on the other
80 mg of atorvastatin                  “80” on one side and “ATV” on the other