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  • Lipitor
    / Pfizer


    Active Ingredient
    Atorvastatin (as calcium) 10, 20, 40, 80 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    30 x 10 mg

    partial basket chart 70539 12484

    Film Coated Tablets

    30 x 20 mg

    partial basket chart 69510 12482

    Film Coated Tablets

    30 x 40 mg

    partial basket chart 68181 12485

    Film Coated Tablets

    30 x 80 mg

    partial basket chart 68417 12483

    Related information


    Dosage

    General: Before instituting therapy with this product , an attempt should be made to control hypercholesterolemia with appropriate diet, exercise and weight reduction in obese patients, and to treat underlying medical problems. patient should continue on a standard cholesterol lowering diet during treatment withthis product. The usual starting dose is 10 mg or 20 mg once daily. The dosage range 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 this product, 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. For full details see prescribing information.


    Indications

    Hypercholesterolemia: Adjunct to diet for the treatment of elevated total and LDL cholesterol, apolipoprotein B and triglycerides and to increase HDL-cholesterol in patients with primary hypercholesterolemia including familial hypercholesterolemia (heterozygous variant) or combined (mixed) hyperlipidemia (Fredrickson Types IIa and IIb) when response to diet and other non-pharmaceutical measures alone has been inadequate. To reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments.
    Pediatric patients (10-17 years of age): As an adjunct to diet to reduce total-C, LDL-C, and apo B levels in boys and postmenarchal girls, with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: a. LDL-C remains equal to or higher than 190 mg/dL, or b. LDL-C remains equal to or higher than 160 mg/dL and there is a positive family history of premature cardiovascular disease or two or more other CVD risk factors are present in the pediatric patient.
    Prevention of cardiovascular disease: Prevention of cardiovascular and/or cerebrovascular events such as MI or stroke: As an adjunct to correction of other risk factors such as hypertension in patients with three or more additional risk factors or diabetes with one additional risk factor.


    Contra-Indications

    This product is contraindicated in patients:
    – with hypersensitivity to any component of this medication
    – with active liver disease or unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit of normal.
    – with myopathy.
    – during pregnancy.
    – while breastfeeding.
    – in women of child-bearing potential not using appropriate contraceptive measures.
    This product 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.


    Special Precautions

    Hepatic Effects: Liver function tests should be performed before the initiation of treatment, at 6 and 12 weeks after initiation of therapy or elevation in dose, and periodically (e.g. semi-annually) thereafter. Patients who develop any signs or symptoms suggestive of liver injury should have liver function tests performed. Patients who develop increased transaminase levels should be monitored until the abnormality(ies) is (are) resolved. Should an increase in transaminases of greater than 3 times the upper limit of normal persist, reduction of dose or withdrawal of LIPITOR is recommended. Atorvastatin can cause an elevation in transaminases . this product  should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease. Active liver disease or unexplained persistent transaminase elevations are contraindications to the use of this product As with other lipid-lowering agents of the same class, moderate (>3 x upper limit of normal [ULN] elevations of serum transaminases have been reported following therapy with this product . Liver function was monitored during pre-marketing as well as post-marketing clinical studies of atorvastatin given at doses of 10, 20, 40 and 80mg. this product  can cause an elevatio intransaminases.  Persistent increases in serum transaminases (>3 x ULN on two or more occasions) occurred in 0.7% of patients who received atorvastatin in these clinical trials. The incidence of these abnormalities was 0.2%, 0.2%, 0.6% and 2.3% for 10, 20, 40 and 80mg respectively. Increases were generally not associated with jaundice or other clinical signs or symptoms. When the dosage of atorvastatin was reduced, or drug treatment interrupted or discontinued, transaminase levels returned to pretreatment levels. Most patients continued treatment on a reduced dose of atorvastatin without sequelae. Active liver disease or unexplained persistent transaminase elevations are contraindications to the use of this product  Liver function tests should be performed at 6 and 12 weeks after initiation of therapy or elevation in dose, and periodically thereafter. Use with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease.
    Skeletal Muscle Effects:  Myalgia has been reported in this product -treated patients. Myopathy, defined asmuscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values >10 x ULN, should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK. Patients should be advised to promptly report unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. The risk of myopathy during treatment with drugs in this class is increased with concurrent administration of cyclosporine, fibric acid derivatives, erythromycin, niacin, azole antifungals, colchicine, the hepatitis C protease inhibitor telaprevir, boceprevir, combinations of HIV protease inhibitors, including saquinavir plus ritonavir, lopinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, and fosamprenavir plus ritonavir. Many of these drugs inhibit cytochrome P450 3A4 metabolism and/or drug-transport. CYP 3A4 is the primary hepatic isozymes known to be involved in the biotransformation of atorvastatin. Physicians considering combined therapy with this product R and fibric acid derivatives, erythromycin, immunosuppressive drugs, azole antifungals, or lipid-modifying doses of niacin, a combination of saquinavir plus ritonavir, lopinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, orfosamprenavir plus ritonavir should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs and symptoms of muscle pain, tenderness, or weakness, particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Therefore, lower starting and maintenance doses should also be considered when taken concomitantly with the aforementioned drugs. Temporary suspension may be appropriate during fusidic acid therapy .medicinal products and other forms of interaction). Periodic creatine phosphokinase (CPK) determinations may beconsidered in such situations, but there is no assurance that such monitoring will prevent the occurrence of severe myopathy. this product  may cause an elevation of creatine phosphokinase.


    Side Effects

    Constipation, flatulence, dyspepsia, abdominal pain, headache, nausea, myalgia, asthenia, diarrhea, insomnia and rash.


    Drug interactions

    The risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concurrent administration of cyclosporin, fibric acid derivatives, lipid-modifying doses of niacin or cytochrome P450 3A4 inhibitors (eg erythromycin, and azole antifungals).
    Inhibitors of cytochrome P450 3A4: Atorvastatin is metabolized by cytochrome P450 3A4. Concomitant administration of atorvastatin with inhibitors of cytochrome P450 3A4 can lead to increases in plasma concentrations of atorvastatin. The extent of interaction and potentiation of effects depends on the variability of effect on cytochrome P450 3A4.
    Transporter Inhibitors: Atorvastatin and atorvastatin – metabolites are substrates of the OATP1B1 transporter. Inhibitors of the OATP1B1 (e.g. cyclosporine) can increase the bioavailability of atorvastatin. Concomitant administration of atorvastatin 10 mg and cyclosporine 5.2 mg/kg/day resulted in a 7.7 fold increase in exposure to atorvastatin.
    Erythromycin/Clarithromycin: Co-administration of atorvastatin and erythromycin (500 mg four times daily), or clarithromycin (500 mg twice daily) known inhibitors of cytochrome P450 3A4, was associated with higher plasma concentrations of atorvastatin.
    Protease inhibitors: Coadministration of atorvastatin and protease inhibitors, known inhibitors of cytochrome P450 3A4, was associated with increased plasma concentrations of atorvastatin.
    Diltiazem hydrochloride: Co-administration of atorvastatin (40mg) with Diltiazem (240mg) was associated with higher plasma concentrations of atorvastatin.
    Cimetidine: An atorvastatin interaction study with cimetidine was conducted, and no clinically significant interactions were seen.
    Itraconazole: Concomitant administration of atorvastatin (20 to 40 mg) and itraconazole (200 mg) was associated with an increase in atorvastatin AUC.
    Grapefruit juice: Contains one or more components that inhibit CYP3A4 and can increase plasma concentrations of drugs metabolized by CYP3A4. Intake of one 240 ml glass of grapefruit juice resulted in an increase in atorvastatin AUC of 37 % and a decreased AUC of 20.4 % for the active orthohydroxy metabolite. However, large quantities of grapefruit juice (over 1.2L daily for 5 days) increased AUC of atorvastatin 2.5 fold and AUC of active (atorvastatin and metabolites) HMG-CoA reductase inhibitors 1.3 fold. Concomitant intake of large quantities of grapefruit juice and atorvastatin is therefore not recommended. Inducers of cytochrome P450 3A: Concomitant administration of atorvastatin with inducers of cytochrome P450 3A4 (eg efavirenz, rifampin) can lead to variable reductions in plasma concentrations of atorvastatin. Due to the dual interaction mechanism of rifampin, (cytochrome P450 3A4 induction and inhibition of hepatocyte uptake transporter OATP1B1), simultaneous coadministration of atorvastatin with rifampin is recommended, as delayed administration of atorvastatin after administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations.
    Digoxin: When multiple doses of digoxin and 10 mg atorvastatin were co-administered, steady – state plasma digoxin concentrations were unaffected. However, digoxin concentrations increased approximately 20% following administration of digoxin with 80 mg atorvastatin daily. Patients taking digoxin should be monitored appropriately.
    Azithromycin: Co-administration of atorvastatin (10 mg once daily) and azithromycin (500 mg once daily) did not alter the plasma
    concentrations of atorvastatin. Coadministration of atorvastatin with an oral contraceptive containing norethindrone and ethinyl estradiol increased AUC values for norethindrone and ethinyl oestradiol by approximately 30% and 20%. These increases should be considered when selecting an oral contraceptive for a woman taking atorvastatin .
    Antipyrine: Because atorvastatin does not affect the pharmacokinetics of antipyrine, interactions with other drugs metabolized via the same cytochrome isozymes are not expected.
    Colestipol: Plasma concentrations of atorvastatin and its active metabolites were lower (approximately 25%) when colestipol was coadministered with atorvastatin. However, lipid effects were greater when atorvastatin and colestipol were coadministered than when either drug was given alone.
    Antacids: Coadministration of Lipitor with an oral antacid suspension containing magnesium and aluminium hydroxides decreased plasma concentrations of atorvastatin by approximately 35%; however, LDL-C reduction was not altered.
    Warfarin: Atorvastatin interaction studies with warfarin was conducted, and no clinically significant interactions were seen. Nevertheless, patients receiving warfarin should be closely monitored when atorvastatin is added to their therapy.
    Colchicine: Although interaction studies with atorvastatin and colchicine have not been conducted, cases of myopathy have been reported with atorvastatin co-administered with colchicine, and caution should be exercised when prescribing atorvastatin with colchicine.
    Phenazone: Coadministration of multiple doses of atorvastatin and phenazone showed little or no detectable effect in the clearance of phenazone.
    Amlodipine: In a drug-drug interaction study in healthy subjects, co-adminstration of atorvastatin 80 mg and amlodipine 10 mg resulted in an 18% increase in exposure to atorvastatin which was not clinically meaningful.
    Fusidic acid: Although interaction studies with atorvastatin and fusidic acid have not been conducted, severe muscle problems such as rhabdomyolysis have been reported in post-marketing experience with this combination. Patients should be closely monitored and temporary suspension of atorvastatin treatment may be appropriate.
    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 all specific agents have not been conducted.
    For full details see prescribing information.


    Pregnancy and Lactation

    This product  is contraindicated in pregnancy and while breast feeding. Women of childbearing potential should use appropriate contraceptive measures. The safety of this product in pregnancy and lactation has not yet been proven. There is evidence from animal studies that HMG-CoA reductase inhibitors may influence the development of embryos or fetuses. The development of rat offspring was delayed and post-natal survival reduced during exposure of the dams to atorvastatin at doses of about 30 times (rat) or 20 times (rabbit) mg/kg/day the human exposure based on surface area (mg/m2).Rare reports of congenital anomalies have been received following intrauterine exposure to HMG-CoA reductase inhibitors. There has been one report of severe congenital bony deformity, tracheoesophagealfistula, and anal atresia (VATER association) in a baby born to a woman who took lovastatin withdextroamphetamine sulfate during the first trimester of pregnancy.
    This product 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. If the patient becomes pregnant while taking this drug, therapy should be discontinued and the patient apprised of the potential hazard to the fetus. It is not known whether this drug is excreted in human milk. Nursing rat pups had plasma and liver drug levels of 50%and 40%, respectively, of that in their mother’s milk. Because of the potential for adverse reactions in nursing infants, women taking this product  should not breast-feed.


    Overdose

    Specific treatment is not available for this product  overdosage. Should an overdose occur, the patient should be treatedsymptomatically and supportive measures instituted, as required. Liver function tests and serum CPK levels should be monitored. Due to extensive drug binding to plasma proteins, haemodialysis is not expected to significantly enhance this product  clearance.


    Manufacturer
    Pfizer Germany
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