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  • Atozet
    / MSD


    Active Ingredient *
    Ezetimibe 10 mg
    Atorvastatin 10, 20, 40, 80 mg

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    Film Coated Tablets

    30 X 10 mg / 10 mg

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    Film Coated Tablets

    30 X 10 mg / 20 mg

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    Film Coated Tablets

    30 X 10 mg / 40 mg

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    Film Coated Tablets

    30 X 10 mg / 80 mg

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    Related information


    Dosage

    Hypercholesterolaemia and/or Coronary Heart Disease (with ACS History): The patient should be on an appropriate lipid-lowering diet and should continue on this diet during treatment with this drug.
    The dose range is 10/10 mg/day through 10/80 mg/day. The typical dose is 10/10 mg once a day. The patient’s low-density lipoprotein cholesterol (LDL-C) level, coronary heart disease risk status, and response to current cholesterol-lowering therapy should be considered when starting therapy or adjusting the dose.
    The dose should be individualised based on the known efficacy of the various dose strengths of and the response to the current cholesterol-lowering therapy. Adjustment of dose should be made at intervals of 4 weeks or more.
    Homozygous Familial Hypercholesterolaemia: The dose in patients with homozygous FH is 10/10 to 10/80 mg daily. The drug  may be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.
    May be taken with or without food.


    Indications

    Prevention of Cardiovascular Events: indicated to reduce the risk of cardiovascular events in patients with coronary heart disease (CHD) and a history of acute coronary syndrome (ACS), either previously treated with a statin or not.
    Hypercholesterolaemia: indicated as adjunctive therapy to diet for use in adults with primary (heterozygous familial and non-familial) hypercholesterolaemia or mixed hyperlipidaemia where use of a combination product is appropriate:
    – patients not appropriately controlled with a statin alone
    – patients already treated with a statin and ezetimibe
    Homozygous Familial Hypercholesterolaemia (HoFH): indicated as adjunctive therapy to diet for use in adults with HoFH. Patients may also receive adjunctive treatments (e.g., low-density lipoprotein [LDL] apheresis).


    Contra-Indications

    Hypersensitivity to the active substances or to any of the excipients.
    Therapy with this drug is contraindicated during pregnancy and breast-feeding, and in women of child-bearing potential not using appropriate contraceptive measures.


    Special Precautions

    Myopathy/Rhabdomyolysis: In post-marketing experience with ezetimibe, cases of myopathy and rhabdomyolysis have been reported. Most patients who developed rhabdomyolysis were taking a statin concomitantly with ezetimibe. However, rhabdomyolysis has been reported very rarely with ezetimibe monotherapy and very rarely with the addition of ezetimibe to other agents known to be associated with increased risk of rhabdomyolysis.
    This formulation contains atorvastatin. Atorvastatin, like other HMG-CoA reductase inhibitors, may in rare occasions affect the skeletal muscle and cause myalgia, myositis, and myopathy that may progress to rhabdomyolysis, a potentially life-threatening condition characterised by markedly elevated creatine phosphokinase (CPK) levels (>10 times ULN), myoglobinaemia and myoglobinuria, which may lead to renal failure.
    Before the treatment: The drug should be prescribed with caution in patients with pre-disposing factors for rhabdomyolysis. A CPK level should be measured before starting treatment in the following situations:
    – Renal impairment,
    – Hypothyroidism,
    – Personal or familial history of hereditary muscular disorders,
    – Previous history of muscular toxicity with a statin or fibrate,
    – Previous history of liver disease and/or where substantial quantities of alcohol are consumed,
    – in elderly (age >70 years), the necessity of such measurement should be considered, according to the presence of other predisposing factors for rhabdomyolysis,
    – situations where an increase in plasma levels may occur, such as interactions and special populations including genetic subpopulations.
    Creatine phosphokinase measurement: Creatine phosphokinase (CPK) should not be measured following strenuous exercise or in the presence of any plausible alternative cause of CPK increase as this makes value interpretation difficult. If CPK levels are significantly elevated at baseline (>5 times ULN), levels should be remeasured within 5 to 7 days later to confirm the results.
    See prescribing information for full details.


    Side Effects

    Common: Diarrhoea, Myalgia.
    See prescribing information for full details.


    Drug interactions

    Multiple mechanisms may contribute to potential interactions with HMG Co-A reductase inhibitors. Drugs or herbal products that inhibit certain enzymes (e.g. CYP3A4) and/or transporter (e.g., OATP1B) pathways may increase atorvastatin plasma concentrations and may lead to an increased risk of myopathy/rhabdomyolysis.
    Ezetimibe:
    Antacids: Concomitant antacid administration decreased the rate of absorption of ezetimibe but had no effect on the bioavailability of ezetimibe. This decreased rate of absorption is not considered clinically significant.
    Cholestyramine: Concomitant cholestyramine administration decreased the mean area under the curve (AUC) of total ezetimibe (ezetimibe + ezetimibe glucuronide) approximately 55%. The incremental low-density lipoprotein cholesterol (LDL-C) reduction due to adding this drug to cholestyramine may be lessened by this interaction.
    Cyclosporine: Caution should be exercised when initiating  this drug  in the setting of ciclosporin. Ciclosporine concentrations should be monitored in patients receiving this drug  and ciclosporine. See prescribing information for full details.
    Atorvastatin:
    CYP3A4 inhibitors: Potent CYP3A4 inhibitors have been shown to lead to markedly increased concentrations of atorvastatin.
    Moderate CYP3A4 inhibitors (e.g., erythromycin, diltiazem, verapamil and fluconazole) may increase plasma concentrations of atorvastatin . An increased risk of myopathy has been observed with the use of erythromycin in combination with statins. Interaction studies evaluating the effects of amiodarone or verapamil on atorvastatin have not been conducted. Both amiodarone and verapamil are known to inhibit CYP3A4 activity and co-administration with this drug  may result in increased exposure to atorvastatin. Therefore, a lower maximum dose of this drug  should be considered and appropriate clinical monitoring of the patient is recommended when concomitantly used with moderate CYP3A4 inhibitors. Appropriate clinical monitoring is recommended after initiation or following dose adjustments of the inhibitor.
    Inhibitors of Breast Cancer Resistant Protein (BCRP): Concomitant administration of products that are inhibitors of BCRP (e.g., elbasvir and grazoprevir) may lead to increased plasma concentrations of atorvastatin and an increased risk of myopathy; therefore a dose adjustment of atorvastatin should be considered depending on the prescribed dose.
    Inducers of cytochrome P450 3A4: Concomitant administration of atorvastatin with inducers of cytochrome P450 3A4 (e.g., efavirenz, rifampicin, St. John’s Wort) can lead to variable reductions in plasma concentrations of atorvastatin. Due to the dual interaction mechanism of rifampicin, (cytochrome P450 3A4 induction and inhibition of hepatocyte uptake transporter OATP1B1), simultaneous co-administration of this drug  with rifampicin is recommended, as delayed administration of atorvastatin after administration of rifampicin has been associated with a significant reduction in atorvastatin plasma concentrations. The effect of rifampicin on atorvastatin concentrations in hepatocytes is, however, unknown and if concomitant administration cannot be avoided, patients should be carefully monitored for efficacy.
    See prescribing information for full details.


    Pregnancy and Lactation

    The drug is contraindicated during pregnancy and breast-feeding, and in women of child-bearing potential not using appropriate contraceptive measures.
    See prescribing information for full details.


    Overdose

    In the event of an overdose, symptomatic and supportive measures should be employed. Liver function tests should be performed and serum CPK levels should be monitored.
    Ezetimibe: In clinical studies, administration of ezetimibe, 50 mg/day to 15 healthy subjects for up to 14 days, or 40 mg/day to 18 patients with primary hyperlipidaemia for up to 56 days, was generally well tolerated. A few cases of overdose have been reported; most have not been associated with adverse experiences. Reported adverse experiences have not been serious. In animals, no toxicity was observed after single oral doses of 5000 mg/kg of ezetimibe in rats and mice and 3000 mg/kg in dogs.
    Atorvastatin: Due to extensive atorvastatin binding to plasma proteins, haemodialysis is not expected to significantly enhance atorvastatin clearance.


    Important notes

    Storage: Store below 30ºC. Store in the original package in order to protect from oxygen.


    Manufacturer
    Merck Sharp & Dohme Corp., USA
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