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Ezetimibe And Simvastatin is a brand name for Simvastatin. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS AND USAGE Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet…
Verbatim from this product's FDA label. Tap a section to expand.
2 DOSAGE AND ADMINISTRATION • Dose range is 10 mg/10 mg/day to 10 mg/40 mg/day. 1 ) • Recommended usual starting dose is 10 mg/10 mg or 10 mg/20 mg/day. , for 12 months or more) without evidence of muscle toxicity. 2 ) • Patients who are currently tolerating the 10 mg/80 mg dose of ezetimibe and simvastatin tablets who need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to an alternative statin or statin-based regimen with less potential for the drug-drug interaction.
2 ) • Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 10 mg/80 mg dose of ezetimibe and simvastatin tablets, patients unable to achieve their LDL-C goal utilizing the 10 mg/40 mg dose of ezetimibe and simvastatin tablets should not be titrated to the 10 mg/80 mg dose, but should be placed on alternative LDL-C-lowering treatment(s) that provides greater LDL-C lowering.
2 ) • Dosing of ezetimibe and simvastatin tablets should occur either ≥ 2 hours before or ≥ 4 hours after administration of a bile acid sequestrant. 1 Recommended Dosing The usual dosage range is 10 mg/10 mg/day to 10 mg/40 mg/day. The recommended usual starting dose is 10 mg/10 mg/day or 10 mg/20 mg/day.
Ezetimibe and simvastatin tablets should be taken as a single daily dose in the evening, with or without food. 73 m 2 ). After initiation or titration of ezetimibe and simvastatin tablets, lipid levels may be analyzed after 2 or more weeks and dosage adjusted, if needed.
1 ) ]. Patients who are currently tolerating the 10 mg/80 mg dose of ezetimibe and simvastatin tablets who need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to an alternative statin or statin-based regimen with less potential for the drug-drug interaction.
Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 10 mg/80 mg dose of ezetimibe and simvastatin tablets, patients unable to achieve their LDL-C goal utilizing the 10 mg/40 mg dose of ezetimibe and simvastatin tablets should not be titrated to the 10 mg/80 mg dose, but should be placed on alternative LDL-C-lowering treatment(s) that provides greater LDL-C lowering.
3 ) ]. 3 ) ]. 5 ) ]. 2 ) ]. , LDL apheresis) in these patients or if such treatments are unavailable. Simvastatin exposure is approximately doubled with concomitant use of lomitapide; therefore, the dose of ezetimibe and simvastatin tablets should be reduced by 50% if initiating lomitapide.
3 ) ] • Common (incidence ≥ 2% and greater than placebo) adverse reactions in clinical trials: headache, increased ALT, myalgia, upper respiratory tract infection, and diarrhea. 1 ) To report SUSPECTED ADVERSE REACTIONS, contact Dr.
Reddy’s Laboratories, Inc. gov/medwatch . 1 Clinical Trials Experience Ezetimibe and Simvastatin Tablets Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
2% of patients on placebo discontinued due to adverse reactions. 8%). Ezetimibe and simvastatin tablets have been evaluated for safety in more than 10,189 patients in clinical trials. Table 2 summarizes the frequency of clinical adverse reactions reported in ≥ 2% of patients treated with ezetimibe and simvastatin tablets (n = 1,420) and at an incidence greater than placebo, regardless of causality assessment, from four placebo-controlled trials.
3 1. Includes two placebo-controlled combination studies in which the active ingredients equivalent to ezetimibe and simvastatin tablets were coadministered and two placebo-controlled studies in which ezetimibe and simvastatin tablets were administered.
2 . All doses. 9 years. 4% vs. 8% among patients allocated to ezetimibe and simvastatin and placebo, respectively. Comparing those allocated to ezetimibe and simvastatin vs. 2% vs. 09% vs. 02%, respectively. 7% vs. 6%, respectively. 5% vs. 9% patients ever reported muscle symptoms in the ezetimibe and simvastatin and placebo groups, respectively.
4% vs. 5% of patients assigned to ezetimibe and simvastatin and placebo, respectively. Ezetimibe Other adverse reactions reported with ezetimibe in placebo-controlled studies, regardless of causality assessment: Musculoskeletal system disorders: arthralgia; Infections and infestations: sinusitis; Body as a whole – general disorders: fatigue.
5 WARNINGS AND PRECAUTIONS Patients should be advised of the increased risk of myopathy, including rhabdomyolysis, with the 10 mg/80 mg dose. 1 ) Patients should be advised to report promptly any unexplained and/or persistent muscle pain, tenderness, or weakness.
Ezetimibe and simvastatin tablets should be discontinued immediately if myopathy is diagnosed or suspected. 1 ). , myopathy and rhabdomyolysis): Risks increase with higher doses and concomitant use of certain medicines. Predisposing factors include advanced age (≥65), female gender, uncontrolled hypothyroidism, and renal impairment.
Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported. 6 ).
Immune-Mediated Necrotizing Myopathy (IMNM):
There have been rare reports of IMNM, an autoimmune myopathy, associated with statin use. IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents.
2 ).
Liver enzyme abnormalities:
Persistent elevations in hepatic transaminases can occur. Check liver enzyme tests before initiating therapy and as clinically indicated thereafter. 1 Myopathy/Rhabdomyolysis Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase above ten times the upper limit of normal (ULN).
Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased elevated plasma levels of simvastatin and simvastatin acid.
1 ) ]. 1 ) ]. 2 ) ]. 3 ) ]. • Women who are pregnant or may become pregnant. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Because HMG-CoA reductase inhibitors (statins), such as simvastatin, decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, ezetimibe and simvastatin tablets may cause fetal harm when administered to a pregnant woman.
Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. There are no adequate and well-controlled studies of ezetimibe and simvastatin tablet use during pregnancy; however, in rare reports congenital anomalies were observed following intrauterine exposure to statins.
In rat and rabbit animal reproduction studies, simvastatin revealed no evidence of teratogenicity. Ezetimibe and simvastatin tablets should be administered to women of childbearing age only when such patients are highly unlikely to conceive.
1 ) ]. • Nursing mothers. It is not known whether simvastatin is excreted into human milk; however, a small amount of another drug in this class does pass into breast milk. 3 ) ]. • Concomitant administration of strong CYP3A4 inhibitors.
1 ) • Concomitant administration of gemfibrozil, cyclosporine, or danazol. 3 )
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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, for 12 months or more, without evidence of muscle toxicity) while taking lomitapide. 73 m 2 ), no dosage adjustment is necessary. 73 m 2 , the dose of ezetimibe and simvastatin tablets is 10 mg/20 mg/day in the evening. 3 ) ]. 3 ) ].
02% for patients on 20 mg/day. 4% compared with 0% for patients on 20 mg/day. The incidence of myopathy, including rhabdomyolysis, was highest during the first year and then notably decreased during the subsequent years of treatment.
In this trial, patients were carefully monitored and some interacting medicinal products were excluded. Other adverse reactions reported with simvastatin in placebo-controlled clinical studies, regardless of causality assessment: Cardiac disorders: atrial fibrillation; Ear and labyrinth disorders: vertigo; Gastrointestinal disorders: abdominal pain, constipation, dyspepsia, flatulence, gastritis; Skin and subcutaneous tissue disorders: eczema, rash; Endocrine disorders: diabetes mellitus; Infections and infestations: bronchitis, sinusitis, urinary tract infections; Body as a whole – general disorders: asthenia, edema/swelling; Psychiatric disorders: insomnia.
3 ) ]. Elevated alkaline phosphatase and γ-glutamyl transpeptidase have been reported. About 5% of patients taking simvastatin had elevations of CK levels of 3 or more times the normal value on one or more occasions. 1 ) ]. 2 Postmarketing Experience Because the below reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
1 ) ]; hepatitis/jaundice; fatal and non-fatal hepatic failure; depression; cholelithiasis; cholecystitis; thrombocytopenia; elevations in liver transaminases; elevated creatine phosphokinase. 1 ) ]. Hypersensitivity reactions, including anaphylaxis, angioedema, rash, and urticaria have been reported.
In addition, an apparent hypersensitivity syndrome has been reported rarely that has included one or more of the following features: anaphylaxis, angioedema, lupus erythematous-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, chills, flushing, malaise, dyspnea, toxic epidermal necrolysis, erythema multiforme, including Stevens-Johnson syndrome.
, memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).
Predisposing factors for myopathy include advanced age (≥ 65 years), female gender, uncontrolled hypothyroidism, and renal impairment. 8) ] The risk of myopathy, including rhabdomyolysis, is dose related. 08% at 20 and 40 mg/day, respectively.
61%) was disproportionately higher than that observed at the lower doses. In these trials, patients were carefully monitored and some interacting medicinal products were excluded. 02% for patients on 20 mg/day. 4% compared with 0% for patients on 20 mg/day.
The incidence of myopathy, including rhabdomyolysis, was highest during the first year and then notably decreased during the subsequent years of treatment. In this trial, patients were carefully monitored and some interacting medicinal products were excluded.
The risk of myopathy, including rhabdomyolysis, is greater in patients on simvastatin 80 mg compared with other statin therapies with similar or greater LDL-C-lowering efficacy and compared with lower doses of simvastatin. 2 ) ]. If, however, a patient who is currently tolerating the 10 mg/80 mg dose of ezetimibe and simvastatin tablets needs to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin, that patient should be switched to an alternative statin or statin-based regimen with less potential for the drug-drug interaction.
Patients should be advised of the increased risk of myopathy, including rhabdomyolysis, and to report promptly any unexplained muscle pain, tenderness or weakness. 2 ) ]. In the Study of Heart and Renal Protection (SHARP), 9,270 patients with chronic kidney disease were allocated to receive ezetimibe and simvastatin tablets 10 mg/20 mg daily (n = 4,650) or placebo (n = 4,620).
02% for placebo. In postmarketing experience with ezetimibe, cases of myopathy and rhabdomyolysis have been reported. Most patients who developed rhabdomyolysis were taking a statin prior to initiating ezetimibe. However, rhabdomyolysis has been reported with ezetimibe monotherapy and with the addition of ezetimibe to agents known to be associated with increased risk of rhabdomyolysis, such as fibric acid derivatives.
Ezetimibe and simvastatin tablets and a fenofibrate, if taking concomitantly, should both be immediately discontinued if myopathy is diagnosed or suspected. All patients starting therapy with ezetimibe and simvastatin tablets or whose dose of ezetimibe and simvastatin tablets is being increased should be advised of the risk of myopathy, including rhabdomyolysis, and told to report promptly any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing ezetimibe and simvastatin tablets.
Ezetimibe and simvastatin tablet therapy should be discontinued immediately if myopathy is diagnosed or suspected. In most cases, muscle symptoms and CK increases resolved when simvastatin treatment was promptly discontinued. Periodic CK determinations may be considered in patients starting therapy with ezetimibe and simvastatin tablets or whose dose is being increased, but there is no assurance that such monitoring will prevent myopathy.
Many of the patients who have developed rhabdomyolysis on therapy with simvastatin have had complicated medical histories, including renal insufficiency usually as a consequence of long-standing diabetes mellitus. Such patients taking ezetimibe and simvastatin tablets merit closer monitoring.
Ezetimibe and simvastatin tablet therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. , sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy.
Drug Interactions The risk of myopathy and rhabdomyolysis is increased by elevated plasma levels of simvastatin and simvastatin acid. Simvastatin is metabolized by the cytochrome P450 isoform 3A4. Certain drugs that inhibit this metabolic pathway can raise the plasma levels of simvastatin and may increase the risk of myopathy.
3 ) ]. Combination of these drugs with ezetimibe and simvastatin tablets is contraindicated. If short-term treatment with strong CYP3A4 inhibitors is unavoidable, therapy with ezetimibe and simvastatin tablets must be suspended during the course of treatment [ see Contraindications ( 4 ) and Drug Interactions ( 7 ) ].
2 ) ]. 7 ) ]. 9 ) ]. 3 )]. Cases of myopathy, including rhabdomyolysis, have been observed with simvastatin coadministered with lipid-modifying doses (≥ 1 g/day niacin) of niacin-containing products. 4 ) ]. Cases of rhabdomyolysis have been reported with ezetimibe and simvastatin tablets administered with daptomycin.
10 )]. 3 ) ]. , for 12 months or more) without evidence of muscle toxicity, do not exceed ezetimibe and simvastatin tablets, 10 mg/40 mg daily when taking lomitapide. 2 immune-mediated necrotizing myopathy There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use.
IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents.
Additional neuromuscular and serologic testing may be necessary. Treatment with immunosuppressive agents may be required. Consider risk of IMNM carefully prior to initiation of a different statin. If therapy is initiated with a different statin, monitor for signs and symptoms of IMNM.
6% for patients treated with ezetimibe and simvastatin tablet 10/80. 6% for patients treated with ezetimibe and simvastatin tablet 10/80. These elevations in transaminases were generally asymptomatic, not associated with cholestasis, and returned to baseline after discontinuation of therapy or with continued treatment.
In SHARP, 9270 patients with chronic kidney disease were allocated to receive ezetimibe and simvastatin tablet 10/20 mg daily (n=4650), or placebo (n=4620). 6% for placebo. It is recommended that liver function tests be performed before the initiation of treatment with ezetimibe and simvastatin tablet, and thereafter when clinically indicated.
There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including simvastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with ezetimibe and simvastatin tablet, promptly interrupt therapy.
If an alternate etiology is not found do not restart ezetimibe and simvastatin tablet. 1)]. ezetimibe and simvastatin tablet should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease.
Active liver diseases or unexplained persistent transaminase elevations are contraindications to the use of ezetimibe and simvastatin tablet. 4 Endocrine Function Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including simvastatin.