ezetimibe and simvastatin
Tablet · Oral
Uses
Ezetimibe and Simvastatin Tablets Ezetimibe and Simvastatin Tablets are a combination of simvastatin and ezetimibe indicated:
• As an adjunct to diet to reduce elevated low density lipoprotein cholesterol (LDL-C):
• In adults with primary hyperlipidemia.
• In adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH).
• As an adjunct to other LDL-C-lowering therapies to reduce elevated LDL-C in adults with homozygous familial hypercholesterolemia (HoFH). Simvastatin Simvastatin, when used as a component of ezetimibe and simvastatin tablets, is indicated to reduce the risk of total mortality by reducing risk of coronary heart disease death, non-fatal myocardial infarction and stroke, and the need for coronary and non-coronary revascularization procedures in adults with established coronary heart disease, cerebrovascular disease, peripheral vascular disease, and/or diabetes, who are at high risk of coronary heart disease events. Ezetimibe and simvastatin tablets are a combination of ezetimibe, a dietary cholesterol absorption inhibitor, and simvastatin, an HMG-CoA reductase inhibitor (statin) indicated: ( 1 )
• As an adjunct to diet to reduce elevated low density lipoprotein cholesterol (LDL-C):
• In adults with primary hyperlipidemia.
• In adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH).
• As an adjunct to other LDL-C lowering therapies to reduce LDL-C in adults with homozygous familial hypercholesterolemia (HoFH). Simvastatin Simvastatin, when used as a component of ezetimibe and simvastatin tablets, is indicated to reduce the risk of total mortality by reducing risk of coronary heart disease death, non-fatal myocardial infarction and stroke, and the need for coronary and non-coronary revascularization procedures in adults with established coronary heart disease, cerebrovascular disease, peripheral vascular disease, and/or diabetes, who are at high risk of coronary heart disease events.
Dosage and administration
• Important Dosage and Administration Information: ( 2.1 )
• Take ezetimibe and simvastatin tablets orally once daily in the evening with or without food.
• Maximum recommended dosage is ezetimibe and simvastatin tablets 10/40 mg once daily. Ezetimibe and simvastatin tablets 10/80 mg daily dosage is restricted to patients who have been taking ezetimibe and simvastatin tablets 10/80 mg daily chronically (e.g., for 12 months or more) without evidence of muscle toxicity.
• For patients that require a high-intensity statin or are unable to achieve their LDL-C goal receiving ezetimibe and simvastatin tablets 10/40 mg daily, prescribe alternative LDL-C-lowering treatment.
• If as dose is missed, take the missed dose as soon as possible. Do not double the next dose.
• Assess LDL-C when clinically appropriate, as early as 2 weeks after initiating ezetimibe and simvastatin tablets, and adjust the dosage if necessary.
• Adults: Recommended dosage range of 10/10 mg to 10/40 mg once daily. ( 2.2 )
• See full prescribing information for ezetimibe and simvastatin tablets dosage modifications due to drug interactions. ( 2.3 )
• Patients with Renal Impairment: Doses exceeding 10/20 mg should be used with caution and close monitoring in patients with moderate to severe renal impairment. ( 2.4 ) 2.1 Important Dosage and Administration Information
• Take ezetimibe and simvastatin tablets orally once daily in the evening with or without food.
• The maximum recommended dosage is ezetimibe and simvastatin tablets 10/40 mg once daily. The ezetimibe and simvastatin tablets 10/80 mg daily dosage is restricted to adult patients who have been taking ezetimibe and simvastatin tablets 10/80 mg daily chronically (e.g., for 12 months or more) without evidence of muscle toxicity [see Warnings and Precautions ( 5.1 )] .
• For patients that require a high-intensity statin or are unable to achieve their LDL-C goal receiving ezetimibe and simvastatin tablets 10/40 mg daily, prescribe alternative LDL-C-lowering treatment.
• If as dose is missed, take the missed dose as soon as possible. Do not double the next dose.
• Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating ezetimibe and simvastatin tablets, and adjust the dosage if necessary. 2.2 Recommended Dosage in Adult Patients The recommended dosage range of ezetimibe and simvastatin tablets 10/10 mg to 10/40 mg once a day. 2.3 Recommended Dosage in Pediatric Patients 10 Years of Age and Older with HeFH The recommended dosage range of ezetimibe and simvastatin tablets 10/10 mg to 10/40 mg once a day. 2.4 Recommended Dosage in Patients with Renal Impairment Renal impairment is a risk factor for statin-associated myopathy. Doses of ezetimibe and simvastatin tablets exceeding 10/20 mg should be used with caution and close monitoring in patients with moderate to severe renal impairment [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.6 )] . There are no dosage adjustment recommendations for patients with mild renal impairment. 2.5 Dosage Modification Due to Drug Interactions Concomitant use of ezetimibe and simvastatin tablets with the following drugs requires dosage modification of ezetimibe and simvastatin tablets [see Warnings and Precautions (5.1) and Drug Interactions ( 7.1 )]. Patients taking Lomitapide Reduce the dosage of ezetimibe and simvastatin tablets by 50%. Do not exceed ezetimibe and simvastatin tablets 10/20 mg once daily (or 10/40 mg once daily for patients who have previously taken ezetimibe and simvastatin tablets 10/80 mg daily chronically while taking lomitapide) [see Dosage and Administration ( 2.1 )]. Patients taking Verapamil, Diltiazem, or Dronedarone Do not exceed ezetimibe and simvastatin tablets 10/10 mg once daily. Patients taking Amiodarone, Amlodipine, or Ranolazine Do not exceed ezetimibe and simvastatin tablets 10/20 mg once daily. Patients taking Bile Acid Sequestrants In patients taking a bile acid sequestrant, administer ezetimibe and simvastatin tablets at least 2 hours before or 4 hours after the bile acid sequestrant.
Dosage forms and strengths
Ezetimibe and simvastatin tablets: 1. Ezetimibe and Simvastatin Tablets 10 mg/10 mg are white to off-white, capsule shaped, uncoated tablets debossed with ‘G’ on one side and ‘321’ on the other side. 2. Ezetimibe and Simvastatin Tablets 10 mg/20 mg are white to off-white, capsule shaped, uncoated tablets debossed with ‘G’ on one side and ‘322’ on the other side. 3. Ezetimibe and Simvastatin Tablets 10 mg/40 mg are white to off-white, capsule shaped, uncoated tablets debossed with ‘G’ on one side and ‘323’ on the other side. 4. Ezetimibe and Simvastatin Tablets 10 mg/80 mg are white to off-white, capsule shaped, uncoated tablets debossed with ‘G’ on one side and ‘324’ on the other side.
• Tablets (ezetimibe mg/simvastatin mg): 10/10, 10/20, 10/40, 10/80 ( 3 )
Contraindications
Ezetimibe and simvastatin tablets are contraindicated in the following conditions:
• Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) [see Drug Interactions ( 7.1 )].
• Concomitant use of cyclosporine, danazol, or danazol [see Drug Interactions ( 7.1 )].
• Acute liver failure or decompensated cirrhosis [see Warnings and Precautions ( 5.3 )].
• Hypersensitivity to simvastatin, ezetimibe, or any excipients in ezetimibe and simvastatin tablets. Hypersensitivity reactions, including anaphylaxis, angioedema, and Stevens-Johnson syndrome, have been reported [see Adverse Reactions ( 6.2 )].
• Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications and nefazodone). ( 4 )
• Concomitant use of cyclosporine, danazol or gemfibrozil. ( 4 )
• Acute liver failure or decompensated cirrhosis. ( 4 )
• Hypersensitivity to simvastatin, ezetimibe or any excipient of ezetimibe and simvastatin tablets. ( 4)
Warnings and precautions
• Myopathy and Rhabdomyolysis: Risk factors include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs, and higher ezetimibe and simvastatin tablets dosage. Chinese patients may be at higher risk for myopathy. Discontinue ezetimibe and simvastatin tablets if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Temporarily discontinue ezetimibe and simvastatin tablets in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis. Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing ezetimibe and simvastatin tablets dosage. Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. ( 5.1 )
• Immune-Mediated Necrotizing Myopathy (IMNM): Rare reports of IMNM, an autoimmune myopathy, have been reported. Discontine ezetimibe and simvastatin tablets if IMNM is suspected. ( 5.2 )
• Hepatic Dysfunction: Increases in serum transaminases have occurred, some persistent. Rare reports of fatal and non-fatal hepatic failure have occurred. Consider testing liver enzyme before initiating therapy and as clinically indicated thereafter. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue ezetimibe and simvastatin tablets. ( 5.3 ) 5.1 Myopathy and Rhabdomyolysis Ezetimibe and simvastatin tablets may cause myopathy and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including ezetimibe and simvastatin tablets. In clinical trials of 24,747 simvastatin-treated patients with a median follow-up of 4 years, the incidence of myopathy, defined as unexplained muscle weakness, pain, or tenderness accompanied by creatinine kinase (CK) increases greater than ten times the upper limit of normal (10 X ULN), were approximately 0.03%, 0.08%, and 0.61% in patients treated with simvastatin 20 mg, 40 mg, and 80 mg daily, respectively. In another clinical trial of 12,064 simvastatin-treated patients (with a history of myocardial infarction) with a mean follow-up of 6.7 years, the incidences of myopathy in patients taking simvastatin 20 mg and 80 mg daily were approximately 0.02% and 0.9%, respectively. The incidences of rhabdomyolysis (defined as myopathy with a CK >40 X ULN) in patients taking simvastatin 20 mg and 80 mg daily were approximately 0% and 0.4%, respectively [see Adverse Reactions ( 6.1 )]. In the Trial of Heart and Renal Protection (SHARP) , 9270 patients with chronic kidney disease were allocated to receive ezetimibe and simvastatin tablets 10/20 mg daily (n=4650) or placebo (n=4620). During a median follow-up period of 4.9 years, the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum creatine kinase [CK] >10 times upper limit of normal [ULN]) was 0.2% for ezetimibe and simvastatin tablets and 0.1% for placebo: the incidence of rhabdomyolysis (defined as myopathy with a CK > 40 times ULN) was 0.09% for ezetimibe and simvastatin tablets and 0.02% 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. Risk Factors for Myopathy Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs (including other lipid-lowering therapies), and higher ezetimibe and simvastatin tablets dosage; Chinese patients on ezetimibe and simvastatin tablets may be at higher risk for myopathy [see Contraindications ( 4 ), Drug Interactions ( 7.1 ), and Use in Specific Populations ( 8.8 )]. The risk of myopathy is increased by elevated plasma levels of simvastatin and simvastatin acid. The risk is also greater in patients taking ezetimibe and simvastatin tablets 80 mg daily compared with patients taking lower ezetimibe and simvastatin tablets dosages and compared with patients using other statins with similar or greater LDL-C-lowering efficacy [see Adverse Reactions ( 6.1 )]. Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis The concomitant use of strong CYP3A4 inhibitors with ezetimibe and simvastatin tablets are contraindicated. If short-term treatment with strong CYP3A4 inhibitors is required, temporarily suspend ezetimibe and simvastatin tablets during the duration of strong CYP3A4 inhibitor treatment. The concomitant use of ezetimibe and simvastatin tablets with gemfibrozil, cyclosporine, or danazol is also contraindicated [see Contraindications ( 4 ) and Drug Interactions ( 7.1 )]. Ezetimibe and simvastatin tablets dosage modifications are recommended for patients taking lomitapide, verapamil, diltiazem, dronedarone, amiodarone, amlodipine or ranolazine [see Dosage and Administration ( 2.5 )]. Ezetimibe and simvastatin tablets use should be temporarily suspended in patients taking daptomycin. Lipid modifying doses (≥1 gram/day) of niacin, fibrates, colchicine, and grapefruit juice may also increase the risk of myopathy and rhabdomyolysis [see Drug Interactions ( 7.1 )]. Use the 80 mg daily dosage of ezetimibe and simvastatin tablets only in patients who have been taking simvastatin 80 mg daily chronically without evidence of muscle toxicity [see Dosage and Administration ( 2.1 )].
Side effects
The following serious adverse reactions are discussed in greater detail in other sections of the label:
• Myopathy and Rhabdomyolysis [see Warnings and Precautions ( 5.1 )]
• Immune-Mediated Necrotizing Myopathy [see Warnings and Precautions ( 5.2 )]
• Hepatic Dysfunction [see Warnings and Precautions ( 5.3 )]
• Increases in HbA1c and Fasting Serum Glucose Levels [see Warnings and Precautions ( 5.4 )]
• Common (incidence ≥2% and greater than placebo) adverse reactions in clinical trials: headache, increased ALT, myalgia, upper respiratory tract infection, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact NorthStar RxLLC at 1-800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience 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. Ezetimibe and simvastatin tablets In the ezetimibe and simvastatin tablets placebo-controlled clinical trials database of 1420 patients (age range 20 to 83 years, 52% female, 87% White, 3% Black or African American, 3% Asians, 5% other races identified as Hispanic or Latino ethnicity) with a median treatment duration of 27 weeks, 5% of patients on ezetimibe and simvastatin tablets and 2.2% of patients on placebo discontinued due to adverse reactions. The most commonly reported adverse reactions (incidence ≥2% and greater than placebo) in controlled clinical trials were: headache (5.8%), increased ALT (3.7%), myalgia (3.6%), upper respiratory tract infection (3.6%), and diarrhea (2.8%). The most common adverse reactions in the group treated with ezetimibe and simvastatin tablets that led to treatment discontinuation and occurred at a rate greater than placebo were: increased ALT (0.9%), myalgia (0.6%), increased AST (0.4%), and back pain (0.4%). Ezetimibe and simvastatin tablets have been evaluated for safety in more than 10,189 patients in clinical trials. Table 1 summarizes the frequency of clinical adverse reactions reported in ≥2% of patients treated with ezetimibe and simvastatin tablets (n=1420) and at an incidence greater than placebo from four placebo-controlled trials. Table 1*: Adverse Reactions Reported ≥2% of Patients Treated with Ezetimibe and Simvastatin Tablets at an Incidence Greater than Placebo Regardless of Causality % Placebo N = 371 % Ezetimibe 10 mg N = 302 % Simvastatin N = 1234 % Ezetimibe and Simvastatin Tablets N = 1420 Headache 5.4 6 5.9 5.8 Upper respiratory tract infection 2.7 5 5 3.6 Myalgia 2.4 2.3 2.6 3.6 Diarrhea 2.2 5 3.7 2.8 Pain in extremity 1.3 3 2 2.3 Influenza 0.8 1 1.9 2.3 Study of Heart and Renal Protection In SHARP , 9270 patients were allocated to ezetimibe and simvastatin tablets 10/20 mg daily (n=4650) or placebo (n=4620) for a median follow-up period of 4.9 years. The proportion of patients who permanently discontinued trial treatment as a result of either an adverse event or abnormal safety blood result was 10.4% vs. 9.8% among patients allocated to ezetimibe and simvastatin tablets and placebo, respectively. Comparing those allocated to ezetimibe and simvastatin tablets vs. placebo, the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum CK >10 times ULN) was 0.2% vs. 0.1% and the incidence of rhabdomyolysis (defined as myopathy with a CK >40 times ULN) was 0.09% vs. 0.02%, respectively. Consecutive elevations of transaminases (>3 X ULN) occurred in 0.7% vs. 0.6%, respectively. Patients were asked about the occurrence of unexplained muscle pain or weakness at each trial visit: 21.5% vs. 20.9% patients ever reported muscle symptoms in the ezetimibe and simvastatin tablets and placebo groups, respectively. Cancer was diagnosed during the trial in 9.4% vs. 9.5% of patients assigned to ezetimibe and simvastatin tablets 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. Simvastatin In a clinical outcome trial in which 12,064 adult patients with a history of myocardial infarction were treated with simvastatin (mean follow-up 6.7 years), the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum creatine kinase [CK] >10 times (1200U/L) upper limit of normal [ULN]) in patients taking simvastatin 20 mg and 80 mg daily was approximately 0.02% and 0.9% respectively. The incidence of rhabdomyolysis (defined as myopathy with a CK >40 times ULN) in patients taking simvastatin 20 mg and 80 mg daily was approximately 0% and 0.4%. The incidence of myopathy and 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 trials: atrial fibrillation; vertigo;abdominal pain, constipation, dyspepsia, flatulence, gastritis; eczema, rash; diabetes mellitus; bronchitis, sinusitis, urinary tract infections; asthenia, edema/swelling; and insomnia. Laboratory Tests Marked persistent increases of hepatic serum transaminases have been noted [see Warnings and Precautions ( 5.3 )] . 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. This was attributable to the noncardiac fraction of CK [see Warnings and Precautions ( 5.1 )] . 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of ezetimibe and simvastatin tablets.
Drug interactions
Ezetimibe and simvastatin tablets
• See full prescribing information for details regarding concomitant use of ezetimibe and simvastatin tablets with other drugs or grapefruit juice that increase the risk of myopathy and rhabdomyolysis. ( 2.3 , 7.1 )
• Cholestyramine: Combination decreases exposure of ezetimibe. ( 2.3 , 7.2 )
• Coumarin Anticoagulants: Obtain INR before ezetimibe and simvastatin tablets initiation and monitor INR during ezetimibe and simvastatin tablets dosage initiation or adjustment. ( 7.3 )
• Digoxin: During ezetimibe and simvastatin tablets initiation, monitor digoxin levels. ( 7.3 )
• Fenofibrates: Combination increases exposure of ezetimibe. If cholelithiasis is suspected in a patient receiving ezetimibe and a fenofibrate, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered. ( 7.3 , 12.3 ) 7.1 Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Ezetimibe and Simvastatin Tablets Ezetimibe and simvastatin tablets are a substrate of CYP3A4 and of the transport protein OATP1B1. ezetimibe and simvastatin tablets plasma levels can be significantly increased with concomitant administration of inhibitors of CYP3A4 and OATP1B1. Table 2 includes a list of drugs that increase the risk of myopathy and rhabdomyolysis when used concomitantly with ezetimibe and simvastatin tablets and instructions for preventing or managing them [see Warnings and Precautions ( 5.1 ) and Clinical Pharmacology ( 12.3 )]. Table 2: Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Ezetimibe and Simvastatin Tablets Strong CYP3A4 inhibitors Clinical Impact: Simvastatin is a substrate of CYP3A4. Concomitant use of strong CYP3A4 inhibitors with ezetimibe and simvastatin tablets increases simvastatin exposure and increases the risk of myopathy and rhabdomyolysis, particularly with higher ezetimibe and simvastatin tablets dosages. Intervention: Concomitant use of strong CYP3A4 inhibitors with ezetimibe and simvastatin tablets are contraindicated [see Contraindications ( 4 )] . If treatment with a CYP3A4 inhibitor is unavoidable, suspend ezetimibe and simvastatin tablets during the course of strong CYP3A4 inhibitor treatment. Examples: Select azole anti-fungals (e.g., itraconazole, ketoconazole, posaconazole, and voriconazole), select macrolide antibiotics (e.g., erythromycin and clarithromycin, telithromycin), select HIV protease inhibitors (e.g., nelfinavir, ritonavir, and darunavir/ritonavir), select HCV protease inhibitors (e.g., boceprevir and telaprevir), cobicistat-containing products, and nefazodone. Cyclosporine, Danazol, or Gemfibrozil Clinical Impact: The risk of myopathy and rhabdomyolysis is increased with concomitant use of cyclosporine, danazol, or gemfibrozil with ezetimibe and simvastatin tablets. Gemfibrozil may cause myopathy when given alone. Intervention: Concomitant use of cyclosporine, danazol, or gemfibrozil with ezetimibe and simvastatin tablets are contraindicated [see Contraindications ( 4 )] . Amiodarone, Dronedarone, Ranolazine, or Calcium Channel Blockers Clinical Impact: The risk of myopathy and rhabdomyolysis is increased by concomitant use of amiodarone, dronedarone, ranolazine, or calcium channel blockers with ezetimibe and simvastatin tablets. Intervention: For patients taking verapamil, diltiazem, or dronedarone, do not exceed ezetimibe and simvastatin tablets 10/10 mg daily . For patients taking amiodarone, amlodipine, or ranolazine, do not exceed ezetimibe and simvastatin tablets 10/20 mg daily [see Dosage and Administration ( 2.3 )] . Lomitapide Clinical Impact: Simvastatin exposure is approximately doubled with concomitant use of lomitapide and the risk of myopathy and rhabdomyolysis is increased . Intervention: Reduce the dose of ezetimibe and simvastatin tablets by 50% if initiating lomitapide. Do not exceed ezetimibe and simvastatin tablets 10/20 mg daily (or ezetimibe and simvastatin tablets 10/40 mg daily for patients who have previously taken ezetimibe and simvastatin tablets 10/80 mg daily chronically) while taking lomitapide [see Dosage and Administration ( 2.1 , 2.3 )] . Daptomycin Clinical Impact: Cases of rhabdomyolysis have been reported with simvastatin administered with daptomycin. Both ezetimibe and simvastatin tablets and daptomycin can cause myopathy and rhabdomyolysis when given alone and the risk of myopathy and rhabdomyolysis may be increased by coadministration. Intervention: If treatment with daptomycin is required, consider temporarily suspending ezetimibe and simvastatin tablets during the course of daptomycin treatment. Niacin Clinical Impact: Cases of myopathy and rhabdomyolysis have been observed with concomitant use of lipid modifying dosages of niacin-containing products (≥1 gram/day niacin) with ezetimibe and simvastatin tablets. The risk of myopathy is greater in Chinese patients. In a clinical trial (median follow-up 3.9 years) of patients at high risk of CVD and with well-controlled LDL-C levels on simvastatin 40 mg/day with or without ezetimibe 10 mg/day, there was no incremental benefit on cardiovascular outcomes with the addition of lipid-modifying doses of niacin Intervention: Concomitant use of ezetimibe and simvastatin tablets with lipid-modifying dosages of niacin is not recommended in Chinese patients [see Use in Specific Populations ( 8.8 )]. For non-Chinese patients, consider if the benefit of using lipid-modifying doses of niacin concomitantly with ezetimibe and simvastatin tablets outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug. Fibrates (other than Gemfibrozil) Clinical Impact: Fibrates may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of fibrates with ezetimibe and simvastatin tablets.
Use in specific populations
• Pregnancy: May cause fetal harm ( 8.1 )
• Lactation : Breastfeeding not recommended during treatment with ezetimibe and simvastatin tablets. ( 8.2 ) 8.1 Pregnancy Ezetimibe and simvastatin tablets Risk Summary Discontinue ezetimibe and simvastatin tablets when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Ezetimibe and simvastatin tablets decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, ezetimibe and simvastatin tablets may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology ( 12.1 )]. In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. Published data from prospective and retrospective observational cohort studies with ezetimibe and simvastatin tablets use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see Data) . In animal reproduction studies, no adverse developmental effects were observed in pregnant rats or rabbits orally administered simvastatin during the period of organogenesis at doses that resulted in 2.5 and 2 times, respectively, the human exposure at the maximum recommended human dosage of 80 mg/day, based on body surface area (mg/m 2 ). In animal reproduction studies, no adverse developmental effects were observed in pregnant rats and rabbits orally administered ezetimibe during the period of organogenesis at doses that resulted in up to 10 and 150 times, respectively, the human exposure at the MRHD, based on AUC (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data Ezetimibe There are insufficient data on ezetimibe use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Simvastatin A Medicaid cohort linkage trial of 1152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods. The relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. There were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. In the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. Trial limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births. Animal Data Ezetimibe In oral (gavage) embryo-fetal development studies of ezetimibe conducted in rats (gestation days 6-15) and rabbits (gestation days 7-19), there was no evidence of maternal toxicity or embryolethality at any dose tested (250, 500, 1000 mg/kg/day) at exposure equivalent to 10 to 150 times the clinical exposure, based on AUC, in rats and rabbits. In rats, increased incidences of common fetal skeletal findings (extra pair of thoracic ribs, unossified cervical vertebral centra, shortened ribs) were observed at 1000 mg/kg/day (~10 times the human exposure at 10 mg daily based on AUC 0 to 24hr for total ezetimibe). In rabbits treated with ezetimibe, an increased incidence of extra thoracic ribs was observed at 1000 mg/kg/day (150 times the human exposure at 10 mg daily based on AUC 0 to 24hr for total ezetimibe). The animal-to-human exposure multiple for total ezetimibe at the no-observed effect level was 6 times for rat and 134 times for rabbit. Fetal exposure to ezetimibe (conjugated and unconjugated) was confirmed in subsequent placental transfer studies conducted using a maternal dose of 1000 mg/kg/day. The fetal maternal plasma exposure ratio (total ezetimibe) was 1.5 for rats on gestation day 20 and 0.03 for rabbits on gestation day 22. The effect of ezetimibe on prenatal and postnatal development and maternal function was evaluated in pregnant rats at doses of 100, 300 or 1000 mg/kg/day (gestation day 6 through lactation day 21). No maternal toxicity or adverse developmental outcomes were observed up to and including the highest dose tested (17 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). Multiple-dose studies of ezetimibe given in combination with statins in rats and rabbits during organogenesis resulted in higher ezetimibe and statin exposures. Reproductive findings occurred at lower doses in combination therapy compared to monotherapy.
Pregnancy
8.1 Pregnancy Ezetimibe and simvastatin tablets Risk Summary Discontinue ezetimibe and simvastatin tablets when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Ezetimibe and simvastatin tablets decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, ezetimibe and simvastatin tablets may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology ( 12.1 )]. In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. Published data from prospective and retrospective observational cohort studies with ezetimibe and simvastatin tablets use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see Data) . In animal reproduction studies, no adverse developmental effects were observed in pregnant rats or rabbits orally administered simvastatin during the period of organogenesis at doses that resulted in 2.5 and 2 times, respectively, the human exposure at the maximum recommended human dosage of 80 mg/day, based on body surface area (mg/m 2 ). In animal reproduction studies, no adverse developmental effects were observed in pregnant rats and rabbits orally administered ezetimibe during the period of organogenesis at doses that resulted in up to 10 and 150 times, respectively, the human exposure at the MRHD, based on AUC (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data Ezetimibe There are insufficient data on ezetimibe use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Simvastatin A Medicaid cohort linkage trial of 1152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods. The relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. There were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. In the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. Trial limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births. Animal Data Ezetimibe In oral (gavage) embryo-fetal development studies of ezetimibe conducted in rats (gestation days 6-15) and rabbits (gestation days 7-19), there was no evidence of maternal toxicity or embryolethality at any dose tested (250, 500, 1000 mg/kg/day) at exposure equivalent to 10 to 150 times the clinical exposure, based on AUC, in rats and rabbits. In rats, increased incidences of common fetal skeletal findings (extra pair of thoracic ribs, unossified cervical vertebral centra, shortened ribs) were observed at 1000 mg/kg/day (~10 times the human exposure at 10 mg daily based on AUC 0 to 24hr for total ezetimibe). In rabbits treated with ezetimibe, an increased incidence of extra thoracic ribs was observed at 1000 mg/kg/day (150 times the human exposure at 10 mg daily based on AUC 0 to 24hr for total ezetimibe). The animal-to-human exposure multiple for total ezetimibe at the no-observed effect level was 6 times for rat and 134 times for rabbit. Fetal exposure to ezetimibe (conjugated and unconjugated) was confirmed in subsequent placental transfer studies conducted using a maternal dose of 1000 mg/kg/day. The fetal maternal plasma exposure ratio (total ezetimibe) was 1.5 for rats on gestation day 20 and 0.03 for rabbits on gestation day 22. The effect of ezetimibe on prenatal and postnatal development and maternal function was evaluated in pregnant rats at doses of 100, 300 or 1000 mg/kg/day (gestation day 6 through lactation day 21). No maternal toxicity or adverse developmental outcomes were observed up to and including the highest dose tested (17 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). Multiple-dose studies of ezetimibe given in combination with statins in rats and rabbits during organogenesis resulted in higher ezetimibe and statin exposures. Reproductive findings occurred at lower doses in combination therapy compared to monotherapy.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of ezetimibe in combination with a statin as an adjunct to diet to reduce LDL-C have been established in pediatric patients 10 years of age and older with HeFH. Use of ezetimibe and simvastatin tablets for this indication is based on a double-blind, placebo-controlled clinical trial in 248 pediatric patients (142 males and 106 postmenarchal females) 10 years of age and older with HeFH [see Clinical Studies ( 14 )]. In this limited controlled trial, there was no significant effect on growth or sexual maturation in the adolescent males or females, or on menstrual cycle length in females. The safety and effectiveness of ezetimibe and simvastatin tablets have not been established in pediatric patients younger than 10 years of age with HeFH, or in pediatric patients with other types of hyperlipidemia.
Geriatric use
8.5 Geriatric Use Advanced age (≥65 years) is a risk factor for ezetimibe and simvastatin tablets-associated myopathy and rhabdomyolysis. Dose selection for an elderly patient should be cautious, recognizing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy. Monitor geriatric patients receiving ezetimibe and simvastatin tablets for the increased risk of myopathy [see Warnings and Precautions ( 5.1 )]. Of the 10,189 patients who received ezetimibe and simvastatin tablets in clinical studies, 3242 (32%) were 65 and older (this included 844 (8%) who were 75 and older). No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients but greater sensitivity of some older individuals cannot be ruled out.
Overdosage
No specific antidotes for ezetimibe and simvastatin tablets are known. In the event of an overdose with ezetimibe and simvastatin tablets, consider contacting the Poison Help Line (1-800-222-1222) or a medical toxicologist for overdosage management recommendations.
Description
Ezetimibe and Simvastatin Tablets contain ezetimibe, a dietary cholesterol absorption inhibitor, and simvastatin, an HMG-CoA reductase inhibitor. The chemical name of ezetimibe is 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone. The molecular formula is C 24 H 21 F 2 NO 3 and its molecular weight is 409.44 g/mol. Ezetimibe is a white, crystalline powder that is freely soluble in ethanol, methanol and acetone and practically insoluble in water. Its structural formula is: Simvastatin, an inactive lactone, is hydrolyzed to the corresponding β-hydroxyacid form, which is an inhibitor of HMG-CoA reductase. Simvastatin is butanoic acid, 2,2-dimethyl-,1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2 H -pyran-2-yl)-ethyl]-1-naphthalenyl ester, [1 S -[1α,3α,7α,8α(2 S* ,4 S* ),-8aβ]]. The molecular formula of simvastatin is C 25 H 38 O 5 and its molecular weight is 418.57 g/mol. Simvastatin is a white to off-white, nonhygroscopic powder that is freely soluble in chloroform, methanol and alcohol, sparingly soluble in propylene glycol, very slightly soluble in hexane and practically insoluble in water. Its structural formula is: Ezetimibe and Simvastatin Tablets are available for oral use as tablets containing 10 mg of ezetimibe, and 10 mg of simvastatin (Ezetimibe and Simvastatin Tablets 10 mg/10 mg), 20 mg of simvastatin (Ezetimibe and Simvastatin Tablets 10 mg/20 mg), 40 mg of simvastatin (Ezetimibe and Simvastatin Tablets 10 mg/40 mg), or 80 mg of simvastatin (Ezetimibe and Simvastatin Tablets 10 mg/80 mg). Each tablet contains the following inactive ingredients: butylated hydroxyanisole, citric acid monohydrate, croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, propyl gallate, and sodium lauryl sulfate. ezetimibe-structure simva-structure
Mechanism of action
12.1 Mechanism of Action Ezetimibe and Simvastatin Tablets Plasma cholesterol is derived from intestinal absorption and endogenous synthesis. Ezetimibe and simvastatin tablets contain ezetimibe and simvastatin, two lipid-lowering compounds with complementary mechanisms of action. Ezetimibe Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine. The molecular target of ezetimibe has been shown to be the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols. Ezetimibe localizes at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood. Simvastatin Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin acid and its metabolites are inhibitors of HMG-CoA reductase, the rate-limiting enzyme converts HMG-CoA to mevalonate, a precursor of cholesterol.
How supplied
Ezetimibe and Simvastatin Tablets 10 mg/10 mg are white to off-white, capsule shaped, uncoated tablets debossed with ‘G’ on one side and ‘321’ on the other side. They are supplied as follows: Bottles of 30 NDC 16714-778-01 Bottles of 90 NDC 16714-778-02 Ezetimibe and Simvastatin Tablets 10 mg/20 mg are white to off-white, capsule shaped, uncoated tablets debossed with ‘G’ on one side and ‘322’ on the other side. They are supplied as follows: Bottles of 30 NDC 16714-779-01 Bottles of 90 NDC 16714-779-02 Ezetimibe and Simvastatin Tablets 10 mg/40 mg are white to off-white, capsule shaped, uncoated tablets debossed with ‘G’ on one side and ‘323’ on the other side. They are supplied as follows: Bottles of 30 NDC 16714-780-01 Bottles of 90 NDC 16714-780-02 Ezetimibe and Simvastatin Tablets 10 mg/80 mg are white to off-white, capsule shaped, uncoated tablets debossed with ‘G’ on one side and ‘324’ on the other side. They are supplied as follows: Bottles of 30 NDC 16714-781-01 Bottles of 90 NDC 16714-781-02 Storage Store at 68°F to 77°F (20°C to 25°C). [see USP Controlled Room Temperature]. Keep container tightly closed.
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information). Myopathy and Rhabdomyolysis Advise patients that ezetimibe and simvastatin tablets may cause myopathy and rhabdomyolysis. Inform patients taking the 80 mg daily dose of simvastatin that they are at an increased risk. Inform patients that the risk is also increased when taking certain types of medication or consuming grapefruit juice and they should discuss all medication, both prescription and over the counter, with their healthcare provider. Instruct patients to inform other healthcare providers prescribing a new medication or increasing the dose of an existing medication that they are taking ezetimibe and simvastatin tablets. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 ), and Drug Interactions ( 7.1 )]. Hepatic Dysfunction Inform patients that ezetimibe and simvastatin tablets may cause liver enzyme elevations and possibly liver failure. Advise patients to promptly report fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice [see Warnings and Precautions ( 5.3 )] . Increases in HbA1c and Fasting Serum Glucose Levels Inform patients that increases in HbA1c and fasting serum glucose levels may occur with ezetimibe and simvastatin tablets. Encourage patients to optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices [see Warnings and Precautions ( 5.4 )]. Pregnancy Advise pregnant patients and patients who can become pregnant of the potential risk to a fetus. Advise patients to inform their healthcare provider of a known or suspected pregnancy to discuss if ezetimibe and simvastatin tablets should be discontinued [see Use in Specific Populations ( 8.1 )]. Lactation Advise patients that breastfeeding is not recommended during treatment with ezetimibe and simvastatin tablets [see Use in Specific Populations ( 8.2 )]. Missed Dose Instruct patients to take ezetimibe and simvastatin tablets only as prescribed. If a dose is missed, it should be taken as soon as possible. Advise patients not to double their next dose. *Trademarks are the properties of their respective owners. Manufactured for: Northstar Rx LLC Memphis, TN 38141. Manufactured by: Glenmark Pharmaceuticals Limited. Pithampur, Madhya Pradesh 454775, India July 2024
Label text from the FDA structured product label by NORTHSTAR RX LLC (revised Sep 1, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Ezetimibe in 28 products
- Simvastatin in 28 products
ezetimibe and simvastatin NDC products (28)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-4772 | Ezetimibe 10 mg/1; Simvastatin 40 mg/1 Tablet | A-S Medication Solutions | ANDA |
| 50090-7047 | Ezetimibe 10 mg/1; Simvastatin 40 mg/1 Tablet | A-S Medication Solutions | ANDA |
| 69238-1158 | Ezetimibe 10 mg/1; Simvastatin 80 mg/1 Tablet | Amneal Pharmaceuticals NY LLC | ANDA |
| 69238-1157 | Ezetimibe 10 mg/1; Simvastatin 40 mg/1 Tablet | Amneal Pharmaceuticals NY LLC | ANDA |
| 69238-1156 | Ezetimibe 10 mg/1; Simvastatin 20 mg/1 Tablet | Amneal Pharmaceuticals NY LLC | ANDA |
| 69238-1155 | Ezetimibe 10 mg/1; Simvastatin 10 mg/1 Tablet | Amneal Pharmaceuticals NY LLC | ANDA |
| 67877-510 | Ezetimibe 10 mg/1; Simvastatin 80 mg/1 Tablet | Ascend Laboratories, LLC | ANDA |
| 67877-509 | Ezetimibe 10 mg/1; Simvastatin 40 mg/1 Tablet | Ascend Laboratories, LLC | ANDA |
| 67877-508 | Ezetimibe 10 mg/1; Simvastatin 20 mg/1 Tablet | Ascend Laboratories, LLC | ANDA |
| 67877-507 | Ezetimibe 10 mg/1; Simvastatin 10 mg/1 Tablet | Ascend Laboratories, LLC | ANDA |
| 59651-837 | Ezetimibe 10 mg/1; Simvastatin 40 mg/1 Tablet | Aurobindo Pharma Limited | ANDA |
| 59651-838 | Ezetimibe 10 mg/1; Simvastatin 80 mg/1 Tablet | Aurobindo Pharma Limited | ANDA |
| 59651-836 | Ezetimibe 10 mg/1; Simvastatin 20 mg/1 Tablet | Aurobindo Pharma Limited | ANDA |
| 59651-835 | Ezetimibe 10 mg/1; Simvastatin 10 mg/1 Tablet | Aurobindo Pharma Limited | ANDA |
| 43598-745 | Ezetimibe 10 mg/1; Simvastatin 80 mg/1 Tablet | Dr.Reddys Laboratories Inc | ANDA |
| 43598-744 | Ezetimibe 10 mg/1; Simvastatin 20 mg/1 Tablet | Dr.Reddys Laboratories Inc | ANDA |
| 43598-743 | Ezetimibe 10 mg/1; Simvastatin 40 mg/1 Tablet | Dr.Reddys Laboratories Inc | ANDA |
| 43598-742 | Ezetimibe 10 mg/1; Simvastatin 10 mg/1 Tablet | Dr.Reddys Laboratories Inc | ANDA |
| 68462-321 | Ezetimibe 10 mg/1; Simvastatin 10 mg/1 Tablet | Glenmark Pharmaceuticals Inc., USA | ANDA |
| 68462-322 | Ezetimibe 10 mg/1; Simvastatin 20 mg/1 Tablet | Glenmark Pharmaceuticals Inc., USA | ANDA |
| 68462-323 | Ezetimibe 10 mg/1; Simvastatin 40 mg/1 Tablet | Glenmark Pharmaceuticals Inc., USA | ANDA |
| 68462-324 | Ezetimibe 10 mg/1; Simvastatin 80 mg/1 Tablet | Glenmark Pharmaceuticals Inc., USA | ANDA |
| 51407-193 | Ezetimibe 10 mg/1; Simvastatin 80 mg/1 Tablet | Golden State Medical Supply, Inc. | ANDA |
| 51407-192 | Ezetimibe 10 mg/1; Simvastatin 40 mg/1 Tablet | Golden State Medical Supply, Inc. | ANDA |
| 51407-191 | Ezetimibe 10 mg/1; Simvastatin 20 mg/1 Tablet | Golden State Medical Supply, Inc. | ANDA |
| 51407-190 | Ezetimibe 10 mg/1; Simvastatin 10 mg/1 Tablet | Golden State Medical Supply, Inc. | ANDA |
| 16714-780 | Ezetimibe 10 mg/1; Simvastatin 40 mg/1 Tablet | NORTHSTAR RX LLC | ANDA |
| 16714-781 | Ezetimibe 10 mg/1; Simvastatin 80 mg/1 Tablet | NORTHSTAR RX LLC | ANDA |
ezetimibe and simvastatin recalls
- D-0462-2025 Jun 18, 2025 · Class III · Ongoing
Failed Impurities/Degradation Specifications: Out of Specification (OOS) for related substances test for Anhydro Simvastatin at the 06-month time point during long-term stability study. - D-0227-2022 Nov 17, 2021 · Class II · Terminated
Failed Excipient Specifications and Presence of Foreign Tablets/Capsules; product manufactured using an excipient found to be OOS for conductivity and some Ezetimibe and Simvastatin Tablets, 10 mg/10 mg were found in… - D-0228-2022 Nov 17, 2021 · Class II · Terminated
Failed Excipient Specification; product manufactured using an excipient found to be OOS for conductivity - D-0081-2022 Nov 10, 2021 · Class II · Terminated
Failed Excipient Specifications; product manufactured using an excipient found to be OOS for conductivity - D-0082-2022 Nov 10, 2021 · Class II · Terminated
Failed Excipient Specifications; product manufactured using an excipient found to be OOS for conductivity - D-0083-2022 Nov 10, 2021 · Class II · Terminated
Failed Excipient Specifications; product manufactured using an excipient found to be OOS for conductivity - D-0084-2022 Nov 10, 2021 · Class II · Terminated
Failed Excipient Specifications; product manufactured using an excipient found to be OOS for conductivity - D-0085-2022 Nov 10, 2021 · Class II · Terminated
Failed Excipient Specifications and Presence of Foreign Tablets/Capsules; product manufactured using an excipient found to be OOS for conductivity and some Ezetimibe and Simvastatin Tablets, 10 mg/10 mg were found in… - D-0484-2021 Jun 2, 2021 · Class II · Terminated
CGMP Deviations: Intermittent exposure to temperature excursion during storage.
Frequently asked questions
What is ezetimibe and simvastatin used for?
Ezetimibe and Simvastatin Tablets Ezetimibe and Simvastatin Tablets are a combination of simvastatin and ezetimibe indicated: • As an adjunct to diet to reduce elevated low density lipoprotein cholesterol (LDL-C): • In adults with primary hyperlipidemia. • In adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH). • As an adjunct to other…
What are the side effects of ezetimibe and simvastatin?
The following serious adverse reactions are discussed in greater detail in other sections of the label: • Myopathy and Rhabdomyolysis [see Warnings and Precautions ( 5.1 )] • Immune-Mediated Necrotizing Myopathy [see Warnings and Precautions ( 5.2 )] • Hepatic Dysfunction [see Warnings and Precautions ( 5.3 )] • Increases in HbA1c and Fasting Serum Glucose Levels [see Warnings and Precautions (… See the full label for the complete list.
Who makes ezetimibe and simvastatin?
ezetimibe and simvastatin is listed by 8 labelers in the FDA NDC directory, including A-S Medication Solutions, Amneal Pharmaceuticals NY LLC, Ascend Laboratories, LLC, Aurobindo Pharma Limited.
Has ezetimibe and simvastatin been recalled?
The FDA enforcement database lists 9 recalls for ezetimibe and simvastatin, most recently D-0462-2025 (class iii): Failed Impurities/Degradation Specifications: Out of Specification (OOS) for related substances test for Anhydro Simvastatin at the 06-month time point during…