EZETIMIBE/SIMVASTATIN TABS 10/40 MG 30CT
Generic: Ezetimibe and Simvastatin
EZETIMIBE/SIMVASTATIN TABS 10/40 MG 30CT
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Identification
Ezetimibe and Simvastatin
Ezetimibe and Simvastatin
Ascend Laboratories, LLC
HUMAN PRESCRIPTION DRUG
Administration
TABLET
ORAL
ANDA209222
Active Ingredients
| Ingredient | Strength |
|---|---|
| EZETIMIBE | 10 mg/1 |
| SIMVASTATIN | 40 mg/1 |
Pharmacological Class
Data sourced from openFDA / DailyMed. For full prescribing information, consult the drug label.
Wholesale compliance resources
Clinical Drug Information
Indications & Usage
1 INDICATIONS AND USAGE Ezetimibe and Simvastatin Ezetimibe and simvastatin is a combination of simvastatin and ezetimibe indicated: • As an adjunct to diet to reduce elevated low density lipoprotein cholesterol (LDL-C): o In adults with primary hyperlipidemia. o 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, 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 is 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): o In adults with primary hyperlipidemia. o 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, 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 & Administration
2 DOSAGE AND ADMINISTRATION Important Dosage and Administration Information: (2.1) Take ezetimibe and simvastatin orally once daily in the evening with or without food. Maximum recommended dosage is ezetimibe and simvastatin 10/40 mg once daily. Ezetimibe and simvastatin 10/80 mg daily dosage is restricted to patients who have been taking ezetimibe and simvastatin 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 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, 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 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 orally once daily in the evening with or without food. The maximum recommended dosage is ezetimibe and simvastatin 10/40 mg once daily. The ezetimibe and simvastatin 10/80 mg daily dosage is restricted to adult patients who have been taking ezetimibe and simvastatin 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 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, and adjust the dosage if necessary. 2.2 Recommended Dosage in Adult Patients The recommended dosage range of ezetimibe and simvastatin 10/10 mg to 10/40 mg once a day. 2.3 Recommended Dosage in Pediatric Patients10 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 Modifications 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.
Adverse Reactions
6 ADVERSE REACTIONS 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 Ascend Laboratories,LLC at 1-877-272-7901 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 (ezetimibe and simvastatin) placebo-controlled clinical trials database of 1,420 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 has 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 6.0 5.9 5.8 Upper respiratory tract infection 2.7 5.0 5.0 3.6 Myalgia 2.4 2.3 2.6 3.6 Diarrhea 2.2 5.0 3.7 2.8 Pain in extremity 1.3 3.0 2.0 2.3 Influenza 0.8 1.0 1.9 2.3 *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 was administered. † All doses. Study of Heart and Renal Protection In SHARP , 9,270 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 (1200 U/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. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Body as Whole: fever, chills, malaise, asthenia Blood and Lymphatic System Disorders: anemia, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia Gastrointestinal Disorders: pancreatitis, nausea, vomiting Hepatobiliary Disorders: cholelithiasis, cholecystitis, elevations in liver transaminases including elevations more than 5 X ULN, hepatitis/jaundice, fatal and non-fatal hepatic failure Immune System Disorders: hypersensitivity syndrome including: anaphylaxis, angioedema, lupus erythematous-like syndrome, dermatomyositis, vasculitis Musculoskeletal and Connective Tissue Disorders: muscle cramps, immune-mediated necrotizing myopathy, rhabdomyolysis, myalgia, arthralgia, polymyalgia rheumatica, arthritis, elevated creatine phosphokinase Nervous System Disorders: dizziness, depression, paresthesia, peripheral neuropathy, rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. Cognitive impairment was generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks). There have been rare reports of new-onset or exacerbation of myasthenia gravis, including ocular myasthenia, and reports of recurrence when the same or a different statin was administered. Skin and Subcutaneous Tissue Disorders: rash, pruritus, alopecia, a variety of skin changes (e.g., nodules, discoloration, dryness of skin/mucous membranes, changes to hair/nails), purpura, lichen planus, urticaria, photosensitivity, flushing, toxic epidermal necrolysis, erythema multiforme, including Stevens-Johnson syndrome. Respiratory and Thoracic: interstitial lung disease, dyspnea Reproductive System Disorders: erectile dysfunction
Information for Patients
17 PATIENT COUNSELING 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. For Patient Information, please visit: http://www.ascendlaboratories.com/pti/ezetim_simvatablets.pdf Manufactured by: Alkem Laboratories Ltd., Mumbai - 400 013, INDIA. Distributed by: Ascend Laboratories, LLC Bedminster, NJ 07921 Revised: January,2025 PT 2626-08
Clinical data sourced from openFDA drug labeling. For complete prescribing information, consult the full drug label.