Simvastatin-Ezetimibe

Simvastatin-Ezetimibe is a combination medication used for the treatment of high blood cholesterol  (hypercholesterolemia). 

• Simvastatin-Ezetimibe is available under the following different brand names: Vytorin.

Common side effects of Simvastatin-Ezetimibe include:

• Headache,
• Nausea,
• Vomiting,
• Diarrhoea,
• Dizziness,
• Depression,
• Memory problems,
• Confusion,
• Back pain,
• Joint pain,
• Muscle pain,
• Numbness or tingly feeling,
• Trouble having an erection,
• Sleep problems (insomnia), or
• Cold symptoms (stuffy nose, sneezing, sore throat).

Serious side effects of Simvastatin-Ezetimibe include:

• Muscle pain, tenderness, and weakness (myopathy). Muscle problems, including muscle breakdown, can be serious in some people and rarely cause kidney damage that can lead to death.
• Unexplained muscle pain, tenderness, or weakness, especially if you have a fever or feel more tired than usual, while you take Vytorin.
• Muscle problems do not go away even after your doctor has advised you to stop taking Vytorin.
• Liver problems. Your doctor should do blood tests to check your liver before you start taking Vytorin and if you have any symptoms of liver problems while you take Vytorin. Call your doctor right away if you have the following symptoms of liver problems:
• Loss of appetite
• Upper belly pain
• Dark urine
• Yellowing of the skin or the whites of the eyes
• Feel tired or weak.

Rare side effects of Simvastatin-Ezetimibe include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out. 

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Tablet

• 10 mg/10 mg
• 10 mg/20 mg
• 10 mg/40 mg
• 10 mg/80 mg

Hypercholesterolemia

Adult dosage

• 10 mg/10 mg/day-10 mg/40 mg/day orally every night at bedtime
• Usual starting dose is 10 mg/20 mg orally every night at bedtime.
• Simvastatin 80 mg/day should only be used for individuals who have been taking a simvastatin dose of 80 mg for 12 months or longer without evidence of myopathy.
• Prescribing information advises if patients are taking simvastatin 40 mg/day without meeting their LDL goal switch to a different statin rather than increase to 80 mg/day.

Heterozygous Familial Hypercholesterolemia

Pediatric dosage

• Below 10 years: Safety and efficacy not established.
• 10-18 years: 10 mg/10 mg/day-10 mg/40 mg/day orally every night at bedtime
• Simvastatin 80 mg/day should only be used for individuals who have been taking a simvastatin dose of 80 mg for 12 months or longer without evidence of myopathy.
• FDA advises if patients are taking simvastatin 40 mg/day without meeting their LDL goal to switch to a different statin rather than increase to 80 mg/day.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Simvastatin-Ezetimibe has severe interactions with at least 32 other drugs.
• Simvastatin-Ezetimibe has serious interactions with the following drugs:
  • abametapir
  • afatinib
  • amiodarone
  • amlodipine
  • apalutamide
  • aprepitant
  • armodafinil
  • artemether/lumefantrine
  • bosentan
  • bosutinib
  • butabarbital
  • butalbital
  • carbamazepine
  • cimetidine
  • colchicine
  • conivaptan
  • cyclosporine
  • darifenacin
• Simvastatin-Ezetimibe has moderate interactions with at least 93 other drugs.
• Simvastatin-Ezetimibe has minor interactions with at least 23 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Hypersensitivity to either component
• Active liver disease, or unexplained elevated transaminases
• Women who are pregnant or may become pregnant.
• Lactation
• Concomitant administration with strong CYP3A4 inhibitors (. g, itraconazole, ketoconazole, erythromycin, clarithromycin, Posaconazole, voriconazole, HIV protease inhibitors, nefazodone, cobicistat), fibrates (including gemfibrozil), cyclosporine, and danazol.

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Simvastatin-Ezetimibe?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Simvastatin-Ezetimibe??”

Cautions

• Discontinue if markedly elevated CPK levels occur or myopathy is diagnosed or suspected.
• Increased HbA1c and fasting serum glucose levels were reported with HMG-CoA reductase inhibitors.
• Avoid use in severe renal impairment.
• High potential for drug interactions
• Liver function
  • Monitor liver function tests before initiating treatment and thereafter when clinically indicated; reports of fatal and non-fatal hepatic failure in patients taking statins.
  • If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, promptly interrupt therapy, if alternate etiology is not found do not restart therapy
  • Note that ALT may emanate from muscle, therefore ALT rising with CK may indicate myopathy.
  • Therapy should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease; active liver diseases or unexplained persistent transaminase elevations are contraindications to the use of this medication
• Simvastatin and myopathy risk
  • Dose adjustment is required when coadministered with niacin, amiodarone, verapamil, diltiazem, amlodipine, and ranolazine.
  • Predisposing factors for myopathy include advanced age (above 65 years), female gender, uncontrolled hypothyroidism, and renal impairment; Chinese patients may be at increased risk for myopathy.
  • Risk of myopathy is increased by elevated plasma levels of simvastatin and simvastatin acid.
  • In clinical trials, the incidence of myopathy, including rhabdomyolysis, was highest during the first year and then notably decreased during subsequent years of treatment.
  • Patients should be advised of the increased risk of myopathy, including rhabdomyolysis, and to report promptly any unexplained muscle pain, tenderness, or weakness; if symptoms occur, treatment should be discontinued immediately.
  • Therapy should be temporarily withheld in any patient experiencing acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis, g, sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy
  • Risk of myopathy is greater in patients taking simvastatin 80 mg/day, especially in the 1st year of treatment.
  • The 10/80-mg dose should be used only in patients who have been taking the 10/80 mg dose chronically (.g, for 12 months or more) without evidence of muscle toxicity; if however, a patient who is currently tolerating the 10/80-mg dose needs to be initiated on an interacting drug that is contraindicated or associated with a dose cap for simvastatin, the patient should be switched to an alternative statin or statin-based regimen with less potential for drug-drug interaction
• Immune-mediated necrotizing myopathy
  • Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, is reported with statin use.
  • IMNM is characterized by muscle biopsy showing necrotizing myopathy without significant inflammation improvement with immunosuppressive agents, proximal muscle weakness, and elevated serum creatine kinase, which persist despite discontinuation of statin treatment.
  • Treatment with immunosuppressive agents may be required.
  • Advice all patients starting therapy or whose dose is being increased, about the risk of myopathy, including rhabdomyolysis.
  • Patients should 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 therapy; additional neuromuscular and serologic testing may be necessary.
  • Therapy should be discontinued immediately if myopathy is diagnosed or suspected.
  • Discontinue therapy if markedly elevated creatine kinase (CK) levels occur or if myopathy is diagnosed or suspected.
  • Therapy should be temporarily withheld in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis, g, sepsis; hypotension; dehydration; major surgery; trauma; severe metabolic, endocrine, and electrolyte disorders; or uncontrolled epilepsy.
  • Consider the risk of IMNM carefully before initiation of a different statin.
  • If therapy is initiated with a different statin, monitor for signs and symptoms of IMNM.
  • Additional neuromuscular and serologic testing may be necessary.
  • Treatment with immunosuppressive agents may be required.
  • Consider the risk of IMNM carefully before initiation of a different statin.
  • If therapy is initiated with a different statin, monitor for signs and symptoms of IMNM.
• Coadministration with niacin
  • Myopathy/rhabdomyolysis was observed with simvastatin administered with lipid-modifying niacin doses (i.e., above 1 g/day); also observed when administered with daptomycin
  • Risk of myopathy is greater in Chinese patients, and therefore, coadministration of simvastatin with lipid-modifying niacin doses is not recommended in Chinese patients.
  • Unknown if this risk applies to other patients of Asian descent.

Pregnancy and Lactation

• Contraindicated in women who are or may become pregnant.
• Lipid-lowering drugs offer no benefit during pregnancy because cholesterol and cholesterol derivatives are needed for normal fetal development.
• Atherosclerosis is a chronic process, and discontinuation of lipid-lowering drugs during pregnancy should have little impact on the long-term outcomes of primary hypercholesterolemia therapy.
• There are no adequate and well-controlled studies on the use of statins during pregnancy; however, there are rare reports of congenital anomalies in infants exposed to statins in utero.
• Lactation
  • Unknown if simvastatin is excreted in human milk; because a small amount of another drug in this class is excreted in human milk and because of the potential for serious adverse reactions in nursing infants, women taking simvastatin should not breastfeed.
  • A decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother