Ezetimibe / Simvastatin Side Effects

Medically reviewed by Drugs.com. Last updated on Mar 5, 2024.

Applies to ezetimibe / simvastatin: oral tablet.

Precautions

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Do not use ezetimibe and simvastatin combination if you are also taking boceprevir (Victrelis®), cobicistat-containing products (Stribild®), cyclosporine (Gengraf®, Neoral®, Sandimmune®), danazol (Danocrine®), gemfibrozil (Lopid®), nefazodone (Serzone®), telaprevir (Incivek®), certain antibiotics (eg, clarithromycin, erythromycin, itraconazole, ketoconazole, posaconazole, telithromycin, voriconazole, Nizoral®), or medicines to treat HIV/AIDS (eg, atazanavir, indinavir, nelfinavir, ritonavir, saquinavir, Crixivan®, Kaletra®, Lexiva®, Norvir®, Prezista®, Reyataz®). Using these medicines together with ezetimibe and simvastatin may increase your risk of muscle injury and could result in kidney problems.

Chinese patients who are taking large amounts of niacin (greater than 1 gram or 1000 milligrams per day) together with this medicine may have an increased risk for muscle injury. Talk to your doctor if you are Chinese or have Chinese ancestry and take large amounts of niacin (Niacor®, Niaspan®).

Call your doctor right away if you have unexplained muscle pain, tenderness, or weakness, especially if you also have unusual tiredness or a fever. These may be symptoms of serious muscle problems, such as myopathy or immune-mediated necrotizing myopathy (IMNM). Myopathy is more common when high doses of simvastatin (80 milligrams) with ezetimibe (10 mg) are used, but some people get myopathy with lower doses.

Check with your doctor right away if you have dark-colored urine, diarrhea, a fever, muscle cramps or spasms, muscle pain or stiffness, or feel very tired or weak. These could be symptoms of a serious muscle problem called rhabdomyolysis, which can cause kidney problems.

Call your doctor right away if you get a headache, stomach pain, vomiting, dark-colored urine, loss of appetite, weight loss, general feeling of tiredness or weakness, light-colored stools, upper right stomach pain, or yellow eyes or skin. These could be symptoms of liver damage.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine if you have a major surgery, a major injury, or you develop other serious health problems.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Other side effects

Some side effects of ezetimibe / simvastatin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Serious side effects

Along with its needed effects, ezetimibe / simvastatin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking ezetimibe / simvastatin:

For healthcare professionals

Applies to ezetimibe / simvastatin: oral tablet.

General adverse events

The more commonly reported adverse effects have included headache, increased ALT, myalgia, upper respiratory tract infection, and diarrhea.

Gastrointestinal

Ezetimibe-simvastatin:

• Common (1% to 10%): Diarrhea

Ezetimibe:

• Common (1% to 10%): Diarrhea, abdominal pain, nausea
• Postmarketing reports: Pancreatitis

Simvastatin:

• Common (1% to 10%): Constipation, nausea, flatulence, diarrhea, dyspepsia, abdominal pain, pancreatitis, anorexia, vomiting, gastritis
• Very rare (less than 0.01%): Protein losing enteropathy^[Ref]

Musculoskeletal

Ezetimibe-simvastatin:

• Common (1% to 10%): Myalgia, extremity pain
• Very rare (less than 0.01%): Tendon rupture (one case)
• Frequency not reported: Back pain
• Postmarketing reports: Muscle cramps

Ezetimibe:

• Common (1% to 10%): Back pain, arthralgia
• Postmarketing reports: Myalgia, elevated creatine phosphokinase, rare reports of myopathy/rhabdomyolysis

Simvastatin:

• Uncommon (0.1% to 1%): Myopathy, rhabdomyolysis
• Frequency not reported: Elevations in creatine kinase, dermatomyositis, arthralgia, myalgia^[Ref]

Simvastatin has been associated with rare cases of severe myopathy and rhabdomyolysis. This is accompanied by elevations in creatine kinase, myoglobinuria, and proteinuria, as well as renal failure. Experience with HMG-CoA reductase inhibitors indicates that concomitant use with gemfibrozil, niacin, cyclosporine, or erythromycin may increase the incidence and the severity of musculoskeletal side effects.

A case of spontaneous biceps tendon rupture developed in a patient after 4 months of treatment with ezetimibe-simvastatin. Upon rechallenge 2 months later, the patient developed pain in the contralateral arm overlying the biceps tendon. Following discontinuation of ezetimibe-simvastatin, pain resolved 2 weeks later. Inhibition of matrix metalloproteinases has been suggested as the contributing factor in the development of tendon rupture.^[Ref]

Renal

Simvastatin:

• Frequency not reported: Myoglobinuria, acute renal failure secondary to rhabdomyolysis^[Ref]

Hepatic

Ezetimibe-simvastatin:

• Common (1% to 10%): Increased ALT
• Frequency not reported: Increased AST

Ezetimibe:

• Postmarketing reports: Elevations in liver transaminases, hepatitis, cholelithiasis, cholecystitis

Simvastatin:

• Common (1% to 10%): Elevations in liver function tests
• Frequency not reported: Hepatitis (including chronic active hepatitis), cholestatic jaundice, fatty changes in the liver, cirrhosis, fulminant hepatic necrosis
• Postmarketing reports: Hepatic failure, jaundice^[Ref]

Persistent elevations in liver function tests three times normal values are reported in up to 1.5% of patients on simvastatin in clinical trials. In one study, this led to the discontinuation of simvastatin in 0.6% of patients. In other patients, elevations in liver function tests were transient and returned to normal with continued simvastatin therapy.^[Ref]

Dermatologic

Simvastatin:

• Frequency not reported: Eczematous, pruritic rash, toxic epidermal necrolysis, photosensitivity, purpura, erythema multiforme, photosensitivity, purpura, alopecia
• Postmarketing reports: A variety of skin changes (e.g., nodules, discoloration, dryness of skin/mucous membranes, changes to hair/nails)^[Ref]

Immunologic

Ezetimibe-simvastatin:

• Frequency not reported: Influenza

Ezetimibe:

• Common (1% to 10%): Viral infection

Simvastatin:

• Very rare (less than 0.01%): Lupus-like syndrome
• Frequency not reported: Positive ANA, ESR increase, polymyalgia rheumatica, vasculitis

Statin use:

• Rare (0.01% to 0.1%): Immune-mediated necrotizing myopathy (IMNM)^[Ref]

Respiratory

Ezetimibe-simvastatin:

• Common (1% to 10%): Upper respiratory tract infection
• Frequency not reported: Interstitial lung disease causing breathing problems including persistent cough and/or shortness of breath or fever

Ezetimibe:

• Common (1% to 10%): Coughing
• Frequency not reported: Sinusitis

Simvastatin:

• Frequency not reported: Sinusitis, pharyngitis^[Ref]

Cardiovascular

Simvastatin:

• Common (1% to 10%): Angina
• Frequency not reported: Atrial fibrillation, edema^[Ref]

Endocrine

Simvastatin:

• Frequency not reported: Gynecomastia, thyroid function abnormalities^[Ref]

Genitourinary

Simvastatin:

• Frequency not reported: Erectile dysfunction, impotence, urinary tract infections^[Ref]

Hematologic

Ezetimibe-simvastatin:

• Postmarketing reports: Epistaxis (one report), anemia

Ezetimibe:

• Postmarketing reports: Thrombocytopenia

Simvastatin:

• Frequency not reported: Hemolytic anemia, thrombocytopenia, leukopenia (possibly manifestations of a hypersensitivity reaction)^[Ref]

A 65-year-old male with hereditary hemorrhagic telangiectasia (HHT) who had a history of minimal epistaxis began to experience profuse epistaxis 8 to 10 weeks after starting ezetimibe-simvastatin, The patient had been treated with simvastatin 20 mg alone for 9 years without any adverse effects. Two months after starting combination therapy with ezetimibe-simvastatin he noticed epistaxis that increased from a few drops every other day to profuse bleeding for 20 to 30 minutes daily. The patient reported initiation of ezetimibe-simvastatin as the only change in his treatment regimen in the past year. When he stopped ezetimibe-simvastatin, his epistaxis decreased. After six weeks without ezetimibe-simvastatin, he had only one moderate nose bleed. Four months later, the patient's hemoglobin was stable. He then started simvastatin 40 mg monotherapy. The profound epistaxis returned and the patient discontinued the medication. It remains unclear whether the patient's accelerated epistaxis was due to the combination therapy or the double dosage of simvastatin.^[Ref]

Hypersensitivity

Ezetimibe:

• Postmarketing reports: Angioedema, anaphylaxis, rash, urticaria

Simvastatin:

• Rare (less than 0.1%): Erythema multiforme, Stevens-Johnson syndrome, anaphylaxis, angioedema, urticaria, fever, chills, flushing, malaise, dyspnea
• Postmarketing reports: Hypersensitivity reactions^[Ref]

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.^[Ref]

Nervous system

Ezetimibe-simvastatin:

• Common (1% to 10%): Headache
• Frequency not reported: Confusion, fatigue

Ezetimibe:

• Postmarketing reports: Dizziness, paraesthesia

Simvastatin:

• Frequency not reported: Cranial nerve dysfunction, tremor, vertigo, memory loss, paraesthesias, peripheral neuropathy, peripheral nerve palsy

Statins:

• Postmarketing reports: Cognitive impairment^[Ref]

A case of memory loss possibly related to simvastatin use has been reported. The patient developed gradual memory loss following 12 months of simvastatin therapy. He was switched to pravastatin, and within a month his memory was intact. Rechallenge with simvastatin was not performed.

There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These reports have been generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).^[Ref]

Ocular

Simvastatin:

• Frequency not reported: Progression of cataracts, ophthalmoplegia^[Ref]

Oncologic

Simvastatin:

• Frequency not reported: Liver, thyroid, and lung adenomas and carcinomas^[Ref]

Psychiatric

Simvastatin:

• Frequency not reported: Depression, suicidal thoughts, delusions, paranoia, agitation, decreased libido, anxiety, insomnia^[Ref]

Metabolic

Simvastatin:

• Frequency not reported: Increases in HbA1c and fasting serum glucose levels

Other

Ezetimibe:

• Frequency not reported: Fatigue, asthenia^[Ref]

See also:

Further information

Ezetimibe/simvastatin side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

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