Ezetimibe / simvastatin Side Effects

Not all side effects for ezetimibe / simvastatin may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to ezetimibe / simvastatin: oral tablet

In addition to its needed effects, some unwanted effects may be caused by ezetimibe / simvastatin. In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking ezetimibe / simvastatin:

Incidence not known
  • Abdominal or stomach fullness
  • bloating
  • chills
  • constipation
  • darkened urine
  • fast heartbeat
  • fever
  • hives
  • hoarseness
  • indigestion
  • itching
  • joint pain
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • loss of appetite
  • nausea
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • rash
  • redness of the skin
  • shortness of breath
  • stiffness
  • swelling of the eyelids, face, lips, hands, or feet
  • tightness in the chest
  • trouble breathing or swallowing
  • vomiting
  • yellow eyes or skin

Some of the side effects that can occur with ezetimibe / simvastatin may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

Less common
  • Body aches or pain
  • cough
  • diarrhea
  • difficulty with breathing
  • difficulty with moving
  • ear congestion
  • general feeling of discomfort or illness
  • headache
  • loss of voice
  • muscle aches and pains or cramping
  • muscle stiffness
  • nasal congestion
  • pain in the arms or legs
  • runny nose
  • shivering
  • sneezing
  • sore throat
  • sweating
  • swollen joints
  • trouble sleeping
  • unusual tiredness or weakness

For Healthcare Professionals

Applies to ezetimibe / simvastatin: oral tablet

Gastrointestinal

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
Very rare (less than 0.01%): Protein losing enteropathy

Musculoskeletal

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.

Very rare (less than 0.01%): Tendon rupture (one case)

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

Simvastatin:
Frequency not reported: Elevations in creatine kinase, myopathy, dermatomyositis, rhabdomyolysis, arthralgia, myalgia

Renal

Simvastatin:
Frequency not reported: Myoglobinuria, acute renal failure secondary to rhabdomyolysis

Hepatic

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.

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

Dermatologic

Simvastatin:
Frequency not reported: Eczematous, pruritic rash, toxic epidermal necrolysis, photosensitivity, purpura, erythema multiforme, photosensitivity, purpura, alopecia

Immunologic

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

Respiratory

Frequency not reported: Upper respiratory tract infection, interstitial lung disease causing breathing problems including persistent cough and/or shortness of breath or fever

Ezetimibe:
Common (1% to 10%): Coughing

Simvastatin:
Frequency not reported: Sinusitis, pharyngitis

Cardiovascular

Simvastatin:
Common (1% to 10%): Angina

Endocrine

Simvastatin:
Frequency not reported: Gynecomastia, thyroid function abnormalities, increases in HbA1c and fasting serum glucose levels

Genitourinary

Simvastatin:
Frequency not reported: Erectile dysfunction, impotence

A patient who had taken lovastatin and pravastatin on different occasions developed reversible impotence. The impotence resolved within 2 weeks after the HMG-CoA reductase inhibitor was discontinued.

Hematologic

Postmarketing reports: Epistaxis in a 65-year-old male

Ezetimibe:
Postmarketing reports: Thrombocytopenia

Simvastatin:
Frequency not reported: Hemolytic anemia, thrombocytopenia, leukopenia (possibly manifestations of a hypersensitivity reaction)

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.

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

Nervous system

Frequency not reported: Headache, confusion, fatigue

Ezetimibe:
Postmarketing reports: Dizziness, paraesthesia

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

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.

Ocular

Simvastatin:
Frequency not reported: Progression of cataracts, ophthalmoplegia

Oncologic

Simvastatin:
Frequency not reported: Liver, thyroid, and lung adenomas and carcinomas

Psychiatric

Simvastatin:
Frequency not reported: Depression, suicidal thoughts, delusions, paranoia, agitation, decreased libido, anxiety, insomnia

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