Ezetimibe/Simvastatin Side Effects

Please note - some side effects for Ezetimibe/Simvastatin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Ezetimibe/Simvastatin - for the Consumer

Ezetimibe/Simvastatin

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Ezetimibe/Simvastatin:

Diarrhea; flu-like symptoms; headache; pain in the arms or legs; tiredness; upper respiratory tract infection.

Severe allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blurred vision or vision changes; change in the amount of urine; chest pain; dark urine; depression; fast heartbeat; fever; loss of appetite; muscle tenderness, pain, or weakness; nausea; numbness, tingling, burning, or weakness in the arms, hands, feet, or legs; pale stools; stomach tenderness; unexplained pain in the stomach or mid-upper back; unusual bruising or bleeding; unusual tiredness; vomiting; yellowing of the skin or eyes.

Side Effects by Body System

Gastrointestinal

Gastrointestinal side effects associated with ezetimibe have included diarrhea (3.7%), abdominal pain (3.0%), and nausea. Pancreatitis has been reported in postmarketing experience.

Gastrointestinal side effects associated with simvastatin have been reported the most frequently. These have included constipation (2.3% to 5.7%), nausea (1.3% to 4.4%), flatulence (1.9% to 3.4%), diarrhea (1.9% to 2.9%), dyspepsia (1.1% to 2.9%), and abdominal pain. A case of protein-losing enteropathy has been reported. Pancreatitis, anorexia, and vomiting have been reported with HMG-CoA reductase inhibitors therapy.

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.

Musculoskeletal side effects associated with ezetimibe including back pain (4.1%) and arthralgia (3.8%) have been reported. Myalgia, elevated creatine phosphokinase, and rare reports of myopathy/rhabdomyolysis have been reported in postmarketing experience.

Musculoskeletal side effects associated with simvastatin including elevations in creatine kinase, myopathy, dermatomyositis, and rhabdomyolysis have been reported. Arthralgia and myalgia associated with HMG-CoA reductase inhibitors have been reported.

Musculoskeletal side effects associated with the combination of ezetimibe-simvastatin include at least one case of tendon rupture.

Renal

Renal side effects associated with simvastatin including myoglobinuria and acute renal failure secondary to rhabdomyolysis have been reported.

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.

Hepatic side effects associated with ezetimibe including elevations in liver transaminases, hepatitis, cholelithiasis, and cholecystitis have been reported in postmarketing experience.

Hepatic side effects associated with simvastatin including elevations in liver function tests (1.5%) have been reported. Hepatitis (including chronic active hepatitis), cholestatic jaundice, fatty changes in the liver, cirrhosis, and fulminant hepatic necrosis have been reported with HMG-CoA reductase inhibitors therapy. Hepatic failure has been reported in postmarketing experience.

Dermatologic

Dermatologic side effects reported with HMG-CoA reductase inhibitors have included eczematous, pruritic rash, toxic epidermal necrolysis, photosensitivity, purpura, and alopecia.

Immunologic

Immunologic side effects associated with ezetimibe including sinusitis (3.6%), pharyngitis (2.3%), and viral infection (2.2%) have been reported.

Immunologic side effects associated with simvastatin (and other HMG-CoA reductase inhibitors) have included a case of lupus-like syndrome. Positive ANA, ESR increase, polymyalgia rheumatica, and vasculitis associated with HMG-CoA reductase inhibitors have been reported.

Respiratory

Respiratory side effects associated with ezetimibe including coughing has been reported in 2.3% of patients.

Cardiovascular

Cardiovascular side effects associated with simvastatin including angina have been reported 3.1% of patients.

Endocrine

Endocrine side effects of HMG-CoA reductase inhibitors have included gynecomastia and thyroid function abnormalities.

Genitourinary

Genitourinary side effects of HMG-CoA reductase inhibitors have included erectile dysfunction and 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

Hematologic side effects associated with ezetimibe including thrombocytopenia have been reported in postmarketing experience.

Hematologic side effects associated with HMG-CoA reductase inhibitors therapy including hemolytic anemia, thrombocytopenia, and leukopenia have been reported. These effects may be manifestations of a hypersensitivity reaction.

Hypersensitivity

Hypersensitivity side effects associated with ezetimibe including angioedema, anaphylaxis, rash, and urticaria have been reported in postmarketing experience.

Hypersensitivity side effects associated with HMG-CoA reductase inhibitors including (transferred from dermatologic) erythema multiforme and Stevens-Johnson syndrome have been reported. Anaphylaxis, angioedema, urticaria, fever, chills, flushing, malaise, and dyspnea have been reported rarely.

Nervous system

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.

Nervous system side effects associated with ezetimibe-simvastatin including headache have been reported. Dizziness and paresthesia have been associated with ezetimibe in postmarketing experience.

Nervous system side effects associated with HMG-CoA reductase inhibitors including cranial nerve dysfunction, tremor, vertigo, memory loss, paresthesias, peripheral neuropathy, and peripheral nerve palsy have been reported.

Ocular

Ocular side effects associated with HMG-CoA reductase inhibitors including progression of cataracts and ophthalmoplegia have been reported.

Oncologic

Oncologic side effects including tumor growth have been associated with many lipid-lowering drugs in rodent studies. Simvastatin has been specifically associated with liver, thyroid, and lung adenomas and carcinomas. Long-term clinical trials will define the risk of cancer in humans.

Psychiatric

Psychiatric side effects associated with simvastatin including depression, suicidal thoughts, delusions, paranoia, and agitation have been reported. In one uncontrolled study of simvastatin, psychiatric side effects were the second most frequent complaint. Decreased libido, anxiety, and insomnia associated with HMG-CoA reductase inhibitors have been reported.

Other

Other side effects associated with ezetimibe-simvastatin including fatigue, influenza, and upper respiratory tract infection have been reported.

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