Zocor Adverse Reactions
- abdominal pain
- alopecia
- asthenia
- cholestasis
- cirrhosis
- constipation
- diarrhea
- drowsiness
- dyspepsia
- elevated hepatic enzymes
- fatigue
- flatulence
- headache
- hepatic failure
- hepatic necrosis
- hepatitis
- infection
- insomnia
- muscle cramps
- musculoskeletal pain
- myalgia
- myasthenia
- myoglobinuria
- myopathy
- nausea/vomiting
- pancreatitis
- rash (unspecified)
- renal tubular obstruction
- rhabdomyolysis
- weakness
Zocor (Simvastatin) Adverse Reactions
Simvastatin was extremely well tolerated in controlled clinical trials. Only 1.4% of subjects were discontinued from therapy due to the adverse effects of simvastatin. Adverse reactions tended to be transient and mild. Constipation (2.3%), dyspepsia (1.1%), flatulence (1.9%), and upper respiratory infection (2.1%) were the only adverse reactions reported at a higher incidence than placebo. The following adverse reactions were reported in greater than 1% of patients receiving simvastatin during clinical trials, but their incidence were similar or higher in the placebo control groups. These adverse reactions include abdominal pain (3.2% vs. 3.2% placebo), asthenia or weakness (1.6% vs. 2.5% placebo), diarrhea (1.9% vs. 2.5% placebo), nausea/vomiting (1.3% vs. 1.9% placebo), and headache (3.5% vs. 5.1% placebo). In a 48 week controlled study of children and adolescents aged 10 - 17 years with heterozygous familial hypercholesterolemia, the safety and tolerability profile of simvastatin was generally similar to placebo. The most common adverse experiences in children included upper respiratory infection, headache, abdominal pain, and nausea.
Myopathy, rhabdomyolysis and acute renal failure (renal tubular obstruction, myoglobinuria) have been reported rarely during simvastatin therapy, but the risk is increased when used in combination with drugs known to inhibit CYP3A4 metabolism or drugs which have an independent risk of myopathy (see Drug Interactions). In the Heart Protection Study, the incidence of myopathy/rhabdomyolysis was < 0.1% in patients treated with simvastatin (40 mg/day). Statin-induced myopathy is generally dose-related. During simvastatin clinical trials where patients were carefuly monitored and some interacting drugs were excluded, the frequency of myopathy/rhabdomyolysis has been reported to be approximately 0.02% for 20 mg, 0.07% for 40 mg, and 0.3% for 80 mg dosing, respectively. Patients should be monitored for symptoms of myopathy or rhabdomyolysis (myalgia, muscle cramps, musculoskeletal pain, lethargy/drowsiness, fatigue, fever, and/or myasthenia) and CPK serum concentrations. CPK concentrations can increase to >= 200,000 during therapy, but correlate poorly with symptoms. Myopathy or myositis can reverse if therapy is discontinued.
Although rare, severe hepatoxicity may occur during HMG-CoA reductase inhibitor therapy. Hepatitis, fatty changes of the liver, cholestasis with jaundice, cirrhosis, fulminant hepatic necrosis, hepatic failure, and pancreatitis have been reported during therapy with HMG-CoA reductase inhibitors. Simvastatin therapy can cause elevated hepatic enzymes. Persistent elevations of serum transaminases have been reported in 1% of patients during clinical studies. These elevations were not associated with jaundice or other signs or symptoms of hepatotoxicity. Enzyme concentrations will decrease to pretreatment concentrations after discontinuation of simvastatin. Liver function tests should be performed at the start of simvastatin therapy, and thereafter when clinically indicated. Before titrating to the 80 mg dose, liver function tests (LFTs) should be measured, and then repeated 3 months after dosage titration, and periodically thereafter (e.g., semiannually) for the first year of treatment with the higher dosage.
A variety of other adverse reactions have been reported during therapy with HMG-CoA reductase inhibitors, but a causal relationship has not been established with simvastatin. Sexual dysfunction including gynecomastia, libido decrease, and impotence has been reported. Rash (unspecified) has been reported for 0.6% of patients receiving simvastatin during the 4S trial, which did not differ from placebo (0.6%). Other infrequent dermatologic reactions during HMG-CoA reductase inhibitor therapy generally may include alopecia, pruritus, erythema multiforme, and toxic epidermal necrolysis. Adverse neurological reactions that have been reported include insomnia, tremor, vertigo, memory loss, paresthesias, and peripheral neuropathy.
[ Last revised: 8/18/2004 5:03:00 PM ]
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