Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027121 (myositis)
 4,538 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholestyramine, colestipol, clofibrate, gemfibrozil, nicotinic acid (niacin), probucol, neomycin, and dextrothyroxine are the most commonly used drugs in the treatment of hyperlipoproteinaemic disorders. While adverse reaction data are available for all of them, definitive data regarding the frequency and severity of potential adverse effects from well-controlled trials using large numbers of patients (greater than 1000) are available only for cholestyramine, clofibrate, nicotinic acid and dextrothyroxine. In adult patients treated with cholestyramine, gastrointestinal complaints, especially constipation, abdominal pain and unpalatability are most frequently observed. Continued administration along with dietary manipulation (e.g. addition of dietary fibre) and/or stool softeners results in diminished complaints during long term therapy. Large doses of cholestyramine (greater than 32 g/day) may be associated with malabsorption of fat-soluble vitamins. Most significantly, osteomalacia and, on rare occasions, haemorrhagic diathesis are reported with cholestyramine impairment of vitamin D and vitamin K absorption, respectively. Paediatric patients have been reported to experience hyperchloraemic metabolic acidosis or gastrointestinal obstruction. Concurrent administration of acidic drugs may result in their reduced bioavailability. Serious adverse reactions to clofibrate will probably limit its role in the future. Of particular concern are ventricular arrhythmias, induction of cholelithiasis and cholecystitis, and the potential for promoting gastrointestinal malignancy which far outweigh the reported benefits in preventing new or recurrent myocardial infarction, cardiovascular death and overall death. Patients with renal disease are particularly prone to myositis, secondary to alterations in protein binding and impaired renal excretion of clofibrate. Drug interactions with coumarin anticoagulants and sulphonylurea compounds may produce bleeding episodes and hypoglycaemia, respectively. Nicotinic acid produces frequent adverse effects, but they are usually not serious, tend to decrease with time, and can be managed easily. Dermal and gastrointestinal reactions are most common. Truncal and facial flushing are reported in 90 to 100% of treated patients in large clinical trials. Significant elevations of liver enzymes, serum glucose, and serum uric acid are occasionally seen with nicotinic acid therapy. Liver enzyme elevations are more common in patients given large dosage increases over short periods of time, and in patients treated with sustained release formulations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Adverse effects of hypolipidaemic drugs. 354 4

Seventy-four patients with plasma low-density lipoprotein cholesterol levels > or = 160 mg/dl after an American Heart Association phase 1 diet were randomized to double-blind treatment with fluvastatin, 20 mg/day, or placebo for 6 weeks. Immediate-release niacin was then added to both treatment regimens and titrated to a maximum of 3 g/day for a further 9 weeks. After 6 weeks of fluvastatin monotherapy, low-density lipoprotein cholesterol levels decreased by 21% (p < 0.001 vs placebo), and after the addition of niacin, response was potentiated to 40% compared with 25% for the niacin control group at study end point (p < 0.001). Fluvastatin, alone and in combination with niacin, also significantly improved high-density lipoprotein cholesterol (increases of about 30%) and triglyceride profiles (decreases of approximately 28%) from baseline. Lipoprotein(a) decreased by 37% in those receiving fluvastatin-niacin but was unaltered in those receiving fluvastatin alone. No serious adverse events were ascribed to fluvastatin, and no cases of myositis were observed. Small, transient, asymptomatic increases in aspartate aminotransferase were noted with fluvastatin-niacin treatment but were not considered clinically relevant. Although the fluvastatin-niacin combination in this study was without evidence of significant transaminitis, myopathy, or rhabdomyolysis, it would seem prudent to continue to monitor its safety with longer term use. In conclusion, fluvastatin, both as monotherapy and in combination with niacin, proved to be an effective, safe, and well-tolerated therapeutic alternative for hypercholesterolemia.
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PMID:Fluvastatin with and without niacin for hypercholesterolemia. 802 79

Fluvastatin sodium (Lescol; Sandoz) the first entirely synthetic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor studied, is structurally distinct from the other HMG-CoA reductase inhibitors currently available, all of which are fungal metabolites and analogues of compactin. Fluvastatin's distinct structure may be responsible for the biopharmaceutical properties that result in its low systemic exposure and, subsequently, low incidence of peripheral adverse events, such as headache and myositis. Fluvastatin is rapidly absorbed from the gastrointestinal tract; has a 30-minute half-life, the shortest of any currently available HMG-CoA reductase inhibitor (lovastatin, 15 hours; pravastatin, 2 hours; simvastatin, 15.6 hours); is highly selective for the liver, undergoing extensive first-pass metabolism; has no active circulating metabolites; and does not penetrate the blood-brain barrier, unlike lovastatin and simvastatin. The low systemic exposure suggests that the occurrence of peripheral adverse events, such as myositis, central nervous system effects, and drug-drug interactions, may be less than what is currently observed with other HMG-CoA reductase inhibitors. Neither niacin nor propranolol had an effect on fluvastatin plasma levels when combined with fluvastatin. In contrast to other HMG-CoA reductase inhibitors, fluvastatin in combination with niacin resulted in no instances of myositis or other serious adverse events. Although the interaction of fluvastatin with cholestyramine resulted in a lower rate and extent of fluvastatin bioavailability, this reduction had no impact on clinical efficacy. Fluvastatin administered to patients chronically receiving digoxin had no effect on the area under the curve (AUC) of digoxin compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical implications of the biopharmaceutical properties of fluvastatin. 819 18

A double-blind, randomized study was undertaken to evaluate the efficacy and safety of fluvastatin as monotherapy and as combination therapy with niacin in the treatment of hypercholesterolemia refractory to diet. Seventy-four patients with plasma low-density lipoprotein cholesterol (LDL-C) levels > or = 160 mg/dL were treated with fluvastatin, 20 mg/d, or placebo for 6 weeks. Thereafter, immediate-release niacin, at a dosage titrated to a maximum of 3 g/d, was added to both regimens for another 9 weeks. All adverse events were monitored, with particular attention to the evaluation of liver and muscle enzymes. Initial analysis of the data shows that fluvastatin and its combination with niacin was well tolerated and was not associated with any serious adverse events. Small, transient, asymptomatic rises in aspartate aminotransferase (AST) occurred in 28.9% of fluvastatin-niacin treated patients compared to 8.3% in the niacin-placebo control arm (p < 0.05). These were considered clinically insignificant in that no transaminase elevations > 3 times the upper limit of normal occurred. No evidence of myopathy, creatine kinase levels exceeding 10 times the upper limit of normal, myositis, or rhabdomyolysis were demonstrated in this short-term trial. The majority of adverse events resulting in patient withdrawals were ascribed to niacin therapy and included cutaneous vasodilatation, flushing, itching, and rash. These preliminary results suggest that fluvastatin, both alone and combined with niacin, is an effective, safe, and well-tolerated treatment for hypercholesterolemia.
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PMID:Combination therapy with fluvastatin and niacin in hypercholesterolemia: a preliminary report on safety. 819 20

To determine the effect of the combination of niacin and gemfibrozil on the lipid profile, a retrospective review was conducted of 161 patients who were prescribed a combination of gemfibrozil and niacin for 6 to 12 months at a community-based lipid clinic. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, ratio of total cholesterol to HDL, alanine aminotransferase (ALT), and weight were measured at entry to the clinic, 2 months after dietary instruction, during single-agent therapy, and during combination therapy. Mean doses of niacin and gemfibrozil were 1,229 mg/day and 1,200 mg/day, respectively. Patient weight decreased significantly after dietary instruction and after institution of combination therapy. There were no significant changes in ALT levels with either single-agent therapy or with combination therapy. The combination of niacin and gemfibrozil produced marked and significant changes in lipid levels: total cholesterol and LDL decreased by 14%, HDL increased by 24%, the ratio of total cholesterol to HDL decreased by 30%, and triglycerides decreased by 52%. The combination of niacin and gemfibrozil in the setting of dietary instruction has a marked beneficial effect on serum lipid levels, and was most effective in patients with initial levels of HDL < 40 mg/dL, triglycerides > 250 mg/dL, and LDL > 160 mg/dL. No episodes of ALT elevation or symptomatic myositis were seen.
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PMID:Effect of a combination of gemfibrozil and niacin on lipid levels. 887 72

The use of lipid-altering drugs has been shown to reduce the progression of atherosclerotic lesions and reduce the risk of atherosclerotic events (such as myocardial infarction and stroke). In general, these lipid-altering drugs are well tolerated but there is the potential for drug interactions. For example, HMG-CoA reductase inhibitors may interact with macrolides, azalides, azole antifungals and cyclosporin. Resins (such as cholestyramine and colestipol) may impair the absorption of many concurrent medications. Fibrates have potential drug interactions with warfarin, furosemide (frusemide), oral hypoglycaemics and probenecid. Nicotinic acid (niacin) may have potential drug interactions with high dose aspirin (acetylsalicylic acid), uricosuric agents (such as sulfapyrazone) and alcohol (ethanol). Finally, probucol may have potential drug interactions with antidysrhythmics, tricyclic antidepressants and phenothiazines. In addition, lipid-altering drugs, used in combination, may have the potential for drug interactions, enhancing some of the risks of adverse effects, such as myositis and hepatotoxicity. Therefore, in order to use lipid-altering drugs in the most effective, and safest manner, it is important for the clinician to have an understanding of the mechanisms of potential drug interactions, which drug interactions may theoretically occur, and specifically, which spe cific drug interactions have already been described.
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PMID:Drug interactions of lipid-altering drugs. 982 49

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are associated with myopathy, myalgias, myositis, and rhabdomyolysis. Rhabdoymyolysis is a rare complication and may cause acute renal failure, which may be fatal. In such cases, alternative therapies should be considered. In this review, we attempted to elucidate the lipid management options in patients with rhabdomyolysis and coronary artery disease. We also describe a case report of a patient who developed rhabdomyolysis from dual antilipid therapy followed by acute renal failure and non-ST elevation myocardial infarction. Such a complex case has not been reported in the literature, and lipid management options may include niacin, omega 3-fatty acids, or bile acid sequestrants. Once alternative therapies are initiated, monitoring a patient closely with evaluation for associated adverse events should be performed.
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PMID:Statin-associated rhabdomyolysis with acute renal failure complicated by intradialytic NSTEMI: a review of lipid management considerations. 2119 42