Creatine therapy

Rl. Reinhold, J. G., and Kingsley, G. R., The chemical composition of voluntary muscle in muscle disease A comparison of progressive muscular dystrophy with other diseases together with a study of the effects of glycine and creatine therapy. /. Clin. Incest. 17, 377 (1938). 

Tabrizi SJ, Blamire AM, Manners DN, Rajagopalan B, Styles P, Schapira AGV, Warner TT (2005) High-dose creatine therapy for Huntington s disease A 2 year clinical and MRS study. Neurology 64 1655-1656. 

Myopathy and neuropathy Colchicine myoneuropathy appears to be a common cause of weakness in patients on standard therapy who have elevated plasma levels caused by altered renal function. It is often unrecognized and misdiagnosed as polymyositis or uremic neuropathy. Proximal weakness and elevated serum creatine kinase are generally present, and resolve in 3 to 4 weeks following drug withdrawal. Maiabsorption of vitamin B-f2- Colchicine induces reversible malabsorption of vitamin B-12, apparently by altering the function of ileal mucosa. 

Creatine kinase activity should be measured in patients receiving potentially interacting drug combinations. In all patients, CK should be measured at baseline. If muscle pain, tenderness, or weakness appears, CK should be measured immediately and the drug discontinued if activity is elevated significantly over baseline. The myopathy usually reverses promptly upon cessation of therapy. If the association is unclear, the patient can be rechallenged under close surveillance. Myopathy in the absence of elevated CK has been reported. Rarely, hypersensitivity syndromes have been reported that include a lupus-like disorder and peripheral neuropathy. 

Adverse effects in clinical trials were mild, including fatigue, headache, abdominal pain, upper respiratory infection, increased creatine phosphokinase levels, and nausea and vomiting. A potential association with peripheral neuropathy is under evaluation. As with other nucleoside analogs, lactic acidosis and severe hepatomegaly with steatosis may occur during therapy as well as flares of hepatitis after discontinuation. 

Combination therapy with fluvastatin and bezafibrate 400 mg/day in 71 patients with persistent hypertriglyceridemia resulted in no significant increase in creatine kinase activity or in the frequency of myalgia (76). 

In a placebo-controlled study of 1142 hypercholestero-lemic patients treated with pravastatin for 8-16 weeks, the numbers of adverse drug experiences were similar in the treated and untreated individuals (1). Rash was the only adverse clinical event that was different (4.0 versus 1.1%). However, in the same patients withdrawal of therapy during follow-up was thought to be necessary in 3.2% of those given pravastatin alone. Myopathy was observed in one instance only, and increases in creatine kinase activity in those taking pravastatin did not differ significantly from controls. There were marked persistent increases in transaminases in 1.1%, with no cases of symptomatic hepatitis. Pravastatin is believed to have a particularly low potential for nervous system-related adverse effects, as it has not been shown to enter the cerebrospinal fluid, and clinical experience suggests that muscle toxicity occurs less often with pravastatin than with lovastatin (2). 

Hypersensitivity reactions, occasionally fatal, have been reported in 2-5% of patients receiving abacavir. Symptoms, which generally occur within the first 6 weeks of therapy, involve multiple organ systems and include fever, malaise, and gastrointestinal complaints. Skin rash may or may not be present. Laboratory abnormalities such as mildly elevated serum aminotransferase or creatine kinase levels are not specific for this reaction. Although the syndrome tends to resolve quickly with discontinuation of medication, rechallenge with abacavir following discontinuation results in return... 

At this time in clinical practice, the role of fibrates is particularly in combination therapy with a statin. Monitoring of creatine phosphokinase levels is appropriate because of the very small, although increased risk of rhabdomyolysis. 

Marcus EL, Vass A, Zislin J. Marked elevation of serum creatine kinase associated with olanzapine therapy. Ann Pharmacother 1999 33(6) 697-700. 

A 30-year-old man with a history of bipolar disorder had substantial weight gain with olanzapine and was switched to risperidone (dose unknown) and lithium carbonate (450 mg bd) (112). A few days later he developed confusion, mild muscle rigidity, a raised temperature, and increased creatine kinase activity. The medications were withdrawn and he responded to supportive therapy. 

Cersosimo RJ, Lee JM. Creatine kinase elevation associated with 5-fluorouracil and levamisole therapy for carcinoma of the colon. A case report. Cancer 1996 77(7) 1250-3. 

F Before initiating statin therapy, it is recommended to have baseline measurements of the lipoprotein profile and LFTs. If the LFTs are more than three times the upper limit of normal (ULN), statins should be avoided. If the LFTs are less than three times the ULN, statin therapy can be initiated, but the patient should be monitored closely. If LFTs become elevated, reversal of the transaminase elevation is common upon discontinuation of the statin. Some experts also recommend obtaining a baseline creatine kinase (CK) level. If the CK level is more than 10 times the ULN while on a statin, the statin should be discontinued. The combination of a statin with niacin or a fibrate should be used cautiously because of an increased risk of myopathy. Although most statins are taken at dinner or bedtime, atorvastatin can be taken at any time of the day due to its longer T /i ( 14 hours). Lovastatin should be taken with food because this increases its bioavailabilty. 

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