Creatine symptoms and conditions

I have been on Lisinopril for approx 5 years, during a routine year end blood work-up, I have developed a problems with my creatine levels 1.48 and Glom Filt Rate, Est 37. My physician had me do a 24 hr urine for further testing but insisted that I no longer take the Lisinopril. Several of the tests have come in and he advised me that I have only 50% blood flow to my kidneys. It appears to me that the Lisinopril has caused some kidney damage. I also have a great deal of muscle pain, but do to my age (55 years) I thought it was jus a part of the aging process. What do you think?

In July 2007, I was put on Levaquin for pneumonia. I was 53 years old, working full-time, active. The pneumonia was caused by aspiration when vomiting. I had never had these problems - pneumonia or aspiration - before. I had gradually worsening generalized joint and muscle pain and stiffness, which I reported to my doctor after about 5 days on the Levaquin. The pain I was experiencing was worse than the pneumonia symptoms (mostly high fever). The course of levaquin was supposed to be 14 days. After 9 days, I could not tolerate it any longer. My doctor put me on a Z-pack (azithromycin) for the remainder of my treatment. It is a year later, and I am still plagued with muscle pain in my back, shoulders, arm, abdomen - and, at its worst, my legs. The only way I'm able to function is on prescription painkillers, which I detest having to take - but they're a lifesaver. I've been seeing a rheumatologist since December '07. He dosen't seem to believe the levaquin - pain connection. He thinks I may have Polymyalgia Rheumatica. I have consistently elevated blood levels of creatine phosphokinase, a muscle enzyme which indicates muscle damage. I was on prednisone 10 mg. from early March '08 which I have just weaned off of after suffering a depressive episode with a suicide attempt at the begining of this month. I can't work now. I'm terrified of becoming permanently disabled. Finding answers has been very difficult but I firmly believe that the Levaquin started all this.

Can Statins Cause Chronic Low-Grade Myopathy?
Statins (hydroxymethyl glutaryl coenzyme A reductase
inhibitors) are highly effective drugs for reducing serum
cholesterol and low-density lipoprotein cholesterol levels.
Clinical trials have shown that they also reduce risk for
coronary heart disease events, coronary procedures, and
stroke by about one third (1). Millions of people in the
United States and worldwide are being treated with statins.
In clinical trials and in clinical practice, statins have proved
to be remarkably safe.
The one notable side effect of statin therapy is myopathy.
A small fraction of patients who are treated with
statins will develop severe myopathy (2). In the worst cases,
severe myoglobinuria, acute renal failure, and even death
can occur. The incidence of severe myopathy is low, perhaps
1 in 1000 patients (2). Predisposing factors for severe
myopathy appear to include advanced age, relatively low
body weight, female sex, certain medications, use of multiple
medications, multisystem disease, and acute illnesses
or major surgery (3). If statins were avoided or used in low
doses in these circumstances, it is likely that the incidence
of severe myopathy could be greatly reduced.
Less severe forms of myopathy undoubtedly occur. In
some patients, fatigue and muscle pain and weakness develop
with moderately high serum creatine kinase levels
but not acute renal failure. In these cases, the myopathy
resolves when statin therapy is discontinued.
Still more patients report various muscle symptoms—
fatigue, pain, and muscle weakness—but have normal creatine
kinase levels. These symptoms probably are unrelated
to statin therapy in many patients. In middle-aged and
older people, muscle, joint, and tendon symptoms are very
common. Naturally, if a patient takes a medication that is
believed to produce muscle problems, symptoms are often
attributed to the medication. On the other hand, the major
controlled clinical trials have not detected a higher prevalence
of muscle symptoms during statin therapy versus placebo
(1). This failure of detection has generally led clinical
trialists to conclude that statin-associated myopathy with
normal creatine kinase levels essentially does not exist or
that, if it does exist, it cannot be detected above the “background
noise” of muscle symptoms in the general clinicaltrial
population.
Many physicians in clinical practice nonetheless believe
that they can identify a subset of statin-treated patients
who have a unique set of statin-related muscle symptoms.
Some patients clearly relate the onset of muscle
symptoms to initiation of statin therapy. These symptoms
may abate after discontinuation of therapy, only to reappear
when statin therapy is restarted. The number of such
patients is not large, and thus it may have been impossible
to identify them in large clinical trials.
In this issue, Phillips and colleagues (4) report on a set
of studies in four patients who had muscle symptoms during
statin therapy that resolved during placebo use. Quantitatively
measured muscle weakness also resolved during
placebo use. Muscle biopsies were performed in three patients
during statin therapy and then during placebo use.
Several pathologic changes were seen on biopsy specimens
obtained during statin therapy: increased lipid content of
mitochondria, fibers that did not stain for cytochrome oxidase
activity, and ragged red fibers. The authors suggest
that these patients had statin-associated myopathy with
normal serum creatine kinase levels.
Despite the study’s small size, we cannot dismiss these
observations as random variation in muscle structure.
However, these highly suggestive results are clearly preliminary.
The number of patients was small, and all appropriate
controls were not used. Nonetheless, this study is novel
because it used quantitative measures of muscle strength
and muscle biopsy to address the question of myopathy
with normal creatine kinase levels during statin therapy.
To be confirmed, the current data would have to be
extended to many more patients in whom muscle symptoms
are closely correlated with statin use. Reproducibility
of symptoms during therapy and symptom resolution after
discontinuation of statin therapy would be necessary. A
definitive study would have to be carefully designed and
executed. It would need to be double-blinded and placebocontrolled
and include sufficient numbers of patients to
provide a valid statistical comparison. In addition, investigators
would have to carefully consider the appropriate
selection of patients. The development of a registry of candidate
patients at multiple sites could facilitate a multicenter
study.
Is a carefully controlled, sizable study of this type
worth the investment of time and effort? To date, no evidence
indicates that prolonged statin therapy leads to permanent
muscle damage or progressive myopathy in patients
with normal creatine kinase levels. Controlled
clinical trials attest to the general safety of statins, and
symptomatic side effects appear to be limited to a relatively
small proportion of treated patients. In addition, no therapy
prevents or treats statin-induced myopathy, short of
withholding the drug. On the other hand, statins are being
prescribed to millions of people, and are usually continued
throughout the patient’s lifetime. It is certain that statins
cause myopathy in some patients. For these reasons, a valid
argument can be made for a more extensive study of lowgrade
myopathy in patients treated with statins.
In the meantime, physicians should recognize the great
benefit of statin therapy in high-risk patients and their
documented safety for most patients. For high-risk persons,
the proven efficacy for preventing cardiovascular disease
outweighs the unlikely possibility of permanent muscle
damage. Phillips and colleagues’ preliminary results
certainly do not provide adequate information on the spec-
Editorial
www.annals.org 1 October 2002 Annals of Internal Medicine Volume 137 • Number 7 617
trum, scope, or prognosis of myopathy with normal creatine
kinase levels during statin therapy. For these reasons,
prescription of statins for eligible patients should continue
despite the current results. Moreover, before discontinuing
therapy, physicians should carefully evaluate any patient
receiving statins who reports muscle symptoms. In most
cases, the symptoms will be found not to be consistent
with chronic myopathy, and often they will not be related
temporally to statin treatment. High-risk patients in particular
should not be deprived of major cardiovascular risk
reduction just because they display symptoms not clearly
documented to be closely related to statin therapy.
Despite these comments, the actions of statin on muscle
metabolism and structure deserve further investigation
to clarify the confusing area of low-grade myopathy apparently
associated with statin use in a few patients.
Scott M. Grundy, MD, PhD
University of Texas Southwestern Medical Center at Dallas
Dallas, TX 75390-9052
Current Author Address: Scott M. Grundy, MD, PhD, Center for
Human Nutrition and the Departments of Clinical Nutrition and Internal
Medicine, University of Texas Southwestern Medical Center at Dallas,
5323 Harry Hines Boulevard, Y3.206, Dallas, TX 75390-9052.
Potential Financial Conflicts of Interest: Honoraria (from Merck &
Co.; Pfizer, Inc.; Bristol-Myers Squibb; and Bayer); Grants (from Merck
& Co. and Pfizer, Inc.)
Ann Intern Med. 2002;137:617-618.
References
1. Executive Summary of The Third Report of The National Cholesterol Education
Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment
of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;
285:2486-97.
2. Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis
. N Engl J Med. 2002;346:539-40.
3. Pasternak RC, Smith SC, Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant
C. ACC/AHA/NHLBI clinical advisory on the use and safety of statins (1)
(2). J Am Coll Cardiol. 2002;40:567-72.
4. Phillips PS, Haas RH, Bannykh S, Hathaway S, Gray NL, Kimura BJ, et al.
Statin-associated myopathy with normal creatine kinase levels. The Scripps Mercy
Clinical Research Center. Ann Intern Med. 2002;137:581-5.
© 2002 American College of Physicians–American Society of Internal
Medicine
Editorial Statins and Low-Grade Myopathy
618 1 October 2002 Annals of Internal Medicine Volume 137 • Number 7 www.annals.org

My Dad was using Efudex and his PT/INR increased above the therapeutic level. Now his creatine has increased. After he was taken off of the Efudex his PT/INR went back to normal. Any thoughts?

I have been taking some form of Lithium Carbonate since 1972. About one year ago after taking a routine blood test prescribed by my psychiatrist, I was told my creatine level was somewhat spiked. The psych referred me to a nephrologist. After examination by the nephrologist, I was told I had 50% less kidney function and he believed to be my long-time intake of lithium carbonate products. The nephrologist also informed me that I would not regain function and perhaps suffer further loss of kidney function which would require dialysis. My psych immediately took me off Lithium and I suffered the extreme side effects of replacement meds like Carbamabazine (generic Tegretol).

After by-pass heart surgery in 2002, my cardilogist put me on 40mg of zocor.
I was in good health with no physical limitations. I had no heart damage. The restriction of heart arteries were found due to my stress test that was performed each year as a part of my annual Physical. After surgery I was on zocor for three years, during that time I experienced a little tiredness, little weakness, a little muscle aches. some tingling in my right arm and shoulder. I went to my heart doctor Jan. 2006 and he changed me to vytorin (10mg zetia and 40mg zocor). about 6 months all of the about symptoms got worse.
By Jan. 2007, my muscles became so stiff, I could not walk, had balance problems, severe muscle aches and cramps, numbness and tingling in both arms and hands, also stifness and pain in my hands, stiffness and pain in both feet, stifness and pain in my back and weird nerve sensations over my entire body. During Jan. and Feb 2007, I was seen by my family doctor, a neurologist, and a muscle doctor. Thanks to the internet, I found info on zocor and zetia, which is the drug vytorin. Warnings described the same symptoms I am experiencing. I stopped vytorin, I am not taking any statins drugs now. My doctor order a blood test to check for muscle damage, It indicated severe damage, a Creatine level of 770. This level should not be over 200. After being off the drugs for 30 days the creatine level dropped to 645. My condition has improved by 25%. I am walking a little better, but I still having muscle problems, there is improvement. I think there will be a very long recovery. There seems to be some evidence that these Statins affect people of age much more than the young. I am 70 years old. PLEASE PEOPLE, IF YOU ARE TAKING STATINS DRUGS, STOPPED NOW! SLOVE YOUR CHOLESTROL PROBLEMS BY OTHER MEANS. Since I stopped my cholestrol has gone from 157 to 280, but I am not going back taking these drugs. I am trying the natural way now. I have read post after post on many web-sites of people with the same symptoms that were using these drugs. The drug companies and the FDA are responsible for the the degradation of people's health taking these statin drugs.