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Zocor-Amiodarone Drug Interaction Causes Rhabdomyolysis; Fifth Such Case Reported

Causation Theory: Zocor Is Metabolized By Same Enzyme Which Is Being Inhibited By Amiodarone

On March 14, 2006 The Annals of Pharmacotherapy published online an article about what the authors described as "the fifth reported instance, as of February 15, 2006, of a severe interaction between simvastatin and amiodarone."  Simvastatin in sold by Merck under the trade name Zocor.  Amiodarone is sold by Wyeth as Cordarone, and by Upsher-Smith as Pacerone; several companies sell a generic version of amiodarone, also.

This latest case report involves a 72-year-old white man who started taking amiodarone (200 mg/day) on July 10, 2004, and on August 13 started taking Zocor (80 mg/day) while continuing the amiodarone. The patient was hospitalized on September 21, 2004 after complaining of thigh weakness and achiness; he also reported having dark urine for 7 days.

At the time of his hospital admission, the patient’s relevant lab results were as follows:

  • creatine kinase (CK) 19,620 U/L (reference range 60-224);
  • blood urea nitrogen 50 mg/dL;
  • creatinine 2.6 mg/dL;
  • aspartate aminotransferase (AST) 912 U/L (30-60);
  • alanine aminotransferase (ALT) 748 U/L (30-60);
  • urine myoglobin 71,100 µg/L (<50); and,
  • serum myoglobin 13,877 µg/L (<110).

Upon admission, the Zocor and amiodarone were discontinued.  The patient was ultimately diagnosed with rhabdomyolysis, renal failure, and possibly hepatotoxicity.  After appropriate treatment, the patient recovered over the course of the next couple of weeks.

The authors of this drug-drug interaction case report in The Annals of Pharmacotherapy arrived at these conclusions:

  1. "An objective causal assessment suggests that rhabdomyolysis, renal failure, and possibly hepatotoxicity were probably related to an amiodarone-simvastatin [i.e., Zocor] interaction."
  2. "[Zocor] is metabolized primarily by CYP3A4, and amiodarone is a recognized inhibitor of this enzyme. This may, therefore, account for the presumed drug interaction."

The authors pointed out that this patient had pre-existing diabetes mellitus, hyperlipidemia, and hypertension, as well as mild azotemia.  They did not, however, believe that these pre-existing medical conditions were substantial contributing causes as concerned the drug-induced rhabdomyolysis.

(Posted by: Tom Lamb)

6 responses to “Zocor-Amiodarone Drug Interaction Causes Rhabdomyolysis; Fifth Such Case Reported”

  1. carl calo Avatar
    carl calo

    Six months on amiodarone for a-fib has caused chaos in my body. The worst is chronic kidney
    disease. My Dr. just stopped amiodarone this week.
    08/02/2007.

    Reply
  2. Tom Lamb Avatar
    Tom Lamb

    I appreciate you taking the time to share your amiodarone experience with us. Hopefully the discontinuation of this drug will result in an improvement as regards your health.
    Thanks for reading Drug Injury Watch.
    Tom Lamb

    Reply
  3. Lou Sagnola Avatar
    Lou Sagnola

    My father is currently in acute renal fialure and on dialysis due to Statin drug (Zocor) induced Rhabdomyolysis.
    His original dosage was 10 mg., but after a very, very slight heart attack about a month ago,his dosage was increased to 80 mg., thus creating the Rhabdomyolysis. Over the last 3 weeks, he was seen by an emergency room doctor for a flu. The ER doctor prescribed Arythromyicin. That didn’t work (because he actually had Rhabdomyolysis). He then went to his family physician for stronger antiboitics. His physician then prescribed stronger antibiotics; never suspecting Rhabdomyolysis. After this didn’t work, my dad went back to his doctor who again mistakenly diagnosed him with Bursitis and gave him an injection. At this point, I’m wondering why they’re not chceking his blood for a reaction to the huge 10mg to 80mg increase in Zocor. In the meantime, his treatment was delayed for weeks. It is a fact that he is suffering from drug induced Rhabdomyolysis, the other issue is that because so much time was lost until he had proper treatment, he is not only in complete renal failure, he is also experiencing pain on a level that I have never witnessed in a human being…and I’ve seen a fair ammount of serious pain and injuries. It is absolutely incredible. In the meantime, we are hopeful that his kidneys will regain function. This is an incredible experience.
    I am a high school teacher and an only child. I live about 2 hours from where my parents live. I’m concerned about when my father is eventually released from the hospital. My mother is going to need serious help. My father won’t be able to get around for quite awhile.
    How do you recommend I proceed?
    Thank you,
    Lou

    Reply
  4. Tom Lamb Avatar
    Tom Lamb

    To start, I hope things inprove for your father.
    I fully understand why you are concerned and upset.
    To the extent you are looking for medical advice, I am only an attorney and cannot help you there.
    As regards the legal aspect, the Zocor package insert, or label, warns about rhabdomyolysis as a known side effect. As such, there is no products liability case to pursue. There could be some negligence in the care and treatment that led up to your father being in the condition he is, now, but I cannot make that determination based on this limited information. Any possible medical malpractice case would be handled by an attorney in the state where the prescribing and treating doctors are found.
    I hope this information is somewhat helpful to you and your family.
    Thanks for reading Drug Injury Watch.
    Tom Lamb

    Reply
  5. Karen Muccino Avatar
    Karen Muccino

    I am writing in hopes to increase public awareness of Amiodarone Induced Pulmonary Toxicity.
    Amiodarone is a very dangerous drug. My father, a retired OBGYN, woke up on January 1 2004, his 69th Birthday, with a temp of 100, general malaise, and sore throat. Typical symptoms of the cold that was going around at the Holidays. He felt a little better on the 2nd. On January 3, our nightmare began as a family; my Dad was short of breath and thought that he might have pneumonia. My mom, his wife of 47 years, took him to the urgent care clinic. He had a Chest X-ray and was immediately admitted to the Hospital, with an initial diagnosis of bilateral pneumonia. On January 4, he was transferred to ICU. He did not respond to antibiotics within 24-48 hours, and his Cardiologist feared that he was suffering from Amiodarone Pulmonary Toxicity. He had a lung biopsy shortly thereafter that confirmed his diagnosis.
    My Dad had been on Amiodarone 200mg qd for 10 months, post oblation for chronic atrial fibrillation. He had no previously lung disease or open-heart surgery.
    He complained of a scratchy throat for 2-3 months. His primary care doctor thought it was ENT related, and referred him to the ENT. The ENT thought it was GI related and sent him to GI. He never made it to that appointment, as he was in ICU.
    He was started on steroids within the first couple of days of his admission, and the amiodarone was discontinues.
    My Father had a normal CT scan of the lungs in the middle of Oct. 2003, just 8 weeks later, fatal lung damage from Amiodarone.
    His condition continued to get worse. He was put on a ventilator on January 18, 2004, which he was unable to tolerate. He was on high pressures and developed subcutaneous emphysema, pneumoperitoneum and pneumopericardium. They changed him to a low tidal volume protocol that was developed by the ARDS Network His lungs were so severely damaged that he still was not getting enough oxygen to sustain his life. He had to be put on Vecuronium in order to tolerate settings, which included 35 breaths/minute. 5 Children and a wife of 47 years, watched over him for 49 days, as his condition deteriorated, and Never improved.
    The half-life of this drug is so dangerous. Once toxicity was diagnosed, it didn’t matter that the drug was discontinued as it continued to do damage. Steroids did not improve his condition at all.
    Someone needs to come up with a new protocol for monitoring lung damage/ lung function much more frequently than q3-6months. A chest x-ray, had it been done even 8 weeks prior to this event, would not have clued anyone into the fact that he was developing Pulmonary Toxicity. He had a CT scan, which was Normal.
    Further, the drug company made over 3 billion dollars in profit for patients on Amiodarone for off-label use. The last drug insert I read for Amiodarone states that adequate studies were NOT performed on people over the age of 65. How irresponsible. If they are making that kind of money, how could they not perform adequate studies? Perhaps studies were done, and the results so poor that they were afraid to publish them. Rather than losing 3 billion dollars they decided to state that adequate studies weren’t performed. The law should require drug companies to conduct adequate studies before a drug can be used for off-label use. In 2005 I was able to push the FDA to force the Drug company to put out stronger warnings to the public, which they did.
    However, the dangers of this drug still continue.
    When I sent the incident report to the FDA, I received a canned response stating, “Thank you for informing us of “YOUR” incident”. It is apparent that they do not even read the incident report. For God sake I was reporting a death.
    I feel compelled to write to as many people as possible, to warn against the dangerous effects of this drug.
    In addition, I think patients should be required to sign a consent form, notifying them of the warnings.
    Further, more needs to be done in the Medical Community to educate Primary Care Physicians of the severe effects of some drugs.
    Red warning labels should be put on the Patients Medical Chart.
    We experienced first hand, the very slight symptoms of Amiodarone Pulmonary Toxicity. My Dad’s symptoms went unnoticed by him, a Physician, as they were so minor. He thought he had developed allergies, or that our air was too dry, and thus the dry cough. He had no other symptoms that would have caused any alarm. Just 6 days prior to being hospitalized, he enjoyed a wine tasting gondola cruise through the marina in Long Beach with his entire family. He was running around, getting in and out of the boat just fine with no Shortness of Breath. I lived with him, and he presented NO symptoms of concern. He was filled with energy and life, just 2 days before being hospitalized.
    Now I am reading new warning about Amiodarone and Simvastatin. He was on Simvastatin 40 mg. However, to my knowledge, did not develop Rhabdomyolysis.
    My story is NOT an isolated incident. I have been notified by many others who lost a family member due to Amiodarone.
    Thank you for the opportunity to write my story.

    Reply
  6. Tom Lamb Avatar
    Tom Lamb

    Thank you for sharing with us, below, this tragic story as well as the facts learned from your research.
    I hope the information you have presented here will get to the doctors and patients who need it, and that it comes to their attention in a timely manner.
    Please continue with your efforts to increase public awareness of Amiodarone Induced Pulmonary Toxicity. What you are doing certainly honors your father and his choice of profession.
    Thanks for reading Drug Injury Watch.
    Tom Lamb

    Reply

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