Drug interactions between colchicine and Lipitor

colchicine ↔ atorvastatin

Applies to:colchicine and Lipitor (atorvastatin)

MONITOR CLOSELY: Coadministration of colchicine and HMG-CoA reductase inhibitors may increase the risk of myopathy due to a combination of pharmacodynamic and pharmacokinetic effects. These agents are individually myotoxic and may have additive or synergistic effects when used together. In addition, colchicine and some HMG-CoA reductase inhibitors are substrates of the CYP450 3A4 isoenzyme and P-glycoprotein efflux transporter, thus competitive inhibition may occur resulting in increased drug absorption and decreased excretion. The interaction has been associated with case reports of patients who developed muscle weakness and markedly elevated creatine kinase levels within weeks to months of taking colchicine in combination with an HMG-CoA reductase inhibitor. Most of these patients were elderly and/or had preexisting renal impairment. One patient developed progressive muscle weakness leading to shortness of breath and respiratory failure, followed by death. The patient was a heart transplant recipient and had been on long-term cyclosporine, prednisone, and mycophenolate. Four months before the development of proximal muscle weakness, his simvastatin dose was doubled and he was also started on colchicine for acute exacerbation of gout. Colchicine and simvastatin were stopped on admission. During hospitalization, he received high-dose methylprednisolone for continued muscle weakness and was sedated with propofol, but creatine kinase increased to 33,580 U/mL. The muscle biopsy revealed toxic vacuolization, mitochondrial damage, and no evidence of inflammation. The interaction has also been associated with severe rhabdomyolysis resulting in myoglobinuric acute renal failure.

MANAGEMENT: Extreme caution is advised if colchicine is used in combination with HMG-CoA reductase inhibitors, particularly in the elderly and patients with underlying renal or hepatic impairment. Some experts recommend checking the creatine kinase level a week or two after coadministration of these agents and after any dose increase, although such monitoring does not reliably prevent the occurrence of severe myopathy. Patients should be advised to contact their physician if they experience symptoms of toxicity such as abdominal pain, nausea, vomiting, diarrhea, fatigue, myalgia, asthenia, hyporeflexia, paraesthesia, and numbness. The drugs should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.