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Ciprofloxacin interacts with thyroid replacement therapy
We report two cases of unexplained hypothyroidism in patients taking oral ciprofloxacin. Nursing staff gave levothyroxine. Prescription charts showed no drug administration errors. Patients did not have nausea, vomiting, or diarrhoea.
An 80 year old woman with advanced thyroid cancer had maintained suppressed concentrations of thyroid stimulating hormone and stable free thyroxine concentations by taking 125 microgram levothyroxine daily. She was admitted with a pathological fracture of the femur and complicating osteomyelitis. After four weeks treatment with oral ciprofloxacin (750 mg twice a day), intravenous dicloxacillin, and subcutaneous heparin, she complained of increasing tiredness. Her thyroid stimulating hormone concentration had increased to 44 mIU/l (reference range 0.4-4.4 mIU/l), free thyroxine had fallen to 4 pmol/l (12-22 pmol/l), and free triiodothyronine was 1.0 pmol/l (3.1-6.3 pmol/l).
Increasing levothyroxine to 200 micrograms daily had no effect. We reduced levothyroxine to 125 microgram daily and stopped ciprofloxacin, and thyroid function tests rapidly became normal. Other drugs (alfacalcidiol, propranolol, ranitidine, furosemide, methenamine hippurate, paracetamol, morphine, and ondansetron) were unchanged. We continued to give dicloxacillin and heparin as thyroid function returned to normal. The patient died of metastatic thyroid cancer three weeks after discharge.
A 79 year old woman with rheumatoid arthritis, manic depression, cardiac failure, chronic obstructive airways disease, and hypothyroidism was admitted with a wound infection after a transfemoral amputation. She had maintained stable thyroid function tests on a daily dose of 150 microgram levothyroxine. After three weeks treatment with oral ciprofloxacin (500 mg twice a day), her concentration of thyroid stimulating hormone had increased from 1.6 to 19 mIU/l and free thyroxine had fallen from 22 to 13 pmol/l. Switching from concomitant administration of levothyroxine and ciprofloxacin to administering the drugs with a six hour gap resulted in rapid normalisation of the thyroid function tests. Other drugs (zuclopenthixol, enalapril, bumetaninde, prednisolone, folic acid, lactulose, acetylcysteine, hydroxychloroquine, paracetamol, ipratropium bromide, salbutamol, nystatin) remained unchanged.
Oral ciprofloxacin may interact with levothyroxine if they are given together. The most plausible explanation is that ciprofloxacin decreases the absorption of levothyroxine. Antacids, laxatives, colestipol, colestyramine, ferrous sulfate, sulcralfate, and raloxifene have been reported to decrease the absorption of levothyroxine, (1-3) but we have not found any previous reports of an interaction between levothyroxine and ciprofloxacin. Neither have the WHO Collaborating Centre for International Drug Monitoring nor the manufacturer of ciprofloxacin. This interaction is important for patients taking long courses of ciprofloxacin. Patients should take levothyroxine and other drugs at different times.
2. Surks MI, Sievert R. Drugs and thyroid function. N Engl J Med 1995;333:1688-94.
3. Siraj ES, Gupta MK, Reddy SS. Raloxifene causing malabsorption of levothyroxine. Arch Intern Med 2003;163:1367-70.
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