Phosphate binders as a cause of hypothyroidism in dialysis patients: practical indications from a review of the literature

Abstract

BackgroundAlthough fatigue is common in dialysis patients, polypharmacy is seldom listed among its causes. In this report, we describe a dialysis patient who developed severe fatigue due to pharmacological interaction between two commonly prescribed drugs, phosphate binders and levothyroxine.Case PresentationA 65-year old woman, on dialysis for 17 years, complained of fatigue (weight 54 Kg, height 1.55 m, BMI: 23 Kg/m2; malnutrition inflammation index: 10; Charlson index 9). She had been treated with lithium for about 20 years. A heavy smoker, she was obese and diabetic when young, but stopped treatment after weight loss. She had undergone thyroidectomy for papillary carcinoma, left hemicolectomy for colon adenocarcinoma, left quadrantectomy followed by radiotherapy for ductal mammary adenocarcinoma, subtotal parathyroidectomy for tertiary hyperparathyroidism. At the time of this report, she was on thrice-weekly hemodiafiltration (Daugirdas 2 Kt/V: 1.6–1.8). Her recent treatment included spironolactone, amlodipine, perindopril, valproate, lamotrigine, levothyroxine, vitamin D, calcium carbonate, sodium polystyrene and sevelamer. After she questioned her doctor about whether her fatigue might be the result of a drug interaction, levothyroxine interference was identified (TSH, previously normal, increased to 13.07 mU/L, after increasing sevelamer dose, and normalized after change of drug schedule).Literature review: only 5 relevant papers on levothyroxine and phosphate binders on dialysis were found on Pubmed and EMBASE (out of 351 titles retrieved). Information was therefore inferred from studies in normal volunteers or in other diseases.Discussion and conclusionsOur case differs from other reports on lower TSH at diagnosis, underlining the need for awareness of the importance of early diagnosis. Integrating the scant literature on dialysis patients with data available in the general population, some working conclusions can be reached: while all phosphate binders potentially interfere with levothyroxine absorption, interference seems to be highest for sevelamer; interference is limited but not excluded by increasing the intervals between drugs; morning fast is usually indicated but, when clashing with the timing of other drugs, a bedtime dose and liquid preparations may be indicated. In the absence of an agreed control schedule, our case supports close monitoring of TSH (1–3 months if unstable, twice-yearly in stable patients).

Thyroid Pathology in End-Stage Renal Disease Patients on Hemodialysis

“…Literature studies are suggesting that patients with chronic kidney disease on renal replacement therapy, especially patients with thyroid disorders on levothyroxine replacement therapy can have a higher rate of hypothyroidism caused by phosphate binders. Phosphate binders can impair levothyroxine absorption leading to hypothyroidism [52]. However, we did not study this aspect in our study; as only 14 patients were on levothyroxine replacement therapy.…”

Charcoal for the management of pruritus and uremic toxins in patients with chronic kidney disease

“…Oral activated charcoal could be a safe, effective, and low-cost therapy for patients with uremic pruritus but also for hyperphosphatemia, especially when other treatments are not available. However, non-selective absorption can impede correct bioavailability of several drugs as well as the absorption of some nutrients; interference with the many drugs often prescribed to dialysis patients has not been studied, a problem in common with several widely used, albeit less selective binders [47,48] Oral Charcoal Therapy: AST-120.…”

Binding interactions with sevelamer and polystyrene sulfonate in vitro

“…Clinical studies and case reports have shown that sevelamer binds to levothyroxine, ciprofloxacin, mycophenolic acid, tacrolimus, cyclosporine, vitamin D analogues, lipid soluble vitamins like vitamins A, E, and K, folic acid, quetiapine, furosemide, and levetiracetam. 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 For polystyrene sulfonate, binding interactions have been described with lithium, quetiapine, and levothyroxine. 21 , 22 , 23 CKD patients often use many different drugs (average of eight drugs a day), and the prevalence of potential drug–drug interactions in CKD patients is high (75%–91%).…”

“…Clinical studies and case reports have shown that sevelamer binds to levothyroxine, ciprofloxacin, mycophenolic acid, tacrolimus, cyclosporine, vitamin D analogues, lipid soluble vitamins like vitamins A, E, and K, folic acid, quetiapine, furosemide, and levetiracetam 6‐21 . For polystyrene sulfonate, binding interactions have been described with lithium, quetiapine, and levothyroxine 21‐23 .…”

“…3 Because of their binding properties, resins are known to bind other drugs in the gastrointestinal tract, decreasing their bioavailability and clinical effectiveness.Clinical studies and case reports have shown that sevelamer binds to levothyroxine, ciprofloxacin, mycophenolic acid, tacrolimus, cyclosporine, vitamin D analogues, lipid soluble vitamins like vitamins A, E, and K, folic acid, quetiapine, furosemide, and levetiracetam. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] For polystyrene sulfonate, binding interactions have been described with lithium, quetiapine, and levothyroxine. [21][22][23] CKD patients often use many different drugs (average of eight drugs a day), and the prevalence of potential drug-drug…”