JOURNAL READING

Oleh
dr Frensi Ayu Primantari
 BACKGROUND

 Fatigue is commonly happen to dialysis patients

 Fatigue usually associated with its common causes such as :

- Anemia
- Malnutrition Inflamatory Syndrome
- Nutritional deficits
- Insuf ficinet dialysis
- Fluid overload
- Depression
- Chronic Pain

 Polypharmacy is seldom listed among Fatigue’s causes

 This report describe a patient on chronic dialysis who
developed severe fatigue due to pharmacological interaction
between :

Phosphate binders Levothyroxine

Interaction
CASE REPORT
 • Sex : Woman
Identity • Age : 65 yo
• Address : France

• Fatigue (getting severe recently)

• On dialysis for 17 yrs (Hemodiafiltration thrice weekly)
Present • Good dialysis tolerance
illness • High dialysis efficiency ( Daugirdas Kt/V : 1,6-1,8)
 • Severe scoliosis (+) pheripheral neuropthy, she uses
painkillers regularly
• Drugs she takes includes : Antihypertensives
(spironolacton 100 mg, amlodipine 20 mg, perindopril 2,5
Present mg), Antipsychotic drugs (valproic acid 600 mg,
illness lamotrigine 100 mg), tyroid hormone replacement
therapy (levothyroxine 150 mcg), Vit D , bicarbonate and
(Cont’d) calcium supplements (calcium carbonate 1 g, sodium
bicarbonat 500 mg, Vit D 25-OH 100.000 UI once a
month), Potassium and phosphate binders (sodium
polystirene sulphonate, sevelamer 2,4 g), darbopoeitin 20
mcg once weekly
 • Treated with lithium (20 yrs old-40 yrs old)
Lithium discontinued after she developed CKD.
Past • Heavy smoker since 19 yrs old (30
Illness
and cigarettes/day)
Medical
History • COPD (+)
• Hypertension (+) since 30 yrs old
• DMT2 since 32 yrs old, lost 20 kg
 • History of total thyroidectomy for papillary
carcinoma at 41 yrs old and started levothyroxine
Past afterwards
Illness • Started hemodialysis at 50 yrs old
• History of hemicolectomy for colon adeno ca at
and the age of 57 yrs old
Medical • History of quadrantectomi + radiotherapy for
History ductal mammary adeno ca at 59 yrs old
• Subtotal parathyroidectomy at age 62 yrs old for
severe tertiary hyperparathyroidisme
 •She is at good psychopshsycal balances
•BMI 23 kg/m2 ( BW : 55 kg, Height :
155 cm)
Physical •Blood pressure : 150/90 mmHg
examination •Mild Hypotension orthostatic (135/85
mmHg)
•Heart rate : 68 times per minute
•Bronchitis (+) by the time of examination
 As mentioned before, patient complained severe fatigue
which is recently increased and she thought it was resulted
from taking too many drugs

 So, it is suspected that there is a drug display potential

interference with levothyroxine : sevelamer
 BIOCHEMICAL SHOWED A RELEVANT
INCREASE IN TSH
Sevelamer dosage : 1x800 mg
TSH level : 4,14 mU/L

Sevelamer dosage : 3 x 800 mg

TSH level : 13,7 mU/L

Patient complain fatigue getting severe

Sevelamer stopped, levothyroxine given in the morning after night fasting

TSH level : In normal ranger

Sevelamer be given again

TSH level : 12,66 mU/L
 SYSTEMATIC REVIEW OF LITERATURE

 Pubmed and EMBASE explored from February 15th 2018

getting papers related to dialysis, levothyroxine and
phosphate binders.
 Keywords of term used were classified into
A B C
Dialysis Phosphate binders Levothyroxine
Hemodialysis Sevelamer Thyroid hormone
replacement therapy
Hemodiafiltration Calcium carbonate
Renal Replacement Calcium acetate
Therapy
Alumunium Hydroxide
Lanthanum carbonate
 Due to low number of papers retrieved, further search was
combining (b) and (c)

 The search strategy and flow chart as it reported :

Author n Study design Phosphate Terapeutic measure
binder

Lovino 1 Case Report Sevelamer Sevelamer at least 4 hrs after levothyroxine

(2014)
- Patient 26 yo woman with Hashimoto
disease
- Hemodialysis (+)
- Mixedema (+)
- TSH level : 650 mU/L, levothyroxine :
150 mcg daily
- Consumed Sevelamer for 18 months
- No clinical improvement even after the
levothyroxine was increased to 300 mcg
- Eutiroidism was finally obtained after
sevelamer be given at least 4 hrs after
levothyroxine

“Sevelamer Carbonate Markedly Reduces

Levothyroxine Absorption”
 Author n Study Phosphate Terapeutic measure
design binder
Granata 1 Case Sevelamer Levothyroxine 2 hrs after dinner
(2011) Report
- 55 yrs old patient with hipothyroid
- HD since 3 yrs ago
- Taking levothyroxine after total tiroidectomi
(100 mcg daily after breakfast)
- Taking sevelamer
- Monthly examination : malaise, intermittent
cramping, and insomnia.
- TSH level : 153 mU/L
- Levothyroxine increased to 150 mcg daily, no
clinical improvement. TSH level 83 mU/L
- Levothyroxine then be given in the morning 30
minutes before breakfast, within 10 days, TSH
back to normal.
- Patient admited after taking levothyroxine, he
ingested chocolate milk dan spontanious
consumption of sevelamer 800 mg
- By the time levothyroxine 100 mcg 2 hrs aftr
dinner , TSH level remained 1 mU/L

“Levothyroxine n sevelamer : Listen to patient”

 DISCUSSION AND CONCLUSION

 Many physiological and pathological conditions can alter

levothyroxine absorption
 Among these causes of levothyroxine malabsorption are :
- Helicobacter infection
- Inflamatorry Bowel Disease
- Intestinal Infection
- Malabsorption
- Several foods and beverages
 Other substances said interfere levothyroxine are these drugs :
calcium carbonate. But it is not explained in this journal.
Probably because of lower interference.
 Phosphate binders are probably the drug most widely used by
dialysis patients

 While sevelamer is composed of a cation hydrogel with multiple

amine groups which become protonated in GIT and bind with
anionic phosphate and other anionic substances, including
certain drugs, inter fering with their absorption

 Thus, it is thought that sevelamer can reduces the levothyroxine

bioavailbility
 A phosphate binder should be taken at an inter val of at least 2
hours after levothyroxine

 Administration of levothyroxine in the morning 30 minutes before

breakfast

 An alternative could be bed time administration of levothyroxine,

which may favorable in particular patient who dine early, and
consume their largest meal at noon, thus minimizing
interference with foods are suggested 2 hrs after meals.

 Better pharmacokinetics and bioavailability of liquid formulation

whose faster absorption and less affected by food and other
drugs
 MONITORING TSH LEVEL

Time to monitor TSH Indication

level
At least every 3 In patient on one phosphate binder + one other potentially
months infertering drug

Monthly monitoring - In unstable TSH level

- If new potentially interferring drug
- Change in dosage of phosphate binder
- Or more than two potentially interferring drugs

Twice a year - Long term stability of TSH level

- No change in treatment