Wednesday, December 16, 2015

Anti Tuberculosis Drugs: Renal Adjustment


  • The recommended initial TB treatment regimen for patients with renal failure or severe renal insufficiency is 2 months of isoniazid, rifampicin, pyrazinamide and ethambutol, followed by 4 months of isoniazid and rifampicin
  • There is significant renal excretion of ethambutol and metabolites of pyrazinamide, and doses should therefore be adjusted
  • Pyrazinamide should be administered after hemodialysis to avoid premature drug removal
  • All four antiTB drugs may be administered after hemodialysis to facilitate directly observed therapy.
  • Because of an increased risk of nephrotoxicity and ototoxicity, streptomycin should be avoided in patients with renal failure.
First Line:
Pyrazinamide
  • adjustment for CrCl less than 30 mL/min or patients receiving hemodialysis
Ethambutol
  • CrCl less than 10 mL/min: The usual dose may be administered every 48 hours.
  • CrCl 10 to 50 mL/min: The usual dose may be administered every 24 to 36 hour  
Second Line: 
Streptomycin
  • If streptomycin need to be used, the dosage is 15 mg/kg, 2 or 3 times per week, to a maximum of 1 gram per dose, and serum levels of the drug should be monitored.
Ofloxacin
  • 50 ml/min : 400mg BD or 15-20mg/kg (maximum 1000mg)
  • 20-50 ml/min :  400mg OD
  • <20 ml/min : 200mg OD

Drug Induced AKI
  • Drug induced renal injury is lower (4.8%)
Drug
Renal Adverse Effect
Isoniazide
·      No established renal SE
Rifampicin
·      elevations in BUN and serum uric acid.
·      Hemoglobinuria, hematuria, interstitial nephritis, acute tubular necrosis, renal insufficiency, and acute renal failure have been reported.
·      generally associated with an immune-mediated reaction which occurs after interruption in rifampin therapy.
·      have been rare case reports of reversible acute renal failure due to glomerulonephritis and renal epithelial cell injury
·      Standard doses may produce orange-colored urine
Ethambutol
·      Renal side effects have rarely included reversible renal insufficiency
·      abnormalities include increases in serum creatinine and idiosyncratic interstitial nephritis
Pyrizinamide
·      Renal side effects have included dysuria and interstitial nephritis
Monitoring:
  • Any increase of serum creatinine above normal limits should be considered acute renal insufficiency.
  • A doubling of serum creatinine above baseline, even if within normal limits, should be considered worrisome for acute renal insufficiency and monitored carefully.
  • Prerenal etiologies include hypovolemia due to dehydration from vomiting or diarrhea as a side effect of anti-TB therapy.
  • Hypotensive shock in critically ill patients can also cause prerenal physiology
  • Discontinue the suspected drug (usually the injectable). If the acute renal failure is severe, then stop all drugs
  • If the acute renal insufficiency is severe or resolving slowly, the dose of other renally excreted drugs should be adjusted
  • Consider other contributing etiologies (prerenal, intrinsic renal, and postrenal).
References:
  1. www.drugs.com
  2. www.lexicomp.com
  3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092156/
  4. CPG: Management of Tuberculosis, 3rd Edition
  5. https://drtbnetwork.org/912-renal-nephrotoxicity-acute-renal-failure
  6. Guidelines for the prevention and management of Mycobacterium tuberculosis infection and disease in adult patients with chronic kidney disease. Thorax 2010;65:559e570.
  7. Treatment of tuberculosis in chronic renal failure, maintenance dialysis and renal transplant. Indian Journal of Nephrology 2003,13,69-71.

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