Drug dose adjustments for disease (Proceedings)


Drug dose adjustments for disease (Proceedings)

Apr 01, 2010

      Drugs that merit dose reductions in renal failure:
          1. Penicillins
                a) Toxicity unlikely, but dose reduction is appropriate and will also decrease the cost of using more expensive beta lactams and related drugs (such as ticarcillin, aztreonem, meropenem) in patients with azotemia
          2. Cephalosporins
                a) Cephalothin can be nephrotoxic at very high doses in humans, so dose reduction of these two drugs in renal failure may be important in dogs and cats
                b) Cephalothin can also be nephrotoxic in combination with gentamicin to elderly humans; avoid this combination in older dogs and cats
          3. Fluoroquinolones
               a) Most fluoroquinolones are renally cleared.
               b) Given the risk of retinal toxicity in cats, always think twice about fluoroquinolone dosing in cats with renal insufficiency.
                c) Although the optimal method is not established, consider extending the dosing interval of enrofloxacin
                     (1) New interval for dosing = normal dosing interval x (patient creatinine / normal creatinine)
                         (a) e.g. enrofloxacin 5 mg/kg every 48 hours instead of every 24 hours
                d) Or choose less retinotoxic fluoroquinolones
                     (1) Retinotoxic potential in cats is marbofloxacin < orbifloxacin << enrofloxacin
          4. Aminoglycosides
                a) Use other agents whenever possible (fluoroquinolones, ticarcillin, cefotetan, aztreonem, meropenem)
               b) When necessary for use in patients with pre-existing renal failure:
                     (1) Always rehydrate first
                     (2) Always use concurrent fluid therapy (IV or SC)
                     (3) Consider possibly less nephrotoxic forms of aminoglycosides
                         (a) Amikacin 15 mg/kg SC q. 24h

                         (b) Netilmicin 6-8 mg/kg SC q. 24h
                    (4) Monitor for tubular damage by examining daily fresh urine sediments for granular casts
                     (5) Reduce the dose by multiplying the dose interval by the serum creatinine
                          (a) New interval for dosing = normal dosing interval x (patient creatinine / normal creatinine)
                         (b) e.g. for a serum creatinine of 2.0 mg/dl, dose every 48 hours instead of every 24 hours
                     (6) Do not use aminoglycosides in patients with urinary obstruction
                     (7) Do not use furosemide or NSAID's concurrently /
                     (8) Limit aminoglycoside therapy to 5 days or less whenever possible
          5. Tetracyclines

Table 1: Conditions that may require drug dosage adjustment in dogs and cats
                a) Use doxycycline, not tetracycline
                    (1) No adjustment needed with renal insufficiency
                b) Tetracyclines can increase BUN, independent of any renal damage, due to protein catabolism (increase is reversible)
                c) Never use outdated tetracyclines (breakdown products are nephrotoxic)
          6. Chloramphenicol
                a) In cats, 25% or more is excreted unchanged in the urine
                b) Avoid use in cats with renal insufficiency
                     (1) Or monitor CBC for dose-dependent leukopenia
          7. Potentiated sulfonamides
                a) Decreased renal clearance and decreased protein binding in renal failure
                     (1) Reduce dose in renal failure
                b) Rehydrate first
                c) Dose accurately
                d) Avoid sulfadiazine (in Tribrissen) in renal failure
                     (1) Sulfadiazine forms drug crystals in the renal tubules and can lead to hematuria in humans
                e) Avoid use with methotrexate (combination can precipitate in urine and cause tubular damage)
                f) Avoid urinary acidifiers
          8. Digoxin
                a) Decreased renal filtration, tubular secretion, and skeletal muscle binding leads to increased serum concentrations in uremia
                b) Reduce dose in azotemia
                c) Measure serum digoxin concentrations
                     (1) Steady state after about 1 week in dogs
                     (2) Draw level 6 to 8 hours after dosing
                    (3) Therapeutic level: 0.8 – 1.2 ng/ml
          9. Furosemide
                a) Can lead to dehydration, hypokalemia, even acute renal failure
                b) Use conservative dosages and monitor carefully
                     (1) Serial BUN, creatinine, potassium, packed cell volume (PCV), and total protein (TP)
          10. Cimetidine / ranitidine / famotidine
                a) CNS disturbances reported in elderly humans with decreased GFR when given H2 blockers without appropriate dose reductions
                b) Reduce dosage in renal failure
                c) Either decrease dose or extend dosing interval (either method used in people)
          11. Metoclopramide
                a) Standard CRI dosages (1-2 mg/kg/day) may cause tremor and ataxia in azotemic patients
               b) Consider 0.25-0.50 mg/kg/day in renal failure, and titrate to dosage that controls emesis without tremor
                c) Or substitute maropitant as antiemetic (but this lacks prokinetic effects)
          12. Atenolol
                a) Renally cleared (unlike propranolol)
                b) Given at 25-50% of standard dosages in humans with moderate to severe renal insufficiency
          13. Angiotensin converting enzyme inhibitors (ACEi)
                a) Benazepril is preferred over enalapril in azotemic patients
                     (1) Benazepril undergoes some hepatic clearance, and does not accumulate in azotemia in dogs or cats
                b) All ACE inhibitors have potential adverse effects on glomerular filtration rate (GFR)
                     (1) Efferent arteriolar dilation can drop GFR
                    (2) May lead to worsened azotemia, particularly with:
                          (a) Concurrent NSAIDs
                          (b) Concurrent furosemide
                          (c) High ACEi dosages
               c) Monitor BUN, creatinine, and electrolytes in patients on ACE inhibitors, especially those with pre-existing azotemia
          14. NSAID's
                a) Decreased renal clearance, decreased protein binding, and adverse effects on GFR
               b) Use alternatives to NSAIDs in azotemic patients with osteoarthritis:
                     (1) Tramadol, buprenorphine
                     (2) Glucosamine/chondroitin
                     (3) Acupuncture
                     (4) S-adenosylmethionine (SAMe)
                          (a) Some efficacy for osteoarthritis in humans
               c) If NSAID is required for pain control and quality of life, use conservative NSAID dosages, and monitor frequently for:
                     (1) Dehydration, inappetance, or increases in BUN and creatinine
                d) Coxibs have same potential to adversely affect GFR
                     (1) COX-2 is constituitively expressed in the kidney
                e) Coxibs are not safer than classical NSAIDs in renal insufficiency