CLINICAL USE

Bisphosphonate:(1) Management of osteolytic lesions, hypercalcaemia and bone pain associated with skeletal metastases in patients with breast cancer or multiple myeloma(2) Hypercalcaemia of malignancy

DOSE IN NORMAL RENAL FUNCTION

(1) Oral: 1.6–3.2 g daily in single or 2 divided doses Loron-520: 2–4 tablets daily(2) Slow

IV infusion

: 300 mg daily for 7–10 days or a single dose infusion of 1.5 g

PHARMACOKINETICS

  • Molecular weight                           :360.9 (as disodium salt)
  • %Protein binding                           :36
  • %Excreted unchanged in urine     : >70
  • Volume of distribution (L/kg)       :0.3
  • half-life – normal/ESRD (hrs)      :1 st phase: 2; 2 nd phase: 13/51

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

    30–50 Dose as in normal renal function 10–30 50% of normal dose

  • <10           : Avoid

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Not dialysed. Dose as in GFR <10 mL/min
  • HD                     :Dialysed. Dose as in GFR <10 mL/min
  • HDF/high flux   :Dialysed. Dose as in GFR <10 mL/min
  • CAV/VVHD      :Unknown dialysability. Dose as in GFR=10–30 mL/min

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs

  • None known

    ADMINISTRATION

    Reconstition

    Route

    Oral,

    IV infusion

    Rate of Administration

    (1) Single infusion: 1500 mg over 4 hours (2) Multiple infusions: 300 mg over at least 2 hours

    Comments

    (1) Single infusion: 1500 mg sodium clodronate to 500 mL sodium chloride 0.9% or glucose 5%(2) Multiple infusions: 300 mg sodium clodronate to 500 mL sodium chloride 0.9% or glucose 5%Multiple infusions should be repeated on successive days until normocalcaemia is achieved or to a maximum of 7–10 daysWhichever method of infusion is employed, most patients will achieve normocalcaemia within 5 days

    OTHER INFORMATION

    Renal failure has been associated with IV use of bisphosphonates. Smaller doses (up to 300 mg daily) over 2–3 hours are less likely to be associated with renal impairment than high doses by short IV infusionReversible elevations of creatinine have been reported. Renal function should be monitored during treatmentOrally: avoid food for one hour before and after treatment, particularly calcium-containing products; also avoid iron, mineral supplements and antacids

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