Bortezomib

CLINICAL USE

Treatment of multiple myeloma for people who have already tried at least 2 prior therapies and have disease progression

DOSE IN NORMAL RENAL FUNCTION

1.3 mg/m2 twice weekly for 2 weeks (days 1, 4, 8 and 11) followed by a 10-day rest period

PHARMACOKINETICS

Molecular weight :384.2

%Protein binding :82.9

%Excreted unchanged in urine : Small amount

Volume of distribution (L/kg) :>500 litres

half-life – normal/ESRD (hrs) :5–15/unknown

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

30–50 Dose as in normal renal function 10–30 Dose as in normal renal function. Monitor carefully.

<10 : A reduced dose may be required. Monitor carefully

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Unlikely to be dialysed. Dose as in GFR <10 mL/min

HD :Unlikely to be dialysed. Dose as in GFR <10 mL/min

HDF/high flux :Unknown dialysability. Dose as in GFR <10 mL/min

CAV/VVHD :Unlikely to be dialysed. Dose as in GFR=10–30 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugsNone known

ADMINISTRATION

Reconstition

3.5 mL sodium chloride 0.9%

Route

IV bolus

Rate of Administration

3 to 5 seconds

Comments

Administer within 8 hours of reconstitution

OTHER INFORMATION

Consecutive doses should be at least 72 hours apart

Normal doses have been used in patients with a GFR of 10–30 mL/min but there is an increased risk of adverse effects. (Jagannath S, Barlogie B, Berenson JR, et al. Bortezomib in recurrent and/or refractory multiple myeloma. Cancer. 2005; 103(6): 1195–1200)

Some trials have used doses of 1 mg/m 2 in patients with a GFR of 10–30 mL/min, with similar efficacy and incidence of side effects

Both hypo- and hyperkalaemia have been reported with bortezomib as has hypophosphataemia and hypomagnesaemia

There have been incidences of renal impairment, renal colic, proteinuria, dysuria, urinary frequency, urinary hesitation and haematuria

Anecdotally, has been used at normal doses in a few haemodialysis patients; in some of the patients platelet infusions have been required

In patients with peripheral neuropathy then bortezomib has a high probability of exacerbating it.

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