Contraindications added after episodes
of severe renal toxicity with cidofovir injection
From the November 20, 1996 issue
Cidofovir (Vistide®, formerly HPMPC) was approved by
FDA last June to delay progression of AIDS- associated CMV
retinitis and help prevent blindness. Although the potential
for nephrotoxicity with cidofovir is listed in official product
labeling, several reports of severe renal impairment, including
at least two cases of acute renal failure resulting in dialysis
and/or contributing to death after just one or two doses of
Vistide®, have caused the drug's manufacturer, Gilead
Sciences, to add new guidelines and contraindications.
The new reports were associated with cidofovir administration
to patients with risk factors for nephrotoxicity, including
preexisting mild renal insufficiency and administration of
the drug soon after completion of aminoglycoside therapy in
a patient with normal serum creatinine.
The new guidelines attempt to ensure proper patient selection,
and proper administration and monitoring. They include contraindication
of therapy initiation in patients with serum creatinine levels
above 1.5 mg/dL, creatinine clearance less than 55 mL/min,
or urine protein above 100 mg/dL (equivalent to 2+ proteinuria
or more). The drug is contraindicated when given with potential
nephrotoxic drugs (e.g., foscarnet, amphotericin B, aminoglycoside
antibiotics, non-steroidal anti-inflammatory agents, and intravenous
pentamidine). Patients should undergo a "washout"
period of at least 7 days following the administration of
the above agents prior to receiving cidofovir. Other guidelines
include the need for IV prehydration with sodium chloride
injection, use of probenecid with each infusion, not exceeding
the recommended cidofovir dose, monitoring of renal function
within 48 hours prior to each dose, and discontinuing the
drug or reducing the dose at the earliest sign of renal compromise.
Cidofovir joins ganciclovir (Cytovene®) and foscarnet
(Foscavir®), which are also approved for this indication.
Both are given by IV infusion. Ganciclovir is also available
in an oral form for maintenance treatment, and as an eye implant
called Vitrasert®. Cidofovir is also under investigation
as an intravitreal formulation. According to the AIDS Treatment
Data Network, another CMV product given by direct injection
into the eye is ISIS 2922. It is in clinical trials but is
available under a compassionate use protocol for patients
who are unable to tolerate other treatments. Patients may
call The Network at 800 445 3235 for a referral.
Gilead Science and FDA medWatch request that you report any
case of nephrotoxicity or other serious toxicity associated
with cidofovir administration to 1-800-Gilead-5 or 1-800-FDA-1088/fax
1-800-FDA- 0178. A complete set of guidelines, treatment log,
and laboratory monitoring guidelines for use of cidofovir
are available from Gilead Sciences.