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DEPOMEDROL
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PHARMACIA
Pharmacia Corporation
Medical & Drug Information
REFORMULATION, EPIDURAL USE
DEPO-MEDROL is not approved by the FDA
for epidural or intrathecal injection and administration by these routes
is not recommended by Pharmacia Corporation.
This applies to both the single dose vial containing myristyl gamma
picolinium chloride (MGPC) as well as the multiple dose vial formulation
containing benzyl alcohol. In fact, the intrathecal route of administration
is specifically contraindicated (with both formulations) in the DEPO-MEDROL
package insert. Reports of severe medical events have been associated
with intrathecal/epidural administration, including arachnoiditis, meningitis,
paraparesis/paraplegia, sensory disturbance, bowel/bladder dysfunction,
headache, and seizures. As noted in the DEPO-MEDROL labeling, the FDA
approved routes of administration are intramuscular, intralesional and
intrasynovial/soft tissue injection.
Benzyl alcohol was chosen to replace MGPC
as the preservative in the multiple dose vial because it is effective
against a wider range of organisms. When DEPO-MEDROL containing MGPC
preservative was used as a multi-dose vial, certain pathogenic organisms
(e.g. Servane marcescens) introduced by inadequate aseptic technique,
could remain viable. The 1 ml single dose vials contain the original
DEPO-MEDROL formula and are not suitable for multi-dose use. Although
preservative is not required in a single dose vial, MGPC remains present
as the suspending agent.
Only multiple dose vials (5mL and 10mL)
are manufactured with benzyl alcohol. Multiple dose use requires special
care to avoid contamination. Although initially sterile, any multidose
use of vials may lead to contraindication unless strict aseptic technique
is observed. Particular care, such as use of disposable sterile syringes
and needles is necessary. There is none evidence that benzallonium chloride
is not an adequate antiseptic for sterilizing DEPO-MEDROL Sterile Aqueous
Suspension multidose vials. A povidone-iodine solution or similar product
is recommended to cleanse the vial top prior to aspiration of contents.
Pharmacia has noto conducted either animal
or clinical studies with the benzyl alcohol containing formulation of
DEPO-MEDROL by the epidural or intrathecal route; therefore, we have
no in-house experience to share. Benzyl alcohol is potentially toxic
when administered locally to neural tissue. A review of the literature
on benzyl alcohol is potentially toxic when administered locally to
neural tissue. A review of the literature on benzyl alcohol and neurotoxicity
identified several relevant citations.
Databases searched were MEDLINE (1996 to June 2002) EMBASE (1998 to
June 2002), and Biologic Abstracts (1970 to June 2002). Only one case
report described neurological sequelae related to inadvertent epidural
administration. Flaccid paraplegia with sensory loss was reported in
a patient who inadvertently received 40mL of normal saline solution
containing 1,5% benzyl alcohol during obstetrical analgesia. Confounding
this report was inadvertent entry for subarachnoid space prior to epidural
catheter placement. Benzyl alcohol has also been implicated in the development
of paraparesis when used in the dituent for intrathecal chemotherapy
regimens with methotrexate or cytarabine. This evidence was reviewed
by Golightly et al who noted the paraparesis may occur immediately following
injection and be transient or the effects may be delayed in onset by
several hours after injection and be progressive. Studies conducted
in animal models suggest that the neurotoxicity of benzyl alcohol in
the intrathecal space may be related to concentration, volume, and time
of exposure. While the evidence for neurotoxicity at concentrations
used clinically (0.9%) is somewhat circumstantial, prudence would dictate
that benzyl alcohol not be administered intraspinally.
French
Bosnian