This info should be reviewed by those taking Bicillin.. just in case.

It will be easier to read by going to the web sites.

http://www.findarticles.com/p/articles/mi_m0906/is_35_48/ai_55807462

In October 1998, the Maryland Department of Health and Mental Hygiene (MDH) was
notified that a public sexually transmitted disease (STD) clinic in a county (county A)
had used a nonrecommended preparation to treat syphilis patients during
January-October 1998.

The clinic had been inadequately treating syphilis patients or syphilis contacts with
Bicillin(r)[*] C-R (a mixture of 1.2 million units [MU] benzathine penicillin G [BPG]
and 1.2 MU procaine penicillin G), rather than with Bicillin(r) L-A (2.4 MU BPG).

Compared with short-acting procaine penicillin G, BPG has a longer half-life considered
essential for effective syphilis treatment because it yields sustained spirochetecidal levels
needed to treat the slowly reproducing agent of syphilis, Treponema pallidum.

The inadvertent use of Bicillin C-R, which contains only half the recommended dose of
BPG for syphilis, was recognized by a health-care provider at the STD clinic in a
neighboring county (county B) approximately 1 month after county B had borrowed BPG
from county A.

This report summarizes the investigation of the use of Bicillin C-R to treat STD patients
in county A and discusses the frequency of Bicillin C-R use in STD clinics nationwide.
Findings of this investigation indicate that inadvertent Bicillin C-R use is more frequent
than previously known and that preventive measures should be taken to minimize such
use.

Three BPG-containing products are marketed by Wyeth-Ayerst Laboratories
(Philadelphia, Pennsylvania): Bicillin L-A, Bicillin C-R, and Bicillin(r) C-R 900/300 (a
mixture of 0.9 MU BPG and 0.3 MU procaine penicillin G).

Besides having similar
proprietary names, the package and label for Bicillin C-R and Bicillin L-A have similar
lettering and colors.

Bicillin L-Ais recommended fortreating syphilis patients and upper respiratory tract
infections caused by susceptible streptococci [1].

The efficacy of Bicillin C-R to treat
syphilis is unknown. The package insert for Bicillin C-R states that this product should
not be used to treat syphilis, gonorrhea, yaws, bejel, or pinta.

To identify patients who might have been treated with Bicillin C-R at county A's STD
clinic, investigators reviewed the clinic's invoice records and the penicillin injection log.

MDH searched its STD surveillance database for residents from county A who were
treated for syphilis or had a positive syphilis serology during January- October 1998.

During December 1997-May 1998, 150 doses of Bicillin C-R were shipped to county A's
STD clinic after orders for Bicillin L-A were placed by telephone. During January-
October 1998, 123 of 160 doses of penicillin administered for syphilis were Bicillin C-R.
Sixty-three patients, including five pregnant women, might have received Bicillin C-R.

Because the efficacy of Bicillin C-R for treatment of patients with syphilis is unknown,
the clinic attempted to contact and treat all patients with Bicillin L-A. During this period,
routine outreach activities were suspended, clinic hours were extended, and personnel
were asked to work overtime.

Clinic workers contacted patients by telephone, and subsequent clinical evaluations were
made by two nurses.

STD field staff visited patients in their homes; multiple attempts
were often needed to locate and counsel patients. Although the five pregnant women
were located and treated with Bicillin L-A, four infants were treated for congenital
syphilis because their mothers had not been treated adequately at least 30 days before
delivery. None of the infants had congenital syphilis.

After 8 weeks of follow-up efforts, 52 (82%) of the 63 patients had been restreated and
retreated; the remaining 11 patients either could not be located (one) or refused
retreatment (10).

The total estimated direct costs of follow-up efforts conducted by
county A's clinic was approximately $24,000.
In county B, 10 syphilis patients received Bicillin C-R during an 11-day period according
to the clinic's syphilis treatment records. Of these, eight were treated with Bicillin L-A,
one was not located, and the other refused further treatment.

To determine the frequency of Bicillin C-R use in STD clinics nationwide and to educate
STD program managers about the possible confusion between Bicillin C-R and Bicillin
L-A, CDC surveyed 65 STD program areas during January-February 1999 about
unintentional Bicillin C-R use from 1993 through 1998.

Fifty-seven of the 65 program
areas were state/city program areas, and the remainder were islands and territories; 55
(96%) of the state/city program areas responded to the survey.

Of these, 45 (82%) used only Bicillin L-A to treat syphilis patients, three used
Permapen(R) exclusively (a BPG product from Pfizer, Inc. [New York, New York]), and
seven used both Permapen and Bicillin L-A.

Besides the Maryland clinics, four program areas reported unintentional Bicillin C-R use
at least once from 1993 through 1998. In two areas, Bicillin C-R was received at the state
health department and was distributed to STD clinics statewide; the administration of a
nonrecommended regimen subsequently occurred at many local STD cl inics.

Two other areas reported unintentional use of Bicillin C-R at individual clinics (one area
reported multiple occurrences). In March 1999, unintentional use of Bicillin C-R was
reported from a program area that had responded negatively to the earlier survey.

The
number of persons who received a nonrecommended regimen in this incident could not
be determined.

Among the 55 state/city program areas that responded to the survey, 31(56%) were
unaware of the possible confusion between Bicillin C-R and Bicillin L-A; 24 (46%)
program areas routinely ordered Bicillin L-A by telephone.

Reported by: D Dwyer, MD, State Epidemiologist, Maryland Dept of Health and Mental
Hygiene. Div of STD Prevention, National Center for HIV, STD, and TB Prevention; and
an EIS Officer, CDC.

Editorial Note: The inadvertent use of Bicillin C-R in county A's STD clinic disrupted
routine public health functions and incurred substantial monetary costs to the clinic and
unnecessary discomfort to patients.

Such incidents may undermine the credibility of and
trust in health departments on the part of affected patients and the broader community.
Although no treatment failures or congenital syphilis cases were associated with this
incident, treatment according to standard guidelines was missed for patients who either
could not be relocated or refused retreatment.

In addition to Maryland, five program areas reported unintentional use of Bicillin C-R
from 1993 through 1998. This number should be viewed as a conservative estimate
because some program areas might have failed to report such use because of concerns
over liability or performance evaluation. Because most program areas surveyed were
unaware of the possible confusion between Bicillin C-R and Bicillin L-A, some
unintentional Bicillin C-R use could have occurred that remained unknown.

Penicillin therapy is the mainstay of treatment and a core element of syphilis prevention
in the United States [2,3]. However, declining syphilis rates may have caused providers
to become less familiar with the penicillin regimens appropriate for syphilis. Less
attention may have been paid to clinician outreach and training for medications used to
treat a disease that has declined as sharply as syphilis (83% decline in primary and
secondary syphilis from 1990 to 1997 in the United States) [4].

Sustained participation by manufacturers in providing diagnostic and therapeutic
products is an essential element of emerging initiatives to eliminate syphilis transmission
in the United States [5].

Increased efforts are needed to re-educate clinic managers and
providers about the existence of different penicillin preparations and their appropriate
usage. Written rather than telephone orders may help to minimize ordering or shipment
errors.

Although the most important safeguard against medication errors is that providers
carefully read package labels, some label and package modifications may help decrease
confusion about Bicillin products and other pharmaceuticals with similar names and
labels.

References
(1.) Bisno AL, Gerber MA, Gwaltney JM, et al. Diagnosis and management of group A
streptococcal pharyngitis: a practice guideline. Clin Infect Dis 1997;25:574-83.
(2.) CDC. Recommendations for treatment of sexually transmitted diseases.
MMWR;47(no. RR-1): 28-40.
(3.) Augenbraun MH, Rolfs R. Treatment of syphilis, 1998: nonpregnant adults. Clin
Infect Dis 1999; 28(suppl 1):S21-S28.
(4.) CDC. Primary and secondary syphilis--United States, 1997. MMWR 1998;47:493-7.
(5.) St. Louis ME, Wasserheit JN. Elimination of syphilis in the United States. Science
1998;281:353-4.

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Information on Bilillin LA:
http://www.destinationrx.com/learningcenter/druginfo/info.asp?prodid=00008016301&n
ame=BICILLIN+L-A

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http://www.findarticles.com/p/articles/mi_m0906/is_9_54/ai_n13500614

In March 2004, the Los Angeles County Department of Health Services (LACDHS) was
notified that a large nonprofit clinic serving the gay and lesbian community in Los
Angeles used a nonrecommended preparation of penicillin to treat syphilis patients
during January 1999-March 2004.

The clinic had inadvertently used Bicillin[R] C-R, a mixture of 1.2 million units (MU)
benzathine penicillin G (BPG) and 1.2 MU procaine penicillin G, rather than Bicillin[R]
L-A, a preparation that contains the 2.4 MU BPG per dose recommended by CDC (1).

Bicillin L-A is recommended for treating syphilis and upper respiratory tract infections
caused by susceptible streptococci (2).
Bicillin C-R is indicated for streptococcal infections of the skin and respiratory tract;
however, its efficacy in treating syphilis is unknown.

The inadvertent use of Bicillin C-R,
which contains only half the recommended dose of BPG for syphilis, was discovered
after a patient treated for syphilis read the product insert, which stated that the
medication was not indicated for treatment of syphilis.

Review of clinic pharmacy records revealed that it received a shipment of Bicillin C-R in
lieu of an unfilled order for Bicillin L-A in late 1998 and that the pharmacy subsequently
ordered Bicillin C-R until March 2004. The clinic used Bicillin C-R as its exclusive
formulation of injectable penicillin during January 1999-March 2004.

This report summarizes the investigation of the misuse of Bicillin C-R at the Los Angeles
clinic, which represents the largest occurrence of inadvertent treatment with Bicillin C-R
to date.

The investigation led to discussions among CDC, the Food and Drug
Administration (FDA), and King Pharmaceuticals, Inc. (Bristol, Tennessee), whose
Monarch Pharmaceuticals subsidiary markets Bicillin products.

As a result, King
Pharmaceuticals agreed to institute packaging and labeling changes to Bicillin products
to prevent inadvertent treatment of syphilis with Bicillin C-R.

Five BPG-containing products are marketed by Monarch: Bicillin L-A, Bicillin[R] L-A
Pediatric (0.6 MU BPG), Bicillin C-R, Bicillin[R] C-R Pediatric (a mixture of 0.3 MU
BPG and 0.3 MU procaine penicillin G), and Bicillin[R] C-R 900/300 (a mixture of 0.9
MU BPG and 0.3 MU procaine penicillin G).

Despite a change in package color in 2002 to distinguish Bicillin C-R from Bicillin L-A
(3), the proprietary names and package appearances remained similar for the two
formulations (Figure).

The product insert sheet included a warning against the use of
Bicillin C-R for treatment of syphilis.

Investigators reviewed databases from the clinic and from the LACDHS Sexually
Transmitted Disease (STD) Program to identify patients who were treated during January
1999-March 2004 for confirmed syphilis infection or because of contact with a person
known or suspected to have syphilis.

All available data on treatment were evaluated.

During January 1999-March 2004, a total of 429 patients were treated with Bicillin C-R
for confirmed syphilis infection at the clinic. An additional 234 patients were treated
with Bicillin C-R at the clinic for reported sexual contact with someone who was known
or suspected to be infected with syphilis (contacts).

Of persons with confirmed syphilis, none were female, and 215 (50%) were known to be
infected with human immunodeficiency virus (HIV).

Five (2%) contacts were female,
and 10 (4%) contacts were known to be infected with HIV. No female patients were
pregnant during or after treatment with Bicillin C-R.

Clinic staff attempted to reach syphilis patients and contacts treated with Bicillin C-R by
letter, up to three telephone calls, and, if necessary, telephone calls to emergency
contacts listed on medical records.

In addition, the clinic and LACDHS issued press releases to inform potentially affected patients and local health-care providers.

LACDHS public health investigators attempted to reach patients whom the clinic was unable to locate or contact.

A standard protocol was developed to retest and retreat all patients and contacts who had
been treated with Bicillin C-R for syphilis. All patients were offered retreatment
regardless of retesting results.

Patients with a confirmed syphilis diagnosis were evaluated by clinic medical staff,
retested with quantitative rapid plasma reagin (RPR) tests, and advised to undergo
lumbar puncture for cerebrospinal fluid analysis if they had either clinical manifestations
suggestive of neurosyphilis or evidence of treatment failure (e.g., less than a fourfold
decline in RPR titer since initial treatment).

Contacts were tested with a specific treponemal test, and those with a reactive test were
managed in the same way as those with a confirmed syphilis diagnosis. Patients were
offered retreatment with a CDC-recommended regimen appropriate for their stage of
infection.

As of January 26, 2005, of the 429 patients with confirmed syphilis, 282 (66%) were
successfully contacted; 255 (59%) were retreated, 19 (4%) refused retreatment, and eight
(2%) are pending evaluation. Of those who were retreated, 19 (4%) underwent lumbar
puncture for suspected treatment Failure.

One patient treated for syphilis with Bicillin C-R subsequently had neurosyphilis
diagnosed. Of the 234 contacts, 116 (50%) were successfully contacted, 98 (42%) were
retested, and 15 (6%) are pending evaluation. Of the 98 contacts who were retested, 22
(22%) had serologic evidence of previous syphilis infection, and 19 (19%) were
retreated; three (3%) refused retreatment.

Operations at the clinic were disrupted for approximately 6 months. The clinic reassigned
professional and clerical staff to the evaluation and retreatment effort, and some clinic
activities were postponed or canceled. In addition, LACDHS dedicated two public health
investigators to this effort for nearly 4 months.

Editorial Note: Inadvertent use of Bicillin C-R for treatment of syphilis was documented
in several STD programs during 1993-1998 (4). However, its misuse in treating
approximately 660 persons in a Los Angeles clinic during January 1999-March 2004 is
the largest reported occurrence to date and posed considerable clinical and programmatic
challenges.
Compared with procaine penicillin G, use of BPG results in detectable serum
concentrations that are prolonged (up to 30 days for BPG, compared with up to 7 days for
procaine penicillin G). Prolonged serum concentration is considered essential for treating
syphilis effectively because sustained spirocheticidal levels are required to treat the
slowly reproducing agent of syphilis, Treponema pallidum.
Treatment of syphilis with half the recommended dose of BPG might have increased the
risk for syphilis treatment Failure and neurosyphilis, particularly among those infected
with HIV (5-7). However, treatment failure and neurosyphilis can occur even with
recommended penicillin regimens in persons with and without HIV infection (8).
Therefore, whether treatment failures that occurred among those treated with Bicillin
C-R represent an excess over what would be expected had they been treated with Bicillin
L-A cannot be determined without additional data.
An investigation by CDC and state and local health departments is assessing whether
treatment failure was more common in patients treated with Bicillin C-R than in a similar
population treated with Bicillin L-A. Such inadvertent use entails discomfort and
inconvenience to patients because it requires retesting and possible retreatment for
syphilis. In addition, inadequate treatment of syphilis might have contributed to an
increase in the local transmission of the disease.
In May 2004, CDC contacted FDA about the inadvertent use of Bicillin C-R. FDA
worked with CDC and King Pharmaceuticals to design and implement changes to the
product labeling, including more easily visible carton-color changes to distinguish L-A
and C-R formulations, and the warning, "not for the treatment of syphilis," printed
directly on syringes and cartons of Bicillin C-R. in November 2004, King
Pharmaceuticals distributed a letter to clinicians, professional societies, and STD
programs throughout the United States, alerting them to the potential for confusing
Bicillin C-R with Bicillin L-A, the appropriate use of each formulation, changes in
product labels, and mechanisms for reporting inadvertent use of Bicillin C-R for
treatment of syphilis.
Education of clinic managers, pharmacists, and providers in the proper use of different
penicillin preparations might help reduce the inappropriate use of Bicillin products.
Providers, STD clinics, and pharmacies should review their product records and tracking
systems for ordering and delivering penicillin treatments for syphilis.
References
(1.) CDC. Sexually transmitted diseases treatment guidelines 2002. MMWR 2002;51
(No. RR-6).

So, if you are lucky enough to get your script filled, make sure it is LA, not CR!

Thanks for the warning.