FDA Updates on ARVs Used as PEP for Occupational HIV Exposures

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U.S. Food & Drug Administration (FDA)-Updated Information Regarding

Antiretroviral Agents Used as HIV Postexposure Prophylaxis for Occupational HIV

Exposures

In 1996, the U.S. Public Health Service first recommended using antiretrovirals

as postexposure prophylaxis (PEP) after occupational exposure to human

immunodeficiency virus (HIV) (1

<http://www.cdc.gov/mmwr/preview/mmwrhtml/00042200.htm> ).

Since the updated HIV PEP recommendations in 2005 (2

<http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5409a1.htm> ), two important

changes to antiretroviral use have occurred that affect the management of

occupational exposures.

First, Kaletra® (Abbott Laboratories, Abbott Park, Illinois), a combination

protease inhibitor, is no longer available in its original formulation:

capsules containing 133 mg of lopinavir and 33 mg of ritonavir. Although the

recommended daily prescribed amount of Kaletra ingredients is unchanged, the

dosing regimen has changed as a result of the new Kaletra formulation.

The previous dosing regimen for the capsule formulation was three capsules

twice daily.Kaletra is now manufactured only in tablet form, with each tablet

containing 200 mg of lopinavir and 50 mg of ritonavir. To achieve the same

recommended daily prescribed amount of the tablet formulation, two tablets of

200 mg of lopinavir and 50 mg of ritonavir should be taken twice daily.

Health-care providers should not prescribe three tablets twice a day of the new

Kaletra formulation; that dose would be the equivalent of 1,200 mg of lopinavir

and 300 mg of ritonavir daily, a higher dose than the recommended 800 mg of

lopinavir and 200 mg of ritonavir daily.

Second, on September 10, 2007, Pfizer, Inc. issued a letter* warning

health-care providers about the use of Viracept® (nelfinavir) (Pfizer, Inc.,

New York, New York), another protease inhibitor, because the Viracept

manufactured in Europe contained high levels of ethyl methane mesylate (EMS).

EMS is a byproduct of the manufacturing process and a known animal carcinogen,

mutagen, and teratogen.

The level at which EMS might become carcinogenic or teratogenic in humans is

not known. The warning in the letter applies to pregnant women and states that

information about the ability of EMS to cross the placenta or to enter breast

milk is currently unknown.

A review of data from the Antiretroviral Pregnancy Registry, which collects

data on approximately 6,000 HIV-infected pregnant women, indicated that, during

January 1989--January 2007, no statistically significant difference was

observed in the prevalence of birth defects among the infants of women who used

Viracept compared with those whose mothers used other antiretroviral therapies

(3).

Nonetheless, the Food and Drug Administration (FDA) recommends that pregnant

women limit their exposure to EMS during pregnancy. Until further notice,

pregnant women who need to begin antiretroviral therapy or HIV PEP should not

be offered regimens containing Viracept.

As a precautionary measure, pregnant women currently receiving Viracept should

be switched to an alternative antiretroviral therapy while Pfizer and FDA work

to implement a long-term EMS specification for Viracept. Specific

recommendations for use of antiretroviral agents in pregnant HIV-1--infected

patients are indicated in the U.S. Department of Health and Human Services

guidelines (4) and can be consulted to determine an alternative treatment

option.

Because nearly 80% of U.S. health-care personnel are female (5) and many of

these women are of child-bearing age, this updated information about Viracept

might be relevant to the choice of drugs included in an HIV PEP regimen taken

by female health-care personnel.

Additional information and guidance regarding management of specific exposures

are available from the National Clinicians' Post-Exposure Prophylaxis Hotline

by telephone (888-448-4911) or online (http://www.ucsf.edu/hivcntr).

References

CDC. Update: provisional Public Health Service recommendations for

chemoprophylaxis after occupational exposure to HIV. MMWR 1996; 45:468--72.

<http://www.cdc.gov/mmwr/preview/mmwrhtml/00042200.htm>

CDC. Updated U.S. Public Health Service guidelines for the management of

occupational exposures to HIV and recommendations for postexposure prophylaxis.

MMWR 2005;54(No. RR-9):1--17.

<http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5409a1.htm>

Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy

Registry international interim report for 1 January 1989 through 31 January

2007. Wilmington, NC: Registry Coordinating Center; 2007. Available at

http://www.apregistry.com <http://www.apregistry.com/> .

US Department of Health and Human Services, Panel on Clinical Practices for

Treatment of HIV Infection. Guidelines for the use of antiretroviral agents in

HIV-1-infected adults and adolescents---December 1, 2007. Available at

http://aidsinfo.nih.gov/contentfiles/adultandadolescentgl.pdf.

US Department of Labor, Bureau of Labor Statistics. Employed persons by

detailed industry and sex, 2006 annual average. Available at

http://www.bls.gov/cps/wlf-table14-2007.pdf.

* Available at http://www.viracept.com/pdf/viracept_hcpletter_9_10_07.pdf.

From the Morbidity and Mortality Weekly Report (MMWR)

<http://www.cdc.gov/mmwr/index.html>

December 14, 2007 / 56(49);1291-1292