ATW1H%ASUACAD.BITNET@oac.ucla.edu (Dr David Dodell) (06/21/89)
--- begin part 4 of 7 cut here ---
infections among the staff members of a health clinic in Florida suggested
that one source of infection may have related to the use of aerosol
pentamidine treatment for two patients who had positive sputum cultures for M.
tuberculosis during the time they received aerosol pentamidine. One of these
two patients coughed profusely both during and after therapy (18). Providers
administering aerosol pentamidine should also review the manufacturer's
instructions for the use of the nebulizer system. The Respirgard II nebulizer
contains a filter designed to remove most of the pentamidine from exhaled
gases. If the nebulizer is improperly used, substantial amounts of pentamidine
can be released into the environment, and health-care workers or others in the
vicinity may be at risk for the same adverse events as the patients who
received the therapy (19).
References
1. Sattler FR, Cowan R, Nielsen DM, Ruskin J. Trimethoprim-sulfamethoxazole
compared with pentamidine for treatment of Pneumocystis carinii pneumonia in
the acquired immunodeficiency syndrome: a prospective, noncrossover study. Ann
Intern Med 1988;109:280-7.
2. Gordin FM, Simon GL, Wofsy CB, Mills J. Adverse reactions to trimethoprim-
sulfamethoxazole in patients with the acquired immunodeficiency syndrome. Ann
Intern Med 1984;100:495-9.
3. Polk BF, Fox R, Brookmeyer R, et al. Predictors of acquired
immunodeficiency syndrome developing in a cohort of seropositive homosexual
men. N Engl J Med 1987;316:61-6.
4. Masur H, Ognibene FP, Yarchoan RY, et al. CD4 counts as predictors of
opportunistic pneumonias in human immunodeficiency virus infected individuals.
Ann Intern Med (in press).
5. Fischl MA, Richman DD, Grieco MH, et al. The efficacy of azidothymidine
(AZT) in the treatment of patients with AIDS and AIDS-related complex. A
double-blind, placebo-controlled study. N Engl J Med 1987;317:185-91.
6. National Institute of Allergy and Infectious Diseases, USA. The safety and
efficacy of two doses of zidovudine in the treatment of patients with AIDS.
Health InfoCom Network News Page 29
Volume 2, Number 25 June 20, 1989
(Abstract) IV International Conference on AIDS. Book 2. Stockholm, June 12-16,
1988:168.
7. Hughes WT, Kuhn S, Chaudhary S, et al. Successful chemoprophylaxis for
Pneumocystis carinii pneumonitis. N Engl J Med 1977;297:1419-26.
8. Hughes WT, Rivera GK, Schell MJ, Thornton D, Lott L. Successful
intermittent chemoprophylaxis for Pneumocystis carinii pneumonia. N Engl J Med
1987;316:1627-32.
9. Fischl MA, Dickinson GM, La Voie L. Safety and efficacy of sulfamethoxazole
and trimethoprim chemoprophylaxis for Pneumocystis carinii pneumonia in AIDS.
JAMA 1988;259:1185-9. 10. Leoung GS, Montgomery AB, Abrams DA, et al. Aerosol
pentamidine for Pneumocystis carinii pneumonia (PCP): a randomized trial of
439 patients. (Abstract) IV International Conference on AIDS. Book 1.
Stockholm, June 12-16, 1988:419. 11. Bach M-A, Phan-Dinh-Tuy F, Bach J-F, et
al. Unusual phenotypes of human inducer T cells as measured by OKT4 and
related monoclonal antibodies. J Immunol 1981;127:980-2.12. CDC. Tuberculosis
and human immunodeficiency virus infection: recommendations of the Advisory
Committee for the Elimination of Tuberculosis (ACET). MMWR 1989;38:236-8,243-
50. 13. Abd AG, Nierman DM, Ilowite JS, Pierson RN, Lomis Bell AL. Bilateral
upper lobe Pneumocystis carinii pneumonia in a patient receiving inhaled
pentamidine prophylaxis. Chest 1988;94:329-31. 14. Poblete RB, Rodriguez K,
Foust RT, Reddy KR, Saldana MJ. Pneumocystis carinii hepatitis in the
acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1989;9:737-8.15.
CDC. Human immunodeficiency virus infection in the United States: a review of
current knowledge. MMWR 1987;36(suppl S-6):1-48. 16. Kidd PG, Vogt RF Jr.
Report of the workshop on the evaluation of T-cell subsets during HIV
infection and AIDS. Clin Immunol Immunopathol 1989 (in press). 17. Taylor
JMG, Fahey JL, Detels R, Giorgi JV. CD4 percentage, CD4 number, and CD4:CD8
ratio in HIV infection: which to choose and how to use. J AIDS 1989;2:114-24.
18. CDC. Mycobacterium tuberculosis transmission in a health clinic--Florida,
1988. MMWR 1989;38:256-64. 19. LyphoMed, Inc. A treatment IND for the use of
aerosolized pentamidine in HIV-infected individuals at high risk for
Pneumocystis carinii pneumonia. Rosemont, Illinois: LyphoMed, Inc., 1989.
*Henry Masur, M.D., National Institutes of Health (Chairman); Carmen Allegra,
M.D., National Cancer Institute; Donald Armstrong, M.D., Memorial Sloan-
Kettering Cancer Center; Victor DeGruttola, D.Sc., Harvard University
Statistical Center; Susan S. Ellenberg, Ph.D., National Institute of Allergy
and Infectious Diseases; David Feigal, M.D., San Francisco General Hospital;
Judith Feinberg, M.D., National Institute of Allergy and Infectious Diseases;
Margaret A. Fischl, M.D., University of Miami School of Medicine; Walter T.
Hughes, M.D., St. Jude Children's Research Hospital; Harold Jaffe, M.D.,
Centers for Disease Control; John Mills, M.D., San Francisco General Hospital;
A. Bruce Montgomery, M.D., SUNY at Stony Brook; Alvaro Munoz, Ph.D., Johns
Hopkins School of Public Health; John P. Phair, M.D., Northwestern University
Medical School; Frank Richards, M.D., Yale University; Fred Sattler, M.D.,
University of Southern California; Gerald Smaldone, M.D., Ph.D., SUNY at Stony
Brook; Carol Braun Trapnell, M.D., Food and Drug Administration; Sten H.
Vermund, M.D., M.Sc., National Institute of Allergy and Infectious Diseases.
Consultants to the Task Force were Judith Falloon, M.D., National Institutes
of Health; Michael Polis, M.D., M.P.H., National Institutes of Health; Michael
Sampson, M.D., SUNY at Stony Brook.
Health InfoCom Network News Page 30
Volume 2, Number 25 June 20, 1989
Health InfoCom Network News Page 31
Volume 2, Number 25 June 20, 1989
===============================================================================
Food & Drug Administration News
===============================================================================
Approval of Aerosolized Pentamidine
P89-29 Food and Drug Administration
FOR IMMEDIATE RELEASE Brad Stone -- (301) 443-3285
June 15, 1989 (Home) -- (703) 892-0468
HHS Secretary Louis W. Sullivan, M.D., today announced Food and Drug
Administration approval of aerosolized pentamidine -- a drug inhaled into the
lungs to help prevent a form of pneumonia that frequently threatens the lives
of AIDS patients.
Although many patients have already been receiving aerosolized pentamidine
treatments through a special pre-approval distribution program, a large number
of these patients have not been able to get medical insurance reimbursement
for it. But today's approval, Dr. Sullivan said, will make the drug
affordable to more patients since it is likely most private insurance
providers will now pay for an approved drug.
"Today's approval will help many of those infected with the AIDS virus
avoid one of the most deadly opportunistic infections associated with AIDS,"
said Secretary Sullivan. "It may help an estimated 100,000 or more individuals
who are at risk of developing first or subsequent episodes of Pneumocystis
carinii pneumonia and will, therefore, significantly improve the quality of
their lives."
Dr. Sullivan noted that the cost of using aerosolized pentamidine to
prevent Pneumocystis carinii pneumonia would probably represent only a
fraction of the cost of treating patients who have developed this pneumonia,
"but, most important, it should improve the quality of life for those at
highest risk from this infection." The FDA, which approved the product, is a
part of the U.S. Public Health Service and Dr. Sullivan's department.
Today's action coincides with the Public Health Service's publication of
guidelines for prophylaxis against Pneumocystis carinii pneumonia in persons
infected with the AIDS virus. The guidelines, which appear in the June 16,
1989 issue of the Centers for Disease Control's Morbidity and Mortality Weekly
Report, are the recommendations from a panel composed of medical experts from
the Public Health Service and leading medical centers. The use of aerosolized
pentamidine to help prevent Pneumocystis carinii pneumonia is prominently
recommended in the guidelines.
Aerosolized pentamidine will be labeled for use in patients who have had
at least one episode of the pneumonia or who have greatly diminished immunity,
as indicated by CD4 helper lymphocyte cell counts of 200 or less. CD4 helper
cells are white blood cells that are critical components of the body's immune
system and which are destroyed by the AIDS virus. Healthy individuals
normally have CD4 helper cell counts of about 1,000 or more.
FDA Commissioner Frank E. Young, M.D., Ph.D., said his agency's approval
was based largely upon clinical data from a community-based study conducted by
the San Francisco Community Consortium. "The approval of this vital drug
heralds a new era of close cooperation among FDA, industry and those community
physicians who are on the front line of dealing with this terrible disease,"
Dr. Young said.
This is the first new drug approval emanating from a clinical trial
sponsored jointly by a community research initiative and a pharmaceutical
Health InfoCom Network News Page 32
Volume 2, Number 25 June 20, 1989
company. The trial, conducted by the San Francisco Community Consortium, a
group of physicians with experience treating people infected with the AIDS
virus, compared three dosages of the drug to determine which dose would be
most effective. In this study, headed by Bruce Montgomery, M.D., David W.
Feigel, M.D., M.P.H., and Gifford Leoung, M.D., individuals infected with the
AIDS virus who were at high risk of developing the pneumonia had a lower
incidence of infection when treated with this drug administered via the
Respirgard II nebulizer at a 300 milligram dose every four weeks than similar
patients treated with lower doses.
In November 1988, LyphoMed Inc. of Rosemont, Ill., which partially
underwrote the San Francisco Community Consortium study, filed the new drug
application that was approved today. Clinical data from this study continued
to be collected through December 1988, and its final results were submitted to
FDA in April 1989. In May 1989, FDA's Anti-Infective Drugs Advisory Committee
unanimously recommended that FDA approve the drug. The company will market
the approved drug under the trade name NebuPent.
The Respirgard II nebulizer, the filtered system specified in the drug's
approved labeling, is manufactured by the Marquest Corp. of Engelwood, Colo.
and is available through home health care retailers and hospital pharmacies.
Since February 1989, aerosolized pentamidine has been made widely
available to patients under the agency's "treatment IND" regulations -- a plan
for the use of an investigational new drug (IND) in selected patients facing
serious or life-threatening conditions. Despite this status, many eligible
patients were unable to receive reimbursement for the costs of this therapy
from private or government health insurance providers. Although some
companies have provided reimbursement, others were reluctant to pay until the
drug was fully approved.
Injectable pentamidine, as distinct from aerosolized pentamidine, was
approved in 1984 for the treatment of those already suffering from
Pneumocystis carinii pneumonia.
Aerosolized pentamidine can provoke severe wheezing and coughing at the
time of administration, as well as other adverse reactions. The long-term
risks associated with its use are unknown.
####
Approval of Selegiline
P89-28 Food and Drug Administration
FOR IMMEDIATE RELEASE Susan Cruzan - (301) 443-3285
June 7, 1989 (Home) -- (301) 340-6042
The Food and Drug Administration today announced approval of a drug called
selegiline to help treat severe Parkinson's Disease, a degenerative disorder
of the central nervous system with symptoms that include slowness of movement,
muscular rigidity and an instability that frequently leads to falls.
Selegiline would be added to the standard therapy using the drug levodopa,
which often decreases in effectiveness, even with increased doses, after
several years.
Currently, as levodopa's effectiveness fades, either Parkinson's
debilitating symptoms return or higher doses are required to suppress them,
with increasingly severe side effects. But selegiline, which differs in its
mode of action, has proved useful in controlled clinical studies in
maintaining function despite use of lower doses of levodopa, without increased
side effects.
Health InfoCom Network News Page 33
Volume 2, Number 25 June 20, 1989
FDA Commissioner Frank E. Young said, "The approval of this new drug is
significant for 20,000 to 50,000 persons, mostly over 40, who have severe
Parkinson's. We have already made this drug available under a 'treatment IND'
to the most severely ill patients while the company continued to gather data
for full marketing approval -- and now we are pleased that this therapy can be
approved in full."
Parkinson's Disease is believed to result from reduced levels in the brain
of a naturally produced substance, dopamine, which helps regulate normal
movement. The progressive loss of this substance produces a number of
increasingly debilitating symptoms, including the slowing down of all
movements, muscular rigidity, difficulty with balance and uncontrollable
tremors of the arms. Levodopa acts to supplement the patient's level of
dopamine and usually alleviates these symptoms in early stages of the disease.
But when decreased effectiveness requires higher doses of levodopa, these
are often accompanied by increases in its side effects: severe nausea and
involuntary bodily movements, flushing, palpitations and confusion.
The drug approved today, selegilene, inhibits an enzyme system within the
body that otherwise would inactivate dopamine. By inhibiting this enzyme,
selegiline conserves the remaining dopamine produced in the brain as well as
that formed from administered levodopa. In recent clinical trials, patients
on selegiline as well as levodopa experienced greater relief of symptoms at
the same time as achieving reductions in levodopa dose.
Selegilene has been designated as an orphan drug by FDA's Office of Orphan
Products Development. This status provides tax and other financial incentives
designed to encourage the development of products that otherwise might be
unprofitable or marginal because they have a relatively small market.
The drug will be distributed under the trade name Eldepryl by Somerset
Pharmaceuticals Inc. of Denville, N.J. It will be manufactured in Hungary.
Since June l988, selegilene has been distributed under the 1987 "treatment
IND" (for investigational new drug) regulations which allow desperately and
seriously ill patients to receive promising experimental therapies before they
are fully approved. This is the second drug which had been available to
patients under the treatment IND program to be approved for marketing by FDA.
The first was the combination therapy, ifofsamide and mesna, for the treatment
of refractory germ cell carcinoma.
####
Low levels of lead
P89-27 Food and Drug Administration
FOR IMMEDIATE RELEASE Emil Corwin - (202) 245-1144
June 6, 1989 (Home) -- (202) 244-6242
Citing new evidence that even very low levels of lead can limit the bodily
growth and intelligence of children, the Food and Drug Administration today
proposed to tighten its lead standards for ceramic pitchers by 25 to 50-fold.
The lead comes from the glaze commonly used to make ceramics smooth and
impervious. Officials are concerned that an acid food like orange juice -- a
popular drink with children -- might pick up sufficient lead over a period of
time to cause a subtle reduction in the child's IQ or physical stature.
Under the proposal, pitchers could be marketed only if they leach no more
than 0.1 micrograms (one tenth of a millionth of a gram) of lead per
Health InfoCom Network News Page 34
Volume 2, Number 25 June 20, 1989
milliliter of an acidic test solution. Currently, pitchers are allowed to
leach 2.5 to 5.0 micrograms per milliliter.
Small cream pitchers, since they are not used for acid foods, would not
have to meet the new standard.
FDA has long advised -- and continues to advise -- that the safest storage
for refrigerated juices is provided by glass or plastic containers, since
older ceramic pitchers may have been produced before FDA established limits in
197l. The agency also advises caution in the use of foreign-bought, craft,
antique or collectible ceramicware which may not have been made to FDA's
specifications.
The currently permitted levels for lead were set by FDA in 1979 based on
recommendations of the World Health Organization.
Recent studies, however, have shown subtle deficits in height, weight
gain, chest circumference and intelligence -- and some increases in behavioral
problems -- in children whose systems contain lead levels once considered
safe. As a result, several federal and international organizations, including
the federal Centers for Disease Control and the World Health Organization have
set lower maximum levels as goals for regulators.
Another part of today's proposal would ensure that high-lead decorative or
commemorative plates and other ceramics not intended to be used for foods are
not inadvertently used for food. The proposal would require that decorative
ceramics have fired into them a permanent, conspicuous warning --"Not for Food
Use -- May Poison Food" -- or have holes to assure they aren't used for food.
FDA asked for comments and suggestions from the public on these proposals
and on alternative ways to reduce lead exposure from other types of ceramic
foodware. Some manufacturers may not be able to meet the proposed standard
using certain current lead based glazes and decorations. FDA is therefore
seeking information on the lowest levels of leachable lead that can be
routinely attained in making ceramicware.
FDA also is asking for data on the actual leaching of lead into foods --
and how that compares with the leaching into FDA's test liquid.
Lead in past years was common in paints, gasoline and many cans used for
food, but federal agencies have banned lead-based interior paints and are
phasing out leaded gasoline. Working with FDA, manufacturers have eliminated
lead-soldered cans from use in infant formula, infant foods and evaporated
milk and has reduced lead solder's use in cans for foods generally from over
90 percent (in 1979) to less than 25 percent.
These reductions have been considered a major governmental "success story"
but the latest studies on lead are encouraging further action by federal
agencies and the ceramic industry. In addition to FDA's proposal, the
Environmental Protection Agency has proposed a new lead standard for drinking
water.
Public comments on FDA's proposal, which was published in the June 1
Federal Register, may be mailed during the following two months to FDA Dockets
Management Branch (HFA-305) at 5600 Fishers Lane, Rockville, MD 20857.
###
Blood proficiency testing
P89-26 Food and Drug Administration
FOR IMMEDIATE RELEASE Brad Stone - (301) 443-3285
June 5, 1989 (Home) -- (703) 440-6042
The Food and Drug Administration, which requires blood banks to test for
Health InfoCom Network News Page 35
Volume 2, Number 25 June 20, 1989
AIDS and hepatitis, today proposed that these blood establishments and
affiliated testing laboratories participate in FDA-approved proficiency
testing programs to ensure testing accuracy.
While most blood establishments already participate in such a proficiency
testing program, FDA's proposed regulation is designed to make sure
participation is universal and standard.
FDA, which licenses and inspects blood establishments, has required that
they test for the presence of AIDS antibody and hepatitis B surface antigen in
all donated blood. Consequently, the risk of AIDS and hepatitis B
contamination in the blood supply has been greatly diminished.
The new rule is designed to build upon this success by requiring blood
establishments and laboratories that conduct the testing for blood
establishments to demonstrate their proficiency through FDA-approved
evaluation programs.
In proficiency testing programs, sets of samples that have been pre-tested
are sent for retesting. The results from this retesting are compared by the
proficiency testing program center to the original results to detect any
discrepancies in the participating blood bank's or laboratory's results.
Under today's proposal, the proficiency testing programs would be
performed in accordance with standards established in a recent Health Care
Financing Administration proposal for ensuring the proficiency of clinical
laboratories.
The proposed FDA regulation complements the HCFA regulation by extending
proficiency testing standards to blood establishments and laboratories that
might be exempt from HCFA's authority. Both regulations are part of an HHS
effort to improve the overall performance of the nation's testing
laboratories.
Under the provisions of the proposed FDA rule, blood establishments and
affected laboratories, as well as the proficiency testing program operators,
would be required to notify FDA immediately if they fail a proficiency testing
program.
In the event of such a failure, FDA would work closely with the blood
establishment or laboratory to improve the quality of its performance. If the
blood establishment or laboratory is unable to meet an adequate level of
proficiency, the agency would take regulatory action.
The proposal will be published in the June 6 Federal Register. Comments
may be sent for 30 days to FDA Dockets Management Branch (HFA-305), Room 4-62,
5600 Fishers Lane, Rockville, Md. 20857.
####
EPO APPROVAL
P89-25 Faye Peterson - (301) 443-3285
FOR IMMEDIATE RELEASE (Home) - (301) 596-9639
June 1, 1989 Eva Kemper - (301) 443-3285
(Home) - (301) 972-9273
The Food and Drug Administration today approved a genetically engineered
treatment for the severe anemia often suffered by patients with chronic kidney
failure. The product, called epoetin, is a copy of the protein called
erythropoietin that normal kidneys make to trigger red blood cell production.
The new treatment should greatly reduce kidney patients' need for
transfusions of blood.
Health InfoCom Network News Page 36
Volume 2, Number 25 June 20, 1989
In healthy individuals, the kidneys not only clear toxins and excess
fluids from the blood stream but produce erythropoietin to stimulate the
reproduction and maturing of the red blood cells in bone marrow. The red
cells in turn carry oxygen, vital to all life processes, throughout the body.
Anemia is the result of a lack of oxygen-carrying red blood cells, and it
can weaken and, if untreated, kill.
HHS Secretary Louis W. Sullivan and FDA Commissioner Frank E. Young --both
physicians -- joined in announcing the approval of the new biotech product.
"In patients with chronic renal failure, there may be as few as half of the
red blood cells needed," Dr. Sullivan said. "As a result, patients often
become weak, have a rapid heartbeat, and, if there is underlying heart
disease, may develop chest pain."
Dr. Young explained, "Although there is not enough naturally occurring
erythropoietin produced to collect it from healthy persons for use in
treatment, gene splicing techniques have permitted its production."
Genetically engineered erythropoietin is produced by inserting the human
erythropoietin gene into Chinese hamster ovary cells. These cells are thereby
programmed to produce large quantities of the substance.
Previously the most common way of treating severe anemia was with blood
transfusions. Patients who receive repeated transfusions may develop
antibodies which may make it more difficult to identify or match a donor for
kidney transplantation or for additional transfusions.
Also, repeated transfusions over many years may result in too much storage
of iron, with potentially adverse health effects. Other risks from
transfusions include blood-borne viral infections, although these risks have
been minimized by routine blood screening for evidence of infection with the
AIDS virus and hepatitis viruses.
The product was developed in 1983 by Dr. Fu-Keun Lin of Amgen Inc.,
Thousand Oaks, Calif. In trials carried out at several locations in the
United States and Europe, the toxic effects seen from thrice weekly injections
of the drug were problems already commonly reported in patients with kidney
failure not receiving epoietin. The most frequent of these includes increased
blood pressure, headache, chest pain and, in a few patients, seizures.
Of about 1,200 patients in the trials, more than 95 percent showed
increases in their red blood cell count. Of patients who were dependent on
red cell transfusions, the transfusion requirement was reduced ten-fold over
the period of the clinical trial and most patients became transfusion
independent.
The epoietin approved today will be marketed by Amgen under the trade name
Epogen.
Amgen's epoietin was designated an orphan drug under the Orphan Drug Act
of 1983, which provides incentives for treatments for a disease or condition
which affects 200,000 or fewer U.S. patients. (About 95,000 Americans are
anemic as a result of chronic kidney disease.) Among the incentives, for
otherwise unpatentable products such as natural substances, is a period of
exclusivity from competitive manufacture of an identical product for seven
years. An application for what may be another, slightly different epoietin
product has been submitted by Chugai Pharmaceutical Company of Tokyo, Japan,
based on a joint effort with the Upjohn Company of Kalamazoo, Mich. Under the
terms of the law, this product could also gain orphan exclusivity because
there is evidence that it is different from the marketed product.
###
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Volume 2, Number 25 June 20, 1989
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Volume 2, Number 25 June 20, 1989
===============================================================================
Columns
===============================================================================
Centers for Disease Control
HIV/AIDS Surveillance Report
June 1989
Table 1. AIDS cases and annual incidence rates per 100,000 population,
by state, reported June 1987 through May 1988 and June 1988
through May 1989; and cumulative totals, by state and age group,
through May 1989
June 1987- June 1988-
May 1988 May 1989
STATE OF RESIDENCE No. Rate No. Rate
Alabama 183 4.5 226 5.5
Alaska 17 3.0 14 2.4
Arizona 310 9.1 269 7.7
Arkansas 68 2.9 75 3.1
California 5,711 20.8 5,747 20.5
Colorado 292 8.8 348 10.3
Connecticut 353 11.0 432 13.4
Delaware 46 7.2 85 13.2
District of Columbia 497 79.6 547 87.9
Florida 1,923 16.1 3,263 26.6
Georgia 646 10.4 906 14.4
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