Hello--
I have carefully researched your questions about spironolactone the
past couple hours and have your answers. Below, you'll see that I've
separated all your questions and answered each.
You should consult your physician and pharmacist before taking any
medication.
1) what it is used for
Spironolactone contains Aldactone. It is a "Potassium Sparing
Diuretic" that is traditionally used to treat high blood pressure and
fluid retention. It is also used to treat patients with hair loss.One
respected company that posts information about prescription medicine,
RxList, states spironolactone is used for:
* Managing primary hyperaldosteronism. RxList states this drug is used
for, "Primary hyperaldosteronism for: Establishing the diagnosis of
primary hyperaldosteronism by therapeutic trial. Short-term
preoperative treatment of patients with primary hyperaldosteronism.
Long-term maintenance therapy for patients with discrete
aldosterone-producing adrenal adenomas who are judged to be p.o.
operative risks or who decline surgery. Long-term maintenance therapy
for patients with bilateral micro- or macronodular adrenal hyperplasia
(idiopathic hyperaldosteronism)."
* Managing edematous conditions. RxList states it's used for patients
with, "Congestive heart failure: For the management of edema and
sodium retention when the patient is only partially responsive to, or
is intolerant of, other therapeutic measures. Aldactone is also
indicated for patients with congestive heart failure taking digitalis
when other therapies are considered inappropriate. Cirrhosis of the
liver accompanied by edema and/or ascites: Aldosterone levels may be
exceptionally high in this condition. Aldactone is indicated for
maintenance therapy together with bed rest and the restriction of
fluid and sodium. The nephrotic syndrome: For nephrotic patients when
treatment of the underlying disease, restriction of fluid and sodium
intake, and the use of other diuretics do not provide an adequate
response."
* Management of hypertension. The company states it's used "Usually in
combination with other drugs, Aldactone is indicated for patients who
cannot be treated adequately with other agents or for whom other
agents are considered inappropriate."
* Management of hypokalemia. "For the treatment of patients with
hypokalemia when other measures are considered inappropriate or
inadequate. Aldactone is also indicated for the prophylaxis of
hypokalemia in patients taking digitalis when other measures are
considered inadequate or inappropriate."
* Used during pregnancy. "The routine use of diuretics in an otherwise
healthy woman is inappropriate and exposes mother and fetus to
unnecessary hazard. Diuretics do not prevent development of toxemia of
pregnancy, and there is no satisfactory evidence that they are useful
in the treatment of developing toxemia. Edema during pregnancy may
arise from pathologic causes or from the physiologic and mechanical
consequences of pregnancy. Aldactone is indicated in pregnancy when
edema is due to pathologic causes just as it is in the absence of
pregnancy.... Dependent edema in pregnancy, resulting from restriction
of venous return by the expanded uterus, is properly treated through
elevation of the lower extremities and use of support hose; use of
diuretics to lower intravascular volume in this case is unsupported
and unnecessary. There is hypervolemia during normal pregnancy which
is not harmful to either the fetus or the mother (in the absence of
cardiovascular disease), but which is associated with edema, including
generalized edema, in the majority of pregnant women. If this edema
produces discomfort, increased recumbency will often provide relief.
In rare instances, this edema may cause extreme discomfort which is
not relieved by rest. In these cases, a short course of diuretics may
provide relief and may be appropriate."
You may read this information directly at RxList's web site. The link
is http://www.rxlist.com/cgi/generic/spiron_ids.htm
2) why
It has an anti-androgen activity. Male and female patterned baldness
is influenced by DHT, an androgen. This medicine binds to hair
receptors on the hair follicles. It then blocks DHT from having its
negative effect on hair follicles.
3) side effects(all)
It has multiple side effects. But it's important to note that all side
effects are rarely seen in all patients.
This is what RxList writes about side effects:
"The following adverse reactions have been reported and within each
category (body system), are listed in order of decreasing severity.
Digestive: Gastric bleeding, ulceration, gastritis, diarrhea and
cramping, nausea, vomiting.
Endocrine: Gynecomastia (see PRECAUTIONS), inability to achieve or
maintain erection, irregular menses or amenorrhea, postmenopausal
bleeding. Carcinoma of the breast has been reported in patients taking
spironolactone but a cause and effect relationship has not been
established.
Hematologic: Agranulocytosis.
Hypersensitivity: Fever, urticaria, maculopapular or erythematous
cutaneous eruptions, anaphylactic reactions, vasculitis.
Nervous system/psychiatric: Mental confusion, ataxia, headache,
drowsiness, lethargy.
Liver/biliary: A very few cases of mixed cholestatic/hepatocellular
toxicity, with one reported fatality, have been reported with
spironolactone administration."
Another company lists other precautions:
"Spironolactone: Adverse Reactions
Spironolactone has a dose-dependent effect on the function of the
sexual hormones: in the long run gynecomastia occurs in more than 10%
(in more than half with doses of 150 mg/day) of the treated men.
Impotence, loss of libido and menstrual irregularities are not
uncommon.
In more than 5% of the treated subjects a hyperkalemia develops
(especially if renal functions are impaired, in diabetics, and the
elderly). Hyponatremia, reduced renal functions and skin reactions
(e.g. urticaria) are rare.
Hematologic anomalies, gastric ulcers and hepatitis are rare as well."
This information can be read online. The link is
http://www.infomed.org/100drugs/spitoc.html
Here is a list of general precautions doctors urge patients to
understand before taking Spironolactone:
"PRECAUTIONS
General
All patients receiving diuretic therapy should be observed for
evidence of fluid or electrolyte imbalance, eg, hypomagnesemia,
hyponatremia, hypochloremic alkalosis, and hyperkalemia.
Serum and urine electrolyte determinations are particularly important
when the patient is vomiting excessively or receiving parenteral
fluids. Warning signs or symptoms of fluid and electrolyte imbalance,
irrespective of cause, include dryness of the mouth, thirst, weakness,
lethargy, drowsiness, restlessness, muscle pains or cramps, muscular
fatigue, hypotension, oliguria, tachycardia, and gastrointestinal
disturbances such as nausea and vomiting. Hyperkalemia may occur in
patients with impaired renal function or excessive potassium intake
and can cause cardiac irregularities, which may be fatal.
Consequently, no potassium supplement should ordinarily be given with
Aldactone.
Concomitant administration of potassium-sparing diuretics and ACE
inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs), eg,
indomethacin, has been associated with severe hyperkalemia.
If hyperkalemia is suspected (warning signs include paresthesia,
muscle weakness, fatigue, flaccid paralysis of the extremities,
bradycardia and shock) an electrocardiogram (ECG) should be obtained.
However, it is important to monitor serum potassium levels because
mild hyperkalemia may not be associated with ECG changes.
If hyperkalemia is present, Aldactone should be discontinued
immediately. With severe hyperkalemia, the clinical situation dictates
the procedures to be employed. These include the intravenous
administration of calcium chloride solution, sodium bicarbonate
solution and/or the oral or parenteral administration of glucose with
a rapid-acting insulin preparation. These are temporary measures to be
repeated as required. Cationic exchange resins such as sodium
polystyrene sulfonate may be orally or rectally administered.
Persistent hyperkalemia may require dialysis.
Reversible hyperchloremic metabolic acidosis, usually in association
with hyperkalemia, has been reported to occur in some patients with
decompensated hepatic cirrhosis, even in the presence of normal renal
function.
Dilutional hyponatremia, manifested by dryness of the mouth, thirst,
lethargy, and drowsiness, and confirmed by a low serum sodium level,
may be caused or aggravated, especially when Aldactone is administered
in combination with other diuretics, and dilutional hyponatremia may
occur in edematous patients in hot weather; appropriate therapy is
water restriction rather than administration of sodium, except in rare
instances when the hyponatremia is life-threatening.
Aldactone therapy may cause a transient elevation of BUN, especially
in patients with preexisting renal impairment. Aldactone may cause
mild acidosis.
Gynecomastia may develop in association with the use of
spironolactone; physicians should be alert to its possible onset. The
development of gynecomastia appears to be related to both dosage level
and duration of therapy and is normally reversible when Aldactone is
discontinued. In rare instances some breast enlargement may persist
when Aldactone is discontinued.
Information for Patients
Patients who receive Aldactone should be advised to avoid potassium
supplements and foods containing high levels of potassium including
salt substitutes.
Laboratory Tests
Periodic determination of serum electrolytes to detect possible
electrolyte imbalance should be done at appropriate intervals,
particularly in the elderly and those with significant renal or
hepatic impairments.
Drug Interactions
See DRUG INTERACTIONS section.
Drug/Laboratory Test Interactions
Several reports of possible interference with digoxin
radioimmunoassays by spironolactone, or its metabolites, have appeared
in the literature. Neither the extent nor the potential clinical
significance of its interference (which may be assay-specific) has
been fully established.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Orally administered spironolactone has been shown to be a tumorigen in
dietary administration studies performed in rats, with its
proliferative effects manifested on endocrine organs and the liver. In
an 18-month study using doses of about 50, 150 and 500 mg/kg/day,
there were statistically significant increases in benign adenomas of
the thyroid and testes and in male rats, a dose-related increase in
proliferative changes in the liver (including hepatocytomegaly and
hyperplastic nodules). In a 24-month study in which the same strain of
rat was administered doses of about 10, 30, 100 and 150 mg
spironolactone/kg/day, the range of proliferative effects included
significant increases in hepatocellular adenomas and testicular
interstitial cell tumors in males, and significant increases in
thyroid follicular cell adenomas and carcinomas in both sexes. There
was also a statistically significant, but not dose-related, increase
in benign uterine endometrial stromal polyps in females.
A dose-related (above 20 mg/kg/day) incidence of myelocytic leukemia
was observed in rats fed daily doses of potassium canrenoate (a
compound chemically similar to spironolactone and whose primary
metabolite, canrenone, is also a major product of spironolactone in
man) for a period of one year. In two year studies in the rat, oral
administration of potassium canrenoate was associated with myelocytic
leukemia and hepatic, thyroid, testicular and mammary tumors.
Neither spironolactone nor potassium canrenoate produced mutagenic
effects in tests using bacteria or yeast. In the absence of metabolic
activation, neither spironolactone nor potassium canrenoate has been
shown to be mutagenic in mammalian tests in vitro. In the presence of
metabolic activation, spironolactone has been reported to be negative
in some mammalian mutagenicity tests in vitro and inconclusive (but
slightly positive) for mutagenicity in other mammalian tests in vitro.
In the presence of metabolic activation, potassium canrenoate has been
reported to test positive for mutagenicity in some mammalian tests in
vitro, inconclusive in others, and negative in still others.
In a three-litter reproduction study in which female rats received
dietary doses of 15 and 50 mg spironolactone/kg/day, there were no
effects on mating and fertility, but there was a small increase in
incidence of stillborn pups at 50 mg/kg/day. When injected into female
rats (100 mg/kg/day for 7 days, i.p.), spironolactone was found to
increase the length of the estrous cycle by prolonging diestrus during
treatment and inducing constant diestrus during a two week
posttreatment observation period. These effects were associated with
retarded ovarian follicle development and a reduction in circulating
estrogen levels, which would be expected to impair mating, fertility
and fecundity. Spironolactone (100 mg/kg/day), administered i.p. to
female mice during a two week cohabitation period with untreated
males, decreased the number of mated mice that conceived (effect shown
to be caused by an inhibition of ovulation) and decreased the number
of implanted embryos in those that became pregnant (effect shown to be
caused by an inhibition of implantation), and at 200 mg/kg, also
increased the latency period to mating.
Pregnancy
Teratogenic Effects: Pregnancy Category C. Teratology studies with
spironolactone have been carried out in mice and rabbits at doses of
up to 20 mg/kg/day. On a body surface area basis, this dose in the
mouse is substantially below the maximum recommended human dose and,
in the rabbit, approximates the maximum recommended human dose. No
teratogenic or other embryotoxic effects were observed in mice, but
the 20 mg/kg dose caused an increased rate of resorption and a lower
number of live fetuses in rabbits. Because of its anti-androgenic
activity and the requirement of testosterone for male morphogenesis,
Aldactone may have the potential for adversely affecting sex
differentiation of the male during embryogenesis. When administered to
rats at 200 mg/kg/day between gestation days 13 and 21 (late
embryogenesis and fetal development), feminization of male fetuses was
observed. Offspring exposed during late pregnancy to 50 and 100
mg/kg/day doses of spironolactone exhibited changes in the
reproductive tract including dose-dependent decreases in weights of
the ventral prostate and seminal vesicle in males, ovaries and uteri
that were enlarged in females, and other indications of endocrine
dysfunction, that persisted into adulthood. There are no adequate and
well-controlled studies with Aldactone in pregnant women.
Spironolactone has known endocrine effects in animals including
progestational and antiandrogenic effects. The antiandrogenic effects
can result in apparent estrogenic side effects in humans, such as
gynecomastia. Therefore, the use of Aldactone in pregnant women
requires that the anticipated benefit be weighed against the possible
hazards to the fetus.
Nursing Mothers
Canrenone, a major (and active) metabolite of spironolactone, appears
in human breast milk. Because spironolactone has been found to be
tumorigenic in rats, a decision should be made whether to discontinue
the drug, taking into account the importance of the drug to the
mother. If use of the drug is deemed essential, an alternative method
of infant feeding should be instituted."
You may read about these precautions online. The link is
http://www.rxlist.com/cgi/generic/spiron_wcp.htm#P
Another company gives this warning: "Spironolactone is highly
efficient against cirrhotic ascites. However, this is almost the only
indication where it can be given to men. For all other cases, other
drugs should be given preference because of the anti-androgenic effect
of spironolactone. In women, the potassium-sparing potential can be
exploited a bit better. Caution with renal failure!"
You may read that warning directly. The link is
http://www.infomed.org/100drugs/spitoc.html
Infomed-Verlags AG lists other information precautions about this
drug. The link is http://www.infomed.org/100drugs/spitoc.html
4) if i could take it with synthroid and proscar.
Yes. It appears as though patients who are taking Synthroid and/or
Proscar do not have negative effects when also taking Spironolactone.
Here is a list of the known drug interactions:
"DRUG INTERACTIONS
ACE inhibitors: Concomitant administration of ACE inhibitors with
potassium-sparing diuretics has been associated with severe
hyperkalemia.
Alcohol, barbiturates, or narcotics: Potentiation of orthostatic
hypotension may occur.
Corticosteroids, ACTH: Intensified electrolyte depletion, particularly
hypokalemia, may occur.
Pressor amines (eg, norepinephrine): Spironolactone reduces the
vascular responsiveness to norepinephrine. Therefore, caution should
be exercised in the management of patients subjected to regional or
general anesthesia while they are being treated with Aldactone.
Skeletal muscle relaxants, nondepolarizing (eg, tubocurarine):
Possible increased responsiveness to the muscle relaxant may result.
Lithium: Lithium generally should not be given with diuretics.
Diuretic agents reduce the renal clearance of lithium and add a high
risk of lithium toxicity.
Nonsteroidal anti-inflammatory drugs (NSAIDs): In some patients, the
administration of an NSAID can reduce the diuretic, natriuretic, and
antihypertensive effect of loop, potassium-sparing and thiazide
diuretics. Combination of NSAIDs, eg, indomethacin, with
potassium-sparing diuretics has been associated with severe
hyperkalemia. Therefore, when Aldactone and NSAIDs are used
concomitantly, the patient should be observed closely to determine if
the desired effect of the diuretic is obtained.
Digoxin: Spironolactone has been shown to increase the half-life of
digoxin. This may result in increased serum digoxin levels and
subsequent digitalis toxicity. It may be necessary to reduce the
maintenance and digitalization doses when spironolactone is
administered, and the patient should be carefully monitored to avoid
over- or underdigitalization.
Drug/Laboratory Test Interactions
Several reports of possible interference with digoxin
radioimmunoassays by spironolactone, or its metabolites, have appeared
in the literature. Neither the extent nor the potential clinical
significance of its interference (which may be assay-specific) has
been fully established."
You may read about these known drug interactions online. The link is:
http://www.rxlist.com/cgi/generic/spiron_ad.htm
5) the most important part is how it helps hair loss and
shedding. i read that it is an anti androgen and helps hair loss. i
need to know how it helps and how much it helps my hair loss problem.
how much of an effect does it have on hair loss shedding and stoping
hair loss????
There is quite a bit of data showing that spironolactone helps
patients with hair loss.
I found a web site where many users of Spironolactone have written
what the drug's effect has been on them. I'm attaching some of the
statements below. The link is
http://www.hairlosshelp.com/html/spironolactoneratings.cfm
"USER RATINGS
Have you tried this product before? If so please tell us what you
think of it.
(If you have have a question about this product please post it on our
message forum)
Rating (Out of five) Title Comments Author Date
Aldactone I have been using aldactone (100 mg) for about one year.
The results have been minimal. In the last month I have increased my
doseage to 100 mg twice a day. I may already seeing a big difference.
After I wash my hair and part it I see lots of new
- Read More - Rose 10/25/2001
Aldactone Hello, I have been on Aldactone for about 9 months. So
far, I find no real difference. I was told it could take up to a year
for it to start any real re-growth. I am still hopeful Bridget
- Read More - Bridget 07/24/2001
No Rating Topical Preparation Contact Dermatitis Ouch! Massive
allergic? reaction to a topical spironolactone preparation. I'm not
sure which ingredient in the preparation evoked this response, but,
for now, I'm off this stuff after a brief (2 week) trial.
- Read More - Cueball 12/04/2000
aldactone helps I have been using aldactone for approximately 2
months gradually increasing the dosage up to 75mg. I still have to get
up to at least 150mg per day. I have noticed a remarkable change in
the amount of shed hair. It has decreased from 250 - 300 hairs
- Read More - olga 11/14/2000"
The company, AfraidToAsk.com, claims this drug is not recommended for
use for treating hair loss, especially in men. It says in women it
disrupts the menstrual cycle. And in men it has severe sexual side
effects.
You may read what this company says about it online. I've also pasted
it below. The link is http://www.afraidtoask.com/hair/index.html
"ANTIANDROGEN THERAPY
This form of treatment decreases androgens (like testosterone) in an
effort to prevent hair loss. CPA (cyproterone acetate) is currently
used in combination with ethinyl-estradiol in the United Kingdom. In
the USA, Spironolactone, a drug used to lower aldosterone levels, is
the counterpart. Aldosterone is a hormone in the body that increases
androgen levels. This drug must be used for 1 to 2 years before
visible results occur. It's recommended within 2 years of onset of
hair loss, and patients must maintain high levels of vitamins and
ferritin (a substance that stores iron). Spironolactone tends to
disrupt the menstrual cycle and increases menstrual bleeding. It is
not intended for men, as it decreases sex drive and increases voice
pitch. Currently, there are not enough clinical data using
spironolactone for hair loss to recommend this medication for this
purpose."
Dr. Mary Lupo has also written about this drug in a
question-and-answer format. What she says is below. The link is
http://www.drmarylupo.com/ask.html
"I have excess facial hair and I had been taking the medication
Spironolactone 100mg daily with good results at first. In addition, I
am on birth control pills. I've recently noticed a worsening of the
facial hair and hair loss on my scalp. Any suggestions?
- Mary, e-mail
Dear Mary: Firstly, you need hormonal tests. These problems are often
associated with underlying ovarian or adrenal dysfunction. Also, make
sure your birth control pill is a higher estrogen level for best
results since you have these male-pattern symptoms. Spironolactone
sometimes must be increased to 200mg daily for best results. Finally,
RogaineÆ may help the scalp hair loss, and certainly for permanent
facial hair reduction, the Light Sheer laser is a great idea. The
Light Sheer laser is FDA approved and we have used it successfully
since December, 1998 at The Lupo Center for Aesthetic & General
Dermatology."
7) how much do i need to take
You should consult your physician or pharmacist before using any
medication. Your physician or pharmacist will tell you exactly which
strength of this medicine you need based on the severity of your
condition, overall level of health, and etc.
But i did find some information about using this solution. When using
the spironolactone solution, you should apply 1 cc to the balding
scalp twice a day (perhaps morning and night). You should allow it to
dry before using any other solution like minoxidil.
Life Extension Magazine had an article about Spironolactone in 1997,
written by a Doctor Proctor. I'm attaching that article below. The
direct link is http://www.lef.org/magazine/mag97/march-inter97.html
"LEF Magazine March 1997
Dr. Proctor Has Achieved an Unprecedented 80% Success Rate in Balding
Patients with this Unique, Patented Hair Growth Formula!
Life Extension Magazine (LEM) recently asked Dr.Proctor to answer
some frequently asked questions about hair loss, baldness and the
treatment of these conditions. Here are his answers.
LEM: Who should be concerned about hair loss and balding?
Dr.P: Many people over the age of 40 has already suffered significant
hair loss caused by aging or disease, even if they think they still
have a full head of hair. Persons below 30 should be especially
concerned with hair loss if baldness runs in their family, or if they
begin to notice the signs of Male Pattern Baldness.
LEM: What are the signs of Male Pattern Baldness?
Dr.P: Hair loss in a "pattern" typically beginning with recession in
front and a bald patch in the back.
LEM: When is the best time to start treatment for hair loss or
baldness?
Dr. P: The best time is as soon as possible after you notice any of
the signs of hair loss. Before you notice any signs of hair loss, you
might want to use shampoo that contains Polysorbate 60 and Polysorbate
80. If you're really concerned about preventing hair loss, you should
use our single-agent Hair Regrowth Formula.
LEM: Have your formulas proved successful in totally bald persons?
Dr. P: No. With the partial exception of Alopecia Areata, where we
have sometimes gotten pretty substantial regrowth of hair.
LEM: How important are anti-androgens in the treatment of the balding
process?
Dr. P: Anti-androgens prevent the action of the hormones which
initiate the balding process. Apparently, we were the first to use
antiandrogens with hair growth stimulators and so can speak with some
authority. For example, the Upjohn Corporation had a European patent
(WO 92/0959) turned down in this area because of our "prior art" (WO
A8700427) patent.
Every five years or so, some new anti-androgen will be touted as the
"ultimate solution for balding". Unfortunateiy, these never seem to
work out. Thus, clinical trials with Cyoctal, a potent topical
anti-androgen, were were terminated because of poor effectiveness.
Apparently, balding is only partly an androgen problem. In fact, the
primary follicle damage may be immunologically-mediated. Thus,
anti-androgens work very poorly alone. However, they do make hair-
growth-stimulators work much better and may prevent tolerance.
Researchers developed the most recent anti-androgen, Proscar, because
more powerful agents such as spironolactone (the one we use) are too
potent to use orally. The idea is that the most important androgen for
balding and prostate enlargement is DHT, while such side effects as
breast growth are due to blockage of other androgens. Block DHT
production alone and you might minimize the side-effects. This does
work some, but Proscar is not entirely free of side-effects, nor does
it work very well. Also, it is not topically effective. Currently, I
prefer to use topical spironolactone because of its minimal
side-effects and better effectiveness.
LEM: What evidence is there that balding is immunologically-mediated?
Dr. P: First, organ transplant drugs like cyclosporine reverse
balding. They are too toxic for cosmetic purposes, but some new ones
have just been patented listing hair loss as one application.
Second, under the microscope the balding hair follicle looks like
organ rejection. Finally, researchers have discovered antibodies to
the hair follicle.
LEM: How do you keep current in hair-loss treatment research?
Dr. P: Because of the commercial applications, most new agents show up
in the patent literature years before the medical literature. At last
count, there were over forty U.S. patents and several hundred foreign
patents covering hair-loss. Because of the expense and hassle of a
patent, you can reasonably assume that it must work...at least in some
young people. We're always being asked about this or that agent. If it
is in the medical or patent literature, we probably know about it. We
are always trying out new things.
LEM: How does your research program compare to those of the major drug
companies?
Dr. P: Patent application dates, which have great legal importance,
indicate we are several years ahead. Similarly, patents filed on our
discoveries by later inventors have reaffirmed them. For example-to
our dismay-the large Japanese drug company recently got a Japanese
hair-growth patent using phenytoin, our invention. Likewise, the U.S.
patent office just issued patents for hair growth using peptides with
superoxide dismutase (SODase)/radical scavenging activity to the
Procyte Corp. and to Proctor and Gamble. In the late 70s, we
discovered this effect, using SODase to treat diabetic rats at Baylor
College of Medicine. In fact, well before anyone else we applied for
patents covering essentially all agents with this and related
activity.
European patents (e.g. EPO 89300785.6) have been granted allowing
these broad claims. Conversely, the U.S. patent office originally
thought our claims too broad for a single patent. But when we
reapplied for patents on every compound, they were granted."
In addition, I found an article, "FDA Censorship Could Cost Lives" by
Daniel Troy of the American Enterprise Institute, a Washington, D.C.
think tank. The article is below. It can also be read online. The link
is http://www.aei.org/oti/oti10753.htm
"FDA Censorship Could Cost Lives
By Daniel E. Troy
Countless pharmaceuticals have beneficial uses other than those for
which they were developed and approved. Although such "off-label" uses
can be a boon to patients, manufacturers, and the economy at large,
the Food and Drug Administration has long forbidden drug producers
from informing doctors about them.
The following article explains the folly and the danger of that
policy. An earlier version of the article appeared in the Wall Street
Journal on July 23. Five days later, U.S. District Judge Royce C.
Lamberth confirmed his preliminary judgment against the ban in a
decision that embraced the article’s argument. The FDA seeks to
continue the ban, however, and is expected to appeal the decision.
Last month brought news that an inexpensive generic drug,
spironolactone, is remarkably effective in reducing congestive heart
failure. The finding is expected to save tens of thousands of lives
and reduce hospital expenditures by billions of dollars every year. So
dramatic are the results that the New England Journal of Medicine
rushed into print a study reporting reduced death rates of 30 percent
over two years.
There’s just one problem. The Food and Drug Administration has for
years forbidden the manufacturers of wonder drugs such as
spironolactone from informing doctors about developments like this.
Under that policy, manufacturers aren’t even allowed to send
physicians reprints of the New England Journal article.
Why? Because spironolactone, a drug approved decades ago to treat
water retention, has not been specifically approved to treat heart
failure. That makes the new use "off label," and the FDA considers any
manufacturer promotion of off-label uses to be "misbranding," a
criminal offense. The FDA has extended this ban to manufacturer
dissemination of independently generated, peer-reviewed research
reports that discuss off-label uses, such as chapters from medical
textbooks and reprints of journal articles.
Off-label use is ubiquitous. Indeed, it often represents the standard
of care, so that in many cases a doctor would be committing
malpractice if he failed to prescribe an off-label use. According to
the General Accounting Office, 25 percent of anticancer drugs were
prescribed off label, and 56 percent of cancer patients have been
given at least one drug off label.
Even an FDA official, in a deposition, said the agency "certainly
believe[s] it’s very appropriate for physicians to get information
about off-label uses from the many sources that they get them." In
other words, the FDA approves of doctors learning about off-label uses
from seminars, textbooks, the Internet, or colleagues. But it does not
permit doctors to receive reprints of medical journal articles from
pharmaceutical manufacturers, even if the reprint discloses that the
use discussed has not been approved by the FDA.
A year ago, federal judge Royce Lamberth struck down these FDA
restrictions. In Washington Legal Foundation v. Friedman, Judge
Lamberth rejected the FDA’s argument that the promotional speech of
drug manufacturers lies entirely outside the scope of the First
Amendment. Instead, he analyzed the FDA’s restrictions on manufacturer
dissemination of so-called enduring materials—textbooks and journal
reprints—under the more lenient standard for government restrictions
on advertising.
Using that standard, Judge Lamberth found that the FDA’s limits were
unconstitutional. He forcefully rejected the agency’s contention that
reprints are inherently misleading when physicians receive them from
drug manufacturers but unobjectionable when doctors obtain them from
any other source. The FDA is not, he declared, a peer-review mechanism
for the scientific community, nor is it the sole arbiter of truth.
The FDA moved to block the decision, arguing that the court had
addressed a policy superseded by the 1997 Food and Drug Administration
Modernization Act (FDAMA). Based on this law, the FDA asked the court
to declare that it need not adhere to the constitutional principles
announced in the court’s opinion. The reason given was that the new
law did indeed permit manufacturers to distribute materials about
off-label uses—but only if they have begun the cumbersome and
expensive process of getting supplemental FDA approval for the new
use.
In answer to these claims, Judge Lamberth in February noted that his
decision about the manufacturers’ free-speech rights was intended to
apply to the principles underlying the FDA’s old rules, and not just a
particular iteration of the rules. He did, however, ask the parties to
address what the scope of his order should be, in light of the 1997
law and the FDA’s implementing regulations. On July 28, 1999, the
judge not only reaffirmed his earlier ruling, he also held
unconstitutional the provisions of the FDAMA that restrict the
dissemination by manufacturers of independently generated,
peer-reviewed reprints.
Specifically, Lamberth held that the changes in FDA policy effected by
the FDAMA had not "brought the FDA into compliance with the First
Amendment." He also rejected as "preposterous" the argument that "the
Court should not apply First Amendment commercial speech scrutiny to
the FDAMA because, in [the FDA’s] words, the act ‘affirmatively
permits’ speech so long as it complies with the statute’s
requirements." Rather, said Lamberth, the First Amendment is based on
the idea that people don’t need to ask the government before they
engage in truthful, nonmisleading speech about lawful activities.
The force of this decision is not likely to deter the FDA, which is
virtually certain to appeal. The agency might even seek to stay the
effect of this decision, which could leave the current restrictions in
place. Either way, the FDA is expected to continue to defend the
restrictions.
Since so many people are affected by the new use of spironolactone—and
because the publicity surrounding this discovery has been so
widespread —it is unlikely that many cardiologists will fail to learn
about its potential, even without the assistance of manufacturers.
But new, lifesaving off-label uses are discovered all the time.
Pharmaceutical manufacturers have the greatest incentive to educate
doctors about such uses. As long as they are only reprinting
independently generated, peer-reviewed scientific information clearly
indicating that the FDA has not approved of the use discussed in the
article or book, there is no reasonable basis for any objection.
Despite a ruling saying that its actions violate the First Amendment,
the FDA continues to defend a ban on the dissemination of information
by manufacturers about lifesaving off-label uses of drugs such as
spironolactone. Once again, it’s left to the courts to rein in an
overzealous FDA.
--------------------------------------------------------------------------------
Daniel E. Troy is an associate scholar at AEI and an attorney. He and
his firm represent the Washington Legal Foundation in its First
Amendment challenge to the FDA’s off-label restrictions. A an earlier
version of this article appeared in the Wall Street Journal on July
23, 1999."
To conduct this research, I searched the following terms:
spironolactone, spironolactone "hair loss," spironolactone
manufacturer
I hope this helps! If you need any clarification, please don't
hesitate to ask!
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