spironolactone Best answer on the web
Posted in: darrelrussell.com edit
07 Jan 2009
Spironolactone is manufactured in doses of 25 mg, 50 mg, and 100 mg. Of course if your physician or pharmicist believes you should have more, he or she can double the dosage.
I found another link that can help you out. RxList wrote the following about Spironolactone:
"Aldactone oral tablets contain 25 mg, 50 mg, or 100 mg of the aldosterone antagonist spironolactone, 17-hydroxy-7alpha-mercapto-3-oxo-17alpha-pregn-4-ene-21-carboxylic acid gamma-lactone acetate. Spironolactone is practically insoluble in water, soluble in alcohol, and freely soluble in benzene and in chloroform. Inactive ingredients include calcium sulfate, corn starch, flavor, hydroxypropyl methylcellulose, iron oxide, magnesium stearate, polyethylene glycol, povidone, and titanium dioxide."
You may read this information directly from the RxList web site. The link is http://www.rxlist.com/cgi/generic/spiron.htm
Please let me know what else I can answer for you.
darrel-ga
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, Rogaine 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.
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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."
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