IRON SUPPLEMENTATION MAY HELP PATIENTS WITH ACE INHIBITOR-INDUCED
Iron supplementation may provide relief for patients suffering from
dry cough induced by an ACE inhibitor.
FDA MOVES AHEAD WITH PLANS TO BAN PPA
Moving ahead with plans to remove phenylpropanolamine (PPA) from
the US market, the US Food and Drug Administration on Tuesday offered
several manufacturers an opportunity for a hearing prior to the
withdrawal of their products.
Iron Supplementation May Help Patients With ACE Inhibitor-Induced
August 17, 2001
By Hope Vanderberg
New York - Iron supplementation may provide relief for patients
suffering from angiotensin-converting enzyme (ACE) inhibitor-induced
dry cough, according to findings published in the August issue of
The ACE inhibitor is one of the most widely used drugs in cardiovascular
medicine. Despite its track record in improving survival rates and
reducing complications in patients with cardiovascular conditions
such as hypertension and heart failure, however, various adverse
effects limit its use. Dry cough is the most frequent adverse effect,
reportedly occurring in 5%-39% of patients. In most cases, patients
with this troublesome complication discontinue the drug. But Korean
investigators may have hit on a simple remedy.
In a randomized, double-blind, placebo-controlled trial, the researchers
studied 19 patients who had developed persistent dry cough while
receiving ACE inhibitors for various heart conditions. The 6 men
and 13 women, whose average age was 60 years, first completed a
diary during a 2-week observation period, while receiving ACE inhibitors
Participants scored their cough severity twice a day using a scale
that ranged from no cough (0) to severe cough that persisted and
interfered with daily activities and sleep (4). At the end of 2
weeks, participants' blood iron levels were sampled using markers
including hemoglobin, hematocrit, serum iron concentration, ferritin
levels, and total iron binding capacity. Participants were then
given either a daily morning tablet of 256 mg ferrous sulfate or
placebo for 4 weeks, during which time monitoring of cough severity
was continued. At the end of 4 weeks, iron levels in the blood were
"Supplementation of iron clearly showed a beneficial effect
in most of these subjects, and this effect could not be found in
the placebo group," says lead author Kyung Pyo Hong, MD, of
the Samsung Medical Center, Sungkyunkwan University School of Medicine,
Eight of 10 patients who received iron showed improvement, and
3 of these patients had a nearly complete end to their coughing
at the end of 4 weeks. The average daily cough score in the iron
group was 3.07 (severe) at the end of the first 2 weeks, and 1.69
(mild) after 4 weeks of iron supplementation. There was no significant
change in cough scores of the placebo group.
Average ferritin levels increased in the iron group after 2 weeks
of iron treatment, but not significantly. Ferritin levels remained
about the same in the placebo group throughout the study. None of
the other markers of iron levels in the blood changed significantly
in either group.
The mechanism of ACE inhibitor-induced dry cough is unclear, but
it is thought to be associated with the increase in nitric oxide
(NO) generation caused by ACE inhibitors. NO is known to have inflammatory
effects on bronchial epithelial cells. Dr. Hong and colleagues embarked
on their study based on reports that iron supplementation decreases
NO generation or diminishes NO-related cell damage.
Dr. Hong says that further investigation is warranted to verify
the findings, which are limited by the relatively small sample size
and the inability to perform a crossover study to confirm the effects
of iron supplementation. Long-term effects of iron supplementation
with ACE inhibitors must also be studied, he says. However, the
dramatic and rapid beneficial effects demonstrated in this study
are promising. "Iron may be a key element in the control of
dry cough," Dr. Hong says.
FDA Moves Ahead With Plans to Ban PPA
WASHINGTON (Reuters Health) Aug 14 - Moving ahead with plans to
remove phenylpropanolamine (PPA) from the US market, the US Food
and Drug Administration on Tuesday offered several manufacturers
an opportunity for a hearing prior to the withdrawal of their products.
In November, the FDA declared its intentions to ban PPA after two
studies and a committee of expert advisors to the agency concluded
that PPA, found in a number of over-the-counter diet aids and cold
medicines, might cause strokes in young, healthy people.
Retailers nationwide already have voluntarily pulled several brands
of those products, and a number of the larger manufacturers of cold
medications have agreed to substitute ingredients. But there is
no alternative to the over-the-counter diet aids, and as a result,
not all manufacturers have joined the bandwagon. Some argue that
the studies were flawed and that the risk of PPA does not outweigh
the benefits of the diet aids, considering the prevalence of obesity
in the US population.
The FDA said that it believes PPA was responsible for about 200
to 500 strokes a year, based on reported events in its proprietary
database. "The burden of proof now falls upon the industry
to show us that it's safe," said Dr. Lois La Gernade, the lead
FDA reviewer. "At a minimum, consumers should be adequately
Still, the FDA agreed that the risk is minimal. And in issuing
its advisory in November, the agency made sure to note that PPA
has been used for about 50 years and that the FDA action was taken
simply to ensure that Americans were not taking an unnecessary risk.
Some experts have speculated that in going after PPA, the FDA actually
was preparing to go after ephedra, which the body converts into
PPA. Also known as ma haung, ephedra is a common ingredient in dietary
supplements that claim to help people lose weight and increase their
Last year, FDA proposed banning the combination of ephedra with
caffeine. Since then, the FDA has hosted a number of meetings regarding
the issue, but it has taken no direct action to push or implement
its proposed ban.
In total, the FDA's current actions involving PPA include the withdrawal
of 16 brand-name drugs and eight generic drugs. The agency said
that the sponsors of these drugs would now have 60 days to request
a hearing or face forced withdrawal of their products. The sponsors
include Novartis, Teva and GlaxoSmithKline, all of which previously
announced removal of PPA from their over-the-counter cold products.