- Schering-Plough ITSELF admits on its Proventil HFA homepage (6th paragraph from the bottom): "RAPID HEART BEAT, VOMITING, CHEST PAIN and PALPITATION OCCURS MORE FREQUENTLY WITH PROVENTIL HFA (than with CFC albuterol) ."
- Look at the Adverse Experience Incidences Chart on page 3 and decide which you would rather take or give to YOUR child: PROVENTIL HFA or ALBUTEROL CFC.
The incidence of TACHYCARDIA (rapid heart beat) during the 12 week clinical trials was over 7% for Proventil HFA vs. 2% for CFC albuterol.
The incidence of VOMITING during the 12 week clinical trials was 7% for Proventil HFA vs. 2% for CFC albuterol.
The incidence of FEVER during the 12 week clinical trials was 6% for Proventil HFA vs. 2% for CFC albuterol.
The incidence of BACK PAIN during the 12 week clinical trials was 4% for Proventil HFA vs. 2% for CFC albuterol.
The incidence of ALLERGIC REACTIONS during the 12 week clinical trials was 6% for Proventil HFA vs. 4% for CFC albuterol.
The incidence of RESPIRATORY DISORDERS during the 12 week clinical trials was 6% for Proventil HFA vs. 4% for CFC albuterol.
- Look at the Adverse Reactions Chart on page 5 and decide which you would rather take or give to YOUR child: VENTOLIN HFA or ALBUTEROL CFC.
The incidence of THROAT IRRITATION in two 12 week clinical trials was 10% for Ventolin HFA vs. 6% for CFC albuterol.
The incidence of VIRAL RESPIRATORY INFECTION in two 12 week clinical trials was 7% for Ventolin HFA vs. 4% for CFC albuterol.
The incidence of COUGH (a common asthma symptom) in two 12 week clinical trials was 5% for Ventolin HFA vs. 2% for CFC albuterol.
NOTE: There were no adverse reactions occurring more frequently in CFC inhalers compared to Ventolin HFA.
- Look at the Adverse Events Chart (Table 3, p.1349) with combined clinical trial data for Proventil HFA, Ventolin HFA, and Proair HFA (about 460 patients in the test arm) vs. CFC albuterol and decide which you would rather take or give to YOUR child: HFA ALBUTEROL or CFC ALBUTEROL.
- GlaxoWellcome (now GlaxoSmithKline) ITSELF admits in its New Drug Application (NDA #20983) to the FDA for 'ethanol-free' Ventolin HFA: "Unfavorable changes in physical examinations were observed in the ears, nose, and throat category as follows: 8% placebo HFA; 13% albuterol HFA; and 5% albuterol CFC." (page 6)
- "However, in the multiple dose adolescent and adult studies, albuterol HFA showed a numerically smaller improvement in FEV1 (forced expiratory volume in 1 second) than was seen with albuterol CFC." (page 3)
- "There was other evidence that the HFA formulation delivers a lower/less effective dose on a per acutation basis than the CFC product. In the single dose, dose ranging study in adults, and in the single dose methacholine challenge study in adults one and two acutations of albuterol CFC were statistically indistinguishable in terms of effect, whereas significant differences were seen between one and two acutations of albuterol HFA. Finally, the combined adolescent/adult studies showed that the HFA formulation had a longer median time to onset of effect(4.2-9.6 minutes versus 3.6-4.2 minutes), had a shorter duration of effect(1.55-3.30 hours versus 2.29 - 3.69 hours), and was associated with more albuterol 'back up' use than the CFC formulation." (page 3)
- "The classic approach of industry and FDA has been to do studies that are too small to conclusively identify that a risk is real," he added. "They can conclude, therefore, that there is no risk." FDA Safety Officer David Graham, MD,MPH
- Graham charged that "FDA standards of evidence give drugs and drug companies a free pass on safety."
- "A more limited or BRIDGING APPROACH was developed for the PRE-CLINICAL SAFETY TESTING of the new (HFA INHALER) formulations... "
-FDA MD John Jenkins
- "Similar to the preclinical safety battery... THE RECOMMENDED CLINICAL DEVELOPMENT PROGRAMS for the most part represent a BRIDGING APPROACH."
-FDA MD John Jenkins
A) THREE OF THE FOUR HFA RESCUE INHALERS AND SEVERAL HFA CONTROL INHALERS USE ETHANOL AS A SOLVENT (UNLIKE CFC INHALERS) AND ETHANOL IN ASTHMA INHALERS IS KNOWN TO PROVOKE BRONCHOCONSTRICTION IN SOME ASTHMA PATIENTS.
B) According to our conversations with technical staff at Schering-Plough (PROVENTIL HFA) and Sepracor (XOPENEX HFA), the CORN RESIDUE in the corn-sourced ETHANOL may well be dangerous for CORN ALLERGIC PATIENTS (and there are MANY). THIS IS A SEPARATE RISK FROM THE ETHANOL ITSELF.
C) Based on two years of research, we believe that HFA-134a itself was never tested on asthma or pulmonary patients. (We have no access to the IPACT-1 results in the FDA's HFA-134a Drug Master File and we call upon the FDA to release this data if it includes test results of HFA-134a vs. CFC-11,12 in patients, if such tests were ever done.) It was tested on mice, rats, rabbits, dogs, and healthy volunteers, but apparently not on the patients who would be inhaling it for life. HEALTHY SUBJECTS DO NOT HAVE SEVERE ALLERGIES AND HYPERREACTIVE, INFLAMED AIRWAYS AND THEREFORE THEY ARE NOT A SUITABLE PROXY FOR ASTHMATIC PATIENTS:
- Human Inhalation Studies on HFC-134a and HFC-227ea
- Acute safety of the CFC-free propellant HFA-134a from a pressurized metered dose inhaler
- Twenty-eight-day double-blind safety study of an HFA-134a inhalation aerosol system in healthy subjects
- Human Safety and Pharmacokinetics of the CFC Alternative Propellants HFC 134a (1,1,1,2-Tetrafluoroethane) and HFC 227 (1,1,1,2,3,3,3-Heptafluoropropane) Following Whole-Body Exposure
D) WE WERE DEALING WITH AN ENTIRELY NEW WITCH'S BREW OF POTENTIALLY DANGEROUS IMPURITIES (KNOWN AS EXCTRACTABLES AND LEACHABLES) WITH HFA ASTHMA INHALERS, AND AS WITH EACH OF THE PROBLEMS LISTED ABOVE, ONLY LARGE-SCALE TRIALS COULD HAVE UNCOVERED THESE POTENTIALLY DEADLY RISKS THAT 40 MILLION AMERICANS ARE NOW UNCOVERING, WITHOUT THE SAFETY OF CFC ASTHMA INHALERS AVAILABLE AS A BACK-UP FOR THE MANY THOUSANDS OF PATIENTS WE NOW KNOW CANNOT TOLERATE HFA INHALERS.
AN INCREASING NUMBER OF PATIENTS, MANY OF WHOM ARE SUFFERING UNPRECEDENTED, SEVERE ADVERSE REACTIONS FROM HFA ASTHMA INHALERS, ARE BEING TOLD BY THEIR DOCTORS THAT THEY ARE ALLERGIC TO OR INTOLERANT OF HFA INHALERS. IF FDA DRS. JENKINS AND MEYER HAD DONE THEIR JOBS PROPERLY, WE WOULD HAVE KNOWN ABOUT THESE PROBLEMS YEARS AGO.
The above-mentioned clinical Proventil HFA, Ventolin HFA and Proair HFA trial results agree with the results of a large postmarketing surveillance study done in the United Kingdom in 1998 comparing the UK version of Proventil HFA (manufactured by 3M, called Airomir HFA) with CFC salbutamol (albuterol):
BMJ 1998;317:926-930 ( 3 October )
General Practice
Postmarketing surveillance study of a non-chlorofluorocarbon inhaler according to the safety assessment of marketed medicines guidelines
J G Ayres, professor, a C D Frost, lecturer, b W F Holmes, general practitioner, c D R R Williams, professor, d S M Ward, clinical research specialist. e
a Department of Respiratory Medicine, Birmingham Heartlands Hospital, Birmingham, B9 5SS, b Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London WC1 7HT, c Sherrington Park Medical Practice, Nottingham NG5 2EJ, d Division of Public Health, Nuffield Institute for Health, Leeds LS2 9PL, e 3M Health Care, Loughborough LE1 11EP
The study included 6,614 patients, and followed them for three months. Some patients were given CFC salbutamol , some patients were given HFA salbutamol. From the paper:
"General practitioners attributed more adverse events to hydrofluoroalkane (HFA) inhalers (3.1%) than to chlorofluorocarbon (CFC) inhalers (0.7%)."
"More patients using the hydrofluoroalkane (HFA) inhaler stopped taking study medication because of adverse events (3.8% compared with 0.2% in the chlorofluorocarbon (CFC) inhaler group)."
"However, more patients using the hydrofluoroalkane (HFA) inhaler than the chlorofluorocarbon (CFC) inhaler withdrew because of adverse events (3.8% and 0.9% respectively)."
As with all drug company sponsored clinical trials and postmarketing studies, we have no interest whatsoever in the author's speculation, spin, or self-serving characterization of the results summarized in the conclusions. Often, the results of these bought and paid for 'clinical trials' contradict the authors' conclusions. Studies that can't help the drug company sell the drug rarely get published (although unfavorable clinical trial data can no longer be suppressed, thanks to recent legislation). We are only interested in the most objective, non-biased results the study provides, and these results are listed above.
Our scepticism about these authors' strangely positive conclusions about the safety of HFA salbutamol is shared by UK General Practitioner M.G. Bamber in a reply to this study:
BMJ 1999;318:810 ( 20 March )
Letters
Postmarketing surveillance study of a non-chlorofluorocarbon inhaler
The first 150 words of the full text of this article appear below.
"EDITOR---The study by Ayres et al may have been selectively designed to promote a product as safe; they endorse it as conforming to unpublished guidelines for postmarketing surveillance studies under safety assessment of marketed medicines.1 Withdrawals from the study are mainly for reasons "not related to safety," and the withdrawal rate of the product under evaluation is almost three times that of the salbutamol inhaler with conventional propellant.
"I have several reservations about the study. Postmarketing surveillance studies initiated by the manufacturer are primarily designed to promote a product to the medical profession and the general public. One incentive for patients to enter such a study is the availability of a prescribed drug without charge. Participating general practitioners receive a generous fee---particularly attractive and effective in medical recruitment to this study since "neither the patient nor doctor had to undertake any procedures related to the study." Criteria . . . [Full text of this article]"
"The study by Ayres et al may have been selectively designed to promote a product as safe..."
"Withdrawals from the study are mainly for reasons "not related to safety," and the withdrawal rate of the product under evaluation (HFA salbutamol) is almost three times that of the salbutamol inhaler with conventional (CFC) propellant."
EVEN WORSE RESULTS FOR HFA INHALERS CAME IN FROM NEW ZEALAND:
In the NON-DRUG COMPANY SPONSORED CLINICAL TRIAL of CFC salbutamol (albuterol) vs. HFA salbutamol conducted in New Zealand by Dr. Shane Reti:
"In this study, half of those on the CFC-free (HFA) inhaler developed unstable asthma and 93% of those remaining had demonstrably worse asthma."
(THIS STUDY USED SALAMOL HFA, MADE BY THE SAME COMPANY THAT MAKES U.S. MARKET LEADER PROAIR HFA).
THERE ARE THOUSANDS OF COMPLAINTS FROM PATIENTS THROUGHOUT THIS SITE (HERE, HERE, HERE, HERE, HERE, HERE AND HERE) AND OUR OTHER SITE, AND ALSO HERE, HERE, AND HERE). SOME OF THESE PATIENTS ARE PHYSICIANS, SURGEONS, PhDs, RNs and RESPIRATORY THERAPISTS.
THEY KNOW HOW TO CLEAN AND USE THE HFA ASTHMA INHALERS, BUT THEY ARE ALLERGIC TO OR INTOLERANT OF THE UNIQUE INACTIVE INGREDIENTS (EXCIPIENTS) AND/OR THE UNIQUE IMPURITIES (INCLUDING, BUT NOT LIMITED TO THEIR EXTRACTABLES AND LEACHABLES) IN THESE POORLY TESTED HFA ASTHMA INHALERS.
A THREE YEAR REVIEW OF THE FDA's OWN MEDWATCH DATA (SUMMARY TABLE BELOW) SHOWED AN INCREDIBLY DISPROPORTIONATE NUMBER OF MEDICAL COMPLAINTS AGAINST HFA RESCUE INHALERS VS. CFC RESCUE INHALERS.
NOTE: The FDA receives adverse drug reaction reports from manufacturers as required by regulation. Health care professionals and consumers send reports voluntarily through the MedWatch program. These are evaluated by clinical reviewers in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) to detect safety signals and to monitor drug safety.
For any given report, there is no certainty that a suspected drug caused the reaction. This is because physicians are encouraged to report suspected reactions; however, the event may have been related to the underlying disease being treated, or caused by some other drug being taken concurrently, or simply occurred by chance at that time.
IS THIS ALL NOISE, OR MIGHT THERE BE A SAFETY SIGNAL LURKING IN THE TABLE BELOW?
| % Average Market Share (based on prescriptions filled) between 6/30/05- 6/30/08 |
% of Total U.S. MedWatch-reported medical complaints filed between 4/1/05-4/1/08 |
% of Total U.S. MedWatch- reported deaths filed between 4/1/05-4/1/08 |
|
| HFA Rescue MDIs | 32 |
63 |
46 |
| CFC Rescue MDIs | 68 | 37 |
54 |
Prescription data is from IMS Health, IMS National Prescription Data.
THIS TABLE IS BASED ON 640 MEDWATCH COMPLAINTS WHICH ARE INCLUDED IN THE FOLLOWING PDFs. THE TOP NUMBER (BELOW) IS THE NUMBER OF U.S. REPORTED COMPLAINTS (some PDFs include foreign complaints but they were NOT included in the SUMMARY TABLE); THE BOTTOM NUMBER IS THE NUMBER OF U.S. REPORTED DEATHS (CLICK THE LINKS TO SEE THE MEDWATCH COMPLAINTS. REMEMBER THAT POSSIBLY LESS THAN 1% OF ALL ADVERSE EVENTS ARE REPORTED TO MEDWATCH).
MedWatch CFC vs. HFA Rescue Inhaler Complaints: April 1, 2005 to April 1, 2008:
(Click on each link to see the MedWatch reports. Internet Explorer works best.)
PROVENTIL HFA VENTOLIN HFA VENTOLIN CFC PROAIR HFA XOPENEX HFA
84 65 91 230 24
10 0 2 0 2
GENERIC CFC (excluding WARRICK CFC) PROVENTIL CFC (including WARRICK CFC)
75 71
1 11
USE THESE ONLINE MEDICAL DICTIONARIES TO HELP UNDERSTAND THE ADVERSE EVENTS MENTIONED IN THE ABOVE MEDWATCH REPORTS:
MEDLINEPLUS
REFERENCE.MD
MONDOFACTO
NOTE: The above MedWatch reports were imported from the FDA's AERS (Adverse Events Reporting System) Database and carefully scrubbed to eliminate duplicate reports. There were numerous inconsistencies in the ways FDA reviewers input these reports into the database (NDA numbers often did not match with the correct manufacturer, drug name, type of drug, method of delivery, etc.) We took every precaution to post only the cleanest, least ambiguous reports possible, and we always erred on the side of quality rather than quantity of reports.
NOTE: The number of prescriptions filled during this three year period VARIES WIDELY between products so the ABSOLUTE NUMBERS of deaths and medical complaints HAVE VERY LITTLE VALUE.
NOTE: ADVERSE EVENTS/REACTIONS are GROSSLY UNDERREPORTED TO MEDWATCH- many doctors believe that less than 1% of all ADVERSE REACTIONS get reported to MEDWATCH. Multiply all numbers above by 100 to get a more realistic idea of the actual numbers of adverse events/reactions that occurred during this time frame.
NOTE: WE ELIMINATED AN ADDITIONAL 14 HFA ALBUTEROL REPORTED DEATHS FROM THE SUMMARY TABLE ABOVE THAT OCCURRED OUTSIDE THE U.S. (6 for Proventil HFA, 2 for Ventolin HFA- these ARE included in the above PDFs- as well as 6 Salbutamol HFA reported deaths which were NOT included in the PDFs because they were 100 mcg instead of 90 mcg). NONE of these 14 foreign HFA reported DEATHS were included in the SUMMARY TABLE.
Similarly, we ELIMINATED 26 NON-FATAL HFA medical complaints from the SUMMARY TABLE that came from outside the U.S. (2 for Proventil HFA and 24 for Ventolin HFA- they are included in the PDFs).
We ELIMINATED 1 foreign reported DEATH and 28 foreign NON-FATAL reported medical complaints from Ventolin CFC- they are included in the PDFs but they are NOT included in the SUMMARY TABLE.
This data is ENTIRELY CONSISTENT with the Proventil HFA, Ventolin HFA and Proair HFA clinical trial adverse reaction data shown above, as well as the UK postmarketing study, and the New Zealand study, and the anecdotal comments from thousands of patients (including MDs, RNs, RRTs, and PhDs).
THE DATA ON THIS PAGE SUPPORTS OUR POSITION THAT HFA ASTHMA INHALERS ARE NOT AS SAFE AND EFFECTIVE AS CFC ASTHMA INHALERS.
PLEASE DONATE TO OUR CAMPAIGN TO PERMANENTLY LEGALIZE CFC MDIs HERE
