Sign the Myodil Action Group e-petition
This is a document showing the major points from the
comprehensive research report conducted by Dr. Susan Parisian
about the production, testing, and use of Pantopaque/Myodil.
original animal test result documents and other mateial she refers to
can be found on this website.
AMERICAN ANIMAL TESTS,
RESULTS AND ADVERSE REACTION REPORTS WHICH
SHOULD HAVE STOPPED PANTOPAQUE (WHICH BECAME MYODIL IN ENGLAND) BEING
1918, Dandy created radiographic
the spinal cord by injecting air in to the spinal column.
1922, Iodinised Poppy Seed Oil
available since 1901) began to be used in doses less than 5cc's, but
was recommended that it be removed.
A 1932 statement of opinion by the
Association had discouraged the introduction of any foreign oily
material into the spinal cord.
1936, Eastman Kodak supply Ethyl
Iodophenylundecylate as the main ingredient of Pantopaque to Lafayette
under trade mark.
1937 to 1938, Warren and Strain
studies using Pantopaque which indicated that a inflammatory reaction
with production of Fibrosis was triggered.
1938, unlicensed Pantopaque was
distributed as a
investigative drug to Physicians without proven safety data.
1941, T.B. Steinhousen's doctoral
Iodinated compounds showed that in his opinion Lipidol (iodinised Poppy
seed oil similar to Pantopaque) was unsafe to use in humans
intrathesically. After reviewing cat studies he found one
after injection, he also cited earlier 1925 Rabbit studies that after
intrathecal injection there was a 47% mortality rate, and a 1938 study
by Metier and Leake reported numerous untoward reactions.
1941 study by Brown and Carr indicated significant danger injecting
iodinated Poppy seed oil in to the spinal canal. His thesis
included a study of the new compound Pantopaque, in a series of tests
using three dogs Pantopaque produced meningial irritation symptoms
ranging slight to severe. In another series using fifteen
46% had slight meningial irritation, 20% moderate, and 7% severe, one
dog was unable to walk, and one dog died of gangrenous terminal
ileum. At termination of the study and autopsy, histological
gross meningial changes were more severe than had been clinically
suggested, including granulamatis foreign body reactions, with acute
inflammatory polymorphonucleocytes (PMNs), phagolytes and fibroblasts
with fibrous adhesions involving the nerve roots, also clear cyst areas
dispersed throughout the spinal column, and scattered
macrophages. Steinhousen did the same test on nine dogs using
iodinised Poppy seed oil, the results were similar plus one dog
died. Steinhousen's research in dogs foreshadowed the acute
long term adverse events that came to be reported in humans.
26/02/1942, Dr. Rigler, University of
wrote reporting his facilities unfavourable clinical experiences with
Pantopaque, indicating in his and his staff's opinion it did not
improve imaging quality and was extremely difficult to remove.
05/09/1942, Major R.G. Spurling wrote
Pantopaque produced as many irritative symptoms as Lipidol.
In 1942 there appears to have been a
decision to disregard clinical ethical conduct and intentionally ignore
clinical findings and fail to provide physicians with test results on
animals and humans but describe Pantopaque as safe using misleading
04/11/1943, Lafayette, America, New Drug
Application, Dr. Walter Van Winkle FDA. requested from Dr. Strain
animal safety data. Dr. Strain stated he did not have very
figures on the acute toxicity. In the 1960's the FDA also
that test results carried out on mice (22/02/1943) were also inadequate
to support Pantopaque safety.
1944, on the basis of safety for use the
hesitant to permit a NDA, the reasons being that reports gave the
impression large numbers of reactions of varying degrees of severity
had been observed, but that the entire product circular created the
impression that reactions were minor and infrequent.
24/02/1944, Major Robert Robertson,
Neurosurgery, Brook General Hospital, Fort Sam, Houston Texas, reported
a patient developed Adhesive Arachnoiditis.
14/04/1944, Despite unfavourable animal
not being supplied to the FDA, Pantopaque NDA was approved in the US,
appearing to have occurred without resolution of Dr. Van Winkle's FDA
concerns regarding product safety issues, but purely on "grandfather
rights" based on a few hundred favourable Military Hospital Myerlograms
1946, Glaxo produce Myodil (Pantopaque)
in the U.K.
21/12/1950, complaints on certain lots
proved to be due to it containing 5% of Iodophenylundecanoic acid,
rather than 0.9%. A letter from Mr. Mees of Kodak's
Products Industries (suppliers of ethyliodophenylundecylate to
Lafayette) sought to create a legal distance from Lafaet's distribution
of Pantopaque assuming no responsibility.
03/12/1953, the American Journal of
Radium Therapy and Nuclear Medicine indicated a usual injection of 6 or
9cc's of Pantopaque, however the 1944 NDA recommended a dose of 2 to
Lafaet's labelling continued to make no
potential serious acute or long term consequences associated with
Pantopaque (the expressed concern of FDA's Dr. Van Winkle), did not
recommend doses of 2 to 5cc, nor emphasise the removal of all material,
but did emphasise injecting a larger dose than had been submitted for
1964, Mr. Hagan of FDA wrote of his
regarding the fever induced from Pantopaque injections which appeared
to be related to the Pyrogenisity of the product.
03/10/1966, FDA's James E. Wilson PhD.
Iophenylate has been on the market for twenty years, but deaths have
been attributed to it's use.
Swartz, 1965, sights a 61 year old woman
who died of
27/11/1967, Lafayette wanted to
introduce a new
drug, Pantopaque ii. New tests were carried out on 24 pure bread Walker
hounds by Hazelton Laboratories, comparing Pantopaque i and
Results showed 5 dogs had clotted blood at the base of the brain and
anterior spinal cord (1 dog Pantopaque i, 4 Pantopaque ii), 8 dogs had
meninges visibly thickened (3 dogs Pantopaque i, 5 Pantopaque ii), in 6
dogs oily material was grossly seen in the meninges (3 dogs Pantopaque
i, 3 dogs Pantopaque ii). At autopsy 2 Pantopaque i dogs had
moderate to severe granulamatis reaction surrounding large vacuoles in
the space under the meninges and surrounding some of the spinal
nerves. There was moderate to severe Fibrosis surrounding the
spinal cord and scattered areas of granulamatis reaction were present
within the white matter of the spinal cord. The spinal cord
surrounded by moderate amounts of old blood present under the
meninges. The following was the summary of Hazelton
In conclusion it can be stated that the intrathecal administration of
Pantopaque i and ii stimulates a Granulamatis Meningitis in the areas
were the compounds appear to localise. The majority of the
inflammatory reactions present in the animals on this study were of a
sub-accute to chronic nature. Pantopaque i stimulated
granulamatis reaction in primarily the lumbar region. Both
Pantopaque i and Pantopaque ii produced severe reaction in the cervical
and thoracic cords.
14/04/1969, FDA recommended Lafayette
statement: the small amount of material left in the sub-arachnoid space
usually is absorbed in two months (it actually remains for many
years). In the adverse reactions section to include severe
Arachnoiditis producing headache, fever, meningismous, pain in the back
and extremities and elevations in the white blood count and the protein
count of the cerebro spinal fluid and instances of lipoid granuleomas
obstruction of the ventricular system and venis intravation producing
pulmonary emboli. In contrainedations section Pantopaque is
contrained in patients with hypersensitivity to Iodine or its
compounds. In precautions section diagnostic tests of thyroid
function involving Iodine maybe invalid for many years, it is my
understanding none of these recommendations were followed..
25/06/1969, Lafayette withdrew NDA for
ii, from the memo and letter to FDA there appears to be no mention of
the adverse findings of the animal studies done by Hazelton
Laboratories relevant to the poor safety performance of Pantopaque I,
the approved product. Therefore the FDA were never informed
the animal toxicity studies which showed Pantopaque i unsafe.
07/02/1972, Two hours after injection of
two patients at Holy Family Hospital, Atlanta, GA, developed Cerebral
Adema, Focal and Grandmal seizures, Hypotension, loss of bowl/bladder
control and Aspiration Pneumonia.
1977, Alcon purchased Lafayette.
18/09/1978, Medical World News Journal,
a Dr. Henry L. Fefer article, "Arachnoiditis Risk after Pantopaque
Myerlography," that of 400,000 yearly Myerlograms 25% will probably
develop Arachnoiditis and patients having two or more, 50%.
Confirmed by animal studies, but denied by Lafayette.
13/08/1979, Dr. Newton reported to a
Pantopaque an adverse reaction. Another physician/father
concern about his 25 year old daughter's condition being in a great
deal of pain, excitable and upset.
June 1982, a paper appeared in
regarding Pantopaque versus Amipaque used in monkeys which outlined
Pantopaque as a causative factor in Arachnoiditis.
July 1982, Johnston and Matheny studied
with Arachnoiditis stating four of the patients had Myerlography after
spinal surgery and all four had severe Arachnoiditis.
25/04/1983, Eastman Kodak, supplier of
Iophenylactulate to Lafayette, became aware of legal activity
surrounding Pantopaque and the falling popularity compared to the new
water-based Amipaque (Metrizamide).
1984, Lafayette released a caution
against the use
of plastic syringes.
29/04/1985, Ms. Galene Tsipis of Drug
information control, Ohio, wrote a irate letter to Alcon
Laboratories (owners of Lafayette) about a adverse drug reaction
(paralysis of the lower extremities) involving a patient in a local
hospital. She requested clinical trial data and adverse
reports on Pantopaque, she was told no information was available and
she felt she was given the run-around.
June 1987, Alcon's drug experience
listed thirteen patient complaints of Arachnoiditis, Focal seizure,
burning in the lower back, Nausea, Allergic phenomenon and suspect
Meningitis, and two suites in Dade County, Florida. Label
were made adding severe Arachnoiditis has been reported.
1987, Alcon ceased production, but had
stock with a
shelf life of five years.
15/03/1990, Scott Kerby reporter for
rang Mr. West (FDA) in connection with a patient who had three
Myerlograms in the early 1970's and was now severely paralysed with
Arachnoiditis and had attempted to sue Alcon Laboratories, but was told
statute of limitations had elapsed. Mr. West indicated in the
1970's the consumer/patient would have been unaware of the risks, but
the occurrence was well documented in Radiological text books.
12/06/1990, Pantopaque was discussed on
consumer show hosted by Geraldo Rivera.
26/09/1990, 25 plaintiffs launched a
suite against Alcon alleging permanent severe injuries, chronic pain,
paraplegia, quadriplegia and death from incurable Arachnoiditis.
30/08/1990, Wall St. Journal reported a
suite of 300
1990, The Management of Pain magazine
noted decrease in Arachnoiditis since the decrease in use of oil based
Myerlograms which was also recognised by the medical fraternity.
Conclusion: Physicians reported
removing all the Pantopaque, not as described by the producers,
Pantopaque primarily remains unabsorbed in the body and is associated
with chemical meningitis, fever, shock, respiratory arrest,
oblitirative Arachnoiditis, neurological deficit, paralysis, focal and
grandmal seizures, blindness, corda equina syndrome, obstructive
hydrocephalus, bowl and bladder dysfunction, syphilis, sexual organ
pain and dysfunction, trauma, numbness, paraplegia, loss of sensory and
motor function, pain in lower trunk abdomen and legs, coma and death,
intractable burning pain worsened by physical activity which stretch
the lumbar nerve roots and not ameliorated by narcotics.
Resulting in a lifetime of severe unremitting
After 40 years doses were increased from
30cc's (the original NDA 2 to 5cc) increasing patient risk.