Tonic-clonic seizures in patients taking sildenafil
BMJ 2002; 325 doi: https://doi.org/10.1136/bmj.325.7369.869 (Published 19 October 2002) Cite this as: BMJ 2002;325:869All rapid responses
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Dear Mr. Woolsey,
On July 20th, 2003, you submitted a rapid response to the medical
article “Drug Points: Tonic-clonic seizures in patients taking
sildenafil” by Ronit Gilad et al (BMJ 2002; 325: 869). Your report brought
to our attention an apparent adverse reaction (seizures) to one of our
drugs i.e., sildenafil citrate (Viagra). We are very interested in
obtaining details of possible adverse reactions to our drugs and
spontaneous reports of adverse events represent an important source of
information. We are committed to following-up on adverse events that occur
during treatment with any of our products. To honor this commitment, and
as required by the United States Food and Drug Administration (FDA)
regulations, we will therefore be contacting you via a separate
communication to follow-up on the adverse event you reported.
Thank you in advance for your collaboration
Competing interests:
Employee of Pfizer
Competing interests: No competing interests
Ladies and Gentlemen:
Twice, not once but twice did I use sildenafil and it caused three
separate seizures. Two in one day and I never knew what hit me -- both
time were after using the drug for three times in three days. Once on a
Sunday and the other on a Saturday. Both seizures occurred approximately
4 to 4.5 hours after the use. Both seizures were incredibly dibilitating
and I have never had anything like it happen before or since. I was
informed by a doctor after the first one there was no way it could have
been the sildenafil. The last seizure had actually two occur and was very
dibilitating and took 10 days to recover. So a person with no history of
seizures and from all the tests I took with no indication of a propensity
to seizures, I disagree with the person from Phizer and the other doctor
there is no indication. There must be some and since I have been fine no
with no other medication for more than 3 months, I have to conclude this
was the cause.
Competing interests:
Former user of Viagra
Competing interests: No competing interests
This article throws light on the possible epileptogenic nature of
sildenafil only in patients with prior history of seizures. There has been
no reports so far with incidence of seizures in normal patients.
It is a well known fact that over excitation and sexual stimulation can
trigger excitatory neuro transmitters which could result in seizures in
epilepsy patients.
It could be most likely that sexual stimulation was the cause of seizures
rather than sildenafil citrate although epilepsy patients will have to be
prescribed sildenafil with a caution and warning.
Competing interests:
None declared
Competing interests: No competing interests
Dear Sir:
We refer to the article by Gilad et al of two patients who reportedly
took sildenafil citrate (Viagra®) for the first time and presented with
tonic-clonic seizures.1 We have reviewed the latest information available
to us from various sources to ascertain whether there is other evidence to
support the authors’ suggestion of a causal relationship.
Clinical data are available from 4,615 patients who received placebo
in double-blind studies, and 11,811 patients who received sildenafil in
placebo-controlled double-blind studies or parent non-comparative open-
label studies. Additionally, 5,773 patients received sildenafil in open-
label extension studies. This database was searched for cases containing
adverse events (AEs) coding to the COSTART term "convulsion" or "grand mal
convulsion." In placebo-controlled double-blind studies, there were two
cases of events coded as "convulsion" in patients receiving placebo and no
events in patients receiving sildenafil. In parent non-comparative
sildenafil studies two events were reported, and in long-term extension
studies seven events were reported. All cases had medical histories with
risk factors for seizures, and none of the events were considered
treatment-related or serious by the trial investigators. Thus, the
clinical trial data provide no evidence of a causal association.
In a recently completed UK prescription event monitoring study conducted
by the Drug Safety Research Unit, wherein general practitioners submitted
AE data from over 20,000 men (receiving UK NHS sildenafil prescriptions)
followed for over a year, there was no signal of possible drug-related
seizures or convulsions.2
Since the approval of sildenafil in 1998, an estimated 20 million men
worldwide have received prescriptions for sildenafil.3 Pfizer receives
spontaneous reports of AEs from healthcare professionals and lay people
around the world. Analysis of this information is often very difficult
because of the differing and often low rates of reporting of events, and
the variable level and quality of information. As expected with such a
large population exposed, we have received a number of reports of events
coding as seizures but no evidence that the rates are above what would be
expected. In some cases ingestion of sildenafil is not confirmed. No
association between sildenafil and onset of seizures has been identified,
and no consistent pattern of reports has been seen. In particular repeat
seizures on re-exposure to sildenafil have not been reported to date.
Spontaneous reports of AEs such as those reported by Gilad et al
continue to be important sources of information. The report that one
patient twice experienced seizures shortly after apparent exposures to
sildenafil is very unusual. However, other factors that might predispose
to seizures such as low blood glucose levels or possible self-medication
with other drugs including alcohol have not been ruled out. As with all
products, Pfizer will continue to monitor the occurrence of all AE reports
including seizures and will periodically review the need to update the
prescribing information.
Ian H. Osterloh, MRCP,* Jeannette A. Barrett, PhD† and Dale B.
Glasser, PhD†
*Pfizer Ltd, Sandwich, Kent, UK
†Pfizer Pharmaceuticals Group, New York, NY, USA
References
1 Gilad R, Lampl Y, Eshel Y, Sadeh M. Tonic-clonic seizures in
patients taking sildenafil. BMJ 2002;325:869.
2 Shakir SAW. Director, Drug Safety Research Unit, Southampton, UK.
Personal Communication, 2002.
3 Padma-Nathan H, Eardley I, Kloner R, Laties AM, Montorsi F. A 4-year
update on the safety of sildenafil citrate (Viagra®). Urology
2002;60(suppl 2B):67-90.
Competing interests:
IHO, JAB, and DBG are employees of Pfizer.
Competing interests: No competing interests
Editor-Gilad et al reported tonic-clonic seizures in 2 patients
taking sildenafil. It is not clear why in both patients, brain CT and MRI,
were performed despite a
normal neurological examination with no deterioration reported.
Furthermore, plasma glucose or BM was not reported. Hypoglycaemia can
also cause seizures.
Their current medications, including over the counter ones, were not
mentioned. Some drugs can lower the convulsive threshold. Forther research
should also identify those adverse drug reactions.
Competing interests:
None declared
Competing interests: No competing interests
Sir,
Viagra is now a known but relatively new drug.
It sells well and makes huge profits for its manufacturers.
However almost beyond question is that for some people it causes
serious, even at times fatal adverse health problems.
The two case studies here are beyond dispute true and correct
findings.
The power of such investigations is two fold.
1 Case Studies show the bad side of a drug and not the (99.9%) good
side of those who are "affected" by it in only a positive way.
2 Case studies are a relatively cheap and powerful way of finding
problems with chemicals and adverse health effects, not "covering them
up".
The very expensive trials which proved this drug to be a toital
success are therefore fatally flawed when they can find the same problem
but dismiss them as not cause related. The 99.9% are OK so its just a
"nothing problem".
This in turn must mean that every safety check on every new drug
could be fatally flawed for the few who are susceptible.
So the question must be if we can allow such dangerous drugs to be
brought into use we need more intensive case studies to highlight not just
viagra but other drugs and identify the small but real adverse health
effects.
The effect to a friend who uses a new antidepressant causing aches in
every bone of the body indicates to me that this drug is not alone in
needing closer case study evidence and scrutiny.
My problem as a private researcher is that there is no public data
base so that it may be possible to identify why some people get these
effects and a screening process enabling prediction of bad effects in
advance for the few. For case study one, the repeat effect shows that this
is indeed a constant adverse effect. The two together give a speed to
disaster that is driven in a very precise bicohemical manner. More
knowledge may even allow us to predict in advance that another man would
experience the same effect at the same time if he too took the drug, but
with secrecy and jealous guarding of profits, it comes down to the
"reverse" of winning a normal "lottery". Pure chance whether it will be
heaven or HELL when you take this drug. Or maybe both?
John Fryer Chemist
Competing interests: No competing interests
there was a lot of hype about this drug especially by pharmaceutical
companies. now drama is unfolding. more and more side effects especially
cardiac are coming to light. now epilepsy. this should alert every
physician.
Competing interests: No competing interests
Re: Re: Former Viagra User
I returned yesterday from a cruise: Galveston, Texas to Mexico. On
Tuesday evening, I took 50 mg of Viagra as I am in the habit of doing. I
have taken Viagra for 2 years and have never had any problems that I know
of with its use. The time was about 10:00 pm and when I awoke, I was in
the ship's doctors office. When my girlfriend had tried to awaken me, I
was unresponsive and she called 911 on the ship. I was taken to the
doctors office and I believed treated with Valium to calm me down. I am
not sure of the tests that she ran on me but her opinion was that I had
had a gran mal seizure brought on by the Viagra. I am on disability for a
brain injury from 11 years ago and had been told that I suffer from petite
mal seizures, but they are very minor.
I dont know if this information is of any use to you but felt like someone
in the medical field should be aware of my experiences with this drug.
Thanks, Jim Lofland
Competing interests:
None declared
Competing interests: No competing interests