Genetic variations symptoms and conditions

Has anyone been in contact with any doctors, hospitals, or researchers who are willing to recognize that Singulair targets a receptor CysLT1, with known genetic variations? As you know, I have been posting that I know of researchers who are doing work about how the genetic variations can determine the efficacy of Singulair. If genetic variations cause differences in efficacy, then, of course, these variations can also cause unpleasant to very serious side effects. These seems to be some kind of disconnect. How can the genetic component be recognized in the area of efficacy and ignored in the area of adverse drug reactions?

16 days ago on Jan 17, 2009 by chris555, #16131
Sorry to disappoint you, but I have no vested interest in Merck or any other pharmaceutical company for that matter. What I have a vested interest in is providing some balance to those parents who come to this blog site and are scared to death. That is what happened to a very good friend of mine. After reading the posts here, she was so panicked she took her 12 year old off Singulair. A kid who had no problems on it by the way. A few days later my friends kid was rushed to the ER and almost died from an asthma attack. That is what I have a problem with. People here telling others the side effects will creep up, that kids should stop their medication right away, etc.

Reply 8 minutes ago on Feb 03, 2009 by concernedcitizen, #16701
To chris555:

Merck warns on it's Singulair website that Singulair is not an effective replacement for fast acting inhalers in the event of sudden symptoms. Originally when Singulair was developed it's purpose was to prevent damage and inflammation that is caused by excessive number of eosinophils in respiratory tissue. There is no evidence at all that Singulair is effective as the only treatment for asthma to prevent or treat acute asthma attacks. And, Merck makes this very clear in the warning notice.

The efficacy and safety of Singulair has a genetic component. That means that it is entirely possible that some people are not compatible with the way in which Singulair works. Adverse side effects are very possibly the result of compatibility problems.

Sadly, Merck has succumbed to the disease of "corporate greed." Meaning that they care more about profitability and the shareholders than they do about the patients. For this callousness, some day this corporation will suffer the punishment. Merck has always known that the cysLT1 receptor is a gene with more than several variations. If they told doctors to watch out for side effects due to genetic variations, then they wouldn't be able to sell this drug like it's harmless - cherry chewable - candy. The adverse side effects are real. Patients started reporting them immediately when the drug was released. Singulair is dangerous to people with gene variations and it causes unnatural biochemical events to take place.

IMPORTANT SAFETY INFORMATION
SINGULAIR will NOT replace fast-acting inhalers for sudden symptoms. You should still have rescue medication available and continue to take your other asthma medications unless your doctor tells you to stop.

To get the real information in regards to what level of research that is going into this investigation is.go to the Institute for Safe medicine practices click on Quarter watch.
To people like chris555, I believe you are engaging people for sport and say very hurtful things,your day will come and it may just be in the unemployment line.I can only imagine that you must work for Merck or you would not feel so threatened by the good that has come from Parents advocating for their childrens safety.I want you to know, that all who knew our family and our child understand what took place and our reasons for trying to get the proper information where it should have been," on the label". When our child died no one knew about all the added side effects from post marketing reports,which is "a reliable way to track a drugs adverse events".Maybe you should do more research on the legitimate information of causal relationship. Don't be so afraid of a possible drop in revenue for the drug company that I believe you might be an employee of.K. M.

My nine year old daughter has been on Singulair for just over a month because of seasonal allergies. Early this morning she woke up with a terrible nose bleed. She has never had a nose bleed in her life before today! Could this be because of the Singulair?

This testimony should help strengthen our case for warnings for Singulair.

Neurologist Sought Warning for Pfizer Drug
By JEREMY SINGER-VINE
June 20, 2008; Page B10

A British neurologist who analyzed effects of the drug Neurontin told a court hearing Thursday that he advised its maker -- now a unit of Pfizer Inc. -- to include a warning on the drug's label for potential side effects of depression and aggression, but his advice wasn't followed.

The University of London neurologist, Michael R. Trimble, was testifying at a hearing to decide whether civil cases brought against Pfizer alleging suicides linked to Neurontin can proceed. The hearing was jointly held by judges for U.S. District Court in Boston and a New York state court who are hearing similar cases. In various lawsuits consolidated in the federal court, plaintiffs allege more than 100 suicides were connected to Neurontin usage.

Dr. Trimble described what he said was a "plausible biological pathway" that could lead from the compound gabapentin -- the chemical name for Neurontin -- to suicidal behavior, hostility, and aggression. Dr. Trimble said that in 1995 and 1996, he was hired to write two confidential reports for Parke-Davis -- now a unit of Pfizer -- because the company "was concerned about psychosis in relation to their drug." Dr. Trimble said he was unable to find a link to psychosis, but noted effects of depression and aggression.

Lawyers for Pfizer argued at the hearing that the evidence linking the drug to suicidal side effects wasn't scientifically sound. Under cross-examination, they challenged his description of a pathway as a patchwork of studies that didn't prove a biological connection. Neurontin and generic forms of gabapentin are approved for treating epileptic convulsions, but have also been prescribed widely "off label" for other conditions.

In five of nine patient cases he analyzed in 1996, Dr. Trimble said he saw depression and aggression in patients who had no previous symptoms of the side effects, so he said he recommended to the company that the drug "should carry some kind of warning" for susceptible patients.

Thursday's proceedings were the initial phase of a hearing requested by Pfizer to challenge the opinions of the plaintiffs' experts. Under cross-examination and a subsequent examination by the plaintiffs' attorney, Dr. Trimble said the biological pathway between Pfizer's Neurontin and suicidal events were plausible and supported by a series of peer-reviewed neurology research.

Here is one for you Artie. Maybe you can go find the statistical profile of studies regarding montelukast and CYP2C8. Originally it was hypothetized that montelukast would inhibit CYP2C8 thus inhibiting steroid (as an example) metabolize. In vitro studies predicted that. Then studies in vivo didn't confirm. Here is another one done in 2006.

Conclusions: Telithromycin increases the plasma concentrations and blood glucose–lowering effect of repaglinide by inhibiting its CYP3A4-catalyzed biotransformation and may increase the risk of hypoglycemia. Unexpectedly, montelukast has no significant effect on repaglinide pharmacokinetics, suggesting that it does not significantly inhibit CYP2C8 in vivo. The low free fraction of montelukast in plasma may explain the lack of effect on CYP2C8 in vivo, despite the low in vitro inhibition constant, highlighting the importance of incorporating plasma protein binding to interaction predictions.

http://www.nature.com/clpt/journal/v79/n3/abs/clpt2006320a.html

The question would be is that always the case or are there genetic variations among people that influence the outcome? Or is there potentially something else that we should be recognizing and we aren't doing that.

I thought of that again when I read this post. We obviously have many questions that should be answered especially when something that we don't expect happens.

Posted by Mindy Miller
Monday, April 14, 2008 4:39 AM EST

I am a pharmacy student and a mother of two sons that take Singular daily. My six year old has been taking it for 4 years, and my three year old for two years. They both have well controlled asthma. I wanted to reply to the questions many have posted about how long it takes to "get out of your system". The half life of Singular is 3-6 hours, so it is gone in a maximum of 18 hours. I came to this website while searching for information about recent FDA warnings. As far as I can tell, there are very few cases documented of mood changes and suicidal thoughts. There are many reasons why children have mood changes, and not feeling well because they have asthma and allergies could also be the source. I wonder if many who start Singular are also taking Prednisone, a steroid, to treat an asthma flare up. Steroids are definitely known to cause mood changes and is one of the reasons they can't be used long term. Please talk to your doctor or pharmacist before taking your children off of medication that may be helping them feel better in the long run.

http://www.injuryboard.com/national-news/fda-issues-early-warning-on-singulair-and-suicides.aspx?googleid=30278

If we had all of the answers, then there would not be such a wide range of symptoms that manifest themselves as a result of Singulair. So I am not trying to spread any conclusions that may be misleading. These are questions and not answers.

UPDATE: Our nightmare with SINGULAIR has not ended! After reading "conerned citizens" report discussing the possiblility of Singulair causing asthma blew me away. My son was put on this drug for food allergies not asthma b/c they thought of his two anaphylaxsis episodes in 5 days. 1 food related the other unknown (maybe outdoor mold?) He had no prior issues with breathing.

He has been off of it for almost 2 weeks however over the last week he has slowly developed some breathing issues. After getting off of it, he still has his ear infection from the second day of being on it and last Friday after playing some basketball began to seem like he was winded so I brought him in. He was having trouble breathing. I called the Dr. and he said it could be excercised induced asthma. He is a very active boy who runs non stop and has NEVER had breathing issues before Singulair! It seemed to pass after a few hours. The next fews days he coughed a few times when playing and I thought what the heck is happening to him. Monday at school they didn't go outside so he was fine b/c he didn't run around. Tuesday, they came to get me b/c he was having trouble breathing and one of his teachers whose son has asthma said I think you better give him an inhaler. I called the Dr. ASAP and he approved us to borrow another child's. He freaked out and wouldn't let us give it to him. After 2 epi-shots in the previous weeks, he wanted nothing to do with that. At school the next day, we made him take the inhaler if he wanted to go out to playso he did. He didn't cough but a few times. No excercise at all. Then last night, he got really bad. He started to cough and couldn't stop to the point of gaging and it seemed as though he had developed a ton of phlem and kept trying to swallow. We ended up in the ER where we were told that he has asthma! I am so furious! I don't get this at all! If this report is accurate and my son got asthma by going on it - this will be devastating. We kept him home today from school and took him into the Dr. b/c he continued to cough all night. He is now on Flovent, Albuterol and has an enebulizer. I'm probably the only one of all of us who child did not have asthma to begin with.

Has anyone who did not have asthma before singulair now have any issues? Please let me know!