Eosinophils symptoms and conditions

My 3 yr old son has been taking Singular for about 1 1/2 years. He has been diagnosed with eosinophilic esophagitis. That dx came after an upper endoscopy. From about 10 months until starting Singular he vomited after every meal. Eventually had failure to thrive. He was on the Singular about 1 wk when he stopped vomiting. I am scared to take him off this med because it seems to work for him (with decreasing the vomiting). It doesn't actually decrease the eosinophils in his esophagus but somehow stops him from vomiting.He is a more difficult child but it is all we have really ever known from him. By difficult I mean- overly emotional, has trouble controlling impulses, occasionally mean. Does anyone have insight?

My daughter, who is eleven, now, was on singulair for about 5 years. She has been having a number of problems for a while now, but we never thought about it being the singulair until recently. She was having anxiety problems, tremors, being very argumentative, irritable, angry, depressed, pulling her hair out, (trichotillomania). I started doing research on her meds. (Zyrtec & Singulair) and was shocked to find so many other people were having these same symptoms, including several with the hair pulling. I took her to her allergy doctor and just told him I wanted to change her meds. and that I didn't care if they say these are "not" side effects. It was worth trying to see if things would get better. Well, she has been off the Singulair for about a month and half, and I am happy to report her hair is growing back, and she says she feels happy again. It breaks my heart to know that medicine that we had been giving her for so long was doing this to her. I also have decided a few days ago to take her off the Zyrtec after reading a lot of the same symptoms for it on this website.

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.

Below is the latest ADR report on Singulair from the United Kingdom. I deleted side effects reports by very small numbers of patients in order to keep the post briefer. This shows the total number of reports since Singulair was approved in the UK.

I don't know the total number of prescriptions for Singulair in the UK. It is considered expensive.

Drug Analysis Print
Drug name: MONTELUKAST
Drug name: MONTELUKAST Report type: Spontaneous
Report run date: 13-May-2008 Report origin: UNITED KINGDOM
Data lock date: 09-May-2008 08:00:02 PM Route of admin: ALL
Period covered: 01-Jul-1963 to 09-May-2008 Reporter type: ALL
Earliest reaction date: 01-Jan-1997 Reaction: ALL

Cardiac disorders-TOTAL 64
Palpitations 29
Myocardial infarction 6
Tachycardia 6
Diarrhoea 84
Dyspepsia 24
Abdominal pain 98
Abdominal pain upper 22
Nausea 84
Vomiting 52
Dry mouth 15
Asthenia 13
Fatigue 45
Malaise 32
Sudden death 1
Pyrexia 10
Chest discomfort 12
Feeling abnormal 16
Influenza like illness 17
Irritability 18
Drug interaction 13
Chest pain 13
Arthralgia 59
Myalgia 38
Muscle spasms 24
Pain in extremity 14
Balance disorder 10
Lethargy 16
Somnolence 23
Psychomotor hyperactivity 25
Headache 221
Dizziness 68
Neuropathy peripheral 7
Convulsion 6
Epilepsy 7
Dysgeusia 7
Hypoaesthesia 6
Tremor 18
Nervous system disorders TOTAL 526
Abnormal behaviour 13
Agitation 12
Anxiety 18
Aggression 30
Depression 23
Insomnia 58
Abnormal dreams 12
Nightmare 49
Hallucination 21
Sleep disorder 15
Psychiatric disorders TOTAL 364
Asthma 36
Allergic granulomatous angiitis 43
Angioedema 12
Swelling face 12
Erythema 13
Pruritus 32
Rash pruritic 17
Rash 55
Urticaria 33

TOTAL NUMBER OF REACTIONS 2841
TOTAL NUMBER OF FATAL ADR REPORTS* 19
TOTAL NUMBER OF ADR REPORTS* 1489

I spent the weekend reading about the development of Singulair. The early studies recognized that the first phase of the acute asthma response bronco-constriction was probably not caused by leukotrienes. They identified histamines and prostaglandins as the probable sources. I don't think that changed because the Singulair literature states that it should not be considered as a treatment for that. Leukotrienes were a source of inflammation caused by eosinophils and mast cells present in greater numbers (than normal) in airway tissue. So, it was beneficial to find a way to decrease that.

The cysLT1 receptor was identified as source of the signals that tell the cells to produce leukotriene. The receptor, a gene, consist of 337 (they think) amino acids. They modified a compound that would bind to that receptor thus blocking the cells ability to produce leukotrienes. This compound is very specific. It was formulated to bind to the "model" receptor. This compound will not even bind to cysLT receptor sub-types. (That is the good thing.) There is an enormous amount of research that discusses the genetic variability of the chemical reactions that occur in the leukotriene (calling it this for simplicity) pathway. We are also seeing that a number of researchers would like to use gene profiles to predict whether patients will respond favorably to different asthma/allergy drugs. ALL PATIENTS HAVE A RIGHT TO KNOW IF IT IS INHERENT THAT SOME PEOPLE WILL NOT RESPOND TO SINGULAIR OR RESPOND ADVERSELY.

There are many studies from the 1998 era that conclude that montelukast is not effective for everyone. Those researchers stated that it can be predicted that those people who are going to respond favorably will do that within the first 14 days or so. That conclusion would be consistent with a genetic component for efficacy and safety of Singulair. Those doctors concluded that those who did not respond within that time frame should not take Singulair for fear of harming them. That makes good sense.

The Italian researchers wanted to know if there was more going on than blocking leukotrienes in the action of montelukast. They set up a "test tube" study regarding montelukast, the cysLT1 receptor, and some t-cells that they selected. Why? Researchers always have something on their minds. They observed the death of these particular t-cells.

Montelukast is a quinoline. We basically know of quinilines and quinolones as compounds that were invented as broad spectrum antibiotics. They work because they interference with bacterial DNA so they cannot replicate themselves. Montelukast is a quinoline modified to bind with the cysLT1 receptor (a gene) and prevent that gene from activating. That's consistent with what a quinoline/quinolone does.

So what does montelukast do in blood plasma if it does not bind to the receptor because of genetic mis-match? (If montelukast does bind, then a chemical reaction has occurred and the liver will break down the by-products. Montelukast metabolized in 10-12 hours.) What happens if it doesn't bind? How long before it breaks down? Does it produce toxic by-products?

I want to know what happens to lymphocytes such as t-cells just because montelukast is a quinoline. Maybe nothing but what's up with the Italians researchers? I want to know if montelukast has the capability to interfere with lymphocytes who can clone themselves. That could be a good thing under circumstances when these lymphocytes are causing inflammation. But it could be a bad thing in the case of normal individuals with no problems.

I want to know if the bad side effects are due to the fact that the body has to break down and metabolize a quinoline that did not bind to the receptor for which it was created. The side effects of Singulair are strangely similar to what is observed in the quinolones such as levaquin. I have not as yet been able to compare montelukast as a quinoline to levaquin as a quinolone. I am hoping to find something on these categories. There may be no reason to worry that they cause similar damage. But frankly, I think that there is. There is some terrible chit happening to some people. The scariest is the neurological damage.

All of these questions would be in the everybody pharma knows to ask category. I don't know where the answers are. I haven't found them as of yet. Maybe there are no answers. We have to remember that Singulair and Vioxx were released in the same year. They have continued to be drugs under the current executive management of Merck. If the Vioxx marketing promoters had their ghost writers, why not the Singulair marketing promoters. The genetic component appears to be widely accepted but we haven't heard one thing about even that.

I think that it is sad that maybe the marketing of Singulair as one stop shopping for asthma/allergies may have destroyed the original concept. I really think from reading the original work that they knew that they couldn't engineer a drug for one size fits all. Everybody gets harmed when information is withheld.

Shame on the allergist who yelled at the mother who wanted to discuss issues. Does he know exactly who is allergic to Singulair and who isn't? Get him a dunce hat. Just because Singulair is marketed for allergies does not mean that you cannot be allergic to it. See the power of Madison Avenue? The ad agencies focus group these drugs to death. The ad agencies cleverly craft the product information. A good piece of legislation would be to prohibit consumer drugs ads.

CysLT1 receptor (the one that Singulair blocks) is also expressed (shows up) in the spleen. I have not seen anything yet that says what it does in the spleen. The spleen has important immune system functions especially in children. It contains B-lymphocytes that fight infection.

: Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:587-97.Links
Cysteinyl leukotriene receptors.Evans JF.
Department of Pharmacology, Merck Research Laboratories, Merck & Co., West Point, PA 19486, USA. jilly_evans@merck.com

The cysteinyl leukotrienes, leukotriene C4 (LTC4), leukotriene D4 (LTD4) and leukotriene E4 (LTE4), activate contractile and inflammatory processes via specific interaction with putative seven transmembrane-spanning receptors that couple to G proteins and subsequent intracellular signaling pathways. Pharmacological characterizations identified at least two subtypes of cysteinyl leukotriene (CysLT) receptor based on agonist and antagonist potency for biological responses. The rank potency of agonist activation for the CysLT1 receptor is LTD4 > LTC4 > LTE4 and for the CysLT2 receptor is LTC4 = LTD4 > LTE4. CysLT1 selective receptor antagonists are efficacious in the treatment of asthma. No selective CysLT2 receptor antagonists have been described. Molecular identification of the human and mouse CysLT1 and CysLT2 receptors has confirmed their structure as putative seven transmembrane domain G protein-coupled receptors and largely confirmed the previous pharmacological characterizations. The CysLT1 receptor is most highly expressed in spleen, peripheral blood leukocytes including eosinophils, and lung smooth muscle cells and interstitial lung macrophages. The CysLT2 receptor is most highly expressed in the heart, adrenal medulla, placenta and peripheral blood leukocytes. The molecular identification of the mouse CysLT1 and CysLT2 receptors show similar but not identical profiles to the orthologous human receptors.

PMID: 12432945

If anyone has any access to databases that can describe the history of drug licensing in other countries and whether Merck had to amend product statements, this is worth investigating. I do know that montelukast was at least not initially licensed for seasonal allergies in the United Kingdom when the FDA granted approval in the US. As of 2006, seasonal allergies were not on the approved listed in the UK.

More to add to the files:

Safety of leukotriene antagonists
United Kingdom — The Medicines Control Agency
has published a review of adverse drug reactions to
a new class of asthma drugs, leukotriene antagonists.
Zafirlukast and moltelukast, competitive cysteinyl
leukotriene type-1 receptor antagonists, were
both marketed for the first time in 1998.
Cysteinyl leukotrienes are inflammatory mediators
and potent constrictors of bronchial smooth muscle
that attract human eosinophils and cause airway
oedema, mucus hypersecretion and reduced
mucociliary clearance. By blocking this action, leukotriene
antagonists can improve respiratory function
and lessen symptoms in patients with asthma.
The pharmacological action of leukotrienes is quite
complex and varying side effects have been
reported. Zafirlukast inhibits the hepatic cytochrome
P4502C9, and interacts with warfarin, theophyllin,
terfenadine, acetylsalicylic acid and erythromycin.
Montelukast is metabolized by hepatic cytochrome
P450CYP3A4 and co-administration of such drugs
as phenytoin, phenobarbitone and rifampicin, which
induce this enzyme, result in a marked reduction in
plasma levels.
Side-effects identified during clinical trials were
headache, abdominal pain, nausea, diarrhoea,
gastro-enteritis, influenza, pharyngitis, sinusitis,
cough, nasal congestion, dizziness, fatigue and insomnia.
Since marketing of montelukast, 173 reports
of 317 suspected adverse drug reactions
have been received in the United Kingdom. These
include oedema (50), psychiatric reactions, including
including agitation/restlessness (15), allergy, including
anaphylaxis, angioedema and urticaria (10), chest
pain (7), tremor (5), mouth dryness (5), vertigo (4)
and arthralgia (3).
Reference: Current Problems in Pharmacovigilance,
Volume 24, August 1998.
https://www.who.ch/druginformation/vol12/12-4.pdf

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!

Unfortunately I also experienced such side effects from Levaquin to the degree that I feel I was poisoned. I was prescribed Levaquin April 2004 and a week later developed a 2" x 1" oval rash on my front hip area and had severe muscle aches and joint pain. My doctor prescribed a fungus cream for the rash (what???) and ran extensive blood and urine tests. The rash began multiplying daily until it covered half my entire body.
More tests (scared me to death -testing for Lupis, HIV, Hepatitis, etc.)
After all negative, he suggested I see a dermatologist and an allergist.
Rash worsened, could not sleep at all, not sure if it was from constant itch?? Non of the prescriptions from the dermatologist worked but a sample packet of "sarna or sarno?" helped dull the itch. Now it was a month since I started the Levaquin. A friend drags me to the ER. They actually get a cop in there to ask me if I have been beaten...um, no...I did it to my self..All the itching has caused me to scratch myself to the point of bruising all over. They ran a few tests and came running in with 2 doses of benedryl shots...said my eosinophils level was off the charts and that I had been having an alergic reaction to "something". Ah!! (duh!!) So I go home and search the internet... severe red rash, itching, insomnia, muscle aches, joint pain, allergic reaction....what comes up...levaquin levaquin and more levaquin. How did my own doctor who prescribed this to me not realize that this was an allergic reaction??? Most of my symtoms subsided 6 weeks later (after filling the scrips from the er for benadryl, prednisone and something else) but it was truly 6 weeks of hell and for a while there, I did not think it was ever going to end. Hope this info helps anyone who thinks they may be having a reaction to levaquin.