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Pharmacogenetics of Drugs Withdrawn From the Market


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From 1922 to the present, numerous severe adverse drug events have occurred from the reduction of white blood cells by aminopyrine to 2010's 'Avandia' event, which has potentially caused tens of thousands of deaths or disabilities. In fact, since 1960, approximately 150 prescription drugs have been removed from the market for various safety issues.[2] We analyzed information and reasons published by the US FDA and previous reports regarding the drugs' recall and withdrawal; the top nine safety reasons for withdrawals were hepatotoxicity (27.9%), cardiovascular toxicity (17.4%), hematologic toxicity (10.4%), cutireaction (7.0%), carcinogenicity (6.3%), neurotoxicity (6.3%), nephrotoxicity (5.6%), allergy (3.5%) and drug abuse (3.5%).[2

Genetic factors and gene polymorphisms not only lead to individual variations in clinical drug effects and toxicities, but may also result in withdrawals due to the ADRs in specific genetic populations. For example, many drugs were withdrawn from the market as they cause long QT syndrome (LQTS). There were five genes and their mutations have been implicated in LQTS:KCNQ1hERGSCN5AKCNE1 and KCNE2.[3] One study explored the mutation rate of these five genes and found that the mutation rate reached 68% in 262 LQTS individuals. Among the mutations, genes KCNQ1 (42%) and hERG (45%) accounted for 87% of identified mutations, and sodium channel genes, SCN5A (8%), KCNE1 (3%) and KCNE2 (2%) accounted for the remaining 13%.[3] Therefore, it is prudent to prescribe some drugs based on variation in these enzymes, for example antiarrhythmics which can lead to acquired LQTS. When the drugs are used in the people that carry mutations in the five risk genes, the risk of LQTS may increase. This review evaluates the possible relationships between other drugs withdrawn from the market and the genes that may imply risk (Table 1).

I was surprised the Gene mutation rate to be 68% it would seem anyone having an SAR would be tested for mutations not just sent out into the world to take their chances with meds. The article goes on to discuss the genetic connection in why these drugs were pulled from the market. 

 

I was also surprised to see some of the drugs that caused death had serotonin and norepinepherine involvement. 

 

 

http://www.medscape.com/viewarticle/757499

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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The Personalized Medicine Product Portfolio Selected Personalized Medicine Drugs, Treatments, and Diagnostics as of September 2011

http://www.ageofpersonalizedmedicine.org/personalized_medicine/portfolio/

 

The drugs and diagnostic tests listed in the table below are the leading edge of a wave of new personalized medicine products likely to emerge over the next several years. They are the dividend from government and pharmaceutical research company investment into biomedical and human genome research.

Therapeutic product label contains pharmacogenomic information as:   Information only   Recommended   Required
 
Unhighlighted products have no pharmacogenomic information, recommendations or requirements in the label

This list is not intended to be comprehensive but reflects commonly used or available products as of September 2011. Some products, for which the FDA recommends or requires pharmacogenomic testing or which have pharmacogenomic information in their label, are listed at the FDA's Web site. Other listed products that are novel, and/or that address large populations, have been identified via websites and public announcements.

Some of the drugs you will find at this link are:

Depakote®(divalproex) Bipolar disorder: “Hyperammonemic encephalopathy, sometimes fatal, has been reported following initiation of valproate therapy in patients with urea cycle disorders [uCDs]...particularly ornithine transcarbamylase deficiency [OTC].”

Coumadin®(warfarin): Cardiovascular disease: DeterminesCYP2C9 and VKORC1 genotypes to predict likelihood of adverse events with warfarin therapy.

Lipitor®(atorvastatin) LDLR Cardiovascular disease: “Doses should be individualized according to the recommended goal of therapy. Homozygous Familial Hypercholesterolemia (10-80mg/day) and heterozygous (10-20mg/day).”

Statins: Cardiovascular disease: Predicts risk of statin-induced neuro-myopathy, based on a patient’s combinatorial genotype for 50 genes.

Tegretol®(carbamazepine):Epilepsy and bipolar disorder: Serious dermatologic reactions are associated with the HLA-B*1502 allele in patients treated with carbamazepine. “Patients with ancestry in genetically at-risk populations should be screened for the presence ofHLA-B*1502 prior to initiating treatment with Tegretol®. Patients testing positive for the allele should not be treated with Tegretol® unless the benefit clearly outweighs the risk.”

Drugs metabolized by Cytochrome P450 test is called...Amplichip®CYP2D6/CYP2C19

Drugs metabolized by Cytochrome P450

2C19: carisoprodol, clopidogrel, dexlansoprazole, diazepam, drospirenone & ethinyl estradiol, esomeprazole, modafinil, nelfinavir, pantoprazole, prasugrel, rabeprazole, ticagrelor, voriconazole

2D6: aripiprazole, atomoxetine, carvedilol, cevimeline, chlordiazepoxide & amitriptyline, citalopram, clomipramine, clozapine, codeine, desipramine, desloratadine & pseudoephedrine, dextromorphan & quinidine, doxepin, fluoxetine, fluoxetine & olanzapine, fluvoxamine, galantamine, gefitinib, iloperidone, imipramine, metoprolol, modafinil, nefazodone, nortriptyline, paroxetine, perphenazine, pimozide, propranolol, propafenone, protriptyline, quinidine, risperidone, terbinafine, tetrabemazine, thioridazine, timolol, tiotropium, tolterodine, tramadol & acetomenophen, trimipramine, venlafaxine

 

Celebrex®(celecoxib) Pain: “Patients who are known or suspected to be P450 2C9 poor metabolizers based on a previous history should be administered celecoxib with caution as they may have abnormally high plasma levels due to reduced metabolic clearance.”

 

Enbrel® (etanercept)

Remicade®(infliximab) Psoriatic arthritis: This sequencing-based assay detects the presence of gene variant MICA-A9, indicative of an increased risk of psoriatic arthritis. Identification of risk could guide monitoring and early treatment with TNF-alpha antagonists.

 

Psychiatric drugs Test: GeneSightRx®Psychiatric disorders: Genetic variants (CYP1A2CYP2D6CYP2C19, serotonin transporter gene SLC6A4, serotonin 2A receptor gene 5HTR2A) in this test may affect a patient’s ability to metabolize, tolerate or respond to 26 psychotropic medications.

 

Risperdal®(resperidone)

Zyprexa®(olanzapine) Test: PhyzioType PIMS Psychiatric disorders: Predicts risk of psychotropic-induced metabolic syndrome, based on a patient’s combinatorial genotype for 50 genes.

 

There are many other drugs and tests at the site I put the ones I hear the most about here.  It seems to me a lot of cancer drugs made the lists for all different types of cancer treatment. 

 

If your not in an emergency situation asking to be tested for these mutations before starting a drug could spare you a Sever Adverse Reaction. 

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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For me this search stated by me trying to find why a drug I use to take for migraine called Wigraine was not longer sold I still don't know as it was not on the list.  I have reacted to other drugs on the list and intend to do some research on those genes I will ask for testing given all my drug reactions,  and maybe save myself some grief. 

If you have reacted badly to drugs in the past checking the links may be in your best interest. 

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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