We have reached note number 9269. For 2010, 2918 new notes were added and approximately 2000 old notes were checked for accuracy, updated and re-written. Since August, more than one hundred and ten drugs have been extensively reviewed and product inserts replaced. including:
azelaic acid topical (Finacea topical)
aztreonam inhaled (Cayston)
brimonidine Ophthalmic (Alphagan)
bromfenac Ophth (Xibrom)
caspofungin (Cancidas )
cisatracurium besylate (Nimbex)
colesevelam hydrochloride (Wechol)
daptomycin ( Cubicin )
ethosuximide (Zarontin )
fenofibric acid (Trilipix )
fingolimod ( Gilenya)
megestrol (Megace ES)
miglustat ( Zavesca)
niacin vitamin B3
paclitaxel [ just product insert, not review of drug} pancrelipase (Creon) pegloticase (Krystexxa) pilocarpine ophth piroxicam (Feldene) pitavastatin
rabeprazole sodium (Aciphex)
solifenacin=== pure cyp3a4 substrate
We are working on separating notes that can refer to drugs that are both drug themselves and active metabolites of other drugs. A complete review will be silently released when finalized.
In addition to extensive notes, drug metabolism information, and drug interaction updates, improvements you will notice include:
- Priority Ordering - Notes are now displayed in ranking order by impact, major interactions will display first.
- Clinical and Algorithm Predictions Color-coded – Background color is displayed for either the clinical or algorithm description whichever is greater.
- Food interactions – If you add food from the standard drug selection list, GeneMedRx will warn you if the medication should not be taken with food.
Survey Question: If emsam and trazodone are entered in the program only emsam currently displays in red with the note:
|Proserotonergic and MAO Inhibitors||Review|
Combinations of these drugs are known to cause the serotonin syndrome and should be avoided.
Note 6206 Reviewed 2010-02-12
|PubMed ID: 18759711|
Since both drugs are impacted should the increase and note display on both or should it be left as is? Email firstname.lastname@example.org with your preference.
In addition to extensive notes (there are now over 8000), drug metabolism information (over 3600 pathways), and drug interaction updates, improvements you will notice include:
- Improved Speed and Usability You will notice improved speed on the new server as well as usability upgrades including patient search functionality for over 20 patients saved, back button logout warning, and logout confirmation.
- Clinical and Algorithm Predictions Displayed Predicted changes for multi-drug interactions now show the algorithm-predicted change for all drugs involved as well as the clinical study results for each drug pair involved. This enables users to take better advantage of the algorithm's ability to predict multi-drug interactions.
- Improved Reporting A number of redundant notes have been eliminated. In addition, we have removed drug class and additive information from the results table to make the information more digestible. Additive information is now only in notes.
- Improved Interaction Predictions Most interactions which have been reported as minor are now included without that designation; this will improve the accuracy of predictions.
- Secure Sharing of Patient Genotype Other authorized healthcare providers can now access patient results with a lab number, patient name, and date of birth.
As always, your feedback and suggestions are encouraged and appreciated. Thanks for working with us to improve this tool for safer and more effective prescribing.
In addition to extensive note and drug interaction updates and improvements you will notice:
- Cytochrome P-450 2C9 Gene-Drug Interaction Update An extensive review of the literature was completed and all relevant drug-gene interactions were entered or updated. Presentations on this and other previous focus updates are available at http://personalizedmedicineblog.com/recommended-presentations.
- Confidence Ratings The confidence ratings given to evidence supporting the interaction notes has been streamlined and made easier to compehend. It now takes less space which reduces scrolling while reading notes.
Narrow Therapeutic Index Medications Highlighted. Medications such as warfarin that have a narrow therapeutic index are displayed with this icon so you are aware that even small changes may be of concern.
Mechanism Based Inhibition Highlighted. If medications with mechanism-based inhibition such as indoramin and citalopram are entered the interaction details will display with a icon. This it to make you aware that the affected enzyme is completely destroyed in the process and that recovery will require several days to two weeks after inhibition is stopped.
Expanded Drug-Gene Interaction Prediction Capability - 5HTT, DPD, HER2, HLA-B*5701, MTHFR, TPMT, and UGT1A1 genotypes have been added to the program, and CYP1A2 genotypes are active again.
Alternative Drug Options Refined. Drugs not available in the US, and drug classes that are not appropriate alternatives are no longer displayed.
- User Interface Update. The interface has been updated to accommodate smaller screens more effectively.
- Shorthand Names Added. Common shorthand names such as ASA for aspirin have been added as alternative names.
- Plavix (Clopidogrel) 2C19 Genetics Update. The recent landmark studies published in the January issue of NEJM on the increased risk of serious cardiac events for patients with 2C19 inactive alleles have been incorporated into the program.
- More Notes. The number of notes is approaching 6000.
- Interaction Prediction Algorithm Refinements. Incorporating the many minor pathways being reported in the literature had the effect of diluting the predicted impact of major pathways. Now each major pathway is assigned at least one third of the total metabolism (unless there are more than three).
- Refined Prediction of Gene-Drug Interactions. For example it now reports correctly the special case of two drugs which normally interact but do not if the person is a poor metabolizer of the CYP involved (2C19 Poor Metabolizer, diazepam and fluvoxamine).
- Invalid Base 64 Error Message Resolution Users may occasionally see an “Invalid Base 64” error when an older record is retrieved from the database and cannot be decrypted. If you see this message the data is still available but the label for it is not valid. If you change the label on the data it will be re-encrypted and work fine in the future.
- Record Saving Error Corrected. Some users were intermittently unable to save some records.
November 19, 2008 Version Upgrade
GeneMedRx will be updated the evening of 11/19/08. In addition to extensive note and drug interaction updates, improvements you will notice include:
Expanded Drug-Gene Interaction Prediction Capability - VKORC1 genotypes for warfarin sensitivity have been added to the program.
Alternative Drug Options Now Printable. The alternatives section now has a print option.
Printing Error Corrected. Some users were unable to generate printed reports that matched the interaction screen. We believe this error has been corrected.
Saving Error Corrected. Some users were intermittently unable to save or retrieve some records. We believe this error has been corrected.
Note 5460 reached
Read A Riley’s review of Prasugrel PMID 18499874 and no new information added. Atorvastatin is a SLCO1B1 inhibitor and repaglinide, a substrate, and therefore genetic variations of the transporter will affect outcome of drug interaction. PMID 18418370.
Oral contraceptives increase levels of melatonin 4-5 fold PMID 18490497. A short review of immunosuppressive drugs by Elbarbry et al PMID 18475175 read and a few drug interactions refined. Erythromycin is a substrate of SLCO1A2 and SLCO1B3 PMID 18509328. Reviewed product insert of etravirine (Intelence) HIV drug approved in 2/08 by FDA.
Diclofenac patch (Flector) product insert reviewed.
Ixabepilone (Ixempra) product insert reviewed. Alteplase, urokinease and tenecteplase product inserts reviewed. Rosuvastatin and atazanavir/ritonavir and fosamprenavir/ ritonavir added PMID 18520949 .
Nifedipine is not a CYP3A4 inhibitor- corrected. Nimodipine product insert reviewed. Diltiazem product insert reviewed.
Thrombolytics added. Aritcle on Clinical phsarmacology and pharmacogentics of thiopurines by S Sahasranaman reviewed and several drug interactions added. Another article on Thiopurine reviewed by Teml A PMID 17328579.
Levodopa/carbodopa was in the program as well as carbodopa/levodopa. Septocaine was in the program as well as its generic. The trade name entry was deleted. Reviewed verapamil DDIs.
Review product insert of Methylphenidate, dxtroamphetamine and Strattera and added several notes. Added Stavzor as new formulation of valproic acid just approved by FDA. Reviewed its product insert for drug interactions and modified some DDIs. Zofran product insert.
Reviewed galantamine product insert. Reviewed letrozole product insert. Reviewed Valsartan product insert. Reviewed Valdecoxib product insert. Reviewed Zelnorm product insert.
Imatinib product insert review. No additional DDIs added to the program. Reduced the drugs with QTc to the known list on Torsade- org. Corrected 2C9 for 2C8 as an inhibitor of Provigil. Article by Funk on hepatic transporters reviewed and all of the drugs known to be transported by the SLCs and ABCs are added to the program- about 40 new entries. A review article on Ivermectin PMID 14881879 proved useless in providing any DDI data. New data on baicalin, an herb as a SLCO1B1-OATP1B1 inhibitor was added. Gabapentin is a substrate of SLC22A4-OCTN1- and was added. Imatinib is a substrate of SLC22A1-OCT1. Review of smoking and the DDIs with drugs was undertaken.
More than 20 new notes were added. This is an old literature- some of it more than 30 years. For drugs like ramelteon, that are CYP1A2 substrates, it is surprising that there are no studies. L Kroons article on smoking was also reviewed and few details added to most important DDIs with smoking. Several drug interactions with ropivicaine were added. Clomiphene was just reported in PubMed to bea substrate of CYP2D6. Article on food interactions and dietary interactions by NJ Anzenbacher added. Robertson et al's article reviewing the drug interactions in the management of HIV infection in 2007 reviewed which was carefully read and several DDis added to or added on PMID18001255. Nexavar updated from the product insert.
Medical Letter reviewed artesunate briefly and search of literature revealed 2 clinical studies of possible DDIs which were entered.
Made sure all of the ritonavir-boosted protease inhibitors were in the class and that they were not listed as mixtures to allow for the possibility that they have a different impact on metabolic pathways than the individual components. Article on SULTs by Lindsay reviewed- disappointing article since few substrates, inhibitors or inducers mentioned. Known DDIs involving ABCB1 were reviewed. An article by Wittkowski on herbs and oral anticoagulants PMID 17906915 discussed the cranberry juice warfarin interaction and dismissed it.
Read an article on SULT1A1 by Hempel PMID 17110154 with little information. Long and detailed article by Koepsell on Cation transporters read and a vast amount of details about these transporters was added to the data base. Goldenseal as a CYP inhibitor was investigated and it is likely to be a CYP2D6, 2E1 and intestinal CYP3A4 inhibitor. Study of etravirine and omprazole or ranitidine added. Article by Shitara et al PMID 15822193 EVALUATION OF DRUG-DRUG INTERACTION IN THE HEPATOBILIARY AND RENAL TRANSPORT OF DRUGS read and a few drug interaction notes beefed up. An article by Jung N on the relevance of the organic cation transorter 1 and 2 for antiretroviral drug therapy in HIV infection PMID 18491433 was reviewed and a few substrates and inhibitors of OCT1 and OCT2 added.
Note 4896 reached
Continued to go through all of the drug entries from Z up to check names, classes and websites. Added all drug interactions from aripiprazole product insert. Added l-methylfolate and drug interactions suggested by a subscriber who received an extra 3 months of subscription. Separated folinic acid from folate in drug entry since they are handled differently by the body and the former is given with methotrexate and the latter may interfere with methotrexate. Article on ABCC4 by Russel FG PMID 18353444 reviewed and substrates and inhibitors listed added. Article by Back D et al on Darunavir PMID 18389894 was reviewed and all of the listed DDIs were reviewed. Only one new DDI was added, with digoxin. Reviewed an article by El-Sheikn PMID 17005917 which discussed studies of methotrexate and NSAIDS- the former use basolateral transporters in the renal proximal cell SLC22A6 and SLC22A8 for uptake and ABCC2 and
ABCC4 in the luminal or apical membrane to extrude methotrexate into the collecting tubules. NSAIDs may block all or some of the pathways. Tried to find drug interactions involving SLCO1B1 by googling it. Found Nelfinavir and pravastatin, and lopinavir/ ritonavir and rosuvastatin as new DDIs. Ritonavir appears to be a
SLCO1B1 inhibitor. Pravastatin is an archetype SLCO1B1 substrate.
Read Niwa’s article about serotonin-3 receptor antagonists and added data PMID 16946512. Antiplatelet class of drugs checked for accuracy. Abciximab product insert reviewed. All glucuronidation substrates and inducers reviewed to make sure they do not contain specific UGTs. On-line review of OCs and HIV products reviewed. All drug combinations already had notes, but efavirenz note strnghtened by suggestion of lab test interference leding to increased OC levels since efavrinez is usually a CYP3A4 inducer. NNRTs and NRTs induction of ABCB1 was reviewed in an article by J Weiss PMID
18037401 and added to the program. Treximet added (sumatriptan and naproxen). All of the aliases for HIV drugs were added and new combination drugs placed in the protease inhibitor class.
a class="answerlink" href="http://www.answers.com/topic/amerisourcebergen-corp?nafid=22">ABC transporters reviewed from article by Calcagno A et al:ABC drug transporters as molecular targets for the prevention of multidrug resistance and drug-drug interactions. Curr Drug Deliv.2007 Oct;4(4):324-33. PMID: 17979652.
Both sulfamethoxazole/ trimethoprim and trimethoprim/sulfamethoxazole were entered. Notes were re-entered as needed.
Article on ABCG2 is reviewed and added to program.
New phase 3 antibiotics dalbavancin and telavancin added. Bailey J, Summers KM. Dalbavancin:a new lipoglycopeptide antibiotic. Am J Health Syst Pharm. 2008 Apr 1;65(7):599-610.
Major project of reviewing all of the drug entries has begun starting with Z. AMD070, a new HIV drug in Phase 3 studies of FDA which is a chemokine coreceptor (CXCR4) was entered into the database.
Trade names of anti-malarials checked.
Induction of CYP2B6 and CYP2C19 for the aremisinin antimalarials entered.
PubMed reviewed for new additions for the following entries: “drug interactions; P450 cytochromes, UGT, glucuronidation, transporters, ABC transporters, SLC transporters, CYP1A2, 2B6, 2C8, 2C9. 2C19, 2D6, 2E1, 2A6, 3A4, 3A5, 3A7″.
Polli JW The Role of Efflux and Uptake Transporters in Lapatinib (Tykerb, GW572016) Disposition and Drug Interactions.Drug Metab Dispos. 2008 Jan 23 reviewed.
Updated the current oral contraceptives with information from Therapeutic Gudelines 2007.
Terbinafine (Lamisil) drug interactions reviewed.
Maraviroc (Selzentry) interactions added from the product insert. This drug is likely to be a CYP2D6 inhibitor at higher dosage (600mg/day).
Bystolic product insert reviewed and drug interactions added.
New formulation names of B12 added. Ki of cinacalcet added; it is amongst the most potent CYP2D6 inhibitors. Reviewed the product insert of tipranavir (given with ritonavir) and about 25 new notes added.
Advicor (a mixture of niacin and lovastatin) added.
Essiac, an herbal mixture was added.
Class of tandospirone added.
There was a glitch in the program regarding multiple notes attached to the same number of note. Bob Patterson fixed the glitch in an elegant way and Note 28 on buspirone and a variety of CYP3A4 inhibitors had to be re- entered.
Added several drugs to the anticholinergic class list and the NMDA antagonist list.
Added huperzine A (Chinese Club Moss) to list of drugs which is metabolized by CYP1A2.
Article about herbals and chronic illness by Gardiner PG reviewed and found minimally helpful. Baciewicz AM, Chrisman CR, Finch CK, Self TH:Update on Rifampin and Rifabutin Drug Interactions.Am J Med Sci. 2008 Feb; 335:126-136 reviewed. Wen X et al. Trimethoprim and sulfamethoxazole are selective inhibitors of CYP2C8 and CYP2C9, respectively. In Drug Metab Dispos. 2002 Jun;30(6):631-5 reviewed. Masters PA, et al:Trimethoprim-sulfamethoxazole revisited.Arch Intern Med. 2003 Feb 24;163:402-10 reviewed. Tirkkonen T et al:Frequency and clinical relevance of drug interactions with lovastatin and simvastatin : an observational database study.Drug Saf. 2008;31(3):231-40 reviewed and added to references. Note 4801 reached.
Reviewed and added drug interactions from product inserts of ribavirin and peginterferon alfa 2a and 2b.
From PubMed, reviewed the last year of UGTs and entered data.
Reviewed Spectrum of Antiepileptic Drug Interactions: Perspective on Valproate by Carol Collins, MD 2005 and added additional information to valproic acid.
Read Drug Interactions in Inflammatory Bowel Disease by Irving et al 2008 and added additional information. Checked new articles from PubMed.
Sevelamer DDIs added with the FDA approval of a new product, Renvela. Ixabepilone (Ixempra), a new breast cancer agent was added. Doripenem, a newly FDA approved antibiotic was added.Reviewed venlafaxine. duloxetine, all of the anticonvulsants, the Triptans, and the “Z” drugs. Added new clinical studies on CYP, UGTs, and transporters from PubMed. </span
Reviewed methadone through excellent on-line review at http://genemedrx.wordpress.com/wp-admin/www.atforum.com/pdf/Drug_Interactions.pdf. Happy to report that all of the major DDIs were already in the program. Added grapefruit juice and methadone which has a modest DDI. Reviewed all of the DDIs of etanercept (Enbrel). Somewhat confusing review article byMahmood I, Green MD. Drug Interaction Studies of TherapeuticProteins or Monoclonal Antibodies.J Clin Pharmacol. 2007 Oct 25; [Epub ahead of print] was reviewed. Carvedilol, inderal, metoprolol reviewed. Nilotinib, a newly FDA approved drug added with DDIs.
September and October 2007
extensive review of solute-linked carrier (SLC) transporters undertaken. Notes 3067-3080 updted.Ambrisentan (Letaris) was added. New PubMed articles reviewed and data added.
July and August 2007
substrates and inhibitors of CYP2D6 reviewed.Extensive review of ATP-binding cassette (ABC) transporters and their DDIs.
CYP2B6 was reviewed and new substrates and inhibitors were added. Oxcarbazepine product insert was reviewed. Leflunomide product insert was reviewed. Excellent review article on drug interaction involving transporters in the kidney by M LI , GD Anderson and J Wand in Expert Opinion 2006 was reviewed. Several transporter names were updated and about 30 new DDIs involving transporters were added. More than 40 pro-drugs were reviewed.Sitaxsentan was reviewed from a review article by Neal J. Benedict, 2007. Notes from 2700 to 2840 reviewed. Tamiflu was reviewed. Most interesting DDI is the inactivation of Tamiflu, a prodrug, by Plavix a prodrug. Shi et al 2006. Venlafaxine DDIs reviewed from product insert and search on PubMed.
May and June 2007
Major review of CYP3A4 inducers. Corrected class of inhaled corticosteroids and added a note for all potent inhibitors of CYP3A4 which can result in Cushings syndrome. Reviewedall DDIs of modafinil in PubMed. Reviewed Vyvanse product insert.Reviewed article by McCabe titled “Drug Interactions between propton pump inhibitors and antiretroviral drugs”. Reviewed invitro inhibition data on artemisinin anntimalarials PMID 17521300.temsirolimus CYP pathway added.
Reviewed notes from note 2840 to 3066. Whether valproic acid is an inducer has been a question for many years, and recent in vitrro evidence shows that it can be an inducer of CYP3A4.Aprepitant product insert was reviewed. It shifts from a mild CYP3A4 inhibitor at low dose to a moderate inhibitor at higher dose and finally to and inducer after 30 days. An older review of clinically relevant DDIs in oncology (PMID 9663808) was reviewed in order not to miss some well known DDIs described in the 1990s. Tenofovir (Viread) product insert was reviewed and added as well as PubMed DDIs and an IV website-http://www.i-base.info/pub/htb/v4/htb4-9/Tenofovir.html.UGT 1A9 added as a minor UGT pathway for indomethacin PMID17245571. Cyclosporine/mycophenolate DDI was reviewed and new infoadded PMID 17201457. Product inserts of Zolinza, Baraclude, Ontak, Seroquel reviewed and DDIs added. Tizanidine revision of product insert added. Sustiva product insert revisions added Sustiva: PMID:17407831. Drug interactions of new direct rennin inhibitor, aliskiren from The Medical Letter April 2007 as well as those found in PubMed added. It is likely renal transporters are involved in the DDIs withketoconazole or furosomide, but no information can be found.Continuing to add transporter information from an excellent review of the liver-specific OAT1B1 and 1B3 by Nicola F Smith et al (PMID 16863454). Starting to separate out the different substrates of individual members of the CYP3A family- CYP3A5 especially. There is considerable new data on the genetics of this subfamily- showing thatCYP3A5 may make an important contribution to metabolism of some drugs like midazolam, testosterone etc. Reviewed the PubMed DDIs of zafirlukast and methylprednisolone and added several new DDIs.
Up to note 4357.