INTERAZIONI con FARMACI
AMIODARONE
Clinical observations with the amiodarone/warfarin interaction. Sanoski Cynthia A
Chest 2002,121,19-23L’amiodarone potenzia in modo importante gli effetti del warfarin.
Quando si aggiunge amiodarone ridurre la dose del warfarin del 30%.
Se si somministrano 400 mg di amiodarone ridurre del 40%.
Se riduco la dose dell’amiodarone a 100 mg aumentare del 5%.Il massimo dell’interazione si verifica alla 7° settimana con necessità di riduzione del 44% della dose del warfarin
L’interazione si completa a 6-8 settimane.
Considerare però che l’amiodarone ha una eliminazione imprevedibile e quindi nel singolo pz non sempre l’andamento dell’interazione è prevedibile.
CELECOXIB
Warfarin and celecoxib interaction in the setting of cytochrome P450(CYP2C9) polymorphism with bleeding complication.
Postgrad Med J 2004, Feb, Feb 80(940): 107-109- Malhi H
GEMFIBROZIL
Effect of gemfibrozil on the pharmacokintics and pharmacodynamics of racemic warfarin in healthy subjects.
Br J Clin Pharmacol 2005, 59, 433-9
Il gemfibrozil in vitro inibisce il citocromo CYP2C9. Inaspettatamente il gemfibrozil riduceva lievemente le concentrazioni di warfarin. Però potrebbe essere diverso nella pratica clinica.
GLUCOSAMINE-CHONDROITIN
Possible augmentation of warfarin effect by glucosamine-chondroitin-letter
Am J Health Syst Pharm 2004, Feb 1 ,61, 306- Rozenfeld V
INIBITORI POMPA PROTONICA
Curr Drug Metab. 2005 Oct;6(5):399-411. Related Articles, Links
Effect of Omeprazole on the Hydroxylation of Warfarin Enantiomers in Human: In-Vitro Studies with Liver Microsomes and cDNA-Expressed Cytochrome P450 Isozymes.
Zhou Q, Zhou S, Chan E.
Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Republic of Singapore. phaelic@nus.edu.sg.
Clinically observed warfarin-omeprazole interaction has been found to be associated with the inhibition of R-warfarin hydroxylation by omeprazole. The present study was conducted in human liver microsomes and cDNA-expressed cytochrome P450s to assess the inhibitory potential of omeprazole on the hydroxylation of warfarin enantiomers, and to identify the cytochrome P450 isozymes involved in the inhibition of hydroxylation of warfarin enantiomers by omeprazole, and to evaluate the extent to which the in vitro data is predictive of the actual pharmacokinetic interaction between warfarin and omeprazole observed in vivo. Omeprazole inhibited the formation of R-6-, R-7- and S-7-hydroxywarfarin with the K(i) values of 40, 22 and 116 microM, respectively. Its inhibitory effect was selective towards R-warfarin. Further study conducted in cDNA-expressed cytochrome P450s (CYPs) demonstrates that the inhibition of the in-vitro biotransformation of warfarin enantiomers by omeprazole is attributed to its inhibitory effect on the activities of CYP1A2, CYP3A4, CYP2C9 and CYP2C19. The extent of the in vivo warfarin-omeprazole interaction was underestimated as based on the K(i) values obtained from the in-vitro inhibition study, suggesting an underestimation of the effective concentration of the inhibitor at the site of interaction or some other mechanisms involve
INIBITORI del REUPTAKE della SEROTONINA (SSRI)
Arch Intern Med 2004,164,2367-70
Users of SSRIs face risk of abnormal bleeding. Studio caso-controllo su 64.000 pazienti.La serotonina interferisce con l’aggregazione piastrinica.
Il rischio di emorragie nei pz trattati con qs farmaci era di 1.9 (OR): emorragie endometriali, epistassi, gastroenteriche, cerebrali, ematuria, emottisi, emartro, ematomi.
Fluoxetina,fluvoxamina,paroxetina,sertralina,citalopram,
Effect of sertraline on protein binding of warfarin.
Clin Pharmacokinet 1997,32,suppl 1, 37-42- Apseloff GLa sertralina ha un effetto lieve sull’isoenzima del citocromo CYP2C9/10
MOXIFLOXACINA
Moxifloxacin and warfarin: additional evidence for a clinically relevant interaction.
Pharmacotherapy. 2005 Jun;25(6):904-7. Arnold LM, Nissen LR, Ng TM.
Department of Pharmacy, Boston Medical Center, Boston, Massachusetts.Several case reports have been published regarding an interaction between fluoroquinolones and warfarin; however, the exact mechanism of the interaction has yet to be established. We describe three patients who were receiving warfarin and experienced increases in international normalized ratio (INR) when moxifloxacin was added. Two of the patients had stable anticoagulation regimens and then experienced persistent elevations in their INRs shortly after therapy with moxifloxacin was started. The third patient experienced a dramatic rise in INR after the first dose of moxifloxacin was administered. These cases strengthen the evidence that an interaction does exist despite manufacturer-generated statements to the contrary. Increased awareness of this potential interaction is necessary to ensure appropriate monitoring and improve therapeutic decision making.
RISPERIDONE
Nose bleeds associated with use of risperidone.
BMJ 2004,Mira Harrison. Segnalati vari casi di epistassi e cefalea. Possibile interferenza con attività piastrinica.
Psychotropic interactions with warfarin-
Acta Psychiatr Scand 2000, 102, 250-5- Sayal KS
Controllare INR dopo 2-3 gg dall’inizio di un nuovo farmaco psicotropo o dalla variazione del dosaggio. Ricontrollare ogni 3-4 gg x almeno 2-3 settimane
I farmaci con emivita lunga come la fluoxetina devono essere monitorati più a lungo.
Le interazioni mediate da una induzione enzimatica possono durare anche un mese, x es carbamazepina.
STATINE
Il warfarin non interagisce con pravastatina e simvastatina. Interagisce con fluvastatina e atorvastatina.
FARMACI di IMPORTAZIONE
Intracerebral hemorrhage associated with use of an imported medication.
Am J Pharmacother. 2004, Sep, 197-200- Haidar WN
Descrive una grave complicanza emorragica secondaria all’assunzione di un farmaco etichettato come antiepilettico, ma in realtà contenente warfarin.
Si segnala il pericolo di rifornirsi via e mail o presso farmacie di altri paesi, perché possono avere un contenuto diverso da quello dell’etichetta.
AMIODARONE
Clinical observations with the amiodarone/warfarin interaction. Sanoski Cynthia A
Chest 2002,121,19-23
L’amiodarone potenzia in modo importante gli effetti del warfarin.
Quando si aggiunge amiodarone ridurre la dose del warfarin del 30%.
Se si somministrano 400 mg di amiodarone ridurre del 40%.
Se riduco la dose dell’amiodarone a 100 mg aumentare del 5%.
Il massimo dell’interazione si verifica alla 7° settimana con necessità di riduzione del 44% della dose del warfarin
L’interazione si completa a 6-8 settimane.
Considerare però che l’amiodarone ha una eliminazione imprevedibile e quindi nel singolo pz non sempre l’andamento dell’interazione è prevedibile.
Settembre 2005