Education grant to fund the project

Size: px
Start display at page:

Download "Education grant to fund the project"

Transcription

1 Education grant to fund the project

2 Author Rachel Therrien, Pharmacist at CHUM s (Centre hospitalier de l Université de Montréal) UHRESS (Unité hospitalière de recherche, d enseignement et de soins sur le sida). Acknowledgements My sincere thanks to everyone who contributed to writing and revising this document: Nathalie Gaudet, Pharmacist at the Centre de santé et de services sociaux du Nord de Lanaudière (CSSSNL); Léa Prince-Duthel, Pharmacist; Jean-Rémi Hoegy, pharmacy intern (France); Geneviève Duplain Cyr, Pharmacist at the CHUS (Centre hospitalier universitaire de Sherbrooke) SAMI (soins ambulatoires en maladies infectieuses) Clinic; Nathacha Beaulieu, Pharmacist (BCC section) and Marie-Claude Berthiaume (antiretroviral metabolism section). Release of liability While the author endeavours to keep up to date on the latest information, she would like to point out that developments in HIV treatment are constantly evolving. This document was designed as a reference only, and the author encourages readers to consult as many health professionals as necessary. Using the information contained in this document shall be at the reader s own risk. The author does not recommend or promote any of the treatments described in this work. Accordingly, she shall not be held liable for any damages, costs and consequences that may result from using this information, or for any errors that may appear in the text. Any decision on specific treatments should be made in consultation with a healthcare professional with the relevant experience. Copyright It is prohibited to reproduce, adapt or translate this work, in whole or in part, without the prior written consent of the copyright holders. January 2012 Website:

3 Foreword Antiretrovirals are known to often be responsible for drug interactions due to their pharmacokinetic properties and their ability to modify the absorption, metabolism and elimination of other drugs. This booklet explores the interactions between antiretrovirals and the various drugs used in cardiology. It was prepared in the aim of reviewing existing literature, initiating reflection and making recommendations based on available information. The document will serve as a basic tool to facilitate discussion among professionals in order to ensure the safest possible management of these drug interactions. We hope, therefore, to avoid the appearance of serious adverse effects, ensure optimal and effective treatment, and prevent treatment non-compliance that is, patients not taking the medications required to treat their HIV or heart disease. Antiretroviral therapy usually involves a combination of at least two classes of antiretrovirals. This document includes information on drug interactions with NNRTIs (non-nucleoside reverse transcriptase inhibitors), PIs (protease inhibitors), maraviroc and raltegravir. Legend The arrows indicate variation in the AUC (potential or observed ) of the associated drug (blue arrows) or antiretroviral (orange arrows). : No interaction is anticipated. : No interaction was observed. Potential increase in the plasma concentration of the associated drug or antiretroviral. A reduction in the dose may be necessary. Monitor the appearance of adverse effects. Observed increase in the plasma concentration of the associated drug or antiretroviral. A reduction in the dose may be necessary. Monitor the appearance of adverse effects. Potential decrease in the plasma concentration of the associated drug or antiretroviral. An increase in the dose may be necessary. Monitor clinical efficacy. Observed decrease in the plasma concentration of the associated drug or antiretroviral. An increase in the dose may be necessary. Monitor clinical efficacy. The background colour indicates the degree of interaction Green: No interaction or the interaction deemed not clinically significant. Yellow: Combination that requires close monitoring. Dose adjustments may be recommended. Orange: Avoid combination. If this is not possible, ensure close monitoring. Red: Combination contraindicated. Chose an alternative to using the associated drug or antiretroviral. Cardiology and HIV 3

4 Glossary Elimination half-life (T½): Time required for the plasma concentration of the drug to decrease by 50% Area under curve (AUC): Total drug exposure during the dosing interval; calculated by integrating repeated measures of the concentration over time following the drug s administration Maximum concentration (Cmax): The maximum or peak concentration in the dosing interval; generally occurs during the absorption phase Minimum concentration (Cmin): The minimum or trough concentration in the dosing interval CYP: Cytochrome NNRTI: Non-nucleoside reverse transcriptase inhibitor PI: Viral protease inhibitor UGT: Uridine diphosphate glucuronosyltransferase INR: International normalized ratio 4 Antiretrovirals and drug interactions

5 Table of contents Metabolism of antiretrovirals... 7 Anticoagulants Antiplatelets Angiotensin II type 1 receptor blockers (ARBs) Antiarrhythmics Beta blockers Calcium channel blockers (CCBs) Angiotensin converting enzyme inhibitors (ACEIs) Hypolipidemics (statins) Hypolipidemics (other) References... 81

6 6 Antiretrovirals and drug interactions

7 Metabolism of non-nucleoside reverse transcriptase inhibitors Substrates Phase I: CYP Phase II: UGT s/inducers Phase I: CYP Phase II: UGT Excretion Transporters Transporters Efavirenz (Sustiva, Atripla) 3A4 and 2B6 (major) Inactive hydroxylated metabolites P-gp (weak) 2C9, 2C19 and 3A4 (moderate) BCRP, MRP1, MRP2, MRP3 (weak) Urine: 14-34% as metabolites Feces: 16-61%, as unchanged drug Inducer 3A4 (strong) CYP2B6 and UGT (weak) T½: Single dose: hours Multiple doses: hours (induces its own metabolism) Etravirine (Intelence) 3A4, 2C9 and 2C19 (major) Main metabolites ~ 10% of etravirine activity against HIV P-gp 2C9 and 2C9 (moderate) P-gp (weak) Inducer 3A4 (strong) Urine: 1% Feces: 94%, up to 86% as unchanged drug T½: 41 hours (± 20 hours) Nevirapine (Viramune) 3A4 (major) 2B6 and 2D6 (minor) Inactive hydroxylated metabolites at 2B6 and 3A4 Inducer : 3A4 (strong) and 2B6 (potentially) 1A2, 2D6 and 3A4 (weak) BCRP, MRP1, MRP2 and MRP3 (weak) Urine: 81%, mainly as metabolites, and less than 3% as unchanged drug Feces: 10% T½: Single dose: 45 hours Multiple doses: hours (induces its own metabolism) Rilpivirine (Edurant, Complera) 3A4 (major) 2C19 (negligible) Inducer : 3A4 (weak) Urine: 6.1%, less than 1% as unchanged drug P-gp (negligible) Feces: 85%, with 25% as unchanged drug T½: hours Cardiology and HIV 7

8 Metabolism of viral protease inhibitors Substrates Phase I: CYP Phase II: UGT Transporters s/inducers Phase I: CYP Phase II: UGT Transporters Excretion Atazanavir (Reyataz) 3A4 (major) Inactive metabolites BCRP, MRP1, MRP2 and P-gp 3A4 ((strong) 2C8 * (moderate) UGT1A1 (moderate) BCRP, MRP1, MRP2, OATP1B1, OATP1B3, OATP2B1, P-gp *Exercise caution if atazanavir without ritonavir is coadministered with other drugs whose metabolism strongly depends on CYP2C8 and have a narrow therapeutic index (e.g. paclitaxel, repaglinide). However, no clinically significant interaction is anticipated during coadministration of the atazanavir/ritonavir combination and CYP2C8 substrates Urine: 13%, with 7% of the total dose as unchanged drug Feces: 79%, with 20% of the total dose as unchanged drug T½: 7-8 hours without ritonavir, 9-18 hours with ritonavir Inducer Increases expression of P-gp and MRP1 Darunavir (Prezista) 3A4 (major) OATP1A2, OATP1B1 and P-gp 3A4 (strong), 2D6 (ritonavir effect) BCRP, MRP1, OATP 1B1, OATP 1B3, P-gp Urine: 14%, with 8% as unchanged drug Feces: 80%, with 41% as unchanged drug Inducer 2C9, 2C19 and 2C8 (ritonavir effect) T½: 15 hours (combined with ritonavir) Fosamprenavir (Telzir) Rapidly and almost completely converted to amprenavir by cellular phosphatases in the intestinal epithelium 3A4 (major) P-gp 3A4 (strong) BCRP, MRP1, OATP 1B1, OATP 1B3 and P-gp Inducer 3A4 (possible, net effect with ritonavir would be inhibition) Urine: 14% as metabolites, with about 1% as unchanged drug Feces: 75%, mainly as metabolites, less than 1% as unchanged drug T½: hours (with ritonavir) 8 Antiretrovirals and drug interactions

9 Metabolism of viral protease inhibitors Substrates Phase I: CYP Phase II: UGT Transporters s/inducers Phase I: CYP Phase II: UGT Transporters Excretion Lopinavir/r (Kaletra) (see also ritonavir below) CYP3A4 (major) 13 metabolites identified, including 5 metabolites linked to the metabolism of ritonavir MRP1, MRP2, P-gp, OATP1A2, OATP1B1 3A4 and 2D6 (strong) BCRP, MPR2, OATP1A2, OATP1B1, OATP1B3, OATP2B1 and P-gp* Inducer 2C19 (strong) 1A2, 2C9 et UGT (moderate) Urine: 10%, with less than 3% as unchanged drug Feces: 83%, with 20% as unchanged drug T½: 5-6 hours P-gp* (moderate) * In vitro data suggest that lopinavir and ritonavir are P-gp inducers, whereas in vivo data show that the net effect of ritonavir is inhibition of P-gp and that the net effect of lopinavir is induction of P-gp during prolonged treatment. Nelfinavir (Viracept) 3A4 (major) 2C19 (major): Active metabolite M8 (activity comparable to nelfinavir) 2C9 and 2D6 (minor) 3A4 (strong) BCRP, MRP1,OATP1A2, OATP1B1, OATP2B1,OCT1, OCT2, P-gp Urine: 1-2% Feces: 98-99%, with 78% as metabolites and 22% as unchanged drug P-gp, MRP1, MRP2 Inducer 2C8, 2C9, 2B6, 2C19, 1A2 (potential) Increases expression of P-gp T½: hours Ritonavir (Norvir) 3A4 and 2D6 (major) 1A2 and 2B6 (minor) 3A4 and 2D6 (strong) Urine: 11%, with 4% as unchanged drug 5 metabolites, including a weak concentration of an active metabolite (M-2) P-gp, MRP1, MRP2 BCRP, OATP1A2, OATP1B, OATP1B3, MRP1, MRP2, OCT1, OCT2 and P-gp Inducer 2B6, 2C8, 2C9, 1A2, 2C19 (moderate) Feces: 86%, with 34% as unchanged drug T½:3-5 hours UGT (moderate) Cardiology and HIV 9

10 Metabolism of viral protease inhibitors Substrates Phase I: CYP Phase II: UGT Transporters s/inducers Phase I: CYP Phase II: UGT Transporters Excretion Saquinavir (Invirase) 3A4 (major), significant first-pass effect in the liver Quickly metabolized into a range of mono- and inactive bi-hydroxylated components 3A4 (moderate) BCRP, MRP1, MRP2, OATP1A2, OATP1B1, OATP1B3, OATP2B1, OCT1, OCT2, P-gp Urine: 1-3% Feces: 81-88% T½: 7-12 hours (with ritonavir) MRP1, MRP2, OTP1A2, OATP1B1, OATP1B3, P-gp Tipranavir (Aptivus) 3A4 (major) P-gp 3A4 and 2D6 (strong) P-gp Urines: 4%, mainly as unchanged drug Feces: 82% Inducer 3A4 (strong) 2C19 and 1A2 (weak) T½: 6 hours with ritonavir P-gp (strong) There may be both an inhibition and induction effect with the tipranavir / ritonavir combination. The net effect is often inhibition, but this depends on the substrate. 10 Antiretrovirals and drug interactions

11 Metabolism of the integrase inhibitor Substrates Phase I: CYP Phase II: UGT Transporters s/inducers Phase I: CYP Phase II: UGT Transporters Excretion Raltegravir (Isentress) UGT1A1 Urine: 32%, with 9% as unchanged drug Feces: 51% as unchanged drug T½: Biphasic Phase 1: 1 hour Phase 2: 9 hours Metabolism of the ccr5 inhibitor Substrates Phase I: CYP Phase II: UGT s/inducers Phase I: CYP Phase II: UGT Excretion Transporters Transporters Maraviroc (Celsentri) 3A4 (major) Inactive metabolites P-gp P-gp According to the product monograph, maraviroc could influence the bioavailability of some drugs transported by P-gp in the intestines. Clinical effect unknown to date. Urine: 20%, with 8% as unchanged drug In the presence of a CYP3A4 inhibitor, renal clearance of maraviroc could increase to 70% Feces: 76%, with 25% as unchanged drug T½: hours Cardiology and HIV 11

12 Metabolism of anticoagulants Substrates Phase I: CYP Phase II: UGT Transporters s/inducers Phase I: CYP Phase II: UGT Transporters Excretion Acenocoumarol (Sintrom) Acenocoumarol is transformed by CYPs into two enantiomers, which produce an anticoagulant effect that is comparable to, or greater than, the effect of the R-enantiomer. S-enantiomer ( ): Metabolized by 2C9 Urine: 60% as metabolites Feces: 29%f as metabolites T½: 8-11 hours R-enantiomer (+): Metabolized by 1A2, 2C19 and 3A4 Apixaban (Eliquis) 3A4/5 (major) 1A2 and 2J2 (minor) 2C8, 2C9 and 2C19 (very minor) SULT 1A1: O-demethyltransferase sulfate (inactive metabolite) P-gp and BCRP According to preclinical studies, the potential for CYP450 inhibition is minimal Urine: 25-28%, with 22-24% as unchanged drug Feces: 56%, mainly as metabolites T½: 8-13 hours 25-30% of the dose is found as inactive metabolites The main metabolite is O-demethyl apixaban sulfate (inactive metabolite) Dabigatran etexilate (Pradax) Prodrug Low bioavailability due to its low solubility at phs greater than 3 and to the action of P-gp in enterocytes Metabolized in the liver to dabigatran, with hydrolysis catalyzed by an esterase Urine: 85% of the total dose Feces: 6%, mainly as unchanged drug T½: hours UGT: Conjugated into active acylglucuronides with 4 isomers, each representing less than 10% of the total quantity of dabigatran P-gp 12 Antiretrovirals and drug interactions

13 Metabolism of anticoagulants Substrates Phase I: CYP Phase II: UGT Transporters s/inducers Phase I: CYP Phase II: UGT Transporters Excretion Rivaroxaban (Xarelto) 3A4 (major) 2J2 (minor) P-gp Urine: 33% as unchanged drug and 33% as inactive metabolites Feces: 33% as inactive metabolites T½: 5-13 hours Warfarine (Coumadin) Racemic mixture of R- and S-enantiomers S-enantiomer exhibits 2-5 times more anticoagulant activity than R-enantiomer 2C9 (moderate) 2C19 (weak) Urine: 92%, mainly as metabolites T½: hours 2C9 (major) 2C19, 2C8, 2C18, 1A2 and 3A4 (minor) CYP2C9: Primary pathway of S-warfarin metabolism. Slow metabolizers of CYP2C9 would require a lower dose of warfarin. Cardiology and HIV 13

14 Anticoagulants and Nnrtis Acenocoumarol (Sintrom) Apixaban (Eliquis) Dabigatran (Pradax) Rivaroxaban (Xarelto) Warfarine (Coumadin) Efavirenz (Sustiva, Atripla) Etravirine (Intelence) Nevirapine (Viramune) Rilpivirine (Edurant, Complera) Legend 1. Possible of the S-enantiomer of acenocoumarol due to CYP2C9 inhibition by efavirenz and etravirine. However, efavirenz and etravirine are CYP3A4 inducers and could the R-enantiomer of acenocoumarol. Actual clinical effect unknown. Recently a case involving the efavirenz/acenocoumarol combination was published. It showed that the dose of acenocoumarol had to be increased to maintain a therapeutic INR. Recommendation: Monitor INR. Monitor for signs and symptoms of efficacy and appearance of adverse effects associated with acenocoumarol (A). Adjust the dose as needed. 2. Although nevirapine and rilpivirine are weak CYP3A4 inducers, no significant clinical effect is expected due to other main metabolic pathways for acenocoumarol. Recommendation: Monitor the clinical efficacy (INR) and safety of acenocoumarol. 3. Possible in apixaban due to possible CYP3A4 induction. However, since apixaban has several metabolic pathways, it is not expected that NNRTIs would have a clinically significant effect on apixaban. One pharmacokinetic study with rifampicin, a potent CYP3A4 inducer, showed a 50% decrease of apixaban (deemed not significant by the author). Recommendation: No change in the dose is recommended since no clinically significant interaction is expected. Monitor clinical efficacy. 14 Antiretrovirals and drug interactions

15 Legend 4. Based on currently available information, no interaction is expected. 5. No clinically significant interaction expecteddue to the potentially weak inhibition effect of P-gp with etravirine. 6. Possible in plasma concentration of rivaroxaban due to CYP3A4 induction by efavirenz, etravirine and nevirapine. The induction effect of rilpivirine is probably not sufficient to cause a clinically significant interaction. Recommendation: Monitor the clinical efficacy of rivaroxaban. 7. INR observed (case report) with the combination of efavirenz and warfarin. After 22 days of efavirenz plus warfarin 5 mg, the patient was hospitalized for hematuria and an INR of 7. The dose of warfarin was decreased and a final dose of 1.25 mg was sufficient to obtain the desired INR. Efavirenz is an inhibitor of CYP2C9 and an inducer of CYP3A4. The net clinical effect is difficult to predict. In this case report, there is most likely an in the S-enantiomer of warfarin due to the inhibition of CYP2C9. Recommendation: Monitor INR. Monitor for signs and symptoms of efficacy and appearance of adverse effects associated with warfarin (B). Adjust the dose as needed. 8. Possible in INR with the combination of etravirine and warfarin, as observed with efavirenz, due to the potential inhibition of CYP2C9. See #7. Recommendation: Monitor INR. Monitor for signs and symptoms of efficacy and the appearance of adverse effects associated with warfarin (B). Adjust the dose as needed. 9. INR observed (case report) with the combination of nevirapine and warfarin. Nevirapine is a CYP3A4 inducer and could potentially increase the metabolism of warfarin and decrease its efficacy. Recommendation: The product monograph recommends monitoring the efficacy and safety of warfarin (B). Adjust dose if necessary. 10. No interaction is expected due to the weak induction effect of rilpivirine on CYP3A4. INR: International normalized ratio A. Adverse effects of acenocoumarol: Bleeding, hemorrhage, nausea, anemia B. Adverse effects of warfarin: Bleeding, hemorrhage, nausea, anemia, headache, skin necrosis Cardiology and HIV 15

16 Anticoagulants and PIs Acenocoumarol (Sintrom) Apixaban (Eliquis) Dabigatran (Pradax) Rivaroxaban (Xarelto) Warfarine (Coumadin) Atazanavir (Reyataz) Atazanavir/r (Reyataz) 1, Darunavir/r (Prezista) 1, Fosamprenavir/r (Telzir) 1, Lopinavir/r (Kaletra) 1, ,11 Nelfinavir (Viracept) 1, ,11 Saquinavir/r (Invirase) 1, Tipranavir/r (Aptivus) 1,2* 4* 6* 8* 10* R : Ritonavir (Norvir) 16 Antiretrovirals and drug interactions

17 Legend 1. Suspected in R-enantiomer due to CYP3A4 inhibition. Clinical effect unknown. Recommendation: Monitor INR. Monitor for signs and symptoms of efficacy and appearance of adverse effects associated with acenocoumarol (A). Adjust the dose as needed. 2. Suspected in R- and S-enantiomers of the active metabolite of acenocoumarol due to the potential induction of CYP2C9 and/or 1A2 with nelfinavir or the protease inhibitors associated with ritonavir. Recently, a case concerning the combination of atazanavir/ritonavir and acenocoumarol was published. It showed that the dose of acenocoumarol had to be increased to maintain a therapeutic INR. The patient was subsequently treated with raltegravir to stop the interaction. A case showing a significant decrease in the effect of acenocoumarol following the administration of a high dose (600 mg BID) of ritonavir had previously been reported. Recommendation: Monitor INR. Monitor for signs and symptoms of efficacy and appearance of adverse effects associated with acenocoumarol (A). Adjust the dose as needed. 3. Possible in apixaban due to possible CYP3A4 inhibition. However, since apixaban has several metabolic pathways, PIs are not expected to have a clinically significant effect on apixaban. One pharmacokinetic study with the potent CYP3A4 inhibitor ketoconazole showed a 100% (twofold) increase in apixaban, deemed not significant by the author. Recommendation: No change in the dose is recommended since no clinically significant interaction is expected. Monitor clinical efficacy and appearance of adverse effects associated with apixaban. 4. Possible or in apixaban due to the possible induction or inhibition of P-gp or CYP3A4. The net effect is difficult to predict. However, since apixaban has several metabolic pathways, PIs are not expected to have a clinically significant impact on apixaban. A pharmacokinetic study with rifampicin, a potent inducer of CYP3A4 and P-gp showed a 50% reduction in apixaban (deemed not significant by the author). A study with ketoconazole, a potent inhibitor of CYP3A4, showed a 100% (twofold) increase of apixaban (deemed not significant by the author). Recommendation: No change in the dose is recommended since no clinically significant interaction is expected. Monitor clinical efficacy and the appearance of adverse effects associated with apixaban. 5. Suspected in dabigatran due to the potential P-gp inhibition by protease inhibitors. The dabigatran monograph states that potent P-gp inhibitors could increase plasma concentrations of the latter. In fact, with amiodarone, ketoconazole, quinidine and verapamil, increases of % in dabigatran AUC were observed. A study with immediate-release verapamil demonstrated an of approximately 150% in the dabigatran AUC. When dabigatran is administered 2 hours before verapamil, an of only 20% is observed in the dabigatran AUC. It is hypothesized that dabigatran had sufficient time to be absorbed at 2 hours following administration. Recommendation: This combination is to be avoided since it has not yet been studied. Choose an alternative to using dabigatran or the protease inhibitor. If this combination cannot be avoided, follow the recommendations in the product monograph for verapamil - namely, a potent P-gp inhibitor. Cardiology and HIV 17

18 Legend A. Prevention of venous thromboembolism (VTE) in patients who have had a total hip or knee replacement: decrease the dose of dabigatran to 150 mg/day and administer 2 hours before the protease inhibitor. B. Atrial fibrillation: No dose adjustment is recommended and administer dabigatran 2 hours before the protease inhibitor. Monitor efficacy and the appearance of adverse effects associated with dabigatran (B). Suspect bleeding in the event of an unexplained drop in hemoglobin and/or hematocrit or a decrease in blood pressure. In patients experiencing bleeding, it may be useful to test activated partial thromboplastin time (APTT) in order to determine if there is an excessive anticoagulant effect. An APTT greater than 80 seconds at the end of the dosing interval (Cmin) of dabigatran is associated with an elevated risk of bleeding. 6. Possible or in dabigatran. The effect is difficult to predict. With nelfinavir or the combination of fosamprenavir/ ritonavir and tipranavir/ritonavir, a P-gp induction effect may be observed. There may, therefore, be a possible decrease in dabigatran. The combination with rifampicin, a significant P-gp inducer, was associated with a decrease of 67% in the dabigatran AUC. Recommendation: Avoid this combination. Monitor clinical efficacy and adverse effects associated with dabigatran (B). 7. Observed in rivaroxaban due to inhibition of CYP3A4 and/or P-gp. In a study involving a high dose of ritonavir (600 mg BID), there was an of 150% (2.5-fold) in rivaroxaban AUC. Recommendation: The product monograph recommends avoiding this combination. Choose an alternative to using dabigatran or the protease inhibitor. If this combination cannot be avoided, monitor clinical efficacy and adverse effects associated with rivaroxaban (C). 8. Possible or in rivaroxaban due to the inhibition or induction of CYP3A4 and/or P-gp with fosamprenavir/ ritonavir, nelfinavir and tipranavir/ritonavir. The net effect is difficult to predict. No pharmacokinetic studies have been conducted to date. Recommendation: The product monograph recommends avoiding this combination. Choose an alternative to using rivaroxaban or the protease inhibitor. If this combination cannot be avoided, monitor clinical efficacy and adverse effects associated with rivaroxaban (C). 9. No clinically significant interaction is anticipated, although a reduction in warfarin metabolism by CYP3A4 is possible. 10. Possible in the S-enantiomer of warfarin due to CYP2C9 induction by ritonavir or nelfinavir. In some case reports, increased dose of warfarin were necessary to maintain a therapeutic INR with ritonavir. An in warfarin can also be expected due to CYP3A4 inhibition. However, according to the reported cases, the clinical effect appears to be a decrease in the effect of warfarin. See also #11. Recommendation: Monitor INR. Monitor clinical efficacy and the appearance of adverse effects associated with warfarin (D). Adjust the dose as needed. Choose an alternative to using the protease inhibitor if it is difficult to obtain a therapeutic INR. 11. Observed of 21% in the S-warfarin AUC with the combination of warfarin and lopinavir/ritonavir, and with the combination of warfarin and darunavir/ritonavir. There have been cases where the warfarin dose had to be increased in order to maintain a therapeutic INR in the presence of lopinavir/ritonavir. 18 Antiretrovirals and drug interactions

19 INR: International normalized ratio A. Adverse effects of acenocoumarol: Hemorrhage that can present in the form of paralysis, paresthesia, headache, chest/abdominal/ joint pain, dizziness, shortness of breath, dyspepsia, difficulty swallowing or breathing, unexplained edema, weakness, hypotension, unexplained shock, hematoma, epistaxis, gingival bleeding B. Adverse effects of dabigatran: Bleeding (suspect bleeding if there is a drop in hemoglobin and/or hematocrit or hypotension), anemia, hematoma, hematuria, epistaxis, gastrointestinal disorders (abdominal pain, diarrhea, dyspepsia and nausea), gastrointestinal and urinary hemorrhage C. Adverse effects of rivaroxaban: Bleeding, hemorrhage, nausea, anemia D. Adverse effects of warfarin: Bleeding, hemorrhage, nausea, anemia, headache, skin necrosis * The combination of tipranavir/ritonavir has been associated with cases of intracranial hemorrhage. Use carefully with anticoagulants.

20 Anticoagulants and Maraviroc/Raltegravir Acenocoumarol (Sintrom) Apixaban (Eliquis) Dabigatran (Pradax) Rivaroxaban (Xarelto) Warfarine (Coumadin) Maraviroc (Celsentri) Raltegravir (Isentress) Legend 1. No interaction is anticipated. 2. Maraviroc is a potential P-gp inhibitor and, as such, may increase dabigatran and rivaroxaban. Clinical significance unknown. Recommendation: As a precautionary measure, administer dabigatran 2 hours before maraviroc. Monitor the clinical efficacy and safety of dabigatran and rivaroxaban. 20 Antiretrovirals and drug interactions

21 Metabolism of Antiplatelets Substrates Phase I: CYP Phase II: UGT Transporters s/inducers Phase I: CYP Phase II: UGT Transporters Excretion Clopidogrel (Plavix) Prodrug Two main pathways: 1. Esterase hydrolysis (85%): Carboxylic acid derivative (inactive) 2B6 (moderate) 2C9 (weak) Urine : 50% Feces : 46% 2. Oxidation in two steps by CYP (15%): Primary oxidation to 2-oxo-clopidogrel, an intermediate metabolite, followed by a second oxidation to a thiol derivative of clopidogrel (active) T½: 8 hours 2C19 and 3A4 (major) 1A2, 2B6 and 2C9 (minor) Prasugrel (Effient) Prodrug Rapidly hydrolyzed in the intestine to thiolactone (inactive), an intermediate metabolite. This is then converted in a single step by CYPs to an active metabolite. 2B6 (weak) Urine: 68% as inactive metabolites Feces: 27%f as inactive metabolites 3A4 and 2B6 (major) 2C9 and 2C19 (minor) T½: 2-15 hours (mean: 7.4 hours) The active metabolite is then metabolized to two inactive compounds by S-methylation or conjugation with cysteine. Ticagrelor (Brilinta) 3A4 and 3A5: Active metabolite that is similar in activity to ticagrelor 3A4 (weak) Feces: Mainly as active metabolites P-gp P-gp (weak) Inducer 3A4 (weak) The inducing or inhibiting effect of ticagrelor on CYP3A4 depends on the associated drug (substrate). T½ of tigagreclor: 6.9 hours T½ of the active metabolite: 5.6 hours Ticlopidine (Ticlid) Prodrug The process of ticlopidine metabolism is not completely clear. It involves the formation of several metabolites (active and inactive) 2C19 et 2D6 (strong) 1A2, 2C9 et 2B6 (moderate) 2E1 and 3A4 (weak) Urine: 60% as metabolites Feces: 23%, with 33% as unchanged drug 2C9 and 2B6: 2-oxo-ticlopidine (active metabolite) 3A4: pyridinium metabolite Ticlopidine would inhibit its own metabolism T½: 4-5 days P-gp Cardiology and HIV 21

22 Antiplatelets and NNRTIs Clopidogrel (Plavix) Prasugrel (Effient) Ticagrelor (Brilinta) Ticlopidine (Ticlid) Efavirenz (Sustiva, Atripla) Etravirine (Intelence) Nevirapine (Viramune) Rilpivirine (Edurant, Complera) Legend 1. Possible in the formation of the active metabolite of clopidogrel due to CYP2C19 inhibition by efavirenz or etravirine. However, CYP3A4 induction could favour ( ) the formation of the active metabolite. To date, no case has been reported and no pharmacokinetic study conducted. Clinical significance unknown. In a study on omeprazole (CYP2C19 inhibitor), a decrease of more than 40% in the active metabolite of clopidogrel was observed, along with a decrease of more than 30% in the effect on platelet aggregation. Several studies have also reported a decrease in clinical efficacy. NB: The inhibition constant [Ki] of etravirine for CYP2C19 would be below that for omeprazole, but above that for pantoprazole. This suggests a possible inhibitory effect on CYP19, but less than that observed with omeprazole. Recommendation: Avoid combining clopidogrel with efavirenz or etravirine, if possible. Monitor clinical efficacy and the appearance of adverse effects associated with clopidogrel (A). Choose an alternative to using the NNRTI or clopidogrel, if deemed necessary. For example, use current data in the literature to determine if prasugrel is a good alternative. 22 Antiretrovirals and drug interactions

23 Legend 2. Possible in the plasma concentration of the active metabolite of clopidogrel due to CYP3A4 induction with nevirapine or rilpivirine. As rilpivirine is a weak CYP3A4 inducer, there may be no clinically significant effect on clopidogrel. Recommendation: Monitor for the appearance of adverse effects associated with clopidogrel (A). Adjust the dose or choose an alternative to the NNRTI or clopidogrel, if deemed necessary. 3. Possible in the plasma concentration of the active metabolite of prasugrel due to CYP3A4 induction. Clinical significance unknown. However, rifampicin, a powerful inducer of CYP3A and CYP2B6, as well as an inducer of CYP2C9, CYP2C19 and CYP2C8, does not significantly alter the pharmacokinetics of prasugrel nor inhibit platelet aggregation (which it induces). No studies or case reports with antiretrovirals have been reported to date. Recommendation: Monitor efficacy and the appearance of adverse effects associated with prasugrel (B). 4. Possible in ticagrelor and possible in its equally potent active metabolite. Clinical significance unknown. With rifampicin, a powerful CYP3A4 inducer, a decrease of 86% in ticagrelor and 46% in its active metabolite was observed. To date, no studies have been conducted on NNRTIs. Clinical significance unknown. Recommendation: If this combination is used, closely monitor the clinical efficacy and safety of ticagrelor (C). 5. Possible in the formation of the active metabolite of ticlopidine due to CYP2C9 inhibition by etravirine and efavirenz. Clinical significance unknown. Possible but probably non-significant increase in etravirine due to CYP2C19 inhibition by ticlopidine. Recommendation: Avoid this combination. Choose an alternative to using ticlopidine or the NNRTI, if deemed necessary. Monitor the clinical efficacy of ticlopidine. 6. According to the information available to date, no interaction is anticipated. A. Adverse effects of clopidogrel: Bleeding, bruising, dyspepsia, diarrhea/constipation, flu-like symptoms and headache B. Adverse effects of prasugrel: Unusual or persistent bleeding (nose, gums and vagina), easy bruising, anemia, weakness, constipation C. Adverse effects of ticagrelor: Bleeding (epistaxis, gastrointestinal/cutaneous hemorrhage), bruising, dyspnea, headache, dizziness, gastrointestinal effects (nausea, vomiting, dyspepsia, diarrhea or constipation), bradycardia Cardiology and HIV 23

Interactions Between Antiretrovirals and Antiplatelet Agents and Novel Oral Anticoagulants

Interactions Between Antiretrovirals and Antiplatelet Agents and Novel Oral Anticoagulants Dosing Metabolism Clopidogrel (Plavix ) 300mg 600mg loading dose 75 mg daily maintenance dose Prodrug activated by CYP2C19 (major), CYP2B6 & metabolism. CYP2B6. 1 Prasugrel (Effient ) 60mg loading dose

More information

Managing HIV Patients with Cardiac Disease: How to Avoid Going Into Heart Failure (the clinician, not the patient)

Managing HIV Patients with Cardiac Disease: How to Avoid Going Into Heart Failure (the clinician, not the patient) Managing HIV Patients with Cardiac Disease: How to Avoid Going Into Heart Failure (the clinician, not the patient) Alice Tseng, Pharm.D., FCSHP, AAHIVP April 25, 2015 Higher Prevalence of Age-Related

More information

Analytical Specifications RIVAROXABAN

Analytical Specifications RIVAROXABAN Page 1 of 9 ANALYTE NAME AND STRUCTURE - RIVAROXABAN SYNONYMS Xarelto CATEGORY Anticoagulant TEST CODE PURPOSE Therapeutic Drug Monitoring GENERAL RELEVANCY BACKGROUND Xarelto (rivaroxaban) is an orally

More information

HIV MEDICATIONS AT A GLANCE. Atripla 600/200/300 mg tablet 02300699 1 tablet daily. Complera 200/25/300 mg tablet 02374129 1 tablet daily

HIV MEDICATIONS AT A GLANCE. Atripla 600/200/300 mg tablet 02300699 1 tablet daily. Complera 200/25/300 mg tablet 02374129 1 tablet daily HIV MEDICATIONS AT A GLANCE Generic Name Trade Name Strength DIN Usual Dosage Single Tablet Regimen (STR) Products Efavirenz/ emtricitabine/ Emtricitabine/ rilpivirine/ elvitegravir/ cobicistat/ emtricitabine/

More information

HCV Interaction Studies presented at the 15 th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy, Washington, April 2014.

HCV Interaction Studies presented at the 15 th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy, Washington, April 2014. Page 1 HCV Interaction Studies presented at the 15 th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy, Washington, April 2014. This report summarises interaction studies relating

More information

TSOAC Initiation Checklist

TSOAC Initiation Checklist Task Establish appropriate dose based on anticoagulant selected, indication and patient factors such as renal function. Evaluate for medication interactions that may necessitate TSOAC dose adjustment.

More information

Treatments for stroke prevention in Atrial Fibrillation as recommended by the Canadian Cardiovascular Society

Treatments for stroke prevention in Atrial Fibrillation as recommended by the Canadian Cardiovascular Society Treatments for stroke prevention in Atrial Fibrillation as recommended by the Canadian Cardiovascular Society Coumadin (Warfarin) Does this medication need ongoing monitoring of blood clotting times? Yes.

More information

Clinically Significant Cardiovascular. Drug Interactions. April 30, 2014 Michael A Militello, PharmD, BCPS Cardiovascular Clinical Pharmacist

Clinically Significant Cardiovascular. Drug Interactions. April 30, 2014 Michael A Militello, PharmD, BCPS Cardiovascular Clinical Pharmacist Clinically Significant Cardiovascular Drug Interactions April 30, 2014 Michael A Militello, PharmD, BCPS Cardiovascular Clinical Pharmacist Introduction Drug interactions represent 3-5% of preventable

More information

HIV 1. A reference guide for prescription HIV-1 medications

HIV 1. A reference guide for prescription HIV-1 medications HIV 1 A reference guide for prescription HIV-1 medications Several different kinds of antiretroviral drugs are currently used to treat HIV-1 infection. These medicines are the ones most commonly used in

More information

Session 3 Topics. Argatroban. Argatroban. Drug Use and Adverse Effects. Laboratory Monitoring of Anticoagulant Therapy

Session 3 Topics. Argatroban. Argatroban. Drug Use and Adverse Effects. Laboratory Monitoring of Anticoagulant Therapy ~~Marshfield Labs Presents~~ Laboratory Monitoring of Anticoagulant Therapy Session 3 of 4 Michael J. Sanfelippo, M.S. Technical Director, Coagulation Services Session 3 Topics Direct Thrombin Inhibitors:

More information

Direct antiviral therapy of hcv and relevant drug drug interactions for ivdu

Direct antiviral therapy of hcv and relevant drug drug interactions for ivdu Direct antiviral therapy of hcv and relevant interactions for ivdu Stefan Mauss Center for HIV and Hepatogastroenterology Duesseldorf, Germany Disclosures Advisory board: Abbvie, BMS, Boehringer Ingelheim,

More information

FDA Approved Oral Anticoagulants

FDA Approved Oral Anticoagulants FDA Approved Oral Anticoagulants Generic (Trade Name) Warfarin (Coumadin, Jantoven ) 1 FDA approved indication Prophylaxis and treatment of venous thromboembolism (VTE) Prophylaxis and treatment of thromboembolic

More information

New oral anticoagulants and antiplatelets: Where do they fit? Meredith Hollinger, PharmD BCPS

New oral anticoagulants and antiplatelets: Where do they fit? Meredith Hollinger, PharmD BCPS New oral anticoagulants and antiplatelets: Where do they fit? Meredith Hollinger, PharmD BCPS Clinical Pharmacy Specialist, Cardiology September 2012 Objectives Describe the mechanisms of action for novel

More information

Drug/Drug and Drug/Food Interactions with Target-Specific Oral Anticoagulants

Drug/Drug and Drug/Food Interactions with Target-Specific Oral Anticoagulants Drug/Drug and Drug/Food Interactions with Target-Specific Oral Anticoagulants Sara R. Vazquez, PharmD, BCPS, CACP Clinical Pharmacist University of Utah Health Care Thrombosis Service Nothing to disclose

More information

New Anticoagulants: Are we Ready to Replace Warfarin? Carole Goodine, RPh Horizon Health Network Stroke Conference 2011

New Anticoagulants: Are we Ready to Replace Warfarin? Carole Goodine, RPh Horizon Health Network Stroke Conference 2011 New Anticoagulants: Are we Ready to Replace Warfarin? Carole Goodine, RPh Horizon Health Network Stroke Conference 2011 Warfarin Decreases stroke risk by 60-70% Superior to ASA and ASA plus clopidogrel

More information

ACUTE STROKE UNIT ORIENTATION

ACUTE STROKE UNIT ORIENTATION ACUTE STROKE UNIT ORIENTATION 2014 TEACHING YOUR STROKE PATIENTS ABOUT THEIR MEDICATION Please refer to Module 8: Secondary Stroke Prevention for additional information Blood Pressure Medication Angiotensin

More information

Current Management of Atrial Fibrillation DISCLOSURES. Heart Beat Anatomy. I have no financial conflicts to disclose

Current Management of Atrial Fibrillation DISCLOSURES. Heart Beat Anatomy. I have no financial conflicts to disclose Current Management of Atrial Fibrillation Mary Macklin, MSN, APRN Concord Hospital Cardiac Associates DISCLOSURES I have no financial conflicts to disclose Book Women: Fit at Fifty. A Guide to Living Long.

More information

Herta Crauwels, et al.: Rilpivirine Drug-Drug Interactions

Herta Crauwels, et al.: Rilpivirine Drug-Drug Interactions AIDS Rev. 2013;15:87 101 Herta Crauwels, et al.: Rilpivirine Drug-Drug Interactions Clinical Perspective on Drug Drug Interactions with the Non-nucleoside Reverse Transcriptase Inhibitor Rilpivirine Herta

More information

862060_Rec Drug Guide.qxd 2/5/14 1:06 PM Page 1. Recreational Drugs and HIV Antiretrovirals. A Guide to Interactions for Clinicians

862060_Rec Drug Guide.qxd 2/5/14 1:06 PM Page 1. Recreational Drugs and HIV Antiretrovirals. A Guide to Interactions for Clinicians 862060_Rec Drug Guide.qxd 2/5/14 1:06 PM Page 1 Recreational Drugs and HIV Antiretrovirals A Guide to Interactions for Clinicians 2014 862060_Rec Drug Guide.qxd 2/5/14 1:06 PM Page 2 Recreational Drugs

More information

Novel Oral Anticoagulants (NOACs) Prescriber Update 2013

Novel Oral Anticoagulants (NOACs) Prescriber Update 2013 Novel Oral Anticoagulants (NOACs) Prescriber Update 2013 Indications/Contraindications Indications Orthopedic VTE Prophylaxis VTE Treatment Stroke Prevention for non-valvular AF Contraindications 150 mg

More information

Introduction to Atrial Fibrillation (AFib)

Introduction to Atrial Fibrillation (AFib) Introduction to Atrial Fibrillation (AFib) Learn About: 1. What is atrial fibrillation? 2. How will I feel? 3. Who gets AFib? 4. Risk of stroke 5. AFib treatment 6. How to live well with AFib 1. What is

More information

Devang M. Desai, MD, FACC, FSCAI Chief of Interventional Cardiology Director of Cardiac Catheterization Lab St. Mary s Hospital and Regional Medical

Devang M. Desai, MD, FACC, FSCAI Chief of Interventional Cardiology Director of Cardiac Catheterization Lab St. Mary s Hospital and Regional Medical Devang M. Desai, MD, FACC, FSCAI Chief of Interventional Cardiology Director of Cardiac Catheterization Lab St. Mary s Hospital and Regional Medical Center A.Fib affects 2.2 million Americans. The lifetime

More information

Atrial Fibrillation Peter Santucci, MD Revised May, 2008

Atrial Fibrillation Peter Santucci, MD Revised May, 2008 Atrial Fibrillation Peter Santucci, MD Revised May, 2008 Atrial fibrillation (AF) is an irregular, disorganized rhythm characterized by a lack of organized mechanical atrial activity. The atrial rate is

More information

Critical Bleeding Reversal Protocol

Critical Bleeding Reversal Protocol Critical Bleeding Reversal Protocol Coagulopathy, either drug related or multifactorial, is a major contributing factor to bleeding related mortality in a variety of clinical settings. Standard therapy

More information

A Patient s Guide to Antithrombotic Therapy in Atrial Fibrillation

A Patient s Guide to Antithrombotic Therapy in Atrial Fibrillation Patient s Guide to Antithrombotic Therapy in Atrial Fibrillation A Patient s Guide to Antithrombotic Therapy in Atrial Fibrillation PATIENT EDUCATION GUIDE What is atrial fibrillation? Atrial fibrillation

More information

Novartis Gilenya FDO Program Clinical Protocol and Highlights from Prescribing Information (PI)

Novartis Gilenya FDO Program Clinical Protocol and Highlights from Prescribing Information (PI) Novartis Gilenya FDO Program Clinical Protocol and Highlights from Prescribing Information (PI) Highlights from Prescribing Information - the link to the full text PI is as follows: http://www.pharma.us.novartis.com/product/pi/pdf/gilenya.pdf

More information

Antiplatelet and Antithrombotic Therapy. Dr Curry Grant Stroke Prevention Clinic Quinte Health Care

Antiplatelet and Antithrombotic Therapy. Dr Curry Grant Stroke Prevention Clinic Quinte Health Care Antiplatelet and Antithrombotic Therapy Dr Curry Grant Stroke Prevention Clinic Quinte Health Care Disclosure of Potential for Conflict of Interest Dr. F.C. Grant Atrial Fibrillation FINANCIAL DISCLOSURE:

More information

Atrial Fibrillation. Patient Information. 828361 Dec 19-12

Atrial Fibrillation. Patient Information. 828361 Dec 19-12 Atrial Fibrillation Patient Information 828361 Dec 19-12 Contents Introduction 1 Treatment & decrease stroke options 2 Information for people who are taking warfarin (Coumadin ) 5 Information for people

More information

ATRIAL FIBRILLATION IN THE 21 ST CENTURY TIMOTHY DOWLING, D.O. FAMILY PHYSICIAN

ATRIAL FIBRILLATION IN THE 21 ST CENTURY TIMOTHY DOWLING, D.O. FAMILY PHYSICIAN ATRIAL FIBRILLATION IN THE 21 ST CENTURY TIMOTHY DOWLING, D.O. FAMILY PHYSICIAN GOALS AND OBJECTIVES At The end of this talk you should understand: What is Atrial Fibrillation Causes of Atrial Fibrillation

More information

Chemotherapy regimen: Dose adjusted EPOCH

Chemotherapy regimen: Dose adjusted EPOCH Chemotherapy regimen: Dose adjusted EPOCH Agents involved Etoposide 50 mg/m 2 /d continuous IV infusion D 1 4 Doxorubicin 10 mg/m 2 /d continuous IV infusion D 1 4 Vincristine 0.4 mg/m 2 /d IV continuous

More information

Opioid Pain and Addiction Management Medications Drug. Interactions with HIV Antiretrovirals. A Drug Interaction Guide for Clinicians.

Opioid Pain and Addiction Management Medications Drug. Interactions with HIV Antiretrovirals. A Drug Interaction Guide for Clinicians. 857106_Pain Bro.qxd 6/11/13 7:49 AM Page 1 Opioid Pain and Addiction Management Medications Drug Interactions with HIV Antiretrovirals A Drug Interaction Guide for Clinicians Spring 2013 NY/NJ AIDS Education

More information

Comparison between New Oral Anticoagulants and Warfarin

Comparison between New Oral Anticoagulants and Warfarin Comparison between New Oral Anticoagulants and Warfarin Warfarin was the mainstay of oral anticoagulant therapy until the recent discovery of more precise targets for therapy. In recent years, several

More information

Anticoagulation: How Do I Pick From All the Choices? Jeffrey H. Neuhauser, DO, FACC BHHI Primary Care Symposium February 28, 2014

Anticoagulation: How Do I Pick From All the Choices? Jeffrey H. Neuhauser, DO, FACC BHHI Primary Care Symposium February 28, 2014 Anticoagulation: How Do I Pick From All the Choices? Jeffrey H. Neuhauser, DO, FACC BHHI Primary Care Symposium February 28, 2014 Atrial Fibrillation 2 Atrial Fibrillation The most common arrhythmia encountered

More information

More information for patients and caregivers can be accessed at http://www.xarelto-us.com/.

More information for patients and caregivers can be accessed at http://www.xarelto-us.com/. Janssen Research & Development Submits Application to U.S. FDA for XARELTO (rivaroxaban) to Reduce Secondary Cardiovascular Events in Patients with Acute Coronary Syndrome RARITAN, DECEMBER 29, 2011 -

More information

Rivaroxaban: Amber Drug Guidance for the prevention of stroke and systemic embolism in patients with non-valvular AF

Rivaroxaban: Amber Drug Guidance for the prevention of stroke and systemic embolism in patients with non-valvular AF Leeds Rivaroxaban: Amber Drug Guidance for the prevention of stroke and systemic embolism in patients with non-valvular AF Amber Drug Level 3 (amber drug with monitoring requirements) We have started your

More information

Helpful HIV Medication Tables for Pharmacists

Helpful HIV Medication Tables for Pharmacists 861837_Pharmguide.qxd 2/5/14 12:55 PM Page 1 Helpful HIV Medication Tables for Pharmacists New York/New Jersey AIDS Education & Training Center (AETC) www.nynjaetc.org Winter 2014 861837_Pharmguide.qxd

More information

Atrial fibrillation (AF) care pathways. for the primary care physicians

Atrial fibrillation (AF) care pathways. for the primary care physicians Atrial fibrillation (AF) care pathways for the primary care physicians by University of Minnesota Physicians Heart, October, 2011 Evaluation by the primary care physician: 1. Comprehensive history and

More information

DABIGATRAN ETEXILATE TARGET Vitamin K epoxide reductase WARFARIN RIVAROXABAN APIXABAN

DABIGATRAN ETEXILATE TARGET Vitamin K epoxide reductase WARFARIN RIVAROXABAN APIXABAN TARGET SPECIFIC ORAL ANTICOAGULANTS (TSOACs) This document is intended as a guideline only and should not replace sound clinical judgment Please refer to UNMH formulary in Lexicomp for approved use(s)

More information

ACLS PHARMACOLOGY 2011 Guidelines

ACLS PHARMACOLOGY 2011 Guidelines ACLS PHARMACOLOGY 2011 Guidelines ADENOSINE Narrow complex tachycardias or wide complex tachycardias that may be supraventricular in nature. It is effective in treating 90% of the reentry arrhythmias.

More information

MEDICATION GUIDE XARELTO (zah-rel-toe) (rivaroxaban) Tablets

MEDICATION GUIDE XARELTO (zah-rel-toe) (rivaroxaban) Tablets MEDICATION GUIDE XARELTO (zah-rel-toe) (rivaroxaban) Tablets Read this Medication Guide before you start taking XARELTO and each time you get a refill. There may be new information. This Medication Guide

More information

Rivaroxaban for the treatment of Deep Vein Thrombosis in patients unsuitable for vitamin K antagonists

Rivaroxaban for the treatment of Deep Vein Thrombosis in patients unsuitable for vitamin K antagonists Rivaroxaban for the treatment of Deep Vein Thrombosis in patients unsuitable for vitamin K antagonists Traffic light classification- Amber 2 specialist initiation Information sheet for Primary Care Prescribers

More information

New oral anticoagulants. Surveillance and follow-up Laurent Fauchier

New oral anticoagulants. Surveillance and follow-up Laurent Fauchier New oral anticoagulants. Surveillance and follow-up Laurent Fauchier Pole Coeur Thorax Vaisseaux Centre Hospitalier Universitaire Trousseau, Tours Disclosures Laurent Fauchier: Lecture fees: Travel grants:

More information

An#- Coagulant An#- Thrombo#c An#- Platelet Drugs

An#- Coagulant An#- Thrombo#c An#- Platelet Drugs An#- Coagulant An#- Thrombo#c An#- Platelet Drugs 1 ANTICOAGULANT CLASSES INHIBITORS OF CLOTTING FACTOR SYNTHESIS WARFARIN (COUMADIN ) Rivaroxaban (Xarelto ) INHIBITORS OF THROMBIN HEPARIN, LEPIRUDIN (REFLUDAN

More information

Dabigatran: Amber Drug Guidance for the prevention of stroke and systemic embolism in patients with non-valvular AF

Dabigatran: Amber Drug Guidance for the prevention of stroke and systemic embolism in patients with non-valvular AF Leeds Dabigatran: Amber Drug Guidance for the prevention of stroke and systemic embolism in patients with non-valvular AF Amber Drug Level 3 (amber drug with monitoring requirements) We have started your

More information

Patient Group Direction Hospital: Bristol Royal Infirmary Department: UHBristol Thrombosis Service University Hospitals Bristol NHS Foundation Trust.

Patient Group Direction Hospital: Bristol Royal Infirmary Department: UHBristol Thrombosis Service University Hospitals Bristol NHS Foundation Trust. Patient Group Direction Hospital: Bristol Royal Infirmary Department: UHBristol Thrombosis Service University Hospitals Bristol NHS Foundation Trust. This Patient Group Direction (PGD) has been written

More information

Dorset Medicines Advisory Group

Dorset Medicines Advisory Group Shared Care Guideline for prescribing rivaroxaban in the prevention of adverse outcomes after acute management of acute coronary syndrome in adults INDICATION In accordance with NICE TA335 rivaroxaban

More information

Management for Deep Vein Thrombosis and New Agents

Management for Deep Vein Thrombosis and New Agents Management for Deep Vein Thrombosis and New Agents Mark Malesker, Pharm.D., FCCP, FCCP, FASHP, BCPS Professor of Pharmacy Practice and Medicine Creighton University 5 th Annual Creighton Cardiovascular

More information

Safety Information Card for Xarelto Patients

Safety Information Card for Xarelto Patients Safety Information Card for Xarelto Patients 15mg Simply Protecting More Patients 20mg Simply Protecting More Patients Keep this card with you at all times Present this card to every physician or dentist

More information

Dabigatran (Pradaxa) Guidelines

Dabigatran (Pradaxa) Guidelines Dabigatran (Pradaxa) Guidelines Dabigatran is a new anticoagulant for reducing the risk of stroke in patients with atrial fibrillation. Dabigatran is a direct thrombin inhibitor, similar to warfarin, without

More information

ANTICOAGULANT DRUG INTERACTIONS. New Agents, New Concerns

ANTICOAGULANT DRUG INTERACTIONS. New Agents, New Concerns ANTICOAGULANT DRUG INTERACTIONS New Agents, New Concerns Ann K Wittkowsky PharmD, CACP, FASHP, FCCP Clinical Professor University of Washington School of Pharmacy Director, Anticoagulation Services UWMedicine

More information

New Treatments for Stroke Prevention in Atrial Fibrillation. John C. Andrefsky, MD, FAHA NEOMED Internal Medicine Review course May 5 th, 2013

New Treatments for Stroke Prevention in Atrial Fibrillation. John C. Andrefsky, MD, FAHA NEOMED Internal Medicine Review course May 5 th, 2013 New Treatments for Stroke Prevention in Atrial Fibrillation John C. Andrefsky, MD, FAHA NEOMED Internal Medicine Review course May 5 th, 2013 Classification Paroxysmal atrial fibrillation (AF) Last < 7

More information

INITIATING ORAL AUBAGIO (teriflunomide) THERAPY

INITIATING ORAL AUBAGIO (teriflunomide) THERAPY FOR YOUR PATIENTS WITH RELAPSING FORMS OF MS INITIATING ORAL AUBAGIO (teriflunomide) THERAPY WARNING: HEPATOTOXICITY AND RISK OF TERATOGENICITY Severe liver injury including fatal liver failure has been

More information

Cardiology Medications New Drugs, New Guidelines

Cardiology Medications New Drugs, New Guidelines Cardiology Medications New Drugs, New Guidelines Ken Kester, PharmD, JD Pharmacy Team Leader Nebraska Heart Hospital August 4, 2014 Cardiology Medications Objectives The attendee will understand Indications,

More information

Practical Management of Patients receiving Rivaroxaban 울산의대 서울아산병원 심장내과 최기준

Practical Management of Patients receiving Rivaroxaban 울산의대 서울아산병원 심장내과 최기준 Practical Management of Patients receiving Rivaroxaban 울산의대 서울아산병원 심장내과 최기준 Contents Converting to/from rivaroxaban Measuring levels of rivaroxaban Patients potentially at higher risk of bleeding Renal

More information

Time of Offset of Action The Trial

Time of Offset of Action The Trial New Antithrombotic Agents DISCLOSURE Relevant Financial Relationship(s) Speaker Bureau - None Consultant Amgen Tom DeLoughery, MD FACP FAWM Oregon Health and Sciences University What I am Talking About

More information

Translating clinical evidence into real-world outcomes

Translating clinical evidence into real-world outcomes Annual Swiss Stroke Society Meeting 31st of January 2013 Symposium: From RE-LY to practice: Changing the attitude on stroke prevention in AF Translating clinical evidence into real-world outcomes Unité

More information

ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS

ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked

More information

DVT/PE Management with Rivaroxaban (Xarelto)

DVT/PE Management with Rivaroxaban (Xarelto) DVT/PE Management with Rivaroxaban (Xarelto) Rivaroxaban is FDA approved for the acute treatment of DVT and PE and reduction in risk of recurrence of DVT and PE. FDA approved indications: Non valvular

More information

The Role of the Newer Anticoagulants

The Role of the Newer Anticoagulants The Role of the Newer Anticoagulants WARFARIN = Coumadin DAGIBATRAN = Pradaxa RIVAROXABAN = Xarelto APIXABAN = Eliquis INDICATION DABIGATRAN (Pradaxa) RIVAROXABAN (Xarelto) APIXABAN (Eliquis) Stroke prevention

More information

Teriflunomide is the active metabolite of Leflunomide, a drug employed since 1994 for the treatment of rheumatoid arthritis (Baselt, 2011).

Teriflunomide is the active metabolite of Leflunomide, a drug employed since 1994 for the treatment of rheumatoid arthritis (Baselt, 2011). Page 1 of 10 ANALYTE NAME AND STRUCTURE TERIFLUNOMIDE Teriflunomide TRADE NAME Aubagio CATEGORY Antimetabolite TEST CODE PURPOSE Therapeutic Drug Monitoring GENERAL RELEVANCY BACKGROUND sclerosis. The

More information

Non-vitamin K antagonist oral anticoagulants in cardiovascular disease management: evidence and unanswered questions

Non-vitamin K antagonist oral anticoagulants in cardiovascular disease management: evidence and unanswered questions Journal of Clinical Pharmacy and Therapeutics, 2014, 39, 118 135 doi: 10.1111/jcpt.12122 Review Article Non-vitamin K antagonist oral anticoagulants in cardiovascular disease management: evidence and unanswered

More information

SAVAYSA (edoxaban) U.S. Opportunity

SAVAYSA (edoxaban) U.S. Opportunity SAVAYSA (edoxaban) U.S. Opportunity February 17, 2015 Ken Keller President, U.S. Commercial DSI, Inc. Key Discussion Points Daiichi Sankyo, Inc. (DSI) in the U.S. SAVAYSA (edoxaban) U.S. Indication NOAC

More information

Oral Anticoagulants: What s New?

Oral Anticoagulants: What s New? Oral Anticoagulants: What s New? Sallie Young, Pharm.D., BCPS (AQ-Cardiology) Clinical Pharmacy Specialist, Cardiology Penn State Hershey Medical Center syoung1@hmc.psu.edu August 2012 Oral Anticoagulant

More information

Update on Antiplatelets and anticoagulants. Outlines. Antiplatelets and Anticoagulants 1/23/2013. Timir Paul, MD, PhD

Update on Antiplatelets and anticoagulants. Outlines. Antiplatelets and Anticoagulants 1/23/2013. Timir Paul, MD, PhD Update on Antiplatelets and anticoagulants Timir Paul, MD, PhD Antiplatelets Indications Doses Long term use (beyond 12 months) ASA and combination use of NSAIDS ASA resistance Plavix resistance Plavix

More information

A practice tool for the new oral anticoagulants

A practice tool for the new oral anticoagulants Peer-reviewed A practice tool for the new oral anticoagulants Anne Massicotte, BPharm, MSc Although warfarin has been the king of oral anticoagulation for the past few decades, its reign is now jeopardized

More information

My remarks today and the information contained in these slides do not necessarily reflect the official views of FDA.

My remarks today and the information contained in these slides do not necessarily reflect the official views of FDA. Possible Criteria that Warrant In Vivo P-Glycoprotein Glycoprotein-Mediated Drug Interaction Studies Based on In Vitro Assessment Lei Zhang, Ph.D. Office of Clinical Pharmacology Office of Translational

More information

1/7/2012. Objectives. Epidemiology of Atrial Fibrillation(AF) Stroke in AF. Stroke Risk Stratification in AF

1/7/2012. Objectives. Epidemiology of Atrial Fibrillation(AF) Stroke in AF. Stroke Risk Stratification in AF Objectives Atrial Fibrillation and Prevention of Thrombotic Complications: Therapeutic Update Andrea C. Flores Pharm.D Pharmacy Resident at the Miami VA Healthcare System Review the epidemiology, pathophysiology

More information

AHA/ASA Scientific Statement Oral Antithrombotic Agents for the Prevention of Stroke in Atrial Fibrillation

AHA/ASA Scientific Statement Oral Antithrombotic Agents for the Prevention of Stroke in Atrial Fibrillation AHA/ASA Scientific Statement Oral Antithrombotic Agents for the Prevention of Stroke in Atrial Fibrillation A Statement for Healthcare Professionals from the American Heart Association/American Stroke

More information

Clinical guide to managing patients treated with Pradaxa

Clinical guide to managing patients treated with Pradaxa Clinical guide to managing patients treated with Pradaxa Updated August 2013 Treatment with Pradaxa (dabigatran etexilate) requires no routine laboratory monitoring. 1 Routine coagulation tests (aptt,

More information

3/25/14. To Clot or Not What s New In Anticoagulation? Clotting Cascade. Anticoagulant drug targets. Anita Ralstin, MS CNS CNP. Heparin.

3/25/14. To Clot or Not What s New In Anticoagulation? Clotting Cascade. Anticoagulant drug targets. Anita Ralstin, MS CNS CNP. Heparin. To Clot or Not What s New In Anticoagulation? Anita Ralstin, MS CNS CNP 1 Clotting Cascade 2 Anticoagulant drug targets Heparin XI VIII IX V X VII LMWH II Warfarin Fibrin clot 1 Who Needs Anticoagulation

More information

Recurrent AF: Choosing the Right Medication.

Recurrent AF: Choosing the Right Medication. In the name of God Shiraz E-Medical Journal Vol. 11, No. 3, July 2010 http://semj.sums.ac.ir/vol11/jul2010/89015.htm Recurrent AF: Choosing the Right Medication. Basamad Z. * Assistant Professor, Department

More information

Efficacy in Hip Arthroplasty. Efficacy in Knee Arthroplasty. Adverse Effects. Drug Interactions

Efficacy in Hip Arthroplasty. Efficacy in Knee Arthroplasty. Adverse Effects. Drug Interactions Objectives Just for the RECORD: Rivaroxaban joins the US Anticoagulation Arsenal Anne P. Spencer, PharmD, FCCP, BCPS (AQ Cardiology) Cardiovascular Care Pharmacy Specialist Roper Saint Francis Healthcare

More information

Guidance for prescribing of Dabigatran (Pradaxa ) Rivaroxaban (Xarelto ) and Apixaban (Eliquis ) in Patients with Non-Valvular AF

Guidance for prescribing of Dabigatran (Pradaxa ) Rivaroxaban (Xarelto ) and Apixaban (Eliquis ) in Patients with Non-Valvular AF Guidance for prescribing of Dabigatran (Pradaxa ) Rivaroxaban (Xarelto ) and Apixaban (Eliquis ) in Patients with Non-Valvular AF Lesley Davey Staffordshire and Lancashire CSU November 2013 (Review November

More information

News Release. Media contacts: Ernie Knewitz Tel: 908.927.2953 Mobile: 917.697.2318 eknewitz@its.jnj.com

News Release. Media contacts: Ernie Knewitz Tel: 908.927.2953 Mobile: 917.697.2318 eknewitz@its.jnj.com News Release Media contacts: Ernie Knewitz Tel: 908.927.2953 Mobile: 917.697.2318 eknewitz@its.jnj.com Shaun Mickus Phone: 908.927.2416 Mobile: 973.476.7144 smickus@its.jnj.com Investor contacts: Stan

More information

Rivaroxaban shared care guidelines for the prevention of stroke and embolism in adult patients with nonvalvular atrial fibrillation.

Rivaroxaban shared care guidelines for the prevention of stroke and embolism in adult patients with nonvalvular atrial fibrillation. South West Essex Rivaroxaban Shared Care Guideline (SCG) Rivaroxaban shared care guidelines for the prevention of stroke and embolism in adult patients with nonvalvular atrial fibrillation. Introduction

More information

ACLS Cardiac Arrest Algorithm Neumar, R. W. et al. Circulation 2010;122:S729-S767

ACLS Cardiac Arrest Algorithm Neumar, R. W. et al. Circulation 2010;122:S729-S767 ACLS Cardiac Arrest Algorithm Neumar, R. W. et al. Circulation 2010;122:S729-S767 Copyright 2010 American Heart Association ACLS Cardiac Arrest Circular Algorithm Neumar, R. W. et al. Circulation 2010;122:S729-S767

More information

Prescriber Guide. 20mg. 15mg. Simply Protecting More Patients. Simply Protecting More Patients

Prescriber Guide. 20mg. 15mg. Simply Protecting More Patients. Simply Protecting More Patients Prescriber Guide 20mg Simply Protecting More Patients 15mg Simply Protecting More Patients 1 Dear Doctor, This prescriber guide was produced by Bayer Israel in cooperation with the Ministry of Health as

More information

Multiple features working in concert

Multiple features working in concert Multiple features working in concert Indication is an antiarrhythmic drug indicated to reduce the risk of hospitalization for atrial fibrillation (AFib) in patients in sinus rhythm with a history of paroxysmal

More information

DOACs. What s in a name? or TSOACs. Blood Clot. Darra Cover, Pharm D. Clot Formation DOACs work here. Direct Oral AntiCoagulant

DOACs. What s in a name? or TSOACs. Blood Clot. Darra Cover, Pharm D. Clot Formation DOACs work here. Direct Oral AntiCoagulant DOACs NOACs or TSOACs Generic Name DOACs Brand Name Mechanism of Action Direct Xa Inhibitor Direct Thrombin Inhibitor Dabigatran Pradaxa X Rivaroxaban Xarelto X Darra Cover, Pharm D Apixaban Eliquis X

More information

Sudden dizziness, trouble walking, loss of balance or coordination

Sudden dizziness, trouble walking, loss of balance or coordination rivaroxaban (Xarelto) Patient Education Information Sheet Veterans Health System Pharmacy Service 119 What is rivaroxaban (Xarelto)? A new anticoagulant ( blood thinner ) that reduces the risk of stroke

More information

http://www.medscape.org/viewarticle/808338_print

http://www.medscape.org/viewarticle/808338_print Page 1 of 18 From Medscape Education Cardiology Pharmacokinetics of Anticoagulants: Why It Matters Matthew A. Cavender, MD, MPH; Robert P. Giugliano, MD, SM CME Released: 07/31/2013 ; Valid for credit

More information

Atrial Fibrillation. Management Strategies Marc D. Schrode, D.O., F.A.C.C.,F.A.C.O.I.

Atrial Fibrillation. Management Strategies Marc D. Schrode, D.O., F.A.C.C.,F.A.C.O.I. Atrial Fibrillation Management Strategies Marc D. Schrode, D.O., F.A.C.C.,F.A.C.O.I. Atrial Fibrillation Estimated that 2.6 to 6.1 million people in the U.S. with Afib as of 2010 By 2050 it is expected

More information

Pharmacotherapy in the Elderly. Judy MY Wong

Pharmacotherapy in the Elderly. Judy MY Wong Pharmacotherapy in the Elderly Judy MY Wong judywong@berkeley.edu Percentage of population with prescription and number of medication per individual increase with age Definitions Pharmacology: pharmakon

More information

**Form 1: - Consultant Copy** Telephone Number: Fax Number: Email: Author: Dr Bernard Udeze Pharmacist: Claire Ault Date of issue July 2011

**Form 1: - Consultant Copy** Telephone Number: Fax Number: Email: Author: Dr Bernard Udeze Pharmacist: Claire Ault Date of issue July 2011 Effective Shared Care Agreement for the treatment of Dementia in Alzheimer s Disease Donepezil tablets / orodispersible tablets (Aricept / Aricept Evess ) These forms (1 and 2) are to be completed by both

More information

COMPARISON OF NEW ORAL ANTICOAGULANTS AND FREQUENTLY- ASKED QUESTIONS FROM PATIENTS. TARGET AUDIENCE: All Canadian health care professionals.

COMPARISON OF NEW ORAL ANTICOAGULANTS AND FREQUENTLY- ASKED QUESTIONS FROM PATIENTS. TARGET AUDIENCE: All Canadian health care professionals. COMPARISON OF NEW ORAL ANTICOAGULANTS AND FREQUENTLY- ASKED QUESTIONS FROM PATIENTS AND PHYSICIANS TARGET AUDIENCE: All Canadian health care professionals. OBJECTIVES: To provide a comparison of the new

More information

Cardiology Medications New Drugs, New Guidelines

Cardiology Medications New Drugs, New Guidelines Cardiology Medications New Drugs, New Guidelines Ken Kester, PharmD, JD Pharmacy Team Leader Nebraska Heart Hospital August 4, 2014 CARDIOLOGY MEDICATIONS Objectives The attendee will understand Indications,

More information

AF, Stroke Risk and New Anticoagulants

AF, Stroke Risk and New Anticoagulants Carmarthen Cardiac Update Course AF, Stroke Risk and New Anticoagulants Dr Hamsaraj Shetty, B.Sc, FRCP (London & Edinburgh) Consultant Physician & Honorary Senior Lecturer University Hospital of Wales,Cardiff

More information

Drug-Drug Interactions

Drug-Drug Interactions Slide 1 Drug-Drug Interactions David Back University of Liverpool UK David Back University of Liverpool C-Hep Berlin October 2012 Interactions with the new HepC drugs are challenging! Slide 2 Number of

More information

Drug Treatment Program Update

Drug Treatment Program Update Drug Treatment Program Update As of May 211 Drug Treatment Program Update A key component of the Centre s mandate is to monitor the impact of HIV/AIDS on British Columbia. The Centre provides essential

More information

Living with a Non-Vitamin K Antagonist Oral Anticoagulant (NOAC)

Living with a Non-Vitamin K Antagonist Oral Anticoagulant (NOAC) Living with a Non-Vitamin K Antagonist Oral Anticoagulant (NOAC) dabigatran (Pradaxa ) rivaroxaban (Xarelto ) apixaban (Eliquis ) Information for patients Produced and made available by the Western Australian

More information

UW MEDICINE PATIENT EDUCATION. Xofigo Therapy. For metastatic prostate cancer. What is Xofigo? How does it work?

UW MEDICINE PATIENT EDUCATION. Xofigo Therapy. For metastatic prostate cancer. What is Xofigo? How does it work? UW MEDICINE PATIENT EDUCATION Xofigo Therapy For metastatic prostate cancer This handout explains how the drug Xofigo is used to treat metastatic prostate cancer. What is Xofigo? Xofigo is a radioactive

More information

Living with a New Oral Anticoagulant (NOAC)

Living with a New Oral Anticoagulant (NOAC) Living with a New Oral Anticoagulant (NOAC) dabigatran (Pradaxa ) rivaroxaban (Xarelto ) apixaban (Eliquis ) Information for patients Produced and made available by the Western Australian Medication Safety

More information

Three new/novel oral anticoagulants (NOAC) have been licensed in Ireland since 2008:

Three new/novel oral anticoagulants (NOAC) have been licensed in Ireland since 2008: Key Points to consider when prescribing NOACs Introduction Three new/novel oral anticoagulants (NOAC) have been licensed in Ireland since 2008: Dabigatran Etexilate (Pradaxa ) 75mg, 110mg, 150mg. Rivaroxaban

More information

STARTING, SWITCHING OR STOPPING NEW ORAL ANTICOAGULANTS: A Practical Approach

STARTING, SWITCHING OR STOPPING NEW ORAL ANTICOAGULANTS: A Practical Approach STARTING, SWITCHING OR STOPPING NEW ORAL ANTICOAGULANTS: A Practical Approach Jeffrey I Weitz, MD, FRCP(C), FACP Professor of Medicine and Biochemistry McMaster University Canada Research Chair in Thrombosis

More information

New Oral Anticoagulants

New Oral Anticoagulants Disclosures The New Oral Anticoagulants: Are they better than Warfarin? Alan P. Agins, Ph.D. does not have any actual or potential conflicts of interest in relation to this CE activity. Alan Agins, Ph.D.

More information

Practical guide to Pradaxa in NVAF

Practical guide to Pradaxa in NVAF Practical guide to Pradaxa in NVAF Pradaxa (dabigatran etexilate) is indicated for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and at least one

More information

Atrial Fibrillation The High Risk Obese Patient

Atrial Fibrillation The High Risk Obese Patient Atrial Fibrillation The High Risk Obese Patient Frederick Schaller, D.O.,F.A.C.O.I. Professor and Vice Dean Touro University Nevada A 56 year old male with a history of hypertension and chronic stable

More information

Treating AF: The Newest Recommendations. CardioCase presentation. Ethel s Case. Wayne Warnica, MD, FACC, FACP, FRCPC

Treating AF: The Newest Recommendations. CardioCase presentation. Ethel s Case. Wayne Warnica, MD, FACC, FACP, FRCPC Treating AF: The Newest Recommendations Wayne Warnica, MD, FACC, FACP, FRCPC CardioCase presentation Ethel s Case Ethel, 73, presents with rapid heart beating and mild chest discomfort. In the ED, ECG

More information

Meeting Report 15 th PK Workshop, Washington, 2014 Produced by www.hiv-druginteractions.org

Meeting Report 15 th PK Workshop, Washington, 2014 Produced by www.hiv-druginteractions.org Page 1 of 7 HIV Interaction Studies presented at the 15 th International Workshop on Clinical Pharmacology of HIV and HCV Therapy, Washington, April 2014. This report summarises interaction studies relating

More information

Dorset Cardiac Centre

Dorset Cardiac Centre P a g e 1 Dorset Cardiac Centre Patients with Atrial Fibrillation/Flutter undergoing DC Cardioversion or Ablation procedures- Guidelines for Novel Oral Anti-coagulants (NOACS) licensed for this use February

More information