Not Recommended - New York and New Jersey AIDS Education

Report
Updated Guidelines for Managing
HIV/HCV Co-Infection
John J Faragon, PharmD, BCPS, AAHIV-P
Regional Pharmacy Director,
NY/NJ AIDS Education and Training Center
Pharmacist, HIV Medicine, Albany Medical Center
www.hcvguidelines.org
Released 1/29/14!
Abbreviations








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BOC – boceprevir
DAA – direct acting antiviral
IFN – interferon
PEG – pegylated interferon
RBV WB – ribavirin, weight based dosing
RGT – response guided therapy
SMV – simeprevir
SOF – sofosbuvir
TVR – telaprevir
www.hcvguidelines.org
IFN Ineligible Definitions
 Intolerance to IFN
 Autoimmune hepatitis and other autoimmune
disorders
 Hypersensitivity to PEG or any of its components
 Decompensated hepatic disease
 History of depression, or clinical features
consistent with depression
 A baseline neutrophil count below 1500/μL, a
baseline platelet count below 90,000/μL or
baseline hemoglobin below 10 g/dL
 A history of preexisting cardiac disease
www.hcvguidelines.org
Standard Dosing




Sofosbuvir – 400mg once daily
Simeprevir – 150mg once daily
Peg Interferon – 180mcg once weekly
Ribavirin – weight based dosing
 <75kg – 1000mg daily in divided doses
 ≥75 kg – 1200mg daily in divided doses
www.hcvguidelines.org
Drug Interactions Considerations
 Sofosbuvir
 Substrate for P-glycoprotein and breast cancer
resistance protein
 Intracellular metabolism mediated by hydrolase
and nucleotide phosphorylation pathways
 Minimal drug interactions expected
 Simeprevir
 Mild inhibitor of CYP1A2 activity and intestinal
CYP3A4
 Does not affect hepatic CYP3A4 activity
 Inhibits OATP1B1/3 and P-glycoprotein
 Multiple drug interactions expected
www.hcvguidelines.org
Sofosbuvir and HIV Medications
(1 of 2)
Concurrent Medication
Recommendation
HIV Protease Inhibitors
All HIV PIs, with or without  Concurrent use at standard doses acceptable. Interactions not
ritonavir, except tipranavir
expected based upon metabolism of sofosbuvir.
Tipranavir (Aptivus®)
 Co-administration not recommended
HIV Non Nucleoside Reverse Transcriptase Inhibitors
All NNRTIs
 Concurrent use at standard doses acceptable.
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Sofosbuvir and HIV Medications
(2 of 2)
Concurrent Medication
Recommendation
HIV Integrase Strand Transfer Inhibitors
Dolutegravir (Tivicay®)
 Concurrent use at standard doses acceptable. Interactions not
expected based upon metabolism of sofosbuvir.
Elvitegravir (contained in  Concurrent use at standard doses acceptable. Interactions not
Stribild®)
expected based upon metabolism of sofosbuvir.
Raltegravir (Isentress®)
 Concurrent use at standard doses acceptable.
HIV Entry Inhibitors
Maraviroc (Selzentry®)
 Concurrent use at standard doses acceptable. Interactions not
expected based upon metabolism of sofosbuvir.
HIV Nucleoside/Nucleotide Reverse Transcriptase Inhibitors
All NRTIs
 Concurrent use at standard doses acceptable. Interactions not
expected based upon metabolism of sofosbuvir.
www.nynjaetc.org
Simeprevir and HIV Medications
(1 of 2)
Concurrent Medication
Recommendation
HIV Protease Inhibitors
All HIV PIs

Efavirenz (Sustiva®),
Etravirine (Intelence®),
Nevirapine (Viramune®)

Significant reductions in simeprevir levels and reduced
simeprevir efficacy due to CYP3A4 induction. Coadministration not recommended.
Rilpivirine (Edurant®)

Concurrent use at standard doses acceptable.
Significant increases or decreases in simeprevir levels
expected when used with any HIV protease inhibitor, when
used with or without ritonavir. Co-administration not
recommended
HIV Non Nucleoside Reverse Transcriptase Inhibitors
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Simeprevir and HIV Medications
(2 of 2)
Concurrent Medication
Recommendation
HIV Integrase Strand Transfer Inhibitors
Dolutegravir (Tivicay®)
 Concurrent use at standard doses acceptable. Interactions
not expected based upon metabolism of simeprevir.
Elvitegravir (contained in
 Significant increase in simeprevir levels expected when used
Stribild®)
with a cobicistat containing regimen. Co-administration not
recommended.
Raltegravir (Isentress®)
 Concurrent use at standard doses acceptable.
HIV Entry Inhibitors
Maraviroc (Selzentry®)
 Concurrent use at standard doses acceptable. Interactions
not expected based upon metabolism of simeprevir.
HIV Nucleoside/Nucelotide Reverse Transcriptase Inhibitors
All NRTIs
 Concurrent use at standard doses acceptable. Interactions
not expected based upon metabolism of simeprevir.
www.nynjaetc.org
HIV/HCV Co-Infection, GT1
Preferred
Alternative
Treatment-naïve, prior PEG/RBV
relapsers, IFN eligible:
SOF + PEG/RBV(WB) x 12 weeks
Treatment-naïve, prior PEG/RBV
relapsers, IFN eligible:
SMV x 12 weeks + PEG/RBV(WB) x 24
weeks
IFN ineligible:
None
IFN ineligible:
SOF + RBV(WB) x 24 weeks
SOF + SMV ± RBV(WB) x 12 weeks
Treatment experienced, prior PEG/RBV
nonresponders, regardless of IFN
eligibility:
SOF + SMV ± RBV(WB) x 12 weeks
Treatment experienced, prior PEG/RBV
nonresponders
IFN eligible: SOF + PEG/RBV(WB) x 12
Weeks
IFN ineligible: SOF + RBV(WB) x 24
Weeks
Not Recommended:
TVR + PEG/RBV x 24 or 48 weeks (RGT), BOC + PEG/RBV x 28 or 48 weeks (RGT)
PEG/RBV x 48 weeks, SMV x 12 weeks + PEG/RBV x 48 wks
www.hcvguidelines.org
HIV/HCV Co-Infection, GT2
Preferred
Alternative
All patients, regardless of treatment
history:
SOF + RBV(WB) x 12 weeks
Treatment naive and prior PEG/RBV
relapsers:
None
Treatment experienced, prior PEG/RBV
Nonresponders:
IFN eligible: SOF + PEG/RBV(WB) X 12
Weeks
IFN ineligible: None
Not Recommended:
PEG/RBV x 24-48 weeks, or any regimen with TVR, BOC, or SMV
www.hcvguidelines.org
HIV/HCV Co-Infection, GT3
Preferred
Alternative
All patients, regardless of treatment
history:
SOF + RBV(WB) x 24 weeks
Treatment naïve, PEG/RBV relapsers:
None
Treatment experienced, prior PEG/RBV
Nonresponders:
IFN eligible: SOF + PEG/RBV(WB) X 12
weeks
IFN ineligible: None
Not Recommended:
PEG/RBV x 24 - 48 weeks, Any regimen with TVR, BOC, or SMV
www.hcvguidelines.org
HIV/HCV Coinfection, GT4
Preferred
Alternative
All patients, regardless of treatment
history:
None
IFN eligible: SOF + PEG/RBV(WB) x 12
weeks
IFN ineligible: SOF + RBV(WB) x 24
weeks
Not Recommended:
PEG/RBV x 48 weeks, any regimen with TVR or BOC
www.hcvguidelines.org
HIV/HCV Coinfection, GT 5,6
Preferred
Alternative
All patients, regardless of treatment
history:
SOF + PEG/RBV(WB) x 12 weeks
None
Not Recommended:
PEG/RBV x 48 weeks, any regimen with TVR, BOC, or SMV
www.hcvguidelines.org
HIV/HCV NOT Recommended
Not Recommended for treatment-naïve or treatment-experienced patients:
PEG/RBV with or without telaprevir or boceprevir for 24 to 48 weeks
Monotherapy with PEG, RBV, or a DAA
www.hcvguidelines.org
Other Drug Interactions with
Sofosbuvir
Medication and or Class
Rationale for Avoiding with Sofosbuvir
Anticonvulsants –

carbamazepine,
oxcarbazepine,
phenobarbital, phenytoin
Co-administration with these medications is likely to reduce
concentrations of sofosbuvir leading to reduced sofosbuvir
efficacy. Co-administration not recommended.
Antimycobacterials –
rifampin, rifabutin,
rifapentin

Co-administration with these medications is likely to reduce
concentrations of sofosbuvir leading to reduced sofosbuvir
efficacy due to intestinal P-glycoprotein (P-gp) induction
from rifampin.
Herbal products – St.
John’s Wort

Co-administration with these medications is likely to reduce
concentrations of sofosbuvir leading to reduced sofosbuvir
efficacy due to intestinal P-glycoprotein (P-gp) induction
associated with St. John’s Wort.
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Other Drug Interactions with
Simeprevir (1 of 2)
Medication and or Class
Rationale for Avoiding with Simeprevir
Anticonvulsants carbamazepine,
oxcarbazepine,
phenobarbital, phenytoin
Antibiotics – clarithromycin,
erythromycin, telithromycin

Co-administration with these medications is likely to reduce
concentrations of simeprevir and lead to reduced simeprevir
efficacy. Co-administration not recommended.

Antifungals – fluconazole,
itraconazole, ketoconazole,
posaconazole, voriconazole

Antimycobacterials –
rifampin, rifabutin,
rifapentine

Co-administration with these medications is likely to
increase concentrations of either simeprevir or the
antibiotic due to CYP3A4 and P-glycoprotein (P-gp)
inhibition. Co-administration not recommended.
Co-administration with these medications is likely to
increase concentrations of simeprevir due to CYP3A4
inhibition from the antifungals. Co-administration not
recommended.
Co-administration with these medications is likely to reduce
concentrations of simeprevir and lead to reduced simeprevir
efficacy. Co-administration not recommended.
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Other Drug Interactions with
Simeprevir (2 of 2)
Medication and or Class
Rationale for Avoiding with Simeprevir
Corticosteroids –
dexamethasone

Co-administration with dexamethasone is likely to decrease
concentrations of simeprevir and lead to reduced simeprevir
efficacy. Co-administration not recommended.
Propulsive – cisapride

Co-administration with cisapride may result in increased
concentrations of cisapride leading to potential cardiac
arrhythmias.
Herbal products – Milk
Thistle, St. John’s Wort

Co-administration with milk thistle is likely to increase
concentrations of simeprevir. Co-administration not
recommended.
Co-administration with St. John’s Wort is likely to reduce
concentrations of simeprevir leading to reduced simeprevir
efficacy, due to intestinal P-glycoprotein (P-gp) induction
associated with St. John’s Wort.

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Select HIV/HCV Resources
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NY/NJ AETC – www.nynjaetc.org
NY/NJ AETC – www.nynjaetc.org

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