Community Pharmacy Considerations for HIV - PowerPoint Presentation

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Community Pharmacy Considerations for HIV & HCV Therapy

Larry Pineda,

PharmD

,

PhC

, BCPS, AAHIVP

Visiting Assistant Professor

UNM College of PharmacySlide2

Conflicts of Interest DisclosureNo conflicts of interest

2Slide3

Learning Objectives – PharmacistList the DHHS recommended HIV antiretroviral regimens

Describe current HCV direct-acting antivirals

Discuss the importance of adherence counseling for HIV

antiretrovirals

and HCV direct-acting antivirals

Recognize common prescription and nonprescription drug interactions with HIV

antiretrovirals and HCV direct-acting antivirals

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Learning Objectives – Pharm TechIdentify common HIV

antiretrovirals

and HCV direct-acting antivirals

State the minimum number of antiretroviral drugs in an appropriate HIV antiretroviral regimen

Understand the importance of adherence counseling for HIV

antiretrovirals

and HCV direct-acting antiviralsDescribe the impact of drug-drug interactions with HIV and HCV medications 

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HIV therapy considerationsSlide6

HIV Antiretroviral TherapyInhibit viral replication

HIV life cycle

Antiretroviral drugs target key steps in replication

https://www.youtube.com/watch?v=odRyv7V8LAE

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Figure: http://collections.infocollections.org/whocountry/en/d/Jh4325e/7.htmlSlide7

HIV Antiretroviral TherapyEntry inhibitors

Attachment

Selz

entry

(

maraviroc

)FusionFuzeon

(

enfuvirtide

)

Reverse transcriptase inhibitors

Nucleoside

Truvada

(

tenofovir

disoproxil

(TDF)/

emtricitabine

)Descovy (tenofovir alafenomide (TAF)/emtricitabine)Epzicom (abacavir/lamivudine)Non-nucleoside Sustiva (efavirenz)Edurant (rilpivirine)

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HIV Antiretroviral TherapyIntegra

se strand transfer

inhibitors

Isentress

(

ral

tegravir)Vitekta (

elvi

tegravir

)

Always with

cobicistat

(booster)

Tivicay

(

dolu

tegravir

)

Protease inhibitorsPrezista (darunavir)Reyataz (atazanavir)Norvir (ritonavir)8Slide9

DHHS Recommended AgentsUpdated July 2016

Available at:

https://

aidsinfo.nih.gov/guidelines

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recommended HAART regimens:

4 integrase-based regimens

1

protease inhibitor-based

regimen

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Integrase-Based RegimensSingle tablet

Triumeq

(

dolutegravir

/

abacavir

/lamivudine)Genvoya (elvitegravir

/

cobicistat

/TAF/

emtricitabine

) or

Stribild

(

elvitegravir

/

cobicistat

/TDF/emtricitabine)Two tabletDolutegravir + TDF/emtricitabine or TAF/emtricitabineRaltegravir* + TDF/emtricitabine or TAF/emtricitabine

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*Twice daily dosing

https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-treatment-guidelines/0/Slide11

Protease Inhibitor-Based Regimen Darunavir/ritonavir

+ TDF/

emtricitabine

or

TAF/

emtricitabineAtazanavir based regimens moved to alternative

Non-nucleoside reverse transcriptase inhibitor based regimens on alternative list

Entry inhibitors typically reserved for patients with resistance to recommended agents

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https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-treatment-guidelines/0/Slide12

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HAARTHighly

A

ctive

A

nti-

R

etroviral Therapy3 active antiretroviral drugs2 nucleoside reverse transcriptase inhibitors

Plus 3

rd

active agent:

Integrase strand transfer inhibitor

Non-nucleoside reverse transcriptase inhibitor

Protease inhibitor with pharmacokinetic enhancer (

cobicistat

, ritonavir)

Goal: undetectable HIV viral load

Adherence

critical for success

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https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-treatment-guidelines/0/Slide14

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Virologic Impact of Adherence

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Patterson DL et al. Ann Intern Med. 2000;133:21-30Slide16

Virologic Impact of Adherence

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Low-Beer S et al. J Acquir Immune Defic Syndr. 2000; 23:360-1Slide17

Adherence ConsiderationsDo not assume prescriber has provided education

Monitor refill history

Offer

adherence devices

Pill box

Blister packaging

Reminders (alarms, logs, apps, visual med calendar)Recognize “outdated” regimens

Screen for polypharmacy

Avoid treatment gaps

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Antiretroviral ConsiderationsDo not dispense partial regimens

Question regimens with < 3 agents

Truvada

for

preexposure

prophylaxis (

PrEP) and nuc

-sparing regimens are exception

Recognize “outdated” regimens

Quality of life

Assist with prior authorizations

Facsimile response monitoring

Drug interactions

Alert fatigue

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Drug InteractionsNew agents have less

drug interactions

Are

not

void of interactions

Keep in mind OTC/supplements/herbals

Bookmark key resourcesDon’t assume provider has checked

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Integrase InhibitorsLow drug interactions

Polyvalent cations

Ca

++

, Fe

++

, Mg++, Zn++

, Al

+++

Chelate integrase inhibitors

Does not include food products

Maalox, Tums, multivitamins

Administer

2 hours before or 6 hours after taking

products containing

polyvalent

cations

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http://www.hiv-druginteractions.org/Slide21

St. John’s Wort

Induction

of UGT1A1 and CYP3A4

Decreased

dolutegravir

exposureDecreased elvitegravir/cobicistat

concentrations

Potentially decreased

raltegravir

exposure

Decreased

darunavir

concentrations

http://www.hiv-druginteractions.org/

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HerbalsInduce CYP3A4

Garlic supplements

Can induce CYP3A4 and/or P-

gp

Inconsistent

data on

allicin containing formulationsDoes not apply to dietary exposure

Dolutegravir

, ritonavir and

cobicistat

Ginkgo biloba

Inhibit CYP3A4

Grapefruit, goldenseal, ginseng

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Pharmaceutical BoostersRitonavir

and

cobicistat

Inhibit CYP3A4, others vary

Anticoagulants

Warfarin (R enantiomer)

Monitor INRApixaban

, dabigatran, rivaroxaban,

ticagrelor

Avoid concomitant use

Anticonvulsants

Carbamazepine, phenobarbital, phenytoin

Decreases

dolutegravir

– UGT1A1, CYP3A4 induction

Alternative –

levetiracetam

(

Keppra

)23http://www.hiv-druginteractions.org/Slide24

CorticosteroidsInteraction with both ritonavir and

cobicistat

Cushing’s syndrome, adrenal suppression

Intranasal

Fluticasone (Flonase)*

Triamcinolone (Nasacort)*

Budesonide (

Rhinocort

)*

Inhaled

Fluticasone/salmeterol (Advair)

Budesonide/formoterol (

Symbicort

)

Alternative

Beclomethasone (QVAR, QNASL)

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*available over the counter

http://www.hiv-druginteractions.org/Slide25

Serotonin Reuptake Inhibitor (SSRI)Paroxetine, fluoxetine, citalopram

Metabolized by CYP2D6

Ritonavir inhibits metabolism

Increased SSRI exposure

Sertraline

Metabolized

by CYP2B6

Ritonavir induces metabolism

Decreased SSRI exposure

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http://www.hiv-druginteractions.org/Slide26

Drug Interaction Resource

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http://www.hiv-druginteractions.org/

Also available as an app:

hivichartSlide27

Hcv

therapy considerationsSlide28

AbbreviationsSVR: sustained

virologic

response

IFN: interferon

RBV: ribavirin

Peg:

pegylated

BOC:

boceprevir

TPV:

telaprevir

SMV:

simeprevir

SOF:

sofosbuvir

PrOD

:

paritaprevir

/ritonavir +

ombitasvir + dasabuvirPrO

:

paritaprevir

/ritonavir +

ombitasvir

DCV:

daclatasvir

EBR/GZR:

elbasvir

/

grazoprevir

LDV/SOF:

ledipasvir

/

sofosbuvir

SOF/VEL:

sofosbuvir

/

velpatasvir

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HCV TreatmentHistorically complex therapy

Gastroenterology, hepatology, infectious diseases

Severe side effects, injectable

Low cure rates

Advent of new direct acting all oral medications has simplified management

Less side effects

Shorter durationHigher cure rates

Goal of treatment is SVR

New agents highly effective SVR rates >90%

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Slide courtesy Paulina Deming, PharmD, PhC

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Evolution

of

HCV Treatment

SVR (%)

IFN

6

mos

PegIFN

RBV

12

mos

IFN

12 mos

IFN/RBV

12

mos

PegIFN

12

mos

2001

1998

2011

Standard

IFN

RBV

PegIFN

1991

BOC and TPV

PegIFN

/

RBV/

BOC or TPV

6-12

mos

IFN/RBV

6

mos

6

16

34

42

39

55

70+

0

20

40

60

80

100

2013

SOF

89+

SMV

80+

PegIFN

/

RBV/

SMV

24-48

wks

PegIFN

/

RBV/

SOF

12-24

wks

2014

LDV/SOF

>90

>90

PrOD

LDV/ SOF

8-12

wks

PrOD

+ RBV

12-24

wks

EBR/ GZR

12-16

wks

SOF + DCV

12

wks

DCV+ SOF

EBR/ GZR

2016

>90

>90

SOF/ VEL

>90

SOF/ VEL

12

wksSlide31

Key Differences in HCV TherapyPegIFN Based

Therapy

Injections

Significant laboratory abnormalities

Pancytopenias

Ribavirin



hemolytic

anemia

Substantial side effect profile

Limited use in advanced liver disease

Limited drug interaction potential

Low

SVR

Direct Acting

Antivirals

All oral

Limited laboratory abnormalities

Ribavirin

 hemolytic anemia Low side effect profileVariable drug interaction potentialVariable use in advanced liver diseaseHigh SVREmerging concerns for HCV resistance

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HCV Treatment HighlightsGuided by HCV genotype

G1a most common in US

Finite

duration of

treatment

Typically ~12 weeks

Adherence vital for treatment successRetreatment

Lower SVR rates

Longer duration,

+

ribavirin

Cost of treatment

high

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http://www.hepatitisc.uw.edu/

http://www.hcvguidelines.org

/Slide33

Cost of HCV Treatment

33

http://www.hepatitisc.uw.eduSlide34

HCV Drug TargetsSlide courtesy Monique, Dodd, PharmD, MLS(ASCP)

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Core

E1

E2

P7

NS2

NS3

4A

NS4B

NS5A

NS5B

5’UTR

3’UTR

Ribavirin

NS3 Protease Inhibitors

NS5A Replication Complex Inhibitors

NS5B Polymerase

(Nucleotide) Inhibitors

NS5B Polymerase

(Non-nucleotide) Inhibitors

Boceprevir

(

BOC)

Telaprevir

(TVR)

Simeprevir

(SMV)

Paritaprevir

(PTV)

Grazoprevir

(GRZ)

Daclatasvir (DCV)

Ledipasvir

(LDV)

Ombitasvir

(OMV)

Elbasvir

(EBR)

Velpatasvir

(VEL)

Sofosbuvir

(SOF)

Dasabuvir

(DSV)

Pulled from marketSlide35

HCV Direct Acting Antivirals (DAAs)

Target

NS3/4A: Protease Inhibitors

(-

previr

)

NS5A: Replication Complex Inhibitors

(-

asvir

)

NS5B: Polymerase Inhibitors

(-

buvir

)

DAA

Boceprevir

*

Telaprevir

*

SimeprevirParitaprevir

Grazoprevir

Ledipasvir

Ombitasvir

Daclatasvir

Elbasvir

Velpatasvir

Nucleotide:

Sofosbuvir

Non-nucleoside:

Dasabuvir

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* Pulled from marketSlide36

Treatment ResourcesJoint guidelines

of the American

Association for the Study of Liver Diseases (AASLD) and Infectious Diseases Society of America (IDSA)

Updated

frequently

– check online for most current version of guidelines

Available at: http://www.hcvguidelines.org

/

Hepatitis C Online (Univ. of Washington)

http://www.hepatitisc.uw.edu

/

HCV medication information, calculators, guidance

HCV course (modules)

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Pharmacy ConsiderationsHigh cost – specialty pharmacy

High

copays, patient assistance networks

Avoid treatment gaps

Time it takes to order medication

Counseling:

Adverse effectsAdherence

Despite short, finite duration

Drug interactions

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Side Effect Profile of DAAsMost commonly reported side effects:

Headache

Fatigue

Nausea

Most common laboratory abnormalities:

ALT elevations with

PrOD and ethinyl-estradiol use; ALT elevations with EBR/GZR

Anemia with concomitant use of ribavirin

Ribavirin causes hemolytic anemia

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http://www.hepatitisc.uw.edu/Slide39

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HCV Therapy AdherenceNo published literature on DAA adherence correlation to

SVR

Optimal adherence yet

to be determined

Recommend

100% adherent to

DAAsAdherence assessment and counseling at all healthcare encounters

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Drug Interaction Concerns for DAAs

Overall have low potential for drug-drug interactions

Amiodarone with

sofosbuvir

and other DAA

Serious symptomatic bradycardia

Potential for other drugs to lower DAA concentrationsStrong CYP3A

inducers (e.g. carbamazepine

, oxcarbazepine, phenobarbital,

phenytoin)

Strong intestinal P-glycoprotein inducers (e.g. rifampin)

St. John’s wort (avoid

all

herbals/supplements)

Statins

Interactions vary by DAA and statin

www.hep-druginteractions.org

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Acid Suppressive Therapy

Ledipasvir

and

velpatasvir

solubility decreases with increases in

pH

Requires acidity for absorption – greatest concern with velpatasvir

Antacids

S

eparate administration

by 4

hours

H2RAs

A

dministered

simultaneously with or 12 hours

apart

PPIs

C

an be administered simultaneously if medically necessary42www.hep-druginteractions.orgSlide43

Drug Interaction Resource

43

www.hep-druginteractions.org

Also available as an app:

hepichartSlide44

Patient CaseDD is a 48 year old HIV+ male with HCV coinfection. His provider has prescribed

Harvoni

(

ledipasvir

/

sofosbuvir

) x 12 weeks. Medications: famotidine prn heartburn, Tums prn heartburn, dolutegravir

,

emtricitabine

/TDF, acyclovir

No known drug allergies

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Questions/considerations?