Barrier to HIV Medication Adherence - PowerPoint Presentation

Slide1

Barrier to HIV Medication Adherence

C. Ryan Tomlin, Pharm.D., BCPS, AAHIVP

Clinical Pharmacist – HIV Medicine

Slide2

Outline

Side Effects

Concerns with Pharmacokinetics

Medication ErrorsResistance

2

Slide3

Side Effects

3

Slide4

Medication Side Effects

Definition: A secondary, often undesirable effect of a medication

Most importance barrier to medication adherence

Adverse effects are decreasingBetter tolerated medicationsMore knowledge of medication effects

4

Slide5

What Case Managers Need to Know

General medication side effects

Educate patients on self-monitoring

Help limit premature discontinuation of medicationsWhen something should be brought to the providers attention urgently

5

Slide6

Antiretroviral Side Effects

Montessori V. et al, CMAJ 2004;170:229-38

6

Slide7

Most Common Side Effects Leading to Treatment Discontinuation

Hypersensitivity reaction

0

5

10

15

20

25

30

Nausea

Diarrhea

Vomiting

Gastrointestinal

Dysphagia

Headache

Insomnia

Fatigue

Dizziness

Neuropathy

Anemia

Neutrophil

Adverse event

27%

18%

16%

12%

11%

7%

7%

6%

6%

5%

5%

5%

5%

7

O’Brien ME, et al.

J

Acquir

Immune

Defic

Syndr

.

2003;34:407-414.

Slide8

Key Points

Evaluate all patients for potential side effects

Preexisting conditions can have higher risks

DiabetesHyperlipidemiaKidney diseaseHematologic problemsOne shoe does not fit all – Side effects will vary by patient

8

Slide9

Common Questions To Ask

How long has this side effect be going on?

How long have you been on your current medication?

Does anything make the side effect worse or better? (examples: sleep? food?)Has anything else changed? Other new medications? Sleep or eating habits?

9

Slide10

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Fewer side effects with newer medications

Lactic Acidosis - Buildup of lactic acid

Less common with tenofovir, abacavir, lamivudine, emtricitabine

Lipoatrophy

10

Slide11

Specific NRTI Side Effects

Abacavir

– Hypersensitivity reaction

Occurs is 5-8% of patientsFever, rash, vomiting, shortness of breathMust contact provider right awayTest for HLA*B 5701 prior to starting abacavir

Tenofovir

DF – Long-term side effects

Kidney dysfunction

Bone mineral loss

Not seen with

tenofovir

alafenamide

11

Slide12

Non-Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Fewer side effects with newer agents

Rash

Refer to providerLiver toxicityProvider will monitor routine labsGastrointestinalNausea and diarrhea

Will usually improve after a few weeks

12

Slide13

Efavirenz

(

Sustiva

®)Also in Atripla®Dizziness/DrowsinessTake at bedtime

Sleep abnormalities

Vivid dreams, Insomnia, Oversleeping

Take on an empty stomach

Worsen depression

False+ for THC in urine drug screen

Letter for patient

Require confirmatory test

13

Slide14

Protease Inhibitors (PIs)

Gastrointestinal (Nausea/Diarrhea)

Take with food

Symptoms often resolve over first few weeksHyperlipidemia / Glucose IntoleranceLess common with newer agentsDiet and exerciseLipohypertrophy

uncommon now

14

Slide15

Specific PI Side Effects

Atazanavir

– Asymptomatic Hyperbilirubinemia

Looks like jaundice, but no liver damageCosmetic side effects can be bothersome to patientsDarunavir – Rash Medication contains a sulfa component

Incidence of rash is similar between people with and without sulfa allergies

Report side effect to MD

15

Slide16

Integrase

Inhibitors

Well tolerated

Most common side effects are GINauseaDiarrheaHeadacheMuscle AcheRefer to medical provider

16

Slide17

Immune Reconstitution Inflammatory Syndrome (IRIS)

Inflammatory reaction at the site of a preexisting infection due to immune system recovery following initiation of ART

Immune system recovers and realizes there is an infection

SymptomsFever, Tiredness/fatigue, Weight lossAdditional symptoms vary based on underlying infection

17

Slide18

IRIS Risk Factors

Low CD4 count prior to medications

Large increase in CD4 following medication

High VL prior to medicationsLarge decrease in VL following medicationsHistory of AIDS-related infectionHistory of fungal infection

18

Slide19

IRIS Management

Continue antiretrovirals in most cases

Anti-inflammatory medications

NSAIDsCorticosteroidsTreat the underlying infection

19

Slide20

ARV Side Effects

Educate patients

What side effects to expect

How to handle common side effectsFollow-up phone call 2 weeks after startingEmpower patientsAsk questionsCall with problems

20

Slide21

Concerns with Pharmacokinetics

21

Slide22

How medications move through the bodyWhat the body does to the medications

22

What is Pharmacokinetics?

Amount of Medication in the Blood

Time

Absorption

Elimination

Slide23

Why Do I Need To Know Pharmacokinetics?

To understand what medication factors impact adherence

To know why taking medication a specified way is important

Time of dayWith/without food

23

Slide24

Consequences of Taking Medication Inappropriately

Toxic Concentrations

More Side Effects

Viral Resistance

Efficacy

Minimally Effective Concentration

24

Dose

Dose

Amount of Medication in the Blood

Time

Slide25

Pharmacokinetic Categories - ADME

A

bsorption – How does the body take in the medication?

Distribution – Once in the body, where does the medication go?Metabolism – How does the body change or break down the medication?Elimination – How does the body remove the medication?

25

Slide26

Absorption: Routes

Oral

Intravenous

BuccalTransdermalSublingualEye, Ear, NoseRectalIntramuscularSubcutaneousInhalationVaginal

Intrathecal

Intrasynovial

Intracardiac

26

Slide27

Absorption: Impact of Food

Food can increase how much medication gets into the body – for better or worse

27

Reyataz

with Food

Good

Atripla

with Food

Bad

Slide28

Distribution

Transfer of medication from one place to another

Some medication stays in the blood, some goes to tissues and organs

28

Slide29

Long-Acting Injectable Medications

Cabotegravir

and

Rilpivirine are being studied as once-monthly injectionsAbsorption Route – Intramuscular (Intragluteal)Distribution – Very Very Slowly

29

Slide30

Metabolism

Many medications are broken down in the liver

This can turn an active medication into waste

This can turn an inactive medication into an active, usable form

How a medication in metabolized is important for determining drug interactions

30

Slide31

Metabolism: Drug Interactions

Many medication are broken down with the same tools in the liver

When given together they compete and the levels of one medication can increase

31

Slide32

“Boosted” Protease Inhibitors (PIs)

Boosters prevent breakdown of PIs in the liver

Result is higher blood levels of the PI for a longer time

32

Slide33

Excretion

How medication is removed from the body

Kidneys

Bile / FecesLungs33

Slide34

Excretion: Dosing Changes

Patients with damaged kidneys may require lower doses since less medication is being removed

34

Amount of Medication in the Blood

Time

Damaged Kidneys

Healthy Kidneys

Slide35

Medication Errors

35

Slide36

Common Causes

Patient Misuse

Poor understating of directions

No knowledge of interactions / OTC medicationsDon’t fully grasp importancePoor Communication/ProceduresLack of standardization with ARTTransitions in care

Lack of Product Knowledge/Training

Specialty area of medicine

36

http://www.fda.gov/Drugs/DrugSafety/MedicationErrors/default.htm

Slide37

Common Errors Made

By Healthcare Professionals

Wrong Medication

Wrong DoseMissing Medications / InformationDrug Interactions

Slide38

Wrong Medication: Look/Sound Alike

Retrovir

/Ritonavir

Nelfinavir/NevirapineViracept/Viramune/

Viread

Invirase

/

Efavirenz

Combivir

/

Trizivir

Isentress

/

Intelence

Prezista

/

PrezcobixReyataz/EvotazGray J et al. AIDS Patient Care and STDs 205;19:803-12. Faragon J et al. AIDS Read 2003;13:268-8038

Slide39

Wrong Medication: Combo Pills

Single medication given in place of the combination

Abacavir dispensed in place of Epzicom (abacavir/lamivudine)

Tivicay (dolutegravir) dispensed in place of Triumeq (dolutegravir/abacavir/lamivudine)

39

Slide40

Wrong Medication: Abbreviations

HIV providers

LOVE

abbreviationsAZT – Zidovudine / AzidothymidineAztreonamAzathioprine

Azithromycin

ART

Example regimen:

ABC/3TC, TDF, DRV/r

How many medications?

How many different prescriptions?

40

Slide41

Wrong Medication Dose or Frequency

Medication dosage make need to be changed based on:

Patient’s kidney function

Past medication resistancePatient’s weight (pediatric patients)Pregnancy

Slide42

Missing Medications/Information

All patients on therapy should have 3 ART

Doesn’t have to be 3 pills

Don’t take one without the othersRitonavir & Cobicistat don’t countJuluca and

Dovato

(2 medications) are the only exceptions

Don’t forget to document time of day taken and relation to food

Ask the patient!

Once daily doesn’t always mean 0900

42

Slide43

Drug Interactions: Liver Enzymes

Enzymes in the liver can be either induced or inhibited

Adapted from Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 9

th

ed.

43

Slide44

Medications Metabolized In The Liver

Antidepressants

Anxiolytics

Cholesterol Medications – StatinsPDE-5 Inhibitors – Viagra, CialisInhaled/Intranasal CorticosteroidsContraceptivesPain Medications – Methadone

Slide45

Common Errors Made

By Patients

Wrong Administration Time

Missed / Late DosesDrug Interactions With Over The Counter Medications / Herbal Medications

Slide46

Wrong Administration Time: Food

Change in Total Drug Level Based on Food

Antiretroviral

With Food

Empty Stomach

Atazanavir

- 70%

Indinavir

- 77%

Nelfinavir

- 3 fold

Saquinavir

- 6 fold

Tipranavir

- 30%

Darunavir

- 30%

Efavirenz

+ 28% (+79%Cmax)

Rilpivirine

- 40%

46

Reyataz

[Product Insert]. Princeton, NJ: Bristol-Myer Squibb;2010.

Crixivan

[Product Insert]. Whitehouse Station, NJ: Merck & Co;2009.

Viracept

[Product Insert]. La Jolla, CA:

Agouron

; 2008.

Invirase

[Product Insert]. Nutley, NJ: Roche Labs;2010.

Aptivus

[Product Insert]. Ridgefield, CT:

Boehringher

Ingelheim;2009.

Prezista

[Product Insert]. Raritan, NJ: Janssen Products;2006.

Sustiva

[Product Insert]. Princeton,

NJ:Bristol-Myer

Squibb;2010.

Edurant

[Product Insert]. Titusville, NJ: Janssen Products;2011

Slide47

Missed / Late Doses

Missed doses can cause:

Detectable viral loads

Increased risk of HIV transmissionDevelopment of HIV resistanceLate doses are better than doses missed entirelyIn general, follow the “Half Way” ruleIf you remember and it is less than half way till your next dose, take it

Never double up on medications

Slide48

Drug Interactions: Heartburn Medication

Atazanavir

and

rilpivirine require stomach acid for absorption

Atazanavir

Rilpivirine

Proton

Pump Inhibitors (ex: Prilosec)

Separate by 12 hours

AVOID

H2 Antagonists (ex: Zantac)

Separate by 10 hours

Cannot be given 12 hours before or 4 hours after RPV

Antacids

(ex: TUMS)

Cannot be given 1 hour before or 2 hours after ATV

Cannot be given 2 hour before or 4 hours after RPV

48

DHHS Guidelines for the Use of ARV Agents in HIV-1-Infected Adults and Adolescents, 5-1-15.

Slide49

Drug Interactions: Inhaled/Intranasal Corticosteroids

49

DHHS Guidelines for the Use of ARV Agents in HIV-1-Infected Adults and Adolescents, 5-1-15.

Slide50

Polyvalent cations: Zinc, Iron, Calcium, Aluminum, Magnesium (ZICAM)

Found in antacids, laxatives, supplements, prenatal vitamins,

sucralfate

Can bind and inactivate raltegravir, elvitegravir, dolutegravir, and bictegravirEach medication has unique guidance on how to avoid this interaction

Drug Interactions: Polyvalent

Cations

50

DHHS Guidelines for the Use of ARV Agents in HIV-1-Infected Adults and Adolescents, 5-1-15.

Slide51

No information ≠ No interactionMinimal information

No studies conducted

Monitor how each medication in metabolized

3A4 inducers: St. John’s wort, gingko biloba extract, echinacea

Drug Interactions: Herbal Products

51

Slide52

Prevention: What Can You Do?

Educate yourself

Keep communication open with all members of the patients healthcare team

Avoid abbreviationsPay attention to timing and how medications should be takenAsk about new medications / Check for interactions

52

Slide53

Prevention: How Can We Empower Clients?

Education! Education! Education!

Goals of therapy

Combinations medicationsAdherence as it relates to resistanceDirections (twice daily vs every 12 hours?)Food requirements

Common drug interactions

Encourage patients to always ask questions of ALL healthcare providers

53

Slide54

Prevention: How Can We Implement System-Wide Processes?

Encourage patients to have only 1 pharmacy

As available, limit barriers to communication between health-systems, medical records, pharmacy, etc.

Be familiar with, or have cheat sheets available of both brand and generic medication namesWhen in doubt, ask the patient!

54