INH and Rifapentine Treatment for LTBI: Expert Opinions About … · 2019-12-18 · INH and...

INH and Rifapentine Treatment for LTBI: Expert Opinions About 3HP Utilization March 17, 2016 Curry International Tuberculosis Center

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INH and Rifapentine Treatment for LTBI: Expert Opinions About 3HP A National Webinar

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Curry International TB Center

Regional Tuberculosis Training and Medical Consultation Center (RTMCC)

For more information visit our website:

http://www.currytbcenter.ucsf.edu/about/rtmcc

Project Funding

This training was funded by the Centers for Disease Control and Prevention's Cooperative Agreement U52/PS004088-01 and is a project of the University of California, San Francisco (UCSF)

The views expressed in written materials and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services, nor does the mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government

http://www.currytbcenter.ucsf.edu/about/rtmcc


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Course Credit

This webinar is approved for a total of 1.5 continuing education contact hours for doctors and nurses.

Course Credit (2)

To receive your continuing education hours, you must:

1. Pre-register

2. Attend the entire webinar

3. Complete the online evaluation

Each registered participant will be emailed an individual evaluation link which cannot be shared.


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Declaration of Disclosure

Our course faculty members have indicated that they do not have a financial relationship or conflict of interest with any commercial interest that may have a direct bearing on the subject matter. In addition, information on investigational or off-label use of pharmaceutical or medical devices will not be included.

- Heidi Behm, RN, MPH

- Marcos Burgos, MD

- Neha Shah, MD, MPH

- Mai Vu, Pharm D

Today’s Facilitator

Heidi Behm, RN, MPH

Tuberculosis Controller Public Health Division Oregon Health Authority Portland, OR


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Webinar Agenda

11:00 - 11:05

Introduction and Overview Heidi Behm, RN, MPH (facilitator) Kelly Musoke

11:05 – 12:05

3HP Discussion Marcos Burgos, MD Neha Shah, MD, MPH Mai Vu, Pharm D

12:05 – 12:30

Q & A / Conclusion Faculty

Learning Objectives

At the end of this webinar, participants will be able to: • Assess for potential drug-drug interactions when

deciding on use of 3HP for patients with latent TB infection (LTBI) undergoing treatment for other medical conditions to ensure successful treatment

• Apply lessons learned from implementation and use of the 3HP regimen for treating LTBI to appropriately plan for and effectively case manage patients on this regimen

• Prevent patient morbidity and mortality from 3HP with recommended monitoring for adverse drug reactions

• Consider practical approaches for addressing LTBI regimen change in patients unable to tolerate the 3HP regimen to ensure successful treatment


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Faculty Panel

Mai Vu,

Pharm D

Marcos Burgos,

MD

Neha Shah,

MD, MPH

Sterling, N Engl J Med, 2011

INH-RPT INH

Administration Directly-observed therapy Self-administered therapy

Frequency Weekly Daily

Duration 12 weeks 9 months

Effectiveness* 1.9 per 1,000 4.3 per 1,000

Completion rate** 82.1% 69.0%

Hepatotoxicity** 0.4% 2.7%

*non-inferior, ** statistically significant


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Post-Marketing Surveillance Project

• 16 volunteer sites participated in study design

• Patients treated from July 2011 - December 2013

• Some type of DOT was used at all sites

National Post-Marketing Implementation Project

• Slide adapted from Ho IAULTD 2014

3,288 Patients eligible to

complete treatment

2,867 (87.2%)

Completed treatment

421 (12.8%)

Discontinued treatment

175 (5.3%)

Discontinued for other

reasons

246 (7.5%)

Discontinued with symptoms


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• Slide adapted from Ho IAULTD 2014


Final Disposition No. (%)

Completed treatment without interruption 2,793 (85.0)

Temporary halted but subsequently completed

treatment 74 (2.3)

Discontinued 3HP and switched to an alternate regimen

(i.e. 9H, 6H, or 4R) 115 (3.5)

Discontinued due to adverse reaction and stopped all

LTBI treatment 131 (4.0)

Discontinuation as a result of loss to follow-up 175 (5.3)


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3HP without DOT

Belknap, Abstract presented at 2015 CROI

Summary

• 3HP and 4RIF can be first choices for LTBI treatment if no contraindications

• Higher treatment completion

• Lower hepatotoxicity

• May be able to give 3HP SAT in the future


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Flu-like Syndrome

Case:

A 42 y.o. male from Mexico has a positive IGRA, normal chest x-ray and no TB symptoms. He is started on 3HP. After the second dose the patient develops fever, headache, dizziness, achiness 2-3 hours after taking the medications.

Question:

What approach do you take when a patient reports flu-like symptoms like this?

Flu-like Syndrome

Sterling, CID 2015


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Flu-like Syndrome

Flu-like Syndrome


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Switching Regimens

Case (continues):

•The patient decides the “flu like” symptoms after taking 3HP are not tolerable. •He has completed 3 doses of 3HP

Questions: What do you do if someone needs to switch from 3HP to a different regimen?

Is “credit” given for doses already taken?

Switching Regimens

• No clinical data or published literature

– Most of it is based on clinical experience

• Would calculate the percent of the first treatment option that patient has completed and giving the second treatment option LESS that amount

– For example: patient completed 3 doses of 3HP, which is equivalent to 25%, and patient now being switch to daily INH. Patient would then finish up with approx. 7 months of INH

– Try to give patient as much as possible


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Missed Doses and Timing

Questions

When a patient is taking 3HP:

1. How many doses are too many in a row to miss?

2. At what point does LTBI treatment need to be started over from the beginning?

Missed Doses and Timing

• Completion of 3HP therapy is defined as completing at least 12 weekly doses (study called > 11 of 12 doses = complete) of treatment within 16 weeks.

• For missed or late doses – give the dose then resume the regularly scheduled day (usually the following week).

– If given in the same week, the 2 doses have to be a least 3 calendar days (72 hours) apart.

• A gap of >4 weeks is not recommended


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High LFTs Prior to Treatment Start

Questions:

1. Which regimen is the best for patients with high baseline liver function tests?

2. How should the patient be monitored?


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• RCT comparing 4RIF versus 9H

• Grade 3 or 4 hepatitis occurred in 16 of 422 (3.8%) isoniazid recipients compared with 3 of 418 (0.7%) rifampin recipients (risk difference, -3.1% [CI, -5% to -1%]; P = 0.003)


Comparing treatment choices:

• The risk of hepatotoxicity is higher with INH compared to 3HP

– HCV and baseline elevated LFT increased the risk of hepatotoxicity

• Rifampin is also associated with reduced risk of hepatotoxicity compared to INH

• Patients at high risk of hepatotoxicity: 3HP or rifampin may be preferred treatment choice

• Ultimate choice of treatment will depend on the patient and provider preference


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• Before offering treatment , balance the benefit versus the risk of treatment

• Close clinical monitoring is required

– Frequent labs and clinical monitoring is advisable

• Consider expert advise in treating and managing patients with pre-existing liver disease

Drug Interactions: Rifampin vs. Rifapentine

Question:

Does Rifapentine have the same drug/drug interactions as Rifampin?


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• Both Rifampin and Rifapentine are inducers of cytochrome 450 isoenzymes

– Induction higher with daily administration than intermittent dosing

– Induction also influenced by dose

• Levels of induction:

Rifampin >> Rifapentine > Rifabutin

• Induction by Rifapentine occurs within 4 days after the first dose

• Induction gone within 14 days after d/c Rifapentine


Take home point:

• Potential drug interactions with Rifapentine should be anticipated for all drugs that have been found to interact with Rifampin (although the magnitude of the interaction may differ)


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LTBI treatment questions:

Special Patient Populations

Methadone

Question:

We want to start treating patients with LTBI in a methadone clinic.

Should we use 3HP for LTBI treatment when the patient is on methadone?


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• Rifapentine will decrease the level or effect of methadone by affecting CYP3A4 metabolism

– Induction is gradual with maximal effect by day 10

– May need to adjust dose until steady state (approximately within 2 weeks)

– Induction property gone 2 weeks after stopping Rifapentine

• Main point: It is a significant interaction that will require close monitoring. It is not an absolute contraindication to use.

Methadone

Coumadin

Question: There may be significant drug interactions between Coumadin and the rifamycins (rifampin, rifapentine).

What are strategies for treating someone with LTBI taking Coumadin?


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• Rifapentine will decrease the level or effect of warfarin by affecting the enzyme CYP2C9/10 and CYP3A4 metabolism.

– Induction is gradual with maximal effect by day 10

– May need to adjust dose until steady state

– Induction property gone 2 weeks after stopping Rifapentine

• It is a significant interaction that will require close monitoring. It is not contraindicated (but generally would not use)

Coumadin

Antiretrovirals

Question:

Is it possible to use 3HP if the patient is on antiretroviral therapy to treat HIV?


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Antiretrovirals

• Current DHHS guidelines does NOT recommend using Rifapentine for HIV(+) patients on any antiretroviral treatment

– Insufficient data characterizing interactions between antiretrovirals and Rifapentine

• Would be concerned with putting patient at risk for virological failure and development of resistance to current HIV regimen

Dialysis

Question:

Patients on dialysis are at high risk for developing TB disease.

How do you use 3HP when a patient is on dialysis?


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Dialysis

• Rifapentine has not been studied in patients on HD

• If able to offer 3HP, try to give treatment on a day that will allow the drugs to stay in their system as long as possible

(Example- give 3HP on a Friday since next dialysis is not until next Monday)

• Give 3HP after dialysis

Elderly, Diabetic

Questions:

1. Are any special precautions needed when using 3HP if the patient is elderly and diabetic?

2. Is 3HP a good regimen for this patient?


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• Information from interaction studies between Rifampin and oral hypoglycemic agents

• Glyburide

– Levels decrease secondary to induction of CYP3A and hepatic transports

• Metformin

– Upregulation of renal organic cation transporters which may result in increased elimination of Metformin

• 3HP probably safe to use but monitor closely

Elderly, Diabetic

Drugs that should not be given and/or avoided with RIF & RPT

Contraindicated Hep C treatment combined medications Rilpivirine

Serious- Use alternative Contraceptives HIV antiretrovirals HMG-CoA reductase inhibitors (except rosuvastatin) Sildenafil Trazodone

Significant- Monitor closely Beta-blockers Calcium channel blockers (labeling recommend avoid with some Ca+ channel blockers)

Clopidogrel (potential drug interaction with INH)

Glipizide, Glyburide Methadone Oxycodone Warfarin


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Questions from Audience

Options to ask questions during webinar:

1. Phone: Press *6 to unmute your phone

2. Enter/type a question on Q & A field

Faculty Panel

Mai Vu,

Pharm D

Marcos Burgos,

MD

Neha Shah,

MD, MPH

Heidi Behm,

RN, MPH


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Webinar Evaluation

• Please remember to complete your online evaluation within 1 week

• The evaluation web link has now been emailed to all registered participants

Contact Information

Curry International Tuberculosis Center University of California, San Francisco Mailing Address: 300 Frank Ogawa Plaza, Suite 520 Oakland, CA 94612 Phone: 510-238-5100

Website: www.currytbcenter.ucsf.edu

Email: [email protected]


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INH and Rifapentine Treatment for LTBI: Expert Opinions About … · 2019-12-18 · INH and...

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