Hepatitis C

Direct acting
antivirals (DAA)
briefing

Evangelin Hii Hui Hui

Pegawai Farmasi UF 44
2020
 INTRODUCTION
 Hepatitis C is a liver disease caused by Hepatitis C virus (HCV)
 The virus is a small (55-65nm)size, enveloped single stranded RNA virus

 HCV causes acute and chronic hepatitis infection

 Wide spectrum severity: mild illness (few weeks) to serious, lifelong illness
 HEPATITIS C
VIRUS
STRUCTURE
 Enveloped RNA virus
 Flaviviridae family
 6 genotypes (GT)
 GLOBAL DISTRIBUTION OF
HEPATITIS C VIRUS
GENOTYPES
 HCV has been classified into six major genotypes
Prevalence of Genotypes in Different Areas
1a : Northern Europe, United States
1b : Global, Southern Europe
2 : Europe, North Africa
3 : Southeast Asia
4 : Middle East
5 : South Africa
6 : Asia

 Some genotypes (genotypes 1, 2 and 3) are

distributed globally, while others (genotypes 4, 5 and
6) are endemic in different geographically restricted
areas.
 Malaysia – mainly Genotype 1(30%)
and Genotype 3(70%)
 NATURAL HISTORY
Acute HCV HEPATITIS C
Chronic HCV VIRUS
Resolved 85% INFECTION
15% Cirrhosis
Stable 15%
80% HCC
Slowly progressive Liver failure
25%
75%
10 20 30
Time/year
Reference : Nancy Reau. ID Week 2015
HCC = hepatocellular carcinoma
 The Disease
Acute Hepatitis C Chronic Hepatitis C
15% 85%
 Clinically mild and typically  Is one of the leading cause of end stage
unrecognized and undiagnosed liver disease (ESLD), Hepatocellular
carcinoma (HCC) and liver related
 Acute resolution of HCV is not deaths
associated with any long term sequelae
 The effect of chronic hepatitis extend
 Treatment is indicated in patients who beyond liver related morbidity and
are deemed to develop chronic impact on the overall quality of life
hepatitis
 Achievement of sustained virologic
response (SVR) is associated with a
reduction in portal hypertension,
hepatic decompression, HCC and liver
related mortality
Reference : Westbrook RH, Dusheiko G. Natural history of hepatitis C. J Hepatol 2014;61:S58–S68.
NATIONAL STRATEGIC PLAN FOR
VIRAL HEPATITIS
VISION
Viral hepatitis transmission is halted and
everyone has access to prevention, care and
treatment for viral hepatitis.

GOAL
To eliminate viral hepatitis as a major health
threat by 2030.
NATIONAL STRATEGIC PLAN FOR
VIRAL HEPATITIS

OBJECTIVE
• To achieve 90% population living with
viral hepatitis are diagnosed.
• To achieve 90% reduction of new
cases of viral hepatitis.
• To reduce mortality due to viral
hepatitis by 65% by 2030.
• To ensure 90% of those ‘eligible
population for treatment’ are
treated by 2030.
Importance of compliance towards hepatitis
treatment (endpoint of treatment)

 To achieve sustained virological response, SVR.

 SVR is the surrogate marker for CURE in Hepatitis C infection.
 Treatment available in Hospital Sibu
 The cure rates for new DAA is between 90% and 100% in
most patients group

 Sofosbuvir and Daclatasvir ± Ribavirin

 Need to take medications for 12-24 weeks (will be

individualized based on patient’s condition)
DAA: Sofosbuvir + Daclatasvir
SOFOSBUVIR RIBAVIRIN

DACLATASVIR 60mg and

30mg
One size fits all
 Treatment duration
Genotype Treatment naive/experience Non cirrhosis Compensated cirrhosis Decompensated cirrhosis
Treatment naive 12 weeks 12 weeks 12 weeks with RBV
Genotype 1a 12 weeks with RBV or 12 weeks with RBV or
Treatment experience 12 weeks with RBV
24 weeks without RBV 24 weeks without RBV
Treatment naive 12 weeks 12 weeks 12 weeks with RBV
Genotype 1b
Treatment experience 12 weeks 12 weeks 12 weeks with RBV
Treatment naive 12 weeks 12 weeks 12 weeks with RBV
Genotype 2
Treatment experience 12 weeks 12 weeks 12 weeks with RBV
Treatment naive 12 weeks 24 weeks with RBV 24 weeks with RBV
Genotype 3 12 weeks with RBV or
Treatment experience 24 weeks with RBV 24 weeks with RBV
24 weeks without RBV
Treatment naive 12 weeks 12 weeks 12 weeks with RBV
Genotype 4 12 weeks with RBV or 12 weeks with RBV or
Treatment experience 12 weeks with RBV
24 weeks without RBV 24 weeks without RB
Treatment naive 12 weeks 12 weeks 12 weeks with RBV
Genotype 5 12 weeks with RBV or 12 weeks with RBV or
Treatment experience 12 weeks with RBV
24 weeks without RBV 24 weeks without RB
Treatment naive 12 weeks 12 weeks 12 weeks with RBV
Genotype 6 12 weeks with RBV or 12 weeks with RBV or
Treatment experience 12 weeks with RBV
24 weeks without RBV 24 weeks without RB

Hepatitis C : Screening, testing & treatment guidelines; MOH October 2017

EASL Recommendations on Hepatitis C Treatment 2016
 Sofosbuvir
 HCV nucleotide polymerase NS5B inhibitor.

 Approximately 80% of sofosbuvir is renally excreted, whereas 15% is excreted in faces.

 Used in patients with eGFR of > 30ml/min/1.73m2. Latest EASL 2018 states that can be used with cautious
in eGFR of less than 30ml/min/1.73m2 and even haemodialysis patients.

 Not metabolized by cytochrome P450.

 Sofosbuvir should not be administered with known P450 inducers, such as rifampin, carbamazepine,
phenytoin or St. John’s wort. Other potential interactions may occur with rifabutin, rifapentine and
modafinil.

 Contraindicated in patients who are being treated with the anti-arrhythmic amiodarone due to the risk of
life-threatening arrhythmias.
 Daclatasvir
First-ever approved HCV NS5A replication complex inhibitor with
pangenotypic activity.

The dose of 60 mg (one tablet) or 30 mg (one tablet) when a

reduced dose is needed, once daily dose.

May interact with other drugs e.g. Anti TB, antibiotics, herbals
containing St John Worts.

Generally well tolerated, not known side effects (SE) of its own.
< 75kg :
400mg/600mg
(1g per day)

≥ 75kg: 600mg BD
(1.2g per day)

15mg/kg/day in 2
divided doses
Common side effects
Generally well
tolerated!
1. Daclatasvir and Sofosbuvir
 Headache and fatigue (more than 10%)

2. Daclatasvir and Sofosbuvir + Ribavirin

 Headache, fatigue, nausea and anemia (more than 10%)
How to take?
 Take the pills/tablets once daily in the morning with or
without food.
 If treatment contains ribavirin, ribavirin need to take with
food especially high fat meal to increase absorption
 Miss dose management
 Ifwithin 18 hours from the usual time, take the dose
and continue the usual timing
 Ifmore than 18 hours, skip the dose and take the next
dose as usual
 Refer counseling checklist

Storage: Keep in room temperature and out of reach of children!

Management of non-adherence
 Treatment interruption
Defined as treatment was interrupted for more than 7 days

Miss dose for Taken Action

treatment for

≤ 7 days Regardless Continue treatment for the remaining duration

> 7 days < 4 weeks Restart treatment

> 7 days ≥ 4 weeks Complete treatment and do HCV RNA after 12 weeks of
treatment completion
Drug-drug interactions
Check interactions
-can access online : https://www.hep-druginteractions.org/
-download the apps (HEP iChart)
 APPS TO CHECK DRUG
drug interaction
 Management of Drugs with Potential Interaction

Stop the particular related drug for the period of treatment (2 weeks
prior to treatment/half life drug should be considered for longer
withhold) e.g.: statin.

Replace the drug with an alternative product without a drug

interaction in the same therapeutic class.

Adapt the dose with a clear monitoring plan.

Dosage adjustment.
 Management of Drugs with Potential Interaction (2)

For example:
Statin
Daclatasvir-statin: increase level of statin
If continue, can separate the timing to 6 hours apart
monitor for sign and sx of rhabdomyolysis
Dr can off the statin for 12 weeks as well in non-high risk
patient

Amlodipine
Off amlodipine and change to alternative
Or separate time of administration: am and pm
Sofosbuvir needs NO dose adjustment
Daclatasvir:
Decrease dose to 30mg: Coadministration with strong
CYP3A inhibitors (Indinavir, Azatanavir/ Ritonavir)
Increase dose to 90mg: Coadministration with strong
CYP3A inducers (e.g. Efavirenz, Nevirapine)
Medication supply workflow in
Hospital Sibu
Before supply

 Please check whether patient is in the waiting list

 Please inform prescriber if patient is not within the list

However, currently we are clearing fast expiry DAA

thus supply DAA whoever been prescribed regardless of
waiting list
 Need to achieve
During filling and transcribing.. at least 2
counseling per
patient!

First •8 weeks
supply
Subsequ •
4 weeks each
ent
First counseling

 Adherence.
 Missed dose management.
 Administration time.
 Drug Storage: room temperature (Below 30°C).
 Suggest patient diary card to record each drug intake (if indicated)
 Bring back all balance medications and empty bottle for each visit
(encouraged)
 Use of any medication or herbal/supplement product not prescribed by a
licensed physician is prohibited.
 Do not share medications with others
Subsequent counseling session

 Check
 Compliance (do pill count if needed)
 Any adverse drug reactions or side effects. Report if
needed
 Any intake of supplements/TCM/medications and check
interaction
 Documentation

 To trace MOPD card

and document if
needed
(eg intervention)

1. To take form from C8 file 2. Fill in Hepatitis C

counseling record form
Documentation Must key phis!

Or
‘Outpatient’

Choose
‘follow up’
for 2nd session
and above

Counseling entry templates