Page 7 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
P. 7
Clinical Practice Guidelines
Table 2. Indications for treatment of chronic hepatitis C in 2015: Who should be treated and when?
Treatment priority Patient group
Treatment is indicated
Treatment should be prioritized • All treatment-naïve and treatment-experienced patients with compensated and
decompensated liver disease
Treatment is justified
Treatment can be deferred • Patients with significant fibrosis (F3) or cirrhosis (F4), including decompensated
Treatment is not recommended cirrhosis
• Patients with HIV coinfection
• Patients with HBV coinfection
• Patients with an indication for liver transplantation
• Patients with HCV recurrence after liver transplantation
• Patients with clinically significant extra-hepatic manifestations
• Patients with debilitating fatigue
• Individuals at risk of transmitting HCV (active injection drug users, men who have
sex with men with high-risk sexual practices, women of child-bearing age who
wish to get pregnant, haemodialysis patients, incarcerated individuals)
• Patients with moderate fibrosis (F2)
• Patients with no or mild disease (F0-F1) and none of the above-mentioned extra-
hepatic manifestations
• Patients with limited life expectancy due to non-liver related comorbidities
Table 3. Approved HCV drugs in the European Union in 2015.
Product Presentation Posology
PegIFN-α2a Solution for injection containing 180, 135 or 90 µg of Once weekly subcutaneous injection of 180 µg
PegIFN-α2a (or less if dose reduction needed)
PegIFN-α2b Solution for injection containing 50 µg per 0.5 ml of Once weekly subcutaneous injection of 1.5 µg/
PegIFN-α2b kg (or less if dose reduction needed)
Ribavirin Capsules containing 200 mg of ribavirin Two capsules in the morning and 3 in the
evening if body weight <75 kg
Sofosbuvir Tablets containing 400 mg of sofosbuvir or
Simeprevir Capsules containing 150 mg of simeprevir Three capsules in the morning and 3 in the
Daclatasvir Tablets containing 30 or 60 mg of daclatasvir evening if body weight ≥75 kg
Sofosbuvir/ledipasvir Tablets containing 400 mg of sofosbuvir and 90 mg of One tablet once daily (morning)
ledipasvir One capsule once daily (morning)
Paritaprevir/ombitasvir/ Tablets containing 75 mg of paritaprevir, 12.5 mg of One tablet once daily (morning)
ritonavir ombitasvir and 50 mg of ritonavir One tablet once daily (morning)
Dasabuvir Tablets containing 250 mg of dasabuvir
Two tablets once daily (morning)
One tablet twice daily (morning and evening)
Ribavirin. The ribavirin dose should be 1000 or 1200 mg/day, headache. The most common adverse events (P20%) observed
based on body weight (<75 kg or P75 kg, respectively).
in combination with PegIFN-a and ribavirin were fatigue, head-
Sofosbuvir should be administered at the dose of 400 mg (one
tablet) once per day. Approximately 80% of sofosbuvir is renally ache, nausea, insomnia and anaemia. Slight elevations of creatine
excreted, whereas 15% is excreted in faeces. The majority of the kinase, amylase and lipase without clinical impact were also
sofosbuvir dose recovered in urine is the dephosphorylation- observed.
derived nucleoside metabolite GS-331007 (78%), while 3.5% is
recovered as sofosbuvir. This indicates that renal clearance is Sofosbuvir is not metabolised by cytochrome P450, but is
the major elimination pathway for GS-331007 with a large part transported by P-glycoprotein (P-gp). Drugs that are potent
actively secreted. Currently, no sofosbuvir dose recommendation P-gp inducers significantly decrease sofosbuvir plasma concentra-
can be given for patients with severe renal impairment (esti- tions and may lead to a reduced therapeutic effect. Thus sofosbuvir
mated glomerular filtration rate [eGFR] <30 ml/min/1.73 m2) or should not be administered with other known inducers of P-gp,
with end-stage renal disease due to higher exposures (up to 20- such as rifampin, carbamazepine, phenytoin or St. John’s wort.
fold) of GS-331007. Sofosbuvir exposure is not significantly chan- Other potential interactions may occur with rifabutin, rifpentine,
ged in patients with mild liver impairment, but it is increased and modafinil. No other significant drug-drug interactions have
2.3-fold in those with moderate liver impairment. been reported, in particular with all of the antiretroviral agents
tested, including emtricitabine, tenofovir, rilpivirine, efavirenz,
Sofosbuvir is well tolerated over 12 to 24 weeks of darunavir/ritonavir, and raltegravir, and there are no potential
administration. The most common adverse events (P20%) drug-drug interactions with the remaining antiretrovirals. Co-
observed in combination with ribavirin were fatigue and administration of amiodarone (and possibly dronedarone) with
sofosbuvir in combination with daclatasvir, simeprevir or
6
Table 2. Indications for treatment of chronic hepatitis C in 2015: Who should be treated and when?
Treatment priority Patient group
Treatment is indicated
Treatment should be prioritized • All treatment-naïve and treatment-experienced patients with compensated and
decompensated liver disease
Treatment is justified
Treatment can be deferred • Patients with significant fibrosis (F3) or cirrhosis (F4), including decompensated
Treatment is not recommended cirrhosis
• Patients with HIV coinfection
• Patients with HBV coinfection
• Patients with an indication for liver transplantation
• Patients with HCV recurrence after liver transplantation
• Patients with clinically significant extra-hepatic manifestations
• Patients with debilitating fatigue
• Individuals at risk of transmitting HCV (active injection drug users, men who have
sex with men with high-risk sexual practices, women of child-bearing age who
wish to get pregnant, haemodialysis patients, incarcerated individuals)
• Patients with moderate fibrosis (F2)
• Patients with no or mild disease (F0-F1) and none of the above-mentioned extra-
hepatic manifestations
• Patients with limited life expectancy due to non-liver related comorbidities
Table 3. Approved HCV drugs in the European Union in 2015.
Product Presentation Posology
PegIFN-α2a Solution for injection containing 180, 135 or 90 µg of Once weekly subcutaneous injection of 180 µg
PegIFN-α2a (or less if dose reduction needed)
PegIFN-α2b Solution for injection containing 50 µg per 0.5 ml of Once weekly subcutaneous injection of 1.5 µg/
PegIFN-α2b kg (or less if dose reduction needed)
Ribavirin Capsules containing 200 mg of ribavirin Two capsules in the morning and 3 in the
evening if body weight <75 kg
Sofosbuvir Tablets containing 400 mg of sofosbuvir or
Simeprevir Capsules containing 150 mg of simeprevir Three capsules in the morning and 3 in the
Daclatasvir Tablets containing 30 or 60 mg of daclatasvir evening if body weight ≥75 kg
Sofosbuvir/ledipasvir Tablets containing 400 mg of sofosbuvir and 90 mg of One tablet once daily (morning)
ledipasvir One capsule once daily (morning)
Paritaprevir/ombitasvir/ Tablets containing 75 mg of paritaprevir, 12.5 mg of One tablet once daily (morning)
ritonavir ombitasvir and 50 mg of ritonavir One tablet once daily (morning)
Dasabuvir Tablets containing 250 mg of dasabuvir
Two tablets once daily (morning)
One tablet twice daily (morning and evening)
Ribavirin. The ribavirin dose should be 1000 or 1200 mg/day, headache. The most common adverse events (P20%) observed
based on body weight (<75 kg or P75 kg, respectively).
in combination with PegIFN-a and ribavirin were fatigue, head-
Sofosbuvir should be administered at the dose of 400 mg (one
tablet) once per day. Approximately 80% of sofosbuvir is renally ache, nausea, insomnia and anaemia. Slight elevations of creatine
excreted, whereas 15% is excreted in faeces. The majority of the kinase, amylase and lipase without clinical impact were also
sofosbuvir dose recovered in urine is the dephosphorylation- observed.
derived nucleoside metabolite GS-331007 (78%), while 3.5% is
recovered as sofosbuvir. This indicates that renal clearance is Sofosbuvir is not metabolised by cytochrome P450, but is
the major elimination pathway for GS-331007 with a large part transported by P-glycoprotein (P-gp). Drugs that are potent
actively secreted. Currently, no sofosbuvir dose recommendation P-gp inducers significantly decrease sofosbuvir plasma concentra-
can be given for patients with severe renal impairment (esti- tions and may lead to a reduced therapeutic effect. Thus sofosbuvir
mated glomerular filtration rate [eGFR] <30 ml/min/1.73 m2) or should not be administered with other known inducers of P-gp,
with end-stage renal disease due to higher exposures (up to 20- such as rifampin, carbamazepine, phenytoin or St. John’s wort.
fold) of GS-331007. Sofosbuvir exposure is not significantly chan- Other potential interactions may occur with rifabutin, rifpentine,
ged in patients with mild liver impairment, but it is increased and modafinil. No other significant drug-drug interactions have
2.3-fold in those with moderate liver impairment. been reported, in particular with all of the antiretroviral agents
tested, including emtricitabine, tenofovir, rilpivirine, efavirenz,
Sofosbuvir is well tolerated over 12 to 24 weeks of darunavir/ritonavir, and raltegravir, and there are no potential
administration. The most common adverse events (P20%) drug-drug interactions with the remaining antiretrovirals. Co-
observed in combination with ribavirin were fatigue and administration of amiodarone (and possibly dronedarone) with
sofosbuvir in combination with daclatasvir, simeprevir or
6
