l CONCEPTION AND CONTRACEPTION Effective
contraception required during treatment—consult product
l PREGNANCY Manufacturers recommend avoid unless
potential benefit outweighs risk (toxicity in animal
l BREAST FEEDING Manufacturers advise avoid—no
l HEPATIC IMPAIRMENT Avoid in severe impairment.
Monitoring Close monitoring required in mild to moderate
l RENAL IMPAIRMENT For further information on
peginterferon alfa use in renal impairment consult product
Dose adjustments Reduce dose in moderate to severe
Monitoring Close monitoring required in renal
l MONITORING REQUIREMENTS Monitoring of lipid
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Peginterferon alfa and ribavirin for mild chronic hepatitis C
(August 2006 and September 2010) NICE TA200
The combination of peginterferon alfa and ribavirin can be
used for treating mild chronic hepatitis C in patients over
18 years. Alternatively, treatment can be delayed until the
disease has reached a moderate stage (‘watchful waiting’).
Peginterferon alfa alone can be used if ribavirin is contraindicated or not tolerated.
▶ Peginterferon alfa, interferon alfa, and ribavirin for moderate
to severe chronic hepatitis C (January 2004 and September
The combination of peginterferon alfa and ribavirin should
be used for treating moderate to severe chronic hepatitis C
in patients aged over 18 years:
. not previously treated with interferon alfa or
. treated previously with interferon alfa alone or in
. whose condition did not respond to peginterferon alfa
alone or to a combination of peginterferon alfa and
ribavirin, or responded but subsequently relapsed;
Peginterferon alfa alone should be used if ribavirin is
contra-indicated or not tolerated. Interferon alfa for either
monotherapy or combined therapy should be used only if
neutropenia and thrombocytopenia are a particular risk.
Patients receiving interferon alfa may be switched to
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
EXCIPIENTS: May contain Benzyl alcohol
▶ Pegasys (Roche Products Ltd)
Peginterferon alfa-2a 180 microgram per 1 ml Pegasys
Peginterferon alfa-2a 270 microgram per 1 ml Pegasys
Peginterferon alfa-2a 360 microgram per 1 ml Pegasys
Other drugs used for Chronic hepatitis C Interferon alfa,
p. 956 . Peginterferon alfa, p. 623
Elbasvir with grazoprevir 24-Apr-2017
l DRUG ACTION Elbasvir is an HCV NS5A inhibitor and
grazoprevir is an HCV NS3/4A protease inhibitor; they
reduce viral load by inhibiting hepatitis C virus RNA
Chronic hepatitis C infection of genotypes 1 or 4 (with or
without ribavirin) (initiated by a specialist)
▶ Adult: 50/100 mg once daily for 12 weeks (may extend
to 16 weeks in some circumstances—consult product
DOSE EQUIVALENCE AND CONVERSION
▶ Dose expressed as x/y mg elbasvir/grazoprevir.
MHRA/CHM ADVICE: DIRECT-ACTING ANTIVIRALS TO TREAT
CHRONIC HEPATITIS C: RISK OF INTERACTION WITH VITAMIN K
ANTAGONISTS AND CHANGES IN INR (JANUARY 2017)
An EU-wide review has identified that changes in liver
antagonists; the MHRA has advised that INR should be
monitored closely in patients receiving concomitant
HEPATITIS B REACTIVATION (JANUARY 2017)
An EU-wide review has concluded that direct-acting
antiviral interferon-free regimens for chronic hepatitis C
can cause hepatitis B reactivation in patients co-infected
with hepatitis B and C viruses; the MHRA recommends
to screen patients for hepatitis B before starting
treatment—patients infected with both hepatitis B and C
viruses must be monitored and managed according to
MHRA/CHM ADVICE: DIRECT-ACTING ANTIVIRALS FOR CHRONIC
HEPATITIS C: RISK OF HYPOGLYCAEMIA IN PATIENTS WITH
glucose metabolism in patients with diabetes and result
in symptomatic hypoglycaemia if diabetic treatment is
The MHRA advises healthcare professionals:
. to monitor glucose levels closely in patients with
diabetes during direct-acting antiviral therapy for
hepatitis C, especially within the first 3 months of
treatment and modify diabetic medication or doses
. to be vigilant for changes in glucose tolerance and
advise patients of the risk of hypoglycaemia;
. to inform the healthcare professional in charge of the
diabetic care of the patient when direct-acting
antiviral therapy is initiated.
l CAUTIONS Hepatitis B co-infection .re-treatment
following previous exposure to elbasvir with grazoprevir,
or to drugs of the same classes (NS5A inhibitors or NS3/4A
inhibitors other than telaprevir, simeprevir, boceprevir)—
l INTERACTIONS → Appendix 1: elbasvir. grazoprevir
▶ Common or very common Alopecia . anxiety . appetite
discomfort. headache . insomnia . irritability . myalgia . nausea . pruritus . vomiting
▶ Uncommon Anaemia .transient ischaemic attack
l PREGNANCY Manufacturer advises use only if potential
l BREAST FEEDING Manufacturer advises avoid—present in
l HEPATIC IMPAIRMENT Manufacturer advises avoid in
moderate to severe impairment.
l MONITORING REQUIREMENTS Manufacturer advises
monitor liver function before treatment, at week 8 in all
patients, at week 12 in patients receiving 16 weeks of
treatment, and then as clinically indicated—consider
discontinuing treatment if alanine aminotransferase (ALT)
is greater than 10 times the upper limit of normal;
discontinue treatment if ALT elevation is accompanied by
signs or symptoms of hepatic impairment or inflammation.
Hepatic effects Manufacturer advises that patients and their
carers should consult a healthcare professional if signs and
symptoms of hepatic dysfunction occur (including fatigue,
weakness, lack of appetite, nausea and vomiting, jaundice
Vomiting Manufacturer advises if vomiting occurs within
4 hours of a dose, an additional dose should be taken.
Missed doses Manufacturer advises if a dose is more than
16 hours late, the missed dose should not be taken and the
next dose should be taken at the normal time.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Elbasvir–grazoprevir for treating chronic hepatitis C (October
Elbasvir with grazoprevir is recommended, within its
marketing authorisation, as an option for treating
genotype 1 or 4 chronic hepatitis C infection:
. of genotype 1a—12 weeks’ treatment (consider use in
combination with ribavirin for 16 weeks in patients with
a baseline hepatitis C virus RNA level of more than
800 000 IU/mL or specific NS5A polymorphisms causing
at least a 5-fold reduction in activity of elbasvir);
. of genotype 1b—12 weeks’ treatment;
. of genotype 4—12 weeks’ treatment (consider use in
combination with ribavirin for 16 weeks in patients with
a baseline hepatitis C virus RNA level of more than
This is contingent on the manufacturer providing the drug
at the same price or lower than that agreed with the
www.nice.org.uk/guidance/ta413
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium advises (December
2016) that Zepatier ® (elbasvir with grazoprevir) is accepted
for use within NHS Scotland for the treatment of chronic
hepatitis C in adults with genotype 1a, 1b or 4; this advice
is contingent upon the continuing availability of the
Patient Access Scheme in NHS Scotland or a list price that
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 3
ELECTROLYTES: May contain Sodium
▶ Zepatier (Merck Sharp & Dohme Ltd) A
Elbasvir 50 mg, Grazoprevir 100 mg Zepatier 50mg/100mg tablets
ANTIVIRALS › NON-STRUCTURAL PROTEIN 5A
Ombitasvir with paritaprevir and
The properties listed below are those particular to the
combination only. For the properties of the components
please consider, ritonavir p. 659.
Chronic hepatitis C of genotype 1 (in combination with
dasabuvir, with or without ribavirin)| Chronic hepatitis C
of genotype 4 (in combination with ribavirin)
▶ Adult: 2 tablets once daily for duration of treatment
consult product literature, to be taken with food
MHRA/CHM ADVICE: DIRECT-ACTING ANTIVIRALS TO TREAT
CHRONIC HEPATITIS C: RISK OF INTERACTION WITH VITAMIN K
ANTAGONISTS AND CHANGES IN INR (JANUARY 2017)
An EU-wide review has identified that changes in liver
antagonists; the MHRA has advised that INR should be
monitored closely in patients receiving concomitant
HEPATITIS B REACTIVATION (JANUARY 2017)
An EU-wide review has concluded that direct-acting
antiviral interferon-free regimens for chronic hepatitis C
can cause hepatitis B reactivation in patients co-infected
with hepatitis B and C viruses; the MHRA recommends
to screen patients for hepatitis B before starting
treatment—patients infected with both hepatitis B and C
viruses must be monitored and managed according to
MHRA/CHM ADVICE: DIRECT-ACTING ANTIVIRALS FOR CHRONIC
HEPATITIS C: RISK OF HYPOGLYCAEMIA IN PATIENTS WITH
glucose metabolism in patients with diabetes and result
in symptomatic hypoglycaemia if diabetic treatment is
The MHRA advises healthcare professionals:
. to monitor glucose levels closely in patients with
diabetes during direct-acting antiviral therapy for
hepatitis C, especially within the first 3 months of
treatment and modify diabetic medication or doses
. to be vigilant for changes in glucose tolerance and
advise patients of the risk of hypoglycaemia;
. to inform the healthcare professional in charge of the
diabetic care of the patient when direct-acting
antiviral therapy is initiated.
l CONTRA-INDICATIONS HIV co-infection without
suppressive antiretroviral therapy
l CAUTIONS Retreatment—efficacy not established
l INTERACTIONS → Appendix 1: HIV-protease inhibitors . ombitasvir. paritaprevir
▶ Common or very common Anaemia . asthenia . insomnia . nausea . pruritus
▶ Rare or very rare Angioedema
▶ Frequency not known Depression . suicidal behaviour
SIDE-EFFECTS, FURTHER INFORMATION Side-effects listed
are reported when ombitasvir with paritaprevir and
BNF 78 Chronic hepatitis C 625
ritonavir is used in combination with dasabuvir, with or
treatment; effective contraception should be used during
l PREGNANCY Manufacturer advises avoid—toxicity in
l BREAST FEEDING Manufacturer advises avoid—present in
l HEPATIC IMPAIRMENT Manufacturer advises avoid in
moderate to severe impairment.
Missed doses If a dose is more than 12 hours late, the
missed dose should not be taken and the next dose should
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Ombitasvir with paritaprevir and ritonavir with or without
dasabuvir for treating chronic hepatitis C NICE TA365
Ombitasvir with paritaprevir and ritonavir with or without
dasabuvir is recommended, within its marketing
authorisation, as an option for treating genotype 1 or 4
chronic hepatitis C in adults, only if the manufacturer
provides it with the discount agreed in the patient access
www.nice.org.uk/guidance/ta365
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 21, 25
EXCIPIENTS: May contain Propylene glycol
Ombitasvir 12.5 mg, Ritonavir 50 mg, Paritaprevir 75 mg Viekirax
12.5mg/75mg/50mg tablets | 56 tablet P £10,733.33
ANTIVIRALS › NUCLEOSIDE ANALOGUES
▶ BY INHALATION OF AEROSOL, OR BY INHALATION OF NEBULISED
▶ Child 1–23 months: Inhale a solution containing
20 mg/mL for 12–18 hours for at least 3 days, maximum
of 7 days, to be administered via small particle aerosol
Life-threatening RSV, parainfluenza virus, and adenovirus
infection in immunocompromised children
(administered on expert advice)
▶ Child: 33 mg/kg for 1 dose, to be administered over
15 minutes, then 16 mg/kg every 6 hours for 4 days,
then 8 mg/kg every 8 hours for 3 days
Chronic hepatitis C (in combination with direct acting
antivirals, or interferon alfa 2a, or peginterferon alfa 2a
with or without direct acting antivirals)
▶ Adult (body-weight up to 75 kg): 400 mg, dose to be taken
in the morning and 600 mg, dose to be taken in the
▶ Adult (body-weight 75 kg and above): 600 mg twice daily
Chronic hepatitis C (in combination with peginterferon
alfa 2b with or without direct acting antivirals)
▶ Adult (body-weight up to 65 kg): 400 mg twice daily
▶ Adult (body-weight 65–80 kg): 400 mg, to be taken in the
morning and 600 mg, to be taken in the evening
▶ Adult (body-weight 81–105 kg): 600 mg twice daily
▶ Adult (body-weight 106 kg and above): 600 mg, to be
taken in the morning and 800 mg, to be taken in the
Chronic hepatitis C genotype 2 or 3 (not previously
treated), or patients infected with HIV and hepatitis C (in
combination with peginterferon alfa)
▶ Adult: Usual dose 400 mg twice daily
Chronic hepatitis C (in combination with interferon alfa
2b, or peginterferon alfa 2b with or without boceprevir)
▶ Adult (body-weight up to 65 kg): 400 mg twice daily
▶ Adult (body-weight 65–80 kg): 400 mg, dose to be taken
in the morning and 600 mg, dose to be taken in the
▶ Adult (body-weight 81–104 kg): 600 mg twice daily
▶ Adult (body-weight 105 kg and above): 600 mg, dose to be
taken in the morning and 800 mg, dose to be taken in
Chronic hepatitis C (in combination with interferon alfa
2b, or peginterferon alfa 2b with or without boceprevir)
▶ Adult (body-weight up to 65 kg): 400 mg twice daily
▶ Adult (body-weight 65–80 kg): 400 mg, dose to be taken
in the morning and 600 mg, dose to be taken in the
▶ Adult (body-weight 81–104 kg): 600 mg twice daily
▶ Adult (body-weight 105 kg and above): 600 mg, dose to be
taken in the morning and 800 mg, dose to be taken in
▶ When used by inhalation in children Inhalation licensed for
use in children (age range not specified by manufacturer).
▶ With intravenous use in children Intravenous preparation not
▶ With systemic use Active severe psychiatric condition (in
children). autoimmune disease (in children). autoimmune
hepatitis (in children). consult product literature for
specific contra-indications when ribavirin used in
combination with other medicinal products . haemoglobinopathies . history of severe psychiatric
uncontrolled cardiac disease in children with chronic
hepatitis C (in children). unstable or uncontrolled cardiac
disease in previous 6 months (in adults)
▶ When used by inhalation maintain standard supportive
respiratory and fluid management therapy
▶ With systemic use anaemia (haemoglobin concentration
should be monitored during the treatment and corrective
action taken) (in adults). cardiac disease (assessment
including ECG recommended before and during
treatment—discontinue if deterioration). consult product
literature for specific cautions when ribavirin used in
combination with other medicinal products . gout (in
adults). haemolysis (haemoglobin concentration should
be monitored during the treatment and corrective action
taken) (in adults). patients with a transplant—risk of
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