DOSE ADJUSTMENTS DUE TO INTERACTIONS
▶Manufacturer advises reduce dose of concurrent H 2 -
receptor antagonist if above a dose comparable to
famotidine 40 mg twice daily.
▶Manufacturer advises reduce dose of concurrent proton
pump inhibitor if above a dose comparable to
omeprazole 20 mg; take at the same time as sofosbuvir
with ledipasvir.
DOSE EQUIVALENCE AND CONVERSION
▶Dose expressed as x/y mg ledipasvir/sofosbuvir.lCAUTIONSRetreatment following treatment failure—
efficacy not established
lINTERACTIONS→Appendix 1 : ledipasvir.sofosbuvir
lSIDE-EFFECTS
▶Common or very commonFatigue.headache.rash
▶Frequency not knownAngioedema.arrhythmia
lPRESCRIBING AND DISPENSING INFORMATIONDispense in
original container (contains desiccant).
lPATIENT AND CARER ADVICE
VomitingIf vomiting occurs within 5 hours of
administration, an additional dose should be taken.
Missed dosesIf a dose is more than 18 hours late, the
missed dose should not be taken and the next dose should
be taken at the normal time.lMEDICINAL FORMS
There can be variation in the licensing of different medicines
containing the same drug.
Tablet
CAUTIONARY AND ADVISORY LABELS 25
▶Harvoni(Gilead Sciences International Ltd)A
Ledipasvir 90 mg, Sofosbuvir 400 mgHarvoni 90 mg/ 400 mg
tablets| 28 tabletP£ 12 , 993. 33Sofosbuvir 09-Nov-2017
lINDICATIONS AND DOSE
Chronic hepatitis C infection
▶BY MOUTH
▶Child 12–17 years: 400 mg once daily, for duration of
treatment consult product literatureIMPORTANT SAFETY INFORMATION
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
function, secondary to hepatitis C treatment with direct-
acting antivirals, may affect the efficacy of vitamin K
antagonists; the MHRA has advised that INR should be
monitored closely in patients receiving concomitant
treatment.
MHRA/CHM ADVICE: DIRECT-ACTING ANTIVIRAL INTERFERON-
FREE REGIMENS TO TREAT CHRONIC HEPATITIS C: RISK OF
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
current clinical guidelines.lCAUTIONS
CAUTIONS, FURTHER INFORMATIONManufacturer advises
in chronic hepatitis C of genotype 1 , 4 , 5 ,or 6 , only use
sofosbuvir with ribavirin dual therapy in those withintolerance or contra-indications to peginterferon alfa
who require urgent treatment.
lINTERACTIONS→Appendix 1 : sofosbuvir
lSIDE-EFFECTS
▶Common or very commonAlopecia.anaemia.anxiety.
appetite decreased.arthralgia.asthenia.chest pain.chills
.concentration impaired.constipation.cough.
depression.diarrhoea.dizziness.dry mouth.dyspnoea.
fever.gastrointestinal discomfort.gastrooesophageal
reflux disease.headaches.influenza like illness.insomnia
.irritability.memory loss.muscle complaints.
nasopharyngitis.nausea.neutropenia.pain.skin
reactions.vision blurred.vomiting.weight decreased
▶Frequency not knownArrhythmia
SIDE-EFFECTS, FURTHER INFORMATIONSide-effects listed
are reported when sofosbuvir is used in combination with
ribavirin or with ribavirin and peginterferon alfa.
lPREGNANCYManufacturer advises avoid—limited
information available.
lBREAST FEEDINGManufacturer advises avoid—present in
milk inanimalstudies.
lRENAL IMPAIRMENTSafety and efficacy not established if
eGFR less than 30 mL/minute/ 1. 73 m^2 —accumulation may
occur.
lPRESCRIBING AND DISPENSING INFORMATIONDispense in
original container (contains desiccant).
lPATIENT AND CARER ADVICE
Missed dosesManufacturer advises if a dose is more than
18 hours late, the missed dose should not be taken and the
next dose should be taken at the normal time.lMEDICINAL FORMS
There can be variation in the licensing of different medicines
containing the same drug.
Tablet
CAUTIONARY AND ADVISORY LABELS21, 25
▶Sovaldi(Gilead Sciences International Ltd)A
Sofosbuvir 400 mgSovaldi 400 mg tablets| 28 tabletP
£ 11 , 660. 98IMMUNOSTIMULANTS›INTERFERONS
Peginterferon alfa
lDRUG ACTIONPolyethylene glycol-conjugated
(‘pegylated’) derivatives of interferon alfa (peginterferon
alfa- 2 aandpeginterferon alfa- 2 b) are available;
pegylation increases the persistence of the interferon in
the blood.lINDICATIONS AND DOSE
PEGASYS®
Chronic hepatitis C (in combination with ribavirin) in
previously untreated children without liver
decompensation
▶BY SUBCUTANEOUS INJECTION
▶Child 5–17 years:(consult product literature)
VIRAFERONPEG®
Chronic hepatitis C (in combination with ribavirin) in
previously untreated children without liver
decompensation
▶BY SUBCUTANEOUS INJECTION
▶Child 3–17 years:(consult product literature)lCONTRA-INDICATIONSSevere psychiatric illness
CONTRA-INDICATIONS, FURTHER INFORMATION
For contra-indications consult product literature.
lCAUTIONS
CAUTIONS, FURTHER INFORMATIONFor cautions consult
product literature.402 Viral infection BNFC 2018 – 2019
Infection5