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: dasabuvir
▶ Common or very common Anaemia . asthenia . insomnia . nausea . pruritus
▶ Rare or very rare Angioedema
▶ Frequency not known Depression . suicidal ideation
SIDE-EFFECTS, FURTHER INFORMATION Side-effects listed
are reported when dasabuvir is used in combination with
Viekirax (ombitasvir with paritaprevir and ritonavir), with
l PREGNANCY Manufacturer advises avoid—no information
l BREAST FEEDING Manufacturer advises avoid—present in
l HEPATIC IMPAIRMENT Manufacturer advises caution in
cirrhosis —monitor for signs and symptoms of hepatic
decompensation and assess hepatic function (including
direct bilirubin) at baseline, during the first 4 weeks of
treatment and thereafter as clinically indicated,
discontinue if hepatic decompensation develops; avoid in
moderate to severe impairment.
Missed doses If a dose is more than 6 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 (November 2015)
Dasabuvir (Exviera ®), in combination with ombitasvir with
paritaprevir and ritonavir p. 625, 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
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 3, 21, 25
Dasabuvir (as Dasabuvir sodium monohydrate) 250 mg Exviera
250mg tablets | 56 tablet P £933.33
Herpes simplex and varicella–zoster infection
The two most important herpesvirus pathogens are herpes
simplex virus (herpesvirus hominis) and varicella–zoster
Herpes infection of the mouth and lips and in the eye is
generally associated with herpes simplex virus serotype 1
(HSV-1); other areas of the skin may also be infected,
especially in immunodeficiency. Genital infection is most
often associated with HSV-2 and also HSV-1. Treatment of
herpes simplex infection should start as early as possible and
usually within 5 days of the appearance of the infection.
In individuals with good immune function, mild infection
of the eye (ocular herpes) and of the lips (herpes labialis or
cold sores) is treated with a topical antiviral drug. Primary
herpetic gingivostomatitis is managed by changes to diet and
with analgesics. Severe infection, neonatal herpes infection
or infection in immunocompromised individuals requires
treatment with a systemic antiviral drug. Primary or
recurrent genital herpes simplex infection is treated with an
antiviral drug given by mouth. Persistence of a lesion or
recurrence in an immunocompromised patient may signal
the development of resistance.
Specialist advice should be sought for systemic treatment
of herpes simplex infection in pregnancy.
Regardless of immune function and the use of any
immunoglobulins, neonates with chickenpox should be
treated with a parenteral antiviral to reduce the risk of severe
disease. Oral therapy in children is not recommended as
absorption is variable. Chickenpox in otherwise healthy
children between 1 month and 12 years is usually mild and
antiviral treatment is not usually required.
Chickenpox is more severe in adolescents and adults than
in children; antiviral treatment started within 24 hours of
the onset of rash may reduce the duration and severity of
symptoms in otherwise healthy adults and adolescents.
Antiviral treatment is generally recommended in
immunocompromised patients and those at special risk (e.g.
because of severe cardiovascular or respiratory disease or
chronic skin disorder); in such cases, an antiviral is given for
10 days with at least 7 days of parenteral treatment.
Pregnant women who develop severe chickenpox may be
at risk of complications, especially varicella pneumonia.
Specialist advice should be sought for the treatment of
Those who have been exposed to chickenpox and are at
special risk of complications may require prophylaxis with
varicella-zoster immunoglobulin (see under Disease Specific
In herpes zoster (shingles) systemic antiviral treatment can
reduce the severity and duration of pain, reduce
complications, and reduce viral shedding. Treatment with
the antiviral should be started within 72 hours of the onset
of rash and is usually continued for 7–10 days.
Immunocompromised patients at high risk of disseminated
or severe infection should be treated with a parenteral
Chronic pain which persists after the rash has healed
(postherpetic neuralgia) requires specific management.
Aciclovir p. 633 is active against herpesviruses but does not
eradicate them. Uses of aciclovir include systemic treatment
of varicella–zoster and the systemic and topical treatment of
herpes simplex infections of the skin and mucous
membranes. It is used by mouth for severe herpetic
stomatitis. Aciclovir eye ointment is used for herpes simplex
infections of the eye; it is combined with systemic treatment
Famciclovir p. 635, a prodrug of penciclovir, is similar to
aciclovir and is licensed for use in herpes zoster and genital
Valaciclovir p. 636 is an ester of aciclovir, licensed for
herpes zoster and herpes simplex infections of the skin and
mucous membranes (including genital herpes); it is also
licensed for preventing cytomegalovirus disease following
solid organ transplantation. Famciclovir or valaciclovir are
suitable alternatives to aciclovir for oral lesions associated
with herpes zoster. Valaciclovir once daily may reduce the
risk of transmitting genital herpes to heterosexual
partners—specialist advice should be sought.
Foscarnet sodium p. 639 is used for mucocutaneous herpes
simplex virus infection unresponsive to aciclovir in
immunocompromised patients; it is toxic and can cause
Inosine pranobex below has been used by mouth for
herpes simplex infections; its effectiveness remains
Ganciclovir p. 637 is related to aciclovir but it is more active
against cytomegalovirus (CMV); it is also much more toxic
than aciclovir and should therefore be prescribed only when
the potential benefit outweighs the risks. Ganciclovir is
administered by intravenous infusion for the initial treatment
of CMV infection. Ganciclovir causes profound
myelosuppression when given with zidovudine p. 655; the
two should not normally be given together particularly
during initial ganciclovir therapy. The likelihood of
ganciclovir resistance increases in patients with a high viral
load or in those who receive the drug over a long duration.
Valaciclovir is licensed for prevention of cytomegalovirus
disease following renal transplantation.
Valganciclovir p. 638 is an ester of ganciclovir which is
licensed for the initial treatment and maintenance treatment
of CMV retinitis in AIDS patients.Valganciclovir is also
licensed for preventing CMV disease following solid organ
transplantation from a cytomegalovirus-positive donor.
Foscarnet sodium is also active against cytomegalovirus; it
is toxic and can cause renal impairment.
See local treatment of CMV retinitis.
ANTIVIRALS › INOSINE COMPLEXES
▶ Adult: 1 g 4 times a day for 7–14 days
Adjunctive treatment of genital warts
▶ Adult: 1 g 3 times a day for 14–28 days
Subacute sclerosing panencephalitis
▶ Adult: 50–100 mg/kg daily in 6 divided doses
l CAUTIONS History of gout. history of hyperuricaemia
reactions . vertigo . vomiting
l PREGNANCY Manufacturer advises avoid.
l RENAL IMPAIRMENT Manufacturer advises caution;
l LESS SUITABLE FOR PRESCRIBING Inosine pranobex is less
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 9
Inosine acedoben dimepranol 500 mg Imunovir 500mg tablets |
ANTIVIRALS › NUCLEOSIDE ANALOGUES
▶ Child 12–17 years: 400 mg twice daily, alternatively
200 mg 4 times a day; increased to 400 mg 3 times a
day, dose may be increased if recurrences occur on
standard suppressive therapy or for suppression of
genital herpes during late pregnancy (from 36 weeks
gestation), therapy interrupted every 6–12 months to
reassess recurrence frequency—consider restarting
▶ Adult: 400 mg twice daily, alternatively 200 mg 4 times
a day; increased to 400 mg 3 times a day, dose may be
increased if recurrences occur on standard suppressive
therapy or for suppression of genital herpes during late
pregnancy (from 36 weeks gestation), therapy
interrupted every 6–12 months to reassess recurrence
frequency—consider restarting after two or more
Herpes simplex, prophylaxis in the immunocompromised
▶ Child 1–23 months: 100–200 mg 4 times a day
▶ Child 2–17 years: 200–400 mg 4 times a day
▶ Adult: 200–400 mg 4 times a day
▶ Adult: 5 mg/kg every 8 hours
Herpes simplex, treatment (non-genital)
▶ Adult: 200 mg 5 times a day usually for 5 days (longer if
new lesions appear during treatment or if healing
Herpes simplex, treatment (non-genital) in
immunocompromised or if absorption impaired
▶ Adult: 400 mg 5 times a day usually for 5 days (longer if
new lesions appear during treatment or if healing
▶ Child 1–23 months: 100 mg 5 times a day usually for
5 days (longer if new lesions appear during treatment
▶ Child 2–17 years: 200 mg 5 times a day usually for 5 days
(longer if new lesions appear during treatment or if
Herpes simplex, treatment, in immunocompromised or if
▶ Child 1–23 months: 200 mg 5 times a day usually for
5 days (longer if new lesions appear during treatment
or if healing incomplete) continued→
BNF 78 Herpesvirus infections 633
▶ Child 2–17 years: 400 mg 5 times a day usually for 5 days
(longer if new lesions appear during treatment or if
Genital herpes simplex, treatment of first episode
▶ Adult: 200 mg 5 times a day, alternatively 400 mg
3 times a day both courses usually for 5 days (longer if
new lesions appear during treatment or if healing
Genital herpes simplex, treatment of first episode, in
immunocompromised or HIV-positive
▶ Adult: 400 mg 5 times a day for 7–10 days (longer if
new lesions appear during treatment or if healing
Severe genital herpes simplex, treatment, initial infection
| Treatment of herpes simplex in the
▶ Adult: Initially 5 mg/kg every 8 hours usually for 5 days,
alternatively 10 mg/kg every 8 hours for at least 14 days
in encephalitis (at least 21 days if also
immunocompromised)—confirm cerebrospinal fluid
negative for herpes simplex virus before stopping
treatment, higher dose to be used only if resistant
organisms suspected or in simplex encephalitis
Genital herpes simplex, treatment of recurrent infection
▶ Adult: 800 mg 3 times a day for 2 days, alternatively
200 mg 5 times a day for 5 days, alternatively 400 mg
Genital herpes simplex, treatment of recurrent infection
in immunocompromised or HIV-positive patients
▶ Adult: 400 mg 3 times a day for 5–10 days
Varicella zoster (chickenpox), treatment| Herpes zoster
▶ Child 1–23 months: 200 mg 4 times a day for 5 days
▶ Child 2–5 years: 400 mg 4 times a day for 5 days
▶ Child 6–11 years: 800 mg 4 times a day for 5 days
▶ Child 12–17 years: 800 mg 5 times a day for 7 days
▶ Adult: 800 mg 5 times a day for 7 days
▶ Adult: 5 mg/kg every 8 hours usually for 5 days
Varicella zoster (chickenpox), treatment in
immunocompromised | Herpes zoster (shingles),
treatment in immunocompromised
▶ Adult: 10 mg/kg every 8 hours usually for 5 days
Herpes zoster (shingles), treatment in
▶ Child 1–23 months: 200 mg 4 times a day continued for
2 days after crusting of lesions
▶ Child 2–5 years: 400 mg 4 times a day continued for
2 days after crusting of lesions
▶ Child 6–11 years: 800 mg 4 times a day continued for
2 days after crusting of lesions
▶ Child 12–17 years: 800 mg 5 times a day continued for
2 days after crusting of lesions
▶ Adult: 800 mg 5 times a day continued for 2 days after
Herpes zoster, treatment in encephalitis | Varicella zoster,
▶ Adult: 10 mg/kg every 8 hours given for 10–14 days in
encephalitis, possibly longer if also
immunocompromised or if severe infection
Varicella zoster (chickenpox), attenuation of infection if
varicella–zoster immunoglobulin not indicated
▶ Child: 10 mg/kg 4 times a day for 7 days, to be started
▶ Adult: 10 mg/kg 4 times a day for 7 days, to be started
DOSES AT EXTREMES OF BODY-WEIGHT
▶ With intravenous use To avoid excessive dosage in obese
patients parenteral dose should be calculated on the basis
▶ With oral use in children Tablets and suspension not licensed
for suppression of herpes simplex or for treatment of
herpes zoster in children (age range not specified by
▶ With oral use Aciclovir doses in BNF may differ from those
in product literature. Attenuation of chickenpox is an
l INTERACTIONS → Appendix 1: aciclovir
▶ With intravenous use Nausea . photosensitivity reaction . skin reactions . vomiting
reaction . skin reactions . vomiting
▶ With intravenous use Anaemia . leucopenia . thrombocytopenia
▶ With intravenous use Crystalluria
▶ With oral use Alopecia . crystalluria
l PREGNANCY Not known to be harmful—manufacturers
advise use only when potential benefit outweighs risk.
l BREAST FEEDING Significant amount in milk after systemic
administration—not known to be harmful but
l RENAL IMPAIRMENT Risk of neurological reactions
increased. Maintain adequate hydration (especially during
Dose adjustments ▶ With intravenous use in adults Use
normal intravenous dose every 12 hours if eGFR
25–50 mL/minute/1.73 m2 (every 24 hours if eGFR
). Consult product literature for
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