▶ Child 13–17 years (body-weight 45 kg and above): 200 mg
once daily, dose to be started 1 week before entering
endemic area and continued for 4 weeks after leaving
▶ Adult: 200 mg once daily, dose to be started 1 week
before entering endemic area and continued for
l UNLICENSED USE Proguanil doses in BNF Publications may
differ from those in product literature.
l INTERACTIONS → Appendix 1: antimalarials
l SIDE-EFFECTS Alopecia . angioedema . bone marrow
l PREGNANCY Benefit of prophylaxis in malaria outweighs
risk. Adequate folate supplements should be given to
l BREAST FEEDING Amount in milk probably too small to be
harmful when used for malaria prophylaxis.
Dose adjustments ▶ In children Use half normal dose if
estimated glomerular filtration rate
on alternate days if estimated glomerular filtration rate
once weekly if estimated glomerular filtration rate less
haematological toxicity in severe impairment.
▶ In adults 100 mg once daily if eGFR
. 50 mg on alternate days if eGFR
. 50 mg once weekly if eGFR less
haematological toxicity in severe impairment.
l DIRECTIONS FOR ADMINISTRATION Tablet may be crushed
and mixed with food such as milk, jam, or honey just
l PATIENT AND CARER ADVICE Warn travellers about
importance of avoiding mosquito bites, importance of
taking prophylaxis regularly, and importance of
immediate visit to doctor if ill within 1 year and especially
l NATIONAL FUNDING/ACCESS DECISIONS
NHS restrictions Drugs for malaria prophylaxis are not
prescribable in NHS primary care; health authorities may
investigate circumstances under which antimalarials are
l EXCEPTIONS TO LEGAL CATEGORY Can be sold to the public
provided it is licensed and labelled for the prophylaxis of
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension, oral
CAUTIONARY AND ADVISORY LABELS 21
▶ Paludrine (Alliance Pharmaceuticals Ltd)
Proguanil hydrochloride 100 mg Paludrine 100mg tablets | 98 tablet p £11.95 DT = £11.95
▶ Adult: 200–300 mg once daily, to be taken at bedtime
▶ Adult: 10 mg/kg every 8 hours (max. per dose 700 mg),
infused over 4 hours, given if patient is unable to take
oral therapy. Change to oral chloroquine as soon as the
patient’s condition permits, reduce dose to 5–7 mg/kg
if parenteral treatment is required for more than
▶ Child: 10 mg/kg every 8 hours (max. per dose 600 mg)
for 7 days, to be given together with or followed by
either doxycycline (in children over 12 years), or
▶ Adult: 600 mg every 8 hours for 5–7 days, to be given
together with or followed by either doxycycline or
▶ Adult: Loading dose 20 mg/kg (max. per dose 1.4 g),
infused over 4 hours, the loading dose of 20 mg/kg
should not be used if the patient has received quinine
or mefloquine during the previous 12 hours, then
maintenance 10 mg/kg every 8 hours (max. per dose
700 mg) until patient can swallow tablets to complete
the 7-day course, maintenance dose to be given
8 hours after the start of the loading dose and infused
over 4 hours, to be given together with or followed by
either doxycycline or clindamycin, reduce maintenance
dose to 5–7 mg/kg if parenteral treatment is required
Falciparum malaria (in intensive care unit)
▶ Adult: Loading dose 7 mg/kg, infused over 30 minutes,
followed immediately by 10 mg/kg, infused over
4 hours, then maintenance 10 mg/kg every 8 hours
(max. per dose 700 mg) until patient can swallow
tablets to complete the 7-day course, maintenance
dose to be given 8 hours after the start of the loading
dose and infused over 4 hours, to be given together
with or followed by either doxycycline or clindamycin,
reduce maintenance dose to 5–7 mg/kg if parenteral
treatment is required for more than 48 hours
DOSE EQUIVALENCE AND CONVERSION
▶ When using quinine for malaria, doses are valid for
quinine hydrochloride, dihydrochloride, and sulfate;
they are not valid for quinine bisulfate which contains
a correspondingly smaller amount of quinine.
▶ Quinine (anhydrous base) 100 mg = quinine bisulfate
169 mg; quinine dihydrochloride 122 mg; quinine
hydrochloride 122 mg; and quinine sulfate 121 mg.
Quinine bisulfate 300 mg tablets are available but
provide less quinine than 300 mg of the
dihydrochloride, hydrochloride, or sulfate.
l UNLICENSED USE Injection not licensed.
MHRA/CHM ADVICE: REMINDER OF DOSE-DEPENDENT QTPROLONGING EFFECTS (NOVEMBER 2017)
caution in patients with risk factors for QT prolongation
or in those with atrioventricular block—see Cautions for
l CONTRA-INDICATIONS Haemoglobinuria . myasthenia
gravis . optic neuritis .tinnitus
l CAUTIONS Atrial fibrillation (monitor ECG during
parenteral treatment). cardiac disease (monitor ECG
during parenteral treatment). conduction defects (monitor
ECG during parenteral treatment). elderly (monitor ECG
l INTERACTIONS → Appendix 1: antimalarials
changes . bronchospasm . cardiotoxicity . cerebral
a very rapid onset) and convulsions (which can be
For details on the management of poisoning, see
Emergency treatment of poisoning p. 1359.
l PREGNANCY High doses are teratogenic in first trimester,
but in malaria benefit of treatment outweighs risk.
l BREAST FEEDING Present in milk but not known to be
Dose adjustments ▶ With intravenous use For treatment of
malaria in severe impairment, reduce parenteral
maintenance dose to 5–7 mg/kg of quinine salt.
Dose adjustments ▶ With intravenous use For treatment of
malaria in severe impairment, reduce parenteral
maintenance dose to 5–7 mg/kg of quinine salt.
▶ With intravenous use Monitor blood glucose and electrolyte
concentration during parenteral treatment.
▶ In adults Patients taking quinine for nocturnal leg cramps
should be monitored closely during the early stages for
adverse effects as well as for benefit.
l DIRECTIONS FOR ADMINISTRATION For intravenous
infusion, give continuously in Glucose 5% or Sodium
Chloride 0.9%. To be given over 4 hours.
l PRESCRIBING AND DISPENSING INFORMATION
▶ With intravenous use Intravenous injection of quinine is so
hazardous that it has been superseded by infusion.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: capsule, oral
suspension, oral solution, solution for infusion
Quinine sulfate 200 mg Quinine sulfate 200mg tablets |
Quinine bisulfate 300 mg Quinine bisulfate 300mg tablets | 28 tablet P £5.50 DT = £1.59
Quinine sulfate 300 mg Quinine sulfate 300mg tablets | 28 tablet P £3.79 DT = £1.94
Toxoplasmosis in pregnancy (in combination with
sulfadiazine and folinic acid)
▶ Adult: 50 mg once daily until delivery
l CAUTIONS History of seizures—avoid large loading doses . predisposition to folate deficiency
l INTERACTIONS → Appendix 1: antimalarials
l PREGNANCY Theoretical teratogenic risk in first trimester
(folate antagonist). Adequate folate supplements should
l BREAST FEEDING Significant amount in milk—avoid
administration of other folate antagonists to infant. Avoid
breast-feeding during toxoplasmosis treatment.
l HEPATIC IMPAIRMENT Manufacturer advises caution.
l RENAL IMPAIRMENT Manufacturer advises caution.
l MONITORING REQUIREMENTS Blood counts required with
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension
▶ Daraprim (GlaxoSmithKline UK Ltd)
Pyrimethamine 25 mg Daraprim 25mg tablets | 30 tablet P £13.00
Treatment for viral hepatitis should be initiated by a
specialist. The management of uncomplicated acute viral
hepatitis is largely symptomatic. Early treatment of acute
hepatitis C with interferon alfa p. 956 [unlicensed indication]
may reduce the risk of chronic infection. Hepatitis B and
hepatitis C viruses are major causes of chronic hepatitis.
Active or passive immunisation against hepatitis A and B
Peginterferon alfa p. 623 is an option for the initial
treatment of chronic hepatitis B and may be preferable to
interferon alfa. The use of peginterferon alfa and interferon
alfa is limited by a response rate of 30–40% and relapse is
frequent. Treatment should be discontinued if no
improvement occurs after 4 months. The manufacturers of
peginterferon alfa-2a and interferon alfa contraindicate use
in decompensated liver disease, but low doses can be used
with great caution in these patients. Although interferon alfa
is contra-indicated in patients receiving immunosuppressant
treatment (or who have received it recently), cautious use of
peginterferon alfa-2a may be justified in some cases.
Entecavir p. 621 or tenofovir disoproxil p. 654 are options
for the initial treatment of chronic hepatitis B. If the
response is inadequate after 6–9 months of treatment, a
change in treatment should be considered. Other drugs that
are licensed for the treatment of chronic hepatitis B include
adefovir dipivoxil p. 623, lamivudine p. 653, or telbivudine
Entecavir alone, tenofovir disoproxil alone, or a
combination of lamivudine with either adefovir dipivoxil or
tenofovir disoproxil can be used in patients with
If drug-resistant hepatitis B virus emerges during treatment,
another antiviral drug to which the virus is sensitive should
be added. Hepatitis B viruses with reduced susceptibility to
lamivudine have emerged following extended therapy.
Adefovir dipivoxil or tenofovir disoproxil can be given with
lamivudine in lamivudine-resistant chronic hepatitis B;
telbivudine or entecavir should not be used because crossresistance can occur.
If there is no toxicity or loss in efficacy, treatment with
adefovir dipivoxil, entecavir, lamivudine, telbivudine, or
tenofovir disoproxil is usually continued until 6 months after
adequate seroconversion has occurred. Treatment is usually
continued long-term in patients with decompensated liver
Tenofovir disoproxil, or a combination of tenofovir
disoproxil with either emtricitabine p. 651 or lamivudine
may be used with other antiretrovirals, as part of ‘highly
active antiretroviral therapy’ in patients who require
treatment for both HIV and chronic hepatitis B. If patients
infected with both HIV and chronic hepatitis B only require
treatment for chronic hepatitis B, they should receive
antivirals that are not active against HIV, such as
peginterferon alfa or adefovir dipivoxil. Treatment may be
continued long-term, even if adequate seroconversion
occurs. Management of these patients should be coordinated
between HIV and hepatology specialists.
Before starting treatment, the genotype of the infecting
hepatitis C virus should be determined and the viral load
measured as this may affect the choice and duration of
treatment. A combination of ribavirin p. 626 and
peginterferon alfa is used for the treatment of chronic
hepatitis C. The combination of ribavirin and interferon alfa
is less effective than the combination of peginterferon alfa
and ribavirin. Peginterferon alfa alone should be used if
ribavirin is contra-indicated or not tolerated. Ribavirin
Daclatasvir is licensed for use in combination with
sofosbuvir p. 628 for the treatment of chronic hepatitis C
infection of genotypes 1 or 4, with or without compensated
cirrhosis; the addition of ribavirin should be considered for
patients with advanced liver disease or with other negative
prognostic factors, such as prior treatment experience. It is
also licensed in combination with sofosbuvir and ribavirin
for the treatment of chronic hepatitis C infection of
genotype 3 in patients who are treatment experienced, with
or without compensated cirrhosis, and in combination with
peginterferon alfa and ribavirin for the treatment of chronic
hepatitis C infection of genotype 4. Daclatasvir must not be
Ombitasvir with paritaprevir and ritonavir p. 625
(Viekirax ®), is licensed for use in combination with dasabuvir
p. 631, with or without ribavirin, for the treatment of chronic
hepatitis C infection of genotype 1 in patients with or
without compensated cirrhosis; it is also licensed for use in
combination with ribavirin for the treatment of chronic
hepatitis C infection of genotype 4 with or without
Ribavirin inhibits a wide range of DNA and RNA viruses. It
is given by mouth for the treatment of chronic hepatitis C
infection, in double therapy with peginterferon alfa,
interferon alfa, or sofosbuvir, or in triple therapy with
peginterferon alfa and one protease inhibitor or sofosbuvir.
Ribavirin is also effective in Lassa fever [unlicensed
Sofosbuvir is a pro-drug of a nucleoside inhibitor that is
effective against hepatitis C virus polymerase NS5B. It is
licensed for use in combination with ribavirin, with or
without peginterferon alfa, for the treatment of chronic
hepatitis C infection of genotypes 1, 2, 3, 4, 5, or 6 in
patients with compensated liver disease. Sofosbuvir
monotherapy is not recommended because it is less effective
Ledipasvir is licensed for use in combination with
sofosbuvir (ledipasvir with sofosbuvir p. 628), with or
without ribavirin, for the treatment of chronic hepatitis C
infections of genotypes 1, 3, 4, 5 or 6.
Sofosbuvir with velpatasvir and voxilaprevir p. 630 is
licensed for the treatment of chronic hepatitis C of all
Other drugs used for Chronic hepatitis B Interferon alfa,
p. 956 . Lamivudine, p. 653 . Tenofovir disoproxil, p. 654
ANTIVIRALS › NUCLEOSIDE ANALOGUES
Chronic hepatitis B in patients with compensated liver
disease (with evidence of viral replication, and
histologically documented active liver inflammation or
fibrosis) not previously treated with nucleoside
▶ Adult: 500 micrograms once daily
Chronic hepatitis B in patients with compensated liver
disease (with evidence of viral replication, and
histologically documented active liver inflammation or
fibrosis) and lamivudine-resistance
▶ Adult: 1 mg once daily, consider other treatment if
inadequate response after 6 months
Chronic hepatitis B in patients with decompensated liver
l CAUTIONS HIV infection—risk of HIV resistance in
CAUTIONS, FURTHER INFORMATION Discontinue if
deterioration in liver function, hepatic steatosis,
progressive hepatomegaly or unexplained lactic acidosis.
▶ Frequency not known Lactic acidosis
l CONCEPTION AND CONTRACEPTION Effective
contraception required during treatment.
l PREGNANCY Toxicity in animal studies—manufacturer
advises use only if potential benefit outweighs risk.
l BREAST FEEDING Manufacturer advises avoid—present in
l RENAL IMPAIRMENT Consult product literature.
Dose adjustments Reduce dose if eGFR less than
l MONITORING REQUIREMENTS Monitor liver function tests
every 3 months, and viral markers for hepatitis B every
3–6 months during treatment (continue monitoring for at
least 1 year after discontinuation—recurrent hepatitis may
BNF 78 Chronic hepatitis B 621
l DIRECTIONS FOR ADMINISTRATION To be taken at least
2 hours before or 2 hours after food.
l PRESCRIBING AND DISPENSING INFORMATION Flavours of
oral liquid formulations may include orange.
l PATIENT AND CARER ADVICE Patients or carers should be
counselled on the administration of entecavir tablets and
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Entecavir for the treatment of chronic hepatitis B (August
Entecavir, within its marketing authorisation, is
recommended as an option for the treatment of people
with chronic HBeAg-positive or HBeAg-negative hepatitis
B in whom antiviral treatment is indicated. This guidance
does not apply to people with chronic hepatitis B who also
have hepatitis C, hepatitis D or HIV.
www.nice.org.uk/guidance/ta153
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Baraclude (Bristol-Myers Squibb Pharmaceuticals Ltd)
Entecavir (as Entecavir monohydrate) 50 microgram per
1 ml Baraclude 0.05mg/ml oral solution sugar-free | 210 ml P £423.80 DT = £423.80
Entecavir (as Entecavir monohydrate) 500 microgram Entecavir
500microgram tablets | 30 tablet P £26.13–£363.26 DT = £363.26
Entecavir (as Entecavir monohydrate) 1 mg Entecavir 1mg tablets
| 30 tablet P £363.26 DT = £363.26
▶ Baraclude (Bristol-Myers Squibb Pharmaceuticals Ltd)
Entecavir (as Entecavir monohydrate) 500 microgram Baraclude
0.5mg tablets | 30 tablet P £363.26 DT = £363.26
Entecavir (as Entecavir monohydrate) 1 mg Baraclude 1mg tablets
| 30 tablet P £363.26 DT = £363.26
Chronic hepatitis B infection with compensated liver
disease, evidence of viral replication, and histologically
documented active liver inflammation or fibrosis, when
other treatment is not appropriate
l CAUTIONS Lamivudine-resistant chronic hepatitis B—risk
CAUTIONS, FURTHER INFORMATION Discontinue if
deterioration in liver function, hepatic steatosis,
progressive hepatomegaly or unexplained lactic acidosis.
l INTERACTIONS → Appendix 1: telbivudine
▶ Uncommon Arthralgia . malaise . muscle complaints . nerve
disorders . pain . sensation abnormal .taste altered
▶ Rare or very rare Lactic acidosis
l PREGNANCY Manufacturer advises use only if potential
l BREAST FEEDING Manufacturer advises avoid—present in
Dose adjustments 600 mg every 48 hours if eGFR
; 600 mg every 72 hours if eGFR
less than 30 mL/minute/1.73 m2
l MONITORING REQUIREMENTS Monitor liver function tests
every 3 months and viral markers of hepatitis B every
3–6 months during treatment (continue monitoring for at
least 1 year after discontinuation—recurrent hepatitis may
Muscle effects and peripheral neuropathy Patients should be
advised to promptly report unexplained muscle pain,
tenderness, or weakness, or numbness, tingling or burning
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Telbivudine for chronic hepatitis B (August 2008) NICE TA154
Telbivudine is not recommended for the treatment of
chronic hepatitis B. Patients currently receiving
telbivudine can continue treatment until they and their
clinician consider it appropriate to stop.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Sebivo (Novartis Pharmaceuticals UK Ltd)
Telbivudine 600 mg Sebivo 600mg tablets | 28 tablet P £290.33
ANTIVIRALS › NUCLEOSIDE REVERSE
Tenofovir alafenamide 26-Feb-2018
Chronic hepatitis B (initiated by a specialist)
▶ Adult: 25 mg once daily (for duration of treatment
l CAUTIONS Decompensated liver disease . HIV co-infection
l INTERACTIONS → Appendix 1: tenofovir alafenamide
▶ Common or very common Abdominal distension
▶ Frequency not known Hepatitis aggravated (during or
l BREAST FEEDING Manufacturer advises avoid—present in
l HEPATIC IMPAIRMENT Manufacturer advises caution in
decompensated hepatic disease (no information available).
l PRE-TREATMENT SCREENING Manufacturer advises HIV
antibody testing should be offered to those with unknown
HIV-1 status before initiation of treatment.
l MONITORING REQUIREMENTS Manufacturer advises
monitor liver function tests at repeated intervals during
treatment and for at least 6 months after last dose—
recurrent hepatitis may occur on discontinuation.
Missed doses Manufacturer 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.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 21
▶ Vemlidy (Gilead Sciences International Ltd) A
Tenofovir alafenamide (as Tenofovir alafenamide fumarate)
25 mg Vemlidy 25mg tablets | 30 tablet P £325.73
ANTIVIRALS › NUCLEOTIDE ANALOGUES
Chronic hepatitis B infection with either compensated
liver disease with evidence of viral replication, and
histologically documented active liver inflammation and
fibrosis, when other treatment not appropriate or
decompensated liver disease in combination with
another antiviral for chronic hepatitis B that has no
CAUTIONS, FURTHER INFORMATION Discontinue if
deterioration in liver function, hepatic steatosis,
progressive hepatomegaly or unexplained lactic acidosis.
l INTERACTIONS → Appendix 1: adefovir
impairment. skin reactions . vomiting
l CONCEPTION AND CONTRACEPTION Effective
contraception required during treatment.
l PREGNANCY Toxicity in animal studies—manufacturer
advises use only if potential benefit outweighs risk.
l BREAST FEEDING Manufacturer advises avoid—no
l RENAL IMPAIRMENT No information available if eGFR less
Dose adjustments 10 mg every 48 hours if eGFR
; 10 mg every 72 hours if eGFR
Monitoring Monitor renal function more frequently in
patients with renal impairment.
▶ Monitor liver function tests every 3 months, and viral
markers for hepatitis B every 3–6 months during treatment
(continue monitoring for at least 1 year after
discontinuation—recurrent hepatitis may occur on
▶ Monitor renal function before treatment then every
3 months, more frequently in patients receiving
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Hepsera (Gilead Sciences International Ltd)
Adefovir dipivoxil 10 mg Hepsera 10mg tablets | 30 tablet P £252.22 DT = £252.22
IMMUNOSTIMULANTS › INTERFERONS
l DRUG ACTION Polyethylene glycol-conjugated
(‘pegylated’) derivatives of interferon alfa (peginterferon
alfa-2a and peginterferon alfa-2b) are available;
pegylation increases the persistence of the interferon in
Combined with ribavirin for chronic hepatitis C |
Monotherapy for chronic hepatitis C if ribavirin not
tolerated or contra-indicated | Monotherapy for chronic
▶ Adult: (consult product literature)
CONTRA-INDICATIONS, FURTHER INFORMATION
For contra-indications consult product literature.
CAUTIONS, FURTHER INFORMATION For cautions consult
l INTERACTIONS → Appendix 1: interferons
discomfort. eye disorders . eye inflammation . feeling
illness . leucopenia . lymphadenopathy . malaise . memory
loss . menstrual cycle irregularities . mood altered . muscle
complaints . muscle tone increased . muscle weakness . nail
▶ Uncommon Diabetes mellitus . hallucination . hypersensitivity . hypertriglyceridaemia . myocardial
ischaemia . CNS haemorrhage . coma . congestive heart
▶ Frequency not known Homicidal ideation . pericardial
effusion . peripheral ischaemia . pulmonary arterial
hypertension . pure red cell aplasia . solid organ transplant
rejection .tongue discolouration
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