l MONITORING REQUIREMENTS Monitor ECG before starting
treatment (do not initiate treatment if QT interval over
450 milliseconds); if baseline QT interval less than
450 milliseconds, monitor ECG during treatment
(particularly 10 days after starting treatment in patients
not previously treated with antiretroviral therapy)—
discontinue if QT interval increases over 480 milliseconds,
if QT interval more than 20 milliseconds above baseline, if
prolongation of PR interval, or if arrhythmias occur.
Arrhythmias Patients should be told how to recognise signs
of arrhythmia and advised to seek medical attention if
symptoms such as palpitation or syncope develop.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 21
▶ Invirase (Roche Products Ltd)
Saquinavir (as Saquinavir mesilate) 500 mg Invirase 500mg
tablets | 120 tablet P £251.26
HIV infection resistant to other protease inhibitors, in
combination with other antiretroviral drugs in patients
previously treated with antiretrovirals–with low-dose
DOSE EQUIVALENCE AND CONVERSION
▶ The bioavailability of tipranavir oral solution is higher
than that of the capsules; the oral solution is not
interchangeable with the capsules on a milligram-formilligram basis.
l CAUTIONS Abnormal liver function tests and/or signs or
symptoms of liver injury (consider delaying treatment if
serum transaminases are greater than 5 times the upper
limit of normal—consult product literature) . patients at
risk of increased bleeding from trauma, surgery or other
l INTERACTIONS → Appendix 1: HIV-protease inhibitors
▶ Rare or very rare Dehydration . hyperbilirubinaemia . intracranial haemorrhage
▶ Frequency not known Bleeding tendency
or symptoms of hepatitis develop or if liver-function
abnormality develops (consult product literature).
l PREGNANCY Manufacturer advises use only if potential
benefit outweighs risk—toxicity in animal studies.
l HEPATIC IMPAIRMENT Manufacturer advises caution in
mild impairment (risk of increased exposure)—monitor
liver function before treatment, then every two weeks for
3 months, then monthly until 48 weeks, then every 8 to
12 weeks thereafter, and discontinue if liver function
worsens; avoid in moderate to severe impairment.
l MONITORING REQUIREMENTS Monitor liver function
before treatment, then every 2 weeks for 1 month, then
every 4 weeks until 24 weeks, then every 8 to 12 weeks
l PRESCRIBING AND DISPENSING INFORMATION Flavours of
oral liquid formulations may include toffee and mint.
l PATIENT AND CARER ADVICE Patients or carers should be
told to observe the oral solution for crystallisation; the
bottle should be replaced if more than a thin layer of
crystals form (doses should continue to be taken at the
normal time until the bottle is replaced).
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 5, 21
EXCIPIENTS: May contain Ethanol
▶ Aptivus (Boehringer Ingelheim Ltd)
Tipranavir 250 mg Aptivus 250mg capsules | 120 capsule P £441.00
l DRUG ACTION Maraviroc is an antagonist of the CCR5
CCR5-tropic HIV infection in combination with other
antiretroviral drugs in patients previously treated with
l CAUTIONS Cardiovascular disease
l INTERACTIONS → Appendix 1: maraviroc
▶ Uncommon Hyperbilirubinaemia . increased risk of
infection . myopathy . postural hypotension . proteinuria . renal failure . seizure
▶ Frequency not known Fever. hypersensitivity . immune
reconstitution inflammatory syndrome . organ dysfunction . osteonecrosis
SIDE-EFFECTS, FURTHER INFORMATION Osteonecrosis
Osteonecrosis has been reported in patients with advanced
HIV disease or following long-term exposure to
combination antiretroviral therapy.
Hepatotoxicity Manufacturer advises consider
discontinuation if signs or symptoms of acute hepatitis, or
increased liver transaminases with systemic symptoms of
l PREGNANCY Manufacturer advises use only if potential
benefit outweighs risk—toxicity in animal studies.
l HEPATIC IMPAIRMENT Manufacturer advises caution in
impairment and in patients with chronic hepatitis
(increased risk of hepatic side-effects; limited information
l RENAL IMPAIRMENT If eGFR less than
l NATIONAL FUNDING/ACCESS DECISIONS
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (October
2008) that maraviroc (Celsentri ®) is not recommended for
use within NHS Scotland as the economic case was not
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Celsentri (ViiV Healthcare UK Ltd)
Maraviroc 25 mg Celsentri 25mg tablets | 120 tablet P £147.09
Maraviroc 75 mg Celsentri 75mg tablets | 120 tablet P £441.27
Maraviroc 150 mg Celsentri 150mg tablets | 60 tablet P £519.14 DT = £519.14
Maraviroc 300 mg Celsentri 300mg tablets | 60 tablet P £519.14 DT = £519.14
Pharmacokinetic enhancer used to increase the effect of
l INTERACTIONS → Appendix 1: cobicistat
l PREGNANCY Manufacturer advises avoid unless essential.
For use with darunavir, see darunavir with cobicistat p. 657
or darunavir with cobicistat, emtricitabine and tenofovir
alafenamide p. 658. For use with elvitegravir, see
elvitegravir with cobicistat, emtricitabine and tenofovir
disoproxil p. 650 or elvitegravir with cobicistat,
emtricitabine and tenofovir alafenamide p. 649.
l HEPATIC IMPAIRMENT Manufacturer advises avoid in
severe impairment—no information available.
l RENAL IMPAIRMENT No dose adjustment required; inhibits
tubular secretion of creatinine; when any co-administered
drug requires dose adjustment based on renal function,
avoid initiating cobicistat if eGFR less than
l PRESCRIBING AND DISPENSING INFORMATION Dispense in
original container (contains desiccant).
Missed doses If a dose is more than 12 hours late, the
missed dose should not be taken and the next dose should
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 21
▶ Tybost (Gilead Sciences International Ltd)
Cobicistat 150 mg Tybost 150mg tablets | 30 tablet P £21.38
emtricitabine and tenofovir alafenamide, p. 658 . Elvitegravir
with cobicistat, emtricitabine and tenofovir alafenamide,
p. 649 . Elvitegravir with cobicistat, emtricitabine and tenofovir
Oseltamivir p. 662 and zanamivir p. 663 are most effective
for the treatment of influenza if started within a few hours of
the onset of symptoms; they are licensed for use within
48 hours of the first symptoms. In otherwise healthy
individuals they reduce the duration of symptoms by about
1–1.5 days. Oseltamivir or zanamivir can reduce the risk of
complications from influenza in the elderly and in patients
Oseltamivir and zanamivir are licensed for post-exposure
prophylaxis of influenza when influenza is circulating in the
community. Oseltamivir should be given within 48 hours of
exposure to influenza while zanamivir should be given
within 36 hours of exposure to influenza. However, in
patients with severe influenza or in those who are
immunocompromised, antivirals may still be effective after
this time if viral shedding continues [unlicensed use].
Oseltamivir and zanamivir are also licensed for use in
exceptional circumstances (e.g. when vaccination does not
cover the infecting strain) to prevent influenza in an
There is evidence that some strains of influenza A virus
have reduced susceptibility to oseltamivir, but may retain
susceptibility to zanamivir. Resistance to oseltamivir may be
greater in severely immunocompromised patients.
Zanamivir should be reserved for patients who are severely
immunocompromised, or when oseltamivir cannot be used,
or when resistance to oseltamivir is suspected. For those
unable to use the dry powder for inhalation, zanamivir is
available as a solution that can be administered by nebuliser
or intravenously [unlicensed].
Amantadine hydrochloride p. 418 is licensed for
prophylaxis and treatment of influenza A but it is no longer
Information on pandemic influenza, avian influenza, and
swine influenza may be found at www.gov.uk/phe.
Immunisation against influenza is recommended for
persons at high risk, and to reduce transmission of infection.
Oseltamivir in children under 1 year of age
Data on the use of oseltamivir in children under 1 year of age
is limited. Furthermore, oseltamivir may be ineffective in
neonates because they may not be able to metabolise
oseltamivir to its active form. However, oseltamivir can be
age. The Department of Health has advised (May 2009) that
during a pandemic, treatment with oseltamivir can be
overseen by healthcare professionals experienced in
ANTIVIRALS › INFLUENZA › NEURAMINIDASE
l DRUG ACTION Reduces replication of influenza A and B
viruses by inhibiting viral neuraminidase.
▶ Child 1–11 months: 3 mg/kg once daily for 10 days for
▶ Child 1–12 years (body-weight 10–15 kg): 30 mg once daily
for 10 days for post-exposure prophylaxis; for up to
▶ Child 1–12 years (body-weight 15–23 kg): 45 mg once daily
for 10 days for post-exposure prophylaxis; for up to
▶ Child 1–12 years (body-weight 23–40 kg): 60 mg once daily
for 10 days for post-exposure prophylaxis; for up to
▶ Child 1–12 years (body-weight 40 kg and above): 75 mg
once daily for 10 days for post-exposure prophylaxis;
for up to 6 weeks during an epidemic
▶ Adult: 75 mg once daily for 10 days for post-exposure
prophylaxis; for up to 6 weeks during an epidemic
▶ Child 1–11 months: 3 mg/kg twice daily for 5 days
▶ Child 1–12 years (body-weight 10–15 kg): 30 mg twice daily
▶ Child 1–12 years (body-weight 15–23 kg): 45 mg twice daily
▶ Child 1–12 years (body-weight 23–40 kg): 60 mg twice daily
▶ Child 1–12 years (body-weight 40 kg and above): 75 mg
▶ Child 13–17 years: 75 mg twice daily for 5 days
▶ Adult: 75 mg twice daily for 5 days
Treatment of influenza, in the immunocompromised
▶ Adult: 75 mg twice daily for 10 days
l UNLICENSED USE Not licensed for use in premature
l INTERACTIONS → Appendix 1: oseltamivir
▶ Common or very common Dizziness . gastrointestinal
discomfort. herpes simplex . nausea . sleep disorders . vertigo . vomiting
▶ Uncommon Arrhythmia . consciousness impaired (in
adults). seizure . skin reactions
▶ Rare or very rare Angioedema . anxiety . behaviour
l PREGNANCY Although safety data are limited, oseltamivir
can be used in women who are pregnant when the
potential benefit outweighs the risk (e.g. during a
l BREAST FEEDING Although safety data are limited,
oseltamivir can be used in women who are breast-feeding
when the potential benefit outweighs the risk (e.g. during
a pandemic). Oseltamivir is the preferred drug in women
▶ In adults Avoid for treatment and prevention if eGFR less
▶ In children Avoid for treatment and prevention if estimated
glomerular filtration rate less than 10 mL/minute/1.73 m2
Dose adjustments ▶ In adults For treatment, use 30 mg twice
daily if eGFR 30–60 mL/minute/1.73 m2 (30 mg once daily
if eGFR 10–30 mL/minute/1.73 m2
30 mg once daily if eGFR 30–60 mL/minute/1.73 m2 (30 mg
every 48 hours if eGFR 10–30 mL/minute/1.73 m2
▶ In children For treatment, use 40% of normal dose twice
daily if estimated glomerular filtration rate
30–60 mL/minute/1.73 m2 (40% of normal dose once daily
if estimated glomerular filtration rate
normal dose once daily if estimated glomerular filtration
rate 30–60 mL/minute/1.73 m2 (40% of normal dose every
48 hours if estimated glomerular filtration rate
l DIRECTIONS FOR ADMINISTRATION If suspension not
available, capsules can be opened and the contents mixed
with a small amount of sweetened food, such as sugar
water or chocolate syrup, just before administration.
l PRESCRIBING AND DISPENSING INFORMATION Flavours of
oral liquid formulations may include tutti-frutti.
Medicines for Children leaflet: Oseltamivir for influenza (flu)
www.medicinesforchildren.org.uk/oseltamivir-influenza-flu
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Oseltamivir, zanamivir, and amantadine for prophylaxis of
influenza (September 2008) NICE TA158
Oseltamivir is not a substitute for vaccination, which
remains the most effective way of preventing illness from
. Oseltamivir is not recommended for seasonal
prophylaxis against influenza.
. When influenza is circulating in the community,
oseltamivir is an option recommended (in accordance
influenza vaccine, and who have been in close contact
with someone suffering from influenza-like illness in the
same household or residential setting. Oseltamivir
should be given within 48 hours of exposure to
influenza. (National surveillance schemes, including
those run by Public Health England, should be used to
indicate when influenza is circulating in the
. During local outbreaks of influenza-like illness, when
there is a high level of certainty that influenza is
present, oseltamivir may be used for post-exposure
prophylaxis in at-risk patients (regardless of influenza
vaccination) living in long-term residential or nursing
At risk patients include those aged 65 years or older or
those who have one or more of the following conditions:
. chronic respiratory disease (including asthma and
chronic obstructive pulmonary disease);
. chronic neurological disease;
The Department of Health in England has advised
(November 2010 and April 2011) that ‘at risk patients’ also
includes patients under 65 years of age who are at risk of
developing medical complications from influenza
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