. older adults and those with cardiac disease;
. patients with chronic lung disease (including chronic
obstructive pulmonary disease) associated with
. patients receiving treatment with negative inotropic
drugs, e.g. calcium channel blockers.
Itraconazole should be avoided in patients with
ventricular dysfunction or a history of heart failure
unless the infection is serious.
l CONTRA-INDICATIONS Acute porphyrias p. 1058
l CAUTIONS Active liver disease . history of hepatotoxicity
with other drugs . susceptibility to congestive heart failure
l INTERACTIONS → Appendix 1: antifungals, azoles
oedema . skin reactions . vision disorders . vomiting
▶ Uncommon Hearing loss .taste altered
reaction . severe cutaneous adverse reactions (SCARs)
▶ Frequency not known Peripheral neuropathy (discontinue)
impairment.tachycardia .tremor. urinary incontinence
▶ With intravenous use Dysphonia . numbness . thrombocytopenia
▶ With oral use Flatulence . increased risk of infection . menstrual disorder
▶ With oral use Erectile dysfunction . leucopenia . sensation
abnormal . serum sickness .tinnitus . urinary frequency
SIDE-EFFECTS, FURTHER INFORMATION Potentially lifethreatening hepatotoxicity reported very rarely —
discontinue if signs of hepatitis develop.
l CONCEPTION AND CONTRACEPTION Ensure effective
contraception during treatment and until the next
menstrual period following end of treatment.
l BREAST FEEDING Small amounts present in milk—may
accumulate; manufacturer advises avoid.
l HEPATIC IMPAIRMENT Use only if potential benefit
outweighs risk of hepatotoxicity.
Dose adjustments Dose reduction may be necessary.
l RENAL IMPAIRMENT Risk of congestive heart failure.
▶ With oral use Bioavailability of oral formulations possibly
▶ With intravenous use Use intravenous infusion with caution
if eGFR 30–80 mL/minute/1.73 m2
infusion if eGFR less than 30 mL/minute/1.73 m2
▶ Absorption reduced in AIDS and neutropenia (monitor
plasma-itraconazole concentration and increase dose if
▶ Monitor liver function if treatment continues for longer
than one month, if receiving other hepatotoxic drugs, if
history of hepatotoxicity with other drugs, or in hepatic
l DIRECTIONS FOR ADMINISTRATION
▶ With intravenous use For intravenous infusion (Sporanox ®),
give intermittently in Sodium Chloride 0.9%; dilute 250 mg
in 50 mL infusion fluid and infuse only 60 mL through an
in-line filter (0.2 micron) over 60 minutes.
▶ With oral use For oral liquid, do not take with food; swish
around mouth and swallow, do not rinse afterwards.
l PRESCRIBING AND DISPENSING INFORMATION Flavours of
oral liquid formulations may include cherry.
l PATIENT AND CARER ADVICE Patients should be told how
to recognise signs of liver disorder and advised to seek
prompt medical attention if symptoms such as anorexia,
nausea, vomiting, fatigue, abdominal pain or dark urine
▶ With oral use Patients or carers should be given advice on
how to administer itraconazole oral liquid.
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
EXCIPIENTS: May contain Propylene glycol
▶ Sporanox (Janssen-Cilag Ltd)
Itraconazole 10 mg per 1 ml Sporanox I.V. 250mg/25ml solution for
infusion ampoules and diluent | 1 ampoule P £79.71
CAUTIONARY AND ADVISORY LABELS 9, 23
▶ Itraconazole (Non-proprietary)
Itraconazole 10 mg per 1 ml Itraconazole 50mg/5ml oral solution
sugar free sugar-free | 150 ml P £58.34–£59.25 DT = £59.25
▶ Sporanox (Janssen-Cilag Ltd)
Itraconazole 10 mg per 1 ml Sporanox 50mg/5ml oral solution
sugar-free | 150 ml P £58.34 DT = £59.25
CAUTIONARY AND ADVISORY LABELS 5, 9, 21, 25
▶ Itraconazole (Non-proprietary)
▶ Sporanox (Janssen-Cilag Ltd)
Itraconazole 100 mg Sporanox-Pulse 100mg capsules |
Sporanox 100mg capsules | 4 capsule P £3.67 | 15 capsule P £13.77 DT = £3.24 | 60 capsule P £55.10
Invasive aspergillosis either refractory to, or in patients
intolerant of, itraconazole or amphotericin | Fusariosis
either refractory to, or in patients intolerant of,
amphotericin | Chromoblastomycosis and mycetoma
either refractory to, or in patients intolerant of,
itraconazole | Coccidioidomycosis either refractory to, or
in patients intolerant of, amphotericin, itraconazole, or
▶ BY MOUTH USING ORAL SUSPENSION
▶ Adult: 400 mg twice daily, to be taken with food,
alternatively 200 mg 4 times a day, if unable to tolerate
▶ BY MOUTH USING TABLETS, OR BY INTRAVENOUS INFUSION
▶ Adult: Loading dose 300 mg twice daily on first day,
then 300 mg once daily, switch from intravenous to
Oropharyngeal candidiasis (severe infection or in
immunocompromised patients only)
▶ BY MOUTH USING ORAL SUSPENSION
▶ Adult: Loading dose 200 mg on first day, then 100 mg
once daily for 13 days, dose to be taken with food
Prophylaxis of invasive fungal infections in patients at
high risk and undergoing high-dose immunosuppressive
therapy for haematopoietic stem cell transplantation or
receiving chemotherapy for acute myeloid leukaemia or
myelodysplastic syndrome and expected to develop
▶ BY MOUTH USING ORAL SUSPENSION
▶ Adult: 200 mg 3 times a day, dose to be taken with
food, for chemotherapy patients, start several days
before the expected onset of neutropenia and continue
for 7 days after neutrophil count rises above
▶ BY MOUTH USING TABLETS, OR BY INTRAVENOUS INFUSION
▶ Adult: Loading dose 300 mg twice daily on first day,
then 300 mg once daily, for chemotherapy patients,
start several days before the expected onset of
neutropenia and continue for 7 days after neutrophil
count rises above 500 cells/mm3
intravenous to oral route when appropriate
DOSE EQUIVALENCE AND CONVERSION
▶ Posaconazole oral suspension is not interchangeable
with tablets on a milligram-for-milligram basis.
▶ Posaconazole oral suspension should be taken with food
(preferably a high fat meal) or nutritional supplement
to ensure adequate exposure for systemic effects.
Where possible, tablets should be used in preference to
suspension because tablets have a higher
l CONTRA-INDICATIONS Acute porphyrias p. 1058
l CAUTIONS Administration by intravenous infusion,
particularly by peripheral catheter—increased risk of QTc
interval prolongation . body-weight over 120 kg—risk of
treatment failure possibly increased . body-weight under
l INTERACTIONS → Appendix 1: antifungals, azoles
interval prolongation .renal impairment.respiratory
l CONCEPTION AND CONTRACEPTION Manufacturer
recommends effective contraception during treatment.
l PREGNANCY Manufacturer advises avoid unless potential
benefit outweighs risk; toxicity in animal studies.
l BREAST FEEDING Manufacturer advises avoid—present in
l HEPATIC IMPAIRMENT Manufacturer advises caution (risk
of increased exposure, limited information available).
l RENAL IMPAIRMENT Manufacturer advises monitor
efficacy in severe impairment—variable exposure
▶ With intravenous use Manufacturer advises caution if eGFR
less than 50 mL/minute/1.73 m2
▶ Monitor electrolytes (including potassium, magnesium,
and calcium) before and during therapy.
▶ Monitor liver function before and during therapy.
l DIRECTIONS FOR ADMINISTRATION
▶ With intravenous use Manufacturer advises for intravenous
®), give continuously in Glucose 5% or
Sodium Chloride 0.9%; dilute requisite dose in infusion
fluid to produce a final concentration of 1–2 mg/mL; give
via a central venous catheter or peripherally inserted
central catheter over approx. 90 minutes (can give a single
dose via peripheral venous catheter if central access not
established—dilute to a final concentration of 2 mg/mL
and give over approx. 30 minutes).
l PRESCRIBING AND DISPENSING INFORMATION Flavours of
oral liquid formulations may include cherry.
▶ With intravenous use Manufacturer advises store in a
Driving and skilled tasks Manufacturer advises patients and
carers should be counselled on the effects on driving and
performance of skilled tasks—increased risk of dizziness
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
ELECTROLYTES: May contain Sodium
▶ Noxafil (Merck Sharp & Dohme Ltd)
Posaconazole 18 mg per 1 ml Noxafil 300mg/16.7ml concentrate for
solution for infusion vials | 1 vial P £211.00 (Hospital only)
CAUTIONARY AND ADVISORY LABELS 3, 9, 21
▶ Noxafil (Merck Sharp & Dohme Ltd)
Posaconazole 40 mg per 1 ml Noxafil 40mg/ml oral suspension | 105 ml P £491.20 (Hospital only)
CAUTIONARY AND ADVISORY LABELS 3, 9, 25
▶ Noxafil (Merck Sharp & Dohme Ltd)
Posaconazole 100 mg Noxafil 100mg gastro-resistant tablets |
24 tablet P £596.96 DT = £596.96 | 96 tablet P £2,387.85
Invasive aspergillosis | Serious infections caused by
Scedosporium spp., Fusarium spp., or invasive
fluconazole-resistant Candida spp. (including C. krusei)
▶ Adult (body-weight up to 40 kg): Initially 200 mg every
12 hours for 2 doses, then 100 mg every 12 hours,
increased if necessary to 150 mg every 12 hours
▶ Adult (body-weight 40 kg and above): Initially 400 mg
every 12 hours for 2 doses, then 200 mg every 12 hours,
increased if necessary to 300 mg every 12 hours
▶ Adult: Initially 6 mg/kg every 12 hours for 2 doses, then
4 mg/kg every 12 hours; reduced if not tolerated to
3 mg/kg every 12 hours; for max. 6 months continued→
DOSE ADJUSTMENTS DUE TO INTERACTIONS
▶ With intravenous use Manufacturer advises increase
maintenance dose to 5 mg/kg every 12 hours with
concurrent use of fosphenytoin, phenytoin or rifabutin.
▶ With oral use Manufacturer advises increase maintenance
dose with concurrent use of fosphenytoin or phenytoin;
400 mg every 12 hours for patients of body-weight 40 kg
use of rifabutin is unavoidable, increase maintenance dose
to 350 mg every 12 hours for patients of body-weight 40 kg
and above; 200 mg every 12 hours for patients of bodyweight less than 40 kg.
l CONTRA-INDICATIONS Acute porphyrias p. 1058
interval prolongation . patients at risk of pancreatitis . symptomatic arrhythmias
l INTERACTIONS → Appendix 1: antifungals, azoles
disorders . eye inflammation . fever. gastrointestinal
tone increased . nausea . neutropenia . oedema . oral
prolongation .renal tubular necrosis . severe cutaneous
adverse reactions (SCARs).taste altered . thrombophlebitis .tinnitus . vertigo
▶ Rare or very rare Angioedema . cardiac conduction
disorders . disseminated intravascular coagulation . hyperthyroidism
▶ With intravenous use Infusion related reaction
SIDE-EFFECTS, FURTHER INFORMATION Hepatotoxicity
Hepatitis, cholestasis, and acute hepatic failure have been
reported; risk of hepatotoxicity increased in patients with
haematological malignancy. Consider treatment
discontinuation if severe abnormalities in liver function
Phototoxicity Phototoxicity occurs uncommonly. If
phototoxicity occurs, consider treatment discontinuation;
if treatment is continued, monitor for pre-malignant skin
lesions and squamous cell carcinoma, and discontinue
l CONCEPTION AND CONTRACEPTION Effective
contraception required during treatment.
l PREGNANCY Toxicity in animal studies—manufacturer
advises avoid unless potential benefit outweighs risk.
l BREAST FEEDING Manufacturer advises avoid—no
l HEPATIC IMPAIRMENT Manufacturer advises caution,
particularly in severe impairment (no information
Dose adjustments Manufacturer advises use usual initial
loading dose then halve maintenance dose in mild to
l RENAL IMPAIRMENT Intravenous vehicle may accumulate
if eGFR less than 50 mL/minute/1.73 m2
infusion only if potential benefit outweighs risk, and
monitor renal function; alternatively, use tablets or oral
suspension (no dose adjustment required).
▶ Monitor liver function before starting treatment, then at
least weekly for 1 month, and then monthly during
l DIRECTIONS FOR ADMINISTRATION
▶ With intravenous use For intravenous infusion, reconstitute
each 200 mg with 19 mL Water for Injections or Sodium
Chloride 0.9% to produce a 10 mg/mL solution; dilute dose
to concentration of 0.5–5 mg/mL with Glucose 5% or
Sodium Chloride 0.9% and give intermittently at a rate not
l PRESCRIBING AND DISPENSING INFORMATION Flavours of
oral liquid formulations may include orange.
l PATIENT AND CARER ADVICE Patients and their carers
should be told how to recognise symptoms of liver
disorder, and advised to seek immediate medical attention
if symptoms such as persistent nausea, vomiting, malaise
Patients and their carers should be advised that patients
should avoid intense or prolonged exposure to direct
sunlight, and to avoid the use of sunbeds. In sunlight,
patients should cover sun-exposed areas of skin and use a
sunscreen with a high sun protection factor. Patients
should seek medical attention if they experience sunburn
or a severe skin reaction following exposure to light or sun.
Patients and their carers should be advised to keep the
alert card with them at all times.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder for solution for infusion
EXCIPIENTS: May contain Sulfobutylether beta cyclodextrin sodium
ELECTROLYTES: May contain Sodium
▶ Voriconazole (Non-proprietary)
Voriconazole 200 mg Voriconazole 200mg powder for solution for
infusion vials | 1 vial P £51.43–£77.14 (Hospital only)
Voriconazole 200 mg VFEND 200mg powder for solution for infusion
vials | 1 vial P £77.14 (Hospital only)
CAUTIONARY AND ADVISORY LABELS 9, 11, 23
Voriconazole 40 mg per 1 ml VFEND 40mg/ml oral suspension | 75 ml P £551.37
CAUTIONARY AND ADVISORY LABELS 9, 11, 23
▶ Voriconazole (Non-proprietary)
Voriconazole 50 mg Voriconazole 50mg tablets | 28 tablet P £275.68 DT = £194.79
Voriconazole 100 mg Voriconazole 100mg tablets | 28 tablet P £275.68
Voriconazole 200 mg Voriconazole 200mg tablets | 28 tablet P £1,102.74 DT = £680.92
Voriconazole 50 mg VFEND 50mg tablets | 28 tablet P £275.68
Voriconazole 200 mg VFEND 200mg tablets | 28 tablet P £1,102.74 DT = £680.92
Systemic yeast and fungal infections | Adjunct to
amphotericin in severe systemic candidiasis and in other
severe or long-standing infections
▶ Adult: Usual dose 200 mg/kg daily in 4 divided doses
usually for not more than 7 days, alternatively
100–150 mg/kg daily in 4 divided doses, lower dose
may be sufficient for extremely sensitive organisms
Cryptococcal meningitis (adjunct to amphotericin)
▶ Adult: 100 mg/kg daily in 4 divided doses for 2 weeks
l UNLICENSED USE Use in cryptococcal meningitis for
2 weeks is an unlicensed duration.
l CAUTIONS Blood disorders . elderly
l INTERACTIONS → Appendix 1: flucytosine
l SIDE-EFFECTS Agranulocytosis . aplastic anaemia . blood
epidermal necrolysis . ventricular dysfunction . vertigo . vomiting
l PREGNANCY Teratogenic in animal studies; manufacturer
advises use only if potential benefit outweighs risk.
l BREAST FEEDING Manufacturer advises avoid.
Dose adjustments Use 50 mg/kg every 12 hours if creatinine
clearance 20–40 mL/minute; use 50 mg/kg every 24 hours
if creatinine clearance 10–20 mL/minute; use initial dose
of 50 mg/kg if creatinine clearance less than 10 mL/minute
and then adjust dose according to plasma-flucytosine
Monitoring In renal impairment liver- and kidney-function
tests and blood counts required weekly.
▶ For plasma concentration monitoring, blood should be
taken shortly before starting the next infusion; plasma
concentration for optimum response 25–50 mg/litre
(200–400 micromol/litre)—should not be allowed to
exceed 80 mg/litre (620 micromol/litre).
▶ Liver- and kidney-function tests and blood counts
required (weekly in blood disorders).
l DIRECTIONS FOR ADMINISTRATION For intravenous
infusion, give over 20–40 minutes.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
ELECTROLYTES: May contain Sodium
▶ Ancotil (Meda Pharmaceuticals Ltd)
Flucytosine 10 mg per 1 ml Ancotil 2.5g/250ml solution for infusion
bottles | 5 bottle P £151.67 (Hospital only)
Dermatophyte infections of the skin, scalp, hair and nails
where topical therapy has failed or is inappropriate
▶ Adult: 500 mg daily, increased if necessary to 1 g daily,
for severe infections; reduce dose when response
occurs, daily dose may be taken once daily or in divided
Tinea capitis caused by Trichophyton tonsurans
▶ Adult: 1 g once daily, alternatively 1 g daily in divided
l UNLICENSED USE Griseofulvin doses in BNF may differ
from those in product literature.
l CONTRA-INDICATIONS Acute porphyrias p. 1058 . systemic
lupus erythematosus (risk of exacerbation)
l INTERACTIONS → Appendix 1: griseofulvin
▶ Common or very common Diarrhoea . epigastric discomfort . headache . nausea . vomiting
▶ Uncommon Appetite decreased . confusion . coordination
reactions .taste altered .toxic epidermal necrolysis
l CONCEPTION AND CONTRACEPTION Effective
contraception required during and for at least 1 month
after administration to women (important: effectiveness of
oral contraceptives may be reduced, additional
contraceptive precautions e.g. barrier method, required).
Men should avoid fathering a child during and for at least
l PREGNANCY Avoid (fetotoxicity and teratogenicity in
l BREAST FEEDING Avoid—no information available.
l HEPATIC IMPAIRMENT Manufacturer advises caution in
mild to moderate impairment (risk of deterioration); avoid
Driving and skilled tasks May impair performance of skilled
tasks (e.g. driving); effects of alcohol enhanced.
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
CAUTIONARY AND ADVISORY LABELS 9, 21
▶ Griseofulvin (Non-proprietary)
Griseofulvin 125 mg Griseofulvin 125mg tablets | 100 tablet P £96.67 DT = £96.67
Pneumonia caused by Pneumocystis jirovecii (Pneumocystis
carinii) occurs in immunosuppressed patients; it is a
common cause of pneumonia in AIDS. Pneumocystis
pneumonia should generally be treated by those experienced
in its management. Blood gas measurement is used to assess
Co-trimoxazole p. 562 in high dosage is the drug of choice
for the treatment of mild to moderate pneumocystis
Atovaquone p. 602 is licensed for the treatment of mild to
moderate pneumocystis infection in patients who cannot
tolerate co-trimoxazole. A combination of dapsone p. 577
with trimethoprim p. 574 is given by mouth for the
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