Microsoft word - adf pi vf 16_2 uk clean.docx

VFEND® (voriconazole)
PRESCRIBING INFORMATION - UK

Please refer to the SPC before prescribing Vfend Film-coated Tablets or Vfend Powder for Solution for Infusion or Vfend
Powder for Oral Suspension.
Presentation: White to off-white film-coated tablets, containing either 50mg or 200mg voriconazole; powder for
solution for infusion (IV) containing 200mg voriconazole; powder for oral suspension containing 40mg/ml
voriconazole when reconstituted. Indications: In adults and children aged 2 years and above: Treatment of invasive
aspergillosis. Treatment of candidaemia in non-neutropenic patients. Treatment of fluconazole-resistant serious
invasive Candida infections (including C. krusei). Treatment of serious fungal infections caused by Scedosporium
spp. and Fusarium spp. Vfend should be administered primarily to patients with progressive, possibly life-
threatening infections. Administration and dosage: After reconstitution and dilution, administer the IV infusion at a
maximum recommended rate of 3 mg/kg per hour over 1 to 3 hours. Take Vfend tablets at least one hour before, or
one hour following, a meal. Take Vfend oral suspension at least one hour before, or two hours following a meal. On
the basis of the high oral bioavailability (96%), switching between IV and oral administration is appropriate when
clinically indicated. Treatment duration should be as short as possible depending on the patient’s clinical and
mycological response. Duration of IV treatment should not exceed 6 months. Adults and adolescents (12 to 14
years and ≥50 kg; 15 to 17 years regardless of body weight):
IV: a loading dose of 6mg/kg every 12 hours (for the
first 24 hours) followed by a maintenance dose of 4 mg/kg twice daily. Orally: Patients 40kg and abovea loading
dose of 400mg (10ml) every 12 hours (for the first 24 hours), followed by a maintenance dose of 200mg (5ml) twice
daily. Patients less than 40kg – a loading dose of 200mg (5ml) every 12 hours (for the first 24 hours), followed by a
maintenance dose of 100mg (2.5ml) twice daily. Children (aged 2 to <12 years) and young adolescents (12 to 14
years and <50 kg):
IV: a loading dose of 9 mg/kg every 12 hours (for the first 24 hours) followed by a maintenance
dose of 8 mg/kg twice daily. Orally: Loading dose not recommended. Maintenance dose of 9 mg/kg twice daily
(maximum dose of 350 mg twice daily). It is recommended to initiate therapy with IV regimen, and oral regimen
should be considered only after there is a significant clinical improvement. Oral suspension formulation
recommended in children aged 2 to <12 years. Use in paediatric patients aged 2 to <12 years with hepatic or renal
insufficiency has not been studied. The safety and efficacy of Vfend in children below 2 years has not been
established. IV administration is recommended in children with malabsorption or very low body weight for age as
oral bioavailability may be limited. Elderly: No dose adjustment. Renal impairment (moderate to severe –
creatinine clearance <50ml/min):
No dose adjustment. Oral administration recommended as accumulation of IV
vehicle, sulphobutylether beta cyclodextrin sodium (SBECD), occurs. Hepatic impairment (mild to moderate –
Child-Pugh A and B):
Use standard loading dose regimen and halve maintenance dose. Vfend has not been studied
in patients with severe chronic hepatic cirrhosis (Child-Pugh C). Contra-indications: Known hypersensitivity to
voriconazole or to any of the excipients; co-administration with ergot alkaloids, terfenadine, astemizole, cisapride,
pimozide, quinidine, rifampicin, carbamazepine, phenobarbital, sirolimus, high dose ritonavir (>400mg twice daily)
and St John’s Wort. Pregnancy: Avoid unless benefit outweighs risk to foetus. Lactation: Stop breast-feeding
when starting Vfend. Warnings and precautions: Use with caution in patients with hypersensitivity to other azoles
and in patients with potentially proarrhythmic conditions. QT interval prolongation and torsades de pointes reported
rarely in patients with other risk factors. Monitor and correct electrolyte disturbances prior to initiation and during
Vfend therapy. Infusion-related reactions, predominantly flushing and nausea, and anaphylactoid-type reactions have
been observed. Monitor hepatic function when starting Vfend and routinely in patients who develop abnormal LFTs.
Liver dysfunction is usually reversible on stopping Vfend. In clinical trials there were uncommon reports of serious
hepatic reactions, primarily in patients with serious underlying medical conditions. Monitor renal function as patients
are likely to be on concomitant nephrotoxic medications or have underlying conditions that affect renal function.
Monitor pancreatic function in patients (especially children) with risk factors for acute pancreatitis such as recent
chemotherapy or HSCT. Dermatological reactions (mild or moderate rash) are common. There have been rare reports
of serious cutaneous reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme
and discoid lupus erythematosis. In patients who develop a rash, stop Vfend if lesions progress. Vfend has been
associated with phototoxicity and pseudoporphyria. Advise patients to avoid sunlight exposure and use protective
clothing and sunscreen. Skin squamous cell carcinoma (SCC) has been reported during long term therapy (> 6
months) in patients with phototoxicity and additional risk factors including immunosuppression. Consider stopping
Vfend if a patient develops a skin lesion consistent with SCC. There have been rare reports of prolonged visual
adverse events, including blurred vision, optic neuritis and papilloedema. Avoid co-administration of phenytoin,
rifabutin and low dose ritonavir (100mg twice daily) unless the benefit outweighs the risk. Monitor for methadone
toxicity (including QTc prolongation) if co-administering with Vfend. Co-administration with efavirenz requires
dose adjustment of both products. Consider reducing the dose of any co-administered short acting (alfentanil,
fentanyl, sufentanil) and long acting opiates (oxycodone, hydrocodone) which are CYP3A4 substrates. Frequent
monitoring of opiate-associated adverse events may be necessary (including a longer respiratory monitoring period).
If voriconazole is used sequentially after fluconazole, monitor for voriconazole associated adverse events. Co-
administration with everolimus is not recommended. Excipient information: Vfend IV contains SBECD and
217.6mg of sodium per vial. Vfend tablets contain lactose, Vfend oral suspension contains sucrose.
Incompatibilities: Vfend IV is not compatible with 4.2% sodium bicarbonate infusion. Do not infuse Vfend IV into
the same line with other IV products or at the same time as any blood product or any short-term infusion of
concentrated solutions of electrolytes, even if the two infusions are running in separate lines. Vfend IV and TPN may
be infused simultaneously but through separate lines. Drug interactions: Voriconazole is metabolised by and also
inhibits the cytochrome P450 isoenzymes CYP2C19, CYP2C9 and CYP3A4. Medicines that inhibit, induce or are
metabolised by these isoenzymes may increase, decrease or have no effect on voriconazole plasma levels and vice
versa. Some interactions can be managed by dose adjustment and careful clinical and/or biological monitoring. See
SPC. Side-effects: Very common (frequency ≥1/10) adverse effects in clinical studies were visual disturbances
including blurred vision, chromatopsia and photophobia, pyrexia, rash, vomiting, nausea, diarrhoea, headache,
peripheral oedema and abdominal pain, generally of mild to moderate severity. Visual disturbances (in 30% of
subjects) were mild, transient and fully-reversible with no clinically significant long-term sequelae. Patients
experiencing visual symptoms must avoid potentially hazardous tasks e.g. driving or operating machinery. Also
dermatological, hepatic, infusion-related reactions and post-marketing reports of pancreatitis in paediatric patients
(see precautions above). Altered taste-perception reported with Vfend oral suspension. See SPC for other side
effects. Legal category: POM. Basic NHS cost: Pack of 28, 50mg tablets [EU/1/02/212/005] £275.68; Pack of 28,
200mg tablets [EU/1/02/212/017] £1,102.74; 30ml vial of 200mg Powder for Intravenous Infusion
[EU/1/02/212/025] £77.14; 100ml bottle of 40mg/ml powder for oral suspension [EU/1/02/212/026] £551.37.
Marketing authorisation holder: Pfizer Limited, Sandwich, Kent CT13 9NJ, United Kingdom.
Pfizer Limited, Walton Oaks, Dorking Road, Tadworth, Surrey KT20 7NS Last revised: February 2012 Ref: VF 16_2 Adverse events should be reported. Reporting forms and information can be found at
www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Pfizer Medical
Information on 01304 616161

Source: http://www.mipath.eu/assets/Adf_PI_VF_16_2_UK_clean.pdf

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