Voriconazole oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of voriconazole.
Drugs List
Therapeutic Indications
Uses
Aspergillosis: treatment
Invasive candidiasis in non-neutropenic adults
Prophylaxis of fungal infection in haematopoietic stem cell transplant pts
Serious fungal infections
Treatment of candidosis when other treatment unsuitable/ineffective
Dosage
Voriconazole has high oral bioavailability (96%) and switching between intravenous and oral administration is appropriate, when clinically indicated.
Treatment duration should be as short as possible depending on the patients' clinical and mycological response. For long term treatment greater than 6 months, a careful assessment of the benefit-risk balance should be made.
Tablets are to be taken at least one hour before or one hour after a meal.
The powder for oral suspension is to be taken at least one hour before or two hours after a meal. The suspension should only be administered using the oral syringe provided with each pack.
Adults
Bodyweight 40kg or above
Initial dose: 400mg every 12 hours, for 24 hours.
Maintenance dose: 200mg twice a day.
The maintenance dose may be increased 300mg twice a day, if the patient's response is inadequate, and may be reduced in 50mg steps to 200mg twice a day dependant on patient tolerance.
Bodyweight less than 40kg:
Initial dose: 200mg every 12 hours, for 24 hours.
Maintenance dose: 100mg twice a day.
The maintenance dose may be increased 150mg twice a day, if the patient's response is inadequate, and may be reduced in 50mg steps to 100mg twice a day dependant on patient tolerance.
Children
It is suggested by the manufacturers to initiate the therapy with the intravenous regimen. Oral therapy should be considered only after there is a significant clinical improvement. Children with malabsorption or very low body weight should receive intravenous voriconazole as oral bioavailability may be limited in these patients.
The oral suspension is recommended in children aged 2 to 12 years as tablets may be absorbed differently to adults in paediatric patients. Bioequivalence between the powder for oral suspension and the tablets has not been investigated in paediatric patients.
Children aged 15 to 18 years
(See Dosage; Adult)
Children aged 12 to 15 years with a bodyweight 50kg and above
(See Dosage; Adult)
Children 2 to 15 years with bodyweight below 50kg
9mg/kg twice a day.
Maximum dose should exceed 350mg twice a day.
The maintenance dose may be increased/decreased in steps of 1mg/kg (or 50mg if the maximum dose is administered), if the patient's response is inadequate/not tolerated.
Patients with Hepatic Impairment
Mild to moderate (Child-Pugh A and B) The standard initial dose should be used but the maintenance dose should be halved.
Severe hepatic (Child-Pugh C) Recommended only if the benefits outweigh the risks. Patients must be carefully monitored for drug toxicity.
Contraindications
Children under 2 years
Breastfeeding
Long QT syndrome
Porphyria
Pregnancy
Torsade de pointes
Precautions and Warnings
Children aged 2 to 12 years
Family history of long QT syndrome
History of cardiotoxic drug therapy
Underweight patients
Acute pancreatitis
Cardiac arrhythmias
Cardiac failure
Cardiomyopathy
Electrolyte imbalance
Galactosaemia
Glucose-galactose malabsorption syndrome
Haematological malignancy
Hepatic impairment
Hereditary fructose intolerance
History of torsade de pointes
Lactose intolerance
Malabsorption syndrome
Sinus bradycardia
Correct electrolyte disorders before treatment
Reduce maintenance dose in hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Oral solution contains sucrose
Some formulations contain lactose
Monitor hepatic function before treatment and regularly during treatment
Monitor serum electrolytes before and during treatment
May cause adrenal suppression
Monitor ECG in patients at risk of QT prolongation
Monitor for signs of cutaneous squamous cell carcinoma
Monitor renal function regularly
Monitor serum amylase in patients at risk of pancreatitis
Monitor serum lipase in patients at risk of pancreatitis
Refer phototoxic reactions to dermatologist
Advise patient to seek medical advice if severe skin reaction occurs
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Consider discontinuing if phototoxic reaction occurs
Consider discontinuing if signs and symptoms of periostitis occur
Discontinue if premalignant skin lesions/squamous cell carcinoma occur
Discontinue if symptoms of hepatic disease occur
Withdraw drug in the case of worsening rash or severe skin reactions
Advise patient not to take St John's wort concurrently
Female: Ensure adequate contraception during treatment
Advise patient on appropriate sun protection methods
Advise patient to avoid exposure to direct sunlight
Advise patients that phototoxic reactions may occur
Advise patients to report skin rash
Avoid excessive exposure to sunlight or sunlamps
Cases of reversible adrenal insufficiency have been reported with voriconazole usage. Patients should be monitored for adrenal cortex dysfunction during and after treatment, and seek immediate medical care if they experience signs of adrenal insufficiency or Cushing's syndrome.
If phototoxic reactions occur and treatment is continued, dermatologic evaluation should occur regularly for early detection of premalignant lesions.
Pregnancy and Lactation
Pregnancy
Voriconazole is contraindicated during pregnancy.
The manufacturer suggests voriconazole must not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the foetus. Briggs suggests because of the close relationship of voriconazole to fluconazole, a suspected teratogen in high doses, that voriconazole should be avoided during pregnancy.
It is unknown whether voriconazole crosses the placenta. The molecular weight is low enough that exposure of the embryo and/or foetus should be expected.
Lactation
Voriconazole is contraindicated in breastfeeding.
The manufacturer suggests breastfeeding must be stopped on initiation of treatment of voriconazole.
The excretion of voriconazole into breast milk has not been investigated. The low molecular weight suggests that voriconazole will be excreted into breast milk. There is potential for toxicity in breastfeeding infants especially during the neonatal period when hepatic function is immature.
Side Effects
Abnormal liver function tests
Acute renal failure
Adrenal cortex insufficiency
Alopecia
Anaphylactoid reaction
Angioedema
Back pain
Blepharitis
Blood dyscrasias
Bone marrow depression
Bradycardia
Bundle branch block
Cardiac arrhythmias
Cerebral oedema
Cheilitis
Chest pain
Cholecystitis
Cholelithiasis
Complete AV block
Confusion
Convulsions
Corneal opacities
Discoid lupus erythematosus
Dizziness
Encephalopathy
Erythema multiforme
Exfoliative dermatitis
Extrapyramidal effects
Fever
Gastro-enteritis
Gastro-intestinal symptoms
Gingivitis
Glossitis
Guillain-Barre syndrome
Haematuria
Hallucinations
Headache
Hepatic coma
Hepatic failure
Hepatitis
Hepatomegaly
Hypercholesterolaemia
Hypersensitivity reactions
Hypoacusis
Hypoaesthesia
Hypoglycaemia
Hypokalaemia
Hypotension
Increase in creatinine
Insomnia
Intravascular coagulation (disseminated)
Jaundice
Lymphadenopathy
Lymphangitis
Mood changes
Musculoskeletal disturbances
Nephritis
Nystagmus
Oculogyration
Oedema
Optic atrophy
Optic neuritis
Pancreatitis
Papilloedema
Paraesthesia
Periostitis
Peripheral neuropathy
Peritonitis
Phlebitis
Prolongation of QT interval
Proteinuria
Pruritus
Pseudomembranous colitis
Psoriasis
Psychiatric disorders
Pulmonary oedema
Purpura
Rash
Renal tubular necrosis
Respiratory distress
Retinal haemorrhage
Scleritis
Serum bilirubin increased
Sinusitis
Skin disorder
Skin photosensitivity
Squamous cell carcinoma
Stevens-Johnson syndrome
Tachycardia
Taste disturbances
Tinnitus
Torsades de pointes
Toxic epidermal necrolysis
Tremor
Vasovagal attacks
Vertigo
Visual disturbances
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: April 2019
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.
Summary of Product Characteristics: VFEND 40 mg/ml powder for oral suspension. Pfizer Ltd. Revised February 2022.
Summary of Product Characteristics: VFEND 50mg Film-Coated Tablets. Pfizer Ltd. Revised February 2022.
Summary of Product Characteristics: VFEND 200mg Film-Coated Tablets. Pfizer Ltd. Revised February 2022.
Summary of Product Characteristics: VFEND 200 mg powder and solvent for solution for infusion. Pfizer Ltd. Revised December 2018.
Summary of Product Characteristics: VFEND 200 mg powder for solution for infusion. Pfizer Ltd. Revised February 2022.
Summary of Product Characteristics: Voriconazole 50mg Film-Coated Tablets. Dr.Reddy's Laboratories. Revised March 2019.
Summary of Product Characteristics: Voriconazole 200mg Film-Coated Tablets. Dr.Reddy's Laboratories. Revised March 2019.
Summary of Product Characteristics: Voriconazole 50mg Film-Coated Tablets. Aspire Pharma Ltd. Revised February 2019.
Summary of Product Characteristics: Voriconazole 200mg Film-Coated Tablets. Aspire Pharma Ltd. Revised February 2019.
Summary of Product Characteristics: Voriconazole Actavis 50mg Film-Coated Tablets. Actavis UK Ltd. Revised November 2016.
Summary of Product Characteristics: Voriconazole Actavis 200mg Film-Coated Tablets. Actavis UK Ltd. Revised November 2016.
NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 03 April 2019
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