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

Administration

For administration as an intravenous infusion after reconstitution and dilution.

It should be given at a maximum rate of 3 mg/kg per hour over 1 to 3 hours.

Contraindications

Children under 2 years
Breastfeeding
Long QT syndrome
Porphyria
Pregnancy
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Restricted sodium intake
Acute pancreatitis
Electrolyte imbalance
Haematological malignancy
Hepatic impairment
History of torsade de pointes
Renal impairment - creatinine clearance below 50ml/minute

Correct electrolyte disorders before treatment
Reduce maintenance dose in hepatic impairment
Sodium content of formulation may be significant
Some formulations contain more than 1mmol (23mg) sodium per dose
Advise ability to drive/operate machinery may be affected by side effects
Monitor hepatic function before treatment and regularly during treatment
Consider monitoring ECG in patients at risk of QT prolongation
If rash develops, consider possibility of Stevens-Johnson Syndrome
Liver function tests recommended - withdraw therapy if abnormal
May cause adrenal suppression
Monitor for signs of cutaneous squamous cell carcinoma
Monitor patient for infusion-associated reactions (IARs)
Monitor renal function regularly
Monitor serum amylase in patients at risk of pancreatitis
Monitor serum creatinine in patients with renal impairment
Monitor serum electrolytes
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
Withdraw drug in the case of worsening rash or severe skin reactions
Maximum treatment duration is 6 months
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

Monitor hepatic function (specifically AST and ALT) before starting treatment, at least weekly for 1 month, and then monthly during treatment. If hepatic function tests become markedly elevated voriconazole should be discontinued, unless the benefit of continuing treatment outweighs the risk to the patient.

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 in pregnancy.

At the time of writing, there is limited information on the use of voriconazole during pregnancy. The manufacturers suggest voriconazole must not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the foetus.

It is unknown whether voriconazole crosses the placenta. The molecular weight is low enough that exposure to the embryo and/or foetus should be expected. Briggs suggests a theoretical risk of teratogenicity, and states that voriconazole should be avoided in the first trimester.

Studies in animals have shown reproductive toxicity.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Voriconazole is contraindicated in breastfeeding.

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.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abnormal liver function tests
Acute renal failure
Adrenal cortex insufficiency
Alopecia
Anaphylactoid reaction
Angioedema
Asthenia
Back pain
Blepharitis
Blood dyscrasias
Bone marrow depression
Bradycardia
Bundle branch block
Cardiac arrhythmias
Cerebral oedema
Cheilitis
Chest pain
Chills
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
Injection site reactions
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

Presentation

Parenteral 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 and switching between intravenous 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. Treatment duration longer than 6 months requires careful assessment of the benefit to risk balance.

Prophylaxis
Initiate on the day of transplant and administer for up to 100 days. Treatment may continue for 6 months in case of continuing immunosuppression or graft versus host disease. Dose adjustments are not recommended in instances of lack of efficacy or voriconazole related adverse reactions. Consider discontinuing voriconazole in the event of adverse effects.

Adults

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Administration

For administration as an intravenous infusion after reconstitution and dilution.

It should be given at a maximum rate of 3 mg/kg per hour over 1 to 3 hours.

Contraindications

Children under 2 years
Breastfeeding
Long QT syndrome
Porphyria
Pregnancy
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Restricted sodium intake
Acute pancreatitis
Electrolyte imbalance
Haematological malignancy
Hepatic impairment
History of torsade de pointes
Renal impairment - creatinine clearance below 50ml/minute

Correct electrolyte disorders before treatment
Reduce maintenance dose in hepatic impairment
Sodium content of formulation may be significant
Some formulations contain more than 1mmol (23mg) sodium per dose
Advise ability to drive/operate machinery may be affected by side effects
Monitor hepatic function before treatment and regularly during treatment
Consider monitoring ECG in patients at risk of QT prolongation
If rash develops, consider possibility of Stevens-Johnson Syndrome
Liver function tests recommended - withdraw therapy if abnormal
May cause adrenal suppression
Monitor for signs of cutaneous squamous cell carcinoma
Monitor patient for infusion-associated reactions (IARs)
Monitor renal function regularly
Monitor serum amylase in patients at risk of pancreatitis
Monitor serum creatinine in patients with renal impairment
Monitor serum electrolytes
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
Withdraw drug in the case of worsening rash or severe skin reactions
Maximum treatment duration is 6 months
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

Monitor hepatic function (specifically AST and ALT) before starting treatment, at least weekly for 1 month, and then monthly during treatment. If hepatic function tests become markedly elevated voriconazole should be discontinued, unless the benefit of continuing treatment outweighs the risk to the patient.

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 in pregnancy.

At the time of writing, there is limited information on the use of voriconazole during pregnancy. The manufacturers suggest voriconazole must not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the foetus.

It is unknown whether voriconazole crosses the placenta. The molecular weight is low enough that exposure to the embryo and/or foetus should be expected. Briggs suggests a theoretical risk of teratogenicity, and states that voriconazole should be avoided in the first trimester.

Studies in animals have shown reproductive toxicity.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Voriconazole is contraindicated in breastfeeding.

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.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abnormal liver function tests
Acute renal failure
Adrenal cortex insufficiency
Alopecia
Anaphylactoid reaction
Angioedema
Asthenia
Back pain
Blepharitis
Blood dyscrasias
Bone marrow depression
Bradycardia
Bundle branch block
Cardiac arrhythmias
Cerebral oedema
Cheilitis
Chest pain
Chills
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
Injection site reactions
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: February 2019

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

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 200mg powder for solution for infusion. Actavis Ltd. Revised March 2017.
Summary of Product Characteristics: Voriconazole 200mg powder for solution for infusion. Aspire Pharma Ltd. Revised October 2017.

NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 19 February 2019

The Drug Database for Acute Porphyria (NAPOS)
Available at: https://www.drugs-porphyria.com/languages/UnitedKingdom/index2.php?l=gbr
Voriconazole.
Last accessed: 19 February 2019.