Fluconazole parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Infusions of fluconazole.
Drugs List
Therapeutic Indications
Uses
Candidiasis - severe systemic
Cryptococcal meningitis
Cryptococcosis - treatment
Mucosal candidiasis
Prevention of relapse of cryptococcal meningitis in patients at risk
Prophylaxis of fungal infection in immunocompromised patients
Mucosal candidiasis including oropharyngeal, oesophageal, non-invasive bronchopulmonary infections, candiduria, mucocutaneous and chronic oral atrophic candidiasis (denture sore mouth) in normal hosts and patients with compromised immune function.
Systemic candidiasis including candidaemia, disseminated candidiasis and other forms of invasive candidal infection including infections of the peritoneum, endocardium and pulmonary and urinary tracts in patients with malignancies, in intensive care units and those receiving cytotoxic or immunosuppressive therapy.
Cryptococcosis, including cryptococcal meningitis and infections of other sites (such as pulmonary or cutaneous). Normal hosts and patients with AIDS, organ transplants or other causes of immunosuppression may be treated. Fluconazole may be used as maintenance therapy to prevent relapse of cryptococcal disease in patients at risk.
Prevention of fungal infections in immunocompromised patients considered at risk as a consequence of neutropenia following cytotoxic chemotherapy or radiotherapy, including bone marrow transplant patients.
Dosage
Adults
Oropharyngeal and oesophageal candidiasis
Loading dose
200mg to 400mg for 1 day.
Maintenance dose
100mg to 200mg daily.
Treatment of oropharyngeal candidiasis is for 7 to 21 days.
Treatment of oesophageal candidiasis is for 14 to 30 days.
Use until candidiasis is in remission. Longer treatment duration may be necessary in severely immunocompromised patients.
Invasive candidiasis
Loading dose
800mg for 1 day.
Maintenance dose
400mg daily.
Maximum 800mg daily in severe infections. Treatment duration is 2 weeks after first negative blood culture result and resolution of signs and symptoms associated with candidaemia.
Chronic mucocutaneous candidiasis
50mg to 100mg daily. Treatment up to 28 days. Longer treatment may be necessary in patients with severe infection or in immunocompromised patients.
Chronic atrophic oral candidiasis
50mg daily for 14 days.
Candiduria
200mg to 400mg daily 7 to 21 days.
Oropharyngeal and oesophageal candidiasis in HIV positive patients who are at risk of relapse
100mg to 200mg daily or 200mg three times weekly. Treatment is indefinite in patients with chronic immune suppression.
Cryptococcal meningitis
Loading dose
400mg for 1 day.
Maintenance dose
200mg to 400mg daily.
In life threatening infections, increase dose to 800mg daily. Treatment duration is 6 to 8 weeks for cryptococcal meningitis.
Cryptococcal meningitis in patients with high risk of recurrence
200mg daily, recommended indefinitely.
Coccidioidomycosis
200mg to 400mg daily. Treatment is 11 months, can be increased longer than 24 months. 800mg daily for some infections and in particular for meningeal disease.
Prophylaxis of candidal infections in immunocompromised patients
200mg to 400mg daily. Start several days before onset of neutropenia and continue for 7 days after neutrophil count rises above 1000 cells per cubic mm.
Children
Children aged 12 to 18 years
100mg, 200mg and 400mg in adults corresponds to a 3mg/kg, 6mg/kg and 12mg/kg dose in children. Maximum licensed dose: 400mg daily.
Children aged 1 month up to 12 years
Mucosal candidiasis
Loading dose: 6mg/kg for 1 day
Maintenance dose: 3mg/kg daily, maximum 100mg.
Invasive candidiasis and cryptococcal meningitis
6mg/kg to 12mg/kg daily. Maximum 800mg (unlicensed). Continue treatment for at least 8 weeks.
Cryptococcal meningitis in patients with risk of recurrence
6mg/kg daily.
Candida infections in immunocompromised patients prophylaxis
3mg/kg to 12mg/kg daily, maximum 400mg. Begin treatment before onset of neutropenia and continue for 7 days after neutrophil count in desirable range.
Neonates
Mucosal candidiasis
Neonates aged 15 to 27 days
Loading dose: 6mg/kg for 1 day.
Maintenance dose: 3mg/kg every 48 hours. Maximum 12mg/kg every 48 hours.
Neonates aged under 15 days
Loading dose: 6mg/kg for 1 day
Maintenance dose: 3mg/kg every 72 hours. Maximum 12mg/kg every 72 hours.
Invasive candidiasis and cryptococcal meningitis
Neonates aged 15 to 27 days
6mg/kg to 12mg/kg every 48 hours. Maximum 12mg/kg every 48 hours.
Neonates aged under 15 days
6mg/kg to 12mg/kg every 72 hours. Maximum 12mg/kg every 72 hours.
Continue treatment for at least 8 weeks.
Prophylaxis of candidal infections in immunocompromised patients
Neonates aged 15 to 27 days
3mg/kg to 12mg/kg every 48 hours. Maximum 12mg/kg every 48 hours.
Neonates aged under 15 days
3mg/kg to 12mg/kg every 72 hours. Maximum 12 mg/kg every 72 hours.
Patients with Renal Impairment
Single dose therapy
No adjustments in single dose therapy are required. For multiple dose therapy, the normal recommended dose (according to indication) should be given on day 1, followed by a daily dose depending on creatinine clearance:
Multiple dose therapy
Loading dose
As normal.
Maintenance dose
Creatinine clearance more than 50ml per minute: 100% of the recommended dose.
Creatinine clearance equal to or less than 50ml per minute (no dialysis): 50% of the recommended dose.
Regular dialysis: 100% of the recommended dose after each dialysis. On non-dialysis days, patients should receive a reduced dose according to their creatinine clearance.
The Renal Drug Handbook suggests the following doses for multiple dose therapy:
GFR 10ml to 50ml per minute: 50 to 100% of normal dose.
GFR less than 10ml per minute: 50% of normal dose.
Additional Dosage Information
When transferring from the oral route to the intravenous route or vice versa, there is no need to change the daily dose. Patient should be switched to oral route as soon as possible.
Administration
For intravenous infusion.
Fluconazole intravenous infusion should be administered at a rate not exceeding 10ml per minute. One manufacturer suggests that the rate of intravenous infusion in children should not exceed 5ml per minute. For premature infants infusion time should be no less than 15 minutes.
Contraindications
Restricted sodium intake
Acute porphyria
Long QT syndrome
Torsade de pointes
Precautions and Warnings
Family history of long QT syndrome
Breastfeeding
Electrolyte imbalance
Hepatic impairment
History of drug induced hepatotoxicity
History of torsade de pointes
Pregnancy
Renal impairment - creatinine clearance below 51ml/minute
Correct electrolyte disorders before treatment
Some formulations contain more than 1mmol (23mg) sodium per dose
Advise ability to drive/operate machinery may be affected by side effects
Consult national/regional policy on the use of anti-infectives
Not all available brands are licensed for all indications
Treatment to be initiated and supervised by a specialist
Perform ECG before and during treatment
If rash develops, consider possibility of Stevens-Johnson Syndrome
Monitor hepatic function on long term therapy
Monitor serum electrolytes
Monitor skin changes
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Discontinue if severe skin reaction occurs
Discontinue if symptoms of hepatic disease occur
Consider dose reduction in renal impairment
Exfoliative cutaneous reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported rarely. If a rash develops in a patient treated for a superficial fungal infection which may be attributed to fluconazole, discontinue treatment. If patients with invasive/systemic fungal infections develop rashes, they should be closely monitored and fluconazole discontinued if bullous lesions or erythema multiforme develop.
Prescribers are advised to take into account the prevalence of resistance in various Candida species to fluconazole as alternative antifungal therapy secondary to treatment failure may be required.
Pregnancy and Lactation
Pregnancy
Use fluconazole with caution in pregnancy.
According to Briggs, there is data to suggest that fluconazole may have a teratogenic effect when used in high continuous daily doses (400mg/day or more) during the first trimester of pregnancy. Smaller doses, such as those prescribed for vaginal fungal infections, are thought to have a relatively low risk of adverse outcomes. In one large study, exposure to oral cumulative doses 450mg or less of fluconazole in first trimester was associated with a small increased risk of musculoskeletal malformations. Data shows no increase in the overall risk of malformations in the fetus when pregnant women being treated with cumulative dose of 150mg or less with fluconazole.
The manufacturer states that fluconazole should not be used in pregnancy unless clearly necessary, with reports of congenital abnormalities in infants whose mothers were treated for at least three months with high daily doses (400mg-800mg) of fluconazole.
An observational study has indicated there may be an increased risk of spontaneous abortion in women treated with fluconazole during the first trimester.
Lactation
Use fluconazole with caution in breastfeeding.
LactMed suggests fluconazole is acceptable in breastfeeding as amounts excreted into breast milk are less than the neonatal fluconazole dosage. Schaefer suggests many authors have cleared the use of fluconazole in breastfeeding due to the good tolerance seen in infancy for intravenously administered fluconazole.
The manufacturer advises that breastfeeding may continue after a single use of a standard dose of 200mg fluconazole or less, but breastfeeding is not recommended after a repeated use or after high dose fluconazole.
Side Effects
Abdominal discomfort
Abdominal pain
Acute generalised exanthematous pustulosis
Agranulocytosis
Alopecia
Alterations in haematological function tests
Alterations in renal function tests
Anaemia
Anaphylaxis
Angioedema
Anorexia
Asthenia
Cholestasis
Constipation
Decreased appetite
Diarrhoea
Dizziness
Dry mouth
Dyspepsia
Exfoliative rash
Facial oedema
Fatigue
Fever
Fixed drug eruption
Flatulence
Headache
Hepatic disorders
Hepatic failure
Hepatic necrosis
Hepatitis
Hepatotoxicity
Hypercholesterolaemia
Hypersensitivity reactions
Hypertriglyceridaemia
Hypokalaemia
Increase in alkaline phosphatase
Increase in serum transaminases
Insomnia
Jaundice
Leucopenia
Malaise
Myalgia
Nausea
Neutropenia
Paraesthesia
Prolongation of QT interval
Pruritus
Rash
Seizures
Serum bilirubin increased
Somnolence
Stevens-Johnson syndrome
Sweating
Taste disturbances
Thrombocytopenia
Torsades de pointes
Toxic epidermal necrolysis
Tremor
Urticaria
Vertigo
Vomiting
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: March 2019
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
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: Diflucan 2mg/ml solution for infusion. Pfizer Ltd. Revised December 2017.
Summary of Product Characteristics: Fluconazole 2mg/ml solution for infusion. Focus Pharmaceuticals Ltd. Revised January 2016.
Summary of Product Characteristics: Fluconazole 2mg/ml solution for infusion. Teva UK Ltd. Revised October 2020
Summary of Product Characteristics: Fluconazole 400mg/200ml solution for infusion bags. Bowmed Ibisqus Ltd. Revised March 2021.
NAPOS - The Drug Database for Acute Porphyria.
Available at: https://www.drugs-porphyria.com
Last accessed: 04 February 2021
NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 04 February 2021
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Fluconazole. Last revised: 31 October 2018..
Last accessed: 8 March 2019
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