- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oral formulations containing posaconazole
Oropharyngeal candidiasis: treatment
Prophylaxis of fungal infection in haematopoietic stem cell transplant pts
Prophylaxis of invasive fungal infection in patients receiving chemotherapy
Treatment of aspergillosis when other treatment unsuitable/ineffective
Treatment of chromoblastomycosis when itraconazole unsuitable/ineffective
Treatment of coccidioidomycosis when other treatment unsuitable/ineffective
Treatment of fusariosis when amphotericin unsuitable/ineffective
Treatment of mycetoma when itraconazole unsuitable/ineffective
Treatment of the following invasive fungal infections in adults:
Invasive aspergillosis in patients who are unresponsive or intolerant to amphotericin B or itraconazole.
Fusariosis in patients who are unresponsive or intolerant to amphotericin B.
Chromoblastomycosis and mycetoma in patients who are unresponsive or intolerant to itraconazole.
Coccidioidomycosis in patients who are unresponsive or intolerant to amphotericin B, itraconazole or fluconazole.
'Unresponsive' is defined as the progression of infection or failure to improve after a minimum of 7 days of prior therapeutic doses of effective antifungal therapy.
Oral suspension only
Oropharyngeal candidiasis: as first line therapy in patients who have severe disease or are immunocompromised, in whom response to topical therapy is expected to be poor.
Prophylaxis of invasive fungal infections in the following patients:
Patients receiving remission-induction chemotherapy for acute myelogenous leukaemia or myelodysplastic syndrome expected to result in prolonged neutropenia and who are at high risk of developing invasive fungal infections.
Haematopoietic stem cell transplant recipients who are undergoing high-dose immunosuppressive therapy for graft versus host disease and who are at high risk of developing invasive fungal infections.
The gastro-resistant tablet and the oral solution are not to be used interchangeably due to dosing differences. The gastro-resistant tablets are the preferred formulation to optimise plasma levels and provide higher plasma drug exposures than the oral suspension.
Treatment of invasive aspergillosis, fusariosis, chromoblastomycosis, mycetoma, or coccidioidomycosis
Duration of therapy should be based on the severity of the infection, the recovery from immunosuppression, and the clinical response to therapy.
300 mg twice a day on the first day then 300 mg once a day thereafter.
200mg posaconazole four times a day. Alternatively, for patients able to tolerate a meal or a nutritional supplement, 400mg twice daily may be given.
Treatment of oropharyngeal candidiasis
200mg once a day on the first day of therapy followed by 100mg once a day for the next 13 days.
Prophylaxis of invasive fungal infections
The duration of therapy is based on recovery from neutropenia or immunosuppression.
For patients with acute myelogenous leukaemia or myelodysplastic syndromes, prophylaxis with posaconazole should begin several days before the anticipated onset of neutropenia and continue for 7 days after the neutrophil count rises above 500 cells per cubic millimetre.
300 mg twice a day on the first day, then 300 mg once a day thereafter.
200mg three times a day.
(See Dosage; Adults).
Children under 18 years
Precautions and Warnings
Family history of long QT syndrome
Glucose-galactose malabsorption syndrome
History of torsade de pointes
Long QT syndrome
Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Not all formulations are licensed for all uses
Treatment to be initiated and supervised by a specialist
Some formulations contain glucose
Adjust dose if switching between solid oral formulations & oral solution
Different oral formulations are not interchangeable (not bioequivalent)
Perform ECG before treatment
If hepatic impairment symptoms occur monitor LFT & consider discontinuation
Monitor ECG in patients at risk of QT prolongation
Monitor electrolytes, esp potassium, magnesium and calcium during therapy
Monitor hepatic function
Monitor pts with severe GI dysfunction for breakthrough fungal infections
Female: Ensure adequate contraception during treatment
The limited data available show that people with hepatic impairment have an increase in plasma exposure compared with those of a normal hepatic function. There have been reports of hepatic reactions during treatment with posaconazole. These reactions included increases in ALT, AST, alkaline phosphatase, and total bilirubin levels and clinical hepatitis. Rarely more severe hepatic reactions with fatal outcomes have been reported, which may be more likely in patients with serious underlying medical conditions. Elevated liver function tests were generally reversible following discontinuation of therapy, and sometimes normalised without interrupting treatment.
Hepatic function (including liver function tests and bilirubin) should be monitored during treatment. Patients who develop abnormal liver functions tests during treatment, should be routinely monitored for the development of more severe hepatic effects. If symptoms of hepatic impairment occur during therapy, consider the discontinuation of posaconazole.
Pregnancy and Lactation
Use posaconazole with caution during pregnancy.
Briggs suggests, due to the limited human data, posaconazole should be avoided during pregnancy, especially during the first trimester. If the condition requires posaconazole and the benefit is considered to outweigh the potential risk, posaconazole may be given at the lowest possible dose. The manufacturer suggests there are insufficient data on the use of posaconazole in pregnant women. Posaconazole must not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the foetus.
Due to the molecular weight (about 701), low metabolism and long half-life of posaconazole, it is considered likely that posaconazole will cross the placenta to the foetus.
Animal studies have shown reproductive toxicity, but due to the absence of human clinical experience the risk of toxicity during human pregnancy is unknown.
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 ).
Posaconazole is contraindicated in breastfeeding.
Briggs suggests the effect of potential exposure to the infant via breast milk is unknown but severe treatment toxicity has been reported in adults. The manufacturer suggests breastfeeding must be stopped on initiation of treatment with posaconazole.
At the time of writing, there are no data on the use of posaconazole during human breastfeeding. Animal studies have shown that posaconazole is excreted in rat milk.
Due to its low molecular weight (about 701), low metabolism (about 17%) and long half-life (range 20 to 66 hours), it is considered likely that posaconazole will be excreted in human breast milk. The effects of posaconazole on a nursing infant are unknown.
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
Altered liver function tests
Changes of blood pressure
Haemolytic uraemic syndrome
Renal tubular acidosis
Serum creatinine increased
Thrombotic thrombocytopenic purpura
Torsades de pointes
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 ).
Last Full Review Date: May 2014
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.
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com [Accessed on April 23, 2014].
Summary of Product Characteristics: Noxafil 100 mg gastro-resistant tablets. Merck Sharp and Dohme. Revised April 2014.
Summary of Product Characteristics: Noxafil 40mg/ml oral suspension. Merck Sharp and Dohme. Revised April 2014.
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