posaconazole
Meaning of posaconazole: One of the broadest antifungal drugs available, valued for covering molds that most others in its class miss.
Definition of posaconazole
Posaconazole is a triazole antifungal medicine used against serious fungal infections, including aspergillosis and mucormycosis, and used to prevent them in people whose immune defenses are severely weakened. It blocks a fungal enzyme needed to make ergosterol, the sterol that keeps the fungal cell membrane intact. It is taken by mouth as a tablet or liquid, or given into a vein.
How does it kill fungi?
Fungal cells build their outer membrane around ergosterol, a molecule that does much the job cholesterol does in human cells. Posaconazole blocks an enzyme called lanosterol 14-alpha-demethylase, an early step in making ergosterol. The membrane that results is leaky and unstable, toxic intermediates pile up behind the block, and growth stops. Human cells make cholesterol by a related route, and the drug's preference for the fungal enzyme is what allows a selective attack. Ergosterol sits in the plasma membrane rather than in the cell wall, which is a common mix up.
What does it cover?
| Organism | Covered |
|---|---|
| Candida species | Yes |
| Aspergillus species | Yes |
| The molds behind mucormycosis | Yes, which is unusual among the azoles |
| Cryptococcus | Yes |
That third row is why this drug is singled out. Most antifungal medicines in the azole family have no useful activity against the molds that cause mucormycosis, so the options there are few.
Why is absorption an issue?
The original liquid was absorbed erratically and had to be taken with fatty food to work reliably. A delayed release tablet and an injectable form were developed to solve that, and both give steadier levels. Measuring the blood concentration is common in serious infection, since too little fails to treat while more does not always help. Medicines that suppress stomach acid reduce uptake of the liquid form.
What does it interact with?
Posaconazole strongly blocks one of the enzymes of the cytochrome P450 enzyme system, which the liver uses to clear a great many drugs. Blocking it raises the blood level of anything cleared by that route, which matters for certain transplant medicines, some statins and several cancer drugs. The drug can also lengthen the QT interval on an electrocardiogram, an effect that compounds when other medicines do the same. Liver blood tests are followed during treatment.
Also known as
Used in a sentence
Posaconazole prophylaxis was continued throughout the period of profound neutropenia.
Good to know
Ergosterol belongs to the fungal cell membrane rather than the cell wall, and posaconazole blocks its manufacture; the drug also inhibits a major liver enzyme, so it raises the blood levels of many other medicines.