Posaconazole

Posaconazole is an azole antifungal. It prevents and treats fungal infections in adults and children over the age of two with weakened immune systems. It is also used to treat invasive aspergillosis in adults and teenagers aged 13 and up. It is a triazole antifungal medication that inhibits enzymes that rely on other enzymes. This prevents the synthesis of ergosterol, a key component of the fungal cell membrane, resulting in a buildup of methylated sterol precursors. This limits fungal cell growth and death, thereby curing the infection. The FDA approved posaconazole in 2006

BRAND NAMES:

Posanol – It contains the active ingredients of posaconazole. It is available in oral suspension used to treat fungal infections.

Noxafil – It contains the active ingredients of posaconazole. It is available in the form of delayed-release tablets used to treat fungal infections.

MECHANISM OF ACTION:

Posaconazole inhibits the enzyme lanosterol 14α-demethylase, which catalyzes an essential step in ergosterol biosynthesis.

PHARMACOKINETICS:

Absorption: Following oral administration of posaconazole the median of Tmax is approximately 3 to 5 hours.

Distribution: The volume of distribution of posaconazole is 1774L.

Metabolism: Posaconazole does not have any major circulating metabolites and its concentrations are unlikely to be altered by inhibitors of CYP450 enzymes. Of the circulating, metabolites the majority of glucuronide conjugates of posaconazole with only less amounts of oxidative metabolites 19 observed.

Excretion: The excretion of metabolites through urine and feces.

PHARMACODYNAMICS:

Posaconazole is an antifungal agent structurally releated to itraconazole. It is a drug derived from itraconazole through the replacement of the chlorine substituents with fluorine in the phenyl ring, as well as hydroxylation of the triazolone side chain. These modifications enhance the potency and spectrum of activity of the drug. Posaconazole can be either fungicial or fungistatic in action.

DOSAGE AND ADMINISTRATION:

Posaconazole is available in three forms: immediate-release oral suspension, delayed-release tablet, and delayed-release oral suspension for oral administration. The delayed-release tablets are typically taken with or without food twice daily for the first day, followed by one day. The delayed-release oral suspension is often given with food twice daily for the first day, then once daily thereafter. Immediate-release oral suspensions are often given one to three times per day with a full meal or within 20 minutes of a meal.

It is available in the form of oral suspension.

It is available in the form of delayed-release tablets

DRUG INTERACTIONS:

Drug interactions with posaconazole may include

Proton pump inhibitor – esomeprazole, pantoprazole
Seizures- phenytoin
Alpha-blockers – alfuzosin, silodosin, and tamsulosin
Benzodiazepines – midazolam
Ergot-alkaloids – ergotamine and dihydroergotamine
Statin drugs – lovastatin and simvastatin

CONTRAINDICATIONS:

Posaconazole is contraindicated when co-administration with sirolimus, ergot alkaloids, and HMG-CoA reductase inhibitors that are primarily metabolized through CYP3A4 or CYP3A4 substrates that prolong the QT interval., hypersensitivity to posaconazole other zole anti-fungal agents or any component of the formulation.

SIDE EFFECTS:

Side effects of posaconazole may include

Fever
Dizziness
Headache
Vomiting
Constipation
Heartburn
Weakness
Chills or shaking
Itching
Cough
Constipation
Increased sweating
Fast, pounding, or irregular heartbeat
Sudden loss of consciousness
Shortness of breath

OVERDOSE:

Symptoms of overdose may include

Anorexia
Vomiting
Fatigue
Nausea
Dark urine
Jaundice
Abdominal pain

TOXICITY:

Posaconazole is not removed by hemodialysis. There is no specific treatment available in the case of overdose with posaconazole symptomatic treatment should be given.

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