Itraconazole
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Itraconazole
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| Systematic (IUPAC) name | |
| 4-[4-[4-[4-[ [2-(2,4-dichlorophenyl)- 2-(1H-1,2,4-triazol-1-ylmethyl)- 1,3-dioxolan-4-
yl]methoxy]phenyl] piperazin-1-yl]phenyl]- 2-(1-methylpropyl)-2,4-dihydro-1, 2,4-triazol- 3-one |
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| Identifiers | |
| CAS number | |
| ATC code | J02 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C35H38Cl2N8O4 |
| Mol. mass | 705.64 |
| Pharmacokinetic data | |
| Bioavailability | 55%, maximal if taken with full meal |
| Protein binding | 99.8% |
| Metabolism | hepatic (CYP3A4) |
| Half life | 21 hours |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
C (safety unknown) |
| Legal status | |
| Routes | Oral and i.v. (US), Oral only (UK) |
Itraconazole (marketed as Sporanox® by Janssen Pharmaceutica) is a triazole antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously.
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[edit] Pharmacology
The mechanism of action of itraconazole is the same as the other azole antifungals: it inhibits cytochrome P450 oxidase-mediated synthesis of ergosterol.
[edit] Indication
Itraconazole has a broader spectrum of activity than fluconazole (but not as broad as voriconazole or posaconazole). In particular, it is active against aspergillus, which fluconazole is not. It is also licenced for use in blastomycosis, histoplasmosis and onychomycosis. Itraconazole is over 99% protein bound and has virtually no penetration into cerebrospinal fluid. Therefore, it should never be used to treat meningitis or other central nervous system infections.[1]
[edit] Dosing
Itraconazole is available as capsules or as an oral solution. The dose is 200 mg once a day, to 400 mg in severe infection. There is an intravenous preparation available in the US, but not in the UK. In the UK, if an intravenous preparation is required, then an alternative antifungal drug should be used.
The main problem with the use of itraconazole is its poor absorption, especially when given in capsule form. The oral solution is much better absorbed and should always be used in preference to the capsule. The cyclodextrin contained in the oral solution can cause an osmotic diarrhoea, and if this is a problem, then half the dose can be given as oral solution and half as capsule in order to reduce the amount of cyclodextrin given. Itraconazole capsules should always be taken with food, as this improves absorption. Itraconazole oral solution should be taken an hour before food, or two hours after food (and likewise if a combination of capsules and oral solution are used). Itraconazole should be taken with orange juice or cola, as absorption is also improved by acid. Absorption of itraconazole is impaired when taken with an antacid, H2-blocker or proton pump inhibitor.
In life-threatening situations, some doctors give an oral loading dose of 200 mg three times a day for three days, before dropping down to the usual dose. Because itraconazole absorption is unreliable, blood levels should be monitored at least once a week in those patients who are being treated for life-threatening (or potentially life-threatening) fungal infections.
In intravenous dosing, four doses of itraconazole 200 mg are given 12 hours apart, before changing the dose to once daily. There is no safety data for giving the intravenous preparation for more than 14 days continuously.
[edit] Adverse effects
Itraconazole is a relatively well tolerated drug (although not as well tolerated as fluconazole or voriconazole) and the range of adverse effects it produces is similar to the other azole antifungals.[2]
- Elevated alanine aminotransferase levels is found in 4% of people taking itraconazole
- "Small but real risk of developing" Congestive Heart Failure[2]
The cyclodextrin that is used to make the syrup preparation can cause diarrhoea. Side-effects that may indicate a greater problem include:
- nausea
- vomiting
- abdominal pain
- fatigue
- loss of appetite
- yellow skin (jaundice)
- yellow eyes
- itching
- dark urine
- pale stool
[edit] Production and marketing
Itraconazole can be consumed orally in blue ⅞ in (22 mm) capsules with tiny 1.5 mm blue pellets inside. Each tablet contains 100 mg and is usually taken multiple times a day such as every twelve hours. Sporanox, the brand name of Itraconazole, has been developed and marketed by Janssen Pharmaceutica Products, L.P. a subsidiary of Johnson and Johnson. Apparently, the three layer structure of these blue capsules are quite complex because Itraconazole is insoluble and is sensitive to pH. The complicated procedure not only requires a specialized machine to create it, but the method used has manufacturing problems. Also, the pill is quite large, making it difficult for many patients to swallow. Parts of the processes of creating Sporinox were discovered by the Korean Patent Laid. The contents of the capsule, the tiny blue pellets, are manufactured in Beerse, Belgium.[3][4]
[edit] Consumption
Itraconazole is marketed as a treatment for at least three months and until test results find no fungal infections. It is also possible that Itraconazole treatment is prescribed indefinitely for some patients. Roughly 180 generic capsules costs $360, which could last anywhere between less than one month and two months. If a patient is prescribed three capsules twice daily for the minimum of three months, the patient would spend more than $1080 and consume over 540 capsules. Motivation to spend thousands of dollars for continued use is the risk and threat of the fungus regrowing in the body.[4]
[edit] Political Economy
Itraconazole is prescribed by family doctors and general practitioners (whose patients have nail fungus), as well as for AIDS patients (to treat an infection).
Since Itraconazole is one of the few aggressive anti-fungal compounds on the market, some doctors and patients depend on Itraconazole.
[edit] Footnotes
- ^ Gilbert DN, Moellering, RC, Eliopoulos GM, Sande MA. The Sanford Guide to antimicrobial therapy 2006. ISBN 1-930808-30-5.
- ^ a b The Safety Of Sporanox® Capsules And Lamisil® Tablets For The Treatment Of Onychomycosis (May 09 2001). Retrieved on August 10, 2006.
- ^ “Composition comprising Itraconazole for oral administration.” 2004. Fresh Patents.com. 26 Oct. 2006. <http://www.freshpatents.com/Composition-comprising-itraconazole-for-oral-administration-dt20051013ptan20050226924.php?type=description>.
- ^ a b “Sporanox (Itraconazole Capsules).’’ June 2006. Janssen. 26 Oct. 2006 http://www.sporanox.com/active/janus/en_US/assets/common/company/pi/sporanox.pdf.
[edit] External links
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|---|---|
| Antibiotics | Griseofulvin, Hitachimycin, Natamycin, Nystatin |
| Topical Azoles | Clotrimazole, Econazole, Fluconazole, Ketoconazole, Miconazole, Oxiconazole, Sertaconazole, Sulconazole, Tioconazole |
| Other topicals | Ciclopirox, Ethylparaben, Flucytosine, Salicylic acid, Selenium sulfide, Terbinafine, Tolnaftate |
| For systemic use | Amphotericin B, Anidulafungin, Caspofungin, Griseofulvin, Itraconazole, Terbinafine, Voriconazole |
| Other | Posaconazole, Thiabendazole, Tea tree oil |
