Itraconazole formulations

Rambali, B., G. Verreck, L. Baert, and D. L. Massart. 2003. Itraconazole formulation studies of the melt extrusion process with mixture desidprug Dev Ind Pharrr 9 641-652. 

PGEi + 646 pg aCD/dose). In slow infusion, the parenteral administration of several grams of a noncrystallizable CD derivative is possible, for example, in a liquid itraconazole formulation the weight ratio of the drug to hydroxypropyl (3CD is 1 40. 

Itraconazole 200 mg PO daily for 6-12 weeks Lipid formulation may be more effective... 

In patients who have failed initial therapy (i.e., salvage), liposomal amphotericin products, itraconazole, or the echinocandin caspofungin can be used. Itraconazole has a response rate of approximately 40%.100 Oral itraconazole exhibits erratic absorption the IV formulation is suspended in cyclodextrin, which is eliminated renally, and thus IV itraconazole should be avoided in patients with a creatinine clearance of less than 30 mL/minute (0.29 mL/s m2).103 Itraconazole also has negative inotropic cardiac effects and increases the serum concentrations of medications (e.g., cyclophosphamide, etopo-side, calcineurin inhibitors, and sirolimus). 

CNS disease Lipid formulation of amphotericin BIV 3-6 mg/kg/day x 6-10 weeks (Note Induction therapy with azoles alone is discouraged.) Amphotericin Brf IV 0.7-1 mg/kg/day + flucytosine 100 mg/kg/ day orally x 2 wk, followed by fluconazole 400 mg orally daily for a minimum of 10 weeks (in patients intolerant to fluconazole, substitute itraconazole 200-400 mg orally daily) or Amphotericin B IV 0.7-1 mg/kg/day + 5-flucytosine 100 mg/kj day orally x 6-10 weeks or Amphotericin Brf IV 0.7-1 mg/kg/day x 10 weeks Refractory disease Intrathecal or intraventricular amphotericin B (continued)... 

Release-related bioavailability problems have been encountered in the pharmaceutical development of formulations for a number of quite different chemical entities, including ciclos-porin, digoxin, griseofulvin, and itraconazole, to name but a few. A thorough knowledge of hydrodynamics is useful in... 

Interchangeability Do not use itraconazole capsules and oral solution interchangeably. Drug exposure is greater with the oral solution than with the capsules when the same dose of drug is given. Additionally, the topical effects of mucosal exposure may be different between the two formulations. 

Invasive aspergillosis For the treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies (ie, amphotericin B, lipid formulations of amphotericin B, itraconazole). Caspofungin has not been studied as initial therapy for invasive aspergillosis. 

Drugs that may affect atazanavir include the following antacids and buffered medications, clarithromycin, didanosine (buffered formulation only), efavirenz, H2-receptor antagonists, indinavir, itraconazole, ketoconazole, nevirapine, proton pump inhibitors, rifampin, ritonavir, St. John s wort, tenofovir, voriconazole. 

HP-P-CD was developed by Janssen as a proprietary inactive ingredient (Encapsin ) and used in both the oral and IV formulation of their anti-fungal itraconazole (Sporanox ). The preclinical safety studies (9) conducted on HP-P-CD in support of Sporanox are highlighted in Table 3. 

On the basis of Hfft-CD, Janssen developed different formulation for Itraconazole (Sporanox), a broad-spectrum antifungal agent. Currently, capsule, IV, as well as oral solution formulations have been approved into market (http //www.accessdata.fda.gov/scripts/cder/ob/docs/tempai.cfm). 

Voriconazole is the newest triazole to be licensed in the USA. It is available in intravenous and oral formulations. The recommended dosage is 400 mg/d. The drug is well absorbed orally, with a bioavailability exceeding 90%, and exhibits less protein binding than itraconazole. Metabolism is predominantly hepatic, but the propensity for inhibition of mammalian P450 appears to be low. Observed toxicities include rash, elevated hepatic enzymes, and transient visual disturbances. 

The original formulation, a buffered powder, has been replaced by chewable and dispersible buffered tablets with greater bioavailability (30-40%) a new enteric-coated formulation further improves patient convenience and tolerability. Since the chewable tablets contain both phenylalanine (36.5 mg) and sodium (1380 mg), caution should be exercised in patients with phenylketonuria and those taking sodium-restricted diets. Didanosine should be taken on an empty stomach and, because of the buffered formulation, should be administered at least 2 hours after administration of drugs requiring acidity for optimal absorption (eg, ketoconazole, itraconazole, dapsone). 

Francois, M., Snoeckx, E., Putteman, R, Wouters, F., De Proost, E., Delaet, U., Peeters, J., and Brewster, M. E. (2003), A mucoadhesive, cyclodextrin-based vaginal cream formulation of itraconazole, AAPS PharmSci, 5, E5. 

ITRACONAZOLE, KETOCONAZOLE DIDANOSINE Possibly 1 efficacy of ketoconazole and itraconazole with buffered didanosine Absorption of the ketoconazole and itraconazole may be l by the buffered didanosine formulation, which raises gastric pH Give the ketoconazole and itraconazole 2 hours before or 6 hours after didanosine. Alternatively, consider using the enteric-coated formulation of didanosine, which does not have to be given separately... 

The safety, tolerability, and pharmacokinetics of itraconazole and its active metabolite hydroxyitraconazole after administration of itraconazole solution in hydroxy-propyl-P-cyclodextrin have been investigated in a multicenter study in 26 infants and children aged 6 months to 12 years with mucosal candidiasis or at risk of invasive fungal disease (50). There was a trend to lower minimum plasma concentrations in children aged 6 months to 2 years. The systemic absorption of the solubilizer hydro-x)q)ropyl-P-cyclodextrin was less than 1%. Given at 5 mg/ kg/day, this formulation provided potentially therapeutic concentrations in plasma, somewhat lower than those attained in adults, and it was well tolerated and safe. 

Hoetelmans RM. Itraconazole as an alternative for ritonavir liquid formulation when combined with saquinavir. AIDS 2000 14(l) 89-90. 

Itraconazole is a triazole with a broad spectrum of activity against filamentous fungi it is particularly effective against Aspergillus spp. Lack of availability of a formulation suitable for topical ophthalmic use may be a problem. A noncommercial, 1% itraconazole-30% dimethyl sulfoxide ointment preparation used topically in trials in the northeastern USA was found to be effective in 8 out of 10 horses with keratomycosis (Ball et al 1997). It may be given orally, at 3 mg/kg twice daily, in conjunction with topical administration, but it is expensive. 

---