Itraconazole Foods

ITRACONAZOLE Give the drug orally with food to increase absorption. When administering IV, use only components provided by the manufacturer for reconstitution. Do not dilute with any other diluent. The drug... 

Itraconazole The drug is taken widi food. Therapy will continue for at least 3 months until infection is controlled. Report unusual fatigue, yellow skin, darkened urine, anorexia, nausea, and vomiting. 

Oral solution/Injectlon The oral bioavailability is maximal when itraconazole oral solution is taken without food. Steady state is reached after 1 to 2 weeks during chronic administration. Peak plasma levels are observed 2 hours (fasting) to 5 hours (with food) following oral administration. Steady-state plasma concentrations are approximately 25% lower when the oral solution is taken with food. 

As a consequence of its high lipophilicity and low aqueous solubility, gastric acidity is also required for itraconazole absorption (Haria et al., 1996). It is best absorbed when administered with food, although there is considerable interpatient variabihty. The oral bioavailability or itraconazole from a 100-mg solution dose was 55%. Like ketoconazole, its bioavailability and half-life are dose-dependent, indicating saturable metabolism. Once absorbed, itraconazole is highly plasma protein bound (99.8%) and widely distributed (10.7 L/kg). Although itraconazole is widely metabolized, it does produce an active metabolite by hydroxylation of the triazolone side-chain. 

Although itraconazole and fluconazole are both triazoles, they are chemically and pharmacologically distinct. Itraconazole (Sporanox) is lipophilic and water insoluble and requires a low gastric pH for absorption. Oral bioavailability is variable, only 50 to 60% when taken with food and 20% or less when the drug is taken on an empty stomach. Itraconazole is highly protein bound (99%) and is metabolized in the liver and excreted into the bile. With initial dosing, the plasma half-life is 15 to 20 hours steady-state serum concentrations are reached only after 2 weeks of therapy, when the half-life is extended to 30 to 35 hours. In lipophilic tissues, drug concentration is 2 to 20 times that found in... 

Although specific drug or food interactions with mifepristone have not been studied, on the basis of this drug s metabolism by CYP3A4, it is possible that ketoconazole, itraconazole, erythromycin, and grapefruit juice may inhibit its metabolism (increasing serum levels of mifepristone). Furthermore, rifampin, dexamethasone, St. John s wort, and certain anticonvulsants (e.g., phenytoin, phenobarbital, and carbamazepine) may induce mifepristone metabolism (lowering serum levels of mifepristone)... 

Fluconazole is well absorbed following oral administration, with a plasma half-life of 30 hours. In view of this long half-life, daily doses of 100 mg are sufficient to treat mucocutaneous candidiasis alternate-day doses are sufficient for dermatophyte infections. The plasma half-life of itraconazole is similar to that of fluconazole, and detectable therapeutic concentrations remain in the stratum corneum for up to 28 days following termination of therapy. Itraconazole is effective for the treatment of onychomycosis in a dosage of 200 mg daily taken with food to ensure maximum absorption for 3 consecutive months. Recent reports of heart failure in patients receiving itraconazole for onychomycosis have resulted in recommendations that it not be given for treatment of onychomycosis in patients with ventricular dysfunction. 

Secondary> hyperparathyroidism 30 mg PO daily Parathyroid carcinoma 30 mg PO bid titrate q2—4wk based on Ca PTH levels swallow whole take w/ food Caution [C, /—] w/ Szs Disp Tabs SE N/V/D, myalgia, dizziness, 4- Ca2+ Interactions T Effects W/ CYP3A4 inhibitors such as ketoconazole, itraconazole, erythromycin T effects OF drugs metabolized at CYP2D6 such as TCA, thioridazine, flecainide, vinblastine EMS Monitor ECG for signs of hypocalcemia (T QT interval) OD May cause severe hypocalcemia calcium salts can be given... 

However, the food-effect study on Sporaffooral solution in healthy subjects observed that oral bioavailability of itraconazole actually decreased by 31 % under fed condition (Van de Velde et al., 1996). Thus, in its product labeling, it is indicated that SporShoral solution should be taken without a meal to ensure maximal absorption. Further, Spof Dcad solution and capsules should not be used interchangeably. 

Zimmermann T, Yeates RA, Laufen H, Pfaff G, Wildfeuer A. In uence of concomitant food intake on the oral absorption oftwo triazole antifungal agents, itraconazole and uconSzra>L Clin Pharmacol, 1994 ... 

Pharmacokinetics Itraconazole is well-absorbed orally and food increases its bioavailability. It is extensively bound to plasma proteins and distributes well throughout most tissues, including bone, sputum and adipose tissues. However, therapeutic concentrations are not attained in the CSF. Like ketoconazole it is extensively metabolized in the liver but does not inhibit androgen synthesis. Little of the parent drug appears in the urine and thus doses do not have to be reduced in renal failure. 

In terms of ADMET, the absorption of celiprolol from the gastrointestinal tract is rapid, and its time to onset of action is only 30-60 min, with a peak effect in about 2-3 h. The presence of food in the gut can reduce absorption by about 30%. Itraconazole increases, while grapefruit juice significantly decreases, plasma concentrations of celiprolol [138]. Likewise, orange juice substantially reduces the bioavailability of celiprolol, and because it is consumed widely, this interaction is like-... 

AZOLES ANTACIDS i plasma concentration of itraconazole and ketoconazole, with risk of therapeutic failure Itraconazole absorption in capsule form requires an acidic gastric environment and thus absorption would l Separate administration of agents that i gastric acidity by 1-2 hours. However, absorption of itraconazole liquid solution does not require an acidic environment and could be used instead it does not need to be given with food. Fluconazole absorption is not pH dependent, and this is a suitable alternative... 

Janssen Research Foundation, Itraconazole Oral Solution, NDA 020657, Food and Drug Administration, Freedom of Information Staff (HFI-35), 5600 Fishers Lane, Rockville MD 20857, http //www.fda.gov/. 

Itraconazole is an orally active, broad-spectrum antifungal agent that has become an important alternative to kettK ona-zole. An acidic environment is requited for optimum solubi-lizoitinn and oral absorption of itraconazole. Drugs such as H2-hi.staminc antagonists and antacid.s, which reduce stomach acidity, reduce its gastrointestinal absorption. Food... 

The oral bioavailability of fluconazole, following administration of cither tablet or oral. suspension do.sagc forms, is excellent. Apparently, the presence of two weakly basic triazole rings in the molecule confers sufficient aqueous solubility to balance the lipophilicity of the 2.4-difluorophenyl group. The oral absorption of fluconazole, in contrast to the oral absorption of ketoconazolc or itraconazole, is not affected by alteration in ga.strointcstinal acidity or the presence of food. 

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