Itraconazole dosing

Patients with disease outside the lungs should be treated with 400 mg/day of an oral azole. For meningeal disease, fluconazole 400 mg/day orally should be used however, some clinicians initiate therapy with 800 mg or 1,000 mg/day and itraconazole doses of 400 to 600 mg/day are comparable. 

Itraconazole Dose reduction of indinavir to 600 mg every 8 hours is recommended when concurrently administering itraconazole 200 mg twice daily. 

For mention of a study in which some patients needed an increase in itraconazole dose when treated with ranitidine and an antacid [not named], see Azoles + H2-receptor antagonists , p.217. 

Rifabutin serum levels raised. A 49-year-old HIV positive man taking rifabutin 300 mg daily was also given itraconazole 600 mg daily. Because of low plasma levels after 3 weeks the itraconazole dose was increased to 900 mg daily. A week later the patient developed anterior uveitis. It was found that the itraconazole trough serum levels were normal but rifabutin trough serum levels were raised to 153 nanograms/mL (expected to be less than 50 nanograms/mL after 24 hours). Rifabutin was stopped and the uveitis was treated. Symptoms resolved after 5 days. ... 

Toxicological studies have demonstrated that there are no important problems with fluconazole. Therapeutic doses of fluconazole may cause enzyme induction in the Hver. This suggests that interactions with other dmgs cannot be excluded. The side effects are similar to those of itraconazole and include nausea, headache, and vertigo. Occasionally, increased Hver enzymes may be noted. Like itraconazole, fluconazole is contraindicated during pregnancy. 

Theoretically buprenorphine metabolism could be inhibited by itraconazole, ketoconazole, grapefruit juice, and erythromycin or any other CYP3A4 inhibitor the effects may be greater than expected for the dose of buprenorphine being given may need to decrease buprenorphine dose. 

Treatment fluconazole, itraconazole, ketoconazole, Amphotericin B Consider liposomal products decrease or stop CSA or TAC to minimize nephrotoxicity Remember to adjust doses of renally eliminated drugs (e.g., acyclovir, ganciclovir, TMP-SMX)... 

The goal of treating recurrent WC is control of the infection, rather than cure. First, any acute episodes are treated, followed by maintenance therapy. For the treatment of acute episodes, intravaginal or oral azoles can be utilized. Although acute episodes of recurrent WC will respond to azole therapy, some patients may require prolonged therapy in order to achieve remission. To achieve remission, a second dose of oral fluconazole 150 mg repeated 3 days after the first dose or 14 days of topical azole therapy can be used. The practitioner should consider that non-albicans infections are more common in recurrent WC therefore fluconazole and itraconazole resistance may make these agents less effective. 

Two to three weeks of fluconazole or itraconazole solution are highly effective and demonstrate similar clinical response rates.32 Doses of 100 to 200 mg are effective in immunocompetent patients but doses up to 400 mg are recommended for immunocompromised patients. Due to variable absorption, ketoconazole and itraconazole capsules should be considered second-line therapy. In severe cases, oral azoles may prove ineffective, warranting the use of amphotericin B for 10 days. Although echinocandins and voriconazole are effective in treatment of esophageal candidiasis, experience remains limited. 

Select azole antifungals (e.g., itraconazole, voriconazole, and posaconazole) and the echinocandins are available for IA treatment. For initial therapy of IA, voriconazole had higher response and survival rates than c-AMB.102 An advantage of voriconazole is its 96% oral bioavailability, making use of this oral drug an attractive and less expensive alternative. The dose of voriconazole was 6 mg/kg IV every 12 hours for two doses, followed by 4 mg/kg IV every 12 hours for at least 7 days, at which time oral voriconazole 200 mg every 12 hours could be administered. Common toxicities reported with voriconazole include infusion-related, transient visual disturbances (i.e., blurred vision, altered color perception, photophobia, and visual hallucinations), skin reactions (i.e., rash, pruritus, and photosensitivity), elevations in hepatic transaminases and alkaline phosphatase, nausea, and headache.102 In addition, voriconazole increases the serum concentrations of medications cleared by cytochrome P-450 2C9, 2C19, and 3A4 (e.g., cyclophosphamide and calcineurin inhibitors) concomitant voriconazole-sirolimus should be avoided.103... 

Itraconazole and ketoconazole (200-800 mg/day orally for 1 year) are effective in 74% to 86% of cases, but relapses are common fluconazole 200-400 mg daily is less effective (64%) than ketoconazole or itraconazole, and relapses are seen in 29% of responders Severe disease Amphotericin B 0.7 mg/kg/day for a minimum total dose of 35 mj kg is effective in 59% to 100% of cases and should be used in patients who require hospitalization or are unable to take itraconazole because of drug interactions, allergies, failure to absorb drug or failure to improve clinically after a minimum of 12 weeks of itiaconazole therapy... 

Patients who fail or are unable to tolerate itraconazole therapy, or who develop CNS disease, should be treated with amphotericin B for a total cumulative dose of 1.5 to 2.5 g. 

Patients may be initiated on amphotericin B and changed to oral itraconazole 200-400 mg orally daily once patient is clinically stabilized and a minimum dose of 500 mg of amphotericin B has been administered. 

Sildenafil doses should be decreased when any potent cytochrome P450 3A4 inhibitor is used (e g., cimetidine, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and saquinavir). Vardenafil doses vary accordingto which agent is used (2.5 mg q 72 h for ritonavir, 2.5 mg q 24 h for indinavir, ketoconazole 400 mg daily, and itraconazole 400 mg daily and 5 mg q 24 h for ketoconazole 200 mg daily, itraconazole200 mg daily, and erythromycin). Tadalafil doses are reduced only when it is used with the most potent cytochrome P450 3A4 inhibitors (e g., ketoconazole or ritonavir). 

Dosage adjustment - Consider a starting dose of 25 mg in the following patients Older than 65 years of age, hepatic impairment, severe renal impairment, and concomitant use of potent cytochrome P450 3A4 inhibitors (eg, erythromycin, ketoconazole, itraconazole, saquinavir). 

Concomitant mecf/caf/ons - The dosage of vardenafil may require adjustment in patients receiving certain CYP3A4 inhibitors. For ritonavir, do not exceed a single dose of 2.5 mg vardenafil in a 72-hour period. For indinavir, ketoconazole 400 mg/day, and itraconazole 400 mg/day, do not exceed a single dose of 2.5 mg vardenafil in a 24-hour period. For ketoconazole 200 mg/day, itraconazole 200 mg/day, and erythromycin, do not exceed a single dose of 5 mg vardenafil in a 24-hour period. 

A4 inhibitors - Patients receiving cytochrome P450 3A4 inhibitors, such as macrolide antibiotics (erythromycin and clarithromycin), antifungal agents (ketoconazole, itraconazole, and miconazole), or cyclosporine or vinblastine should not receive doses of tolterodine greater than 1 mg twice/day (greater than 2 mg/day for ER capsules). 

Coadministration with CYP450 inhibitors- Nhen coadministered with potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, nefazodone), do not exceed a daily dose of darifenacin 7.5 mg. 

Oropharyngeal candidiasis - 200 mg/day for 1 to 2 weeks. Vigorously swish the solution in the mouth (10 ml at a time) for several seconds and swallow. For patients with oropharyngeal candidiasis unresponsive/refractory to treatment with fluconazole tablets, the recommended dose of itraconazole is 100 mg twice daily. Expect clinical response in 2 to 4 weeks. Patients may be expected to relapse shortly after discontinuing therapy. Limited data on the safety of long-term use (more than 6 months) of the oral solution are available at this time. 

ETFN patients with suspected fungal infections - 200 mg IV twice daily for 4 doses, followed by 200 mg once daily for up to 14 days. Continue treatment with 200 mg itraconazole oral solution (20 ml) twice daily until resolution of clinically significant neutropenia. The safety and efficacy of itraconazole use exceeding 28 days in ETFN is not known. 

Metabollsm/Excretion— Itraconazole is metabolized by the cytochrome P450 3A4 to several metabolites including the major metabolite hydroxyitraconazole. Fecal excretion of the parent drug varies between 3% and 18% of the dose. Renal excretion of the parent drug is less than 0.03% of the dose. Itraconazole is not removed by hemodialysis. 

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. 

Children Safety and efficacy have not been established. A small number of patients from 3 to 16 years of age have been treated with 100 mg/day for systemic fungal infections and no serious adverse effects have been reported. Itraconazole oral solution was given to 26 pediatric patients 6 months to 12 years of age. Itraconazole was dosed at 5 mg/kg once daily for 2 weeks, and no serious unexpected adverse events were reported. 

Aprepitant (Emend) [Centrally Acting Antiemetic] Uses Pre-vents N/V assoc w/ emetogenic CA chemo (eg, cisplatin) (use in combo w/ other antiemetics) Action Substance P/neurokinin l(NKi) receptor antagonist Dose 125 mg PO day 1, 1 h before chemo, then 80 mg PO qAM days 2 3 Caution [B, /-] Contra Use w/ pimozide, Disp Caps SE Fatigue, asthenia, hiccups Interactions T Effects W/ clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin T effects OF alprazolam, astem-izole, cisapride, dexamethasone, methylprednisolone, midazolam, pimozide, terfe-nadine, triazolam, chemo agents, eg, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine i effects W/ paroxetine,... 

Budesonide, Oral (Entocort EC) [Anti-inflammatory> Corticosteroid] Uses Mild-mod Crohn Dz Action Steroid, anti-inflammatory Dose Adults. Initial, 9 mg PO qAM to 8 wk max maint 6 mg PO qAM taper by 3 mo avoid grapefruit juice Contra Active TB and fungal Infxn Caution [C, /-] DM, glaucoma, cataracts, HTN, CHF Disp Caps SE HA, cough, hoarseness, Candida Infxn, epistaxis Interactions T Effects W/ erythromycin, indinavir, itraconazole, ketoconazole, ritonavir, grapefruit EMS Monitor ECG and BP for signs of electrolyte disturbances and hypovolemia OD Acute OD unlikely to cause a problem, chronic OD can reduce natural production of certain steroids symptomatic and supportive... 

Buspirone (BuSpar) [Anxiolytic] WARNING Closely monitor for worsening depression or emergence of suicidality Uses Short-term relief of anxiety Action Antianxiety antagonizes CNS serotonin receptors Dose Initial 7.5 mg PO bid T by 5 mg q2-3d to effect usual 20-30 mg/d max 60 mg/d Contra w/ MAOI Caution [B, /-] Avoid w/ severe hepatic/renal insuff Disp Tabs SE Drowsiness, dizziness, HA, N, EPS, serotonin synd, hostility, depression Notes No abuse potential or physical/psychologic d endence Interactions T Effects W/ erythromycin, clarithromycin, itraconazole, ketoconazole, diltiazem, verapamil, grapefruit juice effects W/ carbamazepine, rifampin, phenytoin, dexamethasone, phenobarbital, fluoxetine EMS T Sedation w/ concurrent EtOH use grapefruit juice may T risk of adverse effects OD May cause dizziness, miosis, N/V symptomatic and supportive... 

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