Hepatitis itraconazole

ITRACONAZOLE Although rare, die patient may develop hepatitis during itraconazole administration. The nurse closely monitors die patient for signs of hepatitis, including anorexia, abdominal pain, unusual tiredness, jaundice, and dark urine. The primary healtii care provider may order periodic liver function tests. 

All azole antifungals carry the potential for rash, photosensitivity, and hepatotoxicity. In general, hepatotoxicity is mild and reversible, presenting as asymptomatic increases in liver transaminases. However, fulminant hepatic failure has been reported with itraconazole. Therefore, serial monitoring of liver function... 

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... 

Hypersensitivity to quinazolines (eg, doxazosin, prazosin, terazosin) moderate or severe hepatic insufficiency coadministration with potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, 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). 

Pregnancy (ergotamine s powerful uterine stimulant actions may cause fetal harm) hypersensitivity to ergot alkaloids peripheral vascular disease (eg, thromboangiitis obliterans, leutic arteritis, severe arteriosclerosis, thrombophlebitis, Raynaud s disease) hepatic or renal impairment severe pruritus coronary artery disease hypertension sepsis. The use of potent CYP3A4 inhibitors (ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, troleandomycin, ketoconazole, itraconazole) with dihydroergotamine is contraindicated. 

Hepatotoxicity Itraconazole has been associated with rare cases of serious hepatotoxicity, including liver failure and death. Some of these cases had neither pre-existing liver disease, nor a serious underlying medical condition. If liver function tests are abnormal, discontinue treatment. In patients with raised liver enzymes or an active liver disease or who have experienced liver toxicity with other drugs, do not start treatment unless the expected benefit exceeds the risk of hepatic injury. In such cases, liver enzyme monitoring is necessary. 

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... 

WARNING Chemo agent handle w/ caution Uses Hodgkin Dz NHLs, mycosis fungoides, CAs (testis, renal cell, breast, NSCLC), AIDS-related Kaposi sarcoma, choriocarcinoma, histiocytosis Action X Microtubule assembly Dose 0.1-0.5 mg/kg/wk (4-20 mg/m ) X in hepatic failure Caution [D, ] Contra IT use Disp Inj SE i BM (esp leukopenia), NA, constipation, neurotox, alopecia, rash, myalgia, tumor pain Interactions T Effects W/ erythromycin, itraconazole X effects W/ glutamic acid, tryptophan X effects OF phenytoin EMS T Risk of... 

Contraindications Hepatic disease, concomitant use of ketoconazole, itraconazole, ritonavir... 

Additionally, routine evaluation of hepatic function is recommended for patients receiving itraconazole for onychomycosis. 

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. 

Antifungal imidazoles (ketoconazole, itraconazole, and analogues) compete for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22, 39, 41-43). 

Omeprazole, like cimetidine, can impair benzodiazepine metabolism and lead to adverse effects (SEDA-18, 43). Other drugs, including antibiotics (erythromycin, chloramphenicol, isoniazid), antifungal drugs (ketoconazole, itraconazole, and analogues), some SSRIs (fluoxetine, paroxetine), other antidepressants (nefazodone), protease inhibitors (saquinavir), opioids (fentanyl), calcium channel blockers (diltiazem, verapamil), and disulfiram also compete for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22,39) (SEDA-22,41). 

OPIOIDS ANTIFUNGALS 1, Ketoconazole T effect of buprenorphine 2. Fluconazole and itraconazole T the effect of alfentanil 3. Fluconazole and possibly voriconazole T effect of methadone this is a recognized pharmacokinetic effect but of uncertain clinical significance 1. Ketoconazole 1 the CYP3A4-mediated metabolism of buprenorphine 2.1 clearance of alfentanil 3.1 hepatic metabolism 1. The dose of buprenorphine needs to be 1 (by up to 50%) 2. i dose of alfentanil 3. Watch for T effects of methadone... 

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