Itraconazole adverse effects

One tablet given daily for 12 weeks achieves a cure rate of up to 90% for onychomycosis and is more effective than griseofulvin or itraconazole. Adverse effects are rare, consisting primarily of gastrointestinal upset and headache. Terbinafine does not seem to affect the P450 system and has demonstrated no significant drug interactions to date. 

PPIs are usually well tolerated. Potential adverse effects include headache, dizziness, somnolence, diarrhea, constipation, nausea, and vitamin B12 deficiency. All PPIs can decrease the absorption of drugs such as ketoco-nazole or itraconazole that require an acidic environment for absorption. Other drug interactions vary with each agent. 

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. 

Both itraconazole and its major metabolite, hydroxyitraconazole, are inhibitors of the cytochrome P450 3A4 enzyme system. Coadministration of itraconazole and drugs primarily metabolized by the cytochrome P450 3A4 enzyme system may result in increased plasma concentrations of the drugs that could increase or prolong therapeutic and adverse effects. 

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... 

This adverse effect could have been due to inhibition of the metabolism of budesonide by itraconazole. 

Rhabdomyolysis is a problem with several lipid-lowering drugs (SEDA-13, 1325 SEDA-13, 1328 SEDA-13, 1330 SEDA-19, 409), especially when they are used in combination (37). In individuals with pre-existing renal insufficiency this can lead to an earlier need for chronic dialysis (38). All statins can cause myopathy and rhabdomyolysis, but not all statins are alike. For example, the evidence to date, based on almost 2 decades of experience, points to an extremely low risk of myopathy and rhabdomyolysis with lovastatin, and lovastatin 20 mg tablets are being considered for non-prescription availability in several countries (39). Furthermore, muscle adverse effects do not necessarily occur after a change from one statin to another (40). Interactions between various hypolipidemic drugs and other drugs also sometimes cause rhabdomyolysis (SEDA-18, 426). For instance, itraconazole markedly increases plasma concentrations of lovastatin, and in one subject plasma creatine kinase was increased 10-fold within 24 hours of administration of this combination (41). 

Adverse Effects. Side effects associated with itraconazole include headache, gastrointestinal disturbances (nausea, vomiting), and skin rash. 

Adverse effects Adverse effects include nausea and vomiting, rash (especially in immunocompromised patients), hypokalemia, hypertension, edema, and headache. Drug interactions listed above are also possible with itraconazole. Figure 34.5 summarizes the azole antifungal agents. 

Adverse effects can result from increased plasma concentrations of haloperidol during itraconazole treatment. This has been observed in 13 schizophrenic patients treated with haloperidol 12 or 24 mg/day who took itraconazole 200 mg/day for 7 days (51). Plasma concentrations of haloperidol were significantly increased and neurological adverse effects were more common. Itraconazole is a potent inhibitor of CYP3A4. 

Similar findings in a similar study were reported for brom-peridol and its reduced metabolite, although there were no differences in clinical symptoms or neurological adverse effects during concomitant itraconazole therapy (52). 

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). 

MODAFINIL 1. ANTIBIOTICS-clarithromycin, telithromycin 2. ANTIFUNGALS-itraconazole, ketoconazole 3. ANTIVIRALS-indinavir, nelfinavir, ritonavir, saquinavir t plasma concentrations of modafinil, with risk of adverse effects Due to inhibition of CYP3A4, which has a partial role in the metabolism of modafinil Be aware. Warn patients to report dose-related adverse effects, e.g. headache, anxiety... 

FLUCONAZOLE, ITRACONAZOLE, KETOCONAZOLE, VORICONAZOLE (POSSIBLY POSACONAZOLE) VINCA ALKALOIDS -VINBLASTINE, VINCRISTINE, VINORELBINE t adverse effects of vinblastine and vincristine Inhibition of CYP3A4-mediated metabolism. Also inhibition of P-gp efflux of vinblastine Monitor FBCs and watch for early features of toxicity (pain, numbness, tingling in the fingers and toes, jaw pain, abdominal pain, constipation, ileus). Consider selecting an alternative drug... 

ITRACONAZOLE, KETOCONAZOLE PROTEASE INHIBITORS Possibly t levels of ketoconazole by amprenavir, indinavir and ritonavir (with or without lopinavir). Conversely, indinavir, ritonavir and saquinavir levels t by itraconazole and ketoconazole Inhibition of, or competition for, CYP3A4-mediated metabolism Use itraconazole with caution and monitor for adverse effects. No dose adjustment is recommended for doses <400 mg/day of ketoconazole... 

A prospective nonrandomized study compared the efficacy of 1% itraconazole drops with 5% natamycin for monotherapy of fungal keratitis. In patients with Fusarium keratitis, 79% responded favorably to natamycin compared with 44% to itraconazole (p <.02). Both treatments were well tolerated with no obvious adverse effects reported (Kalavathy et al.). 

Liposomal amphotericin (3 mg/kg/day) has been compared with conventional amphotericin (0.7 mg/kg/day) for induction therapy of moderate to severe disseminated histoplasmosis in a randomized, double-blind, multicenter trial in 81 patients with AIDS (119). The duration of induction was 2 weeks, to be followed by 10 weeks of itraconazole in the case of a response. Clinical success was achieved in 14 of 22 patients treated with conventional amphotericin compared with 45 of 51 patients who received liposomal amphotericin (difference, 24% 95% Cl = 1%, 52%). Culture conversion rates were similar. Three patients treated with conventional amphotericin and one treated with liposomal amphotericin died during induction. Infusion-related adverse effects were more common with conventional amphotericin (63%) than with liposomal amphotericin (25%). Nephrotoxicity occurred in 37% of patients treated with conventional amphotericin and 9% of patients treated with liposomal amphotericin. The results of this study suggest that liposomal amphotericin is less toxic than conventional amphotericin and is associated with improved survival. 

Among the imidazole derivatives, numerous case reports or studies have shown that ketoconazole, fluconazole, and itraconazole can inhibit ciclosporin metabolism and increase blood ciclosporin concentrations (267). Ketoconazole, which is undoubtedly the most potent inhibitor, has been used to reduce the dose, and therefore the cost or adverse effects, of ciclosporin (268-270). There was also a beneficial effect on the rate of rejection or infection. In contrast, interactions with metronidazole and miconazole have only been described in isolated case histories (SEDA-19, 351) (5). 

In a study using the UK General Practice Research Database to determine rates of drug-induced, rare, serious adverse effects on the liver, kidneys, skin, or blood, occurring within 45 days of completing a prescription or refill in 54 803 users of either fluconazole or itraconazole, three had illnesses for which a fluconazole-induced cause could not be ruled out one with thrombocytopenia, one with neutropenia, and one with an abnormal liver function test just after receiving fluconazole (31). The rates were 2.8/100 000 prescriptions (95% Cl = 0.8, 10) for serious, adverse blood events and 1.4/100 000 prescriptions (95% Cl = 0.25, 8.2) for serious, adverse liver events. These results suggest that fluconazole does not commonly have serious adverse effects on the liver, kidneys, skin, or blood. 

In a double-blind comparison in oropharyngeal candidiasis in 244 patients with AIDS, itraconazole oral solution and fluconazole capsules (each 100 mg/day for 14 days) were equally efficacious there were no significant differences in adverse effects (17). 

In patients taking itraconazole capsules for prolonged periods the common adverse effects were nausea and vomiting (in under 10%), hypertriglyceridemia (9%), hypokalemia (6%), raised transaminases (5%), rashes and/or pruritus (2%), headache or dizziness (under 2%), and foot edema (1%) (23). 

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