Ketoconazole adverse effects

Systemic adverse effects associated with vaginal azoles are less frequent than with oral products. Local discomfort such as burning may occur with the first application. Fifteen percent of patients experience gastrointestinal side effects with orally administered antifungal agents.13 Oral ketoconazole is associated with hepatic toxicity at a rate of 1 in 15,000.14... 

Ketoconazole inhibits a variety of cytochrome P450 enzymes, including 11-hydroxylase and 17-hydroxylase. It is highly effective in lowering cortisol in Cushing s disease, and patients can be maintained successfully on therapy for months to years. The most common adverse effects are reversible elevation of hepatic transaminases and GI upset. It can cause gynecomastia and lower plasma testosterone values. 

Androgen synthesis inhibitors provide symptomatic, but brief, relief in approximately 50% of patients. Aminoglutethimide causes adverse effects in 50% of patients, such as lethargy, ataxia, dizziness, and self-limiting rash. The adverse effects of ketoconazole are GI intolerance, transient increases in liver and renal function tests, and hypoadrenalism. 

Ketoconazole is a potent inhibitor of the cytochrome P450 3A4 enzyme system. Coadministration of ketoconazole with other drugs metabolized by the same enzyme system may result in increased plasma concentrations of the drugs that could increase or prolong both therapeutic and adverse effects. Unless otherwise specified, dosage adjustment may be 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... 

The cholinesterase inhibitors cause significant adverse effects, including nausea and vomiting, and other peripheral cholinomimetic effects. These drugs should be used with caution in patients receiving other drugs that inhibit cytochrome P450 enzymes (eg, ketoconazole, quinidine see Chapter 4). Preparations available are listed in Chapter 7. 

Nausea or pruritus occurs in approximately 3% of patients taking ketoconazole. More significant adverse effects include gynecomastia, elevations of hepatic enzyme levels, and hepatitis. Caution is advised when using ketoconazole in patients with a history of hepatitis. Routine evaluation of hepatic function is advisable for patients on prolonged therapy. 

Dicyclomine (Bentyl) [Anrimuscarinic, GI Anrispasmodic/ Anticholinergic] Uses Functional IBS Action Smooth-muscle relaxant Dose Adults. 20 mg PO qid T to 160 mg/d max or 20 mg EM q6h, 80 mg/d - qid then T to 160 mg/d, max 2 wk Feds. Infants >6 mo 5mg/dose tid-qid Children 10 mg/dose tid-qid Caution [B, -] Contra Infants <6 mo, NAG, MyG, severe UC, BOO Disp Caps, tabs, syrup, inj SE Anticholinergic SEs may limit dose Interactions T Anticholinergic effects W/ anticholinergics, antihistamines, amantadine, MAOIs, TCAs, phenothiazides T effects OF atenolol, digoxin X effects H7 antacids X effects OF haloperidol, ketoconazole, levodopa, phenothiazines EMS Avoid procainamide usage, may T adverse effects may T effects of digoxin, monitor... 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Ketoconazole (400 mg/day) has been used for the treatment of hirsutism and acne in women, but adverse effects, such as headache, nausea, loss of scalp hair, hepatitis, and biochemical changes, were impressive (587-589). 

Adverse effects Pancreatitis, which may be fatal, is a major toxicity of ddl treatment, and requires monitoring of serum amylase. The dose-limiting toxicity of didanosine is peripheral neuropathy. [Note The buffering of stomach contents may interfere in the absorption of other drugs that require an acidic milieu for absorption, such as ketoconazole.]... 

Reboxetine is metabolized by CYP3A4. In 11 healthy volunteers ketoconazole, an inhibitor of CYP3A4, increased the plasma AUC of reboxetine by about 50% and prolonged the half-life (7). The adverse effects profile of reboxetine was not altered by ketoconazole, but the... 

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... 

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