Voriconazole (voriconazole)

In adults, the voriconazole 200-mg tablet and 40-mg/mL oral suspension are bioequivalent when administered using a loading dose regimen (400 mg every 12 hours) followed by maintenance dosage (200 mg every 12 hours).

In adults, an oral voriconazole dosage of 200 mg every 12 hours results in an area under the plasma-concentration time curve (AUC) similar to that achieved with an IV dosage of 3 mg/kg every 12 hours; an oral dosage of 300 mg every 12 hours results in an AUC similar to that reported with an IV dosage of 4 mg/kg every 12 hours.

Voriconazole is administered orally or by slow IV infusion.

The IV route usually is used for initial treatment of systemic fungal infections, but may be switched to oral treatment when clinically indicated.

Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypocalcemia) should be corrected prior to initiation of voriconazole. (See IV Infusion under Dosage and Administration: Administration and see Cardiovascular Effects under Warnings/Precautions: General Precautions, in Cautions.)

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

Known hypersensitivity to voriconazole or any ingredient in the formulation.

Concomitant use with astemizole or terfenadine (drugs no longer commercially available in the US), carbamazepine, cisapride (currently commercially available in the US only under a limited-access protocol), ergot alkaloids (e.g., ergotamine, dihydroergotamine), pimozide, quinidine, rifabutin, rifampin, sirolimus, St. John's wort (Hypericum perforatum), or long-acting barbiturates (e.g., phenobarbital, mephobarbital). (See Drug Interactions.)

Concomitant use with ritonavir (400 mg every 12 hours) is contraindicated. Concomitant use with low-dose ritonavir (100 mg every 12 hours) should be avoided, unless potential benefits outweigh risks. (See HIV Protease Inhibitors under Drug Interactions: Antiretroviral Agents.)

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Common adverse effects include visual disturbances (e.g., abnormal vision, blurred vision, color vision change, photophobia), GI effects (nausea, vomiting, diarrhea, abdominal pain), fever, rash, chills, headache, abnormalities in liver function test results, tachycardia, and hallucinations. The most commonly reported adverse effects resulting in discontinuance of voriconazole therapy include elevated liver function test results, rash, and visual disturbances.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

Safety and efficacy of voriconazole have not been established in children younger than 12 years of age.

Voriconazole has been recommended for the treatment of fungal infections in children. Some clinicians consider voriconazole the drug of choice for the treatment of invasive aspergillosis in HIV-infected children+, but state that data are insufficient to recommend use of the drug for the treatment of candidemia or esophageal candidiasis in these children.

In one study, a limited number of pediatric patients 9 months to 15 years of age whose disease was refractory to, or who were intolerant of, other antifungals have received voriconazole for the treatment of aspergillosis, candidiasis, infections caused by Scedosporium, or other invasive fungal infections. At the completion of therapy, 45% of pediatric patients receiving voriconazole had a complete or partial response. Adverse effects in children receiving voriconazole were similar to those reported in adults.

There have been postmarketing reports of pancreatitis in pediatric patients receiving voriconazole. Children with risk factors for acute pancreatitis (e.g., recent chemotherapy, HSCT) should be monitored for the development of pancreatitis during voriconazole therapy.

In a population pharmacokinetic analysis of voriconazole concentrations in children 2 through 12 years of age who received various dosage regimens, systemic exposures of the drug (areas under the concentration-time curve (AUCs)) achieved with an IV dosage of 7 mg/kg twice daily or an oral dosage of 200 mg twice daily (oral suspension) were comparable to values observed in adults receiving usual dosages of the drug. Data from this study also indicated that loading doses do not appear to reduce the length of time required to reach steady-state in children 2 through 11 years of age and appear to offer little benefit in this age group. Based on a comparison of pharmacokinetic data from pediatric patients (2 years to less than 12 years of age) with data from adults, the manufacturer states that the predicted steady-state plasma voriconazole concentrations were similar in pediatric patients or adults (median concentration of 1.19 or 1.16 mcg/mL, respectively) at a maintenance IV dosage of 4 mg/kg every 12 hours in children or 3 mg/kg every 12 hours in adults.

Category D. (See Users Guide.)

Because voriconazole can cause fetal harm, it should not be used during pregnancy except when benefits for the mother clearly outweigh potential risks for the fetus.

In rats, voriconazole was teratogenic (cleft palates, hydronephrosis/hydroureter) at a dosage of 10 mg/kg (0.3 times the recommended human maintenance dosage (RMD) based on mg/m2). Other effects in rats included reduced ossification of sacral and caudal vertebrae, skull, and pubic and hyoid bone; supernumerary ribs; anomalies of sternebrae; and dilatation of the ureter/renal pelvis. Reduced plasma estradiol concentrations in pregnant rats, increased gestational length, and dystocia (associated with increased perinatal pup mortality at a dosage of 10 mg/kg) also were reported. In rabbits, voriconazole was embryotoxic at a dosage of 100 mg/kg (6 times the RMD); increased embryomortality, reduced fetal weight, and increased incidence of skeletal variations, cervical ribs, and extrasternebral ossification sites also were reported.

It is not known whether voriconazole is distributed into milk.

Because many drugs are distributed into human milk and because of the potential for serious adverse reactions to voriconazole in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.

Dosage adjustment based on age is not necessary in geriatric adults.

Clinical experience with voriconazole in geriatric patients is limited. Plasma voriconazole concentrations are increased, but overall safety profile is similar to that in younger adults.