Voriconazole

A to Z Drug Facts

 Actions Inhibition of fungal cytochrome P-450-mediated 14 alpha-lanosterol demethylation, an essential step in fungal ergosterol biosynthesis.

 Indications Treatment of invasive aspergillosis; treatment of Scedosporium apiospermum and Fusarium spp., including Fusarium solani, in patients intolerant of or refractory to, other therapy.

 Contraindications Hypersensitivity to voriconazole or any of it excipients, coadministration of carbamazepine, cisapride, ergot derivatives (eg, ergotamine, dihydroergotamine), long-acting barbiturates, pimozide, quinidine, rifabutin, rifampin, sirolimus.

 Route/Dosage

ADULTS AND CHILDREN (12 yr and older): IV Loading dose of 6 mg/kg q 12 hr for 2 doses, followed by a maintenance dose of 4 mg/kg q 12 hr. If patients are unable to tolerate treatment, reduce the IV maintenance dose to 3 mg/kg q 12 hr.

ADULTS AND CHILDREN (12 yr and older): PO Once an oral dose can be tolerated, patients weighing more than 40 kg should receive 200 mg q 12 hr. If response is inadequate, the oral dose may be increased to 300 mg q 12 hr. If patients are unable to tolerate oral treatment, reduce the oral dose by 50 mg increments to a min of 200 mg q 12 hr. Patients weighing less than 40 kg should receive 100 mg q 12 hr. If the response is inadequate, the oral dose may be increased to 150 mg q 12 hr. If patients weighing less than 40 kg are unable to tolerate oral treatment, reduce the oral dose by 50 mg increments to a min of 100 mg q 12 hr.

Hepatic Insufficiency: ADULTS AND CHILDREN (12 yr and older): IV or PO It is recommended that the standard loading dose regimens be used but that the maintenance dose be halved in patients with mild to moderate hepatic cirrhosis.

 Interactions

Benzodiazepines (eg, alprazolam), cyclosporine, dihydropyridine calcium channel blockers (eg, felodipine), HMG-CoA reductase inhibitors (eg, lovastatin), NNRT (eg, efavirenz), omeprazole, phenytoin, protease inhibitors (eg, ritonavir), sulfonylurea hypoglycemic agents (eg, glipizide), tacrolimus, vinca alkaloids (eg, vinblastine), warfarin: Plasma exposure to these agents may be increased by voriconazole, increasing the pharmacologic and adverse effects. Carbamazepine, cisapride, ergot derivatives (eg, ergotamine, dihydroergotamine), long-acting barbiturates, pimozide, quinidine, rifabutin, rifampin, sirolimus: Coadministration of these agents with voriconazole is contraindicated. Non-nucleoside reverse transcriptase (NNRT) inhibitors (eg, efavirenz), phenytoin: May decrease voriconazole plasma levels, reducing the pharmacologic effect. NNRT inhibitors (eg, efavirenz), Protease inhibitors (eg, ritonavir): May elevate voriconazole plasma levels, increasing the pharmacologic and adverse effect.

Aminofusin 10%. Do not infuse voriconazole into the same line or cannula with other drug infusions, including parenteral nutrition; do not infuse with blood products or electrolyte supplementations; do not dilute with 4.2% sodium bicarbonate infusion.

 Adverse Reactions

CARDIOVASCULAR: Tachycardia; hypertension; hypotension; vasodilation. CNS: Headache; hallucinations, dizziness. DERMATOLOGIC: Rash; pruritus; maculopapular rash; photosensitivity; Stevens-Johnson syndrome; toxic epidermal necrolysis; erythema multiforme. EENT: Visual disturbances; photophobia; chromatopsia; eye hemorrhage; enhanced visual perception; blurred vision; color vision changes. GI: Vomiting; nausea; diarrhea; dry mouth. GU: Abnormal kidney function; acute kidney failure. HEMATOLOGIC: Thrombocytopenia; anemia; leukopenia; pancytopenia. HEPATIC: Abnormal LFTs (eg, increased AST, ALT); cholestatic jaundice; jaundice. METABOLIC: Increased alkaline phosphatase; hypokalemia; hypomagnesemia; peripheral edema; increased creatinine. RESPIRATORY: Respiratory disorder. OTHER: Fever; sepsis; chills; abdominal pain; chest pain; anaphylactoid reactions.

 Precautions

Pregnancy: Category D. LACTATION: Undetermined. CHILDREN: Safety and efficacy not established in children less than 12 yr. Galactose intolerance: The tablets contain galactose and should not be given to patients with hereditary galactose intolerance, Lapp lactose deficiency, or glucose-galactose malabsorption. Hepatic toxicity: Serious hepatic reactions, including hepatitis, cholestasis, and fulminant hepatic failure have been reported.

 Administration/Storage

Injectable

• For IV infusion only. Not for IV bolus, IM, SC, or intradermal administration.
• Follow manufacturer's instructions for reconstitution, dilution, and administration.
• Do not administer if there is any evidence of precipitation or foreign matter.
• Administer loading doses and maintenance doses at max rate of 3 mg/kg/hr over 1 to 2 hr.
• Do not coadminister with other drug infusions, blood products, or electrolyte replacements.
• Store tablets and powder for injection at controlled room temperature (59° to 86°F). Reconstituted solution should be used immediately. If not used immediately, may be stored at 37° to 46°F for up to 24 hr. Discard any unused solution or solution stored for more than 24 hr.

Tablets

• Administer prescribed dose q 12 hr.
• Administer tablets 1 hr before or 1 hr following a meal.

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies. Note history of sensitivity to azole antifungals, galactose intolerance, liver disease, kidney disease, and current use of rifampin, rifabutin, carbamazepine, long-acting barbiturates, sirolimus, cisapride, pimozide, quinidine, or ergot alkaloids.
• Do not administer to pregnant women.
• Ensure that women of child-bearing potential uses effective contraception during therapy.
• Ensure that kidney and liver function tests are done prior to initiating therapy and periodically during therapy.
• Ensure that fungal culture, as appropriate, has been obtained before beginning therapy.
• Ensure that visual acuity, visual field, and color perception are monitored if treatment exceeds 28 days.
• Monitor kidney function closely if injectable dose form is administered to patient with kidney disease.
• Withhold therapy and notify health care provider if signs and symptoms consistent with liver disease are noted.
• Administer reduced maintenance dose to patient with mild to moderate hepatic cirrhosis (Child-Pugh class A and B).
• Administer reduced maintenance dose to patient who cannot tolerate treatment with standard dose.
• Monitor patient during IV infusion for anaphylactoid-type reaction and discontinue infusion if noted.
• Monitor IV infusion site for signs of reaction or phlebitis.
• Assess patient for visual, CNS, GI, cardiovascular, musculoskeletal, dermatologic, and general body side effects. Report to health care provider if noted and significant.
• Convert from IV dose form to tablets when patient can tolerate medication given by mouth.

 Patient/Family Education

• Explain name, dose, action, and potential side effects of drug.
• Advise patient that injectable form of drug will be prepared and administered by a health care professional in a medical facility.
• Explain need for prolonged therapy and for close monitoring during course of therapy.
• Advise patient to report any of the following to health care provider: injection site reaction; visual disturbances; fever; chills; rash; persistent vomiting; nausea or diarrhea; headache; swelling of the feet, ankles, or calves.
• Advise patient to avoid strong, direct sunlight while taking voriconazole.
• Caution patient to not drive at night while taking this medication because it may cause changes in vision including blurring and sensitivity to bright light.
• Advise patient that drug may cause visual changes and to avoid driving or operating machinery if they perceive any change in vision.
• Instruct women of child-bearing potential to use effective contraception while taking voriconazole.
• Instruct women to notify health care provider if pregnant, planning to become pregnant, or are breastfeeding.
• Instruct patient to not take any prescription or OTC medications or dietary supplements unless advised to do so by health care provider.
• Advise patient that follow-up visits and lab tests will be required to monitor therapy and keep appointments.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts