voriconazole

voriconazole,

an antifungal agent used to treat invasive aspergillosis and serious fungal infections.

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voriconazole

a fluconazole derivative with potent activity against fungal pathogens.

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voriconazole

Vfend

Pharmacologic class: Triazole

Therapeutic class: Antifungal

Pregnancy risk category D

Action

Inhibits fungal cytochrome P450-mediated 14-alpha-lanosterol demethylation, preventing fungal biosynthesis and inactivating fungal cell

Availability

Lyophilized powder for injection: 200 mg

Powder for oral suspension: 45 g in 100-ml bottle

Tablets: 50 mg, 200 mg

⊘Indications and dosages

➣ Invasive aspergillosis; serious fungal infections caused by Scedosporium apiospermum and Fusarium species

Adults and children older than age 12: Initially, 6 mg/kg I.V. q 12 hours for two doses (each dose infused over 1 to 2 hours), followed by a maintenance dose of 4 mg/kg I.V. q 12 hours given no faster than 3 mg/kg/hour. Change to oral dosing as described below when patient can tolerate it.

Adults and children older than age 12 weighing more than 40 kg (88 lb): 200 mg P.O. q 12 hours 1 hour before or after a meal; may increase to 300 mg P.O. q 12 hours p.r.n.

Adults and children older than age 12 weighing less than 40 kg (88 lb): 100 mg P.O. q 12 hours at least 1 hour before or after a meal; may increase to 150 mg P.O. q 12 hours p.r.n.

➣ Esophageal candidiasis

Adults and children older than age 12 weighing 40 kg (88 lb) or more: 200 mg P.O. q 12 hours for at least 14 days, and for at least 7 days after symptoms resolve

Adults and children older than age 12 weighing less than 40 kg (88 lb): 100 mg P.O. q 12 hours for at least 14 days, and for at least 7 days after symptoms resolve

Dosage adjustment

• Hepatic cirrhosis
• Renal impairment

Off-label uses

• Febrile neutropenia (as empiric therapy)

Contraindications

• Hypersensitivity to drug or its components
• Concurrent use of long-acting barbiturates, ergot alkaloids, rifabutin, rifampin, CYP450-3A4 substrates (such as astemizole, cisapride, pimozide, quinidine, terfenadine), sirolimus, ritonavir, efavirenz, or carbamazepine

Precautions

Use cautiously in:
• hypersensitivity to other azoles
• renal disease, mild to moderate hepatic cirrhosis, lactose or galactose intolerance
• pregnant or breastfeeding patients.

Administration

• Correct electrolyte disturbances before therapy starts.
☞ Don't give concurrently with astemizole, cisapride, or terfenadine (no longer available in U.S.); carbamazepine; efavirenz; ergot alkaloids; long-acting barbiturates; pimozide; quinidine; rifabutin; rifampin; ritonavir; or sirolimus.
• Reconstitute powder with 19 ml of water for injection, to yield a volume of 20 ml. Shake vial until powder dissolves. Withdraw prescribed dose, then dilute further in compatible I.V. solution to a final concentration of 0.5 to 5 mg/ml. Give I.V. over 1 to 2 hours at a rate not exceeding 3 mg/kg/hour.
• Don't give through same I.V. line with other drugs, blood products, or electrolytes.
• To reconstitute powder for oral suspension, tap bottle to release powder. Add 46 ml of water, and shake vigorously for about 1 minute. Remove cap, push bottle adapter into neck of bottle, and replace cap. After reconstitution, suspension volume is 75 ml, providing usable volume of 70 ml (40 mg/ml). Shake bottle before each use. Use only 5-ml oral dispenser supplied. Don't mix with other drugs, and don't dilute further.
• Give oral suspension 1 hour before or after a meal.

Route	Onset	Peak	Duration
P.O.	1-2 hr	Unknown	Unknown
I.V.	Start of infusion	Unknown	Unknown

Adverse reactions

CNS: dizziness, headache, hallucinations

CV: hypotension, hypertension, tachycardia, chest pain, vasodilation, peripheral edema

EENT: photophobia, blurred vision, visual disturbances, eye hemorrhage, chromatopsia

GI: nausea, vomiting, diarrhea, abdominal pain, dry mouth

GU: renal dysfunction , acute renal failure

Hematologic: anemia, pancytopenia, leukopenia, thrombocytopenia

Hepatic: cholestatic jaundice, hepatic failure

Metabolic: hypomagnesemia, hypokalemia

Respiratory: respiratory disorders

Skin: pruritus, maculopapular rash, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome

Other: chills, fever, sepsis, anaphylaxis

Interactions

Drug-drug. Barbiturates (long-acting), carbamazepine, phenytoin, rifampin: decreased voriconazole blood level

Benzodiazepines: sedation

Calcium channel blockers, HMG-CoA reductase inhibitors: increased blood levels of these drugs

Cyclosporine, sirolimus, tacrolimus: increased blood levels of these drugs, greater risk of nephrotoxicity

CYP450-3A4 substrates: increased blood levels of these drugs, causing prolonged QT interval and risk of torsades de pointes

Ergot alkaloids: increased blood levels of these drugs, resulting in ergotism

Non-nucleoside reverse transcriptase inhibitors, protease inhibitors: inhibited voriconazole metabolism

Rifabutin: decreased voriconazole blood level, increased rifabutin blood level

Sulfonylureas: increased sulfonylurea blood level, greater risk of hypoglycemia

Vinca alkaloids: increased risk of neurotoxicity

Warfarin, other coumarin derivatives: increased partial thromboplastin time

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, creatinine: increased levels

Drug-herbs. Gossypol: increased risk of nephrotoxicity

Patient monitoring

• Monitor kidney and liver function tests. Watch for signs and symptoms of organ toxicity.
• Assess electrolyte levels and CBC, including platelet count.
☞ Monitor ECG. Stay alert for prolonged QT interval.
• Check for vision problems in therapy exceeding 28 days.

Patient teaching

• Explain therapy to patient. Stress importance of follow-up laboratory tests.
• Tell patient using oral form to take doses 1 hour before or after a meal.
• Emphasize importance of taking drug exactly as directed for entire duration prescribed.
• Instruct patient to promptly report adverse reactions.
• Tell female of childbearing age to immediately report pregnancy.
• Caution patient to avoid driving and other hazardous activities, because drug may cause visual disturbances.
• Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.

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voriconazole

Vfend^® Infectious disease A potent antifungal Adverse effects Visual disturbance: enhanced brightness or blurry vision, ↑ LFTs–BR, alk phos–may indicate cholestasis, erythema, rash, photosensitivity. Cf Amphotericin B.