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Pharmacologic class: Triazole
Therapeutic class: Antifungal
Pregnancy risk category D
Inhibits fungal cytochrome P450-mediated 14-alpha-lanosterol demethylation, preventing fungal biosynthesis and inactivating fungal cell
Lyophilized powder for injection: 200 mg
Powder for oral suspension: 40 mg/ml
Tablets: 50 mg, 200 mg
⊘Indications and dosages
➣ Invasive aspergillosis; serious fungal infections caused by Scedosporium apiospermum and Fusarium species
Adults and children ages 12 and older: 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 ages 12 and older 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 ages 12 and older 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 ages 12 and older 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 ages 12 and older 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
➣ Candidemia (in nonneutropenic patients) and other deep-tissue Candida infections
Adults and children ages 12 and older: 6 mg/kg I.V. q 12 hours for first 24 hours, followed by maintenance dose of 3 mg/kg I.V. q 12 hours. Or 200 mg P.O. q 12 hours for candidemia and 4 mg/kg I.V. q 12 hours or 200 mg P.O. q 12 hours for other deep-tissue Candida infections. Patients should be treated for at least 14 days after resolution of symptoms or after last positive culture, whichever is longer.
• Mild to moderate hepatic impairment
• Moderate to severe renal impairment (with I.V. use)
• Adult patients weighing less than 40 kg (88 lb)
• Concurrent use of phenytoin or efavirenz
• Febrile neutropenia (as empiric therapy)
• 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, high-dose ritonavir, St. John's wort, or carbamazepine
Use cautiously in:
• hypersensitivity to other azoles
• renal disease, hepatic dysfunction, risk factors for pancreatitis (such as recent chemotherapy, hematopoietic stem cell transplant)
• hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption (avoid tablet use)
• concurrent use of low-dose ritonavir (avoid use unless benefit-risk to patient justifies use)
• pregnant or breastfeeding patients
• children younger than age 12 (safety and efficacy not established).
• Correct electrolyte disturbances before therapy starts.
Don't give concurrently with astemizole, cisapride, or terfenadine (no longer available in U.S.); carbamazepine; ergot alkaloids; long-acting barbiturates; pimozide; quinidine; rifabutin; rifampin; ritonavir; or sirolimus.
Don't give by I.V. bolus injection.
• 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 and tablets 1 hour before or after a meal.
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, pancreatitis
GU: renal dysfunction, acute renal failure
Hematologic: anemia, pancytopenia, leukopenia, thrombocytopenia
Hepatic: cholestatic jaundice, hepatic failure
Metabolic: hypomagnesemia, hypokalemia
Musculoskeletal: fluorosis, periostitis (with long-term use)
Respiratory: respiratory disorders
Skin: pruritus, maculopapular rash, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome
Other: chills, fever, sepsis, infusion-related reactions including anaphylaxis
Drug-drug.Barbiturates (long-acting), carbamazepine, phenytoin, rifampin: decreased voriconazole blood level
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
St. John's wort: significantly reduced voriconazole plasma exposure
• 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.
During infusion, monitor patient for anaphylactoid-type reactions, including flushing, fever, sweating, tachycardia, chest tightness, dyspnea, faintness, nausea, pruritus, and rash; consider stopping infusion should these reactions occur.
Be aware of postmarketing reports of pancreatitis, especially in children, and monitor appropriately.
Monitor patient receiving longterm therapy for skeletal pain. Discontinue drug if radiologic findings indicate fluorosis or periostitis.
• Check for vision problems in therapy exceeding 28 days.
• 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.
• Advise patient not to use St. John's wort without consulting prescriber.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.
Time/action profile (blood levels)
|PO||rapid||1–2 hr||12 hr|
|IV||rapid||end of infusion||12 hr|
Adverse Reactions/Side Effects
Central nervous system
Ear, Eye, Nose, Throat
- visual disturbances (most frequent)
- eye hemorrhage
- changes in BP
- peripheral edema
- QT interval prolongation
- hepatotoxicity (life-threatening)
- abdominal pain
- melanoma (life-threatening)
- squamous cell carcinoma (life-threatening)
- stevens-johnson syndrome (life-threatening)
Fluid and Electrolyte
- infusion reactions
Drug-Drug interactionVoriconazole is a substrate and inhibitor of the CYP3A4, CYP2C9, and CYP2C19 enzyme systems.Carbamazepine, ritonavir, phenobarbital, St. John's wort, rifabutin, and rifampin ↑ metabolism and ↓ antifungal activity of voriconazole; concurrent use is contraindicated.Efavirenz ↑ metabolism and ↓ antifungal activity of voriconazole; voriconazole also ↓ metabolism and ↑ risk of toxicity of efavirenz ; if used together, ↑ dose of voriconazole to 400 mg q 12 hr and ↓ dose of efavirenz to 300 mg daily.↓ metabolism and ↑ risk of toxicity from dihydroergotamine, ergotamine, pimozide, rifabutin, quinidine, and sirolimus ; concurrent use is contraindicated.Fluconazole ↑ levels and toxicity of voriconazole; avoid concurrent use.↓ metabolism and ↑ risk of toxicity from cyclosporine, HMG-CoA reductase inhibitors, some benzodiazepines (alprazolam, midazolam, triazolam ), fentanyl, hydrocodone, NSAIDs (ibuprofen, diclofenac ), some calcium channel blockers, sulfonylureas (glipizide, glyburide, tolbutamide ), alfentanil, tacrolimus, warfarin, and vinca alkaloids (vincristine, vinblastine ); careful monitoring required during concurrent use.May ↑ methadone levels; may ↑ risk of QT interval prolongation.Oral contraceptives containing ethinyl estadiol and norethindone may ↑ voriconazole levels.Phenytoin ↑ metabolism and ↓ antifungal activity of voriconazole; voriconazole ↑ phenytoin levels and may cause toxicity; careful monitoring required during concurrent use.↑ blood levels of omeprazole ; ↓ omeprazole dose by 50% during concurrent use. Similar effects may occur with other proton-pump inhibitors.May ↓ metabolism and ↑ blood levels and effects of protease-inhibitor antiretrovirals and non-nucleoside reverse transcriptase inhibitor antiretrovirals ; frequent monitoring recommended.Non-nucleoside reverse transcriptase inhibitor antiretrovirals ; may induce or inhibit the metabolism of voriconazole; frequent monitoring recommended.
Hepatic ImpairmentIntravenous (Adults and Children >12 yr) Child-Pugh Class A and B—Use standard loading dose, ↓ maintenance dose by 50%; Child-Pugh Class C—Not recommended.
Availability (generic available)
- Monitor for signs and symptoms of fungal infections prior to and during therapy.
- Obtain specimens for culture and histopathology prior to therapy to isolate and identify organism. Therapy may be started before results are received.
- Monitor visual function including visual acuity, visual field, and color perception in patients receiving more than 28 days of therapy. Vision usually returns to normal within 14 days after discontinuation of therapy.
- Monitor for allergic reactions during infusion of voriconazole (flushing, fever, sweating, tachycardia, chest tightness, dyspnea, faintness, nausea, pruritus, rash). Symptoms occur immediately upon start of infusion. May require discontinuation.
- Monitor patients with risk factors for acute pancreatitis (recent chemotherapy, hematopoietic stem cell transplantation [HSCT]) for the signs of pancreatitis (abdominal pain, ↑ serum amylase and lipase).
- Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.
- Lab Test Considerations: Monitor liver function tests prior to and during therapy. If abnormal liver function tests occur, monitor for development of severe hepatic injury. Discontinue therapy if clinical signs and symptoms of liver disease develop.
- Monitor renal function (serum creatinine) during therapy.
Potential Nursing DiagnosesRisk for infection (Indications)
- Once patient can tolerate oral medication, PO voriconazole may be used.
- Correct electrolyte disturbances (hypokalemia, hypomagnesemia, hypocalcemia) prior to initiation therapy.
- Oral: Administer 1 hr before or 1 hr after a meal.
- Shake suspension well (approximately 10 seconds) before measuring suspension. Do not mix suspension with other medicine, flavored liquid, or syrup.
- pH: 6.0–7.0.
- Intermittent Infusion: Reconstitute each 200-mg vial with 19 mL of sterile water for injection to achieve concentration of 10 mg/mL. Calculate volume of 10 mg/mL solution required for patient dose. Diluent: Withdraw and discard equal volume of diluent from infusion bag or bottle to be used. Withdraw required volume of voriconazole solution from vial(s) and add to appropriate volume of 0.9% NaCl, LR, D5/LR, D5/0.45% NaCl, D5W, 0.45% NaCl, or D5/0.9% NaCl. Reconstituted solution stable for 24 hr if refrigerated. Discard partially used vials.Concentration: Final concentration of infusion should be 0.5–5 mg/mL.
- Rate: Infuse over 1–2 hr at a rate not to exceed 3 mg/kg/hr.
- Y-Site Compatibility: acyclovir, alemtuzumab, alfentanil, allopurinol, amifostine, amikacin, aminophylline, amiodarone, amphotericin B liposome, ampicillin, ampicillin/sulbactam, anidulafungin, argatroban, azithromycin, aztreonam, bivalirudin, bleomycin, buprenorphine, butorphanol, bumetanide, buprenorphine, butorphanol, calcium acetate, calcium chloride, calcium gluconate, carboplatin, carmustine, caspofungin, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftaroline, ceftazidime, ceftriaxone, chloramphenicol, chlorpromazine, ciprofloxacin, cisatracurium, cisplatin, clindamycin, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daptomycin, daunorubicin, dexamethasone, dexmedetomidine, dexrazoxane, digoxin, diltiazem, diphenhydramine, dobutamine, docetaxel, dolasetron, dopamine, doripenem, doxacurium, doxycycline, droperidol, enalaprilat, ephedrine, epinephrine, epirubicin, ertapenem, erythromycin, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, fluconazole, fludarabine, fluorouracil, foscarnet, fosphenytoin, furosemide, ganciclovir, gemcitabine, gentamicin, glycopyrrolate, granisetron, haloperidol, heparin, hydralazine, hydrocortisone, ifosfamide, imipenem/cilastatin, insulin, irinotecan, isoproterenol, ketorolac, labetalol, leucovorin, levofloxacin, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, mechlorethamine, melphalan, meperidine, meropenem, mesna, metaraminol, methohexital, methotrexate, methyldopate, methylprednisolone, metioclopramide, metoprolol, metronidazole, midazolam, milrinone, mitomycin, morphine, mycophenolate, nafcillin, nalbuphine, naloxone, nicardipine, nitroglycerin, norepinephrine, octreotide, ondansetron, oxaliplatin, oxytocin, paclitaxel, pamidronate, pancuronium, pentamidine, pentazocine, pentobarbital, phenobarbital, phentolamine, phenylephrine, piperacillin/tazobactam, potassium acetate, potassium chloride, potassium phosphates, procainamide, promethazine, propranolol, quinupristin/dalfopristin, remifentanil, rocuronium, sodium acetate, sodium bicarbonate, sodium phosphates, streptozocin, succinylcholine, sufentanil, tacrolimus, teniposide, theophylline, thiotepa, ticarcillin/clavulanate, tirofiban, tobramycin, topotecan, trimethoprim/sulfamethoxazole, vancomycin, vasopressin, vecuronium, verapamil, vinblastine, vincristine, vinorelbine, zidovudine, zoledronic acid
- Y-Site Incompatibility: amphotericin B colloidal, amphotericin B lipid complex, busulfan, cefepime, cyclosporine, dantrolene, diazepam, doxorubicin, idarubicin, mitoxantrone, moxifloxacin, nitroprusside, pantoprazole, phenytoin, thiopental
- Advise patient to take voriconazole as directed, on an empty stomach.
- May cause blurred vision, photophobia, and dizziness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known. Also advise patient to avoid driving at night during voriconazole therapy.
- Advise patient to avoid direct sunlight, sunlamps and tanning beds during voriconazole therapy. Use sunscreen and protective clothing to prevent severe sunburn.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
- Advise patient to notify health care professional if rash or signs and symptoms of allergic reaction occur.
- Advise women of childbearing age to use contraception and notify health care professional if pregnancy is planned or suspected or if breast feeding. If pregnancy is detected, discontinue medication as soon as possible.
- Resolution of fungal infections.