Names and pronunciation
(vohr-i-kahn′a-zol) Vfend, Vfend IV
Source page 1382
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Individual generic drug information
Extracted information for voriconazole only.
(vohr-i-kahn′a-zol) Vfend, Vfend IV
Source page 1382
Func. class.: Antifungal, systemic
Source page 1382
Chem. class.: Triazole derivative
Source page 1382
Do not confuse: Vfend/Venofer
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ACTION: Inhibits fungal CYP450- mediation demethylation; needed for biosynthesis; causes leakage from cell membrane
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USES: Invasive aspergillosis, serious fungal infections (Candida sp., Scedosporium apiospermum, Fusarium sp., Monosporium apiospermum)
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Unlabeled uses: Acremonium sp., Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, febrile neutropenia, fungal keratitis, His toplasma capsulatum, oropharyngeal candidiasis, Rhodotorula sp., Scedospo rium sp., cutaneous aspergillosis, candi demia (premature neonates), fungal infections in children ≥12 yr
Source page 1383
Extracted information for voriconazole only.
CONTRAINDICATIONS: Preg nancy, breastfeeding, children, hypersen sitivity, severe bone marrow depression, severe hepatic disease Precautions: Renal disease (IV); patients of Asian/African descent; cardio myopathy, cholestasis, chemotherapy, lactase deficiency, visual disturbances, renal failure, pancreatitis, QT prolonga tion, hypokalemia; ventricular dysrhyth mias, torsades de pointes
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SIDE EFFECTS CNS: Headache, paresthesias, periph eral neuropathy, hallucinations, psycho sis, EPS, depression, Guillain-Barré syn- drome, insomnia, suicidal ideation, dizziness, fever CV: Tachycardia, hypo/hypertension, vasodilation, atrial arrhythmias, atrial fibrillation, AV block, bradycardia, HF, MI, QT prolongation, torsades de pointes, peripheral edema EENT: Blurred vision, eye hemorrhage, visual disturbances GI: Nausea, vomiting, anorexia, diar rhea, cramps, hemorrhagic gastroenteri- tis, acute hepatic failure, hepatitis, intes- tinal perforation, pancreatitis GU: Hypokalemia, azotemia, renal tubu- lar necrosis, permanent renal impairment, anuria, oliguria HEMA: Anemia, eosinophilia, hypomag nesemia, thrombocytopenia, leukopenia, pancytopenia INTEG: Burning, irritation, pain, necrosis at inj site with extravasation, dermatitis, rash, photosensitivity MISC: Respiratory disorder SYST: Stevens-Johnson syndrome, toxic epidermal necrolysis, sepsis; melanoma, photosensitivity reactions
Source page 1384
INTERACTIONS Increase: effects of benzodiazepines, cal cium channel blockers, cycloSPORINE, ergots, HMG-CoA reductase inhibitors, pimozide, quiNIDine, prednisoLONE, siroli mus, sulfonylureas, tacrolimus, vinca alka loids, warfarin, rifabutin, proton pump inhibitors, NNRTIs, protease inhibitors, phenytoin Increase: nephrotoxicity—other nephro toxic antibiotics (aminoglycosides, CISplatin, vancomycin, cycloSPORINE, polymyxin B) Increase: hypokalemia—corticoste roids, digoxin, skeletal muscle relaxants, thiazides Increase: QT prolongation—class IA/III antidysrhythmics, some phenothiazines, β agonists, local anesthetics, tricyclics, haloperidol, chloroquine, droperidol, pent- amidine; CYP3A4 inhibitors (amiodarone, clarithromycin, erythromycin, telithromy- cin, troleandomycin), arsenic trioxide; CYP3A4 substrates (methadone, pimo- zide, QUEtiapine, quiNIDine, risperiDONE, ziprasidone) Drug/Herb • Do not use with St. John’s wort Drug/Food • Avoid use with high-fat meals, take 1 hr before or after meal Drug/Lab Test Increase: AST/ALT, alk phos, creatinine, bilirubin Decrease: HB/Hct, platelets, WBC
Source pages 1384, 1385
Extracted information for voriconazole only.
DOSAGE AND ROUTES Esophageal candidiasis • Adult/geriatric/child ≥12 yr and ≥40 kg: PO/IV 200 mg q12hr; <40 kg, 100 mg q12hr • Child 2-12 yr; 12-14 yr <50 kg: IV 4 mg/kg q12hr; minimum treatment 14 days, ≥7 days after resolution of symp toms Candidemia of the skin, kidney, bladder wall, abdomen (nonneutropenic patients) • Adult/child ≥12 yr: IV loading dose 6 mg/kg q12hr × 24 hr, then 3-4 mg/kg q12hr × ≥14 days and ≥7 days after resolution of symptoms; PO after load ing dose >40 kg 200 mg q12hr × ≥14 days and ≥7 days after resolution of symptoms; <40 kg 100 mg q12hr × ≥14 days and ≥7 days after resolution of symptoms Invasive aspergillosis • Adult/adolescent: IV 6 mg/kg q12hr (loading dose), then 4 mg/kg q12hr, may reduce to 3 mg/kg q12hr if intolerable • Child 12-14 yr ≥50 kg; ≥15 yr: IV: 6 mg/kg q12hr × 2, then 4 mg/kg q12hr. Continue IV ≥7 days, switch to PO when able • Child >12 yr, ≥40 kg: PO loading dose 400 mg bid on day 1, then 200 mg bid × ≤6 mo • Child >12 yr, <40 kg: PO loading dose 200 mg bid on day 1, then 100 mg bid × ≤6 mo Renal dose • Adult: PO CCr <50 mL/min, use orally only Hepatic dose • Adult: PO/IV (Child-Pugh Class A or B) standard loading dose, then 50% of main- tenance dose; (Child-Pugh class C) avoid use
Source page 1383
Available forms: Tabs 50, 200 mg; powder for inj, lyophilized 200 mg, pow der for oral susp 45 g (40 mg/mL after reconstitution)
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Administer: PO route • Oral susp: tap bottle; add 46 mL of wa ter to bottle; shake well; remove cap; push bottle adapter into neck of bottle; replace cap; write expiration date (14 days); shake before each use; give using oral dispenser supplied, 1 hr before or after meals; tabs and susp may be interchanged • Store at room temperature (powder, tabs) Intermittent IV INFUSION route • Product only after C&S confirms or ganism and product needed to treat condition; make sure product used only in life-threatening infections • Reconstitute powder with 19 mL wa ter for inj to 10 mg/mL; shake until dis solved; • Further dilute with NS, LR, D5W by V calculating dosing volume infuse over 1-2 hr at concentration of ≤5 mg/mL; do not admix with other products Y-site compatibilities: Acyclovir, alfentanil, allopurinol, amifostine, amikacin, amino caproic acid, aminophylline, amiodarone, amphotericin B liposome, ampicillin, ampi cillin/sulbactam, anidulafungin, azithromy cin, aztreonam, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium acetate/chloride/gluconate, CARBOplatin, carmustine, caspofungin, ceFAZolin, cefotaxime, cefoTEtan, cefOXi tin, cefTAZidime, ceftizoxime, cefTRIAXone, chloramphenicol, chlorproMAZINE, cimetidine, ciprofloxacin, cisatracurium, CISplatin, clindamycin, cyclophosphamide, cytarabine, dacarbazine, DACTINomycin, DAPTOmycin, DAUNOrubicin, dexametha sone, dexmedetomidine, dexrazoxane, digoxin, diltiaZEM, diphenhydrAMINE, DOBUTamine, DOCEtaxel, dolasetron, DOPamine, doripenem, doxacurium, doxy cycline, droperidol, enalaprilat, ePHED rine, EPINEPHrine, epirubicin, ertapenem, erythromycin, esmolol, etoposide, etopo side phosphate, famotidine, fenoldopam, fentaNYL, fluconazole, fludarabine, fluoro uracil, foscarnet, fosphenytoin, furosemide, ganciclovir, gemcitabine, gentamicin, glyco pyrrolate, granisetron, haloperidol, hepa rin, hydrALAZINE, hydrocortisone, ifos famide, imipenem/cilastatin, inamrinone, insulin, irinotecan, isoproterenol, ketoro lac, labetalol, leucovorin, levoFLOXacin, lidocaine, linezolid, LORazepam, magne sium sulfate, mannitol, mechlorethamine, melphalan, meperidine, meropenem, mesna, metaraminol, methohexital, metho trexate, methyldopate, methylPREDNISo lone, metoclopramide, metoprolol, metro NIDAZOLE, midazolam, milrinone, mitoMYcin, morphine, nafcillin, nalbu phine, naloxone, niCARdipine, nitroglyc erin, norepinephrine, octreotide, ondanse tron, oxaliplatin, oxytocin, PACLitaxel, pamidronate, pancuronium, pentamidine, pentazocine, PENTobarbital, PHENobarbi tal, phentolamine, phenylephrine, piper acillin/tazobactam, potassium chloride/ phosphates, procainamide, promethazine, propranolol, quinupristin/dalfopristin, remifentanil, rocuronium, sodium acetate/ bicarbonate/phosphates, streptozocin, suc cinylcholine, SUFentanil, tacrolimus, teni poside, theophylline, thiotepa, ticarcillin/ clavulanate, tirofiban, tobramycin, topote can, trimethobenzamide, trimethoprim/sul famethoxazole, vancomycin, vasopressin, vecuronium, verapamil, vinBLAStine, vin CRIStine, vinorelbine, zidovudine
Source pages 1383, 1384
Extracted information for voriconazole only.
Assess: • VS q15-30min during first infusion; note changes in pulse, B/P • I&O ratio; watch for decreasing uri nary output, change in specific gravity; discontinue product to prevent perma nent damage to renal tubules • Blood studies: CBC, potassium, so dium, calcium, magnesium, q2wk; BUN, creatinine weekly • Weight weekly; if weight increases >2 lb/wk, edema is present; renal damage should be considered • Renal toxicity: increasing BUN, serum creatinine; if BUN is >40 mg/dL or if se- rum creatinine >3 mg/dL, product may be discontinued or dosage reduced • Hepatotoxicity: increasing AST, ALT, alk phos, bilirubin, baseline and periodi- cally • Allergic reaction: dermatitis, rash; product should be discontinued, antihis- tamines (mild reaction) or EPINEPHrine (severe reaction) administered • Hypokalemia: anorexia, drowsiness, weakness, decreased reflexes, dizziness, increased urinary output, increased thirst, paresthesias • Ototoxicity: tinnitus (ringing, roaring in ears), vertigo, loss of hearing (rare); visual disturbance • QT prolongation: ECG, ejection frac- tion; assess for chest pain, palpitations, dyspnea • Pregnancy/breastfeeding: do not use in pregnancy, may cause fetal harm; do not breastfeed
Source page 1385
Evaluate: • Therapeutic response: decreased fe ver, malaise, rash, negative C&S for in fecting organism
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • That long-term therapy may be needed to clear infection (2 wk-3 mo, depending on type of infection) • To notify prescriber of bleeding, bruis ing, soft-tissue swelling, dark urine, per sistent nausea or diarrhea, headache, rash, yellow skin/eyes • Take 1 hr before or after meal (PO) • Not to drive at night because of vision changes • Avoid strong, direct sunlight • Women of childbearing age should use effective contraceptive
Source page 1385
Extracted information for voriconazole only.
PHARMACOKINETICS By CYP3A4, CYP2C9 enzymes; max serum concentration 1-2 hr after dosing; elimi nated via hepatic metabolism; protein binding 58%; elimination half-life 6 hr (dose dependent)
Source page 1384
Filter the extracted dose blocks for this individual drug.
Esophageal candidiasis
• Adult/geriatric/child ≥12 yr and ≥40 kg: PO/IV 200 mg q12hr; <40 kg, 100 mg q12hr
Candidate age grouping · source page 1383
Esophageal candidiasis
• Child 2-12 yr; 12-14 yr <50 kg: IV 4 mg/kg q12hr; minimum treatment 14 days, ≥7 days after resolution of symp toms Candidemia of the skin, kidney, bladder wall, abdomen (nonneutropenic patients)
Candidate age grouping · source page 1383
Esophageal candidiasis
• Adult/child ≥12 yr: IV loading dose 6 mg/kg q12hr × 24 hr, then 3-4 mg/kg q12hr × ≥14 days and ≥7 days after resolution of symptoms; PO after load ing dose >40 kg 200 mg q12hr × ≥14 days and ≥7 days after resolution of symptoms; <40 kg 100 mg q12hr × ≥14 days and ≥7 days after resolution of symptoms Invasive aspergillosis
Candidate age grouping · source page 1383
Esophageal candidiasis
• Child 12-14 yr ≥50 kg; ≥15 yr: IV: 6 mg/kg q12hr × 2, then 4 mg/kg q12hr. Continue IV ≥7 days, switch to PO when able
Candidate age grouping · source page 1383
Esophageal candidiasis
• Child >12 yr, ≥40 kg: PO loading dose 400 mg bid on day 1, then 200 mg bid × ≤6 mo
Candidate age grouping · source page 1383
Esophageal candidiasis
• Child >12 yr, <40 kg: PO loading dose 200 mg bid on day 1, then 100 mg bid × ≤6 mo Renal dose
Candidate age grouping · source page 1383