Voriconazole (Vfend) is an antifungal medicine that acts by inhibiting fungal enzymes, decreases the formation of fungal cell membranes, and ergosterol synthesis.

It is among the WHO's List of essential medicines.

It is used to treat the following fungal infections in patients ≥2 years of age:

• Invasive aspergillosis

• esophageal candidiasis

• candidemia (in non-neutropenic patients)

• disseminated Candida infections of the skin and abdomen, kidney, bladder wall, and wounds

• Serious infections caused by the fungi Scedosporium apiospermum and Fusarium spp. (including Fusarium solani) in patients who are intolerant of, or refractory to, other therapy

Off Label Usage of Voriconazole in Adults:

• Acute myelogenous leukemia as prophylaxis of fungal infections

• Allogeneic hematopoietic stem cell transplant as prophylaxis of fungal infections

• Allogeneic hematopoietic stem cell transplant patients with graft-versus-host disease as prophylaxis of fungal infection

• Aspergillosis, invasive as prophylaxis during prolonged neutropenia

• Ocular Aspergillosis

•  Endophthalmitis due to Candidiasis

• Esophageal candidiasis

• Candidiasis causing intravascular infections

• oropharyngeal Candidiasis, (fluconazole refractory)

• Coccidioidal meningitis (salvage therapy) (non-HIV infected patients);

• Coccidioidomycosis (treatment/chronic suppressive therapy) in HIV-infected patients.

• Empiric antifungal therapy (neutropenic fever)

• Fungal meningitis or osteoarticular infections (secondary to contaminated steroid products)

• Myelodysplastic Syndrome (prophylaxis of fungal infections)

• Talaromyces marneffei infection in HIV-infected patients

Voriconazole (Vfend) Dose in Adults

Dose in the treatment of invasive Aspergillosis, including disseminated and extrapulmonary infection:

Initial: 6 mg/kg intravenous every 12 hours for 2 doses

• Maintenance dose: 4 mg/kg intravenous every 12 hours

Oral: Maintenance dose:

• Manufacturer's labeling:

Note:

If patient has inadequate clinical response, titrate in 50 mg/dose increments for weight <40 kg and 100 mg/dose increments for weight ≥40 kg.

• Weight <40 kg:
  • 100 mg every 12 hours
• Weight ≥40 kg:
  • 200 mg every 12 hours
• Alternate recommendations:
  • 200 to 300 mg orally every 12 hours or weight-based dosing (3 to 4 mg/kg) every 12 hours.

Note:

In patients able to tolerate oral administration, may consider oral in place of Intravenous.

however, Intravenous administration is recommended in seriously ill patients.

• Duration of therapy:

  • Minimum of 6 to 12 weeks, although duration is highly dependent on the degree and duration of immunosuppression, disease site, and evidence of disease improvement.

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Dose as an alternative agent in the treatment of invasive Aspergillosis (prophylaxis during prolonged neutropenia) (off-label):

• • 200 mg orally twice daily.

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Dose in the treatment of Ocular Aspergillosis (off-label):

• Endophthalmitis:

  • Intravitreal:
    • 100 mcg/0.1 mL of an extemporaneously prepared solution administered intravitreally (need for a repeat dose is at physician discretion).
    • Concomitant systemic (Intravenous or oral) voriconazole therapy is also recommended.

• Keratitis:

  • Ophthalmic:
    • Dosing may vary.
    • The following dosing regimen has been used in trials:
      • 1 drop of an extemporaneously prepared 1% ophthalmic solution applied topically to the cornea of the affected eye every 1 hour while awake for 1 week, then every 2 hours while awake for 2 weeks.
      • The further continuation was at physician discretion.

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Dose in the treatment of Candidemia in non-neutropenic patients and disseminated Candida infections in the skin, and infections in abdomen, kidney, bladder wall and wounds:

Treatment should continue for a minimum of 14 days following resolution of symptoms or following the last positive culture, whichever is longer.

• Initial: 6 mg/kg intravenous every 12 hours for 2 doses
• Maintenance: 3 to 4 mg/kg intravenous every 12 hours

• Manufacturer's labeling:

  • Maintenance dose: Note: If the patient has an inadequate clinical response, titrate in 50 mg/dose increments for weight <40 kg and 100 mg/dose increments for weight ≥40 kg

    • Weight <40 kg:

      • 100 mg orally every 12 hours

    • Weight ≥40 kg:

      • 200 mg orally every 12 hours

• Alternate recommendations:

  • Candidemia in non-neutropenic patients:

    • Initial therapy: 400 mg (6 mg/kg) Intravenous every 12 hours for 2 doses,
    • Followed by 200 mg (3 mg/kg) intravenous or orally every 12 hours.

Note: Voriconazole is considered alternative therapy and offers little advantage over fluconazole as first-line therapy of candidemia.

• Step-down therapy (after the patient has responded to initial therapy):

  • Isolates of C. glabrata (voriconazole-susceptible isolates):

    • 200 to 300 mg orally (3 to 4 mg/kg) twice daily

  • Isolates of C. krusei (selected cases):

    • 200 mg orally every 12 hours

• Duration:

  • Continue for 14 days after the first negative blood culture and resolution of signs/symptoms.
  • step-down therapy to voriconazole (eg, after 5 to 7 days in nonneutropenic patients) is recommended only in select clinically stable patients with certain voriconazole-susceptible isolates and negative repeat cultures.

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Dose in the treatment of Candidiasis, endophthalmitis (with or without vitritis) (off-label):

• Voriconazole-susceptible isolates:

  • Systemic therapy:

    • Loading dose: 400 mg (6 mg/kg) Intravenous twice daily for 2 doses,
    • then 300 mg (4 mg/kg) Intravenous or orally twice daily for at least 4 to 6 weeks until examination indicates resolution.
    • For patients with vitritis or with macular involvement (with or without vitritis), an intravitreal injection of voriconazole or amphotericin B deoxycholate is also recommended.

  • Intravitreal therapy:

    • Patients with vitritis or with macular involvement (with or without vitritis):
    • Intravitreal:
      • 100 mcg of an extemporaneously prepared solution in 0.1 mL sterile water or NS.
      • concomitant antifungal systemic therapy is also recommended.

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Dose in the treatment of Esophageal Candidiasis:

• US labeling:

Treatment should continue for a minimum of 14 days, and for at least 7 days following the resolution of symptoms.

Note: If the patient has an inadequate clinical response, titrate in 50 mg/dose increments for weight <40 kg and 100 mg/dose increments for weight ≥40 kg​​​​​​​

• Weight <40 kg:

  • 100 mg orally every 12 hours; maximum: 300 mg daily

• Weight ≥40 kg:

  • 200 mg orally every 12 hours; maximum: 600 mg daily

• Alternative dosing:

  • Fluconazole-refractory: Oral, Intravenous (off-label route):

    • 200 mg (3 mg/kg) twice daily for 14 to 21 days.

  • HIV-positive patients (alternative to preferred therapy): Oral, Intravenous (off-label route):

    • 200 mg twice daily for 14 to 21 days.

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Dose in the treatment of intravascular infections Candidiasis (off-label):

• Fluconazole resistant/voriconazole-susceptible isolates:

  • Endocarditis, native or prosthetic valve:

    • 200 to 300 mg orally twice daily.
    • voriconazole should only be used as a step-down therapy in clinically stable, culture-negative patients following initial therapy with an amphotericin B lipid formulation (with or without flucytosine) or an echinocandin.
    • antifungal therapy should continue for at least 6 weeks after valve replacement surgery (longer durations recommended in patients with perivalvular abscesses or other complications).

  • Implantable cardiac devices (eg, pacemaker. ICD, VAD):

    • 200 to 300 mg orally twice daily.
    • voriconazole should only be used as a step-down therapy in clinically stable, culture-negative patients following initial therapy with an amphotericin B lipid formulation (with or without flucytosine) or an echinocandin.
    • antifungal therapy should continue for 4 to 6 weeks after device removal (4 weeks for infections limited to generator pockets and at least 6 weeks for infections involving the wires).

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Dose in the treatment of oropharyngeal fluconazole-refractory Candidiasis (off-label):

• • 200 mg orally twice daily for up to 28 days.

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Dose in the treatment of Coccidioidomycosis in HIV-infected patients (alternative to preferred therapy) (off-label):

• Mild infections (eg, focal pneumonia):

  • 200 mg orally twice daily.
  • patients who complete initial therapy should be considered for lifelong suppressive therapy.

• Chronic suppressive therapy:

  • 200 mg orally twice daily

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Dose in the treatment of coccidioidal meningitis (salvage therapy) (non-HIV infected patients) (off-label):

• 6 mg/kg intravenous every 12 hours for two doses, then 4 mg/kg every 12 hours.
• 200 mg orally twice daily.

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Dose in the treatment of Empiric antifungal therapy (neutropenic fever) (off-label):

• Initial: 6 mg/kg intravenous every 12 hours for 2 doses
• Maintenance dose: 4 mg/kg every 12 hours.

Note:

May consider oral therapy in place of Intravenous therapy, with dosing of 200 to 300 mg orally every 12 hours or weight-based dosing (3 to 4 mg/kg) every 12 hours.

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Dose in the treatment of Scedosporiosis, fusariosis:

• Initial: 6 mg/kg intravenous every 12 hours for 2 doses
• Maintenance dose: 4 mg/kg intravenous every 12 hours for >7 days

• Maintenance dose:

Note:

If patient has inadequate clinical response, titrate in 50 mg/dose increments for weight <40 kg and 100 mg/dose increments for weight ≥40 kg.​​​​​​​

• Weight <40 kg:

  • 100 mg orally every 12 hours.

• Weight ≥40 kg:

  • 200 mg orally every 12 hours.

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Dose in the treatment of Infection prophylaxis in graft-versus-host disease (GVHD) (high-risk patients) (off-label):

Note: The optimal duration of prophylaxis in GVHD has not been determined.​​​​​​​

• Weight >40 kg:

  • 200 mg orally every 12 hours

• Weight >40 kg:

  • 4 mg/kg intravenous every 12 hours

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Dose in the treatment of Infection prophylaxis in standard- or high-risk patients with allogeneic hematopoietic stem cell transplant (HSCT) or certain autologous HSCT (off-label):

Note:

Begin prophylaxis at the start of chemotherapy or the day of transplantation.

The ASBMT recommends continuing prophylaxis until engraftment (ie, 30 days) or for 7 days after the ANC reaches >1000 cells/mm³.

The IDSA recommends anti-mold prophylaxis in allograft HSCT patients "through the neutropenic period and beyond," based on a demonstrated survival advantage in patients receiving prophylaxis for 75 days post-HSCT, or until the cessation of immunosuppressive therapy.​​​​​​​

• Weight >40 kg:

  • 200 mg orally every 12 hours

• Weight >40 kg:

  • 4 mg/kg intravenous every 12 hours.

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Dose in the treatment of Meningitis (secondary to contaminated [eg, Exserohilum rostratum ] steroid products) (off-label):

Note:

Consult an infectious disease specialist and current CDC guidelines for specific treatment recommendations.

Therapy duration is ≥3 months.

trough serum concentrations must be maintained between 2 to 5 mcg/mL.

• 6 mg/kg intravenous every 12 hours.
• If the patient does not improve or has severe disease, consider adding amphotericin B (liposomal).

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Dose in the treatment of Osteoarticular infection involving the spine, discitis, epidural abscess or vertebral osteomyelitis (secondary to contaminated [eg, Exserohilum rostratum] steroid products) (off-label):

• 6 mg/kg intravenous every 12 hours for ≥3 months.

Note:

Consult an infectious disease specialist and current CDC guidelines for specific treatment recommendations.

Trough serum concentrations must be maintained between 2 to 5 mcg/mL.

If the patient has severe disease, consider adding amphotericin B (liposomal).

If the condition has improved or stabilized, the patients may then be switched to oral therapy.

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Dose in the treatment of Osteoarticular infection not involving the spine (secondary to contaminated [eg, Exserohilum rostratum] steroid products) (off-label):

Note:

Consult an infectious disease specialist and current CDC guidelines for specific treatment recommendations.

Therapy duration is ≥3 months.

Trough serum concentrations must be maintained between 2 to 5 mcg/mL.

• 6 mg/kg intravenous every 12 hours for 2 doses, then 4 mg/kg every 12 hours.
• If the patient has severe disease, consider adding amphotericin B (liposomal)
• Patients with mild disease who are adherent to the therapy and whose trough concentrations and response to therapy can be closely monitored:
  • 6 mg/kg orally every 12 hours for 2 doses, then 4 mg/kg every 12 hours

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Dose in the treatment of Talaromyces marneffei infection in HIV-infected patients (off-label):

• Acute infection in severely ill patients:

  • 6 mg/kg intravenous every 12 hours for 2 doses,
  • then 4 mg/kg intravenous every 12 hours for at least 3 days,
  • followed by 200 mg orally twice daily for a maximum of 12 weeks;
  • follow with itraconazole chronic maintenance therapy

• Mild disease:

  • 400 mg orally twice daily for 2 doses, then 200 mg twice daily for a maximum of 12 weeks; follow with itraconazole chronic maintenance therapy

• Dosage adjustment in patients with an inadequate response:

  • The maintenance dose may be increased from 3 mg/kg intravenous every 12 hours to 4 mg/kg every 12 hours, depending upon the condition.
  • The maintenance dose may be increased from 200 mg orally every 12 hours to 300 mg every 12 hours in patients weighing ≥40 kg (or to 150 mg every 12 hours in patients <40 kg), depending upon the condition.

• Dosage adjustment in patients unable to tolerate treatment:

  • The maintenance dose may be reduced from 4 mg/kg intravenous every 12 hours to 3 mg/kg every 12 hours, depending upon the condition.
  • The maintenance dose may be reduced in 50 mg decrements to a minimum dosage of 200 mg orally every 12 hours in patients weighing ≥40 kg (or to 100 mg every 12 hours in patients <40 kg), depending upon the condition.

• ---

  Dosage adjustment in patients receiving concomitant CYP450 enzyme inducers or substrates:

  • Efavirenz:

    • Increase maintenance dose of voriconazole to 400 mg orally every 12 hours and reduce efavirenz dose to 300 mg once daily.
    • upon discontinuation of voriconazole, return to the initial dose of efavirenz.

  • Phenytoin:

    • Increase voriconazole maintenance dose to 5 mg/kg intravenous every 12 hours.
    • Increase voriconazole maintenance dose to 400 mg orally every 12 hours in patients ≥40 kg (200 mg every 12 hours in patients <40 kg).

Voriconazole (Vfend) Dose in Childrens

Note:

In pediatric patients <12 years, bioequivalence between the oral tablet and suspension has not been determined. Due to the possible shortened gastric transit time in infants and children, absorption of tablets may be different than adults. Dosing recommendations for infants and children are based on studies with the oral suspension. Data suggests higher doses (mg/kg) than adults are required in patients <15 years and weighing <50 kg.

Dose in the treatment of General dosing for susceptible infection:

Note:

Dosage adjustment may be required if the patient does not have an adequate response, cannot tolerate dose, or adequate trough concentrations are not achieved.

Monitor trough concentrations closely.

• Infants and Children <2 years:

  • Intravenous, Oral (Oral suspension):
    • Initial: 9 mg/kg/dose every 12 hours followed by monitoring of serum trough concentrations typically initiated after 3 to 5 days.
    • Adjust the dose to achieve target trough.
    • The median final dosage: 31.5 mg/kg/day (range: 12 to 71 mg/kg/day) divided every 12 hours.

• Children 2 to <12 years:

Note:

Monitor serum concentrations to maintain trough concentrations of 2 to 6 mcg/mL.​​​​​​​

• Loading dose:

  • 9 mg/kg/dose Intravenous every 12 hours for 2 doses on day 1.

• Maintenance:

  • 8 mg/kg/dose Intravenous every 12 hours.
  • Oral suspension:
    • 9 mg/kg/dose orally every 12 hours.
    • The maximum dose: 350 mg/dose.
• Note:
• In most patients, oral therapy is not recommended as initial therapy for treatment.
• It is recommended to convert from parenteral to oral therapy only after significant clinical improvement has been observed.

• Children ≥12 years and Adolescents ≤14 years:

Note:

In this age group, body weight is more important than age in predicting pharmacokinetics.​​​​​​​

• <50 kg:

  • Loading dose: 9 mg/kg/dose Intravenous every 12 hours for 2 doses.
  • followed by a maintenance dose of 4 to 8 mg/kg/dose every 12 hours.

• ≥50 kg:

  • Loading dose: 6 mg/kg/dose every 12 hours for 2 doses.
  • followed by a maintenance dose of 3 to 4 mg/kg/dose every 12 hours.

• <50 kg:

  • 9 mg/kg/dose orally every 12 hours.
  • The maximum dose: 350 mg/dose.

• ≥50 kg:

  • 200 mg orally every 12 hours.

• Adolescents ≥15 years:

  • Loading dose:

    • 6 mg/kg/dose Intravenous every 12 hours for 2 doses.
    • followed by a maintenance dose of 3 to 4 mg/kg/dose every 12 hours.

  • <40 kg:

    • 100 mg orally every 12 hours.

  • ≥40 kg:

    • 200 mg orally every 12 hours.

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Dose in the treatment of invasive Aspergillosis, including disseminated and extrapulmonary infection:

Note:

The duration of therapy should be a minimum of 6 - 12 weeks, although duration is highly dependent on degree and duration of immunosuppression, disease site, and evidence of disease improvement.

Dosage adjustment may be required if the patient does not have an adequate response, cannot tolerate dose, or adequate trough concentrations are not achieved.

Monitor trough concentrations closely.

Therapeutic drug monitoring is critical to ensure efficacy and minimize toxicity.

May consider switching to oral therapy once patient is stable and able to tolerate.

• Children 2 to <12 years:

  • Loading dose: 9 mg/kg/dose Intravenous every 12 hours for 2 doses on day 1,
  • followed by a maintenance dose of 8 mg/kg/dose every 12 hours.
  • Oral suspension: 9 mg/kg/dose orally every 12 hours.
  • The maximum dose: 350 mg/dose.

• Children ≥12 years and Adolescents ≤14 years:

Note:

In this age group, bodyweight is more important than age in predicting pharmacokinetics.​​​​​​​

• <50 kg:

  • Loading dose: 9 mg/kg/dose Intravenous every 12 hours for 2 doses.
  • followed by a maintenance dose of 8 mg/kg/dose every 12 hours.
  • 9 mg/kg/dose orally every 12 hours.
  • The maximum dose: 350 mg/dose.

• ≥50 kg:

  • Loading dose: 6 mg/kg/dose Intravenous every 12 hours for 2 doses
  • followed by a maintenance dose of 4 mg/kg/dose every 12 hours.
  • The usual maximum dose is 200 to 300 mg orally every 12 hours.

• Adolescents ≥15 years:

  • Loading dose: 6 mg/kg/dose Intravenous every 12 hours for 2 doses
  • followed by a maintenance dose of 4 mg/kg/dose every 12 hours.
  • The usual maximum dose is 200 to 300 mg orally every 12 hours.

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Dose in the prophylactic treatment of Candidiasis for patients at high risk of invasive candidiasis (eg, AML, recurrent ALL, allogeneic HSCT):

• Children 2 to <12 years:

  • Loading dose: 9 mg/kg/dose Intravenous every 12 hours for 2 doses on day 1,
  • followed by a maintenance dose of 8 mg/kg/dose every 12 hours.
  • Oral suspension: 9 mg/kg/dose orally every 12 hours.
  • The maximum dose: 350 mg/dose.

• Children ≥12 years and Adolescents ≤14 years:

Note:

In this age group, bodyweight is more important than age in predicting pharmacokinetics​​​​​​​

• <50 kg:

  • Loading dose: 9 mg/kg/dose Intravenous every 12 hours for 2 doses.
  • followed by a maintenance dose of 8 mg/kg/dose every 12 hours.

• ≥50 kg:

  • 4 mg/kg/dose Intravenous every 12 hours.
  • 200 mg orally every 12 hours

• Adolescents ≥15 years:

  • 4 mg/kg/dose intravenous every 12 hours
  • 200 mg orally every 12 hours.

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Dose in the treatment of invasive Candidiasis:

Note:

Voriconazole is considered an alternative therapy and offers little advantage over fluconazole as first-line therapy of candidemia.

Step-down therapy to oral voriconazole is recommended only in select clinically stable patients with certain voriconazole-susceptible isolates (eg, Candida krusei) and negative repeat cultures.

• Children 2 to <12 years:

  • Loading dose: 9 mg/kg/dose Intravenous every 12 hours for 2 doses on day 1,
  • followed by a maintenance dose of 8 mg/kg/dose every 12 hours.
  • Oral suspension: 9 mg/kg/dose orally every 12 hours.
  • The maximum dose: 350 mg/dose.

• Children ≥12 years and Adolescents ≤14 years:

Note:

In this age group, body weight is more important than age in predicting pharmacokinetics.​​​​​​​

• <50 kg:

  • Loading dose: 9 mg/kg/dose Intravenous every 12 hours for 2 doses.
  • followed by a maintenance dose of 8 mg/kg/dose every 12 hours.
  • 9 mg/kg/dose orally every 12 hours.
  • The maximum dose: 350 mg/dose.

• ≥50 kg:

  • Loading dose: 400 mg (6 mg/kg/dose) Intravenous every 12 hours for 2 doses,
  • followed by 3 to 4 mg/kg/dose every 12 hours.
  • The usual maintenance dose is 200 to 300 mg orally every 12 hours.

• Adolescents ≥15 years:

  • Loading dose: 400 mg (6 mg/kg/dose) Intravenous every 12 hours for 2 doses, followed by 3 to 4 mg/kg/dose every 12 hours.
  • 200 to 300 mg orally every 12 hours.

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Dose in the treatment of Candidiasis, endocarditis/implantable cardiac devices (eg, pacemaker, ICD, VAD):

Note:

Voriconazole should only be used as a step-down therapy in clinically stable, culture-negative patients following initial therapy.

• Children 2 to <12 years:

  • Oral suspension: 9 mg/kg/dose orally every 12 hours.
  • The maximum dose: 350 mg/dose.

• Children ≥12 years and Adolescents ≤14 years:

Note:

In this age group, body weight is more important than age in predicting pharmacokinetics.​​​​​​​

• <50 kg:

  • 9 mg/kg/dose orally every 12 hours; maximum dose: 350 mg/dose.

• ≥50 kg:

  • 200 to 300 mg (3 to 4 mg/kg/dose) orally twice daily.

• Adolescents ≥15 years:

  • 200 to 300 mg (3 to 4 mg/kg/dose) orally twice daily.

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Dose in the treatment of Esophageal Candidiasis:

Note: Voriconazole is not considered first-line therapy for esophageal candidiasis.

• Children 2 to <12 years:

  • 4 mg/kg/dose Intravenous every 12 hours.
  • Oral suspension: 9 mg/kg/dose orally every 12 hours
  • The maximum dose: 350 mg/dose.

• Children ≥12 years and Adolescents ≤14 years:

Note:

In this age group, body weight is more important than age in predicting pharmacokinetics​​​​​​​

• <50 kg:

  • 4 mg/kg/dose Intravenous every 12 hours.
  • 9 mg/kg/dose orally every 12 hours
  • The maximum dose: 350 mg/dose.

• ≥50 kg:

  • 200 mg orally twice daily.

• Adolescents ≥15 years:

  • 200 mg orally twice daily.

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Dose in the treatment of Fluconazole-refractory infection:

Treatment should continue for 14 to 21 days.

• Children 2 to <12 years:

  • Loading dose: 9 mg/kg/ dose Intravenous every 12 hours for 2 doses.
  • followed by a maintenance dose of 8 mg/kg/dose every 12 hours.
  • Oral suspension: 9 mg/kg/dose orally every 12 hours
  • The maximum dose: 350 mg/dose

• Children ≥12 years and Adolescents ≤14 years:

Note:

In this age group, body weight is more important than age in predicting pharmacokinetics​​​​​​​

• <50 kg:

  • Loading dose: 9 mg/kg/dose Intravenous every 12 hours for 2 doses.
  • followed by a maintenance dose of 8 mg/kg/dose every 12 hours.
  • 9 mg/kg/dose orally every 12 hours
  • The maximum dose: 350 mg/dose

• ≥50 kg:

  • Intravenous, Oral: 200 mg (3 mg/kg/dose) twice daily.

• Adolescents ≥15 years:

  • Intravenous, Oral: 200 mg (3 mg/kg/dose) twice daily.

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Dose in the treatment of fluconazole-refractory oropharyngeal Candidiasis: 

Treatment should continue for up to 28 days

• Children 2 to <12 years:

  • Oral suspension: 9 mg/kg/dose orally every 12 hours.
  • The maximum dose: 350 mg/dose.

• Children ≥12 years and Adolescents ≤14 years:

Note:

In this age group, body weight is more important than age in predicting pharmacokinetics​​​​​​​

• <50 kg:

  • 9 mg/kg/dose orally every 12 hours.
  • The maximum dose: 350 mg/dose.

• ≥50 kg:

  • 200 mg orally twice daily.

• Adolescents ≥15 years:

  • 200 mg orally twice daily.

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Dose in the treatment of Candidiasis, endophthalmitis (with or without vitritis), voriconazole-susceptible isolates:

• Systemic therapy:

Note:

For patients with vitritis or with macular involvement (with or without vitritis), intravitreal injection of voriconazole or amphotericin B deoxycholate is also recommended.​​​​​​​

• Children 2 to <12 years:

  • Loading dose: 9 mg/kg/dose Intravenous every 12 hours for 2 doses.
  • followed by a maintenance dose of 8 mg/kg/dose every 12 hours.
  • Oral suspension: 9 mg/kg/dose orally every 12 hours.
  • The maximum dose: 350 mg/dose.

• Children ≥12 years and Adolescents ≤14 years:

Note:

In this age group, body weight is more important than age in predicting pharmacokinetics.​​​​​​​

• <50 kg:

  • Loading dose: 9 mg/kg/dose Intravenous every 12 hours for 2 doses.
  • followed by a maintenance dose of 8 mg/kg/dose every 12 hours.
  • 9 mg/kg/dose orally every 12 hours.
  • The maximum dose: 350 mg/dose.

• ≥50 kg:

  • Loading dose: 400 mg (6 mg/kg/dose) Intravenous every 12 hours for 2 doses,
  • followed by 300 mg (4 mg/kg/dose) twice daily.
  • 300 mg (4 mg/kg/dose) orally twice daily.​​​​​​​

• Adolescents ≥15 years:

  • Loading dose: 400 mg (6 mg/kg/dose) Intravenous every 12 hours for 2 doses,
  • followed by 300 mg (4 mg/kg/dose) twice daily.
  • 300 mg (4 mg/kg/dose) orally twice daily.

• Intravitreal therapy:

• Patients with vitritis or with macular involvement (with or without vitritis):

  • Children ≥2 years and Adolescents:

    • Intravitreal:
      • 100 mcg of an extemporaneously prepared solution in 0.1 mL sterile water or NS.
      • Concomitant systemic antifungal therapy is also recommended.

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Dose in the treatment of Scedosporiosis, fusariosis:

• Children 2 to <12 years:

  • Loading dose: 9 mg/kg/dose Intravenous every 12 hours for 2 doses on day 1,
  • followed by a maintenance dose of 8 mg/kg/dose every 12 hours.
  • Oral suspension: 9 mg/kg/dose orally every 12 hours.
  • The maximum dose: 350 mg/dose.

• Children ≥12 years and Adolescents ≤15 years:

Note:

In this age group, body weight is more important than age in predicting pharmacokinetics​​​​​​​

• <50 kg:

  • Loading dose:
    • 9 mg/kg/dose Intravenous every 12 hours for 2 doses,
    • followed by a maintenance dose of 8 mg/kg/dose every 12 hours.
    • 9 mg/kg/dose orally every 12 hours
    • The maximum dose: 350 mg/dose.

• ≥50 kg:

  • Loading dose: 6 mg/kg/dose Intravenous every 12 hours for 2 doses,
  • followed by 4 mg/kg/dose every 12 hours.
  • The usual dose is 200 mg orally every 12 hours.

• Adolescents ≥15 years:

  • Loading dose: 6 mg/kg/dose Intravenous every 12 hours for 2 doses,
  • followed by 4 mg/kg/dose every 12 hours.
  • The usual dose is 200 mg orally every 12 hours.

• Dosage adjustment for inadequate response:

  • Children ≥2 years and Adolescents <15 years weighing <50 kg:

    • Increase by 1 mg/kg/dose Intravenous increments.
    • Increase by 1 mg/kg/dose or 50 mg orally increments.
    • The maximum dose: 350 mg/dose.

  • Children ≥12 years and Adolescents <15 years weighing ≥50 kg and Adolescents ≥15 years (regardless of weight):

    • Increase by 1 mg/kg/dose Intravenous increments.

    • <40 kg:

      • Titrate in 50 mg/dose orally increments; minimum recommended dose: 100 mg every 12 hours
      • The maximum recommended dose in the manufacturer's labeling: 300 mg/dose.

    • ≥40 kg:

      • Increase to 300 mg orally every 12 hours.

• ---

  Dosage adjustment for patients unable to tolerate treatment:

  • Children ≥2 years and Adolescents <15 years weighing <50 kg:

    • Reduce dose by 1 mg/kg/dose Intravenous increments.
    • Reduce dose by 1 mg/kg/dose orally increments or 50 mg increments.

  • Children ≥12 years and Adolescents <15 years weighing ≥50 kg and Adolescents ≥15 years:

    • Reduce dose by 1 mg/kg/dose Intravenous increments.
    • Reduce dose by 50 mg orally increments. Minimum dose in patients <40 kg:
      • 100 mg/dose;
    • Minimum dose in patients ≥40 kg:
      • 200 mg/dose.

• ---

  Dosage adjustment in patients receiving concomitant CYP450 enzyme inducers or substrates:

  • There are no pediatric-specific recommendations provided.
  • Monitor for efficacy and adverse reactions; adjust dose accordingly.
  • Consider increasing voriconazole maintenance doses with concomitant efavirenz and phenytoin.
  • Adjustment of efavirenz dose is also required.

Pregnancy Risk Factor: D

• If Voriconazole is administered to pregnant women, it can cause fetal harm.
• Voriconazole was embryotoxic and teratogenic in animal studies. It also decreased plasma estradiol levels in animal models.
• Effective contraception should be used during treatment for women with childbearing potential. Only be used in pregnant women if the benefits to mother outweigh the risk to the foetus.

Voriconazole use during breastfeeding:

• It is unknown if voriconazole can be found in breast milk.
• The manufacturer suggests that the mother decide whether to stop nursing her infant or discontinue using the drug.
• This is in consideration of the possibility of serious adverse reactions.

Voriconazole (Vfend) Dose in Renal Disease:

• Intravenous:

  • CrCl ≥50 mL/minute:

    • There are no dosage adjustments provided in the manufacturer’s labeling.

  • CrCl <50 mL/minute:

    • There are no specific dosage adjustments provided in the manufacturer’s labeling.
    • Due to accumulation of the intravenous vehicle (cyclodextrin), the manufacturer recommends the use of oral voriconazole in these patients unless an assessment of the benefit:risk justifies the use of Intravenous voriconazole.
    • If Intravenous therapy is used, closely monitor serum creatinine and change to oral voriconazole when possible.
    • Intravenous therapy has been used in select patients with CrCl <50 mL/minute using varying doses (median duration of treatment 7 to 10 days).

• Oral:

  • Mild to severe impairment:

    • No dosage adjustment is necessary.

  • Dialysis:

    • Poorly dialyzed.
    • No supplemental dose or dosage adjustment necessary, including patients on intermittent hemodialysis (IHD) with thrice-weekly sessions or peritoneal dialysis.

  • Continuous renal replacement therapy (CRRT):

    • Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate.
    • Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate).
    • The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment:
      • CVVH, CVVHD, and CVVHDF:
        • A loading dose of 400 mg every 12 hours for 2 doses, followed by 200 mg every 12 hours.

Voriconazole (Vfend) Dose in Liver Disease:

• Mild to moderate impairment (Child-Pugh class A or B):

  • Following standard loading dose, reduce maintenance dosage by 50%

• Severe impairment (Child-Pugh class C):

  • There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Should only be used if benefit outweighs risk.
  • monitor closely for toxicity

Common Side Effects of Voriconazole (Vfend) Include:

• Cardiovascular:

  • Hypertension

• Dermatologic:

  • Skin Rash

• Endocrine & Metabolic:

  • Hyperkalemia
  • Hypokalemia

• Gastrointestinal:

  • Vomiting
  • Nausea
  • Abdominal Pain
  • Diarrhea

• Hepatic:

  • Increased Serum Alkaline Phosphatase
  • Increased Serum Alanine Aminotransferase
  • Increased Liver Enzymes
  • Increased Serum Aspartate Aminotransferase
  • Hyperbilirubinemia

• Ophthalmic:

  • Visual Disturbance

• Renal:

  • Increased Serum Creatinine

• Respiratory:

  • Epistaxis

• Miscellaneous:

  • Fever

Less Common Side Effects of Voriconazole (Vfend) Include:

• Cardiovascular:

  • Hypotension
  • Peripheral Edema
  • Tachycardia
  • Bradycardia
  • Flushing
  • Palpitations
  • Phlebitis
  • Supraventricular Tachycardia
  • Syncope
  • Acute Myocardial Infarction
  • Atrial Arrhythmia
  • Atrial Fibrillation
  • Atrioventricular Block
  • Bigeminy
  • Bundle Branch Block
  • Cardiac Failure
  • Cardiomegaly
  • Cardiomyopathy
  • Cerebral Ischemia
  • Cerebrovascular Accident
  • Chest Pain
  • Deep Vein Thrombophlebitis
  • Edema
  • Endocarditis
  • Extrasystoles
  • Facial Edema
  • Nodal Arrhythmia
  • Orthostatic Hypotension
  • Prolonged Bleeding Time
  • Prolonged QT Interval On ECG
  • Pulmonary Embolism
  • Substernal Pain
  • Supraventricular Extrasystole
  • Thrombophlebitis
  • Torsades De Pointes
  • Vasodilation
  • Ventricular Arrhythmia
  • Ventricular Fibrillation
  • Ventricular Tachycardia

• Central Nervous System:

  • Headache
  • Hallucination
  • Dizziness
  • Agitation
  • Anxiety
  • Ataxia
  • Chills
  • Depression
  • Emotional Lability
  • Hypothermia
  • Insomnia
  • Lethargy
  • Paresthesia
  • Seizure
  • Vertigo
  • Abnormal Dreams
  • Akathisia
  • Amnesia
  • Cerebral Edema
  • Cerebral Hemorrhage
  • Coma
  • Confusion
  • Delirium
  • Dementia
  • Depersonalization
  • Drowsiness
  • Encephalitis
  • Encephalopathy
  • Euphoria
  • Extrapyramidal Reaction
  • Flank Pain
  • Guillain-Barre Syndrome
  • Hypertonia
  • Hypoesthesia
  • Intracranial Hypertension
  • Myasthenia
  • Neuralgia
  • Neuropathy
  • Pain
  • Psychosis
  • Suicidal Ideation
  • Tonic Clonic Epilepsy
  • Voice Disorder

• Dermatologic:

  • Allergic Dermatitis
  • Alopecia
  • Contact Dermatitis
  • Dermatitis
  • Exfoliative Dermatitis
  • Pruritus
  • Urticaria
  • Cellulitis
  • Cheilitis
  • Diaphoresis
  • Ecchymoses
  • Eczema
  • Erythema Multiforme
  • Furunculosis
  • Maculopapular Rash
  • Psoriasis
  • Skin Discoloration
  • Skin Photosensitivity
  • Stevens-Johnson Syndrome
  • Toxic Epidermal Necrolysis
  • Xeroderma

• Endocrine & Metabolic:

  • Hyperglycemia
  • Hypocalcemia
  • Hypophosphatemia
  • Hypoalbuminemia
  • Hypomagnesemia
  • Hypercalcemia
  • Hypermagnesemia
  • Hyperphosphatemia
  • Hypoglycemia
  • Increased Gamma-Glutamyl Transferase
  • Adrenocortical Insufficiency
  • Albuminuria
  • Decreased Glucose Tolerance
  • Decreased Libido
  • Diabetes Insipidus
  • Glycosuria
  • Hypercholesterolemia
  • Hypernatremia
  • Hyperthyroidism
  • Hyperuricemia
  • Hypervolemia
  • Hyponatremia
  • Hypothyroidism
  • Increased Lactate Dehydrogenase
  • Pseudoporphyria

• Gastrointestinal:

  • Oral Inflammation
  • Abdominal Distention
  • Constipation
  • Abdominal Tenderness
  • Cholestasis
  • Dyspepsia
  • Ageusia
  • Anorexia
  • Cholecystitis
  • Cholelithiasis
  • Clostridioides Difficile Colitis
  • Duodenitis
  • Dysgeusia
  • Dysphagia
  • Esophageal Ulcer
  • Esophagitis
  • Flatulence
  • Gastric Ulcer
  • Gastroenteritis
  • Gastrointestinal Hemorrhage
  • Gingival Hemorrhage
  • Gingival Hyperplasia
  • Gingivitis
  • Glossitis
  • Hematemesis
  • Intestinal Perforation
  • Melanosis
  • Melena
  • Mucous Membrane Disease
  • Oral Mucosa Ulcer
  • Pancreatitis
  • Parotid Gland Enlargement
  • Perforated Duodenal Ulcer
  • Peritonitis
  • Proctitis
  • Rectal Disease
  • Stomatitis
  • Ulcerative Bowel Lesion
  • Xerostomia

• Genitourinary:

  • Abnormal Uterine Bleeding
  • Anuria
  • Blighted Ovum
  • Dysmenorrhea
  • Dysuria
  • Epididymitis
  • Hematuria
  • Hemorrhagic Cystitis
  • Impotence
  • Nephrosis
  • Oliguria
  • Pelvic Pain
  • Scrotal Edema
  • Uremia
  • Urinary Incontinence
  • Urinary Retention
  • Urinary Tract Infection
  • Uterine Hemorrhage
  • Vaginal Hemorrhage

• Hematologic & Oncologic:

  • Thrombocytopenia
  • Anemia
  • Leukopenia
  • Pancytopenia
  • Agranulocytosis
  • Aplastic Anemia
  • Bone Marrow Depression
  • Disseminated Intravascular Coagulation
  • Eosinophilia
  • Granuloma
  • Hemolytic Anemia
  • Lymphadenopathy
  • Lymphangitis
  • Macrocytic Anemia
  • Malignant Melanoma
  • Megaloblastic Anemia
  • Microcytic Anemia
  • Petechia
  • Purpuric Disease
  • Rectal Hemorrhage
  • Splenomegaly
  • Squamous Cell Carcinoma
  • Thrombotic Thrombocytopenic Purpura

• Hepatic:

  • Abnormal Hepatic Function Tests
  • Jaundice
  • Cholestatic Jaundice
  • Ascites
  • Hepatic Coma
  • Hepatic Failure
  • Hepatitis
  • Hepatomegaly

• Hypersensitivity:

  • Hypersensitivity Reaction
  • Angioedema
  • Fixed Drug Eruption
  • Nonimmune Anaphylaxis
  • Tongue Edema

• Immunologic:

  • Graft Versus Host Disease

• Infection:

  • Bacterial Infection
  • Fungal Infection
  • Herpes Simplex Infection
  • Infection
  • Sepsis

• Local:

  • Catheter Pain
  • Injection Site Infection
  • Inflammation At Injection Site
  • Pain At Injection Site

• Neuromuscular & Skeletal:

  • Arthralgia
  • Asthenia
  • Myalgia
  • Arthritis
  • Back Pain
  • Discoid Lupus Erythematosus
  • Increased Creatine Phosphokinase Blood Specimen
  • Lower Limb Cramp
  • Myopathy
  • Ostealgia
  • Osteomalacia
  • Osteonecrosis
  • Osteoporosis
  • Tremor

• Ophthalmic:

  • Photophobia
  • Conjunctivitis
  • Dry Eye Syndrome
  • Keratitis
  • Nystagmus Disorder
  • Accommodation Disturbance
  • Blepharitis
  • Color Blindness
  • Corneal Opacity
  • Diplopia
  • Eye Pain
  • Keratoconjunctivitis
  • Mydriasis
  • Night Blindness
  • Oculogyric Crisis
  • Optic Atrophy
  • Optic Neuritis
  • Papilledema
  • Retinal Hemorrhage
  • Retinitis
  • Scleritis
  • Subconjunctival Hemorrhage
  • Uveitis
  • Visual Field Defect
  • Chromatopsia

• Otic:

  • Tinnitus
  • Deafness
  • Otalgia
  • Otitis Externa
  • Hypoacusis

• Renal:

  • Renal Insufficiency
  • Decreased Serum Creatinine
  • Hydronephrosis
  • Increased Blood Urea Nitrogen
  • Nephritis
  • Renal Pain
  • Renal Tubular Necrosis

• Respiratory:

  • Cough
  • Dyspnea
  • Upper Respiratory Tract Infection
  • Hemoptysis
  • Bronchospasm
  • Nasal Congestion
  • Respiratory Failure
  • Tachypnea
  • Cyanosis
  • Flu-Like Symptoms
  • Hypoxia
  • Pharyngitis
  • Pleural Effusion
  • Pneumonia
  • Pulmonary Edema
  • Respiratory Distress Syndrome
  • Respiratory System Disorder
  • Respiratory Tract Infection
  • Rhinitis
  • Sinusitis

• Miscellaneous:

  • Multiorgan failure

Frequency not defined:

• Dermatologic:

  • Cutaneous lupus erythematosus

• Hepatic:

  • Fulminant hepatitis

• Ophthalmic:

  • Vision color changes

Contraindication to Voriconazole (Vfend) Include:

• Hypersensitivity to voriconazole or any component of the formulation.
• Coadministration with:
  • astemizole
  • barbiturates (long-acting)
  • carbamazepine
  • cisapride
  • efavirenz (≥400 mg daily)
  • ergot derivatives (ergotamine and dihydroergotamine)
  • pimozide
  • quinidine
  • rifampin
  • rifabutin
  • ritonavir (≥800 mg daily; also avoid low dose [eg, 200 mg daily] dosing if possible)
  • sirolimus
  • St John’s wort
  • terfenadine

Warnings and Precautions

• Arrhythmias/ QT prolongation:
  • Voriconazole usage has been linked to a prolongation of the QT interval.
  • Rare cases of arrhythmia, including torsade des pointes, cardiac arrest and sudden death, have been reported in severely ill patients with comorbidities or risk factors (eg prior cardiotoxic chemotherapy, pre-cardiotoxic chemotherapy, cardiomyopathy [especially concomitant with heart failure], electrolyte imbalance or QTc prolonging drugs).
  • Patients with potentially proarrhythmic conditions, such as congenital or acquired QT Syndrome, sinus bradycardia or preexisting symptoms, should be cautious.
  • Before initiating therapy, correct electrolyte abnormalities such as hypokalemia or hypomagnesemia.
• Dermatologic reactions
  • Rare cases of malignancy such as melanoma and squamous cells carcinoma [SCC] have been reported in patients who had previously experienced severe photosensitivity reactions or were exposed to standard dose long term voriconazole treatment. In recipients of lung transplants, SCC increased by 6% every 60 days, with a 28% absolute increase at 5 years.
  • Other exfoliative cutaneous reactions that can be severe, such as Stevens-Johnson Syndrome, toxic epidermal Necrolysis and erythema multiflora, have also been reported.
  • Children and patients, especially children, should avoid direct sunlight. Instead, they should wear protective clothing and high-spray sunscreen.
  • Photosensitivity may occur, particularly if it is used for a long time.
  • Patients who have an exfoliative cutaneous response or a skin lession consistent with melanoma or squamous cells carcinoma should be stopped using the product.
  • It is important to conduct periodic skin checks, especially if you are using the product for a long time.
  • If you experience phototoxic reactions, discontinue treatment and consult a dermatologist.
  • For patients who are continuing therapy, a dermatologic evaluation should always be done on a regular basis. This will allow for early detection and treatment of premalignant lesions.
  • Phototoxicity is especially dangerous for children.
• Hepatic toxicities:
  • Voriconazole has been linked to serious (and sometimes fatal) liver reactions, including cholestasis, hepatitis and fulminant failure.
  • The median time from hepatic toxicity in lung transplant recipients was 14 days, with most cases occurring within 30 days.
  • Patients with severe underlying medical conditions (eg hematologic malignancy) should be cautious.
  • Patients with no known underlying risk factors have experienced hepatic reactions.
  • Children are more at risk for liver enzyme elevations.
  • Therapy discontinuation can often reverse liver dysfunction.
  • Monitor serum transaminase, bilirubin and blood sugar at baseline and every other week for the first month.
  • If there are no abnormalities, the monitoring frequency can be decreased to monthly.
  • Stop using if liver enzymes are elevated above baseline.
• Reactions that are related to infusion:
  • ANaphylactoid-type reactions such as tachycardia and dyspnea, chest tightness or faintness, chest tightness, chest tightness or faintness, nausea, rash (puritus), fever, sweating, flushing, and tachycardia have been reported
  • Symptoms have been noticed immediately after the infusion.
  • If you have severe reactions, or if your clinical signs indicate otherwise, stop infusion.
• Ocular effects
  • Treatment is often associated with visual changes such as blurred vision, changes of color perception and color acuity.
  • Also, postmarketing cases of optic neuritis (lasting >1 months) and papilledema have been reported.
  • It is important to warn patients against tasks that require vision, such as driving or operating machinery.
  • After a brief exposure, and after treatment regimens (=28 day), changes can be reversed.
  • Long-term administration does not allow for reversibility.
  • If the treatment lasts longer than 28 days, it is important to monitor visual function (eg., acuity and visual field, color perception).
• Toxicity in the renal system:
  • It has been reported that there is acute renal failure.
  • Patients receiving concomitant medications containing nephrotoxic substances should be cautious.
  • Assess renal function, especially serum creatinine, at baseline and every other month during treatment.
• Skeletal effects
  • Long-term treatment may result in fluorosis or periostitis.
  • Stop therapy if the patient experiences skeletal pain or radiologic findings of fluorosis, periostitis or skeletal discomfort.
• Toxicity symptoms
  • Voriconazole demonstrates nonlinear pharmacokinetics.
  • Dose modifications can cause unpredictable changes in serum concentrations, which could lead to toxic effects.
  • The strongest correlations for toxicities have been found between voriconazole-trough levels and neurological and dermatological adverse effects.
  • These studies showed that a higher threshold value for toxicities was associated with increased toxicity.
  • We have much less evidence to support the existence of a cutoff threshold or hepatotoxicity.
  • Important to note is that the cutoff threshold values varied widely between studies.
  • For most diseases, however, a maximum of 5.0 mg/L is acceptable.
• An abnormality in the electrolyte:
  • Before initiating therapy, correct electrolyte abnormalities such as hypokalemia or hypomagnesemia.
• Hepatic impairment
  • Take care.
  • Clinical symptoms like jaundice and liver damage, as well as higher liver function test results, have all been connected to voriconazole.
  • A modification to the maintenance dosage may be necessary in cases of mild to moderate hepatic impairment (Child-Pugh classifications A and B).
  • Patients with severe hepatic impairment should only use this medication if it is worth the risk.
  • Assess liver function, including liver function tests and levels of bilirubin, at baseline and every other time during treatment.
• Lactose intolerance:
  • Patients with rare inherited conditions such as glucose-galactose malabsorption, Lapp lactase deficiency, or galactose intolerance should avoid using lactose-containing tablet.
• Pancreatitis
  • Patients (including adults and children) who have undergone recent chemotherapy or a hematopoietic cell transplant and are at a high risk of developing acute pancreatitis should be closely watched.
  • Therapy has shown the presence of pancreatitis.
• Renal impairment
  • Patients with severe renal impairment should not be given intravenous voriconazole.
  • Assess serum creatinine, other renal functions and treatment progress periodically.

Monitor:

• Hepatic function at initiation, weekly during the first month and monthly during the course of treatment.
• Renal function.
• Serum electrolytes (particularly calcium, magnesium, and potassium) prior to initiation and during therapy.
• Visual function (visual acuity, visual field, and color perception) if the treatment course continues >28 days
• Phototoxic reactions (especially in pediatric patients)
• Pancreatic function (in patients at risk for acute pancreatitis).
• Total body skin examination yearly (more frequently if lesions noted).
• Serum trough concentrations should be monitored in the following infections:
  • Invasive aspergillosis treatment (and prolonged prophylaxis)
  • Endophthalmitis
  • Meningitis or osteoarticular infections due to Exserohilum rostratum.
  • For other infections, consider obtaining voriconazole trough level to assure therapeutics serum concentrations in patients failing therapy or in those exhibiting signs of toxicity.
• For meningitis or osteoarticular infections due to Exserohilum rostratum, the CDC recommends obtaining a trough serum concentration on day 5 of therapy and weekly thereafter for the initial 4 to 6 weeks of therapy or when dosing adjustments are made.
• For invasive aspergillosis, IDSA recommends monitoring trough serum concentrations after steady state has been reached (4 to 7 days after therapy initiation).
• The need for continued or repeat monitoring is a patient-specific decision influenced by many factors (eg, infection severity, cost, assay availability)

How to Administer Voriconazole (Vfend)?

Oral administration:

• Administer 1 hour before or 1 hour after a meal.
• Prior to each use, shake the oral suspension for approximately 10 seconds.
• Enteral tube feedings may decrease oral absorption.
• Tube feedings may be withheld for 1 hour before and 1 hour after the dose.

Intravenous administration:

• Infuse over 1 to 3 hours.
• Do not administer as an intravenous bolus injection.
• Do not infuse the drug in the same line or cannula with other drug infusions.
• Concomitant administration, even in separate lines or cannulas with concentrated electrolyte solutions or blood products should be avoided.
• May be infused simultaneously with nonconcentrated electrolytes or TPN through a separate intravenous line.
• Use a different port for Vfend if TPN is infused through a multiple lumen catheter.

Intravitreal administration:

• Administer a prepared solution of 100 mcg/0.1 mL of voriconazole in sterile water or NS intravitreally.

Ophthalmic (off-label):

• Administer an extemporaneously prepared voriconazole 10 mg/mL (1%) ophthalmic solution to the affected eye.

Mechanism of action of Voriconazole:

• Interferes in fungal cytochrome P450 activities (selectively inhibits14-alpha-lanosterol desmethylation), decreasing Ergosterol Synthesis (principal sterol found in fungal cell cell membrane), and inhibiting fungal cells membrane formation.

Notice:

• Voriconazole pharmacokinetics in pediatric patients are complex.
• The pharmacokinetics of children aged 12-14 years, weighing between 50 and 150 kg, and adolescents >=15 year (regardless their weight) are very similar to those of adults.
• Voriconazole pharmacokinetics in pediatric patients aged 12 years are not well understood.
• They exhibit both intra- and interpatient variability. Individualized dosing is advised.

Distribution:

• Extensive tissue distribution
• CSF concentration ~50% of plasma concentration
• Children 2 to <12 years: Biphasic, V (central): 0.81 L/kg; V (peripheral): 2.2 L/kg
• Adults: 4.6 L/kg

Protein binding:

• 58%

Metabolism:

• Hepatic, via CYP2C19 (major pathway) and CYP2C9 and CYP3A4 (less significant).
• Saturable (may demonstrate nonlinearity)
• the N-oxide major metabolite has minimal antifungal activity
• CYP2C19 exhibits genetic polymorphism (15% to 20% Asians may be poor metabolizers of voriconazole
• 3% to 5% Caucasians and African Americans may be poor metabolizers
• In children 2 to 12 years, metabolic clearance is faster than in adults.
• In children 2 to 12 years, the majority of data has shown that the pharmacokinetic parameters of voriconazole are affected by a patient's CYP2C19 genotype although, an initial report suggested CYP2C19 genotype had no apparent effect on exposure in children.

Bioavailability: Oral:

• Children 2 to <12 years: Reported range highly variable: ~45% to 64% and values as high as 80% have been reported.
• Adults: 96%

Half-life elimination:

• Variable and dose-dependent. Steady-state is achieved by day 3 when an Intravenous loading dose is administered and between days 5 and 8 if no loading dose is used.

Time to peak: Oral:

• Children 2 to <12 years: Median: 1.1 hours (range: 0.73 to 8.03 hours) (Driscoll 2011)
• Adults: 1 to 2 hours

Excretion:

• Urine (<2% as unchanged drug) 

International Brands of Voriconazole:

• APO-Voriconazole
• SANDOZ Voriconazole
• TEVA-Voriconazole
• Vfend
• Cantex
• Conazoglob
• Progil
• Vanazole
• Varcon
• Vertimal
• VFEND
• Vfend
• Vonaz
• Vorcum
• Voricon
• Vorigrand
• Vornal
• Vttack
• Vzole
• Vzon200

Voriconazole in Pakistan:

Noric Tab. 200 mg - MTI Voricon Tab. 200 mg - Genome Vorif Tab. 200 mg and 50 mg - Ferozsons

VORICONAZOLE [Tabs 40 mg]
Vorif	Ferozsons Laboratoies Ltd.

 

VORICONAZOLE [Tabs 200 mg]
Vorif	Ferozsons Laboratoies Ltd.