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VFEND(voriconazole)injection, powder, lyophilized, for solut
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HIGHLIGHTS OF PRESCRIBING INFORMATION |
These highlights do not include all the information needed to use VFEND safely and effectively. See full prescribing information for VFEND.
VFEND® (voriconazole) I.V.
Initial U.S. Approval: 2002
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RECENT MAJOR CHANGES
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Warnings and Precautions |
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Drug Interactions (5.1) |
06/2010 |
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Visual Disturbances (5.3) |
06/2010 |
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Dermatological Reactions (5.12) |
06/2010 |
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INDICATIONS AND USAGE
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VFEND is a triazole antifungal drug indicated for use in the treatment of:
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Invasive aspergillosis (1.1)
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Candidemia (nonneutropenics) and disseminated candidiasis in skin, abdomen, kidney, bladder wall, and wounds (1.2)
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Esophageal candidiasis (1.3)
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Serious infections caused by Scedosporium apiospermum and Fusarium spp. including Fusarium solani, in patients intolerant of, or refractory to, other therapy (1.4)
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DOSAGE AND ADMINISTRATION
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Recommended Dosing Regimen (2)
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Infection |
Loading dose |
Maintenance Dose*,†,‡ |
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IV* |
IV |
Oral§ |
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Invasive Aspergillosis¶ |
6 mg/kg q12h for the first 24 hours |
4 mg/kg q12h |
200 mg q12h |
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Candidemia in nonneutropenics and other deep tissue Candida infections |
6 mg/kg q12h for the first 24 hours |
3–4 mg/kg q12h# |
200 mg q12h |
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Esophageal Candidiasis |
not eva luated |
not eva luated |
200 mg q12h |
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Scedosporiosis and Fusariosis |
6 mg/kg q12h for the first 24 hours |
4 mg/kg q12h |
200 mg q12h |
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DOSAGE FORMS AND STRENGTHS
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Powder for Solution for Injection: 200 mg voriconazole and 3200 mg sulfobutyl ether beta-cyclodextrin sodium (SBECD). (3)
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CONTRAINDICATIONS
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Hypersensitivity to voriconazole or its excipients.
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To reduce risk of serious adverse events, do not use VFEND with terfenadine, astemizole, cisapride, pimozide or quinidine, sirolimus (4, 7)
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To prevent loss of VFEND efficacy, do not use with rifampin, carbamazepine, long-acting barbiturates, ritonavir, rifabutin, ergot alkaloids, and St. John's Wort (4, 7)
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WARNINGS AND PRECAUTIONS
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Drug Interactions (5.1): review patient's concomitant medications. Several drugs may significantly alter voriconazole concentrations. Voriconazole may alter PK or PD of several drugs (7)
Hepatic Toxicity (5.2): serious hepatic reactions have been reported. eva luate liver function tests at the start of and during the course of voriconazole therapy
Visual Disturbances (5.3): monitor visual function if treatment continues beyond 28 days
Pregnancy Category D (5.4): do not administer to pregnant women
Arrhythmias and QT Prolongation (5.5): administer with caution to patients with proarrhythmic conditions
Infusion Related Reactions (5.6): anaphylactoid reactions have been reported
Dermatological Reactions (5.12): exfoliative cutaneous reactions and photosensitivity have been reported
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ADVERSE REACTIONS
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Most frequent (all causalities, incidence ≥2%): visual disturbances, fever, nausea, rash, vomiting, chills, headache, liver function test abnormal, tachycardia, hallucinations (6)
To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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DRUG INTERACTIONS
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Inhibitors and inducers of CYP3A4, CYP2C9, and CYP2C19 may alter VFEND concentrations. Adjust the VFEND dose and monitor for adverse events or lack of efficacy (4, 7)
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VFEND may increase the concentrations and activity of drugs that are CYP3A4, CYP2C9 and CYP2C19 substrates. Reduce doses of and monitor for lack of efficacy or adverse events associated with drugs that are substrates of these enzymes (4, 7)
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USE IN SPECIFIC POPULATIONS
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Pregnant or nursing women: VFEND should not be used in pregnant or nursing women (8.1, 8.3)
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Pediatrics: safety/effectiveness in patients <12 years has not been established (8.4)
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Hepatic impairment: use half the maintenance dose in patients with mild to moderate hepatic impairment (Child-Pugh Class A and B) (2.6)
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Renal impairment: avoid intravenous administration in patients with moderate to severe renal impairment (creatinine clearance <50 mL/min) (2.7)
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See 17 for PATIENT COUNSELING INFORMATION |
Revised: 07/2011 |
Back to Highlights and Tabs
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FULL PRESCRIBING INFORMATION: CONTENTS* |
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1INDICATIONS AND USAGE
1.1 Invasive aspergillosis
1.2 Candidemia in nonneutropenic patients and the following Candida infections
1.3 Esophageal candidiasis
1.4Serious fungal infections caused by Scedosporium apiospermum (asexual form of Pseudallescheria boydii) and Fusarium spp. including Fusarium solani, in patients intolerant of, or refractory to, other therapy
2DOSAGE AND ADMINISTRATION
2.1 Instructions for Use in All Patients
2.2 Use of VFEND I.V. with other Parenteral Drug Products
2.3Recommended Dosing in Adults
2.4 Dosage Adjustment
2.5Intravenous Administration
2.6Use in Patients with Hepatic Impairment
2.7 Use in Patients with Renal Impairment
3DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5WARNINGS AND PRECAUTIONS
5.1 Drug Interactions
5.2Hepatic Toxicity
5.3 Visual Disturbances
5.4 Pregnancy Category D
5.5 Arrhythmias and QT Prolongation
5.6 Infusion Related Reactions
5.7 Laboratory Tests
5.8 Patients with Hepatic Impairment
5.9 Patients with Renal Impairment
5.10 Monitoring of Renal Function
5.11 Monitoring of Pancreatic Function
5.12 Dermatological Reactions
6 ADVERSE REACTIONS
6.1 Overview
6.2 Clinical Trial Experience in Adults
6.3 Clinical Laboratory Values
7DRUG INTERACTIONS
8USE IN SPECIFIC POPULATIONS
8.1 Use in Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Women of Childbearing Potential
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.3 Pharmacokinetics
12.4 Microbiology
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Teratogenic Effects
14 CLINICAL STUDIES
14.1 Invasive Aspergillosis
14.2 Candidemia in Non-neutropenic Patients and Other Deep Tissue Candida Infections
14.3 Esophageal Candidiasis
14.4 Other Serious Fungal Pathogens
15 REFERENCES
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
16.2 Storage
17 PATIENT COUNSELING INFORMATION
PRINCIPAL DISPLAY PANEL - 200 mg Vial Carton
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FULL PRESCRIBING INFORMATION
1INDICATIONS AND USAGE
VFEND is indicated for use in patients 12 years of age and older in the treatment of the following fungal infections:
1.1 Invasive aspergillosis
In clinical trials, the majority of isolates recovered were Aspergillus fumigatus. There was a small number of cases of culture-proven disease due to species of Aspergillus other than A. fumigatus [see Clinical Studies (14.1), Microbiology (12.4)].
1.2 Candidemia in nonneutropenic patients and the following Candida infections
disseminated infections in skin and infections in abdomen, kidney, bladder wall, and wounds [see Clinical Studies (14.2), Microbiology (12.4)].
1.3 Esophageal candidiasis
[see Clinical Studies (14.3), Microbiology (12.4)].
1.4Serious fungal infections caused by Scedosporium apiospermum (asexual form of Pseudallescheria boydii) and Fusarium spp. including Fusarium solani, in patients intolerant of, or refractory to, other therapy
[see Clinical Studies (14.4), Microbiology (12.4)].
Specimens for fungal culture and other relevant laboratory studies (including histopathology) should be obtained prior to therapy to isolate and identify causative organism(s). Therapy may be instituted before the results of the cultures and other laboratory studies are known. However, once these results become available, antifungal therapy should be adjusted accordingly.
2DOSAGE AND ADMINISTRATION
2.1 Instructions for Use in All Patients
VFEND I.V. for Injection requires reconstitution to 10 mg/mL and subsequent dilution to 5 mg/mL or less prior to administration as an infusion, at a maximum rate of 3 mg/kg per hour over 1 to 2 hours.
Do not administer as an IV bolus injection.
2.2 Use of VFEND I.V. with other Parenteral Drug Products
Blood products and concentrated electrolytes
VFEND I.V. must not be infused concomitantly with any blood product or short-term infusion of concentrated electrolytes, even if the two infusions are running in separate intravenous lines (or cannulas). Electrolyte disturbances such as hypokalemia, hypomagnesemia and hypocalcemia should be corrected prior to initiation of VFEND therapy [see Warnings and Precautions (5.7)].
Intravenous solutions containing (non-concentrated) electrolytes
VFEND I.V. can be infused at the same time as other intravenous solutions containing (non-concentrated) electrolytes, but must be infused through a separate line.
Total parenteral nutrition (TPN)
VFEND I.V. can be infused at the same time as total parenteral nutrition, but must be infused in a separate line. If infused through a multiple-lumen catheter, TPN needs to be administered using a different port from the one used for VFEND I.V.
2.3Recommended Dosing in Adults
Invasive aspergillosis and serious fungal infections due to Fusarium spp. and Scedosporium apiospermum
See Table 1. Therapy must be initiated with the specified loading dose regimen of intravenous VFEND on Day 1 followed by the recommended maintenance dose regimen. Intravenous treatment should be continued for at least 7 days. Once the patient has clinically improved and can tolerate medication given by mouth, the oral tablet form or oral suspension form of VFEND may be utilized. The recommended oral maintenance dose of 200 mg achieves a voriconazole exposure similar to 3 mg/kg IV; a 300 mg oral dose achieves an exposure similar to 4 mg/kg IV. Switching between the intravenous and oral formulations is appropriate because of the high bioavailabilty of the oral formulation in adults [see Clinical Pharmacology (12)].
Candidemia in nonneutropenic patients and other deep tissue Candida infections
See Table 1. Patients should be treated for at least 14 days following resolution of symptoms or following last positive culture, whichever is longer.
Esophageal Candidiasis
See Table 1. Patients should be treated for a minimum of 14 days and for at least 7 days following resolution of symptoms.
Table 1 Recommended Dosing Regimen
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Infection |
Loading dose |
Maintenance Dose*,† |
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IV |
IV |
Oral‡ |
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Invasive Aspergillosis§ |
6 mg/kg q12h for the first 24 hours |
4 mg/kg q12h |
200 mg q12h |
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Candidemia in nonneutropenic patients and other deep tissue Candida infections |
6 mg/kg q12h for the first 24 hours |
3–4 mg/kg q12h¶ |
200 mg q12h |
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Esophageal Candidiasis |
# |
# |
200 mg q12h |
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Scedosporiosis and Fusariosis |
6 mg/kg q12h for the first 24 hours |
4 mg/kg q12h |
200 mg q12h |
2.4 Dosage Adjustment
If patient response is inadequate, the oral maintenance dose may be increased from 200 mg every 12 hours (similar to 3 mg/kg IV q12h) to 300 mg every 12 hours (similar to 4 mg/kg IV q12h). For adult patients weighing less than 40 kg, the oral maintenance dose may be increased from 100 mg every 12 hours to 150 mg every 12 hours. If patient is unable to tolerate 300 mg orally every 12 hours, reduce the oral maintenance dose by 50 mg steps to a minimum of 200 mg every 12 hours (or to 100 mg every 12 hours for adult patients weighing less than 40 kg).
If patient is unable to tolerate 4 mg/kg IV q12h, reduce the intravenous maintenance dose to 3 mg/kg q12h.
The maintenance dose of voriconazole should be increased when co-administered with phenytoin or efavirenz [see Drug Interactions (7)].
The maintenance dose of voriconazole should be reduced in patients with mild to moderate hepatic impairment, Child-Pugh Class A and B [see Use in Patients with Hepatic Impairment (2.7)]. There are no PK data to allow for dosage adjustment recommendations in patients with severe hepatic impairment (Child-Pugh Class C).
Duration of therapy should be based on the severity of the patient's underlying disease, recovery from immunosuppression, and clinical response.
2.5Intravenous Administration
Reconstitution
The powder is reconstituted with 19 mL of Water For Injection to obtain an extractable volume of 20 mL of clear concentrate containing 10 mg/mL of voriconazole. It is recommended that a standard 20 mL (non-automated) syringe be used to ensure that the exact amount (19.0 mL) of Water for Injection is dispensed. Discard the vial if a vacuum does not pull the diluent into the vial. Shake the vial until all the powder is dissolved.
Dilution
VFEND must be infused over 1–2 hours, at a concentration of 5 mg/mL or less. Therefore, the required volume of the 10 mg/mL VFEND concentrate should be further diluted as follows (appropriate diluents listed below):
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Calculate the volume of 10 mg/mL VFEND concentrate required based on the patient's weight (see Table 2).
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In order to allow the required volume of VFEND concentrate to be added, withdraw and discard at least an equal volume of diluent from the infusion bag or bottle to be used. The volume of diluent remaining in the bag or bottle should be such that when the 10 mg/mL VFEND concentrate is added, the final concentration is not less than 0.5 mg/mL nor greater than 5 mg/mL.
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Using a suitable size syringe and aseptic technique, withdraw the required volume of VFEND concentrate from the appropriate number of vials and add to the infusion bag or bottle. Discard Partially Used Vials.
The final VFEND solution must be infused over 1–2 hours at a maximum rate of 3 mg/kg per hour.
Table 2 Required Volumes of 10 mg/mL VFEND Concentrate
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Volume of VFEND Concentrate (10 mg/mL) required for: |
Body Weight
(kg) |
3 mg/kg dose
(number of vials) |
4 mg/kg dose
(number of vials) |
6 mg/kg dose
(number of vials) |
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30 |
9.0 mL (1) |
12 mL (1) |
18 mL (1) |
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35 |
10.5 mL (1) |
14 mL (1) |
21 mL (2) |
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40 |
12.0 mL (1) |
16 mL (1) |
24 mL (2) |
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45 |
13.5 mL (1) |
18 mL (1) |
27 mL (2) |
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50 |
15.0 mL (1) |
20 mL (1) |
30 mL (2) |
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55 |
16.5 mL (1) |
22 mL (2) |
33 mL (2) |
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60 |
18.0 mL (1) |
24 mL (2) |
36 mL (2) |
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65 |
19.5 mL (1) |
26 mL (2) |
39 mL (2) |
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70 |
21.0 mL (2) |
28 mL (2) |
42 mL (3) |
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75 |
22.5 mL (2) |
30 mL (2) |
45 mL (3) |
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80 |
24.0 mL (2) |
32 mL (2) |
48 mL (3) |
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85 |
25.5 mL (2) |
34 mL (2) |
51 mL (3) |
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90 |
27.0 mL (2) |
36 mL (2) |
54 mL (3) |
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95 |
28.5 mL (2) |
38 mL (2) |
57 mL (3) |
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100 |
30.0 mL (2) |
40 mL (2) |
60 mL (3) |
VFEND I.V. for Injection is a single dose unpreserved sterile lyophile. Therefore, from a microbiological point of view, once reconstituted, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should not be longer than 24 hours at 2° to 8°C (36° to 46°F). This medicinal product is for single use only and any unused solution should be discarded. Only clear solutions without particles should be used.
The reconstituted solution can be diluted with:
9 mg/mL (0.9%) Sodium Chloride USP
Lactated Ringers USP
5% Dextrose and Lactated Ringers USP
5% Dextrose and 0.45% Sodium Chloride USP
5% Dextrose USP
5% Dextrose and 20 mEq Potassium Chloride USP
0.45% Sodium Chloride USP
5% Dextrose and 0.9% Sodium Chloride USP
The compatibility of VFEND I.V. with diluents other than those described above is unknown (see Incompatibilities below).
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Incompatibilities
VFEND I.V. must not be diluted with 4.2% Sodium Bicarbonate Infusion. The mildly alkaline nature of this diluent caused slight degradation of VFEND after 24 hours storage at room temperature. Although refrigerated storage is recommended following reconstitution, use of this diluent is not recommended as a precautionary measure. Compatibility with other concentrations is unknown.
2.6Use in Patients with Hepatic Impairment
In the clinical program, patients were included who had baseline liver function tests (ALT, AST) up to 5 times the upper limit of normal. No dose adjustment is necessary in patients with this degree of abnormal liver function, but continued monitoring of liver function tests for further elevations is recommended [see Warnings and Precautions (5.9)].
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 (Child-Pugh Class A and B) [see Clinical Pharmacology (12.3)].
VFEND has not been studied in patients with severe hepatic cirrhosis (Child-Pugh Class C) or in patients with chronic hepatitis B or chronic hepatitis C disease. VFEND has been associated with elevations in liver function tests and clinical signs of liver damage, such as jaundice, and should only be used in patients with severe hepatic impairment if the benefit outweighs the potential risk. Patients with hepatic insufficiency must be carefully monitored for drug toxicity.
2.7 Use in Patients with Renal Impairment
The pharmacokinetics of orally administered VFEND are not significantly affected by renal impairment. Therefore, no adjustment is necessary for oral dosing in patients with mild to severe renal impairment [see Clinical Pharmacology (12.3 )].
In patients with moderate or severe renal impairment (creatinine clearance <50 mL/min), accumulation of the intravenous vehicle, SBECD, occurs. Oral voriconazole should be administered to these patients, unless an assessment of the benefit/risk to the patient justifies the use of intravenous voriconazole. Serum creatinine levels should be closely monitored in these patients, and, if increases occur, consideration should be given to changing to oral voriconazole therapy [see Warnings and Precautions (5.10)].
Voriconazole is hemodialyzed with clearance of 121 mL/min. The intravenous vehicle, SBECD, is hemodialyzed with clearance of 55 mL/min. A 4-hour hemodialysis session does not remove a sufficient amount of voriconazole to warrant dose adjustment.
3DOSAGE FORMS AND STRENGTHS
Powder for Solution for Injection
VFEND I.V. for Injection is supplied in a single use vial as a sterile lyophilized powder equivalent to 200 mg VFEND and 3200 mg sulfobutyl ether beta-cyclodextrin sodium (SBECD).
4 CONTRAINDICATIONS
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VFEND is contraindicated in patients with known hypersensitivity to voriconazole or its excipients. There is no information regarding cross-sensitivity between VFEND (voriconazole) and other azole antifungal agents. Caution should be used when prescribing VFEND to patients with hypersensitivity to other azoles.
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Coadministration of terfenadine, astemizole, cisapride, pimozide or quinidine with VFEND is contraindicated because increased plasma concentrations of these drugs can lead to QT prolongation and rare occurrences of torsade de pointes [see Drug Interactions (7), Clinical Pharmacology (12.3)].
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Coadministration of VFEND with sirolimus is contraindicated because VFEND significantly increases sirolimus concentrations [see Drug Interactions (7), Clinical Pharmacology (12.3)].
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Coadministration of VFEND with rifampin, carbamazepine and long-acting barbiturates is contraindicated because these drugs are likely to decrease plasma voriconazole concentrations significantly [see Drug Interactions (7), Clinical Pharmacology (12.3)].
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Coadministration of VFEND with high-dose ritonavir (400 mg q12h) is contraindicated because ritonavir (400 mg q12h) significantly decreases plasma voriconazole concentrations. Coadministration of voriconazole and low-dose ritonavir (100 mg q12h) should be avoided, unless an assessment of the benefit/risk to the patient justifies the use of voriconazole [see Drug Interactions (7), Clinical Pharmacology (12.3)].
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Coadministration of VFEND with rifabutin is contraindicated since VFEND significantly increases rifabutin plasma concentrations and rifabutin also significantly decreases voriconazole plasma concentrations [see Drug Interactions (7), Clinical Pharmacology (12.3)].
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Coadministration of VFEND with ergot alkaloids (ergotamine and dihydroergotamine) is contraindicated because VFEND may increase the plasma concentration of ergot alkaloids, which may lead to ergotism [see Drug Interactions (7), Clinical Pharmacology (12.3)].
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Coadministration of VFEND with St. John's Wort is contraindicated because this herbal supplement may decrease voriconazole plasma concentration [see Drug Interactions (7), Clinical Pharmacology (12.3)].
5WARNINGS AND PRECAUTIONS
5.1 Drug Interactions
See Table 7 for a listing of drugs that may significantly alter voriconazole concentrations. Also, see Table 8 for a listing of drugs that may interact with voriconazole resulting in altered pharmacokinetics or pharmacodynamics of the other drug [see Contraindications (4), Drug Interactions (7)].
5.2Hepatic Toxicity
In clinical trials, there have been uncommon cases of serious hepatic reactions during treatment with VFEND (including clinical hepatitis, cholestasis and fulminant hepatic failure, including fatalities). Instances of hepatic reactions were noted to occur primarily in patients with serious underlying medical conditions (predominantly hematological malignancy). Hepatic reactions, including hepatitis and jaundice, have occurred among patients with no other identifiable risk factors. Liver dysfunction has usually been reversible on discontinuation of therapy [see Warnings and Precautions (5.8), Adverse Reactions (6.3)].
Monitoring of hepatic function: Liver function tests should be eva luated at the start of and during the course of VFEND therapy. Patients who develop abnormal liver function tests during VFEND therapy should be monitored for the development of more severe hepatic injury. Patient management should include laboratory eva luation of hepatic function (particularly liver function tests and bilirubin). Discontinuation of VFEND must be considered if clinical signs and symptoms consistent with liver disease develop that may be attributable to VFEND [see Warnings and Precautions (5.8), Dosage and Administration (2.4, 2.6), Adverse Reactions (6.3)].
5.3 Visual Disturbances
The effect of VFEND on visual function is not known if treatment continues beyond 28 days. There have been post-marketing reports of prolonged visual adverse events, including optic neuritis and papilledema. If treatment continues beyond 28 days, visual function including visual acuity, visual field and color perception should be monitored [see Warnings and Precautions (5.3), Adverse Reactions (6.2)].
5.4 Pregnancy Category D
Voriconazole can cause fetal harm when administered to a pregnant woman.
In animals, voriconazole administration was associated with teratogenicity, embryotoxicity, increased gestational length, dystocia and embryomortality. Please refer to section 8.1 (Use in Pregnancy) for additional details.
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to the fetus.
5.5 Arrhythmias and QT Prolongation
Some azoles, including voriconazole, have been associated with prolongation of the QT interval on the electrocardiogram. During clinical development and post-marketing surveillance, there have been rare cases of arrhythmias, (including ventricular arrhythmias such as torsade de pointes), cardiac arrests and sudden deaths in patients taking voriconazole. These cases usually involved seriously ill patients with multiple confounding risk factors, such as history of cardiotoxic chemotherapy, cardiomyopathy, hypokalemia and concomitant medications that may have been contributory.
Voriconazole should be administered with caution to patients with these potentially proarrhythmic conditions.
Rigorous attempts to correct potassium, magnesium and calcium should be made before starting voriconazole [see Clinical Pharmacology (12.3)].
5.6 Infusion Related Reactions
During infusion of the intravenous formulation of voriconazole in healthy subjects, anaphylactoid-type reactions, including flushing, fever, sweating, tachycardia, chest tightness, dyspnea, faintness, nausea, pruritus and rash, have occurred uncommonly. Symptoms appeared immediately upon initiating the infusion. Consideration should be given to stopping the infusion should these reactions occur.
5.7 Laboratory Tests
Electrolyte disturbances such as hypokalemia, hypomagnesemia and hypocalcemia should be corrected prior to initiation of VFEND therapy.
Patient management should include laboratory eva luation of renal (particularly serum creatinine) and hepatic function (particularly liver function tests and bilirubin).
5.8 Patients with Hepatic Impairment
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 (Child-Pugh Class A and B) receiving VFEND [see Clinical Pharmacology (12.3), Dosage and Administration (2.6)].
VFEND has not been studied in patients with severe cirrhosis (Child-Pugh Class C). VFEND has been associated with elevations in liver function tests and clinical signs of liver damage, such as jaundice, and should only be used in patients with severe hepatic insufficiency if the benefit outweighs the potential risk. Patients with hepatic insufficiency must be carefully monitored for drug toxicity.
5.9 Patients with Renal Impairment
In patients with moderate to severe renal dysfunction (creatinine clearance <50 mL/min), accumulation of the intravenous vehicle, SBECD, occurs. Oral voriconazole should be administered to these patients, unless an assessment of the benefit/risk to the patient justifies the use of intravenous voriconazole. Serum creatinine levels should be closely monitored in these patients, and if increases occur, consideration should be given to changing to oral voriconazole therapy [see Clinical Pharmacology (12.3), Dosage and Administration (2.7)].
5.10 Monitoring of Renal Function
Acute renal failure has been observed in patients undergoing treatment with VFEND. Patients being treated with voriconazole are likely to be treated concomitantly with nephrotoxic medications and have concurrent conditions that may result in decreased renal function.
Patients should be monitored for the development of abnormal renal function. This should include laboratory eva luation, particularly serum creatinine.
5.11 Monitoring of Pancreatic Function
Patients with risk factors for acute pancreatitis (e.g., recent chemotherapy, hematopoietic stem cell transplantation [HSCT]) should be monitored for the development of pancreatitis during VFEND treatment.
5.12 Dermatological Reactions
Serious exfoliative cutaneous reactions, such as Stevens-Johnson syndrome, have been reported during treatment with VFEND. If a patient develops an exfoliative cutaneous reaction, VFEND should be discontinued.
In addition VFEND has been associated with |
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