Vfend I.V.

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of voriconazole injection in the elderly.

In the U.S.

• Vfend I.V.

Available Dosage Forms:

• Powder for Solution

Therapeutic Class: Antifungal

Chemical Class: Triazole

Voriconazole injection is used to treat certain serious fungal or yeast infections, such as aspergillosis (fungal infection in the lungs), candidemia (fungal infection in the blood), esophageal candidiasis (candida esophagitis), or other fungal infections (including infections in the skin, stomach, kidney, bladder, and wounds). It may also be used to treat patients with serious fungal or yeast infections who cannot tolerate other types of medicine or who do not respond to other types of medicine.

This medicine is to be given only by or under the direct supervision of your doctor.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of voriconazole injection in children younger than 12 years of age. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of voriconazole injection in the elderly.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Amisulpride
• Astemizole
• Bepridil
• Carbamazepine
• Cisapride
• Conivaptan
• Dihydroergotamine
• Dronedarone
• Efavirenz
• Eletriptan
• Eliglustat
• Eplerenone
• Ergoloid Mesylates
• Ergonovine
• Ergotamine
• Flibanserin
• Fluconazole
• Isavuconazonium Sulfate
• Ivabradine
• Lomitapide
• Lovastatin
• Lurasidone
• Maraviroc
• Mephobarbital
• Mesoridazine
• Methylergonovine
• Methysergide
• Naloxegol
• Nelfinavir
• Nimodipine
• Phenobarbital
• Pimozide
• Piperaquine
• Posaconazole
• Primidone
• Quinidine
• Rifabutin
• Rifampin
• Ritonavir
• Saquinavir
• Simvastatin
• Sirolimus
• Sparfloxacin
• St John's Wort
• Terfenadine
• Thioridazine
• Tolvaptan
• Venetoclax
• Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acenocoumarol
• Ado-Trastuzumab Emtansine
• Alprazolam
• Amiodarone
• Amitriptyline
• Amoxapine
• Anagrelide
• Apomorphine
• Aprepitant
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Artemether
• Asenapine
• Avanafil
• Axitinib
• Azithromycin
• Bedaquiline
• Boceprevir
• Bosutinib
• Brentuximab Vedotin
• Bretylium
• Brexpiprazole
• Brigatinib
• Bromocriptine
• Buserelin
• Cabazitaxel
• Cabozantinib
• Calcifediol
• Cariprazine
• Ceritinib
• Chloramphenicol
• Chloroquine
• Chlorpromazine
• Cilostazol
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clomipramine
• Clozapine
• Cobicistat
• Cobimetinib
• Crizotinib
• Cyclobenzaprine
• Cyclosporine
• Dabrafenib
• Daclatasvir
• Dasabuvir
• Dasatinib
• Deflazacort
• Degarelix
• Delamanid
• Delavirdine
• Desipramine
• Deslorelin
• Deutetrabenazine
• Dicumarol
• Disopyramide
• Docetaxel
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Droperidol
• Elvitegravir
• Entacapone
• Enzalutamide
• Erlotinib
• Erythromycin
• Escitalopram
• Eslicarbazepine Acetate
• Eszopiclone
• Everolimus
• Fentanyl
• Fingolimod
• Flecainide
• Fluoxetine
• Fluticasone
• Fosaprepitant
• Foscarnet
• Fosphenytoin
• Gatifloxacin
• Gemifloxacin
• Glimepiride
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Histrelin
• Hydrocodone
• Hydroxychloroquine
• Hydroxyzine
• Ibrutinib
• Ibutilide
• Idelalisib
• Ifosfamide
• Iloperidone
• Imipramine
• Irinotecan
• Irinotecan Liposome
• Ivacaftor
• Ixabepilone
• Ketoconazole
• Lansoprazole
• Lapatinib
• Leuprolide
• Levofloxacin
• Levomilnacipran
• Lopinavir
• Lumacaftor
• Lumefantrine
• Macitentan
• Manidipine
• Mefloquine
• Methadone
• Metronidazole
• Midostaurin
• Mifepristone
• Moxifloxacin
• Nafarelin
• Nevirapine
• Nifedipine
• Nilotinib
• Norfloxacin
• Nortriptyline
• Octreotide
• Ofloxacin
• Olaparib
• Ombitasvir
• Omeprazole
• Ondansetron
• Palbociclib
• Paliperidone
• Panobinostat
• Paritaprevir
• Pasireotide
• Pazopanib
• Phenprocoumon
• Phenytoin
• Pimavanserin
• Pitolisant
• Ponatinib
• Procainamide
• Prochlorperazine
• Promethazine
• Propafenone
• Protriptyline
• Quetiapine
• Quinine
• Ranolazine
• Reboxetine
• Regorafenib
• Retapamulin
• Ribociclib
• Romidepsin
• Ruxolitinib
• Salmeterol
• Sevoflurane
• Sildenafil
• Simeprevir
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sonidegib
• Sorafenib
• Sotalol
• Sulpiride
• Sunitinib
• Suvorexant
• Tacrolimus
• Tamsulosin
• Telaprevir
• Telavancin
• Telithromycin
• Temsirolimus
• Tetrabenazine
• Thiotepa
• Ticagrelor
• Tizanidine
• Toremifene
• Trabectedin
• Trazodone
• Triazolam
• Trifluoperazine
• Trimipramine
• Triptorelin
• Valbenazine
• Vandetanib
• Vardenafil
• Vemurafenib
• Vilanterol
• Vilazodone
• Vinblastine
• Vincristine
• Vincristine Sulfate Liposome
• Vinflunine
• Vinorelbine
• Vorapaxar
• Warfarin
• Zolpidem
• Zuclopenthixol

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alfentanil
• Amprenavir
• Atorvastatin
• Cerivastatin
• Desogestrel
• Dienogest
• Drospirenone
• Esomeprazole
• Estradiol Cypionate
• Estradiol Valerate
• Ethinyl Estradiol
• Ethynodiol Diacetate
• Etonogestrel
• Etravirine
• Fosamprenavir
• Glipizide
• Glyburide
• Levonorgestrel
• Meloxicam
• Mestranol
• Midazolam
• Norelgestromin
• Norethindrone
• Norgestimate
• Norgestrel
• Oxycodone
• Tolbutamide
• Tretinoin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Cancer treatment (eg, chemotherapy), recent or history of or
• Electrolyte imbalance (eg, low potassium, magnesium, calcium) or
• Heart disease, history of or
• Stem cell transplant—Use with caution. These conditions may increase your risk of having serious side effects.

• Heart rhythm problems (eg, arrhythmia, QT prolongation) or
• Liver disease (including cirrhosis) or
• Kidney disease or
• Pancreas problems—Use with caution. May make these conditions worse.

• Hypocalcemia (low calcium in the blood), uncorrected or
• Hypokalemia (low potassium in the blood), uncorrected or
• Hypomagnesemia (low magnesium in the blood)—Use with caution. These should be corrected first before starting treatment and during treatment with voriconazole.

Loading Dose: 6 mg/kg IV every 12 hours for 2 doses

Maintenance Dose:
IV:
Invasive aspergillosis and serious fungal infections due to Fusarium species and Scedosporium apiospermum: 4 mg/kg IV every 12 hours

Comments:
-Therapy should start with the IV loading dose on Day 1 followed by the maintenance dose.
-IV therapy should continue for at least 7 days.
-Once the patient has clinically improved and can tolerate oral medication, oral voriconazole may be used.

Candidemia in nonneutropenic patients and other deep tissue Candida infections: 3 to 4 mg/kg IV every 12 hours

Comments:
-In clinical trials, candidemia was treated using 3 mg/kg IV every 12 hours as primary therapy, while other deep tissue Candida infections were treated using 4 mg/kg IV every 12 hours as salvage therapy; appropriate dose should be based on the nature and severity of the infection.

Oral:
Less than 40 kg: 100 mg orally every 12 hours
40 kg or more: 200 mg orally every 12 hours

Duration of Therapy:
-Invasive aspergillosis: In a clinical trial, the median duration of IV therapy was 10 days (range 2 to 85 days) and of oral therapy was 76 days (range 2 to 232 days).
-Infectious Diseases Society of America (IDSA) guidelines for invasive aspergillosis: At least 6 to 12 weeks; in immunosuppressed patients, throughout immunosuppression and until lesions resolve
-Candidemia in nonneutropenic patients and other deep tissue Candida infections: At least 14 days after symptoms resolve or after last positive culture, whichever is longer

Uses: Invasive aspergillosis; candidemia in nonneutropenic patients; disseminated Candida infections in skin; Candida infections in abdomen, kidney, bladder wall, wounds; serious fungal infections due to Fusarium species and S apiospermum in patients intolerant of (or refractory to) other therapy

IDSA guidelines for empirical and preemptive therapy:
-IV: 6 mg/kg IV every 12 hours for 2 doses, then 3 mg/kg IV every 12 hours
-Oral: 200 mg orally every 12 hours

Loading Dose: 6 mg/kg IV every 12 hours for 2 doses

Maintenance Dose:
IV:
Invasive aspergillosis and serious fungal infections due to Fusarium species and Scedosporium apiospermum: 4 mg/kg IV every 12 hours

Comments:
-Therapy should start with the IV loading dose on Day 1 followed by the maintenance dose.
-IV therapy should continue for at least 7 days.
-Once the patient has clinically improved and can tolerate oral medication, oral voriconazole may be used.

Candidemia in nonneutropenic patients and other deep tissue Candida infections: 3 to 4 mg/kg IV every 12 hours

Comments:
-In clinical trials, candidemia was treated using 3 mg/kg IV every 12 hours as primary therapy, while other deep tissue Candida infections were treated using 4 mg/kg IV every 12 hours as salvage therapy; appropriate dose should be based on the nature and severity of the infection.

Oral:
Less than 40 kg: 100 mg orally every 12 hours
40 kg or more: 200 mg orally every 12 hours

Duration of Therapy:
-Invasive aspergillosis: In a clinical trial, the median duration of IV therapy was 10 days (range 2 to 85 days) and of oral therapy was 76 days (range 2 to 232 days).
-Infectious Diseases Society of America (IDSA) guidelines for invasive aspergillosis: At least 6 to 12 weeks; in immunosuppressed patients, throughout immunosuppression and until lesions resolve
-Candidemia in nonneutropenic patients and other deep tissue Candida infections: At least 14 days after symptoms resolve or after last positive culture, whichever is longer

Uses: Invasive aspergillosis; candidemia in nonneutropenic patients; disseminated Candida infections in skin; Candida infections in abdomen, kidney, bladder wall, wounds; serious fungal infections due to Fusarium species and S apiospermum in patients intolerant of (or refractory to) other therapy

IDSA guidelines for empirical and preemptive therapy:
-IV: 6 mg/kg IV every 12 hours for 2 doses, then 3 mg/kg IV every 12 hours
-Oral: 200 mg orally every 12 hours

2 to 11 years:
American Academy of Pediatrics recommendations: 9 mg/kg IV or orally every 12 hours
Maximum dose: 350 mg/dose

IDSA guidelines for invasive aspergillosis: 5 to 7 mg/kg IV every 12 hours

12 years or older:
Loading Dose: 6 mg/kg IV every 12 hours for 2 doses

Maintenance Dose:
IV:
Invasive aspergillosis and serious fungal infections due to Fusarium species and S apiospermum: 4 mg/kg IV every 12 hours

Comments:
-Therapy should start with the IV loading dose on Day 1 followed by the maintenance dose.
-IV therapy should continue for at least 7 days.
-Once the patient has clinically improved and can tolerate oral medication, oral voriconazole may be used.

Candidemia in nonneutropenic patients and other deep tissue Candida infections: 3 to 4 mg/kg IV every 12 hours

Comments:
-In clinical trials, candidemia was treated using 3 mg/kg IV every 12 hours as primary therapy, while other deep tissue Candida infections were treated using 4 mg/kg IV every 12 hours as salvage therapy; appropriate dose should be based on the nature and severity of the infection.

Oral:
Less than 40 kg: 100 mg orally every 12 hours
40 kg or more: 200 mg orally every 12 hours

Duration of Therapy:
-Invasive aspergillosis: In a clinical trial, the median duration of IV therapy was 10 days (range 2 to 85 days) and of oral therapy was 76 days (range 2 to 232 days).
-IDSA guidelines for invasive aspergillosis: At least 6 to 12 weeks; in immunosuppressed patients, throughout immunosuppression and until lesions resolve
-Candidemia in nonneutropenic patients and other deep tissue Candida infections: At least 14 days after symptoms resolve or after last positive culture, whichever is longer

Uses: Invasive aspergillosis; candidemia in nonneutropenic patients; disseminated Candida infections in skin; Candida infections in abdomen, kidney, bladder wall, wounds; serious fungal infections due to Fusarium species and S apiospermum in patients intolerant of (or refractory to) other therapy

2 to 11 years:
American Academy of Pediatrics recommendations: 9 mg/kg IV or orally every 12 hours
Maximum dose: 350 mg/dose

IDSA guidelines for invasive aspergillosis: 5 to 7 mg/kg IV every 12 hours

12 years or older:
Loading Dose: 6 mg/kg IV every 12 hours for 2 doses

Maintenance Dose:
IV:
Invasive aspergillosis and serious fungal infections due to Fusarium species and S apiospermum: 4 mg/kg IV every 12 hours

Comments:
-Therapy should start with the IV loading dose on Day 1 followed by the maintenance dose.
-IV therapy should continue for at least 7 days.
-Once the patient has clinically improved and can tolerate oral medication, oral voriconazole may be used.

Candidemia in nonneutropenic patients and other deep tissue Candida infections: 3 to 4 mg/kg IV every 12 hours

Comments:
-In clinical trials, candidemia was treated using 3 mg/kg IV every 12 hours as primary therapy, while other deep tissue Candida infections were treated using 4 mg/kg IV every 12 hours as salvage therapy; appropriate dose should be based on the nature and severity of the infection.

Oral:
Less than 40 kg: 100 mg orally every 12 hours
40 kg or more: 200 mg orally every 12 hours

Duration of Therapy:
-Invasive aspergillosis: In a clinical trial, the median duration of IV therapy was 10 days (range 2 to 85 days) and of oral therapy was 76 days (range 2 to 232 days).
-IDSA guidelines for invasive aspergillosis: At least 6 to 12 weeks; in immunosuppressed patients, throughout immunosuppression and until lesions resolve
-Candidemia in nonneutropenic patients and other deep tissue Candida infections: At least 14 days after symptoms resolve or after last positive culture, whichever is longer

Uses: Invasive aspergillosis; candidemia in nonneutropenic patients; disseminated Candida infections in skin; Candida infections in abdomen, kidney, bladder wall, wounds; serious fungal infections due to Fusarium species and S apiospermum in patients intolerant of (or refractory to) other therapy

2 to 11 years:
American Academy of Pediatrics recommendations: 9 mg/kg IV or orally every 12 hours
Maximum dose: 350 mg/dose

IDSA guidelines for invasive aspergillosis: 5 to 7 mg/kg IV every 12 hours

12 years or older:
Loading Dose: 6 mg/kg IV every 12 hours for 2 doses

Maintenance Dose:
IV:
Invasive aspergillosis and serious fungal infections due to Fusarium species and S apiospermum: 4 mg/kg IV every 12 hours

Comments:
-Therapy should start with the IV loading dose on Day 1 followed by the maintenance dose.
-IV therapy should continue for at least 7 days.
-Once the patient has clinically improved and can tolerate oral medication, oral voriconazole may be used.

Candidemia in nonneutropenic patients and other deep tissue Candida infections: 3 to 4 mg/kg IV every 12 hours

Comments:
-In clinical trials, candidemia was treated using 3 mg/kg IV every 12 hours as primary therapy, while other deep tissue Candida infections were treated using 4 mg/kg IV every 12 hours as salvage therapy; appropriate dose should be based on the nature and severity of the infection.

Oral:
Less than 40 kg: 100 mg orally every 12 hours
40 kg or more: 200 mg orally every 12 hours

Duration of Therapy:
-Invasive aspergillosis: In a clinical trial, the median duration of IV therapy was 10 days (range 2 to 85 days) and of oral therapy was 76 days (range 2 to 232 days).
-IDSA guidelines for invasive aspergillosis: At least 6 to 12 weeks; in immunosuppressed patients, throughout immunosuppression and until lesions resolve
-Candidemia in nonneutropenic patients and other deep tissue Candida infections: At least 14 days after symptoms resolve or after last positive culture, whichever is longer

Uses: Invasive aspergillosis; candidemia in nonneutropenic patients; disseminated Candida infections in skin; Candida infections in abdomen, kidney, bladder wall, wounds; serious fungal infections due to Fusarium species and S apiospermum in patients intolerant of (or refractory to) other therapy

VFEND is indicated for use in the treatment of the following fungal infections:

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 , MICROBIOLOGY ).

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 , MICROBIOLOGY ).

Esophageal candidiasis (see CLINICAL STUDIES , MICROBIOLOGY ).

Serious 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 , MICROBIOLOGY ).

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.