VORICONAZOLE tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

VORICONAZOLE (UNII: JFU09I87TR) (VORICONAZOLE - UNII:JFU09I87TR)

Available from:

Zydus Lifesciences Limited

INN (International Name):

VORICONAZOLE

Composition:

VORICONAZOLE 50 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Voriconazole tablets are indicated in adults and pediatric patients (2 years of age and older) for the treatment of invasive aspergillosis (IA). 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, 14.5) and Microbiology (12.4)].   Voriconazole tablets are indicated in adults and pediatric patients (2 years of age and older) for the treatment of candidemia in non-neutropenic patients and the following Candida infections: disseminated infections in skin and infections in abdomen, kidney, bladder wall, and wounds [see Clinical Studies (14.2, 14.5) and Microbiology (12.4)]. Voriconazole tablets are indicated in adults and pediatric patients (2 years of age and older) for the treatment of esophageal candidiasis (EC) in adults and pediatric patients 2 years of age and older [see Clinical Studies (14.3, 14.5) and Microbiology (12.4)]. Voriconazole tablets are indicated for the treatment of serious fungal infections caused by Scedosporium apiospermum (asexual form of Pseudallescheria boydii ) and Fusarium spp. including Fusarium solani , in adults and pediatric patients 2 years of age and older intolerant of, or refractory to, other therapy [see Clinical Studies (14.4) and 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. - Voriconazole tablets are contraindicated in patients with known hypersensitivity to voriconazole or its excipients. There is no information regarding cross-sensitivity between voriconazole and other azole antifungal agents. Caution should be used when prescribing voriconazole to patients with hypersensitivity to other azoles. - Coadministration of pimozide , quinidine or ivabradine with voriconazole 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) ]. - Coadministration of voriconazole with sirolimus is contraindicated because voriconazole significantly increases sirolimus concentrations [see Drug Interactions (7) and Clinical Pharmacology (12.3) ]. - Coadministration of voriconazole with rifampin, carbamazepine, long-acting barbiturates, and St John's Wort is contraindicated because these drugs are likely to decrease plasma voriconazole concentrations significantly [see Drug Interactions (7) and Clinical Pharmacology (12.3) ]. - Coadministration of standard doses of voriconazole with efavirenz doses of 400 mg every 24 hours or higher is contraindicated, because efavirenz significantly decreases plasma voriconazole concentrations in healthy subjects at these doses. Voriconazole also significantly increases efavirenz plasma concentrations [see Drug Interactions (7) and Clinical Pharmacology (12.3) ]. - Coadministration of voriconazole with high-dose ritonavir (400 mg every 12 hours) is contraindicated because ritonavir (400 mg every 12 hours) significantly decreases plasma voriconazole concentrations. Coadministration of voriconazole and low-dose ritonavir (100 mg every 12 hours) should be avoided, unless an assessment of the benefit/risk to the patient justifies the use of voriconazole [see Drug Interactions (7) and Clinical Pharmacology (12.3) ]. - Coadministration of voriconazole with rifabutin is contraindicated since voriconazole significantly increases rifabutin plasma concentrations and rifabutin also significantly decreases voriconazole plasma concentrations [see Drug Interactions (7) and Clinical Pharmacology (12.3) ]. - Coadministration of voriconazole with ergot alkaloids (ergotamine and dihydroergotamine) is contraindicated because voriconazole may increase the plasma concentration of ergot alkaloids, which may lead to ergotism [see Drug Interactions (7) ]. - Coadministration of voriconazole with naloxegol is contraindicated because voriconazole may increase plasma concentrations of naloxegol which may precipitate opioid withdrawal symptoms [see Drug Interactions (7)] . - Coadministration of voricoazole with tolvaptan is contraindicated because voriconazole may increase tolvaptan plasma concentrations and increase risk of adverse reactions [see Drug Interactions (7) ]. - Coadministration of voriconazole with venetoclax at initiation and during the ramp-up phase is contraindicated in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) due to the potential for increased risk of tumor lysis syndrome [see Drug Interactions(7) ]. - Coadministration of voriconazole with lurasidone is contraindicated since it may result in significant increases in lurasidone exposure and the potential for serious adverse reactions [see Drug Interactions(7) ]. Risk Summary Voriconazole can cause fetal harm when administered to a pregnant woman. There are no available data on the use of voriconazole in pregnant women. In animal reproduction studies, oral voriconazole was associated with fetal malformations in rats and fetal toxicity in rabbits. Cleft palates and hydronephrosis/hydroureter were observed in rat pups exposed to voriconazole during organogenesis at and above 10 mg/kg (0.3 times the RMD of 200 mg every 12 hours based on body surface area comparisons). In rabbits, embryomortality, reduced fetal weight and increased incidence of skeletal variations, cervical ribs and extrasternal ossification sites were observed in pups when pregnant rabbits were orally dosed at 100 mg/kg (6 times the RMD based on body surface area comparisons) during organogenesis. Rats exposed to voriconazole from implantation to weaning experienced increased gestational length and dystocia, which were associated with increased perinatal pup mortality at the 10 mg/kg dose [see Data]. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, inform the patient of the potential hazard to the fetus [see Warnings and Precautions (5.9)]. The background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20% respectively. Data Animal Data Voriconazole was administered orally to pregnant rats during organogenesis (gestation days 6-17) at 10, 30, and 60 mg/kg/day. Voriconazole was associated with increased incidences of the malformations hydroureter and hydronephrosis at 10 mg/kg/day or greater, approximately 0.3 times the recommended human dose (RMD) based on body surface area comparisons, and cleft palate at 60 mg/kg, approximately 2 times the RMD based body surface area comparisons. Reduced ossification of sacral and caudal vertebrae, skull, pubic, and hyoid bone, supernumerary ribs, anomalies of the sternebrae, and dilatation of the ureter/renal pelvis were also observed at doses of 10 mg/kg or greater. There was no evidence of maternal toxicity at any dose. Voriconazole was administered orally to pregnant rabbits during the period of organogenesis (gestation days 7-19) at 10, 40, and 100 mg/kg/day. Voriconazole was associated with increased post-implantation loss and decreased fetal body weight, in association with maternal toxicity (decreased body weight gain and food consumption) at 100 mg/kg/day (6 times the RMD based on body surface area comparisons). Fetal skeletal variations (increases in the incidence of cervical rib and extra sternebral ossification sites) were observed at 100 mg/kg/day. In a peri-and postnatal toxicity study in rats, voriconazole was administered orally to female rats from implantation through the end of lactation at 1, 3, and 10 mg/kg/day. Voriconazole prolonged the duration of gestation and labor and produced dystocia with related increases in maternal mortality and decreases in perinatal survival of F1 pups at 10 mg/kg/day, approximately 0.3 times the RMD. Risk Summary No data are available regarding the presence of voriconazole in human milk, the effects of voriconazole on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for voriconazole and any potential adverse effects on the breastfed child from voriconazole or from the underlying maternal condition. Contraception Advise females of reproductive potential to use effective contraception during treatment with voriconazole. The coadministration of voriconazole with the oral contraceptive, Ortho-Novum® (35 mcg ethinyl estradiol and 1 mg norethindrone), results in an interaction between these two drugs, but is unlikely to reduce the contraceptive effect. Monitoring for adverse reactions associated with oral contraceptives and voriconazole is recommended [see Drug Interactions (7) and Clinical Pharmacology (12.3)]. The safety and effectiveness of voriconazole have been established in pediatric patients 2 years of age and older based on evidence from adequate and well-controlled studies in adult and pediatric patients and additional pediatric pharmacokinetic and safety data. A total of 105 pediatric patients aged 2 to less than 12 [N=26] and aged 12 to less than 18 [N=79] from two, non-comparative Phase 3 pediatric studies and eight adult therapeutic trials provided safety information for voriconazole use in the pediatric population [see Adverse  Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14)] . Safety and effectiveness in pediatric patients below the age of 2 years has not been established. Therefore, voriconazole is not recommended for pediatric patients less than 2 years of age. A higher frequency of liver enzyme elevations was observed in the pediatric patients [see Dosage and Administration (2.5), Warnings  and Precautions (5.1), and Adverse Reactions (6.1)] . The frequency of phototoxicity reactions is higher in the pediatric population. Squamous cell carcinoma has been reported in patients who experience photosensitivity reactions. Stringent measures for photoprotection are warranted. Sun avoidance and dermatologic follow-up are recommended in pediatric patients experiencing photoaging injuries, such as lentigines or ephelides, even after treatment discontinuation [see Warnings and Precautions (5.6)]. Voriconazole has not been studied in pediatric patients with hepatic or renal impairment [see Dosage and Administration (2.5, 2.6)] . Hepatic function and serum creatinine levels should be closely monitored in pediatric patients [see Dosage and Administration (2.6) and Warnings and Precautions (5.1, 5.10)] . In multiple dose therapeutic trials of voriconazole, 9.2% of patients were ≥65 years of age and 1.8% of patients were ≥75 years of age. In a study in healthy subjects, the systemic exposure (AUC) and peak plasma concentrations (Cmax ) were increased in elderly males compared to young males. Pharmacokinetic data obtained from 552 patients from 10 voriconazole therapeutic trials showed that voriconazole plasma concentrations in the elderly patients were approximately 80% to 90% higher than those in younger patients after either IV or oral administration. However, the overall safety profile of the elderly patients was similar to that of the young so no dosage adjustment is recommended [see Clinical Pharmacology (12.3) ].

Product summary:

Voriconazole Tablets, 50 mg are white to off-white, round, biconvex, film-coated tablet debossed with "735" on one side and plain on the other side and are supplied as follows: NDC 65841-830-06 in bottles of 30 tablets with child-resistant closure NDC 65841-830-16 in bottles of 90 tablets with child-resistant closure NDC 65841-830-01 in bottles of 100 tablets with child-resistant closure NDC 65841-830-05 in bottles of 500 tablets NDC 65841-830-10 in bottles of 1000 tablets NDC 65841-830-77 in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets Voriconazole Tablets, 200 mg are white to off-white, oval, biconvex, film-coated tablet debossed with "736" on one side and plain on the other side and are supplied as follows: NDC 65841-831-06 in bottles of 30 tablets with child-resistant closure NDC 65841-831-16 in bottles of 90 tablets with child-resistant closure NDC 65841-831-01 in bottles of 100 tablets with child-resistant closure NDC 65841-831-05 in bottles of 500 tablets NDC 65841-831-10 in bottles of 1000 tablets NDC 65841-831-77 in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Dispense in a tight container (USP).

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

VORICONAZOLE- VORICONAZOLE TABLET
Cadila Healthcare Limited
----------
FDA-APPROVED PATIENT LABELING
Voriconazole (vor i KON a zole) Tablets
Read the Patient Information that comes with Voriconazole Tablets
before you start taking it and each time
you get a refill. There may be new information. This information does
not take the place of talking with your
healthcare provider about your condition or treatment.
What are Voriconazole Tablets?
Voriconazole Tablets are a prescription medicine used to treat certain
serious fungal infections in your blood
and body. These infections are called "aspergillosis," "esophageal
candidiasis," "Scedosporium," "Fusarium,"
and "candidemia".
It is not known if voriconazole tablets are safe and effective in
children younger than 2 years old.
Do not take Voriconazole Tablets if you:
•
are allergic to voriconazole or any of the ingredients in Voriconazole
Tablets . See the end of this
leaflet for a complete list of ingredients in Voriconazole Tablets.
•
are taking any of the following medicines:
•
cisapride
•
pimozide
•
quinidine
•
sirolimus
•
rifampin
•
carbamazepine
•
long-acting barbiturates like phenobarbital
•
efavirenz
•
ritonavir
•
rifabutin
•
ergotamine, dihydroergotamine (ergot alkaloids)
•
St. John's Wort (herbal supplement)
Ask your healthcare provider or pharmacist if you are not sure if you
are taking any of the medicines listed
above.
Do not start taking a new medicine without talking to your healthcare
provider or pharmacist.
Before you take voriconazole , tell your healthcare provider about all
of your medical conditions, including if
you:
•
have or ever had heart disease, or an abnormal heart rate or rhythm.
Your healthcare provider may
order a test to check your heart (EKG) before starting Voriconazole
Tablets.
•
have liver or kidney problems. Your healthcare provider may do blood
tests to make sure you can
take Voriconazole Tablets.
•
have trouble digesting dairy products, lactose (milk sugar), or
regular table sugar. Voriconazole
T

Summary of Product characteristics

VORICONAZOLE- VORICONAZOLE TABLET
ZYDUS LIFESCIENCES LIMITED
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
VORICONAZOLE TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
VORICONAZOLE TABLETS.
VORICONAZOLE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2002
RECENT MAJOR CHANGES
Warnings and Precautions, Photosensitivity (5.6)
10/2022
INDICATIONS AND USAGE
Voriconazole is an azole antifungal indicated for the treatment of
adults and pediatric patients aged 2
years of age and older with:
Invasive aspergillosis (1.1)
Candidemia in non-neutropenics and other deep tissue _Candida_
infections (1.2)
Esophageal candidiasis (1.3)
Serious fungal infections caused by _Scedosporium apiospermum _and
_Fusarium _species including
_Fusarium solani_ , in patients intolerant of, or refractory to, other
therapy (1.4)
DOSAGE AND ADMINISTRATION
DOSAGE IN ADULTS (2.3)
INFECTION
LOADING DOSE
MAINTENANCE DOSE
INTRAVENOUS
INFUSION
INTRAVENOUS
INFUSION
ORAL
INVASIVE ASPERGILLOSIS
6 mg/kg every 12 hours
for the first 24 hours
4 mg/kg every 12 hours
200 mg every
12 hours
CANDIDEMIA IN NONNEUTROPENICS
AND OTHER DEEP TISSUE _CANDIDA_
INFECTIONS
3 to 4 mg/kg every 12
hours
200 mg every
12 hours
SCEDOSPORIOSIS AND FUSARIOSIS
4 mg/kg every 12 hours
200 mg every
12 hours
ESOPHAGEAL CANDIDIASIS
Not Evaluated
Not Evaluated
200 mg every
12 hours
Adult patients weighing less than 40 kg: oral maintenance dose 100 or
150 mg every 12 hours
_Hepatic Impairment:_ Use half the maintenance dose in adult patients
with mild to moderate hepatic
impairment (Child-Pugh Class A and B) (2.5)
_Renal Impairment:_ Avoid intravenous administration in adult patients
with moderate to severe renal
impairment (creatinine clearance <50 mL/min) (2.6)
DOSAGE IN PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER (2.4)
For pediatric patients 2 to less than 12 years of age and 12 to 14
years of age weighing less than 50 kg
see Table below.
INFECTION
LOADING DOSE
MAINTENANCE DOSE
INTRAVENOUS
INFUSION
I