POSACONAZOLE injection, solution

מדינה: ארצות הברית

שפה: אנגלית

מקור: NLM (National Library of Medicine)

מרכיב פעיל:

Posaconazole (UNII: 6TK1G07BHZ) (Posaconazole - UNII:6TK1G07BHZ)

זמין מ:

Fresensius Kabi USA, LLC

מסלול נתינה (של תרופות):

INTRAVENOUS

סוג מרשם:

PRESCRIPTION DRUG

סממני תרפויטית:

Posaconazole injection is indicated for the treatment of invasive aspergillosis in adults and pediatric patients 13 years of age and older. Posaconazole is indicated for the prophylaxis of invasive Aspergillus and Candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus- host disease (GVHD) or those with hematologic malignancies with prolonged neutropenia from chemotherapy [see Clinical Studies (14.1)] as follows: - Posaconazole injection: adults and pediatric patients 2 years of age and older Posaconazole is contraindicated in persons with known hypersensitivity to posaconazole or other azole antifungal agents. Posaconazole is contraindicated with sirolimus. Concomitant administration of Posaconazole with sirolimus increases the sirolimus blood concentrations by approximately 9-fold and can result in sirolimus toxicity [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)] . Posaconazole is contraindicated with CYP3A4 substrates that prolong the QT interval. Concomitant administration of Posaconazole with the CYP3A4 substrates, pimozide and quinidine may result in increased plasma concentrations of these drugs, leading to QTc prolongation and cases of torsades de pointes [see Warnings and Precautions (5.2) and Drug Interactions (7.2)] . Coadministration with the HMG-CoA reductase inhibitors that are primarily metabolized through CYP3A4 (e.g., atorvastatin, lovastatin, and simvastatin) is contraindicated since increased plasma concentration of these drugs can lead to rhabdomyolysis [see Drug Interactions (7.3) and Clinical Pharmacology (12.3)] . Posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism [see Drug Interactions (7.4)] . Coadministration of Posaconzole 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 Warnings and Precautions (5.10) and Drug Interactions (7.16)]. Risk Summary Based on findings from animal data, Posaconazole may cause fetal harm when administered to pregnant women. Available data for use of Posaconazole in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, skeletal malformations (cranial malformations and missing ribs) and maternal toxicity (reduced food consumption and reduced body weight gain) were observed when posaconazole was dosed orally to pregnant rats during organogenesis at doses ≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of Posaconazole in healthy volunteers. In pregnant rabbits dosed orally during organogenesis, increased resorptions, reduced litter size, and reduced body weight gain of females were seen at doses 5 times the exposure achieved with the 400 mg twice daily oral suspension regimen. Doses of ≥ 3 times the clinical exposure caused an increase in resorptions in these rabbits (see Data) . Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Posaconazole resulted in maternal toxicity (reduced food consumption and reduced body weight gain) and skeletal malformations (cranial malformations and missing ribs) when given orally to pregnant rats during organogenesis (Gestational Days 6 through 15) at doses ≥27 mg/kg (≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of drug in healthy volunteers). The no-effect dose for malformations and maternal toxicity in rats was 9 mg/kg, which is 0.7 times the exposure achieved with the 400 mg twice daily oral suspension regimen. No malformations were seen in rabbits dosed during organogenesis (Gestational Days 7 through 19) at doses up to 80 mg/kg (5 times the exposure achieved with the 400 mg twice daily oral suspension regimen). In the rabbit, the no-effect dose was 20 mg/kg, while high doses of 40 mg/kg and 80 mg/kg (3 or 5 times the clinical exposure) caused an increase in resorptions. In rabbits dosed at 80 mg/kg, a reduction in body weight gain of females and a reduction in litter size were seen. Risk Summary There are no data on the presence of posaconazole in human milk, the effects on the breastfed infant, or the effects on milk production. Posaconazole is excreted in the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Posaconazole and any potential adverse effects on the breastfed child from Posaconazole or from the underlying maternal condition. The safety and effectiveness of Posaconazole injection for the prophylaxis of invasive Aspergillus and Candida infections have been established in pediatric patients aged 2 and older who are at high risk of developing these infections due to being severely immunocompromised, such as HSCT recipients with GVHD or those with hematologic malignancies with prolonged neutropenia from chemotherapy. The safety and effectiveness of Posaconazole injection for the treatment of invasive aspergillosis have been established in pediatric patients aged 13 years and older. Use of Posaconazole in these age groups is supported by evidence from adequate and well-controlled studies of Posaconazole in adult and pediatric patients and additional pharmacokinetic and safety data in pediatric patients 2 years of age and older [see Adverse Reactions (6.1), Clinical Pharmacology (12.3) and Clinical Studies (14)] . The safety and effectiveness of Posaconazole have not been established in pediatric patients younger than 2 years of age. No overall differences in the safety of Posaconazole injection were observed between geriatric patients and younger adult patients in the clinical trials; therefore, no dosage adjustment is recommended for any formulation of Posaconazole in geriatric patients. No clinically meaningful differences in the pharmacokinetics of Posaconazole were observed in geriatric patients compared to younger adult patients during clinical trials [see Clinical Pharmacology (12.3)] . Of the 279 patients treated with Posaconazole injection in the Posaconazole Injection Study, 52 (19%) were greater than 65 years of age. Of the 230 patients treated with Noxafil® delayed-release tablets , 38 (17%) were greater than 65 years of age. Of the 288 patients randomized to Posaconazole injection/ Noxafil® delayed-release tablets in the Aspergillosis Treatment Study, 85 (29%) were ≥65 years of age. No overall differences in the pharmacokinetics and safety were observed between elderly and young subjects during clinical trials, but greater sensitivity of some older individuals cannot be ruled out. Posaconazole Injection should be avoided in patients with moderate or severe renal impairment (eGFR <50 mL/min), unless an assessment of the benefit/risk to the patient justifies the use of Posaconazole injection. In patients with moderate or severe renal impairment (eGFR <50 mL/min), receiving the Posaconazole injection, accumulation of the intravenous vehicle, SBECD, is expected to occur. Serum creatinine levels should be closely monitored in these patients, and, if increases occur, consideration should be given to changing to oral Posaconazole therapy [see Dosage and Administration (2.9) and Warnings and Precautions (5.5)] . It is recommended that no dose adjustment of Posaconazole injection is needed in patients with mild to severe hepatic impairment (Child-Pugh Class A, B, or C) [see Dosage and Administration (2) and Warnings and Precautions (5.4)] . However, a specific study has not been conducted with Posaconazole injection. The pharmacokinetics of posaconazole are comparable in males and females. No adjustment in the dosage of Posaconazole is necessary based on gender. The pharmacokinetic profile of posaconazole is not significantly affected by race. No adjustment in the dosage of Posaconazole is necessary based on race. Pharmacokinetic modeling suggests that patients weighing greater than 120 kg may have lower posaconazole plasma drug exposure. It is, therefore, suggested to closely monitor for breakthrough fungal infections.

leaflet_short:

Injection Posaconazole Injection is available in Type I glass vials closed with chlorobutyl rubber stopper and aluminum seal. Posaconazole Injection Posaconazole injection vial should be stored refrigerated at 2° to 8°C (36° to 46°F). Storage conditions for the diluted solution are presented in another section of the prescribing information [see Dosage and Administration (2.4)] .

מצב אישור:

Abbreviated New Drug Application

מאפייני מוצר

POSACONAZOLE- POSACONAZOLE INJECTION, SOLUTION
FRESENSIUS KABI USA, LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
POSACONAZOLE
INJECTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
POSACONAZOLE
INJECTION.
POSACONAZOLE INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2006
RECENT MAJOR CHANGES
Indications and Usage (1)
6/2021
Dosage and Administration (2)
6/2021
Contraindications (4)
1/2022
Warnings and Precautions (5)
1/2022
INDICATIONS AND USAGE
Posaconazole is an azole antifungal indicated as follows:
POSACONAZOLE INJECTION IS indicated for the treatment of invasive
aspergillosis in adults and pediatric
patients 13 years of age and older. (1.1)
POSACONAZOLE is indicated for the prophylaxis of invasive
_Aspergillus_ and _Candida_ infections in
patients who are at high risk of developing these infections due to
being severely
immunocompromised, such as hematopoietic stem cell transplant (HSCT)
recipients with graft-versus-
host disease (GVHD) or those with hematologic malignancies with
prolonged neutropenia from
chemotherapy as follows: (1.2)
POSACONAZOLE INJECTION: adults and pediatric patients 2 years of age
and older
DOSAGE AND ADMINISTRATION
POSACONAZOLE INJECTION must be administered through an in-line filter.
Administer POSACONAZOLE INJECTION by intravenous infusion over
approximately 90 minutes via a
central venous line. (2.1)
Do NOT administer POSACONAZOLE INJECTION as intravenous bolus
injection. (2.1)
TABLE 1: RECOMMENDED DOSAGE IN ADULT PATIENTS
INDICATION
DOSAGE FORM, DOSE, AND DURATION OF THERAPY
Treatment of invasive
Aspergillosis
POSACONAZOLE INJECTION:
Loading dose:
300 mg Posaconazole injection intravenously twice a day on the first
day.
Maintenance dose:
300 mg Posaconazole injection intravenously once a day thereafter.
Recommended total duration of therapy is 6 to 12 weeks. (2.2)
Prophylaxis of
POSACONAZOLE INJECTION:
invasive
Loading dose: 300 mg Posaconazole injection
_Aspergillus_ and
intravenously