Pharmacokinetics of isavuconazonium sulfate and its active metabolite isavuconazole in healthy dogs. Invasive fungal infections (IFIs) are growing in importance in veterinary and human medicine. IFIs such as aspergillosis, blastomycosis, coccidioidomycosis and histoplasmosis remain challenging to treat in dogs. Isavuconazole is a novel antifungal medication that, when compared to currently used was to evaluate the pharmacokinetics of isavuconazole in healthy dogs that received a single dose of the prodrug isavuconazonium sulfate. Using full crossover design, six healthy beagle dogs received isavuconazonium sulfate at a mean (+/- SD) dose of 20.6 (+/- 2.8) mg/kg orally and 21.8 (+/- 4.2) mg/kg intravenously. Plasma was collected for batched pharmacokinetic analysis of prodrug and metabolite
Pharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of Isavuconazonium Sulfate in Healthy Adult Japanese Subjects. Isavuconazonium sulfate is the water-soluble prodrug of the novel, broad-spectrum, triazole antifungal agent isavuconazole. This was a first-in-Japanese study assessing the pharmacokinetics, safety, and tolerability of isavuconazonium sulfate. The study no serious adverse events, and all reported treatment-emergent adverse events were of mild intensity. This study confirmed that isavuconazonium sulfate was safe and well tolerated in healthy adult Japanese subjects.
Enteral feeding tube administration with therapeutic drug monitoring of crushed posaconazole tablets and opened isavuconazonium sulfate capsules. Isavuconazole and posaconazole are commonly used for both prophylaxis and treatment of invasive fungal infections. These agents are formulated for oral administration as a capsule and delayed release (DR) tablet or suspension, respectively. In patients
Cresemba, capsule injection (isavuconazonium sulfate) - To treat adults with invasive aspergillosis and invasive mucormycosis, rare but serious infections Cresemba Capsules & Cresemba Powder for Injection * Skip to main page content * Skip to search * Skip to topics menu * Skip to common linksHHS U.S. Department of Health and Human Services U.S. Food and Drug Administration * Follow FDA * En
Isavuconazonium sulfate (BAL8557) (Cresemba) CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 207500Orig1s000 / 207501Orig1s000 MEDICAL REVIEW(S) Clinical Review Edward Weinstein, MD, PhD NDA 207500 and 207501, 505 (b)(1) Cresemba® (Isavuconazonium Sulfate) 1 CLINICAL REVIEW Application Type NDA 505 (b)(1) Application Number(s) 207500 and 207501 Priority or Standard Priority Submit Date(s) July 8, 2014 Received Date(s) July 8, 2014 PDUFA Goal Date March 8, 2015 Division / Office Division of Anti-Infective Products / Office of Antimicrobial Products Reviewer Name(s) Edward Weinstein, MD, PhD Elizabeth O’Shaughnessy, MD Review Completion Date December 8, 2014 Established Name Isavuconazonium sulfate (BAL8557) (Proposed) Trade Name Cresemba ® Therapeutic Class Azole
Pharmacokinetics and Bioequivalence of Isavuconazole Administered as Isavuconazonium Sulfate Intravenous Solution via Nasogastric Tube or Orally in Healthy Subjects. For critically ill patients with invasive fungal infections, a nasogastric (NG) tube can be an alternative route for administration of isavuconazonium sulfate (ISAVUSULF). This was a randomized, open-label, 2-period, 2-sequence
Achievement of clinical isavuconazole blood concentrations in transplant recipients with isavuconazonium sulphate capsules administered via enteral feeding tube. Isavuconazole is a triazole antifungal available in IV and capsule formulation. Prescribing information states that capsules should not be chewed, crushed, dissolved or opened because the drug was not studied in this manner. However , considering the pharmacokinetics of the capsules, we theorized opening and sprinkling the contents into an enteral feeding tube (EFT) would result in adequate absorption and systemic concentrations of isavuconazole. To determine whether patients receiving isavuconazonium sulphate capsules via EFT would achieve clinical blood concentrations of isavuconazole. Nineteen solid organ and HCT recipients receiving
Tissue Distribution and Elimination of Isavuconazole Following Single and Repeat Oral-Dose Administration of Isavuconazonium Sulfate to Rats. Quantitative whole-body autoradiography was used to assess the distribution and tissue penetration of isavuconazole in rats following single and repeated oral-dose administration of radiolabeled isavuconazonium sulfate, the prodrug of isavuconazole . Following a single-dose administration of radiolabeled isavuconazonium sulfate (labeled on the active moiety), radioactivity was detectable within 1 h postdose in 56 of 65 tissue/fluid specimens. The highest maximum concentrations () were observed in bile and liver (66.6 and 24.7 μg eq/g, respectively). The lowest values were in bone and eye lens (0.070 and 0.077 μg eq/g, respectively). By 144 h postdose
Two Phase 1, Openâ€Label, Mass Balance Studies to Determine the Pharmacokinetics of 14Câ€Labeled Isavuconazonium Sulfate in Healthy Male Volunteers Isavuconazonium sulfate is the water-soluble prodrug of the active triazole isavuconazole. Two phase 1 studies were conducted to identify the metabolic profile and mass balance of isavuconazole and BAL8728 (inactive cleavage product). Seven subjects in study 1 (isavuconazole mass balance) received a single oral dose of [cyano- C]isavuconazonium sulfate corresponding to 200 mg isavuconazole. Six subjects in study 2 (BAL8728 mass balance) received a single intravenous dose of [pyridinylmethyl- C]isavuconazonium sulfate corresponding to 75 mg BAL8728. Pharmacokinetic parameters of radioactivity in whole blood and plasma and of isavuconazole
Safety, outcomes, and pharmacokinetics of isavuconazole as a treatment for invasive fungal diseases in pediatric patients: a non-comparative phase 2 trial. Invasive aspergillosis (IA) and mucormycosis (IM) cause significant morbidity and mortality in immunocompromised and/or hospitalized patients. Isavuconazonium sulfate, a prodrug of the antifungal triazole isavuconazole, has been approved , and Belgium from 2019 to 2022. Patients received 10 mg/kg isavuconazonium sulfate daily (maximum 372 mg; equivalent to 5.4 mg/kg or 200 mg isavuconazole) for up to 84 (IA) or 180 days (IM). Outcomes included rates of all-cause case fatality, overall response, treatment-emergent adverse events (TEAEs), and pharmacokinetics. Of 31 patients enrolled, 61.3% were 1-<12 years old; 58.1% had underlying hematologic
area under the concentration time curve BAL4815 isavuconazole BAL8557 isavuconazonium sulfate (prodrug) BAL8728 Inactive cleavage product of isavuconazonium sulfate β-HCG urine or serum pregnancy test b.i.d. twice daily BLQ below the limit of quantification BMI body mass index BMT bone marrow transplant bpm beats per minute BRCP Breast cancer resistance protein BUN blood urea nitrogen BW body weight not submit a critical report addressing the possible similarity with authorised orphan medicinal products because there is no authorised orphan medicinal product for a condition related to the proposed indication. New active Substance status The applicant requested the active substance isavuconazole (as isavuconazonium sulfate) contained in the above medicinal product to be considered
A Study to Evaluate Isavuconazonium Sulfate for the Treatment of Invasive Aspergillosis (IA) or Invasive Mucormycosis (IM) in Pediatric Participants The purpose of this study is to evaluate the safety, tolerability, and efficacy of isavuconazonium sulfate in pediatric participants. Treatment will begin on Day 1 and then participants will be followed for 60 days post-last dose for safety . Treatment will be administered until the participant has a successful outcome or for a maximum duration of 84 days (IA) or 180 days (IM), whichever occurs first.Participants will receive a loading regimen of isavuconazonium sulfate (via intravenous or oral administration at the investigator's discretion), which consists of a dose every 8 hours (± 2 hours) on Days 1 and 2 (for a total of 6 doses), followed
A Study to Assess Isavuconazole Following a Single Dose of Isavuconazonium Sulfate Intravenous Solution Via Nasogastric (NG) Tube Compared to a Single Dose of Oral Capsules Under Fasting Conditions in Healthy Participants The purpose of this study is to evaluate the bioequivalence of isavuconazole following a single dose of isavuconazonium sulfate intravenous (IV) solution via nasogastric (NG ) tube (test formulation) compared to a single dose of isavuconazonium sulfate capsules for oral administration (i.e., oral capsules administered to nonintubated participants)(reference formulation). In addition, this study will evaluate the safety and tolerability of isavuconazole and the general pharmacokinetic (PK) parameters of isavuconazole when administered as a single dose of isavuconazonium
Pharmacodynamics of Isavuconazole in a Rabbit Model of Cryptococcal Meningoencephalitis. spp., important fungal pathogens, are the leading cause of fungus-related mortality in human immunodeficiency virus-infected patients, and new therapeutic options are desperately needed. Isavuconazonium sulfate, a newer triazole antifungal agent, was studied to characterize the exposure-response relationship in a rabbit model of cryptococcal meningoencephalitis. Rabbits treated with isavuconazonium sulfate were compared with those treated with fluconazole and untreated controls. The fungal burden in the cerebrospinal fluid was measured serially over time, while the yeast concentrations in the brain and the eye (aqueous humor) were determined at the end of therapy. The exposure impact
Tissue distribution and penetration of isavuconazole at the site of infection in Experimental Invasive Aspergillosis in Mice with underlying Chronic Granulomatous Disease. Isavuconazole, the active moiety of the prodrug isavuconazonium sulfate, has potent activity against a wide spectrum of fungal pathogens and is approved for the treatment of invasive aspergillosis, yet little is known about
No Dose Adjustment for Isavuconazole Based on Age or Sex. This phase 1, open-label, single-dose, parallel-group study evaluated the pharmacokinetics (PK) of isavuconazole after a single oral dose of the prodrug isavuconazonium sulfate in healthy nonelderly (age, 18 to 45 years) and elderly (age, ≥65 years) males and females. Overall, 48 subjects were enrolled in the study (=12 each in groups of nonelderly males and females and elderly males and females). All subjects received a single oral dose of 372 mg of isavuconazonium sulfate (equivalent to 200 mg isavuconazole). PK samples were collected for analysis of isavuconazole plasma concentrations from the predose time point up to 336 h postdose. Data were analyzed using population pharmacokinetic (PPK) analysis. The resulting PPK model included two
findings were consistent with fungal infection of the bladder. Isavuconazonium sulfate was used as systemic salvage therapy along with continuous bladder irrigation with amphotericin-B for localized bladder infection after a trial with first-line systemic treatment with intravenous liposomal amphotericin-B failed. A repeat endoscopy showed inflammatory changes with a pathology report in which