Fosdenopterin Hydrobromide
FDA Drug Information • Also known as: Nulibry
- Brand Names
- Nulibry
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION NULIBRY (fosdenopterin) for injection is cyclic pyranopterin monophosphate (cPMP). Fosdenopterin is present as a dihydrate of the hydrobromide salt with the chemical name (4a R ,5a R ,11a R ,12a S )-8-amino-4a,5a,6,9,11,11a,12,12a-octahydro-2,12,12-trihydroxy-1,3,2-dioxaphosphorino[4',5':5,6]pyrano[3,2- g ]pteridin-10(4 H )-one 2-oxide. Fosdenopterin hydrobromide as a dihydrate is a crystalline solid. The molecular formula is C 10 H 14 N 5 O 8 P
What Is Fosdenopterin Hydrobromide Used For?
1 INDICATIONS AND USAGE NULIBRY is indicated to reduce the risk of mortality in patients with molybdenum cofactor deficiency (MoCD) Type A. NULIBRY is cyclic pyranopterin monophosphate (cPMP) indicated to reduce the risk of mortality in patients with molybdenum cofactor deficiency (MoCD) Type A. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Start NULIBRY if known or presumed MoCD Type A. Promptly discontinue if MoCD Type A is not confirmed by genetic testing. ( 2.1 ) Reconstitute before use and complete infusion within 4 hours of reconstitution. ( 2.2 , 2.4 ) Administer as an intravenous infusion once daily at a rate of 1.5 mL/minute with non-DEHP tubing with a 0.2 micron filter. Volumes below 2 mL may require syringe administration through slow intravenous push. ( 2.2 ) See Full Prescribing Information for additional important preparation instructions and administration instructions. ( 2.2 ) See the table below for the recommended dosage in patients less than one year of age. ( 2.3 ) Titration Schedule Preterm Neonates (Gestational Age Less than 37 Weeks) Term Neonates (Gestational Age 37 weeks and Above) Initial Dosage 0.4 mg/kg once daily 0.55 mg/kg once daily Month 1 0.7 mg/kg once daily 0.75 mg/kg once daily Month 3 0.9 mg/kg once daily 0.9 mg/kg once daily Recommended Dosage in Patients One Year of Age or Older: 0.9 mg/kg given as an intravenous infusion once daily. ( 2.3 ) 2.1 Patient Selection Start NULIBRY if the patient has a diagnosis or presumptive diagnosis of MoCD Type A. In patients with a presumptive diagnosis of MoCD Type A, confirm the diagnosis of MoCD Type A immediately after initiation of NULIBRY treatment. In such patients, discontinue NULIBRY if the MoCD Type A diagnosis is not confirmed by genetic testing. 2.2 Important Administration Information NULIBRY is intended for administration by a healthcare provider. If deemed appropriate by a healthcare provider, NULIBRY may be administered at home by the patient's caregiver. If NULIBRY can be administered by a caregiver/patient, advise them to read the detailed instructions on the preparation, administration, storage, and disposal of NULIBRY for caregivers [see Instructions for Use ]. NULIBRY is for intravenous infusion only. Administer with non-DEHP tubing with a 0.2 micron filter. Do not mix NULIBRY with other drugs (note NULIBRY is reconstituted with Sterile Water for Injection, USP). Do not administer as an infusion with other drugs. NULIBRY is given through an infusion pump at a rate of 1.5 mL per minute. Dose volumes below 2 mL may require syringe administration through slow intravenous push. Administration of NULIBRY must be completed within 4 hours of reconstitution [see Dosage and Administration ( 2.5 )] . 2.3 Recommended Dosage and Administration Recommended Dosage and Administration in Patients Less Than One Year of Age (by gestational age) The recommended dosage regimen of NULIBRY in patients less than one year of age (by gestational age) is based on actual body weight as shown in Table 1 . Table 1 Recommended Initial Dosage and Titration Schedule of NULIBRY for Patients Less Than One Year of Age by Gestational Age Titration Schedule Preterm Neonates (Gestational Age Less than 37 Weeks) Term Neonates (Gestational Age 37 Weeks and Above) Initial Dosage 0.4 mg/kg once daily...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The most common adverse reactions (>25%) were catheter-related complications, pyrexia, viral infection, pneumonia, otitis media, vomiting, cough/sneezing, viral upper respiratory infection, gastroenteritis, bacteremia, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sentynl Therapeutcis, Inc. at 888-507-5206 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Overview of Safety Evaluation The safety of NULIBRY was assessed in 37 pediatric patients and healthy adults who received at least one intravenous infusion of NULIBRY or an E. coli derived non-salt, anhydrous form of cPMP (recombinant cPMP or rcPMP, which has the same active moiety and therefore the same biologic activity as NULIBRY). Of these 37 patients/healthy adults, 13 were pediatric patients with MoCD Type A in Studies 1, 2, and 3 [see Clinical Studies ( 14 )] , 6 were pediatric patients with presumptive MoCD Type A but who were later confirmed to not have MoCD Type A, and 18 were healthy adults (without MoCD Type A) in a Phase 1 study. Adverse Reactions Assessment of adverse reactions for NULIBRY is based on data from two open-label, single-arm studies, Study 1 (n=8) and Study 2 (n=1), in patients with a confirmed diagnosis of MoCD Type A (8 of the 9 patients were previously treated with rcPMP). In these studies, patients received a daily intravenous infusion of NULIBRY. The median exposure to NULIBRY was 4.3 years and ranged from 8 days to 5.6 years [see Clinical Studies ( 14 )]. In these studies, 44% of patients were males and 56% were females, 67% were White and 33% were Asian. The mean age was 14 days and ranged from 1 day to 69 days at time of first infusion. Table 2 presents the most common adverse reactions that occurred in NULIBRY-treated patients in Studies 1 and 2. Table 2 Common Adverse Reactions Reported in Two or More NULIBRY-Treated Patients with MoCD Type A (Studies 1 and 2) Abbreviations: MoCD = molybdenum cofactor deficiency 1 Catheter-related complications included complication associated with device, catheter site abscess, catheter site discharge, catheter site extravasation, catheter site pain, catheter site infection, catheter site inflammation, device dislocation, device leakage, device occlusion, and vascular device infection. Adverse Reactions NULIBRY-Treated Patients (N=9) n (%) Catheter-related complications 1 8 (89%) Pyrexia 7 (78%) Viral infection 5 (56%) Pneumonia 4 (44%) Otitis Media 4 (44%) Vomiting 4 (44%) Cough/Sneezing 4 (44%) Upper viral respiratory infection 3 (33%) Gastroenteritis 3 (33%) Diarrhea 3 (33%) Bacteremia 3 (33%) Abdominal pain 2 (22%) Influenza 2 (22%) Lower respiratory tract infection 2 (22%) Viral tonsillitis 2 (22%) Oropharyngeal pain 2 (22%) Rash maculo-papular 2 (22%) Anemia 2 (22%) Eye swelling 2 (22%) Seizure 2 (22%) Agitation 2 (22%) Safety data are also available from 10 patients with MoCD Type A who received rcPMP in Study 3 (an observational study) [see Clinical Studies ( 14 )]. The median time on rcPMP treatment was 1.5 years and ranged from 6 days to 4.4 years. In Study 3, the patient population was evenly distributed between males and females with a mean age of 18 days (range 1, 69) at time of first infusion, 70% were White, and 30% were Asian. In Study 3, one patient died of necrotizing enterocolitis. Adverse reactions for the rcPMP-treated patients were similar to the NULIBRY-treated patients, except for the following additional adverse reactions that were reported in more than one patient: sepsis, oral candidiasis, varicella, fungal skin infection, and eczema.
Contraindications
4 CONTRAINDICATIONS None. None. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no available data on NULIBRY use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction toxicology studies have not been conducted with fosdenopterin. 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 are 2% to 4% and 15% to 20%, respectively.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied NULIBRY (fosdenopterin) for injection is a white to pale yellow lyophilized powder or cake in a single-dose clear glass vial for reconstitution. Each NULIBRY vial contains 9.5 mg of fosdenopterin. Each carton of NULIBRY contains one vial (NDC 73129-001-01 or 42358-295-01). Components are not made with natural rubber latex. Storage Store NULIBRY frozen between -25°C and -10°C (-13°F and 14°F). Store the vial in its original carton to protect from light. For storage recommendations for the reconstituted solution [see Dosage and Administration ( 2.5 )] .
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.