Fosdenopterin (Monograph)

Brand name: Nulibry
Drug class: Other Miscellaneous Therapeutic Agents
Chemical name: (1R,10R,12S,17R)-5-amino-11,11,14-trihydroxy-14-oxo-13,15,18-trioxa-2,4,6,9-tetraza-14lambda5-phosphatetracyclo[8.8.0.03,8.012,17]octadeca-3(8),4-dien-7-one
Molecular formula: C₁₀H₁₄N₅O₈P
CAS number: 150829-29-1

Medically reviewed by Drugs.com on Apr 10, 2023. Written by ASHP.

Introduction

Fosdenopterin hydrobromide is cyclic pyranopterin monophosphate (cPMP).

Uses for Fosdenopterin

Fosdenopterin hydrobromide has the following uses:

Fosdenopterin hydrobromide is indicated to reduce the risk of mortality in patients with molybdenum cofactor deficiency (MoCD) Type A.

Fosdenopterin Dosage and Administration

General

Fosdenopterin hydrobromide is available in the following dosage form(s) and strength(s):

For injection: 9.5 mg of fosdenopterin as a lyophilized powder or cake in a single-dose vial for reconstitution.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Pediatric Patients

Dosage and Administration

• Start fosdenopterin hydrobromide if known or presumed MoCD Type A. Promptly discontinue if MoCD Type A is not confirmed by genetic testing.

• Reconstitute before use and complete infusion within 4 hours of reconstitution.

• 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.

• See the manufacturer's labeling for additional important preparation instructions and administration instructions.

Recommended Dosage in Pediatric Patients Less Than 1 Year of Age (see table below):

Recommended Dosage in Pediatric Patients 1 Year of Age or Older:

0.9 mg/kg given as an intravenous infusion once daily.

Adults

Dosage and Administration

• Start fosdenopterin hydrobromide if known or presumed MoCD Type A. Promptly discontinue if MoCD Type A is not confirmed by genetic testing.

• Reconstitute before use and complete infusion within 4 hours of reconstitution.

• 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.

• See the manufacturer's labeling for additional important preparation instructions and administration instructions.

Recommended Dosage in Adults:

0.9 mg/kg given as an intravenous infusion once daily.

Cautions for Fosdenopterin

Contraindications

None.

Warnings/Precautions

Potential for Photosensitivity

Animal studies have identified that fosdenopterin hydrobromide has phototoxic potential.

Advise fosdenopterin-treated patients or their caregivers to avoid or minimize patient exposure to direct sunlight and artificial UV light exposure (i.e., UVA or UVB phototherapy) and adopt precautionary measures (e.g., have the patient wear protective clothing and hats, use broad spectrum sunscreen with high sun protection factor [SPF] in patients 6 months of age and older, and wear sunglasses when exposed to the sun). If photosensitivity occurs, advise caregivers/patients to seek medical attention immediately and consider a dermatological evaluation.

Specific Populations

Pregnancy

There are no available data on fosdenopterin hydrobromide 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 2–4% and 15–20%, respectively.

Lactation

There are no human or animal data available to assess the presence of fosdenopterin hydrobromide or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production for the mother.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for fosdenopterin hydrobromide and any potential adverse effects on the breastfed infant from fosdenopterin hydrobromide or from the underlying maternal condition.

Pediatric Use

Safety and effectiveness of fosdenopterin hydrobromide for the treatment of MoCD Type A have been established in pediatric patients starting from birth. Use of fosdenopterin hydrobromide for this indication is supported by evidence from two open-label studies (Studies 1 and 2) and one observational study (Study 3), in which 13 pediatric patients aged birth to 6 years of age were treated with fosdenopterin hydrobromide or recombinant cPMP. See the manufacturer's labeling for additional pediatric use information.

Animal studies have identified that fosdenopterin hydrobromide has phototoxic potential. Advise fosdenopterin-treated patients or their caregivers to avoid patient exposure to direct sunlight and artificial UV light exposure (i.e., UVA or UVB phototherapy) and adopt precautionary measures.

Geriatric Use

MoCD Type A is largely a disease of pediatric patients. Clinical studies of fosdenopterin hydrobromide did not include patients 65 years of age and older.

Common Adverse Effects

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.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Patients with MoCD Type A have mutations in the MOCS1 gene leading to deficient MOCS1A/B dependent synthesis of the intermediate substrate, cPMP. Substrate replacement therapy with fosdenopterin hydrobromide provides an exogenous source of cPMP, which is converted to molybdopterin. Molybdopterin is then converted to molybdenum cofactor, which is needed for the activation of molybdenum-dependent enzymes, including sulfite oxidase (SOX), an enzyme that reduces levels of neurotoxic sulfites.

Advice to Patients

Advise patients and/or caregivers to read the FDA-approved patient labeling (Instructions for Use) and complete the treatment logs as appropriate.

Photosensitivity

Advise patients and/or caregivers of the potential for photosensitivity reactions and to ensure that the patient avoids or minimizes exposure to sunlight and artificial UV light exposure (i.e., UVA or UVB phototherapy) during use of fosdenopterin hydrobromide, uses broad spectrum sunscreen with high sun protection factor (patients 6 months of age and older), and wears clothing, a hat, and sunglasses that protect against sun exposure. Instruct patients and/or caregivers to seek medical attention immediately if the patient develops a rash or if they notice symptoms of photosensitivity reactions (redness, burning sensation of the skin, blisters).

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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