Fosdenopterin (Monograph)

Brand name: Nulibry
Drug class: Other Miscellaneous Therapeutic Agents

Medically reviewed by Drugs.com on Dec 16, 2023. Written by ASHP.

Introduction

Cyclic pyranopterin monophosphate (cPMP).

Uses for Fosdenopterin

Molybdenum Cofactor Deficiency Type A

Used to reduce the risk of mortality in patients with molybdenum cofactor deficiency (MoCD) Type A.

Has been designated an orphan drug by FDA for this indication.

Shown to provide a survival benefit in patients with MoCD Type A; there are no other approved treatments. Current treatment generally consists of supportive care, treatment for neurologic symptoms, and supplements (e.g., magnesium, pyridoxine and/or thiamine).

Fosdenopterin Dosage and Administration

General

Patient Monitoring

Monitor for signs and symptoms of photosensivity (e.g., redness, burning sensation of skin, blisters).

Other General Considerations

In patients with a presumptive diagnosis of MoCD Type A, confirm diagnosis immediately after initiation of fosdenopterin treatment. Discontinue fosdenopterin if the MoCD Type A diagnosis is not confirmed by genetic testing.
Limit exposure to sunlight and artificial ultraviolet (UV) light, and wear protective clothing, a hat, and sunglasses during sun exposure. In children ≥6 months of age, use broad-spectrum sunscreen with high sun protection factor (SPF).

Administration

IV Administration

Administer as an IV infusion using an infusion pump.

Administer using a non-diethylhexyl phthalate (DEHP) tubing with a 0.2 micron filter.

Intended for administration by a healthcare professional. If deemed appropriate, may be administered at home by the patient or a caregiver.

If a dose is missed, administer as soon as possible. Ensure ≥6 hours elapse between the missed dose and the next scheduled administration.

Do not mix or infuse with any other drugs.

Available as a lyophilized powder that must be reconstituted prior to administration.

Reconstitution

Reconstitute with sterile water for injection prior to use; must complete infusion within 4 hours of reconstitution.

Prior to reconstitution, allow vials to reach room temperature (by either hand warming for 3—5 minutes or exposing to ambient air for 30 minutes).

Reconstitute each vial with 5 mL of sterile water for injection, and gently swirl vial until powder is dissolved; do not shake.

Once reconstituted, each vial yields a final concentration of 9.5 mg/5 mL (1.9 mg/mL).

Rate of Administration

Administer via infusion pump at a rate of 1.5 mL/minute.

Dose volumes <2 mL may require syringe administration through slow IV push.

Dosage

Available as fosdenopterin hydrobromide; dosage expressed in terms of fosdenopterin.

Pediatric Patients

MoCD Type A

IV

Pediatric patients <1 year of age (based on gestational age): Dosage based on actual body weight (see Table 1).

Table 1. Recommended Initial Dosage and Titration of Fosdenopterin for Patients Less than 1 Year of Age Based on Gestational Age1
Titration Schedule	Preterm Neonates (Gestational Age <37 Weeks)	Term Neonates (Gestational Age ≥37 Weeks)
Initial Dosage	0.4 mg/kg once daily	0.55 mg/kg once daily
Dosage at Month 1	0.7 mg/kg once daily	0.75 mg/kg once daily
Dosage at Month 3	0.9 mg/kg once daily	0.9 mg/kg once daily

Pediatric patients ≥1 year of age: 0.9 mg/kg (based on actual body weight) once daily.

Adults

MoCD Type A

IV

0.9 mg/kg (based on actual body weight) once daily.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Use

No specific dosage recommendations.

Cautions for Fosdenopterin

Contraindications

None.

Warnings/Precautions

Photosensitivity

Based on animal data, potential for phototoxicity.

Advise patients and/or caregivers to avoid and/or minimize exposure to direct sunlight and UV light (i.e., UVA or UVB phototherapy). Use precautionary measures such as wearing protective clothing, hats, and sunglasses during sun exposure; apply high sun protection factor (SPF) sunscreen in patients ≥6 months of age.

Advise patients and caregivers to seek immediate medical attention if photosensitivity occurs, and to consider a dermatological skin evaluation.

Specific Populations

Pregnancy

No data in pregnancy.

Lactation

Not known whether fosdenopterin or its metabolites distribute into human milk. The effects on the breast-fed infant or on milk production are not known.

Pediatric Use

Safety and efficacy established in pediatric patients starting at birth.

Geriatric Use

Clinical studies of fosdenopterin did not include geriatric patients.

Hepatic Impairment

Effects of hepatic impairment on pharmacokinetics not known.

Renal Impairment

Effects of renal impairment on pharmacokinetics not known.

Common Adverse Effects

Most common adverse effects (>25%): catheter-related complications, pyrexia, viral infection, pneumonia, otitis media, vomiting, cough/sneezing, viral upper respiratory infection, gastroenteritis, bacteremia, diarrhea.

Drug Interactions

Does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4/5, nor induces CYP1A2, CYP2B6, or CYP3A4.

Weak substrate of, but not an inhibitor of, multidrug and toxin extrusion (MATE)1. Weak inhibitor of MATE2K and organic anion transporter (OAT)1, but not a substrate of MATE2K or OAT1. Does not inhibit P-gp, breast cancer resistance protein (BCRP), organic anion transporter polypeptide (OATP)1B1, OATP1B3, organic cation transporter (OCT)2, or OAT3. Not a substrate of P-gp, BCRP, OATP1B1, OATP1B3, OCT2, or OAT3.

Potential for CYP or transporter-mediated drug interactions with fosdenopterin is low; no clinical drug interaction studies conducted with the drug.

Fosdenopterin Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations and AUC are approximately dose proportional over IV dose range of 0.075—0.68 mg/kg.

Distribution

Extent

Not known if distributed into human milk.

Plasma Protein Binding

6—12%.

Elimination

Metabolism

Primarily metabolized by nonenzymatic degradation processes to Compound Z, an inactive oxidative product of cyclic pyranopterin monophosphate.

Elimination Route

Approximately 40% of total body clearance via the renal route.

Half-life

Mean of 1.2—1.7 hours.

Special Populations

Pharmacokinetics in pediatric patients with MoCD Type A similar to that of healthy adults.

Stability

Storage

Parenteral

For injection, for IV infusion

Store vials between -25°C to -10°C in the original carton to protect from light.

Store reconstituted solution from 15—25°C or 2—8°C for up to 4 hours (including infusion time).

Actions

Synthetic cyclic pyranopterin monophosphate (cPMP) that serves as a substrate replacement therapy.
MoCD Type A is caused byMOCS1 gene mutations that lead to deficiencies in MOCS1A/B dependent synthesis of cyclic pyranopterin monophosphate (cPMP), an intermediate substrate.
Fosdenopterin provides an exogenous source of cPMP, which undergoes conversion to molybdopterin, and then to molybdenum cofactor, necessary for the activation of sulfite oxidase (SOX), a molybdenum-dependent enzyme that reduces neurotoxic sulfite levels.

Advice to Patients

Advise patients and their caregivers to read the FDA-approved patient labeling (Instructions for Use) and complete treatment logs as necessary.
Advise patients treated with fosdenopterin or their caregivers to avoid and/or minimize exposure to direct sunlight and UV light (i.e., UVA or UVB phototherapy). Patients should use precautionary measures such as wearing protective clothing, hats, and sunglasses during sun exposure; apply high SPF sunscreen in patients 6 months of age and older. Advise patients and caregivers to seek immediate medical attention if photosensitivity occurs, and to consider a dermatological skin evaluation.
Advise patient to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

Fosdenopterin is obtained through designated specialty pharmacies. Contact manufacturer or consult the Nulibry website ([Web]) for specific availability information.