Dosing & Uses
See Pediatric Dosing
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 9.5mg (single-dose vial)
Molybdenum Cofactor Deficiency
Indicated to reduce the risk of mortality in patients with molybdenum cofactor deficiency (MoCD) type A
Doses are based on actual body weight
<1 year (by gestational age)
-
Preterm neonates (gestational age <37 weeks)
-
Term neonates (gestational age ≥37 weeks)
- Initial dose: 0.55 mg/kg IV qDay
- Month 1: 0.75 mg/kg IV qDay
- Month 3: 0.9 mg/kg IV qDay
≥1 year
Dosage Modifications
Renal or hepatic impairment: Effect on pharmacokinetics is unknown
Dosing Considerations
Patient selection
- Start if confirmed or presumptive diagnosis of MoCD type A
- If presumptive diagnosis, confirm diagnosis immediately after initiation; discontinue if not confirmed by genetic testing
Adverse Effects
>10%
Catheter-related complications (89%)
Pyrexia (78%)
Viral infection (56%)
Pneumonia (44%)
Otitis media (44%)
Vomiting (44%)
Cough/sneezing (44%)
Upper viral respiratory tract infection (33%)
Gastroenteritis (33%)
Diarrhea (33%)
Bacteremia (33%)
Abdominal pain (22%)
Influenza (22%)
Lower respiratory tract infection (22%)
Viral tonsillitis (22%)
Oropharyngeal pain (22%)
Rash maculopapular (22%)
Anemia (22%)
Eye swelling (22%)
Seizure (22%)
Agitation (22%)
Warnings
Contraindications
None
Cautions
Potential for photosensitivity
- Animal studies observed phototoxic potential
- Advise to avoid or minimize exposure to direct sunlight and artificial UV light exposure (ie, UVA or UVB phototherapy) and adopt precautionary measures (eg, wear protective clothing and hats, use broad-spectrum sunscreen with high sun protection factor in patients ≥6 months, wear sunglasses)
- If photosensitivity occurs, advise to seek medical attention immediately and consider a dermatological evaluation
Drug interaction overview
- Weak MATE2-K and OAT1 inhibitor; weak MATE1 substrate
Pregnancy & Lactation
Pregnancy
No data are available on use in pregnant females to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
Lactation
No human or animal data are available to assess drug presence or its metabolites in human milk, effects on breastfed infants, or effects on milk production
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Provides an exogenous source of cyclic pyranopterin monophosphate (cPMP)
MoCD-A is caused by a mutation in the molybdenum cofactor synthesis 1 gene (MOCS1), which causes a deficiency in molybdenum cofactor production
The exogenous intermediate substrate cPMP provided by the drug is subsequently converted to molybdenum cofactor, which is required for the activation of essential enzymes (eg, sulfite oxidase) to reduce the levels of neurotoxic sulfites
Decreased sulfite oxidase activity is thought to cause the severe and rapidly progressive CNS damage observed in patients with MoCD-A
Absorption
Peak plasma concentration
- 0.075-mg/kg dose: 285 ng/mL
- 0.24-mg/kg dose: 873 ng/mL
- 0.68-mg/kg dose: 2,800 ng/mL
AUC
- 0.075-mg/kg dose: 523 ng⋅hr/mL
- 0.24-mg/kg dose: 1,790 ng⋅hr/mL
- 0.68-mg/kg dose: 5,960 ng⋅hr/mL
Distribution
Vd: 300 mL/kg
Protein bound: 6-12%
Metabolism
Predominantly metabolized through nonenzymatic degradation processes to Compound Z, an inactive oxidation product of endogenous cPMP
Elimination
Total body clearance: 167-195 mL/hr/kg
Renal clearance: ~40% of total body clearance
Half-life: 1.2-1.7 hr
Administration
IV Preparation
Calculate dose (mg) and total volume (mL) required to determine number of vials required
Remove vials from freezer to allow them to reach room temperature (by hand warming for 3-5 min or exposing to ambient air for ~30 min)
Reconstitute each vial with 5 mL of sterile water for injection (final concentration of reconstituted solution: 9.5 mg/5 mL [1.9 mg/mL])
Gently swirl vial continuously until powder is completely dissolved; NOT shake
Visually inspect reconstituted solution; solution is clear and colorless to pale yellow; discard if particles present or if discolored
Administer total reconstituted dose
IV Administration
May be administered by healthcare provider OR by caregiver if deemed appropriate
If administered by a caregiver, advise to read the detailed instructions on drug preparation, administration, storage, and disposal
Administer as an IV infusion at a rate of 1.5 mL/min with non-DEHP tubing with a 0.2-micron filter
Volumes <2 mL may require syringe administration through slow IV push
Do not mix or infuse with other drugs
Complete administration within 4 hr of reconstitution
Missed dose
- Administer as soon as possible
- Administer next scheduled dose at least 6 hr after administration of missed dose
Storage
Unopen vials
- Store in freezer at -25º to -10ºC (-13 to 14ºF) in its original carton to protect from light
Reconstituted solution
- Store at room temperature 15º-25ºC (59-77ºF) or refrigerated 2-8ºC (36º-46ºF) for up to 4 hr including infusion time
- Do not heat; do not refreeze after reconstitution; do not shake
- Discard all unused reconstituted solution 4 hr after reconstitution
Images
Formulary
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