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Pombiliti Generic Name & Formulations
Legal Class
General Description
Pharmacological Class
How Supplied
Single-dose vial—1, 10, 25
Manufacturer
Generic Availability
NO
Mechanism of Action
Cipaglucosidase alfa-atga provides an exogenous source of GAA. The bis-M6P on cipaglucosidase alfa-atga mediates binding to M6P receptors on the cell surface with high affinity. After binding, it is internalized and transported into lysosomes where it undergoes proteolytic cleavage and N-glycans trimming which are both required to yield the most mature and active form of GAA. Cipaglucosidase alfa-atga then exerts enzymatic activity in cleaving glycogen. Miglustat binds with, stabilizes, and reduces inactivation of cipaglucosidase alfa-atga in the blood after infusion.
Pombiliti Indications
Indications
In combination with Opfolda, for adults with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing ≥40kg and who are not improving on their current enzyme replacement therapy (ERT).
Pombiliti Dosage and Administration
Adult
Consider premedication with antihistamines, antipyretics, and/or corticosteroids prior to initiation; if used with previous ERT, then should premedicate. Start in combination with Opfolda 2 weeks after the last ERT dose. Initiate infusion ~1hr after and within 3hrs of Opfolda administration. Give by IV infusion over ~4hrs. 20mg/kg every other week. Initial infusion rate: 1mg/kg/hr; may gradually increase by 2mg/kg/hr every 30mins, if tolerated, to max 7mg/kg/hr. Dosage and administration modifications, others: see full labeling.
Children
Not established.
Other Modifications
Modifications Due to Hypersensitivity Reactions and/or Infusion-Associated Reactions
If severe hypersensitivity reaction (eg, anaphylaxis) or a severe infusion-associated reaction (IAR) occurs immediately discontinue treatment with Pombiliti, and initiate appropriate medical treatment.
If mild to moderate hypersensitivity reaction or moderate IAR occurs, consider temporarily holding or slowing the infusion rate and initiate appropriate medical treatment.
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If symptoms persist despite holding or slowing the infusion, then stop the infusion for 30 to 60 minutes - monitor and consider resuming the infusion at a reduced rate if symptoms have improved. If symptoms still persist, discontinue the infusion, and consider restarting the infusion within 7 to 14 days.
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If symptoms subside after holding or slowing the infusion, increase the infusion rate to the rate when the reaction occurred and consider continuing to increase the rate (every 30 minutes) in a stepwise manner to the target infusion rate. Monitor closely.
Administration
Inspect the infusion bag for foaming prior to administering. If foaming is present, let foam dissipate before administering. If diluted solution has been refrigerated, allow the solution to equilibrate to room temperature for 30 minutes prior to infusion.
Administer with an inline low protein binding 0.2-micron filter; change filter if it becomes blocked.
Initiate the infusion approximately 1 hour after oral administration of Opfolda. If infusion with Pombiliti was delayed, the starting infusion time should not exceed 3 hours from the oral administration of Opfolda.
Initial recommended infusion rate is 1mg/kg/hour; then gradually increase the infusion rate by 2mg/kg/hour every 30 minutes if no signs of hypersensitivity or IARs until a maximum rate of 7mg/kg/hour is reached; then maintain the infusion rate at 7mg/kg/hour until complete. Approximate total infusion duration is 4 hours.
Recommended Pombiliti infusion volumes and rates by patients weight: see full labeling.
Pombiliti Contraindications
Contraindications
Pregnancy.
Pombiliti Boxed Warnings
Boxed Warning
Severe hypersensitivity reactions or infusion-associated reactions. Risk of acute cardiorespiratory failure in susceptible patients.
Pombiliti Warnings/Precautions
Warnings/Precautions
Must be administered in combination with Opfolda (see full labeling). Have appropriate medical support and resuscitative equipment readily available. Discontinue immediately and treat appropriately if severe hypersensitivity reaction (eg, anaphylaxis) or severe infusion-associated reactions (IARs) occurs; may rechallenge using slower infusion rates. Withhold temporarily or slow the infusion rate if mild or moderate hypersensitivity reactions or moderate IARs occur. Increased risk for IARs in patients with an acute underlying illness or severe complications from IARs in those with advanced Pompe disease. Fluid volume overload, acute underlying respiratory illness, or compromised cardiac/respiratory function (with fluid restriction): risk for acute cardiorespiratory failure; monitor vitals frequently. May impair fertility. Embryo-fetal toxicity. Exclude pregnancy status prior to initiation. Advise females of reproductive potential to use effective contraception during and for at least 60 days after the last dose. Nursing mothers: not recommended.
Pombiliti Pharmacokinetics
Absorption
Maximum serum concentration (in combination with Opfolda): 345 mcg/mL. Plasma concentration-time curve (AUC0-inf) (in combination with Opfolda): 1812 mcg*h/mL.
Distribution
Volume of distribution: ranged from 2.0–4.7 L.
Elimination
Mean total body clearance: 0.8 L/hr. Half-life: 2.1 hours.
Pombiliti Interactions
Not Applicable
Pombiliti Adverse Reactions
Adverse Reactions
Headache, diarrhea, fatigue, nausea, abdominal pain, pyrexia; hypersensitivity reactions, IARs.
Pombiliti Clinical Trials
Pombiliti Note
Not Applicable
