Pombiliti (cipaglucosidase alfa-atga)
Metabolic Disease Enzyme Replacement, Pompe Disease Intravenous Vial (Ea)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Cipaglucosidase alfa-atga is a hydrolytic lysosomal glycogen-specific enzyme.
Pompe disease is an inherited disorder of glycogen metabolism caused by a deficiency of lysosomal acid alpha-glucosidase (GAA) that degrades glycogen to glucose in the lysosome. GAA deficiency results in intra-lysosomal accumulation of glycogen in various tissues. Cipaglucosidase alfa-atga is a hydrolytic lysosomal glycogen-specific recombinant human alpha-glucosidase enzyme that provides an exogenous source of GAA.
The bis-mannose-6-phosphate on cipaglucosidase alfa-atga mediates binding to mannose-6-phosphate 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.
Cipaglucosidase alfa-atga must be given in combination with miglustat; miglustat binds with, stabilizes, and reduces inactivation of cipaglucosidase alfa-atga in the blood after infusion.
When administered in combination with miglustat, the mean half-life of cipaglucosidase alfa-atga is 2.1 hours. Plasma protein binding and the metabolic pathway of cipaglucosidase alfa-atga have not been characterized. Metabolism by cytochrome P-450 enzymes or secretion into bile is not a significant contributor to elimination; cipaglucosidase alfa-atga is expected to be metabolized into small peptides and amino acid via catabolic pathways.
Intact cipaglucosidase alfa-atga is unlikely to be filtered by the kidney or excreted in the urine. Age (18 to 74 years) and sex did not have clinically meaningful effects on the pharmacokinetics of cipaglucosidase alfa-atga.
USES: Cipaglucosidase alfa is used in combination with another medication (miglustat) to treat a certain inherited condition (Pompe disease). It works by breaking down a certain substance (glycogen) that builds up in the body due to this condition. Decreasing glycogen in the body can help improve symptoms of Pompe disease such as muscle weakness, heart problems, and breathing problems.
This medication must be used with miglustat because it helps cipaglucosidase alfa stay active in the blood which helps it work better.
Generic name: cipaglucosidase alfa-atga
Pronunciation: (SIP-a-gloo-KOE-si-dase Al-fa)
Drug class: Metabolic Disease Enzyme Replacement, Pompe Disease
Therapeutic class: Metabolic Disease Enzyme Replacement Agents
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Pombiliti
Indications
The following indications are listed for Pombiliti:
- Lysosomal Alpha-1,4-Glucosidase Deficiency
Also known as: Acid Maltase Deficiency, Glycogen Storage Disease Type 2, Glycogen Storage Disease Type Ii, Glycogenosis Type Ii, Pompe's Disease.
Dosing
No dosing information is available for this tab.
Cipaglucosidase alfa-atga and miglustat combination therapy should be started 2 weeks after the last dose of enzyme replacement therapy.
Cipaglucosidase alfa-atga is administered IV as an infusion by a healthcare professional. Ensure that appropriate medical support is available to manage hypersensitivity and infusion-associated reactions during administration of the drug.
Store vials of unreconstituted powder for injection in a refrigerator at 2-8oC in the original carton to protect from light. Do not freeze.
If reconstituted cipaglucosidase alfa-atga vials are not used immediately, store refrigerated at 2-8oC for up to 24 hours. Do not freeze.
If the diluted solution is not administered immediately, store refrigerated at 2-8oC for up to 16 hours. Storage at room temperature is not recommended. Do not freeze. Discard the diluted solution if refrigerated more than 16 hours or if the diluted solution is not able to be completely infused within 6 hours after removal from the refrigerator.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Pombiliti 105 Mg Vial | Maintenance | Infuse 20 mg/kg over approximately 4 hour(s) by intravenous route every 2 weeks. |
No dosing information is available for this tab.
Drug interactions
No formal drug interaction studies have been conducted to date; cipaglucosidase alfa-atga is unlikely to be involved in cytochrome P-450 (CYP) or transporter-mediated drug interactions.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Pregnancy.
- Lactation
- Acute respiratory failure
- Chronic heart failure
- Pregnancy
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects of cipaglucosidase alfa-atga (>=5% of patients) reported in clinical studies include headache, diarrhea, fatigue, nausea, abdominal pain, and pyrexia.
Less Frequent
- Anaphylaxis
- Hypersensitivity drug reaction
- Paradoxical bronchospasm
- Pharyngeal edema
- Tongue swelling
Rare or Very Rare
- Hypotension
More Frequent
- Acute abdominal pain
- Diarrhea
- Fatigue
- Fever
- Headache disorder
- Nausea
Less Frequent
- Chills
- Dizziness
- Dysgeusia
- Dyspnea
- Flushing
- Muscle spasm
- Pruritus of skin
- Skin rash
- Tachycardia
- Urticaria
Rare or Very Rare
- Arthralgia
- Constipation
- Drowsy
- Dyspepsia
- Flank pain
- General weakness
- Hypertension
- Malaise
- Myalgia
- Pain
- Paresthesia
- Thrombocytopenic disorder
- Tremor
- Vomiting
Precautions
No enhanced messaging available.
Safety and effectiveness of cipaglucosidase alfa-atga in pediatric patients have not been established.
There is insufficient evidence with cipaglucosidase alfa-atga in combination with miglustat in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Based on findings from animal reproduction studies, cipaglucosidase alfa-atga in combination with miglustat may cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy.
In a rabbit embryo-fetal development study, great vessel and cardiac malformations were increased in offspring of pregnant rabbits treated with cipaglucosidase alfa-atga in combination with miglustat at 16-fold and 3-fold, respectively, of the maximum recommended human dose (MRHD) based on plasma AUC exposure. A No Observed Adverse Effect Level (NOAEL) was not identified for the combination.
In a pre- and post-natal development study in rats, increases in pup mortality were seen following maternal treatment with cipaglucosidase alfa-atga (400 mg/kg) in combination with miglustat, or with cipaglucosidase alfa-atga (400 mg/kg) alone. The NOAEL for cipaglucosidase alfa-atga alone is 150 mg/kg (5-fold the cipaglucosidase alfa-atga MRHD margin). A NOAEL for the combination of cipaglucosidase alfa-atga and miglustat was not identified.
There are no data on the presence of cipaglucosidase alfa-atga (alone or in combination with miglustat) in human milk, the effects on the breast-fed child, or the effects on milk production. Cipaglucosidase alfa-atga is present in animal milk. Based on findings in animal studies, the use of cipaglucosidase alfa-atga in combination with miglustat may lead to serious adverse reactions in breast-fed infants. Advise females that breastfeeding is not recommended while receiving treatment with cipaglucosidase alfa-atga in combination with miglustat.
The manufacturer makes no specific dosage recommendations for geriatric patients.
Clinical studies with cipaglucosidase alfa-atga did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently than younger subjects. Of the total number of patients treated with cipaglucosidase alfa-atga in combination with miglustat in clinical trials for late-onset Pompe Disease, 17 (11%) were 65 to 74 years of age, and none were >=75 year of age.
ICD codes
| Code | Type | Description |
|---|---|---|
| Lysosomal alpha-1,4-glucosidase deficiency | ||
| E74.02 | ICD10CM | Pompe disease |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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