pegunigalsidase alfa

Replaces lysosomal enzyme alpha-galactosidase A, which is deficient in Fabry disease. Without this enzyme, globotriaosylceramide accumulates in small blood vessels and tissues, leading to the development of heart disease, renal impairment, and cerebrovascular complications.

Therapeutic effects:

Reduction in number of globotriaosylceramide inclusions per kidney interstitial capillary.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Catabolized into small peptides. Excretion pathway unknown.

Half-Life: 79–121 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

None.

Use Cautiously in:

Presence of antidrug antibodies (↑ risk of hypersensitivity and infusion-associated reactions and ↓ effectiveness);
Compromised cardiac function (↑ risk of severe complications from infusion-associated reactions);
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

EENT: nasopharyngitis, sinusitis

GI: abdominal pain, diarrhea, nausea

GU: proteinuria, glomerulonephritis, hematuria

Local: extravasation

MS: pain

Neuro: fatigue, headache, peripheral neuropathy

Misc: hypersensitivity reactions (including anaphylaxis), infusion-associated reactions

Interactions ⬆ ⬇

Drug-drug:

None reported.

Route/Dosage ⬆ ⬇

IV (Adults ): 1 mg/kg (actual body weight) every 2 wk.

Availability ⬆ ⬇

Solution for injection: 2 mg/mL

Assessment ⬆ ⬇

Assess for hypersensitivity reactions (anaphylaxis) during infusions and 24 hr after completion. Appropriate medical support measures (cardiopulmonary resuscitation equipment, epinephrine) should be available during administration. If severe reactions occurs, stop infusion, implement appropriate treatments and discontinue therapy.
Assess for mild to moderate hypersensitivity reaction or infusion-related reactions. If reactions occur, hold infusion for 15–30 min or ↓ infusion rate by 25–50%, and initiate appropriate medical treatment. If symptoms persist after holding or ↓ infusion rate, stop infusion and monitor. Consider reinitiating infusion in 7–14 days at 25–50% of the rate when the reaction occurred. If symptoms subside after initially holding infusion, resume infusion and ↓ infusion rate by 25–50%. Starting with next infusion, ↑ infusion rate by 25% every 3rd infusion as tolerated until desired rate is reached. If symptoms subside after initially reducing infusion rate, complete infusion at the ↓ rate as tolerated. Starting with next infusion, ↑ rate in increments of 25% every 3rd infusion as tolerated until desired infusion rate is reached.
Assess for pain in extremities (especially hands and feet), skin lesions, sweating abnormalities, and eye and ear problems.

Lab Test Considerations:

Monitor serum creatinine and urinary protein to creatinine ratio. May cause membranoproliferative glomerulonephritis; discontinue therapy if confirmed.

Implementation ⬆ ⬇

Premedicate with antipyretics, antihistamines, and/or corticosteroids. After 4–6 infusions, may ↓ dose of and/or discontinue premedications if tolerating treatment.

IV Administration:

Y-Site Incompatibility: Do not administer other drugs through same IV line.
Home Infusion: Home administration under the supervision of a health care professional may be considered for patients who have reached an infusion duration that is tolerated well, after evaluation and recommendation by a provider. The infusion duration should remain constant, and duration should only be ↓ in a health care facility. If dose is missed or infusion delayed, notify a health care professional.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. If ≥one dose is missed, administer dose as soon as possible and restart the 2-wk interval.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Advise patient that hypersensitivity reactions (anaphylaxis) and infusion-related reactions can occur during the early course of therapy and after extended duration of therapy. If these reactions occur, seek immediate medical care.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is suspected or planned or if breastfeeding. Advise patients exposed to pegunigalsidase alfa during pregnancy about the pregnancy safety study for monitoring pregnancy outcomes. Encourage patient to report the pregnancy to Chiesi USA, Inc., at 1-888-661-9260 and https://chiesirarediseases.com/contact-us/medical-information-form.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇