pegloticase

pegloticase

(peg-loe-ti-kase) ,

Krystexxa

(trade name)

Classification

Therapeutic: antigout agents
Pharmacologic: enzymes
Pregnancy Category: C

Indications

Treatment of chronic gout in adults who have not responded to/cannot tolerate xanthine oxidase inhibitors, including allopurinol.

Action

Consists of recombinant uricase covalently bonded to monomethoxypoly(ethylene glycol) [mPEG]; uricase catalyzes the oxidation of uric acid to allantoin, a water soluble byproduct that is readily excreted in urine.

Therapeutic effects

↓ serum uric acid levels with resultant ↓ in attacks of gout and its sequelae.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Unknown.
Half-life: Unknown.

Time/action profile (effects on serum uric acid)

ROUTEONSETPEAKDURATION
IVrapidwithin 24 hr>300 hr

Contraindications/Precautions

Contraindicated in: genetic implication Glucose-6–phosphate dehydrogenase (G6–PD) deficiency (risk of hemolysis and methemoglobinemia); Lactation: Breast feeding is not recommended.
Use Cautiously in: HF (may ↑ risk of exacerbation);Retreatment after a drug-free interval (↑ risk of allergic reactions, monitor carefully); Geriatric: May be more sensitive to drug effects; Obstetric: Use during pregnancy only if clearly needed; Pediatric: Safety and effectiveness not established.

Adverse Reactions/Side Effects

Cardiovascular

  • chest pain

Ear, Eye, Nose, Throat

  • nasopharyngitis

Gastrointestinal

  • nausea (most frequent)
  • constipation
  • vomiting

Dermatologic

  • contusion/ecchymoses (most frequent)

Metabolic

  • gout flare (most frequent)

Miscellaneous

  • allergic reactions including anaphylaxis (life-threatening)
  • infusion reactions

Interactions

Drug-Drug interaction

May interfere with the action of other PEG-containing therapies.

Route/Dosage

Intravenous (Adults) 8 mg every 2 wk.

Availability

Injection: 8 mg/mL

Nursing implications

Nursing assessment

  • Monitor for joint pain and swelling. Gout flares frequently occur upon initiation of therapy, but do not require discontinuation. Administer prophylactic doses of colchicine or an NSAID at least 1 wk before and concurrently during the first 6 mo of therapy.
  • Monitor for signs and symptoms of anaphylaxis (wheezing, peri-oral or lingual edema, hemodynamic instability, rash, urticaria) during and following infusion. May occur with any infusion, including initial infusion; usually occurs with 2 hr of infusion. Delayed reactions have also been reported. Risk is higher in patients with uric acid level >6 mg/dL.
  • Monitor for infusion reactions (rash, redness of skin, dyspnea, flushing, chest discomfort, chest pain) during and periodically after infusion. If infusion reaction occurs, slow or stop infusion; restart at slower rate. If severe reaction occurs, discontinue infusion and treat as needed. Risk is greater in patients who have lost therapeutic response. Monitor patient for at least 1 hr following infusion.
  • Lab Test Considerations: Monitor serum uric acid levels prior to infusion. Consider discontinuing therapy if levels ↑ to >6 mg/dL, especially if 2 consecutive levels are >6 mg/dL.

Potential Nursing Diagnoses

Chronic pain (Indications)

Implementation

  • Premedicate patient with antihistamines and corticosteroids prior to infusion to minimize risk of anaphylaxis and infusion reaction. Administer in a setting with professionals prepared to manage anaphylaxis and infusion reactions.
    • Discontinue all oral urate-lowering medications prior to and during therapy.
  • Intravenous Administration
  • pH: 4.4–5.6.
  • Intermittent Infusion: Withdraw 1 mL of pegloticase from vial and inject into 250 mL bag of NaCl; discard unused portion. Invert bag several times to mix; do not shake. Solution is clear and colorless; do not administer solutions that are discolored or contain a precipitate. Solution is stable for 4 hr if refrigerated or at room temperature. Store in refrigerator and protect from light; do not freeze. Allow solution to reach room temperature before administering; do not use artificial heating.
  • Rate: Infuse over 120 min. Do not administer via IV push or bolus.
  • Additive Incompatibility: Do not mix with other medications.

Patient/Family Teaching

  • Explain purpose of pegloticase to patient. Instruct patient to read Medication Guide before starting therapy before each infusion.
  • Advise patient to notify health care professional immediately if signs of anaphylaxis or infusion reaction occur.
  • genetic implication Advise patient not to take pegloticase if they have G6PD deficiency.
  • Inform patient that gout flares may initially ↑ at the start of pegloticase. Advise patient to not to stop therapy but to take medication (colchicine, NSAID) to reduce flares regularly for the first few months of pegloticase therapy.
  • Instruct patient to not to take oral urate-lowering medications before or during therapy.
  • Advise female patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.

Evaluation/Desired Outcomes

  • ↓ in uric acid levels with resultant improvement in gout symptoms in patients with chronic gout.
References in periodicals archive ?
No new clinical data is required for pegloticase submission and agreement was reached with the FDA on the content and structure of the planned BLA filing in the treatment-failure gout orphan population.
We also implemented an Open Label Extension clinical trial for patients completing the phase 3 clinical protocols, which provided them with an opportunity to receive pegloticase for 12 months.
Our preliminary analysis indicated that 19 patients or 11% of pegloticase treated patients experienced an infusion reaction termed "serious" or "severe.
Two Patient Reported Outcomes instruments were employed in the pegloticase program, Short Form-36 (SF-36) and the Health Assessment Questionnaire - Disability Index (HAQ-DI), which have been used extensively in Rheumatology studies to assess clinically meaningful change in various rheumatic diseases.
Pegloticase is a pegylated recombinant uricase that converts uric acid to allopurinol.
Infusion-Related Reactions with Pegloticase, a Recombinant Uricase for the Treatment of Chronic Gout Refractory to Conventional Therapy - Baraf HSB, Yood RA, et al.
Pillinger reported being the recipient of research grants from Takeda, which markets colchicine (Colcrys), and Savient, which markets the gout drug pegloticase (Krystexxa).
FDA--Approved Pegylated Therapeutics Commercial Name Drug Name Native Compound PegIntron Peginterferon Interferon alpha-2b alpha-2b Pegasys Peginterferon Interferon alpha-2a alfa-2a Adagen Pegadamase Adenosine deaminase Oncaspar Pegaspargase Asparaginase Krystexxa Pegloticase Mammalian urate oxidase Neulasta Pegfilgrastim Granulocyte colony-stimulating factor Cimzia Certolizumab Therapeutic pegol monoclonal antibody Mircera Polyethylene Epoetin beta glycol-epoetin beta Somavert Pegvisomant Growth hormone receptor antagonist Half- Half- life of life of Native Pegylated Commercial Clinical Compound Compound Name Indication (hours) (hours) PegIntron Hepatitis C, gliomas 9 28 Pegasys Hepatitis C 8 65 Adagen Severe combined 0.
For patients on dual oral therapy at maximum acceptable doses who were still having frequent flares or those with unresolving chronic tophaceous arthropathy, the TFP recommended pegloticase.
There are currently five drugs that can be used to treat gout: allopurinol (Zyloprim), colchicine (Colcrys), febuxostat (Uloric), pegloticase (Krys-texxa), and probenecid.
Therapeutic use: Pegloticase (21-23) is a pegylated enzyme specific for uric acid.
Pillinger call pegloticase a greatly underestimated and underutilized drug"?