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 ?
Latterly FDA-approved urate-lowering agents such a pegloticase, febuxostat and lesinurad provide alternative to alluopurinol in apt settings.
- Irish drugmaker Horizon Therapeutics plc (NASDAQ: HZNP) has initiated a clinical trial evaluating Krystexxa (pegloticase injection) in combination with methotrexate as a strategy to increase the durability of response for patients living with chronic gout refractory to conventional therapies also known as uncontrolled gout, the company said.
Horizon Therapeutics, an Irish-tax registered pharmaceutical company, has started clinical trial assessing KRYSTEXXA (pegloticase injection) in combination with methotrexate as a strategy to increase the durability of response for patients living with chronic gout refractory to conventional therapies, also called uncontrolled gout, it was reported on Friday.
Horizon Therapeutics has initiated a clinical trial evaluating Krystexxa - pegloticase injection - in combination with methotrexate as a strategy to increase the durability of response for patients living with chronic gout refractory to conventional therapies - also known as uncontrolled gout.
Patients with very severe gout accompanied by the formation of large, visible, palpable uric acid deposits known as tophi may require the drug pegloticase (Krystexxa[R]).
Mandell said pegloticase (Krystexxa) via infusion can help patients who don't respond to an XOI but infusion reactions can occur (mainly in nonresponders), and it's extremely expensive (about $20,000 per month).
Available US Food and Drug Administration (FDA)-approved options for lowering sUA include xanthine oxidase inhibitors (allopurinol and febuxostat) that prevent production of uric acid; a uricosuric agent (probenecid) that increases uric acid output in urine; and a uric acid-specific enzyme (pegloticase) that converts uric acid to allantoin.
Horizon Pharma plc presents multiple analyses of KRYSTEXXA (pegloticase injection) clinical trial data underscoring the complex nature of chronic gout refractory to conventional therapies, also known as uncontrolled gout.
Uricases are enzymes, including rasburicase and pegloticase, which decompose uric acid into soluble products for excretion.
Pegloticase is a pegylated recombinant uricase that converts uric acid to allopurinol.