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.
Drug Guide, © 2015 Farlex and Partners
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.
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.