Pegloticase

G6PD is an enzyme in your body that is responsible for helping red blood cells to work properly. Some patients are born with less of this enzyme in their bodies, leading to the destruction of red blood cells. When peglitocase is used in patients with G6PD deficiency, they have a higher chance of experiencing hemolytic anemia (a condition in which the body does not have enough red blood cells to deliver oxygen to your tissues).

G6PD testing may be done to determine whether you are at a higher risk of experiencing hemolytic anemia if you are to be treated with peglitocase.

Pegloticase may be found in some form under the following brand names:

• Krystexxa

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories-A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Pegloticase falls into category C. There are no well-controlled studies that have been done in pregnant women. Pegloticase should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

Usual Adult Dose for Gout:

8 mg via IV infusion every 2 weeks; infuse over no less than 120 minutes via gravity feed, syringe-type pump, or infusion pump

Comment:
-Patients should receive premedications (e.g., antihistamines, corticosteroids) to minimize the risk of anaphylaxis and infusion reactions.

Use: For the treatment of chronic gout in patients who are refractory to conventional therapy (e.g., patients who have failed to normalize serum uric acid and whose signs/symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated)

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Bruising.
• Hard stools (constipation).
• Upset stomach or throwing up.
• Sore throat.
• Nose and throat irritation.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about pegloticase, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about pegloticase. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using pegloticase.

Review Date: October 4, 2017

Pegloticase is a pegylated recombinant form of urate-oxidase enzyme, also known as uricase (an enzyme normally absent in humans and high primates), which converts uric acid to allantoin (an inactive and water soluble metabolite of uric acid); it does not inhibit the formation of uric acid.

Excretion

Urine (as allantoin)

Refer to adult dosing.

Applies to pegloticase: intravenous solution

General

The most commonly reported adverse reactions included gout flares, infusion reactions, nausea, contusion, and ecchymosis.[Ref]

Immunologic

Very common (10% or more): Anti-pegloticase antibodies (up to 92%)[Ref]

Metabolic

Very common (10% or more): Gout flares (up to 77%)[Ref]

An increase in gout flares is frequently observed upon initiation of anti-hyperuricemic therapy due to changing serum uric acid levels resulting from mobilization of urate from tissue deposits. During clinical trials, the frequency of gout flares was 74%, 81%, and 51% for patients receiving 8 mg every 2 weeks, 8 mg every 4 weeks, and placebo, respectively. In the subsequent 3 months, the frequencies were 41%, 57%, and 67%, respectively. Patients were receiving gout flare prophylaxis with colchicine and/or a NSAID.[Ref]

Local

Infusion reactions occurred in 26% of patients receiving this drug every 2-weeks and 41% of patients receiving this drug every 4 weeks. Manifestations have included urticaria, dyspnea, chest discomfort, chest pain, erythema, and pruritus. These symptoms overlap with those that constitute anaphylaxis, but in the individual patient did not satisfy the clinical criteria for anaphylaxis. Infusion reactions are thought to result from the release of various mediators, such as cytokines. They may occur at any time during the course of treatment with approximately 3% occurring with the first infusion and 91% occurring during the time of infusion. Some infusion reactions improved with the slowing of the infusion rate.[Ref]

Very common (10% or more): Infusion reactions (up to 26%)[Ref]

Gastrointestinal

Very common (10% or more): Nausea (up to 12%)
Common (1% to 10%): Constipation, vomiting[Ref]

Dermatologic

Contusions were generally not reported on the day of infusion; most were thought to be related to other factors such as concomitant medications relevant to contusion or ecchymosis, type 1 diabetes mellitus.[Ref]

Very common (10% or more): Contusion (up to 11%), ecchymosis (up to 11%), urticaria (up to 10.8%)
Common (1% to 10%): Erythema, pruritus[Ref]

Cardiovascular

Common (1% to 10%): Chest discomfort, chest pain[Ref]

During clinical trials, 2 cases of congestive heart failure (CHF) exacerbation were reported among patients receiving 8 mg every 2 weeks. During the open-label extension study while patients continued to receive 8 mg every 2 weeks, 4 patients reported CHF exacerbation.[Ref]

Respiratory

Common (1% to 10%): Dyspnea, nasopharyngitis[Ref]

Hypersensitivity

The diagnostic criteria for anaphylaxis included skin or mucosal tissue involvement, and either airway compromise, and/or reduced blood pressure with or without associated symptoms, and a temporal relationship with the injection as well as no other identifiable cause. In clinical trials, 6.5% (n=8) patients receiving this drug every 2-weeks and 4.8% (n=6) of patients receiving this drug every 4 weeks experienced anaphylaxis. All patients had been pretreated with oral antihistamine, IV corticosteroid, and/or acetaminophen. There were no instances in placebo patients.[Ref]

Common (1% to 10%): Anaphylaxis[Ref]

Some side effects of pegloticase may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Data not available

Administration advice:
-This drug should be administered in a healthcare setting by healthcare providers prepared to manage anaphylaxis and infusion reactions.
-Patients should be premedicated with antihistamines and corticosteroids to minimize the risk of anaphylaxis and infusion reactions.
-Administer via IV infusion over no less than 120 minutes; do not give as an IV push or bolus
-If an infusion reaction occurs, the infusion should be slowed or stopped and restarted at a slower rate.

Storage:
Prior to dilution: Store in carton, protect from light, keep under refrigeration (2C to 8C [36F to 46F]) at all times; do not shake or freeze.
-Store diluted solutions under refrigeration (2C to 8C [36F to 46F]); protect from light; use within 4 hours of dilution
-Allow diluted solutions to reach room temperature prior to administration; do not subject vial or diluted solution to artificial heating (e.g. hot water, microwave).

Reconstitution/preparation techniques:
-Visually inspect for particulate matter and discoloration; discard if present.
-Withdraw 1 mL (8 mg) of pegloticase (uricase protein) from vial and inject into 250 mL bag of NS or 0.45% NS.
-Invert infusion bag gently to ensure thorough mixing; do not shake.
-Do not mix or dilute with other drugs.
-Following dilution in infusion bag: Stable for 4 hours at 2C to 8C (36F to 46F) and at room temperature 20C to 25C (68F to 77F); if storage is necessary, preferred storage is refrigeration.

General:
-Prior to initiating therapy, patients should discontinue oral urate-lowering medications and not restart on these agents while receiving this drug.
-Patients should receive gout flare prophylaxis starting at least 1 week before initiating therapy and lasting at least 6 months, unless medically contraindicated or not tolerated.
-The risk of anaphylaxis and infusion reactions is higher in patients who have lost therapeutic response, therefore, monitor serum uric acid levels prior to each infusion and consider discontinuing treatment if levels are greater than 6 mg/dL, especially if 2 consecutive levels exceed 6 mg/dL.
-The optimal treatment duration with this drug is unknown.
-This drug is not recommended for the treatment of asymptomatic hyperuricemia

Monitoring:
-Patients at high-risk for G6PD (e.g. patients of African or Mediterranean ancestry) should be screened for G6PD deficiency before starting therapy.
-Monitor serum uric acid levels prior to each infusion
-Monitor for anaphylaxis and infusion reactions during infusion; monitor for hypersensitivity reactions for an appropriate amount of time after administration.

Patient advice:
-Inform patients of the risk of serious hypersensitivity reactions and infusion reactions and explain to patients the importance of adhering to their treatment plan to help prevent or lessen the severity of these reactions.
-Patients should be aware of the most common signs and symptoms of hypersensitivity and infusion reactions and should be instructed to report these symptoms promptly should they occur during or after an infusion.
-Patients should understand that gout flares may increase when starting therapy and they should not stop this medication if they experience a flare.