Pegloticase - Krystexxa - @-Immunomodulator (Sep 2010)
Drug Name:Pegloticase - Krystexxa - @-Immunomodulator (Sep 2010)
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
No studies of interactions of KRYSTEXXA with other drugs have been conducted.
Because anti-pegloticase antibodies appear to bind to the PEG portion of the drug, there may
be potential for binding with other PEGylated products.
The impact of anti-PEG antibodieson patients’ responses to other PEG-containing
therapeutics is unknown
Indication:
Proprietary Name- Krystexxa
Established Name - Pegloticase
Applicant- Savient
Indication-
Provides for the treatment of intravenous infusion intended for patients
with treatment failure of Gout.
To control hyperuricemia and manage the signs and
symptoms of Gout
Approved by FDA on 14-9-2010 (Ref- FDA approved List- 2010)
Adverse Reaction:
The most common adverse reactions (occurring in at least 5% of
KRYSTEXXA-treated patients) are gout flares, infusion reactions, nausea,
contusion or ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis
and vomiting.
Contra-Indications:
CONTRAINDICATIONS
Glucose-6-phosphate dehydrogenase (G6PD) Deficiency: Before starting KRYSTEXXA,
patients at higher risk for G6PD deficiency (e.g., those of African and Mediterranean
ancestry) should be screened due to the risk of hemolysis and methemoglobinemia.
WARNINGS AND PRECAUTIONS
Anaphylaxis: Anaphylaxis occurred in patients treated with KRYSTEXXA.
Anaphylaxis may occur with any infusion, including a first infusion, and generally
manifests within 2 hours of the infusion. However, delayed-type hypersensitivity
reactions have also been reported.
KRYSTEXXA should be administered in healthcare settings and by healthcare
providers prepared to manage anaphylaxis.
Patients should be pre-medicated with antihistamines and corticosteroids.
Patients should be closely monitored for an appropriate period of time for
anaphylaxis after administration of KRYSTEXXA.
Infusion Reactions: Infusion reactions occurred in patients treated with KRYSTEXXA.
KRYSTEXXA should be administered in a healthcare setting and by healthcare
providers prepared to manage infusion reactions.
Patients should be pre-medicated with antihistamines and corticosteroids.
Monitor patients closely for signs and symptoms of infusion reactions.
In the event of an infusion reaction, the infusion should be slowed, or stopped
and restarted at a slower rate. If a severe infusion reaction occurs,
discontinue infusion and institute treatment as needed.
The risk of an infusion reaction is higher in patients who have lost therapeutic response.
Gout Flares: An increase in gout flares is frequently observed upon initiation of
anti-hyperuricemic therapy, including treatment with KRYSTEXXA.
If a gout flare occurs during treatment, KRYSTEXXA need not be discontinued.
Gout flare prophylaxis (i.e., non-steroidal anti-inflammatory drugs [NSAID]
or colchicine upon initiation of treatment) is recommended for at least the
first 6 months of therapy unless medically contraindicated or not tolerated.
Congestive Heart Failure: KRYSTEXXA has not been formally studied in patients
with congestive heart failure, but some patients in clinical trials experienced exacerbation.
Exercise caution when using KRYSTEXXA in patients who have congestive heart failure
and monitor patients closely following infusion.
Dosages/ Overdosage Etc:
Indication-
Provides for the treatment of intravenous infusion intended for patients
with treatment failure of Gout.
To control hyperuricemia and manage the signs and
symptoms of Gout
INDICATIONS AND USAGE
KRYSTEXXAR (pegloticase) is a PEGylated uric acid specific enzyme
indicated for the treatment of chronic gout in adult patients refractory to
conventional therapy.
Important Limitations of Use:
KRYSTEXXA is not recommended for the treatment of asymptomatic
hyperuricemia.
DOSAGE AND ADMINISTRATION
For adult patients 8 mg given as an intravenous infusion every two weeks.
Do not administer as an intravenous push or bolus.
Discontinue oral urate-lowering agents before starting KRYSTEXXA
Monitor serum uric acid levels before each infusion.
Patients should be pre-medicated with antihistamines and corticosteroids.
Administer in a healthcare setting by healthcare providers prepared to manage
anaphylaxis.
The KRYSTEXXA admixture should only be administered by intravenous infusion
over no less than 120 minutes via gravity feed, syringe-type pump, or infusion pump.
DOSAGE FORMS AND STRENGTHS
1 mL sterile concentrate for dilution containing 8 mg of pegloticase protein,
expressed in uricase protein amounts.
Patient Information:
PATIENT COUNSELING INFORMATION
1.Provide and instruct patients to read the accompanying Medication Guide before
starting treatment and before each subsequent treatment.
2 Anaphylaxis and Infusion Reactions
Anaphylaxis and infusion reactions can occur at any infusion while on therapy.
Counsel patients on the importance of adhering to any prescribed medications
to help prevent or lessen the severity of these reactions.
3.Educate patients on the signs and symptoms of anaphylaxis, including wheezing
, peri-oral or lingual edema, hemodynamic instability, and rash or urticaria.
4.Educate patients on the most common signs and symptoms of an infusion reaction
, including urticaria (skin rash), erythema (redness of the skin), dyspnea
(difficulty breathing), flushing, chest discomfort, chest pain, and rash.
5.Advise patients to seek medical care immediately if they experience any symptoms
of an allergic reaction during or at any time after the infusion of KRYSTEXXA.
•
6.Advise patients to discontinue any oral urate-lowering agents before starting on
KRYSTEXXA and not to take any oral urate-lowering agents while on KRYSTEXXA.
7. Glucose-6-phosphate dehydrogenase (G6PD) Deficiency
Inform patients not to take KRYSTEXXA if they have a condition known as G6PD
deficiency.
Explain to patients that G6PD deficiency is more frequently found
in individuals of African or Mediterranean ancestry and that they may be tested to
determine if they have G6PD deficiency, unless already known.
8. Gout Flares
Explain to patients that gout flares may initially increase when starting treatment with
KRYSTEXXA, and that medications to help reduce flares may need to be taken
regularly for the first few months after KRYSTEXXA is started.
Advise patients that they should not stop KRYSTEXXA therapy if they have a flare.
Pharmacology/ Pharmacokinetics:
1 Mechanism of Action
KRYSTEXXA is a uric acid specific enzyme which is a recombinant uricase and
achieves its therapeutic effect by catalyzing the oxidation of uric acid to allantoin,
thereby lowering serum uric acid. Allantoin is an inert and water soluble purine
metabolite. It is readily eliminated, primarily by renal excretion
2 Pharmacokinetics
Pegloticase levels were determined in serum based on measurements of uricase enzyme
activity.Following single intravenous infusions of 0.5 mg to 12 mg pegloticase in 23 patients
with symptomatic gout, maximum serum concentrations of pegloticase increased in
proportion to the dose administered.
The population pharmacokinetic analysis showed that age, sex, weight, and creatinine
clearance did not influence the pharmacokinetics of pegloticase.
Significant covariates included in the model for determining clearance and
volume of distribution were found to be body surface area and anti-pegloticase antibodies
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1 Pregnancy
Pregnancy Category C
It is not known whether KRYSTEXXA can cause fetal harm when administered to a
pregnant woman or can affect reproductive capacity. There are no adequate and
well-controlled studies in pregnant women. KRYSTEXXA should be used during
pregnancy only if clearly needed.
2. Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are
excreted in human milk and because of the potential for serious adverse reactions
in nursing infants, it is not recommended to administer KRYSTEXXA to a nursing mother.
3. Pediatric Use
The safety and effectiveness of KRYSTEXXA in pediatric patients less than 18 years
of age have not been established.
4. Geriatric Use
No overall differences in safety or effectiveness were observed between older
and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
No dose adjustment is needed for patients 65 years of age and older
