Elitek

Elitek (rasburicase) is a recombinant urate-oxidase produced by a genetically modified Saccharomyces cerevisiae strain. The cDNA coding for rasburicase was cloned from a strain of Aspergillus flavus.

Rasburicase is a tetrameric protein with identical subunits. Each subunit is made up of a single 301 amino acid polypeptide chain with a molecular mass of about 34 kDa. The drug product is a sterile, white to off-white, lyophilized powder intended for intravenous administration following reconstitution with a diluent. Elitek is supplied in 3 mL and 10 mL colorless, glass vials containing rasburicase at a concentration of 1.5 mg/mL after reconstitution.

• Elitek 1.5 mg presentation contains 1.5 mg rasburicase, 10.6 mg mannitol, 15.9 mg Lalanine, between 12.6 and 14.3 mg of dibasic sodium phosphate (lyophilized powder), and a diluent (1 mL Water for Injection, USP, and 1 mg Poloxamer 188).
• Elitek 7.5 mg presentation contains 7.5 mg of rasburicase, 53 mg mannitol, 79.5 mg Lalanine, and between 63 and 71.5 mg dibasic sodium phosphate (lyophilized powder) and a diluent (5 mL Water for Injection, USP, and 5 mg Poloxamer 188).

Dosage Forms & Strengths

injection, powder for reconstitution

• 1.5mg/vial
• 7.5 mg/vial

Hyperuricemia Caused by Tumor Lysis

Indicated for the initial management of plasma uric acid levels in pediatric and adult patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anticancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid

0.2 mg/kg IV infused over 30 minutes qDay for up to 5 days 

Dosing Considerations

Limitation of use: indicated only for a single course of treatment

Dosing beyond 5 days or administration of more than 1 course is not recommended

Dosage Forms & Strengths

injection, powder for reconstitution

• 1.5mg/vial
• 7.5 mg/vial

Hyperuricemia Caused by Tumor Lysis

Indicated for the initial management of plasma uric acid levels in pediatric and adult patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anticancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid

0.2 mg/kg IV infused over 30 min qDay for up to 5 days 

Dosing Considerations

Limitation of use: indicated only for a single course of treatment

Dosing beyond 5 days or administration of more than 1 course is not recommended

Elitek is a prescription medication used to reduce high uric acid levels in adults and children with leukemia, lymphoma, and solid tumor malignancies who are receiving chemotherapy medications.

When cancer cells are destroyed by chemotherapy, certain substances are released. As the body breaks these substances down, uric acid levels increase and may be harmful. Elitek is in a class of medications called urate oxidase enzymes. It works by breaking down uric acid so that the body can eliminate it.

This medication comes in an injectable form to be given directly into a vein (IV) once daily for up to 5 days.

Common side effects include nausea, vomiting, anxiety, and stomach pain.

Elitek is part of the drug class:

• Detoxifying agents for antineoplastic treatment

Common side effects include:

• nausea
• vomiting
• anxiety
• stomach pain
• mouth sores
• throat pain
• fever
• headache
• swelling of the hands, feet, ankles, or lower legs

Tell your doctor about any side effect that bothers you or that does not go away. 

These are not all the possible side effects with Elitek. For more information, ask your doctor or pharmacist.

Elitek comes as a solution (liquid) to be injected intravenously (into a vein) by a healthcare professional. It is usually given over a period of 30 minutes once a day for up to 5 days. This medication is given as a single course of treatment that will not be repeated.

Get emergency medical help if you have signs of an allergic reaction: hives, rash; wheezing, chest pain and tightness, difficult breathing; feeling light-headed; swelling of your face, lips, tongue, or throat.

Your treatment with rasburicase may be permanently discontinued if you have a serious allergic reaction.

Tell your caregivers or call your doctor at once if you have:

• pale or yellowed skin, dark colored urine;

• sores or white patches in or around your mouth, trouble swallowing or talking, dry mouth, bad breath, altered sense of taste;

• fever, flu symptoms, rapid heart rate, rapid and shallow breathing, fainting; or

• signs of a serious blood disorder--blue-colored skin or lips, headache, feeling weak or tired, trouble breathing, feeling like you might pass out, pounding heartbeats or fluttering in your chest.

Common side effects may include:

• nausea, vomiting, stomach pain;

• diarrhea, constipation;

• anxiety;

• fever; or

• swelling in your hands or feet.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Contraindications

• G-6-PD deficiency.1 (See Hemolysis under Cautions.)

• Known hemolytic reactions to rasburicase or any ingredient in the formulation.1 (See Hemolysis under Cautions.)

• Known methemoglobinemia reactions to rasburicase or any ingredient in the formulation.1 (See Methemoglobinemia under Cautions.)

• Known hypersensitivity to rasburicase or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Potential for severe (e.g., grade 3 or 4) hemolytic reactions associated with G-6-PD deficiency; reported within 2–4 days of initiation of therapy.1

Immediately and permanently discontinue the drug if evidence of hemolysis appears; initiate appropriate patient monitoring and supportive measures (e.g., transfusion support).1

Contraindicated in patients with G-6-PD deficiency because hydrogen peroxide is a major product of the conversion of uric acid to allantoin.1

Prior to initiating therapy, screen patients at increased risk of G-6-PD deficiency (e.g., patients of African or Mediterranean descent).1

Risk of methemoglobinemia, resulting in serious hypoxemia requiring medical intervention.1

Immediately and permanently discontinue if methemoglobinemia develops and implement supportive measures (e.g., transfusion support, methylene blue administration).1

Unknown whether a deficiency of cytochrome b5 reductase (methemoglobin reductase) or of other antioxidant enzymes increases risk for methemoglobinemia or hemolytic anemia.1

Sensitivity Reactions

Risk of severe hypersensitivity reactions (e.g., anaphylaxis); may occur any time during treatment, even during the first dose.1

If a serious hypersensitivity reaction occurs(e.g., bronchospasm, chest pain and tightness, dyspnea, hypoxia, hypotension, shock, and/or urticaria), immediately and permanently discontinue drug and initiate appropriate therapy.1

Safety in patients with atopic allergy or asthma is unknown.2 3 6

General Precautions

Maintain adequate hydration according to standard medical practice for the management of plasma uric acid in patients at risk for tumor lysis syndrome.1 Alkalinization of the urine is not needed.6 9

Antibodies to rasburicase may develop; may be associated with inhibition of rasburicase activity.1

Specific Populations

Category C.1

Not known whether rasburicase is distributed into milk; discontinue nursing or the drug.1

Safety and efficacy not established in infants <1 month of age.a

Insufficient experience in those ≥65 years of age to determine whether they respond differently than pediatric patients.a

Insufficient experience in adults to determine whether they respond differently than pediatric patients.a

Common Adverse Effects

Vomiting, fever, nausea, headache, abdominal pain, constipation, diarrhea, mucositis, rash.1

• Risk of hypersensitivity reactions (e.g., anaphylaxis).1 Importance of immediately seeking medical attention if symptoms of severe sensitivity (e.g., chest pain, dyspnea, hypotension, urticaria) occur.1

• Risk of adverse hematologic effects (e.g., hemolysis, methemoglobinemia).1

• Importance of women informing clinicians immediately if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.a

• Importance of informing patients of other important precautionary information. (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

• If you need to store Elitek at home, talk with your doctor, nurse, or pharmacist about how to store it.

The maximum reported overdosage of Elitek is a single dose of 1.3 mg/kg. No adverse events occurred in reported cases of overdosage. Monitor patients who receive an overdose and initiate supportive measures if required.

Mechanism of Action

In humans, uric acid is the final step in the catabolic pathway of purines. Rasburicase catalyzes enzymatic oxidation of poorly soluble uric acid into an inactive and more soluble metabolite (allantoin).

Pharmacodynamics

The measurement of plasma uric acid was used to evaluate the effectiveness of rasburicase in clinical studies. Following administration of either 0.15 or 0.20 mg/kg rasburicase daily for up to 5 days, plasma uric acid levels decreased within 4 hours and were maintained below 7.5 mg/dL in 98% of adult and 90% of pediatric patients for at least 7 days. There was no evidence of a dose response effect on uric acid control for doses between 0.15 and 0.20 mg/kg rasburicase.

Pharmacokinetics

The pharmacokinetics of rasburicase were evaluated in both pediatric and adult patients with leukemia, lymphoma or other hematological malignancies. Rasburicase exposure, as measured by AUC0–24 hr and Cmax, tended to increase with a dose range from 0.15 to 0.2 mg/kg. The mean terminal half-life was similar between pediatric and adult patients and ranged from 15.7 to 22.5 hours. The mean volume of distribution of rasburicase ranged from 110 to 127 mL/kg in pediatric patients and from 75.8 to 138 mL/kg in adult patients, respectively. Minimal accumulation of rasburicase (<1.3 fold) was observed between days 1 and 5 of dosing. In adults, age, gender, baseline liver enzymes and creatinine clearance did not impact the pharmacokinetics of rasburicase. A cross-study comparison revealed that after administration of rasburicase at 0.15 or 0.20 mg/kg, the geometric mean values of body-weight normalized clearance were approximately 40% lower in Japanese (n=20) than that in Caucasians (n=22).

Applies to rasburicase: intravenous powder for solution

Along with its needed effects, rasburicase (the active ingredient contained in Elitek) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking rasburicase:

• Cracked lips
• diarrhea
• difficulty with swallowing
• sores, ulcers, or white spots on the lips, tongue, or inside the mouth

• Abdominal or stomach pain
• agitation
• black or red, tarry, stools
• bleeding gums
• bluish color of the fingernails, lips, skin, palms, or nail beds
• changes in skin color
• changes in vision
• chest pain or discomfort
• chills
• coma
• confusion
• convulsions (seizures)
• cough
• coughing that sometimes produces a pink, frothy sputum
• coughing up blood
• decreased urination
• depression
• dilated neck veins
• dizziness
• dry mouth
• fainting
• fast, slow, or irregular heartbeat
• fever
• headache
• hostility
• increased menstrual flow or vaginal bleeding
• increased sweating
• increased thirst
• irritability
• itching, pain, redness, swelling, tenderness, or warmth on the skin
• lightheadedness
• lower back or side pain
• muscle twitching
• nausea
• no blood pressure or pulse
• nosebleeds
• pain or discomfort in the arms, jaw, back, or neck
• pain, tenderness, or swelling of the foot or leg
• painful or difficult urination
• pains in the chest, groin, or legs, especially calves of the legs
• pale skin
• paralysis
• prolonged bleeding from cuts
• red or dark brown urine
• severe constipation
• severe headaches of sudden onset
• shortness of breath
• skin rash
• sneezing
• sore throat
• stopping of heart
• stupor
• sudden loss of coordination
• sudden onset of shortness of breath for no apparent reason
• sudden onset of slurred speech
• sunken eyes
• sweating
• swelling of the face, fingers, feet, or lower legs
• swollen glands
• temporary blindness
• thirst
• tightness in the chest
• troubled breathing
• unconsciousness
• unexplained or unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting
• weight gain
• wheezing
• wrinkled skin

• Back pain
• hives
• itching, puffiness, or swelling of the eyelids or around the eyes, face, lips, or tongue
• yellow eyes or skin

Some side effects of rasburicase may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• feeling of warmth
• feeling unusually cold
• redness of the face, neck, arms, and occasionally, upper chest
• shivering