pegaspargase (Rx)

Brand and Other Names:Oncaspar, PEG L Asparaginase

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution

  • 750 units/mL (5-mL single-dose vial)

Acute Lymphoblastic Leukemia

Indicated fas a component of a multiagent chemotherapeutic regimen for:

  • First-line treatment of acute lymphoblastic leukemia (ALL) OR
  • Treatment of ALL and with hypersensitivity to native forms of L-asparaginase
  • 2,000 international units/m2 IM or IV no more frequently than q14Days  

Dosage Modifications

Infusion reactions or hypersensitivity reactions

  • Grade 1: Reduce infusion rate by 50%
  • Grade 2: Interrupt infusion; treat symptoms; once symptoms resolve, resume infusion, and reduce infusion rate by 50%
  • Grade 3-4: Permanently discontinue

Thrombosis

  • Uncomplicated deep vein thrombosis (DVT)
    • Hold therapy
    • Treat with appropriate antithrombotic therapy
    • Once symptoms resolve, consider resuming therapy while continuing antithrombotic therapy
  • Severe or life-threatening thrombosis
    • Permanently discontinue
    • Treat with appropriate antithrombotic therapy

Pancreatitis

  • Grade 3-4: Hold therapy for elevations of lipase or amylase >3x ULN until enzyme levels stabilize or are declining
  • Permanently discontinue if clinical pancreatitis is confirmed

Hemorrhage

  • Grade 3-4: Hold therapy
  • Evaluate for coagulopathy and consider clotting factor replacement as needed
  • Resume therapy with next dose if bleeding is controlled

Hepatotoxicity

  • Total bilirubin [TB] >3 to ≤10x ULN: Hold therapy until TB ≤1.5x ULN
  • TB >10x ULN: Discontinue therapy and do not make up for missed doses

Renal or hepatic impairment

  • Impact of renal and hepatic impairment on the pharmacokinetics is unknown

Dosing Considerations

Monitor parameters

  • Bilirubin, AST/ALT, glucose, and clinical examinations: Monitor at least weekly until recovery from cycle
  • Conduct pregnancy testing in females of reproductive potential prior to starting treatment

Dosage Forms & Strengths

injectable solution

  • 750 units/mL (5-mL single-dose vial)

Acute Lymphoblastic Leukemia

Indicated as a component of a multiagent chemotherapeutic regimen for:

  • First-line treatment of adult and pediatric patients with acute lymphoblastic leukemia (ALL) OR
  • Treatment for adult and pediatric patients with ALL and with hypersensitivity to native forms of L-asparaginase
  • ≤21 years: 2,500 international units/m2 IM or IV no more frequently than q14Days
  • >21 years: 2,000 international units/m2 IM or IV no more frequently than q14Days

Dosage Modifications

Infusion reactions or hypersensitivity reactions

  • Grade 1: Reduce infusion rate by 50%
  • Grade 2: Interrupt infusion; treat symptoms; once symptoms resolve, resume infusion, and reduce infusion rate by 50%
  • Grade 3-4: Permanently discontinue

Thrombosis

  • Uncomplicated deep vein thrombosis (DVT)
    • Hold therapy
    • Treat with appropriate antithrombotic therapy
    • Once symptoms resolve, consider resuming therapy while continuing antithrombotic therapy
  • Severe or life-threatening thrombosis
    • Permanently discontinue
    • Treat with appropriate antithrombotic therapy

Pancreatitis

  • Grade 3-4: Hold therapy for elevations of lipase or amylase >3x ULN until enzyme levels stabilize or are declining
  • Permanently discontinue if clinical pancreatitis is confirmed

Hemorrhage

  • Grade 3-4: Hold therapy
  • Evaluate for coagulopathy and consider clotting factor replacement as needed
  • Resume therapy with next dose if bleeding is controlled

Hepatotoxicity

  • Total bilirubin [TB] >3 to ≤10x ULN: Hold therapy until TB ≤1.5x ULN
  • TB >10x ULN: Discontinue therapy and do not make up for missed doses

Renal or hepatic impairment

  • Impact of renal and hepatic impairment on the pharmacokinetics is unknown

Dosing Considerations

Monitor parameters

  • Bilirubin, AST/ALT, glucose, and clinical examinations: Monitor at least weekly until recovery from cycle
  • Conduct pregnancy testing in females of reproductive potential prior to starting treatment
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Interactions

Interaction Checker

and pegaspargase

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            Contraindicated (0)

              Serious - Use Alternative (0)

                Monitor Closely (41)

                • antithrombin alfa

                  pegaspargase increases effects of antithrombin alfa by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • antithrombin III

                  pegaspargase increases effects of antithrombin III by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • argatroban

                  pegaspargase increases effects of argatroban by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • aspirin

                  pegaspargase increases effects of aspirin by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • aspirin/citric acid/sodium bicarbonate

                  pegaspargase increases effects of aspirin/citric acid/sodium bicarbonate by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • bivalirudin

                  pegaspargase increases effects of bivalirudin by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • celecoxib

                  pegaspargase increases effects of celecoxib by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • cholera vaccine

                  pegaspargase decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.

                • dabigatran

                  pegaspargase increases effects of dabigatran by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • dalteparin

                  pegaspargase increases effects of dalteparin by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • diclofenac

                  pegaspargase increases effects of diclofenac by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • diflunisal

                  pegaspargase increases effects of diflunisal by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • enoxaparin

                  pegaspargase increases effects of enoxaparin by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • etodolac

                  pegaspargase increases effects of etodolac by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • fenoprofen

                  pegaspargase increases effects of fenoprofen by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • flurbiprofen

                  pegaspargase increases effects of flurbiprofen by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • fondaparinux

                  pegaspargase increases effects of fondaparinux by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • heparin

                  pegaspargase increases effects of heparin by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • ibuprofen

                  pegaspargase increases effects of ibuprofen by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • ibuprofen IV

                  pegaspargase increases effects of ibuprofen IV by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • indomethacin

                  pegaspargase increases effects of indomethacin by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • ketoprofen

                  pegaspargase increases effects of ketoprofen by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Increased risk of bleeding events.

                • ketorolac

                  pegaspargase increases effects of ketorolac by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • meclofenamate

                  pegaspargase increases effects of meclofenamate by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • mefenamic acid

                  pegaspargase increases effects of mefenamic acid by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • meloxicam

                  pegaspargase increases effects of meloxicam by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • methotrexate

                  pegaspargase decreases effects of methotrexate by pharmacodynamic antagonism. Use Caution/Monitor. It is recommended to give pegaspargase at least 10-14 days prior to methotrexate or shortly after methotrexate administration.

                • nabumetone

                  pegaspargase increases effects of nabumetone by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • naproxen

                  pegaspargase increases effects of naproxen by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • ofatumumab SC

                  ofatumumab SC, pegaspargase. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.

                • oxaprozin

                  pegaspargase increases effects of oxaprozin by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • pegloticase

                  pegloticase will decrease the level or effect of pegaspargase by Other (see comment). Use Caution/Monitor. According to the manufacturer, potential for anti-PEG antibody development that may bind to other pegylated drugs; clinical significance unknown

                • pegvaliase

                  pegvaliase, pegaspargase. Other (see comment). Use Caution/Monitor. Comment: The majority of patients treated with pegvaliase develop anti-polyethylene glycol (PEG) IgM and IgG antibodies. Risk of coadministration with different PEGylated products is unknown. There is a case report of anaphylaxis following a medroxyprogesterone acetate injectable suspension that contained PEG 3350. Carefully read all drug labels, including OTC drugs to check contents for PEG. Note: Unable to include an exhaustive product list for this interaction.

                • piroxicam

                  pegaspargase increases effects of piroxicam by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • protamine

                  pegaspargase increases effects of protamine by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • salicylates (non-asa)

                  pegaspargase increases effects of salicylates (non-asa) by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • salsalate

                  pegaspargase increases effects of salsalate by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • siponimod

                  siponimod and pegaspargase both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

                • sulfasalazine

                  pegaspargase increases effects of sulfasalazine by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • sulindac

                  pegaspargase increases effects of sulindac by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                • tolmetin

                  pegaspargase increases effects of tolmetin by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

                Minor (4)

                • aspirin rectal

                  pegaspargase increases effects of aspirin rectal by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of bleeding events.

                • choline magnesium trisalicylate

                  pegaspargase increases effects of choline magnesium trisalicylate by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of bleeding events.

                • ketorolac intranasal

                  pegaspargase increases effects of ketorolac intranasal by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of bleeding events.

                • taurine

                  pegaspargase decreases levels of taurine by unspecified interaction mechanism. Minor/Significance Unknown. Taurine was found to reduce platelet aggregation and may increase the risk of bleeding.

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                Adverse Effects

                >10%

                Grade 3 and 4

                • Elevated AST/ALT (3-66%)
                • Febrile neutropenia (40%)
                • Hypertriglyceridemia (30%)
                • Hypoalbuminemia (28%)
                • Bilirubin increased (25%)
                • Hyperglycemia (5-24%)
                • Pancreatitis (2-24%)
                • Abnormal clotting studies (21%)

                1-10%

                Grade 3 and 4

                • Embolic and thrombotic events (8%)
                • Hypersensitivity (7%)
                • Thrombosis (3%)
                • Coagulopathy (2%)
                • Hyperbilirubinemia (2%)
                • Allergic reactions to asparaginase (2%)

                Postmarketing Reports

                Blood and lymphatic system disorders: Coagulopathy

                Gastrointestinal disorders: Hepatic impairment, pancreatic cyst, pancreatitis

                Immune system disorders: Anaphylactic shock, hypersensitivity reaction

                Investigations: Blood cholesterol increased

                Metabolism and nutrition disorders: Hyperglycemia, hyperammonemia

                Musculoskeletal and connective tissue disorders: Osteonecrosis

                Vascular disorders: Hemorrhage including central nervous system hemorrhage, thrombosis including superior sagittal sinus thrombosis

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                Warnings

                Contraindications

                Serious hypersensitivity reactions, including anaphylaxis, to pegaspargase or to any of the excipients

                Severe hepatic impairment

                Related to prior L-asparaginase therapy

                • History of serious thrombosis
                • History of pancreatitis, including pancreatitis
                • History of serious hemorrhagic events

                Cautions

                Serious thrombotic events, including sagittal sinus thrombosis can occur; discontinue therapy in patients with serious thrombotic events

                Pancreatitis, including hemorrhagic or necrotizing pancreatitis reported; consult on sign and symptoms of pancreatitis; assess serum amylase and/or lipase levels to confirm early signs of pancreatic inflammation; discontinue treatment in patients where pancreatitis is suspected; if pancreatitis is confirmed, do not resume therapy

                Glucose intolerance may occur; in some cases, glucose intolerance is irreversible; monitor serum glucose

                Increased prothrombin time (PT), increased partial thromboplastin time (PTT), and hypofibrinogenemia reported; evaluate patients with signs and symptoms of hemorrhage with coagulation parameters including PT, PTT, fibrinogen; discontinue drug for severe or life-threatening hemorrhage

                Hepatotoxicity and abnormal liver function, including elevated AST/AST, bilirubin (direct and indirect), reduced serum albumin, and plasma fibrinogen may occur; evaluate bilirubin and AST/ALT at least weekly during treatment cycles, including through at least 6 weeks after the last dose; in the event of serious liver toxicity, discontinue treatment and provide supportive care

                Anaphylaxis and serious hypersensitivity reactions

                • Anaphylaxis and serious hypersensitivity reaction may occur
                • Risk of serious hypersensitivity reaction is higher in patients known hypersensitivity to E. coli derived L-asparaginase formulations
                • Other hypersensitivity reactions can include angioedema, lip swelling, eye swelling, erythema, blood pressure decreased, bronchospasm, dyspnea, pruritus, and rash
                • Premedicate patients 30-60 minutes prior to administration of drug; observe patients for 1 hour after administration in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (for example, epinephrine, oxygen, intravenous steroids, antihistamines); discontinue treatment in patients with serious hypersensitivity reactions

                Drug interaction overview

                • Glucocorticoids
                  • Pegaspargase may increase the risk of glucocorticoid-induced toxicities, including osteonecrosis, through a potential increase in exposure of dexamethasone
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                Pregnancy & Lactation

                Pregnancy

                There are no available data on the use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage or adverse maternal or fetal outcomes

                Published literature studies in pregnant animals suggest asparagine depletion may cause harm to animal offspring

                Verify pregnancy in females of reproductive potential before initiating

                Contraception

                • Females of reproductive potential: Use effective nonhormonal contraceptive methods during treatment during treatment and for at least 3 months after last dose
                • Since there is a potential for an indirect interaction between therapy and oral contraceptives, concomitant use of drug and oral contraceptives is not recommended

                Lactation

                There are no data on presence of drug in human milk, effects on breastfed children, or on milk production

                Advise lactating women not to breastfeed while receiving drug and for 1 month after last dose

                Pregnancy Categories

                A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                NA: Information not available.

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                Pharmacology

                Mechanism of Action

                L-asparaginase is an enzyme that catalyzes conversion of amino acid L-asparagine into aspartic acid and ammonia

                Mechanism of action believed to be based on the killing of leukemic cells due to depletion of plasma asparagine

                Leukemic cells with low expression of asparagine synthetase have a reduced ability to synthesize asparagine, and therefore depend on an exogenous source of asparagine for survival

                Absorption

                Peak plasma concentration: 1.6 IU/mL (single IV infusion)

                AUC: 16.6 IU/mL⋅day (single IV infusion)

                Distribution

                Vd (steady-state): 1.86 L/m2 (single IM dose)

                Elimination

                Clearance

                • Single IM dose: 0.17 L/m2/day
                • Single IV infusion: 0.2 L/day

                Half-life

                • Single IM dose: 5.8 days
                • Single IV infusion: 5.3 days
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                Administration

                IV Incompatibilities

                Do not infuse other drugs through same IV line during administration

                IV Compatibilities

                0.9% NaCl

                D5W

                Preparation

                Administer in a healthcare setting with appropriate medical support and resuscitation equipment to manage hypersensitivity reactions, should they occur

                Solution is a clear and colorless solution; visually inspect vial before administration; if any particulate matter, cloudiness, or discoloration is present, discard

                IM

                • Limit volume at a single injection site to 2 mL

                IV

                • Dilute drug with 100-mL of 0.9% NaCl or D5W, using aseptic technique.
                • After dilution, administer immediately into a running infusion of either 0.9% NaCl or D5W, respectively

                Premedication

                Premedicate with acetaminophen, a H-1 receptor blocker (ie, diphenhydramine), and a H-2 receptor blocker (eg, famotidine) 30-60 min before administration

                Administration

                Observe patients for 1 hr after administration in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (eg, epinephrine, oxygen, IV steroids, antihistamines)

                IM

                • Administered intramuscularly
                • If administered volume >2 mL, use multiple injection sites

                IV

                • Infuse over 1-2 hr

                Storage

                Unused Vials

                • Does not contain preservatives; discard unused product
                • Use only 1 dose per vial
                • Refrigerate at 2-8°C (36-46°F) in the original carton to protect from light
                • Do not shake or freeze product
                • May store at room temperature (15-25°C [59-77°F]) for >48 hr

                Diluted IV infusion

                • If not used immediately, refrigerate at 2-8°C (36-46°F)for up 48 hr
                • Protect infusion bags from direct sunlight
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                Images

                BRAND FORM. UNIT PRICE PILL IMAGE
                Oncaspar injection
                -
                750 unit/mL vial

                Copyright © 2010 First DataBank, Inc.

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                Patient Handout

                Patient Education
                pegaspargase injection

                PEGASPARGASE - INJECTION

                (peg-ASP-are-gace)

                COMMON BRAND NAME(S): Oncaspar

                USES: This medication is usually used to treat acute lymphocytic leukemia (ALL), especially in patients who are allergic to L-asparaginase. It works by starving tumor cells of a certain amino acid (asparagine), causing the tumor cells to die.

                HOW TO USE: This medication is given by injection into a vein or a muscle by a health care professional. The dosage is based on your body size and response to treatment.To help prevent side effects (infusion and allergic reactions), your doctor may direct you to use other medications before you receive this medication. Use these additional medications exactly as directed by your doctor.

                SIDE EFFECTS: Nausea, vomiting, weakness, loss of appetite, diarrhea, or pain/swelling/redness at injection site may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: severe stomach/abdominal pain, signs of an infection (such as fever), increased thirst/urination, easy bruising/bleeding, dark urine, yellowing eyes/skin, pain/redness/swelling/numbness/tingling of the arms or legs.Get medical help right away if you have any very serious side effects, including: sudden shortness of breath, chest pain, severe headache, seizures, trouble speaking, confusion, vision changes, weakness on one side of the body.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

                PRECAUTIONS: Before using pegaspargase, tell your doctor or pharmacist if you are allergic to it; or to L-asparaginase; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: history of a serious reaction to L-asparaginase (such as bleeding, blood clots, pancreatitis), diabetes, clotting/bleeding disorders, liver disease, pancreatitis.Do not have immunizations/vaccinations without the consent of your doctor, and avoid contact with people who have recently received oral polio vaccine or flu vaccine inhaled through the nose.Wash your hands well to prevent the spread of infections.To lower your risk of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.This drug may rarely make your blood sugar rise, which can cause or worsen diabetes. If you have diabetes, check your blood sugar regularly as directed and share the results with your doctor. Tell your doctor right away if you have symptoms of high blood sugar such as increased thirst/urination. Your doctor may need to adjust your diabetes medication, exercise program, or diet.Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while using pegaspargase. Pegaspargase may harm an unborn baby. Your doctor should order a pregnancy test before you start this medication. Ask about reliable forms of non-hormonal birth control (such as condoms, diaphragm with spermicide) while using this medication and for 3 months after the last dose. If you become pregnant, talk to your doctor right away about the risks and benefits of this medication.It is unknown if this drug passes into breast milk. Because of the possible risk to the infant, breast-feeding is not recommended while using this drug and for at least 1 month after stopping treatment. Consult your doctor before breast-feeding.

                DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

                OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

                NOTES: Lab and/or medical tests (such as prothrombin time, complete blood counts, liver function tests, amylase levels, blood sugar) should be done while you are using this medication. Keep all medical and lab appointments. Consult your doctor for more details.

                MISSED DOSE: It is important to get each dose of this medication as scheduled. If you miss a dose, ask your doctor or pharmacist right away for a new dosing schedule.

                STORAGE: Not applicable. This medication is given in a clinic and will not be stored at home.

                MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

                Information last revised February 2023. Copyright(c) 2023 First Databank, Inc.

                IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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                Formulary

                FormularyPatient Discounts

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                The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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                NC NOT COVERED – Drugs that are not covered by the plan.
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                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.