Name of the Chemotherapeutic Drugs -Miscellaneous
- L-asparaginase
- Pegaspargase
1. L-asparaginase
| L-asparaginase |
| Availability: Injection: 10,000 international units/vial (with mannitol) |
| Administration and Handling: Administer intradermal skin test as ordered at start of therapy and when drug hasn’t been given for 1 week or more. Follow prescriber’s orders for drug desensitization when indicated (usually before therapy starts and again during retreatment). Know that drug may be carcinogenic, mutagenic, or teratogenic. Follow appropriate facility policy for handling and preparing. Before starting drug, give allopurinol as prescribed to lower risk of Neuropathy. Add sterile water or normal saline solution (5 ml for I.V. dose, 2 ml for I.M. dose) to powdered drug in vial. Filter through 5-micron filter. For I.V. use, inject into normal saline solution or dextrose 5% in water and infuse over 30 minutes. For I.M. use, give a maximum of 2 ml at any one site. Don’t use solution unless it’s clear. If drug touches skin or mucous membranes, rinse with copious amounts of water for at least 15 minutes. Provide adequate fluid intake to prevent tumor lysis. |
| Acute lymphocytic leukemia (given with other drugs, such as prednisone or vincristine, as part of antineoplastic regimen) Children: 1,000 international units/kg I.V. daily for 10 successive days, with asparaginase initiated on day 22 of regimen, or 6,000 international units/m2 I.M. on days 4, 7, 10, 13, 16, 19, 22, 25, and 28 |
| Sole agent used to induce remission of acute lymphocytic leukemia: Adults and children: 200 international units/kg I.V. daily for 28 days |
| Drug desensitization regimen : Adults and children: Initially, 1 international unit I.V. Then double the dosage q 10 minutes until total planned daily dosage has been given. |
Mechanism of Action:
Hydrolyzes asparagine (an amino acid needed for malignant cell growth in acute lymphocytic leukemia), resulting in leukemic cell death.
Indications:
- Acute lymphocytic leukemia (given with other drugs, such as prednisone or vincristine, as part of antineoplastic regimen)
- Sole agent used to induce remission of acute lymphocytic leukemia
- Drug desensitization regimen
Cautions & Contraindications:
- Hypersensitivity to drug
- Pancreatitis or history of pancreatitis
- Use cautiously in:
- Bone marrow depression, hepatic or renal disease, CNS depression, clotting abnormalities, infection
- Pregnant or breastfeeding patients
- Women of childbearing age.
Metabolism and Half- Life:
- Peak asparaginase activity of native E. coli asparaginase can be observed in 24 to 48 hours following administration
- Plasma half-life of L-asparagine derived from E. coli following intravenous injection was 8-30 hrs.
- Plasma half-life was 34 to 49 hours after intramuscular injection.
- Half-life (mean ± SD) of native E. coli asparaginase is approximately 1.28 ± 0.35 days.
Drug Interactions:
- Methotrexate: decreased methotrexate efficacy
- Prednisone: hyperglycemia, increased drug toxicity
- Vincristine: hyperglycemia, increased drug toxicity, increased risk of neuropathy
- Drug-diagnostic tests. Alanine aminotransferase, ammonia, aspartate aminotransferase, blood urea nitrogen, glucose, uric acid: increased levels
- Calcium, hemoglobin, white blood cells: decreased levels
- Thyroid function tests: interference with test interpretation
Side- Effects:
- CNS: confusion, drowsiness, depression, hallucinations, fatigue, agitation, headache, lethargy, irritability, seizures, coma, intracranial hemorrhage and fatal bleeding
- GI: nausea, vomiting, anorexia, abdominal cramps, stomatitis, hemorrhagic pancreatitis, fulminant pancreatitis
- GU: glycosuria, polyuria, uric acid nephropathy, uremia, renal failure
- Hematologic: anemia, leukopenia, hypofibrinogenemia, depression of clotting factor synthesis, bone marrow depression
- Hepatic: fatty liver changes, hepatotoxicity
- Metabolic: hyperglycemia, hyperuricemia, hypocalcemia, hyperammonemia, hypoglycemia
- Musculoskeletal: joint pain
- Skin: rash, urticaria
- Other: chills, fever, weight loss, hypersensitivity reactions, anaphylaxis, fatal hyperthermia
Nursing Considerations
- Observe for signs and symptoms of anaphylaxis.
- Monitor for bleeding and hemorrhage.
- Watch closely for signs and symptoms of intracranial hemorrhage
- Assess vital signs, temperature, and neurologic status.
- Monitor CBC, blood and urine glucose levels, and liver, kidney, and bone marrow function test results.
- Monitor fluid intake and output.
Patient teaching
- Instruct patient to immediately report allergic response, severe abdominal pain, and unusual bleeding or bruising.
- Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
- Advise patient to drink plenty of fluids to ensure adequate urine output.
- Tell patient to monitor urine output and report significant changes.
- Instruct patient to avoid activities that can cause injury. Tell him to use soft toothbrush and electric razor to avoid injury to gums and skin.
- Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.
- Tell patient that he’ll undergo regular blood testing during therapy.
2.Pegaspargase
| Pegaspargase |
| Availability: Injection: 750 international units/ml, 5-ml vial in phosphate-buffered saline solution |
| Administration and Handling: 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 (e.g., 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 |
| Follow facility protocol for handling, preparing, and disposing of chemotherapeutic drugs. Avoid inhaling vapors and contact with skin or mucous membranes. Keep resuscitation equipment, epinephrine, oxygen, steroids, and antihistamines readily available. Know that I.M. route is preferred because it’s less likely to cause hepatotoxicity, coagulopathy, and GI or renal disorders. For single I.M. injection, don’t exceed volume of 2 ml. For I.V. use, dilute in 100 ml of normal saline solution or dextrose 5% in water. Infuse over 1 to 2 hours. Don’t freeze; freezing inactivates drug. |
| Acute lymphoblastic leukemia: Adults and children with body surface area (BSA) greater than 0.6 m2: 2,500 international units/m2 I.M. or I.V. q 14 days Adults and children with BSA less than 0.6 m2: 82.5 international units/m2 I.M. or I.V. q 14 days |
Mechanism of Action:
Stimulates production of effector proteins, such as serum neopterin and 2′, 5′ oligoadenylate synthetase; raises body temperature and reversibly lowers white blood cell and platelet counts
Indications:
- Acute Lymphoblastic Leukemia
- ALL and hypersensitivity to native forms of L-asparaginase
Cautions & Contraindications:
- Hypersensitivity or previous serious allergic reaction (such as generalized urticaria, bronchospasm, laryngeal edema, hypotension) to drug
- Pancreatitis or history of pancreatitis
- Previous hemorrhagic events related to L-asparaginase therapy
Use cautiously in:
- Renal or hepatic disease, CNS disorders
- Concurrent use of hepatotoxic agents, anticoagulants, aspirin or other nonsteroidal anti-inflammatory drugs (nsaids)
- Pregnant or breastfeeding patients.
Metabolism and Half- Life:
Peak plasma concentration: 1.6 IU/mL (single IV infusion)
Elimination
- 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
Drug Interactions:
- Aspirin, dipyridamole, heparin, NSAIDs, warfarin: increased risk of bleeding or thrombosis
- Methotrexate: decreased methotrexate action
- Drug-diagnostic tests. Amylase, blood urea nitrogen, creatinine, lipase, uric acid: increased levels
- Glucose: increased or decreased level
- Liver function tests: abnormal results
- Lymphoblasts: decreased count
Side – Effects:
- CNS: dizziness, headache, confusion, hallucinations, emotional lability, drowsiness, neuritis, Parkinson-like syndrome, malaise, coma, seizures
- CV: hypertension, hypotension, chest pain, peripheral edema, tachycardia, endocarditis
- GI: nausea, vomiting, diarrhea, constipation, abdominal pain, flatulence, anorexia, pancreatitis
- GU: glycosuria, polyuria, urinary frequency, hematuria
- Hematologic: hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia, disseminated intravascular coagulation
- Hepatic: jaundice, fatty liver deposits, hepatotoxicity, hepatomegaly
- Metabolic: hypoproteinemia, hyperuricemia, hyperammonemia, hyponatremia, hyperglycemia, hypoglycemia Respiratory: dyspnea, cough, bronchospasm
- Skin: rash, urticaria, pruritus, night sweats, alopecia
- Other: increased appetite and thirst, weight loss, chills, fever, injection site reaction, facial or lip edema, hypersensitivity reactions including anaphylaxis, septic shock
Nursing Considerations
- Watch for anaphylaxis and other hypersensitivity reactions, especially during first hour of therapy.
- Monitor CBC (including platelet count); fibrinogen; prothrombin and partial thromboplastin times; International Normalized Ratio; and serum amylase, lipase, and uric acid levels.
- Assess neurologic status. Stay alert for decreased level of consciousness and evidence of impending seizure.
- Check for signs and symptoms of bleeding, infection, and hyperglycemia.
- Monitor heart rate, blood pressure, respiratory rate, temperature, and fluid intake and output.
Patient teaching
- Teach patient to recognize and immediately report signs and symptoms of hypersensitivity reactions, bleeding, infection, and other adverse reactions.
- Tell patient drug is likely to cause reversible hair loss.
- Stress importance of undergoing follow- up laboratory tests.
- Advise patient to avoid situations that increase risk for infection.
- Instruct patient to consult prescriber before taking other prescription drugs or over-the-counter preparations.
REFERENCES
- Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
- McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
- April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
- Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
- Nursebro.com, Search – Nursebro
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