Drug Interaction:
Antineuoplastic agents include-
Interferon ALFA 2a, Interferon ALFA -2b, Interferon ALFA -n3, Levamisole, Altretamine, Cladribine, Hydroxyurea, Aldesleukin, Paclitaxel, Docetaxel,Tretinion, Procarbazine,Dacarbazine, Gemcitabine, Mitotane, Asparaginase, Pegaspargase,Porfimer Sodium
Interacting drugs- summary
Aspariginase +
Methotrexate
asparginase diminish or abolish methotrexate effect on malignant cells this effect persists as long as plasma asparagine levels are suppressed. Do not use methotrexate with or following aspariginase, while aspariginase levels are below normal.
+Aspariginase
Vincristine/ Prednisolone
IV administration of aspariginase concurrently with or immediately before a course of these drugs may be associated with increased toxicity
Drug/lab test interaction:
L-asparaginase may interfere with the interpretation of thyroid function tests by producing a rapid and marked reduction in serum concentration of thyroxine-binding globulin within 2 days after the first dose.
Serum concentration of thyroxine-binding globulin returned to pre-treatment values within 4 weeks of the last dose of l-asparaginase
Indication:
Acute lyphocytic leukemia primararily in combination with other chemotherapeutic agents.
Antineuoplastic agents include-
Interferon ALFA 2a, Interferon ALFA -2b, Interferon ALFA -n3, Levamisole, Altretamine, Cladribine, Hydroxyurea, Aldesleukin, Paclitaxel, Docetaxel,Tretinion, Procarbazine,Dacarbazine, Gemcitabine, Mitotane, Asparaginase, Pegaspargase,Porfimer Sodium
Adverse Reaction:
Hypersentivity- skin rashes, urticaria, arthalgia, respiratory distress, and acute anaphylaxis,
CNS- depression, somnloence, fatigue, coma, confusion, agitation, and hallucinations (mild to severe), headache, irritability,
Parkinson-like-syndrome with tremor and pogressive increase in muscular tone. These effcets are normally reversed spontaneously after stopping treatment.
Renal- azoteam, usually prerenal (frequent), proteinuria, (infrequent) acute renal shutdown and fatal insufficiency
Hepatic- elevations of serum glutamic-oxalocaetic transaminase (SGOT) serum glutamic -pyruvic transaminase (SGPT)alkaline phosphatase,bilirubin (direct and indirect) and depression of serum albumin, cholesterol (total and esters)and plasma fibronogen. Increase and decreases of total lipids marked hypoalbuminemia associated with peripheral edema.
GI- nausea, vomiting, anorexia, abdominal cramps, (usually mild) pancreatitis, sometimes fulminant and acute hemorrhagic pancreattitis, both may be fatal
Miscellaneous- chills, fever,weight loss, (usually mild) fatal hyperthermia hyperglycemia
Contra-Indications:
Anaphylactic reactions to asparaginase,pancreatitis or history of pancreatitis.
Special precautions:
Due to possible severe reactions, including anaphylaxis and sudden death, administer only in hospital setting under the supervision of physician qualified by training and experience in antineoplastic agents.
Be prepared to treat anaphylaxis at each administration.
Precautions- Monitoring- fall in circulating lymphoblasts is often quite marked , normal or below normal leucocytes counts are noted frequently several days after initiating therapy and may be accompanied by a marked rise in serum uric acid.
Uric acid nephropathy may develop, take appropiate preventive measures (eg. allopurinol ,increased fliud intake, alkalisation of urine.
Monitor peripheral blood count and bone marrow frequently Obtain frequent serum amylase determinations to detect early evidence of pancreatitis.
If panreatitis occur, discontinue therapy.
Warnings
Hematologic- bone marrow depression, leukopenia, thrombosis, and clotting factors depressed , increase in blood ammonia, during the conversion ofaspraginase to asparatic acid by the enzyme.
Bone marrow depression- rarely transcient bone marrow depression has been seen evidenced by a delay in return of hemoglobulin or hemotocrit levels to normal in patients undergoing remission of leukemia.
Bleeding- bleeding has been a problem in few patients, however intracranial hemorrhage and fatal bleeding associated with low fibrinogen levels have been reported.
Hyperglycemia- with glucosuria and poluria has been reported in low incidence. serum and urine acetone are usually absent or negligible. It usuallay responds to drug discontinuation and judicious use of IV fluid and insulin., but it may be fatal.
Hepatoxicity- occurs in majority of patients . Therapy may increase preexisting liver impairment caused by prior therapy or underlying disease . Asparaginase may increase the toxicity of other medicines.
Hypersensitivity- reactions are frequent and may occur during primary course of therapy. They are not completely predicatable based on the intradermal skin test. Anaphylaxis and death have occurred.
Pregnancy- use during pregnancy only if the potentail benefits justifies the potentail risk to the fetus.
Lactation- because of the potentail for serious adverse reactions in nursing infants, discontinue nursing or discontinue the drug considering the importance of the drug to the mother.
Children- asparaginase toxicity is reported to be greater in adults than in children.
Dosages/ Overdosage Etc:
Indications:
Acute lyphocytic leukemia primararily in combination with other chemotherapeutic agents.
Dosage:
Perform an interdermal skin test before initial admin. Progressively increase the dose after doing the sensitisation test.
Storage: Store at 2 to 8C. Because it does not contain a preservative, discard reconstituted solution after 8 hours or sooner if it turns cloudy.
Missed dose-
1. If you miss a dose of this medicine, take it as soon as possible.
2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.
3. Do not double doses.
Patient Information:
Asparginase- Systemic
1.Allergies-
Tell your doctor if you have ever had any unusual or allergic reaction to
asparaginase
2.Pregnancy-
Asparginase has not been studied in pregnant women. However, studies in
mice and rats have shown that asparginase in doses 5 times the usual human
dose slows the weight gain in infants and may also increase the risk of birth
defects or cause decrease in successful pregnancies. In addition, doses
slightly less than the human dose caused birth defects in babies
3. Breast-feeding-
It is not known whether asparaginase passes into breast milk. However, because
asparginase may cause serious side effects, breast-feeding is generally not
recommended while you are receiving it.
4.Children-
This medicine has been tested in children and has not shown to cause different
side effects than it does in adults. In fact the side effects of this medicine seem
to be less severe in children than in adults.
5.Older adults-
Many medicines have not been studied specifically in older people. Therefore
it may not be known whether they work in the same way they do in younger adults
or if they cause different side effects or problems in older people. There is no
specific information comparing use of asparginase in the elderly with use in other
age groups.
6.Other medicines-
Although certain medicines or dietary supplements should not be used together
at all, in other cases two different medicines may be used together even interaction
might occur. In such cases your doctor may want to change the dose , or other
precautions may be necessary.
When you are receiving asparginase it is especially important that your health care
professional know if you taking any of the following-
Probenecid (eg.Benemid) or
Sulfinpyrazole (eg.Anturane) -asparginase may raise the concentration of the uric
acid in the blood. Since these medicines are used to lower uric acid levels, they
may not work as well in patients receiving asparaginase
If you ever been treated with radiation or cancer medicines- asparginase may
increase the total effects of these medication and radiation therapy
7.Other medical problems-
The presence of other medical problems may affect the use of asparginase
Make sure you tell your doctor if you have other any other medical problems,
especially-
Chickenpox (including recent exposure ) or
Herpes zoster (shingles) - risk of severe disease affecting other parts of the body
Diabetes mellitus (sugar diabetes) asparginase may increase glucose (sugar)
in the blood.
Gout or
Kidney stones-asparginase may increase levels of uric acid in the body, which
can cause gout or kidney stones
Infection- asparginase can reduce bodys abilty to fight infection
Liver disease- asparginase may worsen the condition
Pancreatitis ( inflammation of the pancreas) asparginase may cause pancreatitis
Pharmacology/ Pharmacokinetics:
Pharmacology:
Asparaginase contains the enzyme L-asparaginase amidohydrolase. Administration of asparaginase hydrolyses serum asparagine to nonfunctional asparatic acid and ammonia, depriving tumor cells of required amino acid.
Pharmacokinetics:
Plasma half-life varies from 8 to 30 hours. Half-life is not influenced by dosage. Only minimal urinary and biliary excretion occurs.
Interaction with Food:
Not available
Pregnancy and lactation:
Pregnancy-
Use during pregnancy only if the potentail benefits justifies the potentail risk to the fetus.
Lactation-
Because of the potentail for serious adverse reactions in nursing infants, discontinue nursing or discontinue the drug considering the importance of the drug to the mother.
Children-
Asparaginase toxicity is reported to be greater in adults than in children.
