Drug Information

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.

Asparaginase-L - @ - Antineoplatics

Drug Interaction

Indication

Adverse Reaction

Contra-Indications

Dosages/ Overdosage Etc

Patient Information

Pharmacology/ Pharmacokinetics

Interaction with Food

Pregnancy and lactation