LASPAR POWDER FOR INJECTION

INDICATIONS CONTRA-INDICATIONS DOSAGE SIDE-EFFECTS PREGNANCY OVERDOSE IDENTIFICATION PATIENT INFORMATION

LASPAR POWDER FOR INJECTION

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

LASPAR POWDER FOR INJECTION

COMPOSITION:
Laspar is L-Asparaginase (amidohydrolase) from Escherichia coli. Each vial contains 10 000 KU L-Asparagine amidohydrolase, in the form of freeze-dried powder.
(1 KU of L-Asparaginase is equivalent to the amount of enzyme producing 1 µmol ammonia for 1 minute from L-Asparagine at 37°C.)

PHARMACOLOGICAL CLASSIFICATION:
A 26 Cytostatic agents

PHARMACOLOGICAL ACTION:
The tumour cells of acute leukaemia require exogenous L-Asparagine as an essential nutrient for their growth. L-Asparaginase is an enzyme which catalyses the hydrolysis of L-Asparagine to aspartic acid and ammonia, thus interfering with the metabolism of the malignant cells.

INDICATIONS:
Lymphoblastic leukaemia (acute lymphatic leukaemia).
The different mechanism of action of Laspar and the fact that no cross resistance with other anti-leukaemic agents exists always justify a therapeutic trial when resistance against conventional cytostatiscs has developed.

CONTRA-INDICATIONS:
Pregnancy.
Safety during lactation has not been established.
Patients with a history of hypersensitivity to L-asparaginase.

DOSAGE AND DIRECTIONS FOR USE:
The dry powder in the vial is dissolved, agitating slightly, with the added solvent i.e. 5% glucose or xylitol or sterile physiological saline solution. The solution should be injected within 24 hours of being made up, if stored at 5°C. The product is usually administered at doses of 200 to 800 KU/kg daily or on every other day. The dose should be adjusted according to the age and general condition of the patient.
According to clinical data the maximum tolerable dose is 2 000 KU/kg daily. Some authors recommend that the continuous dose after remission is 50 KU/kg daily. The duration of administration is usually 2 weeks. Treatment should be carried out as in-patient therapy.
Laspar is administered by slow intravenous injection or a rapid intravenous infusion (20 to 30 minutes) with physiological sodium chloride solution.
Laspar can be combined with differently acting cytostatics and/or corticosteroids. The stated dosage for
Laspar can be maintained. In order to exclude the possibility of hypersensitivity the following tests should, as a rule, be performed prior to administration or before resuming treatment after an interruption. The detailed procedures of the tests should follow the routine ones in each laboratory.

a.	Intracutaneous injection: 1 to 10 KU of Laspar in a volume of 0,1 mL is to be injected intracutaneously on the palmar side of the forearm. The absence of abnormal signs should be confirmed 30 minutes to several hours after the injection.
b.	Intravenous injection: Laspar, dissolved in a maximum of 250 mL of glucose solution, is administered by drop-infusion at doses of 50 - 100 KU/kg depending on the age of the patient. The condition of the patient should be observed for one day and absence of any abnormal reaction confirmed.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Shock
Shock symptoms may occur infrequently. If any symptoms such as clouding of consciousness, convulsions, blood pressure decrease, chills, fever or vomiting are observed, discontinue administration immediately and adequate measures should be taken.
Hypersensitivity
Hypersensitivity reactions such as rash may occur.
Haematology
Since severe abnormality of coagulation (decrease of fibrinogen, prothrombin, plasminogen AT III and protein C etc) such as cerebral haemorrhage, cerebral infarction and pulmonary haemorrhage may occur, monitor the patient carefully by frequent laboratory examinations. *
Furthermore thrombocytopenia and anaemia may occur.
Hepatic
Since hyperammonemia with disturbance of consciousness may occur, monitor the patient carefully by periodical examinations. *
Furthermore, hepatic disorder and fatty liver may occur.
Renal
Proteinurea, diuretic failure, azotemia and oedema may occur.
Pancreatic
Since acute pancreatitis may occur and secretion dysfunction of pancreas (necrosis of Langerhans' islets) may induce diabetes, monitor the patients carefully. *
Brain
Death has been reported due to the wide range organic dysfunction of the brain.
Gastrointestinal
Anorexia, nausea, vomiting and diarrhoea may occur.
Pshychoneurologic
Malaise, headache, and infrequently somnolence, anxiety, disturbance of consciousness and coma may occur.
Other
Fever and glucose tolerance abnormality may occur.

*	If any abnormal findings are observed, discontinue administration or adequate measures should be taken.

Great care should be taken at the beginning of the administration. In view of the risk of sensitization once treatment has begun it should not be interrupted.
If, however, an interruption should become unavoidable then treatment must be resumed with small doses (beginning with 10 KU/kg of body mass). If tolerance remains good the dose may be increased to the full daily dose in the course of 5 days.
It should be given cautiously to patients with impaired liver function. In patients with pancreatitis or a history of pancreatitis, acute haemorrhagic-pancreatitis has been reported following L-Asparaginase administration.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Treatment is symptomatic and supportive.

IDENTIFICATION:
A white, lyophilised powder.

PRESENTATION:
Vials containing 10 000 KU of L-Asparaginase.

STORAGE INSTRUCTIONS:
Store in a refrigerator (2° - 8°C)
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
C/26/163

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Intramed (Pty) Ltd
6 Gibaud Road
PORT ELIZABETH
6001

DATE OF PUBLICATION OF THIS PACKAGE INSERT:

MARCH 1971	12-271/3-95
	Tradepak