CYTARABINE SOLUTION FOR INJECTION 100 MG/ML [SIN05521P]

Product Info

CYTARABINE SOLUTION FOR INJECTION 100 MG/ML

[SIN05521P]

INDICATIONS

Cytarabine is indicated primarily for:

• Induction and maintenance of remission in acute myelocytic leukemia of both adults and children.

It has also been found to be useful in the treatment of other leukemias such as:

• Acute lymphocytic leukemia.

• Chronic myelocytic leukemia (blast phase).

Cytarabine may be used alone or in combination with other antineoplastic agents, the best results are often obtained with combination therapy. Children with non-Hodgkin’s lymphoma have benefited from a combination drug program (LSA2L2) that includes cytarabine. Remissions induced by cytarabine not followed by maintenance treatment have been brief. Maintenance therapy has extended these and provided useful and comfortable remissions with relatively little toxicity. Cytarabine has been used intrathecally in meningeal leukemia. Focal leukemic involvement of the central nervous system (CNS) may not respond to intrathecal cytarabine and may better be treated with radiotherapy.

DOSAGE AND ADMINISTRATION

Cytarabine may be administered by intravenous injection or infusion, or subcutaneously. It has been administered intrathecally as a special application.

Thrombophlebitis has occurred at the site of drug injection or infusion in some patients, and rarely patients have noted pain and inflammation at subcutaneous injection sites. In most instances, however, the drug has been well tolerated.

Patients can tolerate higher total doses when they receive the drug by rapid intravenous injection as compared with slow infusion. This phenomenon is related to the drug's rapid inactivation and brief exposure of susceptible normal and neoplastic cells to significant levels after rapid injection. Normal and neoplastic cells seem to respond in somewhat parallel fashion to these different modes of administration and no clear-cut clinical advantage has been demonstrated for either.

Dose regimens are usually at the discretion of the attending physician. Clinical and haematological responses and tolerance vary between patients and a dose which gives optimal therapeutic effect with minimum toxicity should be used.

Normal Adult Dosage, Single Agent Therapy:
Doses of up to 200 mg/m² daily as a continuous intravenous infusion for five days (120 hours) repeated at approximately two weekly intervals have been used. Modification must be made based on results of daily haematological monitoring. After each five day treatment, drug therapy should be withdrawn to allow for bone marrow recovery.

Dilutions of cytarabine should be made in Glucose 5% or Sodium Chloride 0.9% Intravenous Infusions to concentrations as low as 0.1 mg/mL. In order to reduce any microbiological hazard it is recommended that dilution should be effected immediately prior to use and infusion commenced as soon as practicable after preparation of the admixture. Infusion should be completed within 24 hours of preparation and any residue discarded. Any storage should be between 2°C and 8°C, protected from light.

Maintenance of Acute Myelocytic Leukaemia in Adults:
Maintenance programs are generally modifications of induction programs. Similar schedules of drug therapy to those used for induction are normally employed. Most programs have a greater interval between courses of therapy during remission maintenance.

Induction and Maintenance of Acute Myelocytic Leukaemia (AML) in Children:
Childhood AML has been shown to respond better than adult AML given similar regimes. Where the adult dosage is given in terms of body weight or surface area, the paediatric dosage may be calculated on the same basis, being adjusted on the consideration of such factors as age, body weight or body surface area.

Conditions Requiring Dosage Adjustment:
Myelosuppression: The dose of cytarabine should be modified if signs of severe myelosuppression appear, e.g., consideration of discontinuation of the drug if the polymorphonuclear granulocyte count falls below 1 x 10⁹ L or the platelet count falls below 50 x 10⁹ L.

Combination Therapy: Dosage modifications may have to be made when cytarabine is used in combination with other myelosuppressive drugs. Before instituting a programme of combined therapy, the physician should be familiar with the adverse effects, precautions, contraindications and warnings applicable to all the drugs in the programme.

Intrathecal Use in Meningeal Leukaemia: Cytarabine has been used intrathecally in acute leukaemia in doses ranging from 5 mg/m² to 75 mg/m² of body surface area. The frequency of administration varied from once a day for 4 days to once every 4 days. The most frequently used dose was 30 mg/m² every 4 days until cerebrospinal fluid findings were normal, followed by one additional treatment. The dosage schedule is usually governed by the type and severity of central nervous system manifestations and the response to previous therapy.

Incompatibilities
Cytarabine must not be mixed with other medicinal products except those mentioned above. Cytarabine has been known to be physically incompatible with heparin, insulin, fluorouracil, penicillins such as oxacillin and penicillin G sodium, and methylprednisolone sodium succinate.

Handling Precautions
As with all antineoplastic agents, trained personnel should prepare Cytarabine Injection. This should be performed in a designated area (preferably a cytotoxic laminar flow cabinet). Protective gown, mask, gloves and appropriate eye protection should be worn when handling cytarabine. Where solution accidentally contacts skin or mucosa, the affected area should be immediately washed thoroughly with soap and water. It is recommended that pregnant personnel not handle cytotoxic agents such as cytarabine.

Luer-Lock fitting syringes are recommended. Large bore needles are recommended to minimise pressure and possible formation of aerosols. Aerosols may also be reduced by using a venting needle during preparation. Items used to prepare cytarabine, or articles associated with body waste, should be disposed of by placing in a double sealed polythene bag and incinerating at 1100°C.

Spills and Disposal
If spills occur, restrict access to the affected area. Wear two pairs of gloves (latex rubber), a respirator mask, a protective gown and safety glasses. Limit the spread of the spill by covering with a suitable material such as absorbent towel or adsorbent granules. Spills may also be treated with 5% sodium hypochlorite. Collect up absorbent/adsorbent material and other debris from spill and place in a leak proof plastic container and label accordingly. Cytotoxic waste should be regarded as hazardous or toxic and clearly labeled ‘CYTOTOXIC WASTE FOR INCINERATION AT 1100°C’. Waste material should be incinerated at 1100°C for at least 1 second. Cleanse the remaining spill area with copious amounts of water.

CONTRAINDICATIONS

Known hypersensitivity to cytarabine.