DEPOCYTE Suspension for injection Ref.[2692] Active ingredients: Cytarabine

DepoCyte should be administered only under the supervision of a physician experienced in the use of cancer chemotherapeutic agents.

Posology

Paediatric population

Safety and efficacy in children aged under 18 years have not been established. Currently available data are described in section 5.1 but no recommendation on a posology can be made. DepoCyte is not recommended for use in children and adolescents until further data become available.

Adults and the elderly

For the treatment of lymphomatous meningitis, the dose for adults is 50 mg (one vial) administered intrathecally (lumbar puncture or intraventricularly via an Ommaya reservoir). The following regimen of induction, consolidation and maintenance therapy is recommended:

Induction therapy: 50 mg administered every 14 days for 2 doses (weeks 1 and 3).

Consolidation therapy: 50 mg administered every 14 days for 3 doses (weeks 5, 7 and 9) followed by an additional dose of 50 mg at week 13.

Maintenance therapy: 50 mg administered every 28 days for 4 doses (weeks 17, 21, 25 and 29).

Method of administration

DepoCyte is to be administered by slow injection over a period of 1-5 minutes directly into the cerebrospinal fluid (CSF) via either an intraventricular reservoir or by direct injection into the lumbar sac. Following administration by lumbar puncture, it is recommended that the patient should be instructed to lie flat for one hour. All patients should be started on dexamethasone 4 mg twice daily either orally or intravenously for 5 days beginning on the day of injection of DepoCyte.

DepoCyte must not be administered by any other route of administration. DepoCyte must be used as supplied; it must not be diluted (see section 6.2). Patients should be observed by the physician for immediate toxic reactions.

If neurotoxicity develops, the dose should be reduced to 25 mg. If it persists, treatment with DepoCyte should be discontinued.

No overdoses with DepoCyte have been reported. An overdose with DepoCyte may be associated with severe arachnoiditis including encephalopathy.

In an early uncontrolled study without dexamethasone prophylaxis, single doses up to 125 mg were administered. One patient at the 125 mg dose level died of encephalopathy 36 hours after receiving DepoCyte intraventricularly. This patient, however, was also receiving concomitant whole brain irradiation and had previously received intraventricular methotrexate.

There is no antidote for intrathecal DepoCyte or unencapsulated cytarabine released from DepoCyte. Exchange of cerebrospinal fluid with isotonic sodium chloride solution has been carried out in a case of intrathecal overdose of free cytarabine and such a procedure may be considered in the case of DepoCyte overdose. Management of overdose should be directed at maintaining vital functions.

18 months.

After first opening: from a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 4 hours at 18 to 22°C.

Store in a refrigerator (2°C-8°C).

Do not freeze.

Type I glass vial closed with a fluororesin faced butyl rubber stopper and sealed with an aluminium flip-off seal containing 50 mg cytarabine in 5 ml suspension.

DepoCyte is supplied in individual cartons each containing one single-dose vial.

Preparation of DepoCyte

Given its toxic nature, special precautions should be taken in handling DepoCyte. See ‘Precautions for the handling and disposal of DepoCyte’ below.

Vials should be allowed to warm to room temperature (18°C-22°C) for a minimum of 30 minutes and be gently inverted to resuspend the particles immediately prior to withdrawal from the vial. Vigorous shaking should be avoided. No further reconstitution or dilution is required.

DepoCyte administration

DepoCyte must only be administered by the intrathecal route.

DepoCyte should be withdrawn from the vial immediately before administration. Since it is a single use vial and does not contain any preservative, the medicinal product should be used within 4 hours of withdrawal from the vial. Unused medicinal product must be discarded and not used subsequently. DepoCyte must not be mixed with any other medicinal products (see section 6.2). The suspension must not be diluted.

In-line filters must not be used when administering DepoCyte. DepoCyte is administered directly into the CSF via an intraventricular reservoir or by direct injection into the lumbar sac. DepoCyte should be injected slowly over a period of 1-5 minutes. Following administration by lumbar puncture, the patient should be instructed to lie flat for one hour. Patients should be observed by the physician for immediate toxic reactions.

All patients should be started on dexamethasone 4 mg twice daily either orally or intravenously for 5 days beginning on the day of DepoCyte injection.

Precautions for the handling and disposal of DepoCyte

The following protective recommendations are given due to the toxic nature of this substance:

• personnel should be trained in good technique for handling anticancer agents;
• male and female staff who are trying to conceive and female staff who are pregnant should be excluded from working with the substance;
• personnel must wear protective clothing: goggles, gowns, disposable gloves and masks;
• a designated area should be defined for preparation (preferably under a laminar flow system). The work surface should be protected by disposable, plastic backed, absorbent paper;
• all items used during administration or cleaning should be placed in high risk, waste-disposal bags for high temperature incineration;
• in the event of accidental contact with the skin, exposed areas should be washed immediately with soap and water;
• in the event of accidental contact with the mucous membranes, exposed areas should be treated immediately by copious lavage with water; medical attention should be sought.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.