CARMUSTINE OBVIUS Powder and solvent for solution for infusion Ref.[6549] Active ingredients: Carmustine

Carmustine Obvius must be administered only by specialists experienced in the field of chemotherapy and under appropriate medical supervision

Posology

Initial doses

The recommended dose of Carmustine Obvius as a single agent in previously untreated patients is 150 to 200 mg/m² intravenously every 6 weeks. This may be given as a single dose or divided into daily infusions such as 75 to 100 mg/m² on two successive days.

When Carmustine Obvius is used in combination with other myelosuppressive medicinal products or in patients in whom bone marrow reserve is depleted, the doses should be adjusted according to the haematologic profile of the patient as shown below.

Monitoring and subsequent doses

A repeat course of Carmustine Obvius should not be given until circulating blood elements have returned to acceptable levels (platelets above 100,000/mm³, leukocytes above 4,000/mm³), and this is usually in six weeks. Blood counts should be monitored frequently and repeat courses should not be given before six weeks because of delayed haematologic toxicity.

Doses subsequent to the initial dose should be adjusted according to the haematologic response of the patient to the preceding dose, in both monotherapy as well as in combination therapy with other myelosuppressive medicinal products. The following schedule is suggested as a guide to dosage adjustment:

Table 1:

In cases where the nadir after initial dose does not fall in the same row for leucocytes and platelets (e.g. leucocytes >4,000 and platelets <25,000) the value given the lowest percentage of prior dose should be used (e.g. platelets <25,000 then a maximum of 50% of prior dose should be given).

There are no limits for the period of application of carmustine therapy. In case the tumor remains incurable or some serious or intolerable adverse reactions appear, the carmustine therapy must be terminated.

Special populations

Paediatric population

Carmustine is contraindicated in children and adolescents aged <18 years (see section 4.3)

Elderly

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dose range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and take into consideration concomitant disease or therapy with other medicinal products. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and the glomerular filtration rate should be monitored and the dose reduced according to this.

Renal impairment

For patients with renal impairment the dose of Carmustine Obvius should be reduced if the glomerular filtration rate is reduced.

Method of administration

Carmustine Obvius is for intravenous use after reconstitution and further dilution.

By reconstituting the powder with the solvent provided, a solution has to be prepared by adding additional 27 ml water for injections. Reconstitution and dilution, as recommended, results in a clear, colourless to light yellow stock solution which has to be further diluted with 500 ml sodium chloride 9 mg/ml (0.9%) solution for injection, or glucose 50 mg/ml (5%) solution for injection.

The resulting ready-to-use solution for infusion should then be administered immediately by intravenous drip over a one- to two-hour period protected from light. The duration of infusion should not be less than one hour, otherwise it leads to burning and pain in the injected area. The injected area should be monitored during the administration.

For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.

The main symptom of intoxication is myelosuppression. In addition, the following serious adverse reactions may occur: liver necrosis, interstitial pneumonitis, encephalomyelitis. A specialized antidote is not available.

Unopened vial: 2 years.

After reconstitution and dilution: After reconstitution and dilution, the solution should be administered within 3 hours after reconstitution and dilution of the product. The solution should be protected from light until end of administration.

Store and transport refrigerated (2°C-8°C).

Keep the vial and ampoule in the outer carton in order to protect from light.

For storage conditions after reconstitution and further dilution of the medicinal product, see section 6.3.

Powder: Brown type I hydrolytic glass vial (50 ml) with light grey 20 mm bromobutyl rubber stopper and sealed with a dark red aluminium flip-off cap.

Solvent: Clear type I glass ampoule (5 ml).

One pack contains one vial with 100 mg of powder for concentrate for solution for infusion and one ampoule with 3 ml of solvent.

The carmustine powder for concentrate for solution for infusion contains no preservative and is not intended as a multiple dose vial. Reconstitution and further dilutions should be carried out under aseptic conditions.

The dry frozen product does not contain any preservatives and is suitable only for one use. The lyophilisate can appear as a fine powder, however handling can cause it to appear as a more heavy and lumpy lyophilisate than as a powdery lyophilisate due to the mechanical instability of the freeze drying cake. The presence of an oily film can be an indication of melting of the medicinal product. Such products are not accepted for use due to the risk of temperature excursions to more than 30°C.This medicinal product should not be used any further. When you are not clear about the fact whether the product is adequately cooled, then you should immediately inspect each and every vial in the carton. For verification, hold the vial in bright light.

Reconstitution and dilution of the powder for concentrate for solution for infusion

Dissolve the Carmustine (100 mg powder) with 3 ml of the supplied sterile refrigerated ethanol solvent in the primary packaging (brown glass vial). Carmustine must be completely dissolved in ethanol before sterile water for injections is added.

Then aseptically add 27 ml of sterile water for injection to the alcohol solution. The 30 ml stock solution needs to be mixed thoroughly. Reconstitution, as recommended, results in a clear, colourless to light yellow stock solution.

The 30 ml stock solution is to be diluted immediately by adding the 30 ml stock solution to either 500 ml 5% glucose or 500 ml sodium chloride 9 mg/ml (0.9%) solution for injection in glass containers. The 530 ml diluted solution (i.e. the ready-to-use solution) should be mixed for at least 10 seconds before administration. The Ready-to-Use solution should be administered over 1-2 hours and administration should be finalised within 3 hours from reconstitution of the product.

Administration of the infusion should be performed using a PVC free PE infusion set. During administration of the medicinal product, the container shall be of suitable glass ware. Further, the ready-to-use solution solution needs to be protected from light (e.g. using alu-foil wrapped around the container of the ready-to-use solution) and preferably kept at temperatures below 20-22°C as Carmustine degrades faster at higher temperatures.

Infusion of Carmustine Obvius in less than one hour may produce intense pain and burning at the site of injection (see section 4.2).

Guidelines for the safe handling and disposal of antineoplastic agents must be observed.