Pharmaceutical particulars : מידע רוקחי

6. Pharmaceutical particulars
6.1. List of excipients
P owder
Povidone
Hydrochloric acid
S olvent
Sodium citrate dihydrate
Propylene glycol
Ethanol 96 %
Water for injection
6.2. Incompatibilities

Melphalan is not compatible with infusion solutions containing dextrose and it is recommended that ONLY sodium chloride 9 mg/ml (0.9%) solution for injection is used.

6.3. Shelf life

Unopened powder and solvent: The expiry date of the product is indicated on the packaging materials .
Reconstituted Solution: Once reconstituted the product should be used immediately. Any unused portion should be discarded. The reconstituted solution should not be kept in the refrigerator since the active substance may precipitate.
Melphalan has a limited shelf-life and the rate of decomposition increases rapidly as the temperature increases.
Reconstituted and further diluted solution for infusion: The total time from the preparation of reconstituted solution to the completion of infusion should not exceed 1.5 hours at room temperature (approximately 25°C).

6.4. Special precautions for storage

This medicinal product does not require any special temperature storage conditions but it is recommended to be stored in room temperature. Keep the vial in the outer carton, in order to protect from light. For storage conditions of the medicinal product after reconstitution and dilution, see section 6.3.

6.5. Nature and contents of container

Powder: Clear type I glass vial sealed with omniflex 3G coated bromobutyl rubber stopper and flip off aluminium seal having orange colour polypropylene button with matte finish.
Vials may or may not be sleeved with shrink sleeves.
Pack size: 1 vial containing 50 mg melphalan.
Solvent: Clear type I glass vial sealed with coated bromobutyl rubber stopper and flip off aluminium seal having orange colour polypropylene button with matte finish.
Pack size: 1 vial containing 10 ml sterile solvent.
Each pack contains 1 vial with powder and 1 vial with solvent.


6.6. Special precautions for disposal and other handling
Procedures for proper handling and disposal of cytotoxic medicinal products should be observed: - The employees are to be instructed in the reconstitution of the drug.
- Pregnant women should be excluded from handling this medicine.
- The personnel should wear suitable protective clothing with face masks, safety goggles and gloves when reconstituting the preparation.
- Any items used for administration or cleaning, including gloves, should be disposed of in waste containers for contaminated material to high-temperature combustion. Liquid waste can be discharged with plenty of water.
In case of accidental eye contact with Melphalan immediately rinse with sodium chloride eyewash or plenty of water and immediately consult a doctor. In case of skin contact, immediately wash the affected areas with soap and plenty of cold water and consult a doctor immediately. The spilled solution should be immediately wiped with a damp paper towel, which must then be disposed of safely. The contaminated surfaces must be washed with plenty of water.
Reconstitution
Melphalan should be prepared at room temperature (approximately 25°C), by reconstituting the powder with the solvent-diluent provided.

It is important that both the powder and the solvent provided are at room temperature (approximately 25°C) before starting reconstitution.

10 ml of the solvent should be added quickly as a single quantity into the vial containing the powder, using a sterile needle and syringe. A 21 gauge or higher gauge needle should be used for piercing of vial stopper during reconstitution. For smooth and effective penetration, the needle should be inserted perpendicularly into the stopper, not too fast or too rough without twisting. Immediately shake the vial vigorously (for approximately 5 minutes) until a clear solution, without visible particles, is obtained. Rapid addition of diluent followed by immediate vigorous shaking is important for proper dissolution.

Shaking of the formulation leads to a significant amount of very small air bubbles. These bubbles can remain for 2 to 3 minutes as the resulting solution is quite viscous. This can make it difficult to assess the clarity of the solution.

Each vial must be reconstituted individually in this manner. The resulting solution contains the equivalent of 5 mg per ml anhydrous melphalan. Failure to follow above mentioned preparation steps may result in incomplete dissolution of Melphalan.

Melphalan solution has limited stability and should be prepared immediately before use.
The reconstituted solution should not be refrigerated as this will cause precipitation.

Admixture
Take 10 ml of above reconstituted solution having concentration of 5 mg/ml of anhydrous melphalan into infusion bag containing 100 ml of 0.9% Sodium chloride injection. Mix this diluted solution thoroughly to give nominal concentration of 0.45 mg/ml of anhydrous melphalan.

When further diluted in an infusion solution, Melphalan has reduced stability and the rate of degradation increases rapidly with rise in temperature. If Melphalan is infused at a room temperature of approximately 25°C, the maximum time from preparation of the solution to the completion of infusion should not exceed
1.5 hours.

Melphalan is not compatible with infusion solutions containing dextrose and it is recommended that only sodium chloride 9 mg/ml (0.9%) solution for injection is used.
Should any visible turbidity or crystallisation appear in the reconstituted or diluted solutions, the preparation must be discarded.

Disposal
Any solution unused after 1.5 hours should be discarded according to standard guidelines for handling and disposal of cytotoxic medicinal products.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements for cytotoxic medicinal products.