pms-Bortezomib Dosage/Direction for Use

The dose of PMS-BORTEZOMIB will be worked out according to the patient's height and weight (body surface area). The usual starting dose of PMS-BORTEZOMIB is 1.3 mg/m² body surface area twice a week.
The dose and total number of treatment cycles may be changed, depending on the patient's response to the treatment on the occurrence of certain side effects and on the underlying conditions (e.g. liver problems).
Progressive multiple myeloma: When PMS-BORTEZOMIB is given alone, the patient will receive 4 doses of PMS-BORTEZOMIB intravenously or subcutaneously on days 1, 4, 8 and 11, followed by a 10-day 'rest period' without treatment. This 21-day period (3 weeks) corresponds to one treatment cycle. The patient might receive up to 8 cycles (24 weeks).
The patient may also be given PMS-BORTEZOMIB together with the medicines pegylated liposomal doxorubicin or dexamethasone.
When PMS-BORTEZOMIB is given together with pegylated liposomal doxorubicin, the patient will receive PMS-BORTEZOMIB intravenously or subcutaneously as a 21-day treatment cycle and pegylated liposomal doxorubicin 30 mg/m² is given on day 4 of the PMS-BORTEZOMIB 21-day treatment cycle as an intravenous infusion after the PMS-BORTEZOMIB injection.
The patient might receive up to 8 cycles (24 weeks).
When PMS-BORTEZOMIB is given together with dexamethasone, the patient will receive PMS-BORTEZOMIB intravenously or subcutaneously as a 21-day treatment cycle and dexamethasone 20 mg is given orally on days 1, 2, 4, 5, 8, 9, 11, and 12, of the PMS-BORTEZOMIB, 21-day treatment cycle.
The patient might receive up to 8 cycles (24 weeks).
Previously untreated multiple myeloma: If the patient has not been treated before for multiple myeloma, and is not suitable for blood stem cell transplantation, the patient will receive PMS-BORTEZOMIB together with two other medicines; melphalan and prednisone.
In this case, the duration of a treatment cycle is 42 days (6 weeks). The patient will receive 9 cycles (54 weeks).
In cycles 1 to 4, PMS-BORTEZOMIB is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29 and 32.
In cycles 5 to 9, PMS-BORTEZOMIB is administered once weekly on days 1, 8, 22 and 29.
Melphalan (9 mg/m²) and prednisone (60 mg/m²) are both given orally on days 1, 2, 3 and 4 of the first week of each cycle.
If the patient has not been treated before for multiple myeloma, and is suitable for blood stem cell transplantation, the patient will receive PMS-BORTEZOMIB intravenously or subcutaneously together with the medicines dexamethasone, or dexamethasone and thalidomide, as induction treatment.
When PMS-BORTEZOMIB is given together with dexamethasone, the patient will receive PMS-BORTEZOMIB intravenously or subcutaneously as a 21-day treatment cycle and dexamethasone 40 mg is given orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the PMS-BORTEZOMIB 21-day treatment cycle.
The patient will receive 4 cycles (12 weeks).
When PMS-BORTEZOMIB is given together with thalidomide and dexamethasone, the duration of a treatment cycle is 28 days (4 weeks).
Dexamethasone 40 mg is given orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the PMS-BORTEZOMIB 28-day treatment cycle and thalidomide is given orally daily at 50 mg up to day 14 of the first cycle, and if tolerated the thalidomide dose is increased to 100 mg on days 15-28 and may be further increased to 200 mg daily from the second cycle onwards.
The patient might receive up to 6 cycles (24 weeks).
How PMS-BORTEZOMIB is given: This medicine is for intravenous or subcutaneous use. PMS-BORTEZOMIB will be administered by a health care professional experienced in the use of cytotoxic medicines. PMS-BORTEZOMIB powder has to be dissolved before administration. This will be done by a healthcare professional. The resulting solution is then either injected into a vein or under the skin. Injection into a vein is rapid, taking 3 to 5 seconds. Injection under the skin is in either the thighs or the abdomen.
Only the 3.5 mg vial can be administered subcutaneously.
Reconstitution for Intravenous Injection and Subcutaneous Injection: Note: PMS-BORTEZOMIB is a cytotoxic agent. Therefore, caution should be used during handling and preparation. Use of gloves and other protective clothing to prevent skin contact is recommended.
Aseptic technique must be strictly observed throughout handling of PMS-BORTEZOMIB since no preservative is present.
1. Preparation of the 3.5 mg vial: Intravenous Injection: carefully add 3.5 ml of sterile, 9 mg/ml (0.9%) sodium chloride solution for injection to the vial containing the PMS-BORTEZOMIB powder by using a syringe of the appropriate size without removing the vial stopper. Dissolution of the lyophilized powder is completed in less than 2 minutes.
The concentration of the resulting solution will be 1 mg/ml. The solution will be clear and colourless, with a final pH of 4 to 7. There is no need to check the pH of the solution.
Subcutaneous Injection: carefully add 1.4 ml of sterile, 9 mg/ml (0.9%) sodium chloride solution for injection to the vial containing the PMS-BORTEZOMIB powder by using a syringe of the appropriate size without removing the vial stopper. Dissolution of the lyophilised powder is completed in less than 2 minutes.
The concentration of the resulting solution will be 2.5 mg/ml. The solution will be clear and colourless, with a final pH of 4 to 7. There is no need to check the pH of the solution.
2. Before administration, visually inspect the solution for particulate matter and discolouration. If any discolouration or particulate matter is observed, the solution should be discarded. Be sure that the correct dose is being given for the intravenous route of administration (1 mg/ml) or for the subcutaneous route of administration (2.5 mg/ml).
3. The reconstituted solution/product is preservative free and should be used immediately after preparation. However, the chemical and physical in-use stability has been demonstrated for 8 hours at 25°C stored in the original vial and/or a syringe. The total storage time for the reconstituted medicinal product should not exceed 8 hours prior to administration. If the reconstituted solution is not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.
It is not necessary to protect the reconstituted medicinal product from light.
Administration: Once dissolved, withdraw the appropriate amount of the reconstituted solution according to calculated dose based upon the patient´s Body Surface Area.
Confirm the dose and concentration in the syringe prior to use (check that the syringe is marked as intravenous/subcutaneous administration).
Intravenous Injection: Inject the solution as a 3-5 second bolus intravenous injection through a peripheral or central intravenous catheter into a vein.
Flush the peripheral or intravenous catheter with sterile, 9 mg/ml (0.9%) sodium chloride solution.
Subcutaneous Injection: Inject the solution subcutaneously, under a 45-90° angle.
The reconstituted solution is administered subcutaneously through the thighs (right or left) or abdomen (right or left).
Injection sites should be rotated for successive injections.
If local injection site reactions occur following PMS-BORTEZOMIB injection subcutaneously, either a less concentrated PMS-BORTEZOMIB solution (1 mg/ml instead of 2.5 mg/ml) may be administered subcutaneously or a switch to intravenous injection is recommended.
PMS-BORTEZOMIB 3.5 mg powder for solution for injection IS FOR SUBCUTANEOUS OR INTRAVENOUS USE. Do not give by other routes. Intrathecal administration has resulted in death.