Pfizer Bortezomib Dosage/Direction for Use

Pfizer Bortezomib Powder for Injection treatment must be initiated under supervision of a physician experienced in the treatment of cancer patients, however Pfizer Bortezomib Powder for Injection may be administered by a healthcare professional experienced in use of chemotherapeutic agents. Pfizer Bortezomib Powder for Injection must be reconstituted by a healthcare professional (see Cautions for Usage).
Monotherapy: Pfizer Bortezomib Powder for Injection is administered via intravenous or subcutaneous injection at the recommended dose of 1.3 mg/m² body surface area twice weekly for two weeks on days 1, 4, 8 and 11 followed by a 10-day rest period (days 12-21) in a 21-day treatment cycle. This 3-week period is considered a treatment cycle. It is recommended that patients receive 2 cycles of Pfizer Bortezomib Powder for Injection following a confirmation of a complete response. It is also recommended that responding patients who do not achieve a complete remission receive a total of 8 cycles of Pfizer Bortezomib Powder for Injection therapy. At least 72 hours should elapse between consecutive doses of Pfizer Bortezomib Powder for Injection.
Dose adjustments during treatment and re-initiation of treatment for monotherapy: Pfizer Bortezomib Powder for Injection treatment must be withheld at the onset of any Grade 3 nonhaematological or any Grade 4 haematological toxicities, excluding neuropathy as discussed as follows (see also Precautions). Once the symptoms of the toxicity have resolved, Pfizer Bortezomib Powder for Injection treatment may be re-initiated at a 25% reduced dose (1.3 mg/m² reduced to 1.0 mg/m², 1.0 mg/m² reduced to 0.7 mg/m²). If the toxicity is not resolved or if it recurs at the lowest dose, discontinuation of Pfizer Bortezomib Powder for Injection must be considered unless the benefit of treatment clearly outweighs the risk.
Neuropathic pain and/or peripheral neuropathy: Patients who experience bortezomib-related neuropathic pain and/or peripheral neuropathy are to be managed as presented in Table 7 (see Precautions). Patients with pre-existing severe neuropathy may be treated with Pfizer Bortezomib Powder for Injection only after careful risk/benefit assessment. (See Table 7.)

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Combination therapy with pegylated liposomal doxorubicin: Pfizer Bortezomib Powder for Injection is administered via intravenous or subcutaneous injection at the recommended dose of 1.3 mg/m² body surface area twice weekly for two weeks on Days 1, 4, 8, and 11 in a 21-day treatment cycle. This 3-week period is considered a treatment cycle. At least 72 hours should elapse between consecutive doses of Pfizer Bortezomib Powder for Injection.
Pegylated liposomal doxorubicin is administered at 30 mg/m² on Day 4 of the Pfizer Bortezomib Powder for Injection treatment cycle as a 1 hour intravenous infusion administered after the injection of Pfizer Bortezomib Powder for Injection.
Up to 8 cycles of this combination therapy can be administered as long as patients have not progressed and tolerate treatment. Patients achieving a complete response can continue treatment for at least 2 cycles after the first evidence of complete response, even if this requires treatment for more than 8 cycles. Patients whose levels of paraprotein continue to decrease after 8 cycles can also continue for as long as treatment is tolerated and they continue to respond.
For additional information concerning pegylated liposomal doxorubicin, see the corresponding Summary of Product Characteristics.
Combination with dexamethasone: Pfizer Bortezomib Powder for Injection is administered via intravenous or subcutaneous injection at the recommended dose of 1.3 mg/m² body surface area twice weekly for two weeks on Days 1, 4, 8, and 11 in a 21 day treatment cycle. This 3-week period is considered a treatment cycle. At least 72 hours should elapse between consecutive doses of Pfizer Bortezomib Powder for Injection.
Dexamethasone is administered orally at 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 of the Pfizer Bortezomib Powder for Injection treatment cycle.
Patients achieving a response or a stable disease after 4 cycles of this combination therapy can continue to receive the same combination for a maximum of 4 additional cycles.
For additional information concerning dexamethasone, see the corresponding Summary of Product Characteristics.
Dose adjustments for combination therapy for patients with progressive multiple myeloma: For Pfizer Bortezomib Powder for Injection dosage adjustments for combination therapy follow dose modification guidelines described under monotherapy as previously mentioned.
Combination therapy with melphalan and prednisone: Pfizer Bortezomib Powder for Injection is administered via intravenous or subcutaneous injection in combination with oral melphalan and oral prednisone as shown in Table 8. A 6-week period is considered a treatment cycle. In Cycles 1-4, Pfizer Bortezomib Powder for Injection is administered twice weekly on Days 1, 4, 8, 11, 22, 25, 29 and 32. In Cycles 5-9, Pfizer Bortezomib Powder for Injection is administered once weekly on Days 1, 8, 22 and 29. At least 72 hours should elapse between consecutive doses of Pfizer Bortezomib Powder for Injection.
Melphalan and prednisone should both be given orally on Days 1, 2, 3 and 4 of the first week of each Pfizer Bortezomib Powder for Injection treatment cycle.
Nine treatment cycles of this combination therapy are administered. (See Table 8.)

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Dose adjustments during treatment and re-initiation of treatment for combination therapy with melphalan and prednisone: Prior to initiating a new cycle of therapy: Platelet counts should be ≥70 × 10⁹/l and the absolute neutrophils count should be ≥1.0 × 10⁹/l; Non-haematological toxicities should have resolved to Grade 1 or baseline. (See Table 9.)

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For additional information concerning melphalan and prednisone, see the corresponding Summary of Product Characteristics.
Combination therapy with dexamethasone and thalidomide: Pfizer Bortezomib Powder for Injection is administered via intravenous or subcutaneous injection at the recommended dose of 1.3 mg/m² body surface area twice weekly for two weeks on Days 1, 4, 8, and 11 in a 28-day treatment cycle. This 4-week period is considered a treatment cycle. At least 72 hours should elapse between consecutive doses of Pfizer Bortezomib Powder for Injection.
Dexamethasone is administered orally at 40 mg on Days 1, 2, 3, 4, 8, 9, 10 and 11 of the Pfizer Bortezomib Powder for Injection treatment cycle.
Thalidomide is administered orally at 50 mg daily on Days 1-14 and if tolerated the dose is increased to 100 mg on Days 15-28, and thereafter may be further increased to 200 mg daily from cycle 2 (see Table 10).
Four treatment cycles of this combination are administered. It is recommended that patients with at least partial response receive 2 additional cycles. (See Table 10.)

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Dosage adjustments for transplant eligible patients: For Pfizer Bortezomib Powder for Injection dosage adjustments, dose modification guidelines described for monotherapy should be followed.
In addition, when Pfizer Bortezomib Powder for Injection is given in combination with other chemotherapeutic medicinal products, appropriate dose reductions for these products should be considered in the event of toxicities according to the recommendations in the Summary of Product Characteristics.
Special populations: Elderly: There is no evidence to suggest that dose adjustments are necessary in patients over 65 years of age with multiple myeloma or with mantle cell lymphoma.
There are no studies on the use of bortezomib in elderly patients with previously untreated multiple myeloma who are eligible for high-dose chemotherapy with haematopoietic stem cell transplantation. Therefore no dose recommendations can be made in this population.
In a study in previously untreated mantle cell lymphoma patients, 42.9% and 10.4% of patients exposed to bortezomib were in the range 65-74 years and ≥75 years of age, respectively. In patients aged ≥75 years, both regimens, BR-CAP as well as R-CHOP, were less tolerated (see Adverse Actions).
Hepatic impairment: Patients with mild hepatic impairment do not require a dose adjustment and should be treated per the recommended dose. Patients with moderate or severe hepatic impairment should be started on Pfizer Bortezomib Powder for Injection at a reduced dose of 0.7 mg/m² per injection during the first treatment cycle, and a subsequent dose escalation to 1.0 mg/m² or further dose reduction to 0.5 mg/m² may be considered based on patient tolerability (see Table 11 and Precautions and Pharmacology: Pharmacokinetics under Actions). (See Table 11.)

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Renal impairment: The pharmacokinetics of bortezomib are not influenced in patients with mild to moderate renal impairment (Creatinine Clearance [CrCL] >20 ml/min/1.73 m²); therefore, dose adjustments are not necessary for these patients. It is unknown if the pharmacokinetics of bortezomib are influenced in patients with severe renal impairment not undergoing dialysis (CrCL <20 ml/min/1.73 m²). Since dialysis may reduce bortezomib concentrations, Pfizer Bortezomib Powder for Injection should be administered after the dialysis procedure (see Pharmacology: Pharmacokinetics under Actions).
Paediatric population: The safety and efficacy of bortezomib in children below 18 years of age have not been established (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions). Currently available data are described in Pharmacology: Pharmacodynamics under Actions but no recommendation on a posology can be made.
Method of administration: Pfizer Bortezomib Powder for Injection is available for intravenous or subcutaneous administration.
Pfizer Bortezomib Powder for Injection should not be given by other routes. Intrathecal administration has resulted in death.
Intravenous injection: Pfizer Bortezomib Powder for Injection reconstituted solution is administered as a 3-5 second bolus intravenous injection through a peripheral or central intravenous catheter followed by a flush with sodium chloride 9 mg/ml (0.9%) injection. At least 72 hours should elapse between consecutive doses of Pfizer Bortezomib Powder for Injection.
Subcutaneous injection: Pfizer Bortezomib Powder for Injection reconstituted solution is administered subcutaneously through the thighs (right or left) or abdomen (right or left). The solution should be injected subcutaneously, at a 45-90° angle.
Injection sites should be rotated for successive injections.
If local injection site reactions occur following Pfizer Bortezomib Powder for Injection subcutaneous injection, either a less concentrated Pfizer Bortezomib Powder for Injection solution (Pfizer Bortezomib Powder for Injection to be reconstituted to 1 mg/ml instead of 2.5 mg/ml) may be administered subcutaneously or a switch to intravenous injection is recommended.
When Pfizer Bortezomib Powder for Injection is given in combination with other medicinal products, refer to the Summary of Product Characteristics of these products for instructions for administration.