Bortezomib Taro 3.5 mg

/ Taro International Ltd

General Dosing Guidelines: The recommended starting dose of Bortezomib is 1.3 mg/m². Bortezomib may be administered intravenously at a concentration of 1 mg/mL, or subcutaneously at a concentration of 2.5 mg/mL. When administered intravenously, Bortezomib is administered as a 3 to 5 second bolus intravenous injection.
Because each route of administration has a different reconstituted concentration, caution should be used when calculating the volume to be administered.
BORTEZOMIB IS FOR INTRAVENOUS OR SUBCUTANEOUS USE ONLY.
Bortezomib must not be administered by any other route. Intrathecal administration has resulted in death.
Dosage in Previously Untreated Multiple Myeloma: Bortezomib is administered in combination with oral melphalan and oral prednisone for nine 6-week treatment cycles as shown in Table 1 at the attached doctor’s leaflet. In Cycles 1-4, Bortezomib is administered twice weekly (days 1, 4, 8, 11, 22, 25, 29 and 32). In Cycles 5-9, Bortezomib is administered once weekly (days 1, 8, 22 and 29).
At least 72 hours should elapse between consecutive doses of Bortezomib.
Dose Regimen for Patients with Previously Untreated Multiple Myeloma: Please see prescribing information for full details.

Multiple Myeloma
Mantle Cell Lymphoma: For the treatment of patients with mantle cell lymphoma who have received at least one prior therapy.
Bortezomib Taro 3.5 mg in combination with rituximab, cyclophosphamide, doxorubicin and prednisone is indicated for the treatment of adult patients with previously untreated mantle cell lymphoma who are unsuitable for haematopoietic stem cell transplantation.

Hypersensitivity to bortezomib, boron or mannitol. Acute diffuse infiltrative pulmonary and pericardial disease. Intrathecal administration.
See prescribing information for full details.

Patients with pre-existing symptoms of peripheral neuropathy (numbness, pain or a burning feeling in the feet or hands) may experience worsening during treatment. Patients with a history of syncope, patients receiving medications known to be associated with hypotensions and patients who are dehydrated. Patients with risk factors for or existing heart disease. Patients with renal impairment: No clinical information is available on patients with creatinine clearance values less than 13 ml/minute and patients on hemodialysis. The safety and effectiveness in children have not been established.
See prescribing information for full details.

Asthenic conditions (including fatigue, malaise and weakness), hypotension, nausea, vomiting, diarrhea, constipation, decreased appetite, thrombocytopenia, neutropenia, peripheral neuropathy (including peripheral sensory neuropathy and aggravated peripheral neuropathy), pyrexia, anemia, herpes virus infection.
See prescribing information for full details.

Bortezomib is a substrate of cytochrome P450 enzyme 3A4, 2C19 and 1A2.
CYP3A4 inhibitors: Co-administration of ketoconazole, a strong CYP3A4 inhibitor, increased the exposure of bortezomib by 35% in 12 patients. Monitor patients for signs of bortezomib toxicity and consider a bortezomib dose reduction if bortezomib must be given in combination with strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir).
CYP3A4 inducers: Co-administration of rifampin, a strong CYP3A4 inducer, is expected to decrease the exposure of bortezomib by at least 45%. Because the drug interaction study (n=6) was not designed to exert the maximum effect of rifampin on bortezomib PK, decreases greater than 45% may occur.
Efficacy may be reduced when bortezomib is used in combination with strong CYP3A4 inducers; therefore, concomitant use of strong CYP3A4 inducers is not recommended in patients receiving bortezomib (e.g., rifampicin, carbamazepine, phenytoin, phenobarbital).
St. John’s Wort (Hypericum perforatum) may decrease bortezomib exposure unpredictably and should be avoided.
Melphalan-Prednisone: Co-administration of melphalan-prednisone increased the exposure of bortezomib by 17% in 21 patients. However, this increase is unlikely to be clinically relevant.
See prescribing information for full details.

Pregnancy: Category D. Bortezomib may cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies in pregnant women. If bortezomib is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus.
Lactation: Not known if excreted in beast milk.

There is no known specific antidote for bortezomib overdosage. In humans, fatal outcomes following the administration of more than twice the recommended therapeutic dose have been reported, which were associated with the acute onset of symptomatic hypotension (5.2) and thrombocytopenia (5.7). In the event of an overdosage, the patient’s vital signs should be monitored and appropriate supportive care given to maintain blood pressure (such as fluids, pressors, and/or inotropic agents) and body temperature.
Studies in monkeys and dogs showed that intravenous bortezomib as low as 2 times the recommended clinical dose on a mg/m² basis were associated with increases in heart rate, decreases in contractility, hypotension, and death. In dog studies, a slight increase in the corrected QT interval was observed at doses resulting in death. In monkeys, doses of 3.0 mg/m² and greater (approximately twice the recommended clinical dose) resulted in hypotension starting at 1 hour post-administration, with progression to death in 12 to 14 hours following drug administration.

Stability: Unopened vials are stable until the date indicated on the package when stored in the original package protected from light.
Do not store above 25°C.
From a microbiological point of view, the reconstituted solution should be used immediately after preparation. If the reconstituted solution is not used immediately, in-use storage times and conditions prior to use are the responsibility of the user. However, the chemical and physical in-use stability of the reconstituted solution 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.