Mantle Cell Lymphoma (MCL) Treatments
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Generic Name
Bortezomib
Brand Names
Boruzu, Velcade
FDA approval date: May 13, 2003
Classification: Proteasome Inhibitor
Form: Injection
What is Boruzu (Bortezomib)?
BORUZU is a proteasome inhibitor indicated for: treatment of adult patients with multiple myeloma.
Approved To Treat
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Related Clinical Trials
A Phase I/II Trial of Allogeneic Reduced-Intensity, HLA-Haploidentical Allogeneic Hematopoietic Cell Transplantation Followed by GVHD Prophylaxis With Cyclophosphamide, Bortezomib and Maraviroc for Hematologic Malignancies in People Living With HIV (PLWH)
Background: People living with HIV(PLWH) are at a higher risk for cancers that may be curable with a bone marrow transplant. HIV infection itself is no longer a reason to not get a transplant, for patients who otherwise have a standard reason to need transplant.
A Phase 3, Two-Stage, Randomized, Multicenter, Open-Label Study Comparing Mezigdomide (CC-92480), Bortezomib and Dexamethasone (MEZIVd) Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) in Subjects With Relapsed or Refractory Multiple Myeloma (RRMM): SUCCESSOR-1
Summary: The purpose of this study is to compare the efficacy and safety of mezigdomide (CC-92480), bortezomib and dexamethasone (MeziVd) versus pomalidomide, bortezomib and dexamethasone (PVd) in participants with relapsed or refractory multiple myeloma (RRMM) who received between 1 to 3 prior lines of therapy and who have had prior lenalidomide exposure.
A Phase III Open-label, Randomised, Multicentre Study Comparing AZD0120, a Dual-Targeting Autologous Chimeric Antigen Receptor T-cell (CART) Therapy Directed Against BCMA and CD19, Versus Standard Regimens in Participants With Relapsed Refractory Multiple Myeloma.
Summary: This is a randomised, multicentre, controlled, open-label, Phase III global study comparing the efficacy and safety of AZD0120 versus standard regimens (DKd \[daratumumab, carfilzomib, and dexamethasone\], DPd \[daratumumab, pomalidomide, and dexamethasone\], PVd \[pomalidomide, bortezomib and dexamethasone\], or Kd \[carfilzomib and dexamethasone\]) in participants with RRMM.
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Brand Information
BORUZU (Bortezomib)
1DOSAGE FORMS AND STRENGTHS
Injection: supplied as a sterile clear to light yellow solution available as a 3.5 mg/1.4 mL (2.5 mg/mL) in a single-dose vial.
2CONTRAINDICATIONS
BORUZU is contraindicated in patients with hypersensitivity (not including local reactions) to bortezomib, boron, or mannitol. Reactions have included anaphylactic reactions
BORUZU is contraindicated for intrathecal administration. Fatal events have occurred with intrathecal administration of BORUZU.
3ADVERSE REACTIONS
The following clinically significant adverse reactions are also discussed in other sections of the labeling:
- Peripheral Neuropathy
- Hypotension
- Cardiac Toxicity
- Pulmonary Toxicity
- Posterior Reversible Encephalopathy Syndrome (PRES)
- Gastrointestinal Toxicity
- Thrombocytopenia/Neutropenia
- Tumor Lysis Syndrome
- Hepatic Toxicity
- Thrombotic Microangiopathy
3.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Summary of Clinical Trial in Patients with Previously Untreated Multiple Myeloma
Table 9 describes safety data from 340 patients with previously untreated multiple myeloma who received bortezomib (1.3 mg/m2) administered intravenously in combination with melphalan (9 mg/m2) and prednisone (60 mg/m2) in a prospective randomized study.
The safety profile of bortezomib in combination with melphalan/prednisone is consistent with the known safety profiles of both bortezomib and melphalan/prednisone.
Table 9: Most Commonly Reported Adverse Reactions (≥ 10% in the Bortezomib, Melphalan and Prednisone Arm) with Grades 3 and ≥ 4 Intensity in the Previously Untreated Multiple Myeloma Study
Relapsed Multiple Myeloma Randomized Study of Bortezomib vs Dexamethasone
The safety data described below and in
Among the 331 bortezomib-treated patients, the most commonly reported (> 20%) adverse reactions overall were nausea (52%), diarrhea (52%), fatigue (39%), peripheral neuropathies (35%), thrombocytopenia (33%), constipation (30%), vomiting (29%), and anorexia (21%). The most commonly reported (> 20%) adverse reaction reported among the 332 patients in the dexamethasone group was fatigue (25%). Eight percent (8%) of patients in the bortezomib-treated arm experienced a Grade 4 adverse reaction; the most common reactions were thrombocytopenia (4%) and neutropenia (2%). Nine percent (9%) of dexamethasone-treated patients experienced a Grade 4 adverse reaction. All individual dexamethasone-related Grade 4 adverse reactions were less than 1%.
Serious Adverse Reactions and Adverse Reactions Leading to Treatment Discontinuation in the Relapsed Multiple Myeloma Study of Bortezomib vs Dexamethasone
Serious adverse reactions are defined as any reaction that results in death, is life-threatening, requires hospitalization or prolongs a current hospitalization, results in a significant disability, or is deemed to be an important medical event. A total of 80 (24%) patients from the bortezomib treatment arm experienced a serious adverse reaction during the study, as did 83 (25%) dexamethasone-treated patients. The most commonly reported serious adverse reactions in the bortezomib treatment arm were diarrhea (3%), dehydration, herpes zoster, pyrexia, nausea, vomiting, dyspnea, and thrombocytopenia (2% each). In the dexamethasone treatment group, the most commonly reported serious adverse reactions were pneumonia (4%), hyperglycemia (3%), pyrexia, and psychotic disorder (2% each).
A total of 145 patients, including 84 (25%) of 331 patients in the bortezomib treatment group and 61 (18%) of 332 patients in the dexamethasone treatment group were discontinued from treatment due to adverse reactions. Among the 331 bortezomib-treated patients, the most commonly reported adverse reaction leading to discontinuation was peripheral neuropathy (8%). Among the 332 patients in the dexamethasone group, the most commonly reported adverse reactions leading to treatment discontinuation were psychotic disorder and hyperglycemia (2% each).
Four deaths were considered to be bortezomib-related in this relapsed multiple myeloma study: one case each of cardiogenic shock, respiratory insufficiency, congestive heart failure and cardiac arrest. Four deaths were considered dexamethasone-related: two cases of sepsis, one case of bacterial meningitis, and one case of sudden death at home.
Most Commonly Reported Adverse Reactions in the Relapsed Multiple Myeloma Study of Bortezomib vs Dexamethasone
The most common adverse reactions from the relapsed multiple myeloma study are shown in
Table 10: Most Commonly Reported Adverse Reactions (≥ 10% in Bortezomib Arm), with Grades 3 and 4 Intensity in the Relapsed Multiple Myeloma Study of Bortezomib vs Dexamethasone (N=663)
Safety Experience from the Phase 2 Open-Label Extension Study in Relapsed Multiple Myeloma
In the Phase 2 extension study of 63 patients, no new cumulative or new long-term toxicities were observed with prolonged bortezomib treatment. These patients were treated for a total of 5.3 to 23 months, including time on bortezomib in the prior bortezomib study
Safety Experience from the Phase 3 Open-Label Study of Bortezomib Subcutaneous vs Intravenous in Relapsed Multiple Myeloma
The safety and efficacy of bortezomib administered subcutaneously were evaluated in one Phase 3 study at the recommended dose of 1.3 mg/m
Table 11: Most Commonly Reported Adverse Reactions (≥ 10%), with Grade 3 and ≥ 4 Intensity in the Relapsed Multiple Myeloma Study (N=221) of Bortezomib Subcutaneous vs Intravenous
In general, safety data were similar for the subcutaneous and intravenous treatment groups. Differences were observed in the rates of some Grade ≥ 3 adverse reactions. Differences of ≥ 5% were reported in neuralgia (3% subcutaneous vs 9% intravenous), peripheral neuropathies (6% subcutaneous vs 15% intravenous), neutropenia (13% subcutaneous vs 18% intravenous), and thrombocytopenia (8% subcutaneous vs 16% intravenous).
A local reaction was reported in 6% of patients in the subcutaneous group, mostly redness. Only two (1%) patients were reported as having severe reactions, one case of pruritus and one case of redness. Local reactions led to reduction in injection concentration in one patient and drug discontinuation in one patient. Local reactions resolved in a median of six days.
Dose reductions occurred due to adverse reactions in 31% of patients in the subcutaneous treatment group compared with 43% of the intravenously-treated patients. The most common adverse reactions leading to a dose reduction included peripheral sensory neuropathy (17% in the subcutaneous treatment group compared with 31% in the intravenous treatment group); and neuralgia (11% in the subcutaneous treatment group compared with 19% in the intravenous treatment group).
Serious Adverse Reactions and Adverse Reactions Leading to Treatment Discontinuation in the Relapsed Multiple Myeloma Study of Bortezomib Subcutaneous vs Intravenous
The incidence of serious adverse reactions was similar for the subcutaneous treatment group (20%) and the intravenous treatment group (19%). The most commonly reported serious adverse reactions in the subcutaneous treatment arm were pneumonia and pyrexia (2% each). In the intravenous treatment group, the most commonly reported serious adverse reactions were pneumonia, diarrhea, and peripheral sensory neuropathy (3% each).
In the subcutaneous treatment group, 27 patients (18%) discontinued study treatment due to an adverse reaction compared with 17 patients (23%) in the intravenous treatment group
Two patients (1%) in the subcutaneous treatment group and one (1%) patient in the intravenous treatment group died due to an adverse reaction during treatment. In the subcutaneous group the causes of death were one case of pneumonia and one case of sudden death. In the intravenous group the cause of death was coronary artery insufficiency.
Safety Experience from the Clinical Trial in Patients with Previously Untreated Mantle Cell Lymphoma
Table 12 describes safety data from 240 patients with previously untreated mantle cell lymphoma who received bortezomib (1.3 mg/m2) administered intravenously in combination with rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and prednisone (100 mg/m2) (BR-CAP) in a prospective randomized study.
Infections were reported for 31% of patients in the BR-CAP arm and 23% of the patients in the comparator (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]) arm, including the predominant preferred term of pneumonia (BR-CAP 8% vs R-CHOP 5%).
Table 12: Most Commonly Reported Adverse Reactions (≥ 5%) with Grades 3 and ≥ 4 Intensity in the Previously Untreated Mantle Cell Lymphoma Study
The incidence of herpes zoster reactivation was 4.6% in the BR-CAP arm and 0.8% in the R-CHOP arm. Antiviral prophylaxis was mandated by protocol amendment.
The incidences of Grade ≥ 3 bleeding events were similar between the two arms (four patients in the BR-CAP arm and three patients in the R-CHOP arm). All of the Grade ≥ 3 bleeding events resolved without sequelae in the BR-CAP arm.
Adverse reactions leading to discontinuation occurred in 8% of patients in BR-CAP group and 6% of patients in R-CHOP group. In the BR-CAP group, the most commonly reported adverse reaction leading to discontinuation was peripheral sensory neuropathy (1%; three patients). The most commonly reported adverse reaction leading to discontinuation in the R-CHOP group was febrile neutropenia (< 1%; two patients).
Integrated Summary of Safety (Relapsed Multiple Myeloma and Relapsed Mantle Cell Lymphoma)
Safety data from Phase 2 and 3 studies of single agent bortezomib 1.3 mg/m
In the integrated analysis, the most commonly reported (> 20%) adverse reactions were nausea (49%), diarrhea (46%), asthenic conditions including fatigue (41%) and weakness (11%), peripheral neuropathies (38%), thrombocytopenia (32%), vomiting (28%), constipation (25%), and pyrexia (21%). Eleven percent (11%) of patients experienced at least one episode of ≥ Grade 4 toxicity, most commonly thrombocytopenia (4%) and neutropenia (2%).
In the Phase 2 relapsed multiple myeloma clinical trials of bortezomib administered intravenously, local skin irritation was reported in 5% of patients, but extravasation of bortezomib was not associated with tissue damage.
Serious Adverse Reactions and Adverse Reactions Leading to Treatment Discontinuation in the Integrated Summary of Safety
A total of 26% of patients experienced a serious adverse reaction during the studies. The most commonly reported serious adverse reactions included diarrhea, vomiting and pyrexia (3% each), nausea, dehydration, and thrombocytopenia (2% each) and pneumonia, dyspnea, peripheral neuropathies, and herpes zoster (1% each).
Adverse reactions leading to discontinuation occurred in 22% of patients. The reasons for discontinuation included peripheral neuropathy (8%), and fatigue, thrombocytopenia, and diarrhea (2% each).
In total, 2% of the patients died and the cause of death was considered by the investigator to be possibly related to study drug: including reports of cardiac arrest, congestive heart failure, respiratory failure, renal failure, pneumonia and sepsis.
Most Commonly Reported Adverse Reactions in the Integrated Summary of Safety
The most common adverse reactions are shown in
Table 13: Most Commonly Reported (≥ 10% Overall) Adverse Reactions in Integrated Analyses of Relapsed Multiple Myeloma and Relapsed Mantle Cell Lymphoma Studies Using the 1.3 mg/m
Description of Selected Adverse Reactions from the Integrated Phase 2 and 3 Relapsed Multiple Myeloma and Phase 2 Relapsed Mantle Cell Lymphoma Studies
Gastrointestinal Toxicity
A total of 75% of patients experienced at least one gastrointestinal disorder. The most common gastrointestinal disorders included nausea, diarrhea, constipation, vomiting, and appetite decreased. Other gastrointestinal disorders included dyspepsia and dysgeusia. Grade 3 adverse reactions occurred in 14% of patients; ≥ Grade 4 adverse reactions were ≤ 1%. Gastrointestinal adverse reactions were considered serious in 7% of patients. Four percent (4%) of patients discontinued due to a gastrointestinal adverse reaction. Nausea was reported more often in patients with multiple myeloma (51%) compared to patients with mantle cell lymphoma (36%).
Thrombocytopenia
Across the studies, bortezomib-associated thrombocytopenia was characterized by a decrease in platelet count during the dosing period (Days 1 to 11) and a return toward baseline during the ten day rest period during each treatment cycle. Overall, thrombocytopenia was reported in 32% of patients. Thrombocytopenia was Grade 3 in 22%, ≥ Grade 4 in 4%, and serious in 2% of patients, and the reaction resulted in bortezomib discontinuation in 2% of patients
Peripheral Neuropathy
Overall, peripheral neuropathies occurred in 38% of patients. Peripheral neuropathy was Grade 3 for 11% of patients and ≥ Grade 4 for < 1% of patients. Eight percent (8%) of patients discontinued bortezomib due to peripheral neuropathy. The incidence of peripheral neuropathy was higher among patients with mantle cell lymphoma (54%) compared to patients with multiple myeloma (36%).
In the bortezomib vs dexamethasone Phase 3 relapsed multiple myeloma study, among the 62 bortezomib-treated patients who experienced ≥ Grade 2 peripheral neuropathy and had dose adjustments, 48% had improved or resolved with a median of 3.8 months from first onset.
In the Phase 2 relapsed multiple myeloma studies, among the 30 patients who experienced Grade 2 peripheral neuropathy resulting in discontinuation or who experienced ≥ Grade 3 peripheral neuropathy, 73% reported improvement or resolution with a median time of 47 days to improvement of one grade or more from the last dose of bortezomib.
Hypotension
The incidence of hypotension (postural, orthostatic and hypotension NOS) was 8% in patients treated with bortezomib. Hypotension was Grade 1 or 2 in the majority of patients and Grade 3 in 2% and ≥ Grade 4 in < 1%. Two percent (2%) of patients had hypotension reported as a serious adverse reaction, and 1% discontinued due to hypotension. The incidence of hypotension was similar in patients with multiple myeloma (8%) and those with mantle cell lymphoma (9%). In addition, < 1% of patients experienced hypotension associated with a syncopal reaction.
Neutropenia
Neutrophil counts decreased during the bortezomib dosing period (Days 1 to 11) and returned toward baseline during the ten day rest period during each treatment cycle. Overall, neutropenia occurred in 15% of patients and was Grade 3 in 8% of patients and ≥ Grade 4 in 2%. Neutropenia was reported as a serious adverse reaction in < 1% of patients and < 1% of patients discontinued due to neutropenia. The incidence of neutropenia was higher in patients with multiple myeloma (16%) compared to patients with mantle cell lymphoma (5%). The incidence of ≥ Grade 3 neutropenia also was higher in patients with multiple myeloma (12%) compared to patients with mantle cell lymphoma (3%).
Asthenic Conditions (Fatigue, Malaise, Weakness, Asthenia)
Asthenic conditions were reported in 54% of patients. Fatigue was reported as Grade 3 in 7% and ≥ Grade 4 in < 1% of patients. Asthenia was reported as Grade 3 in 2% and ≥ Grade 4 in < 1% of patients. Two percent (2%) of patients discontinued treatment due to fatigue and < 1% due to weakness and asthenia. Asthenic conditions were reported in 53% of patients with multiple myeloma and 59% of patients with mantle cell lymphoma.
Pyrexia
Pyrexia (> 38
Herpes Virus Infection
Consider using antiviral prophylaxis in subjects being treated with bortezomib. In the randomized studies in previously untreated and relapsed multiple myeloma, herpes zoster reactivation was more common in subjects treated with bortezomib (ranging between 6 to 11%) than in the control groups (3 to 4%). Herpes simplex was seen in 1 to 3% in subjects treated with bortezomib and 1 to 3% in the control groups. In the previously untreated multiple myeloma study, herpes zoster virus reactivation in the bortezomib, melphalan and prednisone arm was less common in subjects receiving prophylactic antiviral therapy (3%) than in subjects who did not receive prophylactic antiviral therapy (17%).
Retreatment in Relapsed Multiple Myeloma
A single-arm trial was conducted in 130 patients with relapsed multiple myeloma to determine the efficacy and safety of retreatment with intravenous bortezomib. The safety profile of patients in this trial is consistent with the known safety profile of bortezomib-treated patients with relapsed multiple myeloma as demonstrated in
Adverse reactions leading to discontinuation occurred in 13% of patients. The reasons for discontinuation included peripheral neuropathy (5%) and diarrhea (3%).
Two deaths considered to be bortezomib-related occurred within 30 days of the last bortezomib dose; one in a patient with cerebrovascular accident and one in a patient with sepsis.
Additional Adverse Reactions from Clinical Studies
The following clinically important serious adverse reactions that are not described above have been reported in clinical trials in patients treated with bortezomib administered as monotherapy or in combination with other chemotherapeutics. These studies were conducted in patients with hematological malignancies and in solid tumors.
Blood and Lymphatic System Disorders: Anemia, disseminated intravascular coagulation, febrile neutropenia, lymphopenia, leukopenia
Cardiac Disorders: Angina pectoris, atrial fibrillation aggravated, atrial flutter, bradycardia, sinus arrest, cardiac amyloidosis, complete atrioventricular block, myocardial ischemia, myocardial infarction, pericarditis, pericardial effusion, Torsades de pointes, ventricular tachycardia
Ear and Labyrinth Disorders: Hearing impaired, vertigo
Eye Disorders: Diplopia and blurred vision, conjunctival infection, irritation
Gastrointestinal Disorders: Abdominal pain, ascites, dysphagia, fecal impaction, gastroenteritis, gastritis hemorrhagic, hematemesis, hemorrhagic duodenitis, ileus paralytic, large intestinal obstruction, paralytic intestinal obstruction, peritonitis, small intestinal obstruction, large intestinal perforation, stomatitis, melena, pancreatitis acute, oral mucosal petechiae, gastroesophageal reflux
General Disorders and Administration Site Conditions: Chills, edema, edema peripheral, injection site erythema, neuralgia, injection site pain, irritation, malaise, phlebitis
Hepatobiliary Disorders: Cholestasis, hepatic hemorrhage, hyperbilirubinemia, portal vein thrombosis, hepatitis, liver failure
Immune System Disorders: Anaphylactic reaction, drug hypersensitivity, immune complex mediated hypersensitivity, angioedema, laryngeal edema
Infections and Infestations: Aspergillosis, bacteremia, bronchitis, urinary tract infection, herpes viral infection, listeriosis, nasopharyngitis, pneumonia, respiratory tract infection, septic shock, toxoplasmosis, oral candidiasis, sinusitis, catheter-related infection
Injury, Poisoning and Procedural Complications: Catheter-related complication, skeletal fracture, subdural hematoma
Investigations: Weight decreased
Metabolism and Nutrition Disorders: Dehydration, hypocalcemia, hyperuricemia, hypokalemia, hyperkalemia, hyponatremia, hypernatremia
Musculoskeletal and Connective Tissue Disorders: Arthralgia, back pain, bone pain, myalgia, pain in extremity
Nervous System Disorders: Ataxia, coma, dizziness, dysarthria, dysesthesia, dysautonomia, encephalopathy, cranial palsy, grand mal convulsion, headache, hemorrhagic stroke, motor dysfunction, neuralgia, spinal cord compression, paralysis, postherpetic neuralgia, transient ischemic attack
Psychiatric Disorders: Agitation, anxiety, confusion, insomnia, mental status change, psychotic disorder, suicidal ideation
Renal and Urinary Disorders: Calculus renal, bilateral hydronephrosis, bladder spasm, hematuria, hemorrhagic cystitis, urinary incontinence, urinary retention, renal failure (acute and chronic), glomerular nephritis proliferative
Respiratory, Thoracic and Mediastinal Disorders: Acute respiratory distress syndrome, aspiration pneumonia, atelectasis, chronic obstructive airways disease exacerbated, cough, dysphagia, dyspnea, dyspnea exertional, epistaxis, hemoptysis, hypoxia, lung infiltration, pleural effusion, pneumonitis, respiratory distress, pulmonary hypertension
Skin and Subcutaneous Tissue Disorders: Urticaria, face edema, rash (which may be pruritic), leukocytoclastic vasculitis, pruritus
Vascular Disorders: Cerebrovascular accident, cerebral hemorrhage, deep venous thrombosis, hypertension, peripheral embolism, pulmonary embolism, pulmonary hypertension
3.2Postmarketing Experience
The following adverse reactions have been identified from the worldwide postmarketing experience with bortezomib. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:
Cardiac Disorders: Cardiac tamponade
Ear and Labyrinth Disorders: Deafness bilateral
Eye Disorders: Optic neuropathy, blindness, chalazion/blepharitis
Gastrointestinal Disorders: Ischemic colitis
Infections and Infestations: Progressive multifocal leukoencephalopathy (PML), ophthalmic herpes, herpes meningoencephalitis
Nervous System Disorders: Posterior reversible encephalopathy syndrome (PRES, formerly RPLS), Guillain-Barre syndrome, demyelinating polyneuropathy
Respiratory, Thoracic and Mediastinal Disorders: Acute diffuse infiltrative pulmonary disease
Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), acute febrile neutrophilic dermatosis (Sweet’s syndrome)
4OVERDOSAGE
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.
Studies in monkeys and dogs showed that intravenous bortezomib doses as low as two times the recommended clinical dose on a mg/m
5DESCRIPTION
Bortezomib, a proteasome inhibitor, is an antineoplastic agent available for intravenous or subcutaneous injection. The chemical name for bortezomib {(1
The structural formula is as follows:
The molecular formula of bortezomib is C
BORUZU is available as a single-dose vial containing 3.5 mg of bortezomib as a sterile solution. Each 1 mL of solution contains 2.5 mg bortezomib, 25 mg mannitol, sodium chloride for isotonicity and water for injection.
6REFERENCES
1. “OSHA Hazardous Drugs” (refer to antineoplastic weblinks including OSHA Technical Manual) OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html
7HOW SUPPLIED/STORAGE AND HANDLING
BORUZU
BORUZU
Store refrigerated at 2°C to 8°C (36°F to 46°F) in original package to protect from light.
Follow guidelines for handling and disposal for hazardous drugs, including the use of gloves and other protective clothing to prevent skin contact
8PATIENT COUNSELING INFORMATION
Discuss the following with patients prior to treatment with BORUZU:
Peripheral Neuropathy
Advise patients to report the development or worsening of sensory and motor peripheral neuropathy to their healthcare provider
Hypotension
Advise patients to drink adequate fluids to avoid dehydration and to report symptoms of hypotension to their healthcare provider
Instruct patients to seek medical advice if they experience symptoms of dizziness, light headedness or fainting spells, or muscle cramps.
Cardiac Toxicity
Advise patients to report signs or symptoms of heart failure to their healthcare provider
Pulmonary Toxicity
Advise patients to report symptoms of ARDS, pulmonary hypertension, pneumonitis, and pneumonia immediately to their healthcare provider
Posterior Reversible Encephalopathy Syndrome (PRES)
Advise patients to seek immediate medical attention for signs or symptoms of PRES
Gastrointestinal Toxicity
Advise patients to report symptoms of gastrointestinal toxicity to their healthcare provider and to drink adequate fluids to avoid dehydration. Instruct patients to seek medical advice if they experience symptoms of dizziness, light headedness or fainting spells, or muscle cramps
Thrombocytopenia/Neutropenia
Advise patients to report signs or symptoms of bleeding or infection immediately to their healthcare provider
Tumor Lysis Syndrome
Advise patients of the risk of tumor lysis syndrome and to drink adequate fluids to avoid dehydration
[see .
Hepatic Toxicity
Advise patients to report signs or symptoms of hepatic toxicity to their healthcare provider
Thrombotic Microangiopathy
Advise patients to seek immediate medical attention if any signs or symptoms of thrombotic microangiopathy occur
Ability to Drive or Operate Machinery or Impairment of Mental Ability
BORUZU may cause fatigue, dizziness, syncope, orthostatic/postural hypotension. Advise patients not to drive or operate machinery if they experience any of these symptoms
Embryo-Fetal Toxicity
Advise females of the potential risk to the fetus and to use effective contraception during treatment with BORUZU and for seven months following the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with BORUZU and for four months following the last dose. Instruct patients to report pregnancy to their physicians immediately if they or their female partner becomes pregnant during treatment or within seven months following last dose
Lactation
Advise women not to breastfeed while receiving BORUZU and for two months after last dose
Concomitant Medications
Advise patients to speak with their physicians about any other medication they are currently taking.
Diabetic Patients
Advise patients to check their blood sugar frequently if using an oral antidiabetic medication and to notify their physicians of any changes in blood sugar level.
Dermal
Advise patients to contact their physicians if they experience rash, severe injection site reactions
Other
Instruct patients to contact their physicians if they develop an increase in blood pressure, bleeding, fever, constipation, or decreased appetite.
Manufactured by:
Amneal Oncology Pvt. Ltd.
Telangana 509301, INDIA
Distributed by:
Amneal Pharmaceuticals LLC
Bridgewater, NJ 08807
Rev. 07-2025-01
9PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 70121-2484-1
BORUZU
3.5 mg/1.4 mL (2.5 mg/mL)
For Intravenous or Subcutaneous use
Rx only
Vial Label
Amneal Pharmaceuticals LLC
NDC 70121-2484-1
BORUZU
3.5 mg/1.4 mL (2.5 mg/mL)
For Intravenous or Subcutaneous use
Rx only
Carton - Front Side
Amneal Pharmaceuticals LLC
NDC 70121-2484-1
BORUZU
3.5 mg/1.4 mL (2.5 mg/mL)
For Intravenous or Subcutaneous use
Rx only
Carton Label - Inner Side
Amneal Pharmaceuticals LLC
BORUZU
3.5 mg/1.4 mL (2.5 mg/mL)
For Intravenous or Subcutaneous use
Rx only
Sticker Label
Amneal Pharmaceuticals LLC