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Bortezomib 3.5 mg/3.5mL Injection, Powder, Lyophilized, For Solution, 1 vial — NDC 83090-008-01 (Billing 83090-0008-01)

by Sintetica US LLC · 1 VIAL, SINGLE-DOSE in 1 CARTON / 3.5 mL in 1 VIAL, SINGLE-DOSE

This is a package of 1 vial of Bortezomib 3.5 mg/3.5mL Injection, Powder, Lyophilized, For Solution from Sintetica US LLC, marketed since Jul 2023 and currently FDA-listed. It is this product's only package size.

NDC 83090-0008-01
🏷️ FDA NDC (as labeled) 83090-008-01 billing pads the product segment with a zero
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
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Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 83090-008-01
Product NDC 83090-008
11-digit billing NDC 83090000801
NCPDP billing unit EA — each (per item)
RxCUI 402243
UNII 69G8BD63PP
Application # ANDA209622
SPL Set ID d79a71ec-b46d-4961-ad05-8980915cba94
Established class (EPC) Proteasome Inhibitor
Mechanism of action Proteasome Inhibitors
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2023-07-15
Route INTRAVENOUS, SUBCUTANEOUS
Dosage form INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Substance BORTEZOMIB
TE code (Orange Book) AP · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GCN Seq No 052124
GCN 19656
HICL code 025202
Ingredient (HICL) Bortezomib
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V1Q
Therapeutic class — specific (HIC3) Antineoplastic Systemic Enzyme Inhibitors
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name BORTEZOMIB 3.5 MG VIAL
FDB brand name Bortezomib
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 052124
  • GCN: 19656
  • HICL (First Databank): 025202
  • AHFS class code: 10:00.00.00
  • RxCUI (RxNorm): 402243
Why two NDCs? The FDA registers this code as 83090-008-01 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 83090-0008-01. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Proteasome Inhibitor class.

Pharmacologic class Proteasome Inhibitor
Drug family (ATC) Proteasome inhibitors
How it works Proteasome Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name BORTEZOMIB 3.5 MG VIAL Ingredient Bortezomib
📗 Our plain-language guide HelloPharmacist
  • It treats adults with multiple myeloma and mantle cell lymphoma. These are both cancers affecting blood-forming cells. Your oncology team decides how it fits into your plan.
  • A healthcare professional gives it as an injection, into a vein or under the skin depending on the product. Your team sets the dose and schedule for you. You do not take it at home...
  • Nausea, diarrhea, constipation, tiredness, low blood counts and numbness or tingling are common. Tell your team about them, since medicines can often help. Do not wait if the nerve...
  • Call for fainting or severe dizziness, new shortness of breath or swelling, seizures, confusion, vision changes, unusual bleeding, or severe vomiting or diarrhea. These can signal...
📖 Read our full Bortezomib guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
83090-0008-01 You're viewing this Main listing 1 VIAL, SINGLE-DOSE in 1 CARTON / 3.5 mL in 1 VIAL, SINGLE-DOSE 2023-07-15 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
bortezomib 3.5 mg 00143-9098-01 Hikma 1 vial — AP FDA listed —
Bortezomib 3.5 mg 00409-1700-01 Hospira, 1 vial — AP FDA listed —
Bortezomib 3.5 mg 25021-0262-10 Sagent 1 vial — AP FDA listed —
Bortezomib 3.5 mg 31722-0303-31 Camber 1 vial — AP FDA listed —
Bortezomib 3.5 mg 43598-0426-60 Dr.Reddy's 1 vial — AP FDA listed —
Bortezomib 3.5 mg 51817-0586-01 Pharmascience 1 vial — AP FDA listed —
Bortezomib 3.5 mg 55150-0337-01 Eugia 1 vial — AP FDA listed —
Bortezomib 3.5 mg 60505-6050-04 Apotex 1 vial — AP FDA listed —
Velcade 3.5 mg 63020-0049-01 Takeda 1 vial — AP FDA listed —
Bortezomib 3.5 mg 63323-0821-10 Fresenius 1 vial — AP FDA listed —
Bortezomib 3.5 mg 68001-0534-36 BluePoint 1 vial — AP FDA listed —
Bortezomib 3.5 mg 68001-0540-36 BluePoint 1 vial — AP FDA listed —
Bortezomib 3.5 mg/3.5mL 68001-0541-36 BluePoint 1 vial — AP FDA listed —
Bortezomib 3.5 mg/3.5mL 70069-0836-01 Somerset 1 vial — AP FDA listed —
Bortezomib 1 mg/mL 70710-1411-01 Zydus 1 vial — AP FDA listed —
Bortezomib 1 mg/mL 70771-1708-01 Zydus 1 vial — AP FDA listed —
Bortezomib 3.5 mg 71288-0118-10 Meitheal 1 vial — AP FDA listed —
Bortezomib 3.5 mg/3.5mL 72205-0183-01 Novadoz 1 vial — AP FDA listed —
Bortezomib 3.5 mg 72338-0200-01 Waverley 1 vial — AP FDA listed —
Bortezomib 3.5 mg 72603-0270-01 NorthStar 1 vial — AP FDA listed —
Bortezomib 3.5 mg 75007-0501-31 Ningbo 10 vials — AP FDA listed —
Bortezomib 3.5 mg/3.5mLthis 83090-0008-01 Sintetica 1 vial — AP FDA listed —
Bortezomib 3.5 mg 83634-0208-10 Avenacy, 1 vial — AP FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2023
On the market since
Jul 2023
📍
2026
Currently FDA-listed
3 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerSintetica US LLC
Application holderMSN LABORATORIES PRIVATE LTD
FDA applicationANDA209622 (ANDA)
Labeler code83090
First marketedJul 2023
Product typeHuman Prescription Drug
Portfolio5 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📚 References 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 70 words ▾

1 INDICATIONS AND USAGE Bortezomib for injection is a proteasome inhibitor indicated for: treatment of adult patients with multiple myeloma ( 1.1 ) treatment of adult patients with mantle cell lymphoma ( 1.2 )

1.1Multiple Myeloma Bortezomib for injection is indicated for the treatment of adult patients with multiple myeloma.

1.2Mantle Cell Lymphoma Bortezomib for injection is indicated for the treatment of adult patients with mantle cell lymphoma.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION For subcutaneous or intravenous use only. Each route of administration has a different reconstituted concentration. Exercise caution when calculating the volume to be administered.

( 2.1 , 2.10 ) The recommended starting dose of bortezomib for injection is 1.3 mg/m 2 administered either as a 3 to 5 second bolus intravenous injection or subcutaneous injection. ( 2.2 , 2.4 , 2.6 ) Retreatment for Multiple Myeloma: May retreat starting at the last tolerated dose. ( 2.6 ) Hepatic Impairment: Use a lower starting dose for patients with moderate or severe hepatic impairment.

( 2.8 ) Dose must be individualized to prevent overdose. ( 2.10 )

2.1Important Dosing Guidelines Bortezomib for injection is for intravenous or subcutaneous use only. Do not administer bortezomib for injection by any other route. Because each route of administration has a different reconstituted concentration, use caution when calculating the volume to be administered.

The recommended starting dose of bortezomib for injection is 1.3 mg/m 2 . Bortezomib for injection is administered intravenously at a concentration of 1 mg/mL, or subcutaneously at a concentration of 2.5 mg/mL [see Dosage and Administration ( 2.10 )]. Bortezomib for injection retreatment may be considered for patients with multiple myeloma who had previously responded to treatment with bortezomib for injection and who have relapsed at least six months after completing prior bortezomib for injection treatment.

Treatment may be started at the last tolerated dose [see Dosage and Administration ( 2.6 )] . When administered intravenously, administer bortezomib for injection as a 3 to 5 second bolus intravenous injection.

2.2Dosage in Previously Untreated Multiple Myeloma Bortezomib for injection is administered in combination with oral melphalan and oral prednisone for 9, six week treatment cycles as shown in Table 1 . In Cycles 1 to 4, bortezomib for injection is administered twice weekly (Days 1, 4, 8, 11, 22, 25, 29 and 32). In Cycles 5 to 9, bortezomib for injection is administered once weekly (Days 1, 8, 22 and 29).

At least 72 hours should elapse between consecutive doses of bortezomib for injection. Table 1: Dosage Regimen for Patients with Previously Untreated Multiple Myeloma Twice Weekly Bortezomib for Injection (Cycles 1 to 4) Week 1 2 3 4 5 6 Bortezomib for Injection (1.3 mg/m 2 ) Day 1 -- -- Day 4 Day 8 Day 11 rest period Day 22 Day 25 Day 29 Day 32 rest period Melphalan (9 mg/m 2 ) Prednisone (60 mg/m 2 ) Day 1 Day 2 Day 3 Day 4 -- -- rest period -- -- -- -- rest period Once Weekly Bortezomib for Injection (Cycles 5 to 9 when used in combination with Melphalan and Prednisone) Week 1 2 3 4 5 6 Bortezomib for Injection (1.3 mg/m 2 ) Day 1 -- -- Day 8 rest period Day 22 Day 29 rest period Melphalan (9 mg/m 2 ) Prednisone (60 mg/m 2 ) Day 1 Day 2 Day 3 Day 4 -- -- rest period -- -- -- -- rest period

2.3Dose Modification Guidelines for Bortezomib for Injection When Given in Combination with Melphalan and Prednisone Prior to initiating any cycle of therapy with bortezomib for injection in combination with melphalan and prednisone: Platelet count should be at least 70 x 10 9 /L and the absolute neutrophil count (ANC) should be at least 1 x 10 9 /L Nonhematological toxicities should have resolved to Grade 1 or baseline Table 2: Dose Modifications during Cycles of Combination Bortezomib for Injection, Melphalan and Prednisone Therapy Toxicity Dose Modification or Delay Hematological toxicity during a cycle: If prolonged Grade 4 neutropenia or thrombocytopenia, or thrombocytopenia with bleeding is observed in the previous cycle Consider reduction of the melphalan dose by 25% in the next cycle If platelet count is not above 30 x 10 9 /L or ANC is not above 0.75 x 10 9 /L on a bortezomib for injection dosing day (other than Day 1) Withhold bortezomib for injection dose If several bortezomib for injection doses in consecutive cycles are withheld due to toxicity Reduce bo… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 73 words ▾

3 DOSAGE FORMS AND STRENGTHS For injection: Each single-dose vial of bortezomib for injection contains 3.5 mg of bortezomib as a sterile white to off white lyophilized cake or powder for reconstitution and withdrawal of the appropriate individual patient dose [see Dosage and Administration ( 2.10) ] . For injection: Single-dose vial contains 3.5 mg of bortezomib as lyophilized powder for reconstitution and withdrawal of the appropriate individual patient dose. ( 3 )

⛔ Contraindications 70 words ▾

4 CONTRAINDICATIONS Bortezomib is contraindicated in patients with hypersensitivity (not including local reactions) to bortezomib, boron, or mannitol. Reactions have included anaphylactic reactions [see Adverse Reactions ( 6.1) ] . Bortezomib is contraindicated for intrathecal administration.

Fatal events have occurred with intrathecal administration of bortezomib. Patients with hypersensitivity (not including local reactions) to bortezomib, boron, or mannitol, including anaphylactic reactions. ( 4 ) Contraindicated for intrathecal administration.

( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Peripheral Neuropathy: Manage with dose modification or discontinuation. ( 2.7 ) Patients with pre-existing severe neuropathy should be treated with bortezomib only after careful risk-benefit assessment. ( 2.7 , 5.1 ) Hypotension: Use caution when treating patients taking antihypertensives, with a history of syncope, or with dehydration.

( 5.2 ) Cardiac Toxicity: Worsening of and development of cardiac failure has occurred. Closely monitor patients with existing heart disease or risk factors for heart disease. ( 5.3 ) Pulmonary Toxicity: Acute respiratory syndromes have occurred.

Monitor closely for new or worsening symptoms and consider interrupting bortezomib therapy. ( 5.4 ) Posterior Reversible Encephalopathy Syndrome: Consider MRI imaging for onset of visual or neurological symptoms; discontinue bortezomib if suspected. ( 5.5 ) Gastrointestinal Toxicity: Nausea, diarrhea, constipation, and vomiting may require use of antiemetic and antidiarrheal medications or fluid replacement.

( 5.6 ) Thrombocytopenia or Neutropenia: Monitor complete blood counts regularly throughout treatment. ( 5.7 ) Tumor Lysis Syndrome: Closely monitor patients with high tumor burden. ( 5.8 ) Hepatic Toxicity: Monitor hepatic enzymes during treatment.

Interrupt bortezomib therapy to assess reversibility. ( 5.9 ) Thrombotic Microangiopathy: Monitor for signs and symptoms. Discontinue bortezomib if suspected.

( 5.10 ) Embryo-Fetal Toxicity: Bortezomib can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.11 )

5.1Peripheral Neuropathy Bortezomib treatment causes a peripheral neuropathy that is predominantly sensory; however, cases of severe sensory and motor peripheral neuropathy have been reported. Patients with pre-existing symptoms (numbness, pain or a burning feeling in the feet or hands) and/or signs of peripheral neuropathy may experience worsening peripheral neuropathy (including ≥Grade 3) during treatment with bortezomib. Patients should be monitored for symptoms of neuropathy, such as a burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, neuropathic pain or weakness.

In the Phase 3 relapsed multiple myeloma trial comparing bortezomib subcutaneous vs intravenous, the incidence of Grade ≥2 peripheral neuropathy was 24% for subcutaneous and 39% for intravenous. Grade ≥3 peripheral neuropathy occurred in 6% of patients in the subcutaneous treatment group, compared with 15% in the intravenous treatment group [see Adverse Reactions ( 6.1 )] . Starting bortezomib subcutaneously may be considered for patients with pre-existing or at high risk of peripheral neuropathy.

Patients experiencing new or worsening peripheral neuropathy during bortezomib therapy may require a decrease in the dose and/or a less dose-intense schedule [see Dosage and Administration ( 2.7) ] . In the bortezomib vs dexamethasone Phase 3 relapsed multiple myeloma study, improvement in or resolution of peripheral neuropathy was reported in 48% of patients with ≥Grade 2 peripheral neuropathy following dose adjustment or interruption. Improvement in or resolution of peripheral neuropathy was reported in 73% of patients who discontinued due to Grade 2 neuropathy or who had ≥Grade 3 peripheral neuropathy in the Phase 2 multiple myeloma studies.

The long-term outcome of peripheral neuropathy has not been studied in mantle cell lymphoma.

5.2Hypotension The incidence of hypotension (postural, orthostatic, and hypotension NOS) was 8% [see Adverse Reactions ( 6.1 )] . These events are observed throughout therapy. Patients with a history of syncope, patients receiving medications known to be associated with hypotension, and patients who are dehydrated may be at increased risk of hypotension.

Management of orthostatic/postural hypotension may include adjustment of antihypertensive medications, hydration, and… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are also discussed in other sections of the labeling: Peripheral Neuropathy [see Warnings and Precautions ( 5.1 )] Hypotension [see Warnings and Precautions ( 5.2 )] Cardiac Toxicity [see Warnings and Precautions ( 5.3 )] Pulmonary Toxicity [see Warnings and Precautions ( 5.4 )] Posterior Reversible Encephalopathy Syndrome (PRES) [see Warnings and Precautions ( 5.5 )] Gastrointestinal Toxicity [see Warnings and Precautions ( 5.6 )] Thrombocytopenia/Neutropenia [see Warnings and Precautions ( 5.7 )] Tumor Lysis Syndrome [see Warnings and Precautions ( 5.8 )] Hepatic Toxicity [see Warnings and Precautions ( 5.9 )] Thrombotic Microangiopathy [see Warnings and Precautions ( 5.10 )] Most commonly reported adverse reactions (incidence ≥20%) in clinical studies include nausea, diarrhea, thrombocytopenia, neutropenia, peripheral neuropathy, fatigue, neuralgia, anemia, leukopenia, constipation, vomiting, lymphopenia, rash, pyrexia, and anorexia.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sintetica US at 1-888-815-3345 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical 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/m 2 ) administered intravenously in combination with melphalan (9 mg/m 2 ) and prednisone (60 mg/m 2 ) 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 Bortezomib, Melphalan and Prednisone Melphalan and Prednisone (n=340) (n=337) Body System Total Toxicity Grade, n (%) Total Toxicity Grade, n (%) Adverse Reaction n (%) 3 ≥4 n (%) 3 ≥4 Blood and Lymphatic System Disorders Thrombocytopenia 164 (48) 60 (18) 57 (17) 140 (42) 48 (14) 39 (12) Neutropenia 160 (47) 101 (30) 33 (10) 143 (42) 77 (23) 42 (12) Anemia 109 (32) 41 (12) 4 (1) 156 (46) 61 (18) 18 (5) Leukopenia 108 (32) 64 (19) 8 (2) 93 (28) 53 (16) 11 (3) Lymphopenia 78 (23) 46 (14) 17 (5) 51 (15) 26 (8) 7 (2) Gastrointestinal Disorders Nausea 134 (39) 10 (3) 0 70 (21) 1 (<1) 0 Diarrhea 119 (35) 19 (6) 2 (1) 20 (6) 1 (<1) 0 Vomiting 87 (26) 13 (4) 0 41 (12) 2 (1) 0 Constipation 77 (23) 2 (1) 0 14 (4) 0 0 Abdominal pain upper 34 (10) 1 (<1) 0 20 (6) 0 0 Nervous System Disorders Peripheral neuropathy * 156 (46) 42 (12) 2 (1) 4 (1) 0 0 Neuralgia 117 (34) 27 (8) 2 (1) 1 (<1) 0 0 Paresthesia 42 (12) 6 (2) 0 4 (1) 0 0 General Disorders and Administration Site Conditions Fatigue 85 (25) 19 (6) 2 (1) 48 (14) 4 (1) 0 Asthenia 54 (16) 18 (5) 0 23 (7) 3 (1) 0 Pyrexia 53 (16) 4 (1) 0 19 (6) 1 (<1) 1 (<1) Infections and Infestations Herpes Zoster 39 (11) 11 (3) 0 9 (3) 4 (1) 0 Metabolism and Nutrition Disorders Anorexia 64 (19) 6 (2) 0 19 (6) 0 0 Skin and Subcutaneous Tissue Disorders Rash 38 (11) 2 (1) 0 7 (2) 0 0 Psychiatric Disorders Insomnia 35 (10) 1 (<1) 0 21 (6) 0 0 * Represents High Level Term Peripheral Neuropathies NEC Relapsed Multiple Myeloma Randomized Study of Bortezomib vs Dexamethasone The safety data described below and in Table 10 reflect exposure to either bortezomib (n=331) or dexamethasone (n=332) in a study of patients with relapsed multiple myeloma.

Bortezomib was administered intravenously at doses of 1.3 mg/m 2 twice weekly for two out of three weeks (21 day cycle). After eight, 21 day cycles p… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 148 words ▾

7 DRUG INTERACTIONS Strong CYP3A4 Inhibitors: Closely monitor patients with concomitant use. ( 7.1 ) Strong CYP3A4 Inducers: Avoid concomitant use. (7.3)

7.1Effects of Other Drugs on Bortezomib Strong CYP3A4 Inducers Coadministration with a strong CYP3A4 inducer decreases the exposure of bortezomib [see Clinical Pharmacology ( 12.3 )] which may decrease bortezomib efficacy. Avoid coadministration with strong CYP3A4 inducers. Strong CYP3A4 Inhibitors Coadministration with a strong CYP3A4 inhibitor increases the exposure of bortezomib [see Clinical Pharmacology ( 12.3 )] which may increase the risk of bortezomib toxicities.

Monitor patients for signs of bortezomib toxicity and consider a bortezomib dose reduction if bortezomib must be given in combination with strong CYP3A4 inhibitors.

7.2Drugs Without Clinically Significant Interactions with Bortezomib No clinically significant drug interactions have been observed when bortezomib was coadministered with dexamethasone, omeprazole, or melphalan in combination with prednisone [see Clinical Pharmacology ( 12.3 )] .

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Patients with diabetes may require close monitoring of blood glucose and adjustment of anti-diabetic medication. ( 8.8 )

8.1Pregnancy Risk Summary Based on its mechanism of action [see Clinical Pharmacology ( 12.1 )] and findings in animals, bortezomib can cause fetal harm when administered to a pregnant woman. There are no studies with the use of bortezomib in pregnant women to inform drug-associated risks. Bortezomib caused embryo-fetal lethality in rabbits at doses lower than the clinical dose (see Data) .

Advise pregnant women of the potential risk to the fetus. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Bortezomib was not teratogenic in nonclinical developmental toxicity studies in rats and rabbits at the highest dose tested (0.075 mg/kg; 0.5 mg/m 2 in the rat and 0.05 mg/kg; 0.6 mg/m 2 in the rabbit) when administered during organogenesis. These dosages are approximately 0.5 times the clinical dose of 1.3 mg/m 2 based on body surface area.

Bortezomib caused embryo-fetal lethality in rabbits at doses lower than the clinical dose (approximately 0.5 times the clinical dose of 1.3 mg/m 2 based on body surface area). Pregnant rabbits given bortezomib during organogenesis at a dose of 0.05 mg/kg (0.6 mg/m 2 ) experienced significant postimplantation loss and decreased number of live fetuses. Live fetuses from these litters also showed significant decreases in fetal weight.

8.2Lactation Risk Summary There are no data on the presence of bortezomib or its metabolites in human milk, the effects of the drug on the breastfed child, or the effects of the drug on milk production. Because many drugs are excreted in human milk and because the potential for serious adverse reactions in a breastfed child from bortezomib is unknown, advise nursing women not to breastfeed during treatment with bortezomib and for two months after treatment.

8.3Females and Males of Reproductive Potential Based on its mechanism of action and findings in animals, bortezomib can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )]. Pregnancy Testing Conduct pregnancy testing in females of reproductive potential prior to initiating bortezomib for injection treatment. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with bortezomib for injection and for seven months after the last dose.

Males Males with female partners of reproductive potential should use effective contraception during treatment with bortezomib for injection and for four months after the last dose. Infertility Based on the mechanism of action and findings in animals, bortezomib for injection may have an effect on either male or female fertility [see Nonclinical Toxicology ( 13.1 )].

8.4Pediatric Use Safety and effectiveness have not been established in pediatric patients. The activity and safety of bortezomib in combination with intensive reinduction chemotherapy was evaluated in pediatric and young adult patients with lymphoid malignancies (pre-B cell ALL 77%, 16% with T-cell ALL, and 7% T-cell lymphoblastic lymphoma (LL)), all of whom relapsed within 36 months of initial diagnosis in a single-arm multicenter, nonrandomized cooperative group trial. An effective reinduction multiagent chemotherapy regimen was administered in three blocks.

Block 1 included vincristine, prednisone, doxorubicin and pegaspargase; Block 2 included cyclophosphamide, etoposide and methotrexate; Block 3 included high-dose cytosine arabinoside and asparaginase. Bortezomib was administered at a dose of 1.3 mg/m 2 as a bolus intra… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary Based on its mechanism of action [see Clinical Pharmacology ( 12.1 )] and findings in animals, bortezomib can cause fetal harm when administered to a pregnant woman. There are no studies with the use of bortezomib in pregnant women to inform drug-associated risks. Bortezomib caused embryo-fetal lethality in rabbits at doses lower than the clinical dose (see Data) .

Advise pregnant women of the potential risk to the fetus. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Bortezomib was not teratogenic in nonclinical developmental toxicity studies in rats and rabbits at the highest dose tested (0.075 mg/kg; 0.5 mg/m 2 in the rat and 0.05 mg/kg; 0.6 mg/m 2 in the rabbit) when administered during organogenesis. These dosages are approximately 0.5 times the clinical dose of 1.3 mg/m 2 based on body surface area.

Bortezomib caused embryo-fetal lethality in rabbits at doses lower than the clinical dose (approximately 0.5 times the clinical dose of 1.3 mg/m 2 based on body surface area). Pregnant rabbits given bortezomib during organogenesis at a dose of 0.05 mg/kg (0.6 mg/m 2 ) experienced significant postimplantation loss and decreased number of live fetuses. Live fetuses from these litters also showed significant decreases in fetal weight.

🧒 Pediatric Use ~1 min read ▾

8.4Pediatric Use Safety and effectiveness have not been established in pediatric patients. The activity and safety of bortezomib in combination with intensive reinduction chemotherapy was evaluated in pediatric and young adult patients with lymphoid malignancies (pre-B cell ALL 77%, 16% with T-cell ALL, and 7% T-cell lymphoblastic lymphoma (LL)), all of whom relapsed within 36 months of initial diagnosis in a single-arm multicenter, nonrandomized cooperative group trial. An effective reinduction multiagent chemotherapy regimen was administered in three blocks.

Block 1 included vincristine, prednisone, doxorubicin and pegaspargase; Block 2 included cyclophosphamide, etoposide and methotrexate; Block 3 included high-dose cytosine arabinoside and asparaginase. Bortezomib was administered at a dose of 1.3 mg/m 2 as a bolus intravenous injection on Days 1, 4, 8, and 11 of Block 1 and Days 1, 4, and 8 of Block 2. There were 140 patients with ALL or LL enrolled and evaluated for safety.

The median age was ten years (range: 1 to 26), 57% were male, 70% were white, 14% were black, 4% were Asian, 2% were American Indian/Alaska Native, 1% were Pacific Islander. The activity was evaluated in a prespecified subset of the first 60 evaluable patients enrolled on the study with pre-B ALL ≤21 years and relapsed <36 months from diagnosis. The complete remission (CR) rate at day 36 was compared to that in a historical control set of patients who had received the identical backbone therapy without bortezomib.

There was no evidence that the addition of bortezomib had any impact on the CR rate. No new safety concerns were observed when bortezomib was added to a chemotherapy backbone regimen as compared with a historical control group in which the backbone regimen was given without bortezomib. The BSA-normalized clearance of bortezomib in pediatric patients was similar to that observed in adults.

🧓 Geriatric Use 155 words ▾

8.5Geriatric Use Of the 669 patients enrolled in the relapsed multiple myeloma study, 245 (37%) were 65 years of age or older: 125 (38%) on the bortezomib arm and 120 (36%) on the dexamethasone arm. Median time to progression and median duration of response for patients ≥65 were longer on bortezomib compared to dexamethasone [5.5 mo vs 4.3 mo, and 8.0 mo vs 4.9 mo, respectively]. On the bortezomib arm, 40% (n=46) of evaluable patients aged ≥65 experienced response (CR + PR) vs 18% (n=21) on the dexamethasone arm.

The incidence of Grade 3 and 4 events was 64%, 78% and 75% for bortezomib patients ≤50, 51 to 64 and ≥65 years old, respectively [see Adverse Reactions ( 6.1 ); Clinical Studies ( 14.1 )]. No overall differences in safety or effectiveness were observed between patients ≥age 65 and younger patients receiving bortezomib; but greater sensitivity of some older individuals cannot be ruled out.

🆘 Overdosage 151 words ▾

10 OVERDOSAGE 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 2 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/m 2 and greater (approximately twice the recommended clinical dose) resulted in hypotension starting at one hour postadministration, with progression to death in 12 to 14 hours following drug administration.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Bortezomib is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome in mammalian cells. The 26S proteasome is a large protein complex that degrades ubiquitinated proteins. The ubiquitin-proteasome pathway plays an essential role in regulating the intracellular concentration of specific proteins, thereby maintaining homeostasis within cells.

Inhibition of the 26S proteasome prevents this targeted proteolysis, which can affect multiple signaling cascades within the cell. This disruption of normal homeostatic mechanisms can lead to cell death. Experiments have demonstrated that bortezomib is cytotoxic to a variety of cancer cell types in vitro .

Bortezomib causes a delay in tumor growth in vivo in nonclinical tumor models, including multiple myeloma.

12.2Pharmacodynamics Following twice weekly administration of 1 mg/m 2 and 1.3 mg/m 2 bortezomib doses, the maximum inhibition of 20S proteasome activity (relative to baseline) in whole blood was observed five minutes after drug administration. Comparable maximum inhibition of 20S proteasome activity was observed between 1 and 1.3 mg/m 2 doses. Maximal inhibition ranged from 70% to 84% and from 73% to 83% for the 1 mg/m 2 and 1.3 mg/m 2 dose regimens, respectively.

12.3Pharmacokinetics Following intravenous administration of 1 mg/m 2 and 1.3 mg/m 2 doses, the mean maximum plasma concentrations of bortezomib (C max ) after the first dose (Day 1) were 57 and 112 ng/mL, respectively. When administered twice weekly, the mean maximum observed plasma concentrations ranged from 67 to 106 ng/mL for the 1 mg/m 2 dose and 89 to 120 ng/mL for the 1.3 mg/m 2 dose. Following an intravenous bolus or subcutaneous injection of a 1.3 mg/m 2 dose to patients with multiple myeloma, the total systemic exposure after repeat dose administration (AUC last ) was equivalent for subcutaneous and intravenous administration.

The AUC last geometric mean ratio (90% confidence interval) was 0.99 (0.80 to 1.23). The C max after subcutaneous administration (20.4 ng/mL) was lower than after intravenous administration (223 ng/mL) with repeat dose administration. Distribution The mean distribution volume of bortezomib ranged from approximately 498 to 1884 L/m 2 following single- or repeat-dose administration of 1 mg/m 2 or 1.3 mg/m 2 to patients with multiple myeloma.

The binding of bortezomib to human plasma proteins averaged 83% over the concentration range of 100 to 1,000 ng/mL. Elimination The mean elimination half-life of bortezomib upon multiple dosing ranged from 40 to 193 hours after the 1 mg/m 2 dose and 76 to 108 hours after the 1.3 mg/m 2 dose. The mean total body clearances were 102 and 112 L/h following the first dose for doses of 1 mg/m 2 and 1.3 mg/m 2 , respectively, and ranged from 15 to 32 L/h following subsequent doses for doses of 1 and 1.3 mg/m 2 , respectively.

Metabolism Bortezomib is primarily oxidatively metabolized to several inactive metabolites in vitro via cytochrome P450 (CYP) enzymes 3A4, CYP2C19, and CYP1A2, and to a lesser extent by CYP2D6 and CYP2C9. Excretion The pathways of elimination of bortezomib have not been characterized in humans. Specific Populations No clinically significant differences in the pharmacokinetics of bortezomib were observed based on age, sex, or renal impairment (including patients administered bortezomib after dialysis).

The effect of race on bortezomib pharmacokinetics is unknown. Patients with Hepatic Impairment Following administration of bortezomib doses ranging from 0.5 to 1.3 mg/m 2 , mild (total bilirubin ≤1x ULN and AST >ULN, or total bilirubin >1 to 1.5x ULN and any AST) hepatic impairment did not alter dose-normalized bortezomib AUC when compared to patients with normal hepatic function. Dose normalized mean bortezomib AUC increased by approximately 60% in patients with moderate (total bilirubin >1.5 to 3x ULN and any AST) or severe (total bilirubin >3x ULN and any AST) hepa… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 114 words ▾

12.1Mechanism of Action Bortezomib is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome in mammalian cells. The 26S proteasome is a large protein complex that degrades ubiquitinated proteins. The ubiquitin-proteasome pathway plays an essential role in regulating the intracellular concentration of specific proteins, thereby maintaining homeostasis within cells.

Inhibition of the 26S proteasome prevents this targeted proteolysis, which can affect multiple signaling cascades within the cell. This disruption of normal homeostatic mechanisms can lead to cell death. Experiments have demonstrated that bortezomib is cytotoxic to a variety of cancer cell types in vitro .

Bortezomib causes a delay in tumor growth in vivo in nonclinical tumor models, including multiple myeloma.

📦 How Supplied / Storage and Handling 89 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Bortezomib for Injection is supplied as individually cartoned 10 mL vials containing 3.5 mg of bortezomib as a white to off-white cake or powder. NDC 83090-008-01 3.5 mg single-dose vial Unopened vials may be stored at 25°C (77°F); excursions permitted from 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature]. Retain 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 1 .

📋 Description 158 words ▾

11 DESCRIPTION Bortezomib for injection, a proteasome inhibitor, contains bortezomib which is an antineoplastic agent. Bortezomib is a modified dipeptidyl boronic acid. The chemical name for bortezomib, the monomeric boronic acid, is [(1R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl) amino]propyl]amino]butyl] boronic acid.

Bortezomib has the following chemical structure: The molecular weight is 384.24. The molecular formula is C 19 H 25 BN 4 O 4. The solubility of bortezomib, The solubility of bortezomib, is freely soluble in N, N dimethyl fornamide, soluble in methanol and practically insoluble in n-Hexane.

Bortezomib is available for intravenous injection or subcutaneous use. Each single-dose vial contains 3.5 mg of bortezomib as a sterile lyophilized powder. It also contains the inactive ingredient: 35 mg mannitol, USP.

The product is provided as a mannitol boronic ester which, in reconstituted form, consists of the mannitol ester in equilibrium with its hydrolysis product, the monomeric boronic acid. The drug substance exists in its cyclic anhydride form as a trimeric boroxine. Chemical Structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Discuss the following with patients prior to treatment with bortezomib for injection: Peripheral Neuropathy Advise patients to report the development or worsening of sensory and motor peripheral neuropathy to their healthcare provider [see Warnings and Precautions (5.1)]. Hypotension Advise patients to drink adequate fluids to avoid dehydration and to report symptoms of hypotension to their healthcare provider [see Warnings and Precautions (5.2)]. 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 [see Warnings and Precautions (5.3)] . Pulmonary Toxicity Advise patients to report symptoms of ARDS, pulmonary hypertension, pneumonitis, and pneumonia immediately to their healthcare provider [see Warnings and Precautions (5.4)]. Posterior Reversible Encephalopathy Syndrome (PRES) Advise patients to seek immediate medical attention for signs or symptoms of PRES [see Warnings and Precautions (5.5)].

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 [see Warnings and Precautions (5.6)]. Thrombocytopenia/Neutropenia Advise patients to report signs or symptoms of bleeding or infection immediately to their healthcare provider [see Warnings and Precautions (5.7)].

Tumor Lysis Syndrome Advise patients of the risk of tumor lysis syndrome and to drink adequate fluids to avoid dehydration [see Warnings and Precautions (5.8)]. Hepatic Toxicity Advise patients to report signs or symptoms of hepatic toxicity to their healthcare provider [see Warnings and Precautions (5.9)]. Thrombotic Microangiopathy Advise patients to seek immediate medical attention if any signs or symptoms of thrombotic microangiopathy occur [see Warnings and Precautions (5.10)].

Ability to Drive or Operate Machinery or Impairment of Mental Ability Bortezomib may cause fatigue, dizziness, syncope, orthostatic/postural hypotension. Advise patients not to drive or operate machinery if they experience any of these symptoms [see Warnings and Precautions (5.2, 5.5)]. Embryo-Fetal Toxicity Advise females of the potential risk to the fetus and to use effective contraception during treatment with bortezomib and for seven months following the last dose.

Advise male patients with female partners of reproductive potential to use effective contraception during treatment with bortezomib 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 [see Warnings and Precautions (5.11)]. Lactation Advise women not to breastfeed while receiving bortezomib and for two months after last dose [see Use in Specific Populations (8.2)].

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 [see Dosage and Administration (2.9)] , or skin pain.

Discuss with patients the option for antiviral prophylaxis for herpes virus infection [see Adverse Reactions (6.1)]. Other Instruct patients to contact their physicians if they develop an increase in blood pressure, bleeding, fever, constipation, or decreased appetite. Manufactured by: MSN Laboratories Private Limited Telangana – 509 228, INDIA Distributed by: Sintetica U… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~2 min read ▾

12.3Pharmacokinetics Following intravenous administration of 1 mg/m 2 and 1.3 mg/m 2 doses, the mean maximum plasma concentrations of bortezomib (C max ) after the first dose (Day 1) were 57 and 112 ng/mL, respectively. When administered twice weekly, the mean maximum observed plasma concentrations ranged from 67 to 106 ng/mL for the 1 mg/m 2 dose and 89 to 120 ng/mL for the 1.3 mg/m 2 dose. Following an intravenous bolus or subcutaneous injection of a 1.3 mg/m 2 dose to patients with multiple myeloma, the total systemic exposure after repeat dose administration (AUC last ) was equivalent for subcutaneous and intravenous administration.

The AUC last geometric mean ratio (90% confidence interval) was 0.99 (0.80 to 1.23). The C max after subcutaneous administration (20.4 ng/mL) was lower than after intravenous administration (223 ng/mL) with repeat dose administration. Distribution The mean distribution volume of bortezomib ranged from approximately 498 to 1884 L/m 2 following single- or repeat-dose administration of 1 mg/m 2 or 1.3 mg/m 2 to patients with multiple myeloma.

The binding of bortezomib to human plasma proteins averaged 83% over the concentration range of 100 to 1,000 ng/mL. Elimination The mean elimination half-life of bortezomib upon multiple dosing ranged from 40 to 193 hours after the 1 mg/m 2 dose and 76 to 108 hours after the 1.3 mg/m 2 dose. The mean total body clearances were 102 and 112 L/h following the first dose for doses of 1 mg/m 2 and 1.3 mg/m 2 , respectively, and ranged from 15 to 32 L/h following subsequent doses for doses of 1 and 1.3 mg/m 2 , respectively.

Metabolism Bortezomib is primarily oxidatively metabolized to several inactive metabolites in vitro via cytochrome P450 (CYP) enzymes 3A4, CYP2C19, and CYP1A2, and to a lesser extent by CYP2D6 and CYP2C9. Excretion The pathways of elimination of bortezomib have not been characterized in humans. Specific Populations No clinically significant differences in the pharmacokinetics of bortezomib were observed based on age, sex, or renal impairment (including patients administered bortezomib after dialysis).

The effect of race on bortezomib pharmacokinetics is unknown. Patients with Hepatic Impairment Following administration of bortezomib doses ranging from 0.5 to 1.3 mg/m 2 , mild (total bilirubin ≤1x ULN and AST >ULN, or total bilirubin >1 to 1.5x ULN and any AST) hepatic impairment did not alter dose-normalized bortezomib AUC when compared to patients with normal hepatic function. Dose normalized mean bortezomib AUC increased by approximately 60% in patients with moderate (total bilirubin >1.5 to 3x ULN and any AST) or severe (total bilirubin >3x ULN and any AST) hepatic impairment.

A lower starting dose is recommended in patients with moderate or severe hepatic impairment. Drug Interaction Studies Clinical Studies No clinically significant differences in bortezomib pharmacokinetics were observed when coadministered with dexamethasone (weak CYP3A4 inducer), omeprazole (strong CYP2C19 inhibitor), or melphalan in combination with prednisone. Strong CYP3A4 Inhibitor Coadministration with ketoconazole (strong CYP3A4 inhibitor) increased bortezomib exposure by 35%.

Strong CYP3A4 Inducer Coadministration with rifampin (strong CYP3A4 inducer) decreased bortezomib exposure by approximately 45%. In Vitro Studies Bortezomib may inhibit CYP2C19 activity and increase exposure to drugs that are substrates for this enzyme.

🧬 Pharmacodynamics 76 words ▾

12.2Pharmacodynamics Following twice weekly administration of 1 mg/m 2 and 1.3 mg/m 2 bortezomib doses, the maximum inhibition of 20S proteasome activity (relative to baseline) in whole blood was observed five minutes after drug administration. Comparable maximum inhibition of 20S proteasome activity was observed between 1 and 1.3 mg/m 2 doses. Maximal inhibition ranged from 70% to 84% and from 73% to 83% for the 1 mg/m 2 and 1.3 mg/m 2 dose regimens, respectively.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Multiple Myeloma Randomized, Open-Label Clinical Study in Patients with Previously Untreated Multiple Myeloma A prospective, international, randomized (1:1), open-label clinical study (NCT00111319) of 682 patients was conducted to determine whether bortezomib administered intravenously (1.3 mg/m 2 ) in combination with melphalan (9 mg/m 2 ) and prednisone (60 mg/m 2 ) resulted in improvement in time to progression (TTP) when compared to melphalan (9 mg/m 2 ) and prednisone (60 mg/m 2 ) in patients with previously untreated multiple myeloma.

Treatment was administered for a maximum of nine cycles (approximately 54 weeks) and was discontinued early for disease progression or unacceptable toxicity. Antiviral prophylaxis was recommended for patients on the bortezomib study arm. The median age of the patients in the study was 71 years (48;91), 50% were male, 88% were Caucasian and the median Karnofsky performance status score for the patients was 80 (60;100).

Patients had IgG/IgA/Light chain myeloma in 63%/25%/8% instances, a median hemoglobin of 105 g/L (64;165), and a median platelet count of 221,500/microliter (33,000;587,000). Efficacy results for the trial are presented in Table 14 . At a prespecified interim analysis (with median follow-up of 16.3 months), the combination of bortezomib, melphalan and prednisone therapy resulted in significantly superior results for time to progression, progression-free survival, overall survival and response rate.

Further enrollment was halted, and patients receiving melphalan and prednisone were offered bortezomib in addition. A later, prespecified analysis of overall survival (with median follow-up of 36.7 months with a hazard ratio of 0.65, 95% CI: 0.51, 0.84) resulted in a statistically significant survival benefit for the bortezomib, melphalan and prednisone treatment arm despite subsequent therapies including bortezomib based regimens. In an updated analysis of overall survival based on 387 deaths (median follow-up 60.1 months), the median overall survival for the bortezomib, melphalan and prednisone treatment arm was 56.4 months and for the melphalan and prednisone treatment arm was 43.1 months, with a hazard ratio of 0.695 (95% CI: 0.57, 0.85).

Table 14: Summary of Efficacy Analyses in the Previously Untreated Multiple Myeloma Study Efficacy Endpoint Bortezomib, Melphalan and Prednisone ( n=344) Melphalan and Prednisone ( n=338) Time to Progression Events n (%) 101 (29) 152 (45) Median* (months) (95% CI) 20.7(17.6, 24.7) 15.0(14.1, 17.9) Hazard ratio † (95% CI) 0.54(0.42, 0.70) p-value ‡ 0.000002 Progression-Free Survival Events n (%) 135 (39) 190 (56) Median* (months) (95% CI) 18.3(16.6, 21.7) 14.0(11.1, 15.0) Hazard ratio † (95% CI) 0.61(0.49, 0.76) p-value † 0.00001 Response Rate CR § n (%) 102 (30) 12 (4) PR § n (%) 136 (40) 103 (30) nCR n (%) 5 (1) 0 CR + PR § n (%) 238 (69) 115 (34) p-value ¶ <10 -10 Overall Survival at Median Follow-Up of

36.7Months Events (deaths) n (%) 109 (32) 148 (44) Median* (months) (95% CI) Not Reached(46.2, NR) 43.1(34.8, NR) Hazard ratio † (95% CI) 0.65(0.51, 0.84) p-value † 0.00084 Note: All results are based on the analysis performed at a median follow-up duration of 16.3 months except for the overall survival analysis. * Kaplan-Meier estimate † Hazard ratio estimate is based on a Cox proportional-hazard model adjusted for stratification factors: beta 2 -microglobulin, albumin, and region. A hazard ratio less than one indicates an advantage for bortezomib, melphalan and prednisone ‡ p-value based on the stratified log-rank test adjusted for stratification factors: beta 2 -microglobulin, albumin, and region § EBMT criteria ¶ p-value for Response Rate (CR + PR) from the Cochran-Mantel-Haenszel chi-square test adjusted for the stratification factors TTP was statistically significantly longer on the bortezomib, melphalan and prednisone arm (see Figure 1).

(median follow-up 16.3 months) Figure 1: Time to Progression Bortezomib, M… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~1 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been conducted with bortezomib. Bortezomib showed clastogenic activity (structural chromosomal aberrations) in the in vitro chromosomal aberration assay using Chinese hamster ovary cells. Bortezomib was not genotoxic when tested in the in vitro mutagenicity assay (Ames test) and in vivo micronucleus assay in mice.

Fertility studies with bortezomib were not performed but evaluation of reproductive tissues has been performed in the general toxicity studies. In the six month rat toxicity study, degenerative effects in the ovary were observed at doses ≥0.3 mg/m 2 (one-fourth of the recommended clinical dose), and degenerative changes in the testes occurred at 1.2 mg/m 2 .

13.2Animal Toxicology and/or Pharmacology Cardiovascular Toxicity Studies in monkeys showed that administration of dosages approximately twice the recommended clinical dose resulted in heart rate elevations, followed by profound progressive hypotension, bradycardia, and death 12 to 14 hours postdose. Doses ≥1.2 mg/m 2 induced dose-proportional changes in cardiac parameters. Bortezomib has been shown to distribute to most tissues in the body, including the myocardium.

In a repeated dosing toxicity study in the monkey, myocardial hemorrhage, inflammation, and necrosis were also observed. Chronic Administration In animal studies at a dose and schedule similar to that recommended for patients (twice weekly dosing for two weeks followed by one week rest), toxicities observed included severe anemia and thrombocytopenia, and gastrointestinal, neurological and lymphoid system toxicities. Neurotoxic effects of bortezomib in animal studies included axonal swelling and degeneration in peripheral nerves, dorsal spinal roots, and tracts of the spinal cord.

Additionally, multifocal hemorrhage and necrosis in the brain, eye, and heart were observed.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 111 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been conducted with bortezomib. Bortezomib showed clastogenic activity (structural chromosomal aberrations) in the in vitro chromosomal aberration assay using Chinese hamster ovary cells. Bortezomib was not genotoxic when tested in the in vitro mutagenicity assay (Ames test) and in vivo micronucleus assay in mice.

Fertility studies with bortezomib were not performed but evaluation of reproductive tissues has been performed in the general toxicity studies. In the six month rat toxicity study, degenerative effects in the ovary were observed at doses ≥0.3 mg/m 2 (one-fourth of the recommended clinical dose), and degenerative changes in the testes occurred at 1.2 mg/m 2 .

📚 References 16 words ▾

15 REFERENCES 1. "OSHA Hazardous Drugs" (refer to antineoplastic weblinks including OSHA Technical Manual). OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

📄 Package Label / Principal Display Panel 44 words ▾

PACKAGE LABEL PRINCIPAL DISPLAY PANEL SECTION Bortezomib For Injection 3.5 mg/vial - Vial Label viallabel

Bortezomib For Injection 3.5 mg/vial - Carton Label cartonlabel

Bortezomib For Injection 3.5 mg/vial - Sticker Label IV stickerlabel

Bortezomib For Injection 3.5 mg/vial - Sticker Label SC stickerlabel

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Bortezomib — the program that covers self-administered drugs. 10 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Bortezomib. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$459.5K
Claims incl. refills
998
Beneficiaries
438
Spend / beneficiary
$1,049.13
Spend / claim
$460.44
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

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Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Sintetica US LLC. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Sintetica US LLC is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 83089-0101-02 · Hanmi 83090-0009-01 · Sintetica →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.