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bortezomib

( bore-THE-zo-mib )
Funding:
New Drug Funding Program
  • Bortezomib - Previously Untreated - Multiple Myeloma
  • Bortezomib - Previously Untreated - Multiple Myeloma Pre-Stem Cell Transplant
  • Bortezomib - Relapsed or Refractory Multiple Myeloma
Other Name(s): Velcade®
Appearance: Colourless solution
A - Drug Name

bortezomib

COMMON TRADE NAME(S):   Velcade®

 
B - Mechanism of Action and Pharmacokinetics

Bortezomib is a modified dipeptidyl boronic acid. It is a reversible inhibitor of the 26S proteasome, a large protein complex that degrades ubiquitinated proteins. Inhibition of the proteasome pathway leads to activation of multiple signaling cascades cell-cycle arrest, and apoptosis.



Absorption

Comparable exposure was observed following repeated intravenous or subcutaneous doses.


Distribution

After IV administration, more than 90% of the drug is rapidly cleared from the plasma within minutes. Distributed widely to peripheral tissues.

Cross blood brain barrier? no
PPB 83%
Metabolism
Active metabolites no
Inactive metabolites

yes

Elimination

Not characterized in humans. Route of elimination appeared to be species-specific.

Half-life

Multiple dosing:

  • 1 mg/m2: 40 to 193 hours
  • 1.3 mg/m2: 49 to 109 hours
 
C - Indications and Status
Health Canada Approvals:

  • Treatment of progressive multiple myeloma in patients who have received at least one prior treatment and who have already undergone, or are unsuitable for, stem cell transplantation.

  • As part of a medically recognized combination therapy for induction treatment of patients with previously untreated multiple myeloma who are suitable for stem cell transplantation

  • As part of combination therapy for the treatment of patients with previously untreated multiple myeloma who are unsuitable for stem cell transplantation

  • As part of combination therapy for the treatment of patients with previously untreated mantle cell lymphoma who are unsuitable for stem cell transplantation.

  • Treatment of patients with mantle cell lymphoma who have relapsed or were refractory to at least one prior therapy



 
D - Adverse Effects

Emetogenic Potential:  

Low

Extravasation Potential:   None

The following table contains adverse effects that occurred in ≥10% of patients in single agent intravenous randomized studies in myeloma or were considered severe or life-threatening from other clinical studies or post-marketing.

ORGAN SITE SIDE EFFECT* (%) ONSET**
Auditory Hearing impaired (rare) E
Cardiovascular Arrhythmia (rare) I  E
Arterial thromboembolism (rare) E  D
Cardiotoxicity (rare) E
Hypotension (11%) (orthostatic) I  E
Pericarditis (<1%) (rare) I  E
Pulmonary hypertension (rare) E
QT interval prolonged (rare) I  E
Sudden death (rare, with induction therapy)
Venous thromboembolism (rare) E  D
Dermatological Rash (24%) I  E
Gastrointestinal Abdominal pain (16%) I  E
Anorexia, weight loss (34%) E
Constipation (42%) (2% severe) E
Diarrhea (58%) I  E
Dyspepsia (10%) E
GI obstruction (rare) E
GI perforation (rare) E
Nausea, vomiting (57%) I
General Edema (17%) (including effusions) E
Fatigue (61%) E
Fever (35%) E
Rigors (11%) E
Hematological Disseminated intravascular coagulation (rare) E
Hemolytic uremic syndrome (rare) E
Myelosuppression ± infection, bleeding (35%) (including atypical, viral reactivation) (26% severe) E
Hepatobiliary ↑ LFTs (rare; may be severe) E
Pancreatitis (rare) E
Hypersensitivity Hypersensitivity (rare, may be severe) I
Immune Other (Graft loss - rare)
Injection site Injection site reaction (6% for SC, rare for IV) I
Metabolic / Endocrine Abnormal electrolyte(s) (13%) (K, Mg, Ca, Na, PO4) E
Tumor lysis syndrome (rare) E
Musculoskeletal Musculoskeletal pain (24%) E
Nervous System Cognitive disturbance (rare) E
Dizziness (14%) I  E
Headache (26%) E
Insomnia (18%) E
Leukoencephalopathy (PML - rare) E
Neuropathy (36%) (sensory, motor, including Guillan-Barre - rare; autonomic - may be severe) E
Optic neuritis (rare) E
RPLS / PRES (rare) E
Seizure (rare) E
Ophthalmic Blurred vision (11%) E
Renal Nephrotoxicity (rare) E
Proteinuria (nephrotic syndrome - rare) E
Respiratory Cough, dyspnea (25%) E
Pneumonitis (rare) E


* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.

** I = immediate (onset in hours to days)     E = early (days to weeks)
D = delayed (weeks to months)      L = late (months to years)

The most common side effects for bortezomib include fatigue, diarrhea, nausea, vomiting, constipation, neuropathy, fever, myelosuppression ± infection, bleeding, anorexia, weight loss, headache, cough and dyspnea.

Patients at risk of tumour lysis syndrome (i.e. high tumour burden) should have appropriate prophylaxis and be monitored closely.

Myelosuppression was more common in the myeloma studies, while neuropathy and rash were more common in the mantle cell lymphoma studies. Myelosuppression is not cumulative and nadirs usually occur at ± 8-11 days. Thrombocytopenia is common, dose-related and more severe in patients with low platelets prior to therapy. Hemorrhage (including GI and CNS) due to low platelet count has been observed.

Bortezomib treatment can cause nausea, vomiting, and diarrhea, sometimes requiring the use of antiemetics or antidiarrheals. Fluid and electrolyte replacement should be administered to prevent dehydration. Constipation may occur as well as ileus.

Viral reactivation, including herpes zoster, has been reported in up to 14% of patients. Prophylaxis is recommended. Rare cases of JC virus, resulting in fatal progressive multifocal leukoencephalopathy (PML) have been reported. New onset or worsening neurological symptoms should be referred to a neurologist.

Bortezomib may cause a dose-related and cumulative peripheral neuropathy that is predominantly sensory, although severe cases of mixed sensory-motor or motor neuropathy (including Guillain-Barre) have also been reported. The incidence is lower when given subcutaneously. 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 during treatment with bortezomib. Subcutaneous bortezomib could be considered. The neuropathy appears reversible in most patients. Autonomic neuropathy may occur and may be severe.

Bortezomib treatment can cause orthostatic/postural hypotension. Some cases are also associated with syncope. These events can occur throughout therapy and may be more common in patients with pre-existing hypertension.

Hypertension has also been reported, and rarely, patients may present with posterior reversible leukoencephalopathy syndrome (PRES) with hypertension, headache and visual loss.

Acute development or exacerbation of congestive heart failure and/or new onset of decreased left ventricular ejection fraction has been seen, even in patients who do not have risk factors or existing heart disease.

Rare cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions. There is limited re-challenge information in these patients.

Rare fatal cases of pulmonary disorders including pneumonitis have been reported. Patients should be promptly investigated if any new or worsening pulmonary symptoms occur and bortezomib discontinued if pneumonitis is confirmed.

When given subcutaneously, there is a lower incidence of peripheral neuropathy but more hypertension, weight loss, fever and injection site reactions.

 
E - Dosing

Refer to protocol by which patient is being treated.

Bortezomib has a narrow therapeutic index and should be used with caution.

Consider the use of antiviral prophylaxis against herpes zoster (shingles) during bortezomib therapy.

Patients at risk of tumour lysis syndrome (i.e. high tumour burden) should have appropriate prophylaxis and be monitored closely.

Doses should be administered at least 72 hours apart to minimize drug accumulation and missed doses should not be made up.

Bortezomib is used as a single agent (q3w) for relapsed myeloma and for mantle cell lymphoma, and in combination with a standard melphalan and prednisone regimen (q6w) for previously untreated myeloma or medically recognized combination therapy for induction treatment prior to stem cell transplantation.



Adults:

Single Agent in Relapsed Multiple Myeloma or Mantle Cell Lymphoma:


Intravenous / Subcutaneous: 1.3 mg/m² on Days 1, 4, 8, 11; q 3 weeks for up to 8 cycles.

For patients with continuing response after 8 cycles, consider continuation with a q 5 weeks schedule (Day 1, 8, 15, 22, q 5 weeks)


As Part of Induction therapy for Previously Untreated Multiple Myeloma Pre-Stem Cell Transplantation:


Intravenous / Subcutaneous: 1.3 mg/m² Days 1, 4, 8, 11; q 3 weeks for 3-6 cycles
(Although not approved by Health Canada, some clinical trials have used bortezomib 1.5 mg/m2 IV weekly on Days 1, 8, 15, and 22; q 4 weeks)
 

With Melphalan and Prednisone, in Multiple Myeloma Patients Unsuitable for Stem Cell Transplantation:

Intravenous / Subcutaneous:
Cycles 1-4 -  1.3 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29, 32; q 6 weeks
Cycles 5-9 -  1.3 mg/m2 on Days 1, 8, 22, 29; q 6 weeks



(Refer to BMP regimen monograph)


As part of combination therapy (bortezomib-rituximab-cyclophosphamide-doxorubicin-prednisone) in Previously Untreated Mantle Cell Lymphoma: 
 
Intravenous / Subcutaneous: 1.3 mg/m² on days 1, 4, 8, 11; q 3 weeks for 6 cycles (2 additional cycles may be given if the first response is documented at cycle 6)
 
With

Day 1: rituximab 375 mg/m2 IV, doxorubicin 50 mg/m2 IV, cyclophosphamide 750 mg/mIV;

Days 1-5: prednisone 100 mg/m2 PO




Dosage with Toxicity:

Dose Level Bortezomib Dose (mg/m2)
0 1.3
-1 1
-2 0.7
 
Patients with symptoms of pneumonitis or ARDS should have treatment withheld and be appropriately investigated.
 
 
Table A: 
  • Single Agent for Relapsed/Refractory Myeloma or Mantle Cell Lymphoma
  • As Part of Induction therapy for Previously Untreated transplant eligible Multiple Myeloma (i.e.CYBORD)
     
    Toxicity Grade Bortezomib Dose
    ANC <0.5 x 109/L Hold+ until recovery; restart at 1 dose level ↓.
    Platelets < 25 x 109/L
    Drug-related fluid retention* Grade 2 Continue at 1 dose level ↓.
    ≥ Grade 3 Discontinue.
    Non-hematologic toxicity (see table D for neurotoxicity) ≥ Grade 3

    Hold+ until ≤ grade 1 or baseline; restart at 1 dose level ↓.

    Consider discontinuing for grade 4.

    Pneumonitis   Hold and investigate; discontinue if confirmed.
    PRES/ PML/ or dose-limiting toxicity at 0.7 mg/m2 Any Discontinue.

    + If no recovery after delay, discontinue.

    *Used in mantle cell lymphoma trial by Belch et al.

     

Table B:
  • Previously untreated transplant ineligible multiple myeloma (In Combination with Melphalan and Prednisone)
     
    Toxicity in Previous Cycle / Toxicity Day 1 of Cycle Dose Modification and Action
    Day 1 ANC < 1 x 109/L or platelets < 70 x 109/L Delay until recovery.
    Prolonged (≥ 5 days) grade 4 ANC or platelets or febrile neutropenia or thrombocytopenic bleeding in previous cycle Consider ↓ melphalan dose by 25%.
    Bortezomib held (≥ 3 times in a cycle during twice weekly administration, or ≥ 2 times in a cycle during weekly administration) ↓ bortezomib by 1 dose level.
    Grade 3 or 4 non-hematologic toxicity (see table D for neurotoxicity) Hold until ≤ grade 1/baseline; restart with 1 dose level ↓. Consider discontinuing for grade 4.
    Pneumonitis Hold and investigate; discontinue if confirmed.
    Any grade PRES/ PML/ or dose-limiting toxicity at 0.7 mg/m2 Discontinue.
    Toxicity Within Cycle
    ANC ≤ 0.75 x 109/L or platelet ≤ 30 x 109/L Hold both bortezomib and melphalan (if applicable).
    Grade 3 or 4 non-hematologic toxicity (see table D for neurotoxicity)

    Hold until ≤ grade 1/baseline; restart with 1 dose level ↓.

    Consider discontinuing for grade 4.

    Pneumonitis Hold and investigate; discontinue if confirmed.
    Any grade PRES/ PML/ or dose-limiting toxicity at 0.7 mg/m2 Discontinue.

     

Table C:
  • Previously Untreated Mantle Cell Lymphoma (in Combination with Rituximab, Cyclophosphamide, Doxorubicin and Prednisone )
     
    Toxicity Prior Cycle Bortezomib Dose Modification and Action
    ≥ Grade 3 neutropenia with fever, grade 4 neutropenia lasting more than 7 days, or a platelet count < 10 × 109/L

    Delay until recovery.

    Hold for up to 2 weeks until the patient has an ANC ≥ 0.75 × 109/L and a platelet count ≥ 25 × 109/L; restart at 1 dose level ↓.

    Discontinue if no recovery within 2 weeks.

    Grade 3 or 4 non-hematologic toxicity (see table D for neurotoxicity)

    Hold until recovery to ≥ grade 2; restart at 1 dose level ↓.

    Consider discontinuing for grade 4 toxicity.

    Day 1 of Cycle: Do not start until platelets ≥ 100 x 109/L, ANC ≥ 1.5 x 109/L, hemoglobin ≥ 80 g/L and other toxicities ≤ grade 1.
    If platelet counts < 100 × 109/L. or ANC < 1.5 × 109/L and hemoglobin < 80 g/L Delay until recovery.
    Grade 3 or 4 non-hematologic toxicity (see table D for neurotoxicity)

    Hold until recovery to ≥ grade 2; restart at 1 dose level ↓.

    Consider discontinuing for grade 4 toxicity.

    Toxicity Within Cycle
    If platelet counts < 25 × 109/L or ANC < 0.75 × 109/L

    Hold bortezomib for up to 2 days (ensure at least 72 hours elapse after this dose until Day 8 or Day 11).

    If cannot be given within 2 days, skip dose and do not make up later in the cycle.

    ≥ Grade 3 neutropenia with fever, grade 4 neutropenia lasting more than 7 days, or a platelet count < 10 × 109/L

    Delay until recovery.

    Hold for up to 2 weeks until the patient has an ANC ≥ 0.75 × 109/L and a platelet count ≥ 25 × 109/L; restart at 1 dose level ↓.

    Discontinue if no recovery within 2 weeks.

    Grade 3 or 4 non-hematologic toxicity (see table D for neurotoxicity)

    Hold until recovery to ≥ grade 2; restart at 1 dose level ↓.

    Consider discontinuing for grade 4 toxicity.

    Pneumonitis Hold and investigate; discontinue if confirmed.
    Any grade PRES/ PML/ or dose-limiting toxicity at 0.7 mg/m2 Discontinue.

     

Table D:

  • Dosage for Neurotoxicity
     
    Severity of Peripheral Neuropathy Bortezomib Dosage and Regimen Modification
    Grade 1 (paresthesia, weakness and/or loss of reflexes) without pain or loss of function No action.
    Grade 1 with pain or grade 2 (interfering with function but not with activities of daily living) Restart at 1 dose level ↓
    Grade 2 with pain or grade 3 (interfering with activities of daily living) Hold until toxicity resolves; restart at 2 dose level ↓ (0.7mg/m2 ) and give once per week.
    Grade 4 (sensory neuropathy which is disabling or motor neuropathy that is life-threatening or leads to paralysis, and/or severe autonomic neuropathy) Discontinue.

     



Dosage with Hepatic Impairment:

Bortezomib is metabolized by liver enzymes and exposure is increased in patients with moderate to severe hepatic impairment.  Patients with hepatic impairment should be treated with extreme caution and should be closely monitored for toxicities, and dose reduction should be considered.

Suggested dose modifications:

Bilirubin

AST

Starting Dose

≤ 1 x ULN

> ULN

No change

> 1 – 1.5 x ULN

Any

No change

> 1.5 – 3 x ULN

Any

 

First cycle: ↓ to 0.7mg/m2.

Subsequent cycles: Consider ↑ dose to 1mg/m2 or further ↓ dose to 0.5mg/m2 based on patient tolerability.

> 3 x ULN

Any

 

 

 

 



Dosage with Renal Impairment:

Dose adjustments are not necessary in patients with renal insufficiency (Dimopolous 2010). Patients with compromised renal function should be monitored carefully when treated with bortezomib, especially if creatinine clearance is less than 30mL/min.  Bortezomib should be given after dialysis.



Dosage in the elderly:

No dose adjustment is necessary.



Children:

The safety and effectiveness of bortezomib in children have not been established.

 



 
F - Administration Guidelines

  • Bortezomib may be administered:

    • Intravenously (1 mg/mL concentration) as a 3 to 5 second bolus injection or

    • Subcutaneous (2.5 mg/mL concentration)

  • Bortezomib should only be reconstituted with 0.9% sodium chloride injection.

  • Bortezomib is FATAL IF GIVEN INTRATHECALLY.

  • Bortezomib has a narrow therapeutic range. If a different reconstituted concentration is used for each route of administration, exercise caution when reconstituting and calculating the dose volume.

  • If local injection site reactions occur following subcutaneous bortezomib, consider using a less concentrated solution subcutaneously (1 mg/mL), or administer as IV.

  • For subcutaneous use, bortezomib solution is injected into the right or left sides of the thighs or abdomen. Rotate injection sites with subsequent injections. Give new injections at least 2.5 cm from an old site and never into areas where the site is tender, bruised, erythematous, or indurated.

  • Unopened vials may be stored between 15 and 30º C. Retain in original package and protect from light.



 
G - Special Precautions
Contraindications:

  • Patients with hypersensitivity to bortezomib, boron, mannitol, or other excipients

  • Bortezomib is NOT for intrathecal use. Fatal if given intrathecally. 

Other Warnings/Precautions:

  • Caution should be exercised when driving or using machinery, and in patients on medication(s) that may lead to hypotension, or patients with dehydration or history of syncope, due to the risk of hypotension and dizziness.

  • Use with caution in patients with amyloidosis or risk factors for seizures.

  • Use with caution in patients with risk factors for or existing cardiac disease.

  • Use with caution in patients with pre-existing peripheral or autonomic neuropathy; patients with pre-existing severe neuropathy should be treated with bortezomib only after careful risk/benefit assessment.


Other Drug Properties:

  • Carcinogenicity: Unknown

    Carcinogenicity studies have not been conducted.

Pregnancy and Lactation:
  • Clastogenicity: Yes
  • Fetotoxicity: Yes
  • Mutagenicity: Unlikely
  • Teratogenicity: Unlikely

    Women of childbearing potential should avoid becoming pregnant while being treated with bortezomib.  Adequate contraception should be used by both genders during bortezomib treatment and for 3 months after treatment completion. 

  • Excretion into breast milk: Unknown

    Breastfeeding is not recommended.

  • Fertility effects: Probable
 
H - Interactions

Bortezomib is metabolized primarily by CYP3A4 and 2C19. Bortezomib is a poor inhibitor of CYP 1A2, 2C9, 2D6, 3A4 and 2C19 and does not induce CYP1A2 or CYP3A4 in vitro. In addition, bortezomib does not appear to be a substrate for p-glycoprotein (Pgp) and several other drug efflux pumps. No significant drug-drug interaction was observed with bortezomib and omeprazole (potent CYP2C19 inhibitor).

AGENT EFFECT MECHANISM MANAGEMENT
Hypoglycemic agents (e.g. glyburide, metformin, pioglitazone, rosiglitazone, repaglinide etc.) Potential hypoglycemia or hyperglycemia Unknown Close monitoring of blood glucose and dose adjustment of antidiabetic agent as necessary
CYP3A4 inhibitors (i.e. ketoconazole, voriconazole, clarithromycin, ritonavir, fruit or juice from grapefruit, Seville oranges, starfruit or pomegranate ) ↑ bortezomib exposure (up to 35%) and potential ↑ in toxicity ↓ metabolism of bortezomib Caution for use of strong CYP3A4 inhibitors; monitor for toxicity
CYP3A4 inducers (i.e. phenytoin, rifampin, dexamethasone, carbamazepine, phenobarbital, St. John’s Wort, etc) ↓ bortezomib exposure (up to 45%) and potential ↓ in efficacy ↑ metabolism of bortezomib Avoid strong CYP3A4 inducers; no significant effect observed for dexamethasone (weaker CYP3A4 inducer)
Drugs Associated with Peripheral Neuropathy (e.g. amiodarone, statins) Potential ↑ in neurotoxicity Additive effect Monitor and adjust dose accordingly
Hypotensive Agents Potential ↑ in hypotension Additive effects Monitor and adjust hypotensive agents accordingly
High dose cytarabine and daunorubicin ↑ risk of ARDS Unknown Avoid concomitant use
Green tea and preparations containing green tea In laboratory studies, may reduce bortezomib activity Unknown Avoid use during treatment duration
Vitamin C supplements In laboratory studies, may suppress or eliminate bortezomib activity Formation of inactive complex with bortezomib; appears to be dose-dependent Avoid use of vitamin C supplements during treatment. If must give, suggest vitamin C (up to 500mg) given at least 12 h before or after bortezomib
 
I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

Monitor Type Monitor Frequency

Chest x-ray

Baseline, then CXR and lung function assessment if ILD is suspected

CBC with differential

Baseline and as clinically indicated (at minimum, prior to each cycle); monitor platelets before each dose

Liver and renal function tests, electrolytes

 

Baseline, at each cycle and as clinically indicated

Blood glucose levels, especially in patients using antidiabetic medications

 
Baseline and as clinically indicated

Clinical toxicity assessment of fatigue, hypotension, neurotoxicity, infection, bleeding, respiratory symptoms, tumour lysis syndrome, cardiovascular, skin, neurologic and GI side effects

At each visit

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version



Suggested Clinical Monitoring

Monitor Type Monitor Frequency

LVEF monitoring in patients with cardiac risk factors

Baseline and as clinically indicated
 
J - Supplementary Public Funding

New Drug Funding Program (NDFP Website )

  • Bortezomib - Previously Untreated - Multiple Myeloma
  • Bortezomib - Previously Untreated - Multiple Myeloma Pre-Stem Cell Transplant
  • Bortezomib - Relapsed or Refractory Multiple Myeloma

 
K - References

Belch A, Kouroukis CT, Crump M, et al. A phase II study of bortezomib in mantle cell lymphoma: the National Cancer Institute of Canada Clinical Trials Group trial IND.150. Annals of Oncology 2007; 18: 116-21.

Channan-Khan A, Sonneveld P, Schuster MW et al. Analysis of herpes zoster events among bortezomib-treated patients in the phase III APEX study. J Clin Oncol 2008: 26; 4784-90.

Dimopoulos MA, Terpos E, Chanan-Khan A, et al. Renal impairment in patients with multiple myeloma: a consensus statement on behalf of the International Myeloma Working Group. J Clin Oncol. 2010 Nov 20;28(33):4976-84.

Golden EB, Lam PY, Kardosh A, et al. Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid based proteasome inhibitors. Blood 2009; 113(23); 5927-37.

Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncology 2011;12:431-40.

Perrone G, Hideshima T, Ikeda H, et al.  Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia 2009;23(9):1679-86.

Product Monograph: Velcade ® (bortezomib). Janssen Inc., March 2016.

Rajkumar S V, Richardson PG, Hideshima T et al. Proteasome inhibition as a novel therapeutic target in human cancer. J Clin Oncol, 2005; 23:630-639.

Richardson PG, Barlogie B, Berenson J et al. A Phase 2 Study of Bortezomib in Relapsed, Refractory Myeloma. N Engl J Med 2003; 348:2609-17.

San Miguel JF, Schlag R, Nuriet K, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. NEJM 2008: 359; 906-17.

Zou W, Yue P, Lin N, et al. Vitamin C inactivates the proteasome inhibitor PS-341 in human cancer cells. Clin Cancer Res 2006;12(1):273-80.


July 2019 Updated monograph format.

 
L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.

The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.

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