You are using an outdated browser. We suggest you update your browser for a better experience. Click here for update.
Close this notification.
Skip to main content Skip to search

COVID-19: Get the latest updates or take a self-assessment.

Chemotherapy and other systemic treatment regimens may change due to COVID-19. Find out more at Systemic Treatment Regimens During COVID-19.

riTUXimab

( rit-TUCKS-ee-mab )
Funding:
New Drug Funding Program
  • Rituximab (Biosimilar IV) and Rituximab SC in Combination with Chemotherapy - Indolent B-cell Lymphoma
  • Rituximab (Biosimilar IV) and Rituximab SC - Second Line - Chronic Lymphocytic Leukemia
  • Rituximab (Biosimilar IV) and Rituximab SC - Retreatment - Indolent Lymphoma
  • Rituximab (Biosimilar IV) and Rituximab SC - Retreatment - Aggressive Histology Lymphoma
  • Rituximab (Biosimilar IV) and Rituximab SC - Previously Untreated Chronic Lymphocytic Leukemia
  • Rituximab (Biosimilar IV) and Rituximab SC - Maintenance Treatment - Lymphoma
  • Rituximab (Biosimilar IV) and Rituximab SC - In Combination with Venetoclax - Relapsed Chronic Lymphocytic Leukemia
  • Rituximab (Biosimilar IV) and Rituximab SC - HIV-Related Aggressive Histology B-cell Lymphoma
  • Rituximab (Biosimilar IV) and Rituximab SC - Aggressive Histology Lymphoma
  • Rituximab (Biosimilar IV) - Single Agent - Indolent Lymphoma
  • Rituximab (Biosimilar IV) - In Combination with Idelalisib - Relapsed Chronic Lymphocytic Leukemia
  • Rituximab (Biosimilar IV) - As Part of the MATRix Regimen in Newly Diagnosed Previously Untreated PCNSL
Other Name(s): Rituxan®, Truxima™, Riximyo™, Ruxience™
Appearance: Clear, colourless solution mixed into larger bags of fluids
A - Drug Name

riTUXimab

COMMON TRADE NAME(S):   Rituxan®; Truxima™; Riximyo™; Ruxience™

 
B - Mechanism of Action and Pharmacokinetics

Rituximab is a chimeric mouse-human monoclonal IgG1κ antibody. It binds to the CD20 antigen (human B-lymphocyte-restricted differentiation antigen, Bp35), a hydrophobic transmembrane protein, which is expressed on B-lymphocytes and on > 90% of B cell non-Hodgkin’s lymphomas.  CD20 is not shed from the cell surface and does not internalize upon antibody binding.  Rituximab is thought to deplete CD20-positive cells via antibody-dependent cell-cytotoxicity and complement-mediated cell lysis. 



Distribution

Binds to lymphoid tissues with little or no binding to non-lymphoid tissues. Pharmacokinetics are dose proportional. Circulating B-cells were observed to be depleted within the first 3 doses in most patients and sustained for up to 6-9 months post-treatment; levels started to recover at 6 months after treatment and median B-cell levels returned to normal by 12 months after treatment completion.

Cross blood brain barrier? no information found
PPB no information found
Metabolism

The metabolism of rituximab is not fully understood.

Active metabolites no
Inactive metabolites no
Elimination

Clearance of rituximab decreases markedly with accumulation of the drug which occurs after multiple infusions. Detectable in serum for 3 to 6 months after completion of treatment.

Half-life

60 hours (after 1st infusion)
174 hours (after 4th infusion)

Urine no information found
 
C - Indications and Status
Health Canada Approvals:

  • Treatment of patients with relapsed or refractory low grade or follicular, CD20 positive, B-cell Non-Hodgkin’s lymphoma (NHL)
  • Treatment of patients with previously untreated Stage III/IV follicular, CD20+, B-cell NHL in combination with CVP
  • Treatment of CD20+ diffuse large B-cell NHL in combination with CHOP                   
  • Maintenance treatment of patients with follicular NHL who have responded to induction therapy with either CHOP or CHOP plus rituximab
  • Single-agent maintenance treatment of previously untreated patients with advanced follicular non-Hodgkin's lymphoma with high tumour burden and who have responded to induction therapy with either CHOP plus rituximab or CVP plus rituximab
  • Treatment of patients with previously untreated or previously treated B-cell chronic lymphocytic leukemia (B-CLL), Binet stage B or C, in combination with fludarabine and cyclophosphamide (FC)1
(1)  Efficacy of Rituximab-FC in previously treated CLL patients has not been studied. Approval in CLL is based on improvements in progression-free survival; no improvement in overall survival has been demonstrated.

Refer to the rituximab product monograph for non-oncologic indications.

 



Other Uses:

  • Relapsed or refractory hairy cell leukemia 
  • Acute lymphoblastic leukemia
 
D - Adverse Effects

Emetogenic Potential:  

Minimal

Extravasation Potential:   None

Side effects in the table below are from monotherapy with rituximab, or severe/life-threatening events from other uses.

ORGAN SITE SIDE EFFECT* (%) ONSET**
Cardiovascular Arrhythmia (1%) I
Arterial thromboembolism (1-2%) E
Cardiotoxicity (rare) E
Hypertension (5%) I  E
Hypotension (10%) I
Venous thromboembolism (3%) E
Dermatological Alopecia (1-10%) E
Rash (11%) (may be severe) I  E
Gastrointestinal Abdominal pain (7%) I  E
Anorexia, weight loss (3%) E
Constipation (1%) I
Diarrhea (4%) I
Dyspepsia (3%) E
GI obstruction (<1%) E  D
GI perforation (<1%) E  D
Mucositis (1%) E
Nausea, vomiting (17%) I
General Edema (5%) E
Fatigue (18%) I
Flu-like symptoms (>10%) I  E
Hematological Hemolysis (<1%) E
Hyperviscosity (Waldenstrom's; rare) I  E
Immunosuppression (± opportunistic infections, ≥ 10%) E
Myelosuppression ± infection, bleeding (11%) (higher incidence with chemotherapy, may be severe) E
Hypersensitivity Hypersensitivity (77%) (7% severe; with first infusion) I
Immune Antibody response (1%) (antichimeric antibodies) E
Other Viral reactivation (including hepatitis B; rare) D
Metabolic / Endocrine Abnormal electrolyte(s) (2%) E
Hyperglycemia (5%) E
Tumor lysis syndrome (<1%) I
Musculoskeletal Musculoskeletal pain (8%) (or stiffness) I  E
Neoplastic Secondary malignancy (5%) (with chemotherapy) L
Nervous System Anxiety (2%) E
Dizziness (7%) E
Headache (13%) I  E
Leukoencephalopathy (PML - rare) E
Neuropathy (rare, peripheral or cranial) E  D
Paresthesia (16%) E
RPLS / PRES (rare) E
Sleep disorder (2%) E
Ophthalmic Conjunctivitis (1%) E
Optic nerve disorder (rare) E
Watering eyes (3%) E
Renal Nephrotoxicity (1-10%) E
Respiratory Cough, dyspnea (8%) I  E
Pneumonitis (rare) I  E
Vascular Vasculitis (rare) E  D


* "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 adverse effects are infusion-related symptoms, fatigue, headache, rash, neutropenia and infections. Adverse effects are more frequent in older patients, and in patients with high bulk disease. In clinical trials, there was a higher incidence of severe neutropenia in rituximab-containing arms as compared to the chemotherapy-only arms.

 

 

Acute reactions:

  • Infusion-related symptoms, which may be related to cytokine release, include fever and chills/rigors, urticaria, bronchospasm, ARDS, angioedema, hypotension and flushing; they usually occur 30 minutes to 2 hours after the start of the first infusion and may be fatal.  The majority of serious infusion reactions were observed with the first infusion, in which approximately 80% of fatal infusion reactions were reported. The incidence decreases with subsequent infusions. Infusion reactions are more common in patients with high tumour burdens and are fatal in up to 0.07% of patients.  Autoimmune diseases or other co- morbidities may have contributed to the fatal outcome.
  • Anaphylaxis (including fatalities) may occur, usually with the second or subsequent infusion. These may not be clinically distinguishable from infusion-related reactions.
  • Severe pulmonary reactions with dyspnea, bronchospasm, hypoxia, and pulmonary infiltrates or edema have been reported, and are more common in patients with pulmonary involvement or disease. Acute symptoms appear within 1-2 hours of the initiation of the first infusion, while pneumonitis may appear 1-4 weeks after the infusion.
  • Signs and symptoms of tumour lysis syndrome (TLS) have been reported to occur within 1 to 2 hours after the first infusion. Patients at risk (high tumour burden) should be closely monitored and prophylaxis considered.
  • Symptoms of these acute reactions usually resolve with slowing or interruption of the rituximab infusion and aggressive treatment (IV saline, diphenhydramine and acetaminophen ± bronchodilators, IV corticosteroids or epinephrine). However, deterioration may occur after initial improvement of pulmonary or severe infusion-related symptoms and patients should be carefully monitored until complete symptom resolution.   TLS should be excluded.
  • Patients with pre-existing cardiac conditions, including arrhythmias and angina, should be carefully monitored throughout the infusion and in the immediate post-infusion period. Infusions should be discontinued in serious or life-threatening cardio-pulmonary events.

Serious Reactions:

Arterial thromboembolism, such as stroke, has been described in elderly patients who received rituximab especially in combination. Patients with cardiovascular disease or risk factors should be carefully monitored for signs of cerebral ischemia.

Severe mucocutaneous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, paraneoplastic pemphigus, lichenoid dermatitis or vesiculobullous dermatitis) have been described and may be fatal. The onset of these reactions can vary from days to several months following exposure to rituximab.

Bowel obstruction and perforation (some fatal cases) have been reported. The mean time of onset for these GI symptoms is 6 days.

Infections are common, including opportunistic infections. Reactivation of tuberculosis or hepatitis B virus (HBV) infection may occur during treatment, with fulminant hepatitis, hepatic failure and death, including in patients with normal hepatitis B surface antigen but who are seropositive. The risk is increased in patients receiving steroids and/or chemotherapy. Patients should be screened (hepatitis B surface antigen, HbsAg and hepatitis B core antibody, HbcAb status) prior to treatment. HBsAg positive patients should receive antiviral prophylaxis during and after rituximab. HBsAg negative, but HBcAb positive patients should be considered for antiviral prophylaxis and be closely monitored for viral reactivation by an HBV expert (2015 rituximab guidelines).

Cases of Pneumocystis Jiroveci Pneumonia (PJP) have been reported.  Infections have been reported in some patients with prolonged hypogammaglobulinemia (>11 months after rituximab exposure).

There have been isolated reports of JC virus reactivation in NHL patients, resulting in fatal progressive multifocal leukoencephalopathy (PML). Rituximab should be held at first signs or symptoms suggestive of PML, which may progress over days to weeks and can include progressive unilateral weakness, clumsiness of limbs, confusion, cognitive or personality changes. Patients suspected of having PML should be investigated with MRI and lumbar puncture to evaluate JC viral DNA.

Posterior reversible leukoencephalopathy syndrome (PRES) has been reported rarely; brain imaging confirms diagnosis. Risk factors include hypertension and concomitant immunosuppressive therapy.

Other viral infections (including fatal cases), such as CMV, herpes simplex, varicella, hepatitis C, West Nile, etc. have been reported up to one year following rituximab cessation. Patients who are HIV-positive with Kaposi’s sarcoma have been reported to have rapid Kaposi’s sarcoma progression.

Patients who develop human anti-murine antibodies (HAMA) or human anti-chimeric antibodies for rituximab (HACA) may have allergic or hypersensitivity reactions when treated with rituximab or other murine or chimeric monoclonal antibodies.

 

 
E - Dosing

Note:  Different rituximab products are not interchangeable.
 

Refer to protocol by which patient is being treated. Rituximab infusion should be administered in a setting where full resuscitation facilities are immediately available, and under the close supervision of someone experienced and capable of dealing with severe infusion-related reactions. Rituximab must not be administered as an IV bolus or push.

Patients should be screened for hepatitis B status prior to treatment initiation. Since transient hypotension may occur during rituximab infusion, consideration should be given to withhold antihypertensive medication 12 hours prior to and throughout the rituximab infusion.
 

Pre-medication:

Administer at least 30 minutes prior to IV rituximab (prophylaxis for infusion reactions):

  • Oral antipyretic (e.g. acetaminophen)
  • H1-receptor antagonist (e.g. diphenhydramine)
  • Corticosteroid (e.g. methylprednisolone 80 mg IV) in patients with high bulk disease or pulmonary involvement if no corticosteroids are already being given as part of the chemotherapy regimen.
     

Other supportive care:

  • Prophylaxis for tumour lysis (high bulk disease)
  • HBsAg positive patients should receive antiviral prophylaxis during and after rituximab. HBsAg negative, but HBcAb positive patients should be considered for antiviral prophylaxis and be closely monitored for viral reactivation by an HBV expert.


Adults:

Setting
Initial treatment (IV)
Maintenance (after response to induction therapy) (IV)
Low Grade/Follicular
Single Agent
375 mg/m2  q1w x 4 doses

Previously untreated with advanced high-tumour burden: 375mg/m2 q 2-3 months, for max 12 doses (2 years)(2)

 

Previously treated patients: 375 mg/m2 q 3 months until disease progression (max 2 years)

With CVP(1)
 
 
With CHOP(1,2)

►375 mg/m2  q3w x 8 cycles   

 

►375 mg/m q3w x 6-8 cycles

Setting
Initial treatment
Maintenance (after response to induction therapy)
Diffuse Large B Cell
With CHOP(1)

375 mg/m2  q3w x 6-8 cycles(2)

Not applicable
CLL
With FC
Cycle 1:  375 mg/m2 day 1 (3)

then Cycles 2-6: 500 mg/m2 day 1 (3)

 
1 Give on day 1 POST-steroid and PRE-cytotoxic regimen.
2 Hematology disease site group guideline recommends q3 month dosing as a reasonable schedule.  NDFP funds up to a maximum of 8 doses (over 2 years).
3 Consider methylprednisolone IV ±  slower infusion or split dose over 2 days for cycles where bulky disease or lymphocyte counts > 25 x 109/L.

Dosage with Toxicity:

Toxicity
Rituximab Dose* / Infusion Rate
Myelosuppression 
No adjustment required.
Other grade 3 toxicity
Delay infusion until ≤ grade 2
  • Any pulmonary toxicity 
  • Other grade 4  toxicity
  • Severe mucocutaneous toxicity
  • Serious/life-threatening cardio-pulmonary events
  • Reactivation of tuberculosis or hepatitis B
  • Evidence of active hepatitis
  • PML / PRES
Discontinue

*Missed or delayed doses may be administered at a later time point, based on physician’s discretion.


Management of Infusion-related reactions:

Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.

 

Grade Management Re-challenge
1 or 2
  • Stop or slow the infusion.
  • Manage the symptoms.
     

Restart:

  • Once symptoms have resolved, restart at 50% of the rate at which the IR occurred.
  • Re-challenge at 50% of the administration rate at which the IR occurred and with pre-medications.
  • Consider adding oral montelukast ± oral acetylsalicylic acid.
3 or 4
  • Stop the infusion.
  • Aggressively manage symptoms.
  • Consider clinical benefit and risks of further treatment. Consider patient factors, severity and nature of the IR and availability of suitable alternative treatment.
  • Consider desensitization for patients with recurrent reactions despite pre-medications and a slower infusion rate.


Dosage with Hepatic Impairment:

No dosage adjustment required; stop if evidence of hepatitis.



Dosage with Renal Impairment:

No dosage adjustment required.

 



Dosage in the elderly:

No dose adjustment required. Exercise caution as older patients are more likely to experience serious adverse events (including cardiac, pulmonary, or other grade 3/4 toxicity).



Children:

Safety and effectiveness in children have not been established.  Hypogammaglobulinemia has been observed in pediatric patients and may be severe, requiring long-term immunoglobulin substitution therapy.



 
F - Administration Guidelines

Note:  Different rituximab products are not interchangeable.

Rituximab IV and Subcutaneous formulations are not interchangeable.  The dosing and concentrations of these products are different.

For details on rituximab subcut administration, refer to rituximab (subcut) drug monograph.

Rituximab should be administered in a setting where full resuscitation facilities are immediately available, and under the close supervision of someone experienced and capable of dealing with severe infusion-related reactions.

  • DO NOT administer as an IV push or bolus.
  • Dilute to a final concentration of 1-4 mg/mL in normal saline or D5W.
  • To avoid foaming, gently invert the bag to mix the solution.
  • Do not admix with other drugs.
  • Administer rituximab through a dedicated line.
  • Compatible with PVC or polyethylene bags.
  • Keep vials refrigerated; do not freeze.  Protect from light.

 
Infusion rates:

First infusion:

  • Recommended to be administered over a graduated rate:  initial rate of 50 mg/h, then escalate rate in 50 mg/h increments every 30 minutes, to a maximum of 400 mg/h (about 4.25 hours in total).

Subsequent infusions:

  • If no severe infusion reaction (grade 3 or 4) occurred with the first cycle, a rapid infusion of IV rituximab over a total of 90 minutes can be initiated with cycle 2 (20% of the dose in the first 30 min then the remaining 80% over 60 min).

  • OR initial rate of 100 mg/h, then escalate rate in 100 mg/h increments every 30 minutes, to a maximum of 400 mg/h as tolerated (about 3.25 hours in total).

  • Alternatively, subcutaneous administration of rituximab can be considered starting with cycle 2.


When bulky disease present or WBC > 25-50 x 109/L, consider:

  • A slower infusion rate, or
  • Split dosing over days 1-2, or
  • Delaying rituximab treatment until chemotherapy has reduced the lymphocyte count
     

Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.



 
G - Special Precautions
Contraindications:

  • Patients with known hypersensitivity and anaphylactic reactions to proteins of similar mouse or human origin, to Chinese Hamster Ovary (CHO) cell proteins or to any component of this product.
  • Patients who have or have had PML, have active and/or severe infections, active hepatitis B, or severely immunocompromised (e.g. AIDS patients with very low CD4 or CD8 counts). 
  • Avoid the use of live vaccines.
 

Other Warnings/Precautions:

  • Exercise caution in patients with a history of recurring or chronic infections or with underlying conditions which may further predispose patients to serious infection. Patients may have increased risk of infection following rituximab treatment.
  • Prior to starting rituximab in HBV seropositive patients, consultation with a liver disease expert is recommended to determine ongoing monitoring of HBV reactivation and its management.
  • Exercise caution in patients with neutrophil counts < 1.5 x 109/L and/or platelets < 75 x 109/L due to limited experience in this patient group.
  • Use with extreme caution in patients with pre-existing cardiovascular disease or in patients with high tumour burden. Consider steroids ± slow infusions or infusions split over 2 days for patients with bulky disease or > 25 x 109/L circulating malignant cells.
  • Use with caution in patients with pulmonary insufficiency or lung tumour infiltration, and in patients with myelosuppression.
  • Reduced immunogenicity may occur with the use of vaccines.

 


Other Drug Properties:

  • Carcinogenicity: Unknown

Pregnancy and Lactation:
  • Teratogenicity: No
  • Mutagenicity: Unknown
  • Fetotoxicity: Unknown
    Rituximab should not be used during pregnancy.  IgGs are known to pass the placental barrier.  There have been reports of infants with transient B-cell depletion and lymphocytopenia.  Adequate contraception is recommended for both sexes with childbearing potential, during rituximab treatment and up to 12 months after the last dose.
  • Breastfeeding: Not recommended

    IgG is excreted into breast milk; women should therefore be advised to discontinue nursing during treatment and until rituximab levels are no longer detectable.

  • Fertility effects: Unknown
 
H - Interactions

Formal drug interaction studies have not been performed with rituximab.

AGENT EFFECT MECHANISM MANAGEMENT
Antihypertensive agents potentiation of hypotension with infusion Additive effects consider withholding temporarily (12 hours before and during infusion)
cisplatin renal failure Unknown use with extreme caution; monitor renal function closely
 
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

CBC

baseline and at each visit

LFTs

baseline and at each visit

Renal functions tests

baseline and at each visit

The Hematology Disease Site group recommends screening patients for hepatitis B surface antigen (HBsAg) and core antibody (HBcAb) prior to starting treatment. If seropositive, consult with an expert in HBV and monitor closely.

Close observation for tumour lysis syndrome, treatment-related reactions, pulmonary and skin toxicities

for 24 hours after the dose

Clinical assessment of infusion-related reactions, tumour lysis syndrome, infection, bleeding, GI, pulmonary, skin, CNS, cardiovascular 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

Monitor cardiovascular symptoms in patients who have cardiac conditions or recurrent cardiac events with rituximab

At each visit
 
J - Supplementary Public Funding

New Drug Funding Program (NDFP Website )

  • Rituximab (Biosimilar IV) and Rituximab SC in Combination with Chemotherapy - Indolent B-cell Lymphoma
  • Rituximab (Biosimilar IV) and Rituximab SC - Second Line - Chronic Lymphocytic Leukemia
  • Rituximab (Biosimilar IV) and Rituximab SC - Retreatment - Indolent Lymphoma
  • Rituximab (Biosimilar IV) and Rituximab SC - Retreatment - Aggressive Histology Lymphoma
  • Rituximab (Biosimilar IV) and Rituximab SC - Previously Untreated Chronic Lymphocytic Leukemia
  • Rituximab (Biosimilar IV) and Rituximab SC - Maintenance Treatment - Lymphoma
  • Rituximab (Biosimilar IV) and Rituximab SC - In Combination with Venetoclax - Relapsed Chronic Lymphocytic Leukemia
  • Rituximab (Biosimilar IV) and Rituximab SC - HIV-Related Aggressive Histology B-cell Lymphoma
  • Rituximab (Biosimilar IV) and Rituximab SC - Aggressive Histology Lymphoma
  • Rituximab (Biosimilar IV) - Single Agent - Indolent Lymphoma
  • Rituximab (Biosimilar IV) - In Combination with Idelalisib - Relapsed Chronic Lymphocytic Leukemia
  • Rituximab (Biosimilar IV) - As Part of the MATRix Regimen in Newly Diagnosed Previously Untreated PCNSL

 
K - References

McEvoy GK, editor. AHFS Drug Information 2013. Bethesda: American Society of Health-System Pharmacists, p. 1181-9.

Product Monograph: Rituxan® (rituximab). Roche Canada, October 2016.

Sehn LH, Donaldson J, Filewich A, et al. Rapid infusion rituximab in combination with steroid containing chemotherapy can be given safely and substantially reduces resource utilization. Blood 2004; 104(11): A1407.

Salar A, Casao D, Cervera M, et al. Rapid infusion of rituximab with or without steroid-containing chemotherapy: 1-yr experience in a single institution. Eur J Haematol 2006: 77: 338–340.


August 2020 Updated NDFP forms and Administraiton guidelines section

 
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.

Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.

While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.

CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.