Important Safety Information
Back
  • SIMPONI® (golimumab)

    INDICATIONS

    SIMPONI® is a tumor necrosis factor (TNF) blocker indicated for the treatment of adult patients with:

    • Moderately to severely active rheumatoid arthritis (RA), in combination with methotrexate (MTX)
    • Active psoriatic arthritis (PsA) alone, or in combination with MTX
    • Active ankylosing spondylitis (AS)
    • Moderately to severely active ulcerative colitis (UC) who have demonstrated corticosteroid dependence or who have had an inadequate response to or failed to tolerate oral aminosalicylates, oral corticosteroids, azathioprine, or 6-mercaptopurine for:
      • Inducing and maintaining clinical response
      • Improving endoscopic appearance of the mucosa during induction
      • Inducing clinical remission
      • Achieving and sustaining clinical remission in induction responders

    IMPORTANT SAFETY INFORMATION

    SERIOUS INFECTIONS

    Patients treated with SIMPONI® (golimumab) are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue SIMPONI® if a patient develops a serious infection.

    Reported infections with TNF blockers, of which SIMPONI® is a member, include:

    • Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before SIMPONI® use and during therapy. Treatment for latent infection should be initiated prior to SIMPONI® use.
    • Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.
    • Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

    The risks and benefits of treatment with SIMPONI® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Do not start SIMPONI® in patients with clinically important active infections, including localized infections. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with SIMPONI®, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy, who are on treatment for latent TB, or who were previously treated for TB infection.

    Risk of infection may be higher in patients greater than 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressant therapy. Other serious infections observed in patients treated with SIMPONI® included sepsis, pneumonia, cellulitis, abscess and hepatitis B infection.

    MALIGNANCIES

    Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers of which SIMPONI® is a member.

    Approximately half the cases were lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma. The other cases represented a variety of malignancies, including rare malignancies usually associated with immunosuppression and malignancies not usually observed in children or adolescents. Malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.

    In the controlled portions of clinical trials of all TNF-blocking agents including SIMPONI®, more cases of lymphoma have been observed among patients receiving TNF-blocking treatment compared with control patients. In the Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA), and Ankylosing Spondylitis (AS) clinical trials, the incidence of lymphoma per 100 patient-years of follow-up was 0.21 (95% CI: 0.03, 0.77) in the combined SIMPONI® group compared with an incidence of 0 (95% CI: 0, 0.96) in the placebo group. In clinical trials, the incidence of malignancies other than lymphoma was not increased with exposure to SIMPONI® and was similar to what would be expected in the general population. In controlled and uncontrolled portions of the Phase 2/3 studies in ulcerative colitis (UC) with a mean follow-up of approximately 1 year, there were no cases of lymphoma with SIMPONI®. Short follow-up periods, such as those of 1 year or less in the studies above, may not adequately reflect the true incidence of malignancies. Cases of acute and chronic leukemia have been reported with TNF-blocker use, including SIMPONI®. The risks and benefits of TNF-blocker therapy should be considered prior to initiating therapy in patients with a known malignancy or who develop a malignancy.

    Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers. These cases have had a very aggressive disease course and have been fatal. Nearly all reported cases have occurred in patients with Crohn’s disease or UC, and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. A risk for the development for HSTCL in patients treated with TNF blockers cannot be excluded.

    Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocking agents, including SIMPONI®. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.

    HEPATITIS B REACTIVATION

    The use of TNF-blocking agents including SIMPONI® has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic hepatitis B carriers. In some instances, HBV reactivation occurring in conjunction with TNF-blocker therapy has been fatal. The majority of these reports have occurred in patients who received concomitant immunosuppressants.

    All patients should be tested for HBV infection before initiating TNF-blocker therapy. For patients who test positive for hepatitis B surface antigen, consult a physician with expertise in the treatment of hepatitis B before initiating TNF-blocker therapy. Exercise caution when prescribing SIMPONI® for patients identified as carriers of HBV and closely monitor for active HBV infection during and following termination of therapy with SIMPONI®. Discontinue SIMPONI® in patients who develop HBV reactivation, and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of SIMPONI®, and monitor patients closely.

    HEART FAILURE

    Cases of worsening congestive heart failure (CHF) and new-onset CHF have been reported with TNF blockers, including SIMPONI®. Some cases had a fatal outcome. Exercise caution and monitor patients with heart failure. Discontinue SIMPONI® if new or worsening symptoms of heart failure appear.

    DEMYELINATING DISORDERS

    TNF-blocking agents, of which SIMPONI® is a member, have been associated with rare cases of new-onset or exacerbation of demyelinating disorders, including multiple sclerosis (MS) and Guillain-Barré syndrome. Cases of central demyelination, MS, optic neuritis, and peripheral demyelinating polyneuropathy have rarely been reported with SIMPONI®. Exercise caution in considering the use of SIMPONI® in patients with these disorders. Consider discontinuation if these disorders develop.

    AUTOIMMUNITY

    Treatment with TNF blockers, including SIMPONI®, may result in the formation of antinuclear antibodies and, rarely, in the development of a lupus-like syndrome. Discontinue treatment if symptoms suggestive of a lupus-like syndrome develop.

    HEMATOLOGIC CYTOPENIAS

    There have been reports of pancytopenia, leukopenia, neutropenia, agranulocytosis, aplastic anemia, and thrombocytopenia in patients receiving SIMPONI®. Exercise caution when using SIMPONI® in patients who have or had significant cytopenias.

    USE WITH OTHER DRUGS

    The concomitant use of a TNF blocker and abatacept or anakinra was associated with a higher risk of serious infections; therefore, the use of SIMPONI® in combination with these products is not recommended. Care should be taken when switching from one biologic to another since overlapping biological activity may further increase the risk of infection. A higher rate of serious infections has also been observed in RA patients treated with rituximab who received subsequent treatment with a TNF blocker. The concomitant use of SIMPONI® with biologics approved to treat RA, PsA, or AS is not recommended because of the possibility of an increased risk of infection.

    VACCINATIONS/THERAPEUTIC INFECTIOUS AGENTS

    People receiving SIMPONI® can receive vaccinations, except for live vaccines. Use of live vaccines could result in clinical infections, including disseminated infections. Administration of live vaccines to infants exposed to SIMPONI® in utero is not recommended for 6 months following the mother’s last SIMPONI® injection during pregnancy due to an increased risk of infection. It is recommended that therapeutic infectious agents not be given concurrently with SIMPONI® due to the possibility of clinical infections, including disseminated infections.

    HYPERSENSITIVITY REACTIONS

    Serious systemic hypersensitivity reactions (including anaphylactic reaction) have been reported with SIMPONI®, some occurring after the first dose. If an anaphylactic or other serious allergic reaction occurs, discontinue SIMPONI® immediately and institute appropriate therapy.

    ADVERSE REACTIONS

    The most serious adverse reactions were serious infections and malignancies.

    Upper respiratory tract infection and nasopharyngitis were the most common adverse reactions reported in the combined Phase 3 trials through Week 16, occurring in 7% and 6% of patients treated with SIMPONI® as compared with 6% and 5% of patients in the control group, respectively. The rate of injection-site reactions was 6% with patients treated with SIMPONI® compared with 2% of patients in the control group.

    In the Phase 2/3 trials in UC evaluating SIMPONI®-treated patients, no new adverse drug reactions were identified, and the frequency of adverse drug reactions was similar to the safety profile observed in patients with RA, PsA, and AS.

    Please see the full Prescribing Information and Medication Guide for SIMPONI®. Provide the Medication Guide to your patients and encourage discussion.

    cp-51205v1

    INDICATIONS
Click on the left to see the Important Safety Information

INDICATIONS

IMPORTANT SAFETY INFORMATION

Prescribing Information
Back
  • https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/SIMPONI-pi.pdf
    https://www.janssenlabels.com/package-insert/product-patient-information/SIMPONI-medication-guide.pdf

ICD-10 Codes

Downloadable Forms
X
JCP
Hover on a document on the left for a quick document preview
 
 
 

ICD-10 Codes

  1. Janssen CarePath
  2. SIMPONI®
  3. Reimbursement

The table below lists ICD-10 diagnosis codes that you may need for patients treated with SIMPONI®. These codes are not intended to be promotional or to suggest a use that is inconsistent with FDA-approved use. The list is not exhaustive and additional codes may apply. ICD-10 codes use 3 to 7 alpha and numeric characters. A code is invalid if it does not use the full number of characters required, including the seventh character, if applicable.

Click below to see the ICD-10 codes.

Click below to see the ICD-10 codes.

Rheumatoid Arthritis and Other Inflammatory Polyarthropathies / Other Rheumatoid Arthritis

ICD-10 Indication ICD-10 Code
... of unspecified site M05.70
... of right shoulder M05.711
... of left shoulder M05.712
... of unspecified shoulder M05.719
... of right elbow M05.721
... of left elbow M05.722
... of unspecified elbow M05.729
... of right wrist M05.731
... of left wrist M05.732
... of unspecified wrist M05.739
... of right hand M05.741
... of left hand M05.742
... of unspecified hand M05.749
... of right hip M05.751
... of left hip M05.752
... of unspecified hip M05.759
... of right knee M05.761
... of left knee M05.762
... of unspecified knee M05.769
... of right ankle and foot M05.771
... of left ankle and foot M05.772
... of unspecified ankle and foot M05.779
... of multiple sites M05.79
... of unspecified site M05.80
... of right shoulder M05.811
... of left shoulder M05.812
... of unspecified shoulder M05.819
... of right elbow M05.821
... of left elbow M05.822
... of unspecified elbow M05.829
... of right wrist M05.831
... of left wrist M05.832
... of unspecified wrist M05.839
... of right hand M05.841
... of left hand M05.842
... of unspecified hand M05.849
... of right hip M05.851
... of left hip M05.852
... of unspecified hip M05.859
... of right knee M05.861
... of left knee M05.862
... of unspecified knee M05.869
... of right ankle and foot M05.871
... of left ankle and foot M05.872
... of unspecified ankle and foot M05.879
... of multiple sites M05.89
Rheumatoid arthritis with rheumatoid factor, unspecified M05.9
Other Rheumatoid Arthritis M06
..., unspecified site M06.00
..., right shoulder M06.011
..., left shoulder M06.012
..., unspecified shoulder M06.019
..., right elbow M06.021
..., left elbow M06.022
..., unspecified elbow M06.029
..., right wrist M06.031
..., left wrist M06.032
..., unspecified wrist M06.039
..., right hand M06.041
..., left hand M06.042
..., unspecified hand M06.049
..., right hip M06.051
..., left hip M06.052
..., unspecified hip M06.059
..., right knee M06.061
..., left knee M06.062
..., unspecified knee M06.069
..., right ankle and foot M06.071
..., left ankle and foot M06.072
..., unspecified ankle and foot M06.079
..., vertebrae M06.08
..., multiple sites M06.09
..., unspecified site M06.80
..., right shoulder M06.811
..., left shoulder M06.812
..., unspecified shoulder M06.819
..., right elbow M06.821
..., left elbow M06.822
..., unspecified elbow M06.829
..., right wrist M06.831
..., left wrist M06.832
..., unspecified wrist M06.839
..., right hand M06.841
..., left hand M06.842
..., unspecified hand M06.849
..., right hip M06.851
..., left hip M06.852
..., unspecified hip M06.859
..., right knee M06.861
..., left knee M06.862
..., unspecified knee M06.869
..., right ankle and foot M06.871
..., left ankle and foot M06.872
..., unspecified ankle and foot M06.879
..., vertebrae M06.88
..., multiple sites M06.89
Rheumatoid arthritis, unspecified M06.9

Psoriatic Arthritis

ICD-10 Indication ICD-10 Code
Arthropathic psoriasis, unspecified L40.50
Distal interphalangeal psoriatic arthropathy L40.51
Psoriatic arthritis mutilans L40.52
Psoriatic spondylitis L40.53
Other psoriatic arthropathy L40.59

Ankylosing Spondylitis

ICD-10 Indication ICD-10 Code
Ankylosing spondylitis of multiple sites in spine M45.0
... occipito-atlanto-axial region M45.1
... cervical region M45.2
... cervicothoracic region M45.3
... thoracic region M45.4
... thoracolumbar region M45.5
... lumbar region M45.6
... lumbosacral region M45.7
... sacral and sacrococcygeal region M45.8
... unspecified sites in spine M45.9

Ulcerative Colitis

ICD-10 Indication ICD-10 Code
Ulcerative Colitis K51
Ulcerative (chronic) pancolitis without complications K51.00
Ulcerative (chronic) pancolitis with complications K51.01
Ulcerative (chronic) proctitis without complications K51.20
Ulcerative (chronic) proctitis with complications K51.21
Ulcerative (chronic) rectosigmoiditis without complications K51.30
Ulcerative (chronic) rectosigmoiditis with complications K51.31
Left sided colitis without complications K51.50
Left sided colitis with complications K51.51
Other ulcerative colitis without complications K51.80
Other ulcerative colitis with complications K51.81
Ulcerative colitis, unspecified, without complications K51.90
Ulcerative colitis, unspecified, with complications K51.91

Collected in 10/21 and may change.

This information is not a promise of coverage or payment. It is not intended to give reimbursement advice or increase reimbursement by any payer. Legal requirements and plan information can be updated frequently. Contact the plan for more information about current coverage, reimbursement policies, restrictions, or requirements that may apply.

For more information on ICD-10, visit the CMS website.

SOURCE
ICD-10-CM 2022: The Complete Official Codebook. American Medical Association, 2021.

Important Safety Information For

  • SIMPONI®

    INDICATIONS

    SIMPONI® is a tumor necrosis factor (TNF) blocker indicated for the treatment of adult patients with:

    • Moderately to severely active rheumatoid arthritis (RA), in combination with methotrexate (MTX)
    • Active psoriatic arthritis (PsA) alone, or in combination with MTX
    • Active ankylosing spondylitis (AS)
    • Moderately to severely active ulcerative colitis (UC) who have demonstrated corticosteroid dependence or who have had an inadequate response to or failed to tolerate oral aminosalicylates, oral corticosteroids, azathioprine, or 6-mercaptopurine for:
      • Inducing and maintaining clinical response
      • Improving endoscopic appearance of the mucosa during induction
      • Inducing clinical remission
      • Achieving and sustaining clinical remission in induction responders

    IMPORTANT SAFETY INFORMATION

    SERIOUS INFECTIONS

    Patients treated with SIMPONI® (golimumab) are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue SIMPONI® if a patient develops a serious infection.

    Reported infections with TNF blockers, of which SIMPONI® is a member, include:

    • Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before SIMPONI® use and during therapy. Treatment for latent infection should be initiated prior to SIMPONI® use.
    • Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.
    • Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

    The risks and benefits of treatment with SIMPONI® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Do not start SIMPONI® in patients with clinically important active infections, including localized infections. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with SIMPONI®, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy, who are on treatment for latent TB, or who were previously treated for TB infection.

    Risk of infection may be higher in patients greater than 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressant therapy. Other serious infections observed in patients treated with SIMPONI® included sepsis, pneumonia, cellulitis, abscess and hepatitis B infection.

    MALIGNANCIES

    Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers of which SIMPONI® is a member.

    Approximately half the cases were lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma. The other cases represented a variety of malignancies, including rare malignancies usually associated with immunosuppression and malignancies not usually observed in children or adolescents. Malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.

    In the controlled portions of clinical trials of all TNF-blocking agents including SIMPONI®, more cases of lymphoma have been observed among patients receiving TNF-blocking treatment compared with control patients. In the Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA), and Ankylosing Spondylitis (AS) clinical trials, the incidence of lymphoma per 100 patient-years of follow-up was 0.21 (95% CI: 0.03, 0.77) in the combined SIMPONI® group compared with an incidence of 0 (95% CI: 0, 0.96) in the placebo group. In clinical trials, the incidence of malignancies other than lymphoma was not increased with exposure to SIMPONI® and was similar to what would be expected in the general population. In controlled and uncontrolled portions of the Phase 2/3 studies in ulcerative colitis (UC) with a mean follow-up of approximately 1 year, there were no cases of lymphoma with SIMPONI®. Short follow-up periods, such as those of 1 year or less in the studies above, may not adequately reflect the true incidence of malignancies. Cases of acute and chronic leukemia have been reported with TNF-blocker use, including SIMPONI®. The risks and benefits of TNF-blocker therapy should be considered prior to initiating therapy in patients with a known malignancy or who develop a malignancy.

    Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers. These cases have had a very aggressive disease course and have been fatal. Nearly all reported cases have occurred in patients with Crohn’s disease or UC, and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. A risk for the development for HSTCL in patients treated with TNF blockers cannot be excluded.

    Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocking agents, including SIMPONI®. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.

    HEPATITIS B REACTIVATION

    The use of TNF-blocking agents including SIMPONI® has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic hepatitis B carriers. In some instances, HBV reactivation occurring in conjunction with TNF-blocker therapy has been fatal. The majority of these reports have occurred in patients who received concomitant immunosuppressants.

    All patients should be tested for HBV infection before initiating TNF-blocker therapy. For patients who test positive for hepatitis B surface antigen, consult a physician with expertise in the treatment of hepatitis B before initiating TNF-blocker therapy. Exercise caution when prescribing SIMPONI® for patients identified as carriers of HBV and closely monitor for active HBV infection during and following termination of therapy with SIMPONI®. Discontinue SIMPONI® in patients who develop HBV reactivation, and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of SIMPONI®, and monitor patients closely.

    HEART FAILURE

    Cases of worsening congestive heart failure (CHF) and new-onset CHF have been reported with TNF blockers, including SIMPONI®. Some cases had a fatal outcome. Exercise caution and monitor patients with heart failure. Discontinue SIMPONI® if new or worsening symptoms of heart failure appear.

    DEMYELINATING DISORDERS

    TNF-blocking agents, of which SIMPONI® is a member, have been associated with rare cases of new-onset or exacerbation of demyelinating disorders, including multiple sclerosis (MS) and Guillain-Barré syndrome. Cases of central demyelination, MS, optic neuritis, and peripheral demyelinating polyneuropathy have rarely been reported with SIMPONI®. Exercise caution in considering the use of SIMPONI® in patients with these disorders. Consider discontinuation if these disorders develop.

    AUTOIMMUNITY

    Treatment with TNF blockers, including SIMPONI®, may result in the formation of antinuclear antibodies and, rarely, in the development of a lupus-like syndrome. Discontinue treatment if symptoms suggestive of a lupus-like syndrome develop.

    HEMATOLOGIC CYTOPENIAS

    There have been reports of pancytopenia, leukopenia, neutropenia, agranulocytosis, aplastic anemia, and thrombocytopenia in patients receiving SIMPONI®. Exercise caution when using SIMPONI® in patients who have or had significant cytopenias.

    USE WITH OTHER DRUGS

    The concomitant use of a TNF blocker and abatacept or anakinra was associated with a higher risk of serious infections; therefore, the use of SIMPONI® in combination with these products is not recommended. Care should be taken when switching from one biologic to another since overlapping biological activity may further increase the risk of infection. A higher rate of serious infections has also been observed in RA patients treated with rituximab who received subsequent treatment with a TNF blocker. The concomitant use of SIMPONI® with biologics approved to treat RA, PsA, or AS is not recommended because of the possibility of an increased risk of infection.

    VACCINATIONS/THERAPEUTIC INFECTIOUS AGENTS

    People receiving SIMPONI® can receive vaccinations, except for live vaccines. Use of live vaccines could result in clinical infections, including disseminated infections. Administration of live vaccines to infants exposed to SIMPONI® in utero is not recommended for 6 months following the mother’s last SIMPONI® injection during pregnancy due to an increased risk of infection. It is recommended that therapeutic infectious agents not be given concurrently with SIMPONI® due to the possibility of clinical infections, including disseminated infections.

    HYPERSENSITIVITY REACTIONS

    Serious systemic hypersensitivity reactions (including anaphylactic reaction) have been reported with SIMPONI®, some occurring after the first dose. If an anaphylactic or other serious allergic reaction occurs, discontinue SIMPONI® immediately and institute appropriate therapy.

    ADVERSE REACTIONS

    The most serious adverse reactions were serious infections and malignancies.

    Upper respiratory tract infection and nasopharyngitis were the most common adverse reactions reported in the combined Phase 3 trials through Week 16, occurring in 7% and 6% of patients treated with SIMPONI® as compared with 6% and 5% of patients in the control group, respectively. The rate of injection-site reactions was 6% with patients treated with SIMPONI® compared with 2% of patients in the control group.

    In the Phase 2/3 trials in UC evaluating SIMPONI®-treated patients, no new adverse drug reactions were identified, and the frequency of adverse drug reactions was similar to the safety profile observed in patients with RA, PsA, and AS.

    Please see the full Prescribing Information and Medication Guide for SIMPONI®. Provide the Medication Guide to your patients and encourage discussion.

    cp-51205v1

    INDICATIONS

IMPORTANT SAFETY INFORMATION

INDICATIONS
  • Minimize
  • Expand
  • Full Screen
  • Return to Website

INDICATIONS

IMPORTANT SAFETY INFORMATION