Semantic Coherence: Amgen (AVSOLA) – Signal Evidence & AI Readability

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[H3]

[H3]
FDA = Food and Drug Administration.
Important Safety Information
SERIOUS INFECTIONS: Patients treated with infliximab products 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 AVSOLA® if a patient develops a serious infection or sepsis.

Reported infections 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 AVSOLA® use and during therapy. Treatment for latent infection should be initiated prior to AVSOLA® use.

Invasive fungal infections including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, pneumocystosis and cryptococcosis. Patients may present with disseminated, rather than localized, disease. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.

Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella, Listeria, and Salmonella.

The risks and benefits of treatment with AVSOLA® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with AVSOLA®, 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, pediatric patients, patients with co-morbid conditions and/or patients taking concomitant immunosuppressant therapy. In clinical trials, other serious infections observed in patients treated with infliximab products included pneumonia, cellulitis, abscess, and skin ulceration.
[H5] MALIGNANCIES

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including infliximab products. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.
Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including infliximab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported cases have occurred in patients with Crohn's disease or ulcerative colitis and most were in adolescent and young adult males. Almost all patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF-blocker at or prior to diagnosis. Carefully assess the risks and benefits of treatment with AVSOLA®, especially in these patient types.
In clinical trials of all TNF inhibitors, more cases of lymphoma were observed compared with controls and the expected rate in the general population. However, patients with Crohn’s disease, rheumatoid arthritis, or plaque psoriasis may be at higher risk for developing lymphoma. In clinical trials of some TNF inhibitors, including infliximab products, more cases of other malignancies were observed compared with controls. The rate of these malignancies among patients treated with infliximab products was similar to that expected in the general population, whereas the rate in control patients was lower than expected. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use. As the potential role of TNF inhibitors in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD).
Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocker therapy, including infliximab products. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.
A population-based retrospective cohort study found a 2- to 3-fold increase in the incidence of invasive cervical cancer in women with rheumatoid arthritis treated with infliximab compared to biologics-naïve patients or the general population, particularly those over 60 years of age. A causal relationship between infliximab products and cervical cancer cannot be excluded. Periodic screening should continue in women treated with AVSOLA®.
[H5] CONTRAINDICATIONS
The use of AVSOLA® at doses >5 mg/kg is contraindicated in patients with moderate or severe heart failure. AVSOLA® is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab or any of the inactive ingredients of AVSOLA® or any murine proteins (severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness).
[H5] HEPATITIS B REACTIVATION
TNF inhibitors, including infliximab products, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients should be tested for HBV infection before initiating AVSOLA®. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Exercise caution when prescribing AVSOLA® for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with AVSOLA®. Discontinue AVSOLA® in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of TNF-blocker therapy and monitor patients closely.
[H5] HEPATOTOXICITY
Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis have been reported in patients receiving infliximab products postmarketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (eg, ≥ 5 times the upper limit of normal) develop, AVSOLA® should be discontinued, and a thorough investigation of the abnormality should be undertaken.
[H5] HEART FAILURE
In a randomized, placebo-controlled study in patients with moderate or severe heart failure (NYHA Functional Class III/IV), higher mortality rates and a higher risk of hospitalization were observed at Week 28 at a dose of 10 mg/kg and higher rates of cardiovascular events were observed at both 5 mg/kg and 10 mg/kg. There have been postmarketing reports of new onset and worsening heart failure, with and without identifiable precipitating factors. Patients with moderate or severe heart failure taking infliximab (≤5 mg/kg) or patients with mild heart failure should be closely monitored and treatment should be discontinued if new or worsening symptoms appear.
[H5] HEMATOLOGIC REACTIONS
Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported in patients receiving infliximab products. The causal relationship to infliximab product therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of AVSOLA® in patients who develop significant hematologic abnormalities.
[H5] HYPERSENSITIVITY
Infliximab products have been associated with hypersensitivity reactions that differ in their time of onset. Anaphylaxis, urticaria, dyspnea, and hypotension have occurred in association with infusions of infliximab products. Medications for the treatment of hypersensitivity reactions should be available.
[H5] CARDIOVASCULAR AND CEREBROVASCULAR REACTIONS DURING AND AFTER INFUSION
Serious cerebrovascular accidents, myocardial ischemia/infarction (some fatal), hypotension, hypertension, and arrhythmias have been reported during and within 24 hours of initiation of infliximab product infusion. Cases of transient visual loss have been reported during or within 2 hours of infusion of infliximab. Monitor patients during infusion and if a serious reaction occurs, discontinue infusion. Manage reactions according to signs and symptoms.
[H5] NEUROLOGIC REACTIONS
Agents that inhibit TNF have been associated with CNS manifestation of systemic vasculitis, seizure, and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering AVSOLA® in patients with these disorders and consider discontinuation if these disorders develop.
[H5] CONCURRENT ADMINISTRATION WITH OTHER BIOLOGICS
Concomitant use of AVSOLA® with anakinra, abatacept, tocilizumab, or other biologics used to treat the same conditions as AVSOLA® is not recommended because of the possibility of an increased risk of infection. Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection.
[H5] AUTOIMMUNITY
Treatment with infliximab products may result in the formation of autoantibodies and in the development of a lupus-like syndrome. Discontinue treatment with AVSOLA® if symptoms of a lupus-like syndrome develop.
[H5] VACCINATIONS AND USE OF LIVE VACCINES/THERAPEUTIC INFECTIOUS AGENTS
Bring patients up to date with all vaccinations prior to initiating AVSOLA®. Live vaccines or therapeutic infectious agents should not be given with AVSOLA® due to the possibility of clinical infections, including disseminated infections.
At least a 6-month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to infliximab products.
[H5] ADVERSE REACTIONS
In clinical trials with infliximab products, the most common adverse reactions occurring in >10% of patients included infections (eg, upper respiratory, sinusitis, and pharyngitis), infusion-related reactions, headache, and abdominal pain.

[H5] Indications
AVSOLA® is indicated for:
Crohn’s Disease: Reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy. AVSOLA® is indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn’s disease.
Pediatric Crohn’s Disease: Reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age or older with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy.
Ulcerative Colitis: Reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.
Pediatric Ulcerative Colitis: Reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.
Rheumatoid Arthritis in combination with methotrexate: Reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis.
Ankylosing Spondylitis: Reducing signs and symptoms in adult patients with active ankylosing spondylitis.
Psoriatic Arthritis: Reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in adult patients with psoriatic arthritis.
Plaque Psoriasis: The treatment of adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. AVSOLA® should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.
Please see full Prescribing Information.
AVSOLA® is a registered trademark of Amgen, Inc.

Open

[H5]

Important Safety Information
SERIOUS INFECTIONS:
Patients treated with infliximab products 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 AVSOLA® if a patient develops a serious infection or sepsis.Reported infections include:

[H4] AVSOLA® helps treat the following diseases of the immune
system:1

INFLAMMATORY ARTHRITIS DISEASES Chronic inflammation in joints and other
tissues

Moderately to
severely active Rheumatoid Arthritis (RA)

Active Psoriatic Arthritis
(PsA)

Active Ankylosing
Spondylitis (AS)

INFLAMMATORY BOWEL DISEASES Chronic inflammation in parts of the
digestive tract

Moderately to severely
active Crohn's disease (CD)

Moderately to severely
active Ulcerative colitis (UC)

[H5] Understanding
Rheumatoid Arthritis (RA)6
RA is the most common type of autoimmune arthritis, affecting more than 1.3
million Americans. RA is a chronic condition that causes joint pain,
stiffness, swelling, and decreased movement, most commonly affecting the small
joints in the hands and feet.
[H4] How AVSOLA® can help in moderately to severely active
Rheumatoid Arthritis (RA)1,*†
AVSOLA® is approved by the FDA as a biosimilar to Remicade® for
the treatment of the same diseases. It was tested in a global multicenter study for
safety and efficacy.1

[IMG: ra-circle]

Improvements in:
Pain and stiffness
Physical function

Helps stop further joint damage

*In combination with methotrexate.
†Individual results may vary.

AVSOLA® has similar safety to
Remicade®4
Can I take AVSOLA® if I've already started
Remicade®?
In a comparative study, patients who switched from
Remicade® to AVSOLA® experienced similar
safety and effectiveness.4
You and your doctor may consider treatment with AVSOLA® if you are new
to infliximab therapy, or if you are currently stable on Remicade®.

[H5] HELPFUL RESOURCES FOR YOU THROUGHOUT YOUR TREATMENT JOURNEY
Links to these third-party organizations are for your information only. Amgen does
not endorse and is not responsible for the content included by these organizations.
Visit these websites for more information about your inflammatory
disease and support groups near you.

[IMG: Arthritis Foundation Logo]

[IMG: GHLF Creakyjoints Logo]

[IMG: American college of rheumatology]

[H5] Understanding Psoriatic
Arthritis (PsA)7,8
PsA typically attacks the joints and areas where tissues attach to bone, like
fingers, toes, wrists, and knees. Most people have skin symptoms before
joint symptoms, as about 30% of people with psoriasis (a condition that
causes redness and itching) develop PsA. Unlike many other autoimmune diseases, men
and women are equally at risk for developing PsA.
[H4] How AVSOLA® can help in active Psoriatic Arthritis
(PsA)1,*
AVSOLA® is approved by the FDA as a biosimilar to Remicade® to
treat the same inflammation diseases.

[IMG: ra-circle]

Improvements in:
Pain and stiffness
Skin symptoms

Helps stop further joint damage

AVSOLA® has similar safety to
Remicade®4
Can I take AVSOLA® if I've already started
Remicade®?
In a comparative study, patients who switched from
Remicade® to AVSOLA® experienced similar
safety and effectiveness.4
You and your doctor may consider treatment with AVSOLA® if you are new
to infliximab therapy, or if you are currently stable on Remicade®.
*Individual results may vary.

[H5] HELPFUL RESOURCES FOR YOU THROUGHOUT YOUR TREATMENT JOURNEY
Links to these third-party organizations are for your information only. Amgen does not
endorse and is not responsible for the content included by these organizations.
Visit these websites for more information about your inflammatory disease
and support groups near you.

[IMG: National psoriasis Foundation]

[IMG: Arthritis Foundation Logo]

[IMG: American college of rheumatology]

[IMG: GHLF Creakyjoints Logo]

[H5] UNDERSTANDING
ANKYLOSING SPONDYLITIS (AS)9
AS is a type of arthritis that affects the spine, causing redness, heat,
swelling, and pain in the spine or in the joint where the bottom of the
spine meets the pelvic bone. In severe cases, swelling can cause bones in the spine
to fuse together.
[H4] How AVSOLA® can help in active Ankylosing Spondylitis
(AS)1,*
AVSOLA® is approved by the FDA as a biosimilar to Remicade® to
treat the same inflammation diseases.

[IMG: ra-circle]

Improvements in:
Pain and inflammation

AVSOLA® has similar safety to
Remicade®4
Can I take AVSOLA® if I've already started
Remicade®?
In a comparative study, patients who switched from
Remicade® to AVSOLA® experienced similar
safety and effectiveness.4
You and your doctor may consider treatment with AVSOLA® if you are new
to infliximab therapy, or if you are currently stable on Remicade®.
*Individual results may vary.

[H5] HELPFUL RESOURCES FOR YOU
THROUGHOUT YOUR TREATMENT JOURNEY
Links to these third-party organizations are for your information only. Amgen does not
endorse and is not responsible for the content included by these organizations.
Visit these websites for more information about your inflammatory disease
and support groups near you.

[IMG: Spondylitis Association of America Logo]

[IMG: GHLF Creakyjoints Logo]

[IMG: Arthritis Foundation Logo]

[H5] UNDERSTANDING CROHN’S
DISEASE (CD)10
CD is an inflammatory bowel disease that causes chronic inflammation in your
digestive tract. CD can affect any part of the digestive tract, but
it most commonly affects the end of the small intestine where it joins the beginning
of the colon. Inflammation in your digestive tract can lead to abdominal
pain, persistent diarrhea, fatigue, and other symptoms.
[H4] How AVSOLA® can help in moderately to severely active
Crohn’s Disease (CD)1,*
AVSOLA® is approved by the FDA as a biosimilar to Remicade® to
treat the same inflammation diseases.

[IMG: ra-circle]

Improvements in:
Signs and symptoms

AVSOLA® has similar safety to
Remicade®4
Can I take AVSOLA® if I've already started
Remicade®?
In a comparative study, patients who switched from
Remicade® to AVSOLA® experienced similar
safety and effectiveness.4
You and your doctor may consider treatment with AVSOLA® if you are new
to infliximab therapy, or if you are currently stable on Remicade®.
*Individual results may vary.

[H5] HELPFUL RESOURCES FOR YOU THROUGHOUT YOUR TREATMENT
JOURNEY
Links to these third-party organizations are for your information only. Amgen does not
endorse and is not responsible for the content included by these organizations.
Visit these websites for more information about your inflammatory disease
and support groups near you.

[IMG: Crohn]

[IMG: American Gastroenterological Association Logo]

[H5] UNDERSTANDING
ULCERATIVE COLITIS (UC)11
UC is an inflammatory bowel disease that causes chronic inflammation in your
digestive tract. UC causes inflammation in the innermost lining of the large
intestine (colon) and rectum.
[H4] How AVSOLA® can help in moderately to severely active
Ulcerative Colitis (UC)1,*
AVSOLA® is approved by the FDA as a biosimilar to Remicade® to
treat the same inflammation diseases.

[IMG: ra-circle]

Improvements in:
Signs and symptoms
Digestive tract healing

AVSOLA® has similar safety to
Remicade®4
Can I take AVSOLA® if I've already started
Remicade®?
In a comparative study, patients who switched from
Remicade® to AVSOLA® experienced similar
safety and effectiveness.4
You and your doctor may consider treatment with AVSOLA® if you are new
to infliximab therapy, or if you are currently stable on Remicade®.
*Individual results may vary.

[H5] HELPFUL RESOURCES FOR YOU THROUGHOUT YOUR TREATMENT
JOURNEY
The link to this third-party organization is for your information only. Amgen does not
endorse and is not responsible for the content included by this organization.
Visit this website for more information about your inflammatory disease and
support groups near you.

[IMG: Crohn]

[IMG: American Gastroenterological Association Logo]

Close

[H3]

[H3]
FDA = Food and Drug Administration.
Important Safety Information
SERIOUS INFECTIONS: Patients treated with infliximab products 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 AVSOLA® if a patient develops a serious infection or sepsis.

Reported infections 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 AVSOLA® use and during therapy. Treatment for latent infection should be initiated prior to AVSOLA® use.

Invasive fungal infections including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, pneumocystosis and cryptococcosis. Patients may present with disseminated, rather than localized, disease. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.

Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella, Listeria, and Salmonella.

The risks and benefits of treatment with AVSOLA® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with AVSOLA®, 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, pediatric patients, patients with co-morbid conditions and/or patients taking concomitant immunosuppressant therapy. In clinical trials, other serious infections observed in patients treated with infliximab products included pneumonia, cellulitis, abscess, and skin ulceration.
[H5] MALIGNANCIES

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including infliximab products. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.
Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including infliximab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported cases have occurred in patients with Crohn's disease or ulcerative colitis and most were in adolescent and young adult males. Almost all patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF-blocker at or prior to diagnosis. Carefully assess the risks and benefits of treatment with AVSOLA®, especially in these patient types.
In clinical trials of all TNF inhibitors, more cases of lymphoma were observed compared with controls and the expected rate in the general population. However, patients with Crohn’s disease, rheumatoid arthritis, or plaque psoriasis may be at higher risk for developing lymphoma. In clinical trials of some TNF inhibitors, including infliximab products, more cases of other malignancies were observed compared with controls. The rate of these malignancies among patients treated with infliximab products was similar to that expected in the general population, whereas the rate in control patients was lower than expected. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use. As the potential role of TNF inhibitors in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD).
Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocker therapy, including infliximab products. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.
A population-based retrospective cohort study found a 2- to 3-fold increase in the incidence of invasive cervical cancer in women with rheumatoid arthritis treated with infliximab compared to biologics-naïve patients or the general population, particularly those over 60 years of age. A causal relationship between infliximab products and cervical cancer cannot be excluded. Periodic screening should continue in women treated with AVSOLA®.
[H5] CONTRAINDICATIONS
The use of AVSOLA® at doses >5 mg/kg is contraindicated in patients with moderate or severe heart failure. AVSOLA® is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab or any of the inactive ingredients of AVSOLA® or any murine proteins (severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness).
[H5] HEPATITIS B REACTIVATION
TNF inhibitors, including infliximab products, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients should be tested for HBV infection before initiating AVSOLA®. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Exercise caution when prescribing AVSOLA® for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with AVSOLA®. Discontinue AVSOLA® in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of TNF-blocker therapy and monitor patients closely.
[H5] HEPATOTOXICITY
Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis have been reported in patients receiving infliximab products postmarketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (eg, ≥ 5 times the upper limit of normal) develop, AVSOLA® should be discontinued, and a thorough investigation of the abnormality should be undertaken.
[H5] HEART FAILURE
In a randomized, placebo-controlled study in patients with moderate or severe heart failure (NYHA Functional Class III/IV), higher mortality rates and a higher risk of hospitalization were observed at Week 28 at a dose of 10 mg/kg and higher rates of cardiovascular events were observed at both 5 mg/kg and 10 mg/kg. There have been postmarketing reports of new onset and worsening heart failure, with and without identifiable precipitating factors. Patients with moderate or severe heart failure taking infliximab (≤5 mg/kg) or patients with mild heart failure should be closely monitored and treatment should be discontinued if new or worsening symptoms appear.
[H5] HEMATOLOGIC REACTIONS
Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported in patients receiving infliximab products. The causal relationship to infliximab product therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of AVSOLA® in patients who develop significant hematologic abnormalities.
[H5] HYPERSENSITIVITY
Infliximab products have been associated with hypersensitivity reactions that differ in their time of onset. Anaphylaxis, urticaria, dyspnea, and hypotension have occurred in association with infusions of infliximab products. Medications for the treatment of hypersensitivity reactions should be available.
[H5] CARDIOVASCULAR AND CEREBROVASCULAR REACTIONS DURING AND AFTER INFUSION
Serious cerebrovascular accidents, myocardial ischemia/infarction (some fatal), hypotension, hypertension, and arrhythmias have been reported during and within 24 hours of initiation of infliximab product infusion. Cases of transient visual loss have been reported during or within 2 hours of infusion of infliximab. Monitor patients during infusion and if a serious reaction occurs, discontinue infusion. Manage reactions according to signs and symptoms.
[H5] NEUROLOGIC REACTIONS
Agents that inhibit TNF have been associated with CNS manifestation of systemic vasculitis, seizure, and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering AVSOLA® in patients with these disorders and consider discontinuation if these disorders develop.
[H5] CONCURRENT ADMINISTRATION WITH OTHER BIOLOGICS
Concomitant use of AVSOLA® with anakinra, abatacept, tocilizumab, or other biologics used to treat the same conditions as AVSOLA® is not recommended because of the possibility of an increased risk of infection. Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection.
[H5] AUTOIMMUNITY
Treatment with infliximab products may result in the formation of autoantibodies and in the development of a lupus-like syndrome. Discontinue treatment with AVSOLA® if symptoms of a lupus-like syndrome develop.
[H5] VACCINATIONS AND USE OF LIVE VACCINES/THERAPEUTIC INFECTIOUS AGENTS
Bring patients up to date with all vaccinations prior to initiating AVSOLA®. Live vaccines or therapeutic infectious agents should not be given with AVSOLA® due to the possibility of clinical infections, including disseminated infections.
At least a 6-month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to infliximab products.
[H5] ADVERSE REACTIONS
In clinical trials with infliximab products, the most common adverse reactions occurring in >10% of patients included infections (eg, upper respiratory, sinusitis, and pharyngitis), infusion-related reactions, headache, and abdominal pain.

[H5] Indications
AVSOLA® is indicated for:
Crohn’s Disease: Reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy. AVSOLA® is indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn’s disease.
Pediatric Crohn’s Disease: Reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age or older with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy.
Ulcerative Colitis: Reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.
Pediatric Ulcerative Colitis: Reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.
Rheumatoid Arthritis in combination with methotrexate: Reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis.
Ankylosing Spondylitis: Reducing signs and symptoms in adult patients with active ankylosing spondylitis.
Psoriatic Arthritis: Reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in adult patients with psoriatic arthritis.
Plaque Psoriasis: The treatment of adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. AVSOLA® should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.
Please see full Prescribing Information.
AVSOLA® is a registered trademark of Amgen, Inc.

Open

[H5]

Important Safety Information
SERIOUS INFECTIONS:
Patients treated with infliximab products 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 AVSOLA® if a patient develops a serious infection or sepsis.Reported infections include:

Close

[H3]

[H3]
FDA = Food and Drug Administration.
Important Safety Information
SERIOUS INFECTIONS: Patients treated with infliximab products 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 AVSOLA® if a patient develops a serious infection or sepsis.

Reported infections 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 AVSOLA® use and during therapy. Treatment for latent infection should be initiated prior to AVSOLA® use.

Invasive fungal infections including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, pneumocystosis and cryptococcosis. Patients may present with disseminated, rather than localized, disease. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.

Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella, Listeria, and Salmonella.

The risks and benefits of treatment with AVSOLA® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with AVSOLA®, 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, pediatric patients, patients with co-morbid conditions and/or patients taking concomitant immunosuppressant therapy. In clinical trials, other serious infections observed in patients treated with infliximab products included pneumonia, cellulitis, abscess, and skin ulceration.
[H5] MALIGNANCIES

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including infliximab products. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.
Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including infliximab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported cases have occurred in patients with Crohn's disease or ulcerative colitis and most were in adolescent and young adult males. Almost all patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF-blocker at or prior to diagnosis. Carefully assess the risks and benefits of treatment with AVSOLA®, especially in these patient types.
In clinical trials of all TNF inhibitors, more cases of lymphoma were observed compared with controls and the expected rate in the general population. However, patients with Crohn’s disease, rheumatoid arthritis, or plaque psoriasis may be at higher risk for developing lymphoma. In clinical trials of some TNF inhibitors, including infliximab products, more cases of other malignancies were observed compared with controls. The rate of these malignancies among patients treated with infliximab products was similar to that expected in the general population, whereas the rate in control patients was lower than expected. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use. As the potential role of TNF inhibitors in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD).
Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocker therapy, including infliximab products. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.
A population-based retrospective cohort study found a 2- to 3-fold increase in the incidence of invasive cervical cancer in women with rheumatoid arthritis treated with infliximab compared to biologics-naïve patients or the general population, particularly those over 60 years of age. A causal relationship between infliximab products and cervical cancer cannot be excluded. Periodic screening should continue in women treated with AVSOLA®.
[H5] CONTRAINDICATIONS
The use of AVSOLA® at doses >5 mg/kg is contraindicated in patients with moderate or severe heart failure. AVSOLA® is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab or any of the inactive ingredients of AVSOLA® or any murine proteins (severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness).
[H5] HEPATITIS B REACTIVATION
TNF inhibitors, including infliximab products, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients should be tested for HBV infection before initiating AVSOLA®. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Exercise caution when prescribing AVSOLA® for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with AVSOLA®. Discontinue AVSOLA® in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of TNF-blocker therapy and monitor patients closely.
[H5] HEPATOTOXICITY
Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis have been reported in patients receiving infliximab products postmarketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (eg, ≥ 5 times the upper limit of normal) develop, AVSOLA® should be discontinued, and a thorough investigation of the abnormality should be undertaken.
[H5] HEART FAILURE
In a randomized, placebo-controlled study in patients with moderate or severe heart failure (NYHA Functional Class III/IV), higher mortality rates and a higher risk of hospitalization were observed at Week 28 at a dose of 10 mg/kg and higher rates of cardiovascular events were observed at both 5 mg/kg and 10 mg/kg. There have been postmarketing reports of new onset and worsening heart failure, with and without identifiable precipitating factors. Patients with moderate or severe heart failure taking infliximab (≤5 mg/kg) or patients with mild heart failure should be closely monitored and treatment should be discontinued if new or worsening symptoms appear.
[H5] HEMATOLOGIC REACTIONS
Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported in patients receiving infliximab products. The causal relationship to infliximab product therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of AVSOLA® in patients who develop significant hematologic abnormalities.
[H5] HYPERSENSITIVITY
Infliximab products have been associated with hypersensitivity reactions that differ in their time of onset. Anaphylaxis, urticaria, dyspnea, and hypotension have occurred in association with infusions of infliximab products. Medications for the treatment of hypersensitivity reactions should be available.
[H5] CARDIOVASCULAR AND CEREBROVASCULAR REACTIONS DURING AND AFTER INFUSION
Serious cerebrovascular accidents, myocardial ischemia/infarction (some fatal), hypotension, hypertension, and arrhythmias have been reported during and within 24 hours of initiation of infliximab product infusion. Cases of transient visual loss have been reported during or within 2 hours of infusion of infliximab. Monitor patients during infusion and if a serious reaction occurs, discontinue infusion. Manage reactions according to signs and symptoms.
[H5] NEUROLOGIC REACTIONS
Agents that inhibit TNF have been associated with CNS manifestation of systemic vasculitis, seizure, and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering AVSOLA® in patients with these disorders and consider discontinuation if these disorders develop.
[H5] CONCURRENT ADMINISTRATION WITH OTHER BIOLOGICS
Concomitant use of AVSOLA® with anakinra, abatacept, tocilizumab, or other biologics used to treat the same conditions as AVSOLA® is not recommended because of the possibility of an increased risk of infection. Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection.
[H5] AUTOIMMUNITY
Treatment with infliximab products may result in the formation of autoantibodies and in the development of a lupus-like syndrome. Discontinue treatment with AVSOLA® if symptoms of a lupus-like syndrome develop.
[H5] VACCINATIONS AND USE OF LIVE VACCINES/THERAPEUTIC INFECTIOUS AGENTS
Bring patients up to date with all vaccinations prior to initiating AVSOLA®. Live vaccines or therapeutic infectious agents should not be given with AVSOLA® due to the possibility of clinical infections, including disseminated infections.
At least a 6-month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to infliximab products.
[H5] ADVERSE REACTIONS
In clinical trials with infliximab products, the most common adverse reactions occurring in >10% of patients included infections (eg, upper respiratory, sinusitis, and pharyngitis), infusion-related reactions, headache, and abdominal pain.

[H5] Indications
AVSOLA® is indicated for:
Crohn’s Disease: Reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy. AVSOLA® is indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn’s disease.
Pediatric Crohn’s Disease: Reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age or older with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy.
Ulcerative Colitis: Reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.
Pediatric Ulcerative Colitis: Reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.
Rheumatoid Arthritis in combination with methotrexate: Reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis.
Ankylosing Spondylitis: Reducing signs and symptoms in adult patients with active ankylosing spondylitis.
Psoriatic Arthritis: Reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in adult patients with psoriatic arthritis.
Plaque Psoriasis: The treatment of adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. AVSOLA® should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.
Please see full Prescribing Information.
AVSOLA® is a registered trademark of Amgen, Inc.

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[H5]

Important Safety Information
SERIOUS INFECTIONS:
Patients treated with infliximab products 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 AVSOLA® if a patient develops a serious infection or sepsis.Reported infections include: