Avsola (infliximab-axxq)

Avsola can cause serious side effects, including:

Serious Infections

• Some patients, especially those 65 years and older have had serious infections while receiving infliximab products, such as Avsola. These serious infections include TB and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some patients die from these infections. If you get an infection while receiving treatment with Avsola your doctor will treat your infection and may need to stop your Avsola treatment.
• Tell your doctor right away if you have any of the following signs of an infection while receiving or after receiving Avsola:
  • a fever
  • have flu-like symptoms
  • feel very tired
  • warm, red, or painful skin
  • have a cough
• Your doctor will examine you for TB and perform a test to see if you have TB. If your doctor feels that you are atrisk for TB, you may be treated with medicine for TB before you begin treatment with Avsola and during treatment with Avsola.
• Even if your TB test is negative, your doctor should carefully monitor you for TB infections while you are receiving Avsola. Patients who had a negative TB skin test before receiving infliximab products have developed active TB.
• If you are a chronic carrier of the hepatitis B virus, the virus can become active while you are being treated with Avsola. In some cases, patients have died as a result of hepatitis B virus being reactivated. Your doctor should do a blood test for hepatitis B virus before you start treatment with Avsola and occasionally while you are being treated. Tell your doctor if you have any of the following symptoms:
  • feel unwell
  • tiredness (fatigue)
  • poor appetite
  • fever, skin rash, or joint pain

Heart Failure

If you have a heart problem called congestive heart failure, your doctor should check you closely while you are receiving Avsola. Your congestive heart failure may get worse while you are receiving Avsola. Be sure to tell your doctor of any new or worse symptoms including:

• shortness of breath
• sudden weight gain
• swelling of ankles or feet

Treatment with Avsola may need to be stopped if you get new or worse congestive heart failure.

Other Heart Problems

Some patients have experienced a heart attack (some of which led to death), low blood flow to the heart, or abnormal heart rhythm within 24 hours of beginning their infusion of infliximab products. Symptoms may include

• chest discomfort or pain,
• arm pain,
• stomach pain,
• shortness of breath,
• anxiety,
• lightheadedness,
• dizziness,
• fainting,
• sweating,
• nausea,
• vomiting,
• fluttering or pounding in your chest, and/or
• a fast or a slow heartbeat.

Tell your doctor right away if you have any of these symptoms.

Liver Injury

Some patients receiving infliximab products have developed serious liver problems. Tell your doctor if you have:

• jaundice (skin and eyes turning yellow)
• dark brown-colored urine
• pain on the right side of your stomach area (right-sided abdominal pain)
• fever
• extreme tiredness (severe fatigue)

Blood Problems

In some patients receiving infliximab products, the body may not make enough of the blood cells that help fight infections or help stop bleeding. Tell your doctor if you:

• have a fever that does not go away
• look very pale
• bruise or bleed very easily

Nervous System Disorders

Some patients receiving infliximab products have developed problems with their nervous system. Tell your doctor if you have:

• changes in your vision
• numbness or tingling in any part of your body
• weakness in your arms or legs
• seizures

Some patients have experienced a stroke within approximately 24 hours of their infusion with infliximab products. Tell your doctor right away if you have symptoms of a stroke which may include: numbness or weakness of the face, arm or leg, especially on one side of the body; sudden confusion, trouble speaking or understanding; sudden trouble seeing in one or both eyes, sudden trouble walking, dizziness, loss of balance or coordination or a sudden, severe headache.

Allergic Reactions

Some patients have had allergic reactions to infliximab products. Some of these reactions were severe. These reactions can happen while you are getting your Avsola treatment or shortly afterward. Your doctor may need to stop or pause your treatment with Avsola and may give you medicines to treat the allergic reaction. Signs of an allergic reaction can include:

• hives (red, raised, itchy patches of skin)
• high or low blood pressure
• difficulty breathing
• fever
• chest pain
• chills

Some patients treated with infliximab products have had delayed allergic reactions. The delayed reactions occurred 3 to 12 days after receiving treatment with infliximab products. Tell your doctor right away if you have any of these signs of delayed allergic reaction to Avsola:

• fever
• muscle or joint pain
• rash
• swelling of the face and hands
• headache
• difficulty swallowing
• sore throat

Lupus-like Syndrome

Some patients have developed symptoms that are like the symptoms of Lupus. If you develop any of the following symptoms, your doctor may decide to stop your treatment with Avsola.

• chest discomfort or pain that does not go away
• joint pain
• shortness of breath
• rash on the cheeks or arms that gets worse in the sunli>

Psoriasis

Some people receiving infliximab products had new psoriasis or worsening of psoriasis they already had. Tell your doctor if you develop red scaly patches or raised bumps on the skin that are filled with pus. Your doctor may decide to stop your treatment with Avsola.

The most common side effects of infliximab products include:

• respiratory infections, such as sinus
• coughing
• infections and sore throat
• stomach pain
• headache

Infusion reactions can happen up to 2 hours after your infusion of Avsola.

Symptoms of infusion reactions may include:

• fever
• shortness of breath
• chills
• rash
• chest pain
• itching
• low blood pressure or high blood pressure

Children with Crohn's disease showed some differences in side effects compared with adults with Crohn's disease. The side effects that happened more in children were:

• anemia (low red blood cells),
• leukopenia (low white blood cells),
• flushing (redness or blushing),
• viral infections,
• neutropenia (low neutrophils, the white blood cells that fight infection),
• bone fracture,
• bacterial infection and
• allergic reactions of the breathing tract.

Among patients who received infliximab for ulcerative colitis in clinical studies, more children had infections as compared with adults.

Tell your doctor about any side effect that bothers you or does not go away. These are not all of the side effects with Avsola.

Ask your doctor or pharmacist for more information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Crohn's Disease

• The recommended dose of Avsola is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of adults with moderately to severely active Crohn's disease or fistulizing Crohn's disease.
• For adult patients who respond and then lose their response, consideration may be given to treatment with 10 mg/kg.
• Patients who do not respond by Week 14 are unlikely to respond with continued dosing and consideration should be given to discontinue Avsola in these patients.

Pediatric Crohn's Disease

• The recommended dose of Avsola for pediatric patients 6 years and older with moderately to severely active Crohn's disease is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks.

Ulcerative Colitis

• The recommended dose of Avsola is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of adult patients with moderately to severely active ulcerative colitis.

Pediatric Ulcerative Colitis

• The recommended dose of Avsola for pediatric patients 6 years and older with moderately to severely active ulcerative colitis is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks.

Rheumatoid Arthritis

• The recommended dose of Avsola is 3 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 3 mg/kg every 8 weeks thereafter for the treatment of moderately to severely active rheumatoid arthritis. Avsola should be given in combination with methotrexate.
• For patients who have an incomplete response, consideration may be given to adjusting the dose up to 10 mg/kg or treating as often as every 4 weeks bearing in mind that risk of serious infections is increased at higher doses.

Ankylosing Spondylitis

• The recommended dose of Avsola is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 6 weeks thereafter for the treatment of active ankylosing spondylitis.

Psoriatic Arthritis

• The recommended dose of Avsola is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of psoriatic arthritis. Avsola can be used with or without methotrexate.

Plaque Psoriasis

• The recommended dose of Avsola is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of chronic severe (i.e., extensive and/or disabling) plaque psoriasis.

Monitoring To Assess Safety

• Prior to initiating Avsola and periodically during therapy, patients should be evaluated for active tuberculosis and tested for latent infection.

Use With Anakinra Or Abatacept

• An increased risk of serious infections was seen in clinical studies of other TNFa-blocking agents used in combination with anakinra or abatacept, with no added clinical benefit.
• Because of the nature of the adverse reactions seen with these combinations with TNF-blocker therapy, similar toxicities may also result from the combination of anakinra or abatacept with other TNFa-blocking agents. Therefore, the combination of Avsola and anakinra or abatacept is not recommended.

Use With Tocilizumab

• The use of tocilizumab in combination with biological DMARDs such as TNF antagonists, including Avsola, should be avoided because of the possibility of increased immunosuppression and increased risk of infection.

Use With Other Biological Therapeutics

• The combination of Avsola with other biological therapeutics used to treat the same conditions as Avsola is not recommended.

Methotrexate (MTX) And Other Concomitant Medications

• Specific drug interaction studies, including interactions with MTX, have not been conducted. The majority of patients in rheumatoid arthritis or Crohn's disease clinical studies received one or more concomitant medications.
<li>In rheumatoid arthritis, concomitant medications besides MTX were non-steroidal anti-inflammatory agents (NSAIDs), folic acid, corticosteroids and/or narcotics.
• Concomitant Crohn's disease medications were antibiotics, antivirals, corticosteroids, 6-MP/AZA and aminosalicylates.
• In psoriatic arthritis clinical trials, concomitant medications included MTX in approximately half of the patients as well as NSAIDs, folic acid and corticosteroids. Concomitant MTX use may decrease the incidence of anti-drug antibody production and increase infliximab product concentrations.

Immunosuppressants

• Patients with Crohn's disease who received immunosuppressants tended to experience fewer infusion reactions compared to patients on no immunosuppressants.
• Serum infliximab concentrations appeared to be unaffected by baseline use of medications for the treatment of Crohn's disease including corticosteroids, antibiotics (metronidazole or ciprofloxacin) and aminosalicylates.

Cytochrome P450 Substrates

• The formation of CYP450 enzymes may be suppressed by increased levels of cytokines (e.g., TNFα, IL-1, IL-6, IL-10, IFN) during chronic inflammation.
• Therefore, it is expected that for a molecule that antagonizes cytokine activity, such as infliximab products, the formation of CYP450 enzymes could be normalized.
• Upon initiation or discontinuation of Avsola in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) is recommended and the individual dose of the drug product may be adjusted as needed.

Live Vaccines/Therapeutic Infectious Agents

• It is recommended that live vaccines not be given concurrently with Avsola. It is also recommended that live vaccines not be given to infants after in utero exposure to infliximab products for at least 6 months following birth.
• It is recommended that therapeutic infectious agents not be given concurrently with Avsola.

• Available data from published literature on the use of infliximab products during pregnancy have not reported a clear association with infliximab products and adverse pregnancy outcomes.
• Infliximab products cross the placenta and infants exposed in utero should not be administered live vaccines for at least 6 months after birth.
•  In a development study conducted in mice using an analogous antibody, no evidence of maternal toxicity, embryotoxicity or teratogenicity was observed.
• Available information is insufficient to inform the amount of infliximab products present in human milk, and the effects on the breastfed infant.
• There are no data on the effects of infliximab products on milk production.
• The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for an infliximab product and any potential adverse effects on the breastfed infant from infliximab products or from the underlying maternal condition.