Infliximab Side Effects
Some side effects of infliximab may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.
For the Consumer
Applies to infliximab: intravenous powder for injection
Some people receiving an infliximab injection have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you feel dizzy, nauseated, light-headed, itchy or tingly, swollen, short of breath, or have a headache, fever, chills, flu symptoms, muscle or joint pain, pain or tightness in your throat, chest pain, or trouble swallowing during the injection. Infusion reactions may also occur within 1 or 2 hours after injection.
Get emergency medical help if you have any of these signs of an allergic reaction while taking infliximab: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Stop using infliximab and call your doctor right away if you have any of these symptoms of lymphoma:
fever, night sweats, weight loss, tiredness;
feeling full after eating only a small amount;
pain in your upper stomach that may spread to your shoulder;
easy bruising or bleeding, pale skin, feeling light-headed or short of breath, rapid heart rate; or
nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).
Call your doctor at once if you have any of these other serious side effects:
signs of infection (fever, chills, flu symptoms, confusion, or pain, warmth, or redness of your skin);
chest pain, ongoing cough, coughing up mucus or blood;
shortness of breath with swelling of your ankles or feet, rapid weight gain;
numbness or tingling;
easy bruising or bleeding, pale skin, unusual weakness;
weak feeling in your arms or legs;
problems with vision;
neck stiffness, seizure (convulsions);
pain or burning when you urinate; or
red, purple, or scaly skin rash, hair loss, joint or muscle pain, mouth sores.
Less serious side effects of infliximab may include:
stuffy nose, sinus pain, headache;
mild stomach pain;
mild skin rash; or
flushing (warmth, redness, or tingly feeling).
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.
For Healthcare Professionals
Applies to infliximab: intravenous powder for injection
Most of the following data reflect infliximab exposure in 4779 patients, including 2625 and 374 patients exposed beyond 30 weeks and 1 year, respectively. One of the most common reasons for treatment discontinuation was infusion-related reactions (e.g., dyspnea, flushing, headache, and rash). Approximately 3% of patients discontinued infliximab due to infusion reactions.
The types and frequencies of side effects reported were similar in infliximab-treated rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and Crohn's disease patients except for abdominal pain.
Immunologic side effects have included treated infections in 36% of patients. The most common infections reported were respiratory tract infections (including sinusitis, pharyngitis, and bronchitis) and urinary tract infections. Serious infections reported included pneumonia, cellulitis, abscess (skin, throat, and perirectal), skin ulceration, sepsis, and bacterial infection. During clinical studies, 7 opportunistic infections were reported; 2 cases each of coccidioidomycosis and histoplasmosis (1 case each was fatal), and 1 case each of pneumocystosis, nocardiosis, and cytomegalovirus. During clinical trials, tuberculosis was reported in 14 patients, with 4 deaths due to miliary tuberculosis. During one study, 15% of patients with fistulizing Crohn's disease developed a new fistula-related abscess. Constitutional symptoms (such as fever, chills, weight loss, and fatigue) may precede the onset of serious infections; however, signs or symptoms localized to the site of infection may also precede the majority of serious infections. Development of antibodies to infliximab (up to 51%), development of antinuclear antibodies (about 50%), newly detected anti-dsDNA antibodies (about 20%), moniliasis (5%), lupus and lupus-like syndromes (uncommon), listeriosis, sporotrichosis, and Borrelia infection have been reported. At least one case each of disseminated Salmonella typhimurium infection, disseminated cryptococcal infection, phaeohyphomycosis, and protothecosis have been reported. Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, or parasitic organisms (including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, and tuberculosis) have been reported with TNF blockers. Listeria monocytogenes infections (with some cases resulting in death), other cases of tuberculosis (including miliary and disseminated), and infections with various pathogens (including viral, bacterial, fungal, and protozoal organisms) have been reported in postmarketing experience.
Inflammation and modulation of cellular immune response are mediated by TNF-alpha. It is possible that therapy with infliximab could affect normal immune responses. A meta-analysis has reported that there is evidence of an increased risk of serious infections in patients with rheumatoid arthritis treated with anti-TNF antibody therapy.
Most cases of tuberculosis occurred within the first two months after the start of infliximab therapy and may reflect recrudescence of latent disease.
Cutaneous and miliary tuberculosis, as a result of tuberculosis reactivation, has been reported in a 56-year-old white male with a history of Crohn's disease treated with infliximab.
Infections have been observed in all organ systems and have been reported in patients receiving infliximab alone or in combination with immunosuppressive agents.
Patients with antibodies to infliximab were more likely to have higher rates of clearance, reduced efficacy, and to experience an infusion reaction.
Crohn's patients with (+) ANA prior to infliximab were approximately 2 times as likely to develop anti-dsDNA antibodies.
Various case reports of non-Crohn's and Crohn's patient, developed clinical symptoms of a lupus-like syndrome. Symptoms resolved and antibodies disappeared when infliximab was discontinued.
Disseminated Salmonella typhimurium infection has been reported in a Fijian Indian man while undergoing his twenty-eighth week of infliximab therapy for the treatment of psoriasis and psoriatic arthritis. Patient's symptoms resolved after treatment with intravenous ciprofloxacin.
Disseminated cryptococcal infection has been reported in a 72-year-old male after his second infusion of infliximab for rheumatoid arthritis.
A 56-year-old male developed protothecosis after a stem cell transplantation coincident with infliximab therapy. He was administered infliximab for graft-versus-host disease. Two weeks later, he became lethargic and developed bilateral olecranon bursitis and bullous skin lesions. Blood cultures grew Klebsiella pneumoniae and Prototheca wickerhamii. The patient subsequently developed multiorgan failure and died after 5 weeks of hospitalization. The use of infliximab likely played a role in this case.
Most of the cases of tuberculosis occurred within the first two months after the start of infliximab therapy and may reflect recrudescence of latent disease.
Life-threatening histoplasmosis (n=9) reported in postmarketing experience developed within 1 week to 6 months after the first dose.
A 34-year-old male with a 15-year history of seronegative arthritis with both peripheral and axial features experienced pulmonary sarcoidosis coincident with infliximab therapy. The patient was administered infliximab at 5 mg/kg every 8 weeks intravenously, which led to a prompt and dramatic improvement in the manifestations of his disease. However, after about 5 years of disease remission, he developed pleuritic chest pain, a productive cough, and dyspnea. The patient was diagnosed with sarcoidosis based on pathological findings. A chest radiograph revealed persistent mediastinal hilar adenopathy with clear lung fields. He was treated with prednisone 40 mg per day, which resulted in complete resolution of his pulmonary symptoms. A follow-up thorax CT after 4 months of steroid treatment showed that the left pleural effusion had resolved but the mediastinal lymphadenopathy was unchanged.
A 36-year-old female with history of Crohn disease experienced pneumocystis carinii jiroveci pneumonia (PCP) coincident with infliximab therapy. She presented with complaints of fever and shortness of breath for one day. Two months before presentation, she required hospitalization for partial small bowel obstruction, at which time infliximab was initiated. Bronchoalveolar lavage showed PCP on silver stain. Intravenous Bactrim (sulfamethoxazole-trimethoprim) and Solumedrol (methylprednisolone) were started. The patient had a slow recovery with subsequent chest x-ray showing clearing of the lung infiltrates.
Respiratory side effects have included upper respiratory tract infections (up to 32%), sinusitis (up to 14%), pharyngitis (up to 12%), coughing (up to 12%), bronchitis (up to 10%), rhinitis (up to 8%), adult respiratory distress syndrome, lower respiratory tract infection (including pneumonia), pleural effusion, pleurisy, pulmonary edema, respiratory insufficiency, pulmonary embolism, and shortness of breath. Serious and sometimes fatal opportunistic infections including tuberculosis, histoplasmosis, and pneumocystosis have also been reported. At least one case each of streptococcal pharyngitis, pulmonary sarcoidosis, and pneumocystis carinii jiroveci pneumonia have been reported. Interstitial lung disease (including pulmonary fibrosis/interstitial pneumonitis and very rare rapidly progressive disease) has been reported during postmarketing experience.
Other side effects have included infusion reactions (up to 20%), fatigue (up to 11%), fever (up to 10%), pain (8%), diaphragmatic hernia, edema, surgical/procedural sequela, influenza-like illness, and falls. Nonspecific symptoms (such as fever or chills; 3%), cardiopulmonary reactions (primarily chest pain, hypotension, hypertension, or dyspnea; 1%), and pruritus, urticaria, or the combined symptoms of pruritus/urticaria and cardiopulmonary reactions (less than 1%) accompanied infliximab infusions. Serious infusion reactions (including anaphylaxis, convulsions, erythematous rash, and hypotension) were reported in less than 1% of patients. Serious infusion reactions (symptoms included, but were not limited to, dyspnea, urticaria, facial edema, and hypotension) have also been reported following retreatment.
An infusion reaction was defined in clinical trials as any adverse event occurring during an infusion or within 1 to 2 hours after an infusion. Patients who became positive for antibodies to infliximab were approximately 2- to 3-fold more likely to have an infusion reaction than patients who were negative. Use of concomitant immunosuppressant agents appeared to reduce infusion reaction frequency.
During a clinical trial of psoriasis patients that assessed the efficacy of long-term maintenance versus retreatment with an induction regimen after disease flare, serious infusion reactions were reported in 4% of patients in the retreatment arm versus less than 1% in the maintenance arm. Patients in this trial did not receive concomitant immunosuppressant therapy. Most of the serious infusion reactions occurred during the second infusion at Week 2. In all cases, infliximab was discontinued and/or other treatment instituted with complete resolution of signs and symptoms.
Hypersensitivity side effects have included possible delayed hypersensitivity reaction, generally reported as serum sickness or a combination of arthralgia and/or myalgia with fever and/or rash, in about 1% of patients during psoriasis studies. Reactions occurring following readministration in Crohn's disease patients were reported 3 to 12 days after infusion and the signs and symptoms included myalgia and/or arthralgia with fever and/or rash, with some patients also experiencing pruritus, facial, hand, or lip edema, dysphagia, urticaria, sore throat, and headache. Allergic reaction, leukocytoclastic vasculitis, and allergic bronchopulmonary aspergillosis have been reported. Anaphylactic-like reactions (including laryngeal/pharyngeal edema and severe bronchospasm) have been associated with infliximab administration during postmarketing experience.
In order to avoid the development of delayed severe systemic reactions, some researchers recommend multiple early infusions of infliximab if retreatment is anticipated.
Delayed hypersensitivity reactions during psoriasis studies generally occurred within 2 weeks following repeat infusion.
During one clinical trial, Crohn's disease patients were retreated following 2 to 4 years without infliximab. Patients experiencing side effects following readministration did not have infusion-related side effects associated with their initial infliximab treatment.
One patient reported hypoesthesia in the left leg eight hours after her first infliximab infusion.
Another patient reported dysesthesia in the distribution of the left peroneal nerve, after her 6th intravenous infliximab infusion.
Although demyelination observed in postmarketing experience did not show causal relationship between adverse events and infliximab, the neurologic side effects resolved, partially or completely, on discontinuation of therapy.
A 51-year-old female with Crohn's disease experienced meningitis coincident with infliximab therapy. The patient developed a headache, fever, arthralgia, myalgia, and meningismus after receiving an infliximab infusion. Cerebrospinal fluid analysis was remarkable for a neutrophilic pleocytosis and elevated protein. Other potential causes of meningitis were ruled out. The patient's symptoms completely resolved within 24 hours of presentation.
A 28-year-old female with a 7-year history of Crohn disease experienced acute neuropathy with multiple conduction blocks coincident with infliximab therapy. Infliximab (5 mg/kg, 4 infusions in 2 years) therapy was added to azathioprine (150 mg per day) 5 years into her disease. Three weeks after the overall fourth dose of infliximab treatment, she developed left radial nerve palsy and slight weakness of left foot flexion and extension. Neurologic examination and motor nerve conduction studies were positive for acute neuropathy with multiple conduction blocks.
A 66-year-old male with rheumatoid arthritis experienced West Nile virus (WNV) coincident with infliximab therapy. The patient presented with a 2-day history of fever, headache, confusion, agitation, nausea, malaise, myalgias, gait instability, and rapidly worsening lower extremity weakness. He had received infliximab 3 weeks prior to symptom onset. His only other medications were amlodipine (5 mg per day) and methotrexate (15 mg per week). WNF was confirmed by with cerebral spinal fluid positive for WNV IgM antibodies by ELISA capture technique. The patient eventually died due to WNF infection.
A 41-year-old female with erosive rheumatoid arthritis experienced neurosarcoidosis coincident with infliximab therapy. She had been successfully treated with infliximab 3 mg/kg every 6 to 8 weeks together with methotrexate, without side effects. Approximately five years later, after receiving an infliximab infusion, she experienced feeling tired, a low grade fever, and headache. Two weeks later, she presented without any neurological symptoms besides headache. She was hospitalized one week later. The headache remained unchanged and 4 weeks after admission, she developed diplopia. At neuron-ophthalmological examination, nerve palsy of the left eye and a severe papilledema in both eyes were observed. Further, bilateral granulomatous iridocyclitis and retinal periphlebitis, typical for sarcoidosis, were noted. The sarcoidosis diagnosis was supported by the increased activity in the mediastinal lymph nodes bilaterally and in the parotid glands observed with In-DTPA-octreotide scintigraphy. She received a ventriculoperitoneal shunt 5 weeks after being admitted. Following surgery, the patient became free of headache and the pathological ophthalmologic changes slowly subsided.
A 62-year-old female reported she was hospitalized for five days due to a reaction characterized by shaking uncontrollably due to taking infliximab. The patient did not know the date of admission stating it was a long time ago when she was in her twenties. The patient reported being diagnosed with Crohn's disease at age 21.
Nervous system side effects have included headache (up to 23%), meningitis, brain infarction, neuritis, peripheral neuropathy, dizziness, and syncope. Infliximab and other tumor necrosis factor blockers have been associated in rare cases with central nervous system (CNS) manifestation of systemic vasculitis, seizure and new onset or exacerbation of clinical symptoms and/or radiographic evidence of CNS demyelinating disorders (including multiple sclerosis and optic neuritis), and peripheral demyelinating disorders (including Guillain-Barre syndrome). Rheumatoid vasculitis has also been reported rarely. It presents with peripheral nervous system symptoms involvement. Herpes zoster and Miller Fisher syndrome have been reported. At least one case each of hypoesthesia, dysesthesia, West Nile virus meningoencephalitis and acute flaccid paralysis, and neurosarcoidosis and at least two cases of acute neuropathy with multiple conduction blocks have been reported. Seizure associated with infliximab administration, peripheral demyelinating disorders (such as Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy), transverse myelitis, and neuropathies have been reported during postmarketing experience.
Gastrointestinal side effects have included nausea (up to 21%), abdominal pain (Crohn's disease: 26%; other indications: up to 12%), diarrhea (up to 12%) dyspepsia (10%), vomiting, constipation, gastrointestinal hemorrhage, ileus, abdominal hernia, abscess, intestinal obstruction, intestinal perforation, intestinal stenosis, pancreatitis, peritonitis, and proctalgia. Gastrointestinal infection, sialadenitis, dental/periodontal infection, and oral mycosis have also been reported. At least four cases of gum infection and at least one case each of rectal abscess and stomatitis have been reported.
Cardiovascular side effects have included higher incidences of mortality and hospitalization due to worsening heart failure and trends towards increased dyspnea, hypotension, angina, and dizziness in patients with moderate to severe heart failure. Cardiopulmonary reactions (primarily chest pain, hypotension, hypertension, or dyspnea; 1%) or the combined symptoms of pruritus/urticaria and cardiopulmonary reactions (less than 1%) have accompanied infliximab infusions. Hypertension (7%), circulatory failure, hypotension, arrhythmia, bradycardia, cardiac arrest, tachycardia, myocardial infarction, thrombophlebitis, and palpitations have been reported. Heart block has been reported in at least two patients during infliximab infusion. At least one patient also developed bradycardia with the ECG showing second-degree atrioventricular block thirty minutes into the infliximab infusion. Pericardial effusion, vasculitis (systemic and cutaneous), worsening heart failure (with and without identifiable precipitating factors), and new-onset heart failure (including heart failure in patients without known preexisting cardiovascular disease) have been reported during postmarketing experience. Cases of myocardial ischemia/infarction associated with infliximab administration (during or within 2 hours of infusion) have also been rarely reported during postmarketing experience.
A higher incidence of mortality and hospitalization for worsening heart failure have been reported among patients with moderate to severe (NYHA class III-IV) heart failure treated with the higher dose of infliximab (10 mg/kg). At 1 year, eight patients in the infliximab 10 mg/kg group had died compared with four deaths each in the infliximab 5 mg/kg and the placebo group.
Heart failure (n=18) reported in postmarketing experience developed on average 6 months after initiation of infliximab therapy.
Bradycardia with second degree atrioventricular (AV) block has been reported to occur, as soon as 30 minutes into the infliximab infusion, in a 52-year-old woman with fistulizing Crohn's disease who had no previous history of cardiac disease. The bradycardia, and second degree AV block, persisted for 36 hours after infliximab was discontinued. After a cardiology consult, and placement of a pacemaker, patient resumed her infliximab therapy without adverse events reported.
A 70-year-old man with fistulizing Crohn's disease, and a prior history of coronary artery disease and taking atenolol, developed dyspnea, chest heaviness, and dizziness while receiving his third infusion of infliximab. He had reported chills and pruritus during previous infusions of infliximab. He presented with a drop in heart rate with ECG showing type 2 Sinoatrial block. Patient received a permanent pacemaker. Infliximab therapy was stopped and patient had surgery for fistulizing Crohn's disease.
Dermatologic side effects have included rash (up to 10%), pruritus (7%), cellulitis, increased sweating, ulceration, and interstitial granulomatous dermatitis. Pruritus, urticaria, or the combined symptoms of pruritus/urticaria and cardiopulmonary reactions (less than 1%) have accompanied infliximab infusions. Furunculosis reported as a serious event occurred at a frequency of less than 2%. Psoriasiform eruption (erythematous, slightly scaling, well-shaped pruriginous plaques) has been reported following a third dose of infliximab. Vasculitis and/or vasculitic rash has been reported in a case series (n=8) of patients with rheumatoid arthritis after receiving infliximab infusions. Patients recovered after discontinuation of infliximab and treatment with cyclophosphamide and a corticosteroid. Furuncle/folliculitis, erysipelas cellulitis paronychia, wound infection, fungal skin infection, and severe atopic dermatitis have been reported. At least one case each of necrotizing fasciitis, bullous skin lesions, acne, tinea corporis, primary cutaneous Nocardia otitidiscaviarum infection, atypical varicella exanthema, skin leishmaniosis after injury, palmoplantar pustulosis, alopecia areata, and herpes labialis have been reported. At least two cases of aggressive cutaneous T-cell lymphomas and at least two cases of leprosy and type 1 leprosy reactions have been reported. Psoriasis-like skin lesions have been associated with TNF blockers. Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and new-onset and worsening psoriasis (all subtypes including pustular, primarily palmoplantar) have been reported during postmarketing experience.
Necrotizing fasciitis resulting in death has been reported in a 54-year-old man with rheumatoid arthritis receiving infliximab every 8 weeks along with intramuscular methotrexate weekly dosage. Blood cultures and skin swabs grew hemolytic group A streptococcus.
Bullous skin lesions have been reported in a 72-year-old white man one day after his fourth dose of infliximab for the treatment of severe rheumatoid arthritis. Although proximity of symptoms point to infliximab, causality was not definitive.
Two cases of aggressive cutaneous T-cell lymphomas that progressed rapidly have been reported during therapy with infliximab. Sezary syndrome developed in one patient after 18 months of treatment and systemic anaplastic large cell lymphoma with cutaneous involvement developed in the other patient four weeks following the third dose of infliximab.
A 40-year-old female with Crohn disease experienced acne coincident with infliximab therapy. The patient had been administered infliximab 5 mg/kg with rapid and effective symptomatic control. Several weeks after initiating infliximab therapy, the patient developed a papulopustular eruption on the face and back with some comedones. The eruption persisted, albeit with fluctuating severity, and dermatological opinion was obtained. Histology was consistent with the clinical diagnosis of acne and other Crohn disease-associated dermatoses were excluded. Infliximab was not discontinued because of the excellent control of the bowel disease. Instead, the patient was treated with minocycline 100 mg daily.
A 70-year-old male with rheumatoid arthritis (RA) experienced a primary cutaneous Nocardia otitidiscaviarum infection after a skin injury coincident with infliximab therapy. He was treated for RA with infliximab (3 mg/kg) for 3 years, as well as methotrexate (20 mg/week), and corticosteroids. Two weeks before the 18th infusion of infliximab, he was injured, and had a deep wound in his right palm. The hand lesion was not inflamed, but an erythematous pustular lesion appeared on the anterior side of his right forearm. Two weeks later the lesion spontaneously drained and formed a cutaneous nonpainful ulcer covered by white pus, with erythematous periphery. Nocardia otitidiscaviarum was subsequently isolated from the ulcer and biological samples showed inflammation. Infliximab therapy was discontinued. He was treated with combination clindamycin and ofloxacin antibiotic therapy for 3 months. Twenty days later, the skin ulcer had completely healed.
A 63-year-old female with a history of rheumatoid arthritis (RA) experienced atypical varicella exanthema coincident with infliximab therapy. The patient presented with a 10-day history of pruritic generalized papulovesicles which quickly progressed to flaccid vesicles, pustules, or erosions accompanied by fever and sore throat. Her RA had been treated with methotrexate (10 mg per week) and bucillamine (200 mg per day) for 6 years. Despite this medication, her RA was poorly controlled, so infliximab (3 mg/kg) was additionally administered twice, separated by 2-weekly intervals. Two days after the second course of infliximab therapy, a cutaneous eruption developed abruptly. Polymerase chain reaction showed varicella zoster virus. Based on these findings, the patient was diagnosed with varicella and was promptly started on a course of intravenous acyclovir and prophylactic antibiotics for 7 days. Three weeks later, her recovery was complete with minimal scars.
A 60-year-old male with a 5-year history of diffuse polyarthritis experienced leprosy and type 1 leprosy reaction coincident with infliximab therapy. The patient had been given 3 courses of infliximab; the last had been given 3 months prior to admission. One month after he received the first dose of infliximab, the patient developed a rash on 1 extremity that progressed to all extremities. Results of a skin biopsy suggested leprosy or Hansen disease. He was treated with multidrug therapy (MDT) of dapsone (100 mg daily), clofazimine (50 mg daily), and rifampin (300 mg monthly). One month after starting this treatment, the patient developed "reversal," or type 1, reactions. After 4 years, the cutaneous lesions had resolved, and MDT was withdrawn. Results of a skin biopsy performed 5 years after diagnosis showed advanced regression of the lesion with no residual bacilli.
A 37-year-old female with Crohn disease developed palmoplantar pustulosis (PPP) coincident with infliximab therapy. The patient was given a regimen of infliximab of 5 mg/kg resulting in complete remission of her bowel symptoms. One month later, she experienced classic PPP together with a mild psoriasiform eruption on the lower legs. In particular, the patient's feet were painful, which adversely affected her mobility. As treatment, she was prescribed betamethasone dipropionate twice daily, polythene occlusion at night, and soap-free wash and moisturizer. Over the following 3 to 4 weeks, the patient improved clinically and symptomatically and did not need additional psoriasis therapy.
Alopecia areata has been reported in a 51-year-old white woman with rheumatoid arthritis and Sjogren syndrome after 11 months of infliximab therapy. The hair loss eventually involved 100% of the scalp as well as her eyebrows and eyelashes.
Oncologic side effects have included malignancies (including lymphoma, nonmelanoma skin cancer, and neoplasms [basal cell and breast]). The majority of malignancies in chronic obstructive pulmonary disease (COPD) patients developed in the lung or head and neck. Other malignancies, reported to occur with similar incidence to the general population, have included breast, colorectal, and melanoma. At least one case of acute lymphoblastic leukemia and at least one case of Sezary syndrome have been reported. Malignancies (including non-Hodgkin's lymphoma and Hodgkin's disease) and lymphoproliferative disorders (including hepatosplenic T-cell lymphomas) have been reported during postmarketing experience. Cases of acute and chronic leukemia have been reported with TNF blockers during postmarketing experience.
Clinical trials of infliximab have reported a 3-fold higher incidence than expected in the general population of developing lymphomas among rheumatoid arthritis patients. Among patients diagnosed with Crohn's disease and rheumatoid arthritis, there is 6-fold higher incidence than expected in the general population. Patients with highly active disease and/or chronic exposure to immunosuppressants may be at a higher risk (up to several fold) than the population at large for the development of lymphoma.
During a controlled clinical trial studying the use of infliximab in 157 patients with moderate to severe COPD who were either current smokers or ex-smokers, 9 patients developed a malignancy, including 1 lymphoma.
Acute lymphoblastic leukemia has been diagnosed in a patient eight days after receiving a third infusion of infliximab 5 mg/kg for the treatment of Crohn's disease. A causal relationship was not clearly established.
Postmarketing adverse events reports have included lymphoproliferative disorders (n=8) that developed, on average, 8 weeks after initiation of therapy with infliximab. The majority of cases (81%) were non-Hodgkin's lymphomas.
A meta-analysis has reported that there is dose-dependent increased risk of malignancies in patients with rheumatoid arthritis treated with anti-TNF antibody therapy.
A 75-year-old male with ankylosing spondylitis experienced Sezary syndrome coincident with infliximab therapy. He had been initially treated with nonsteroidal antiinflammatory drugs, then with prednisone 10 mg daily for 6 months, and thereafter treatment was switched to infliximab 3 mg/kg at 2 monthly intervals. After 17 months of this therapy, he was diagnosed with Sezary syndrome. Cutaneous lesions partially remitted following infliximab discontinuation and methotrexate treatment.
Hepatic side effects have rarely included severe liver injury, including acute liver failure and autoimmune hepatitis. Reactivation of hepatitis B virus has been reported in patients who are chronic carriers of this virus (i.e., surface antigen positive). Elevated aminotransferases (ALT more common than AST), biliary pain, cholecystitis, cholelithiasis, and hepatitis have been reported. At least one case of cholestatic liver disease and one case of cytomegalovirus hepatitis have been reported. Severe hepatic reactions (including acute liver failure, jaundice, hepatitis, cholestasis, and autoimmune hepatitis) have been reported during postmarketing experience. Some of the cases resulted in death or the need for liver transplantation.
Severe hepatic reactions have occurred between weeks two to more than a year after initiation of infliximab.
In general, patients who developed elevated ALT and AST were asymptomatic, and the abnormalities decreased or resolved with either continuation or discontinuation of infliximab, or modification of concomitant medications.
Cholestatic liver disease has been reported in a 44-year-old woman 19 days after a single dose of infliximab.
A 45-year-old female with a history of Crohn disease experienced cytomegalovirus hepatitis coincident with infliximab therapy. She had been administered mercaptopurine 50 mg per day for the past 8 years until intravenous infliximab 5 mg/kg at 4 to 8 week intervals was added for better control of the disease. Approximately one year later, the patient was admitted to the hospital with a 4-week history of daily fever and chills unresponsive to several courses of empirical antimicrobial therapy. Histological examination of a liver biopsy specimen showed intranuclear inclusion bodies, confirmed by cytomegalovirus by paraffin immunoperoxidase staining with antibody against this virus. After intravenous ganciclovir 5 mg/kg twice daily therapy, the patient's symptoms and laboratory values improved within a few days.
Some cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia had a fatal outcome.
Hematologic side effects have included pancytopenia, thrombocytopenia, anemia, hemolytic anemia, leukopenia, lymphadenopathy, aplastic anemia, splenic infarction, and splenomegaly. Neutropenia, idiopathic thrombocytopenic purpura, and thrombotic thrombocytopenic purpura have been reported during postmarketing experience.
Musculoskeletal side effects have included back pain (up to 8%), arthralgia (8%), intervertebral disk herniation, tendon disorder, myalgia, and infective arthritis. At least one case of swelling of fingers and one case of paresthesia in the forearm region have been reported.
IgA nephropathy has been reported in a 38-year-old male with fistulizing Crohn's ileocolitis and perianal disease two years after the start of treatment with infliximab infusions every 8 weeks and 6-mercaptopurine.
Renal side effects have included renal calculus, renal failure, pyelonephritis, and kidney infarction (reported within a group of serious events). At least one case of IgA nephropathy has been reported.
Metabolic side effects have included dehydration and extra-high levels of VLDL-triglycerides.
Local side effects have included injection site reactions that were mainly erythema, pruritus, rash, and pain of mild to moderate severity. At least one case of repeated local infections has also been reported.
Genitourinary side effects have included urinary tract infections (8%), menstrual irregularity, herpes simplex, and endometritis. Serious genitourinary events have included dysuria and urethral obstruction.
A 55-year-old woman diagnosed with rheumatoid arthritis developed decreased vision in the left eye accompanied by pain with eye movement 3 days after her 9th infusion (at 1 year of treatment) with infliximab. Patient's vision slowly improved and her visual field deficit resolved after treatment with 1 g methylprednisolone injection per day for 3 days followed by a tapering dose of oral prednisone over 10 days.
A week after the seventh infusion of infliximab 5 mg/kg, a 45-year-old woman with type 2 diabetes mellitus and Crohn's disease developed pain and blurred vision in the left eye. Visual acuity was 20/70. Patient recovered after treatment with intravenous methylprednisolone, followed by a tapering dose of oral prednisone. On examination 3 months later she had 20/20 visual acuity, normal color vision, mild residual left-sided headache, and a normal-appearing optic nerve in the left eye.
A 42-year-old male developed severe unilateral orbital cellulitis while receiving infliximab therapy for ankylosing spondylitis during a clinical trial. Cultures showed Staphylococcus aureus. Infliximab therapy was stopped and the patient made a full recovery after receiving appropriate antibiotic therapy. Infliximab treatment was resumed after three weeks.
A 47-year-old male with rheumatoid arthritis experienced third nerve palsy coincident with infliximab therapy. He received monthly infusions of 300 mg of infliximab for the disease. He initially presented with painless ptosis of his right upper eyelid along with double vision in left and up gaze. Brain magnetic resonance imaging (MRI) showed gadolinium enhancement of the cisternal segment of the right oculomotor nerve. After stopping infliximab therapy, the diplopia and ptosis gradually resolved during 3 months. Repeat MRI imaging showed resolution of the oculomotor nerve enhancement.
Ocular side effects have been extremely rare. Retrobulbar optic neuritis of the left eye has been reported after the seventh infusion of infliximab in one patient and after the ninth infusion on another patient. At least one case of orbital cellulitis and at least one case of third nerve palsy have been reported. Uveitis has been reported during postmarketing experience. Cases of transient visual loss associated with infliximab administration (during or within 2 hours of infusion) have also been rarely reported during postmarketing experience.
Psychiatric side effects have included confusion and suicide attempt.
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