Infliximab intravenous infusion
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Infusion formulation of infliximab.
Drugs List
Therapeutic Indications
Uses
Fistulating Crohn's disease
Moderate to severe plaque psoriasis: Second line treatment
Moderate/severe ulcerative colitis: when other treatment is inappropriate
Rheumatoid arthritis when inadequate response to DMARDs incl. methotrexate
Severe active rheumatoid arthritis
Severe ankylosing spondylitis in adults if conventional therapy inadequate
Severe Crohn's disease
Treatment of active & progressive psoriatic arthritis when DMARD inadequate
Adult Rheumatoid arthritis (in combination with methotrexate) Reduction of signs and symptoms as well as the improvement in physical function in patients with: Active disease when the response to disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate, has been inadequate. Severe, active progressive disease not previously treated with methotrexate or other DMARDs.
Adult Crohn's disease Treatment of moderate to severely active disease in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant or who are intolerant to or have medical contraindications for such therapies and when surgery is inappropriate. Treatment of fistulating disease, in patients who have not responded despite a full and adequate course of therapy with conventional treatment (including antibiotics, drainage and immunosuppressive therapy). Paediatric Crohn's disease (studied only in combination with conventional immunosuppressive therapy and when surgery is inappropriate) Treatment of severe, active Crohn's disease, in paediatric patients aged 6 to 17 years, who have not responded to conventional therapy including a corticosteroid, an immunomodulator and primary nutrition therapy; or who are intolerant to or have contraindications for such therapies. Ulcerative colitis Treatment of moderately to severely active ulcerative colitis in adult patients who have an inadequate response, intolerance or medical contraindication to conventional therapy such as corticosteroids and mercaptopurine (6-MP) or azathioprine (AZA).
Paediatric ulcerative colitis
Treatment of severely active ulcerative colitis in patients aged 6 to 17 years, who have had an inadequate response to conventional therapy including corticosteroids and 6-MP or AZA, or who are intolerant to or have medical contraindications for such therapies. Ankylosing spondylitis Treatment of adult patients who have severe active ankylosing spondylitis and who have responded inadequately to conventional therapy.
Psoriatic Arthritis Treatment of active and progressive psoriatic arthritis in adult patients who have responded inadequately to DMARDs. Use in combination with methotrexate, or alone in patients who show intolerance to methotrexate or for whom methotrexate is contraindicated. Psoriasis Treatment of moderate to severe plaque psoriasis in adults who failed to respond to, are intolerant to or have a contraindication for other systemic therapy (including ciclosporin, methotrexate or PUVA).
Dosage
Increasing the product free interval may increase the risk for delayed hypersensitivity reactions.
Adults
Rheumatoid arthritis
3mg/kg by intravenous infusion followed by 3mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter.
Must be given concurrently with methotrexate.
If a patient has an inadequate response or loses response after 12 weeks, consider increasing the dose step-wise by 1.5mg/kg, to maximum of 7.5mg/kg every 8 weeks. Alternatively, administration of 3mg/kg, up to every 4 weeks may be considered. If adequate response is achieved, patients should be continued on the selected dose or dose frequency.
Continued therapy should be carefully considered in patients who show no evidence of therapeutic benefit within the first 12 weeks of treatment or after dose adjustment.
If signs and symptoms recur, repeat treatment within 16 weeks of the last infusion. Re-administration of infliximab with a drug free interval of less than one year following a previous infusion has been associated with a delayed hypersensitivity reaction. Re-administration after a drug free interval of more than 16 weeks cannot be recommended.
Moderate to severely active Crohn's disease
5mg/kg by intravenous infusion followed by another 5mg/kg infusion two weeks later. If a patient does not respond after two doses, treatment with infliximab should be stopped.
In responding patients, the alternative strategies for continued treatment are: Additional infusion of 5mg/kg at 6 weeks after the initial dose, followed by infusions every 8 weeks OR re-administration of infusion of 5mg/kg if signs and symptoms of the disease recur.
Patients who initially responded to 5mg/kg infusion but then lost response suggests response may be regained with dose escalation.
If signs and symptoms recur, repeat treatment within 16 weeks of the last infusion. Re-administration of infliximab with a drug free interval of less than one year following a previous infusion has been associated with a delayed hypersensitivity reaction. Re-administration after a drug free interval of more than 16 weeks cannot be recommended.
Fistulating Crohn's disease
5mg/kg by intravenous infusion followed by 5mg/kg infusion doses after 2 and 6 weeks. If a patient does not respond after three doses, treatment should be stopped.
In responding patients, the alternative strategies are: Additional infusions of 5mg/kg every 8 weeks OR re-administration of an infusion of 5mg/kg every 8 weeks, if signs and symptoms of the disease recur.
Patients who initially responded to 5mg/kg infusion but then lost response suggests response may be regained with dose escalation.
If signs and symptoms recur, repeat treatment within 16 weeks of the last infusion. Re-administration of infliximab with a drug free interval of less than one year following a previous infusion has been associated with a delayed hypersensitivity reaction. Re-administration after a drug free interval of more than 16 weeks cannot be recommended.
Ulcerative colitis
5mg/kg by intravenous infusion followed by 5mg/kg infusion doses after 2 and 6 weeks, then every 8 weeks. If the patient does not respond after these three doses, continued treatment should be carefully considered.
Ankylosing spondylitis
5mg/kg by intravenous infusion followed by 5mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 6 to 8 weeks. If a patient does not respond after two doses, no additional treatment with infliximab should be given.
Psoriatic arthritis
5mg/kg by intravenous infusion followed by 5mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks.
Psoriasis
5mg/kg by intravenous infusion followed by 5mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks. If a patient fails to respond after four doses, no additional treatment with infliximab should be given.
Limited experience from retreatment following disease flare by a re-induction regimen and from retreatment with one single infliximab dose in psoriasis after an interval of 20 weeks, suggests reduced efficacy and higher incidence infusion reactions.
Re-administration across indications
If maintenance therapy is interrupted, use of a re-induction regimen is not recommended. In this situation, infliximab should be re-initiated as a single dose followed by the maintenance dose recommendations described above.
Children
Severe active Crohn's Disease (Children aged 6 to 17 years)
Initially 5mg/kg, followed by 5mg/kg doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter.
Some patients may require a shorter dosing interval to maintain clinical benefit, while for others a longer dosing interval may be sufficient. Available data do not support further infliximab treatment in paediatric patients not responding within the first 10 weeks of treatment.
Severe active Ulcerative Colitis (Children aged 6 to 18 years)
Initially 5mg/kg, then further 5mg/kg doses 2 weeks and 6 weeks after the initial dose, then 5mg/kg every 8 weeks. Discontinue if no response within 8 weeks of initial dose.
Fistulating Crohn's disease (unlicensed)
Children aged 6 to 18 years: Initially 5mg/kg, then 5mg/kg 2 weeks and 6 weeks after initial dose, then if condition has responded, consult the literature for guidance on further doses.
Administration
For intravenous infusion following reconstitution and dilution.
Infliximab should be administered intravenously over a 2 hour period. In selected adult patients who have tolerated three, 2 hour infusions, consideration may be given to administering subsequent infusions over a period of not less than 1 hour. Shortened infusions at doses greater than 6mg/kg have not been studied.
Infusion rate may be slowed in order to decrease the risk of infusion-related reactions especially if infusion-related reactions have occurred previously.
Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter (pore size 1.2 micrometre or less).
Contraindications
Abscess
Children under 6 years
Sepsis
Severe infection
New York Heart Association class III failure
Tuberculosis
Precautions and Warnings
Children aged 6 to 18 years
Elderly
Females of childbearing potential
History of immunosuppressant treatment
History of recurrent infection
Infection
Tobacco smoking
Breastfeeding
Central nervous system demyelinating disorder
Hepatic impairment
Hepatitis B
History of cancer
Latent or healed tuberculosis
Malignant neoplasm
New York Heart Association class I failure
Pregnancy
Renal impairment
Administration of live vaccines is not recommended
Consider anti-TB therapy in patients with latent TB
Disease reactivation may occur in patients with latent TB
May mask symptoms or signs of infections
Advise ability to drive/operate machinery may be affected by side effects
Before initiating screen at risk patients for hepatitis B infection
Before starting therapy ensure immunisations are up to date
Consider pre-medication with antihistamines and/or antipyretics
Consider premedication with a corticosteroid
Exclude tubercular infection before treatment
Dilute and use as an infusion
Record name and batch number of administered product
Treatment to be administered under the supervision of a specialist
Monitor all parameters for at least 6 months post treatment cessation
Monitor closely any patient who develops new infection while on treatment
Monitor for dysplasia in patients at increased risk of colon cancer
Monitor retreated patients for symptoms of delayed hypersensitivity
Monitor skin changes
Use only when equipment adequate for cardiac/respiratory monitoring/support
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Advise patient to seek med advice if signs/symptoms of tuberculosis develop
Anaphylactic reactions may occur within seconds or few hours after infusion
Antibodies to ingredient may develop and are not always detectable in serum
Immunosuppressive drugs may increase risk of malignancy
Monitor for hypersensitivity reactions for 1 hour after administration
Reactivation of hepatitis B may occur in chronic carriers
False negative tuberculin test results in immunosupp./severely ill patients
Consider discontinuation if demyelinating disorders develop or worsen
Consider discontinuation if severe haematological events occur
Discontinue and investigate if symptoms of lupus-like syndrome develop
Discontinue at the first signs of cardiac failure
Discontinue if ALT level exceeds 5 times the upper limit of normal
Discontinue if hypersensitivity reactions occur
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if worsening symptoms of cardiac failure develop
Discontinue treatment if patient develops a serious infection
Not licensed for all indications in all age groups
Female: Contraception advised during and for 6 months after treatment
Breastfeeding: Do not breastfeed during & for 6 months after treatment
Advise patient to seek medical advice if delayed adverse event(s) occurs
Remind patient of importance of carrying Alert Card with them at all times
Periodic skin examination is recommended, particularly for patients with risk factors for skin cancer as melanoma and Merkel cell carcinoma have been reported with TNF blocker therapy, including infliximab.
Infusion reactions and hypersensitivity
Antibodies directed towards infliximab may develop and have been associated with increased frequency of infusion reactions and reduced duration of response. Concomitant administration of immunomodulators has been associated with lower incidence of antibodies and a reduction in infusion reactions. The effect of immunomodulators was greater in patients treated episodically rather than those on maintenance treatment. If serious reactions occur, symptomatic treatment must be given and further infusion of infliximab must not be administered.
Infections
Before starting treatment, all patients must be evaluated for both active and inactive (latent) tuberculosis (TB). Appropriate screening tests, i.e. tuberculin skin test, interferon gamma release assay and chest X-ray, should be performed in all patients (local recommendations may apply). It is recommended that the conduct of these tests should be recorded in the patient's alert card.
If latent tuberculosis is diagnosed, prophylactic anti-tuberculosis therapy must be started before initiation of infliximab therapy in accordance with local recommendations. Consideration of treatment with anti-tuberculosis therapy should be given to patients with several or significant risk factors for TB (but have a negative test for latent TB) and in patients with a history of TB in whom an adequate course of treatment cannot be confirmed. Patients should be advised to seek medical advice if signs/symptoms suggestive of infection occur.
Chronic carriers of hepatitis B should be evaluated and monitored prior to, during and for several months after treatment has finished. In patients who develop active hepatitis B, infliximab should be stopped and an effective anti-viral with supportive treatment should be initiated.
Vaccinations
It is recommended that all patients, if possible, be brought up to date with all vaccinations in agreement with current vaccination guidelines prior to initiating therapy. Administration of live vaccines to infants exposed to infliximab in utero is not recommended for 6 months after the mother's last infliximab treatment during pregnancy.
Live vaccines or therapeutic infectious products should not be given during treatment with infliximab.
Pregnancy and Lactation
Pregnancy
Use infliximab with caution in pregnancy.
The manufacturer recommends that infliximab should only be used during pregnancy if clearly needed.
Post marketing reports from approximately 1100 pregnancies exposed to infliximab do not indicate unexpected effects on pregnancy outcome.
Due to its inhibition of TNF alpha, infliximab administered during pregnancy could affect normal immune responses in the newborn. In an animal study inhibiting TNF alpha activity, there was no indication of maternal toxicity, embryotoxicity or teratogenicity.
Infliximab crosses the placenta and has been detected for up to 6 months in the serum of infants born to women exposed to infliximab during pregnancy. These infants may be at an increased risk of infection.
Schaefer (2015) recommends that infliximab does not need to be stopped when planning a pregnancy. A detailed foetal ultrasound should be offered in cases of first trimester exposure to confirm normal foetal development. Infliximab in the second half of pregnancy should also result in the close monitoring of the pregnant woman and the foetus sonographically monitored.
Lactation
Use infliximab with caution in breastfeeding.
The manufacturer states that it is not known if infliximab is excreted in human milk or absorbed systemically after ingestion. They recommend that mothers must not breastfeed for at least 6 months after treatment.
Lactmed (2018) states the despite the manufacturer recommendations, other sources state that the drug is a low risk to the nursing infant and breastfeeding can continue during infliximab use.
Side Effects
Abscess
Agitation
Agranulocytosis
Alopecia
Amnesia
Anaemia
Antibody formation
Apathy
Arrhythmias
Bronchospasm
Cardiac disorders
Cardiac failure
Cheilitis
Chills
Cholecystitis
Circulatory failure
Complement factor abnormality
Confusion
Conjunctivitis
Cyanosis
Delayed hypersensitivity reactions
Demyelinating disorders
Depression
Diverticulitis
Dizziness
Dyspnoea
Ecchymosis
Endophthalmitis
Epistaxis
Fatigue
Fever
Flushing
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Gastro-intestinal symptoms
Granulomatous lesions
Haematoma
Haemolytic anaemia
Headache
Hepatic failure
Hepatic impairment
Hepatitis
Hordeolum
Hypersensitivity reactions
Hypertension
Hypoaesthesia
Hypotension
Idiopathic thrombocytopenic purpura (ITP)
Impaired healing
Infections
Injection site reactions
Insomnia
Interstitial pneumonitis
Jaundice
Kaposi's Sarcoma
Leukopenia
Linear IgA bullous dermatosis
Lupus erythematosus-like syndrome
Lymphadenopathy
Lymphocytosis
Lymphopenia
Malignancies
Meningitis
Myocardial infarction
Myocardial ischaemia
Nervousness
Neuropathy
Neutropenia
Oedema
Pain
Palpitations
Pancreatitis
Pancytopenia
Paraesthesia
Pericardial effusion
Periorbital oedema
Peripheral ischaemia
Pleural effusion
Pleurisy
Pulmonary oedema
Pyelonephritis
Reactivation of hepatitis B
Seizures
Sepsis
Serum sickness-like reactions
Sinusitis
Skin reactions
Somnolence
Stevens-Johnson syndrome
Syncope
Thrombocytopenia
Thrombophlebitis
Thrombotic thrombocytopenic purpura
Toxic epidermal necrolysis
Transverse myelitis
Tuberculosis
Urticaria
Vasculitis
Vasospasm
Vertigo
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: March 2019
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Flixabi 100mg powder for concentrate for solution for infusion. Biogen Idec Ltd. Revised January 2019.
Summary of Product Characteristics: Inflectra 100mg powder for concentrate for solution for infusion. Hospira UK Ltd. Revised February 2019.
Summary of Product Characteristics: Remicade 100mg powder for concentrate for solution for infusion. Merck Sharp and Dohme Limited. Revised January 2019.
Summary of Product Characteristics: Remsima 100mg powder for concentrate for solution for infusion. Napp Pharmaceuticals Limited. Revised October 2020.
Summary of Product Characteristics: Zessly 100mg powder for concentrate for solution for infusion. Sandoz Limited. Revised October 2020.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 25 March 2019
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Infliximab Last revised: 31 October, 2018
Last accessed: 25 March 2019
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