Drugs List

Therapeutic Indications

Uses

Rheumatoid arthritis when inadequate response to DMARDs incl. methotrexate
Severe active rheumatoid arthritis

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.

Administration

Infliximab pre-filled device and pre-filled syringe are administered by subcutaneous injection only. Full instructions for use are provided in the patient information leaflet. The prescriber should ensure appropriate follow-up with patients if any systemic or localised injection reactions occur after the initial subcutaneous injection.

Contraindications

Abscess
Children under 18 years
Sepsis
Severe infection
Hereditary fructose intolerance
New York Heart Association class III failure
Tuberculosis

Precautions and Warnings

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
Treatment to be initiated and supervised by a specialist
Contains polysorbate
Presentations with sorbitol unsuitable in hereditary fructose intolerance
For subcutaneous use only
Record name and batch number of administered product
Monitor all parameters for at least 6 months post treatment cessation
Monitor closely any patient who develops new infection while on treatment
Monitor retreated patients for symptoms of delayed hypersensitivity
Monitor skin changes
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
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.

Injection reactions and hypersensitivity
Antibodies directed towards infliximab may develop and have been associated with increased frequency of infusion reactions when administered by intravenous infusion 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 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, 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 hepatitis B reactivation, 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 at least 6 months after birth.

Live vaccines or therapeutic infectious products should not be given during treatment with infliximab.

Pregnancy and Lactation

Pregnancy

Use infliximab with caution during 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 during the first trimester do not indicate an increased rate of malformation in the newborn.

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. Treatment in the second/third trimester should be reserved for justifiable indications. Discontinuation of therapy is recommended by gestational week 30. A detailed foetal ultrasound may be offered 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 during 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 (2020) 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
Anaphylactic reaction
Antibody formation
Apathy
Arrhythmias
Bronchospasm
Cardiac disorders
Cardiac failure
Cerebrovascular accident
Cheilitis
Chest pain
Chills
Cholecystitis
Circulatory failure
Complement factor abnormality
Confusion
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
Haematological reactions
Haematoma
Haemolytic anaemia
Headache
Hepatic failure
Hepatic impairment
Hepatitis
Hypersensitivity reactions
Hypertension
Hypoaesthesia
Hypotension
Idiopathic thrombocytopenic purpura (ITP)
Impaired healing
Infections
Injection site reactions
Insomnia
Interstitial lung disease
Jaundice
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
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
Vasculitis
Vasospasm
Vertigo
Visual disturbances

Presentation

Solution for injection of infliximab.

Drugs List

Therapeutic Indications

Uses

Rheumatoid arthritis when inadequate response to DMARDs incl. methotrexate
Severe active rheumatoid arthritis

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.

Dosage

Increasing the infliximab free interval may increase the risk for delayed hypersensitivity reactions.

Adults

Additional Dosage Information

Administration

Infliximab pre-filled device and pre-filled syringe are administered by subcutaneous injection only. Full instructions for use are provided in the patient information leaflet. The prescriber should ensure appropriate follow-up with patients if any systemic or localised injection reactions occur after the initial subcutaneous injection.

Contraindications

Abscess
Children under 18 years
Sepsis
Severe infection
Hereditary fructose intolerance
New York Heart Association class III failure
Tuberculosis

Precautions and Warnings

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
Treatment to be initiated and supervised by a specialist
Contains polysorbate
Presentations with sorbitol unsuitable in hereditary fructose intolerance
For subcutaneous use only
Record name and batch number of administered product
Monitor all parameters for at least 6 months post treatment cessation
Monitor closely any patient who develops new infection while on treatment
Monitor retreated patients for symptoms of delayed hypersensitivity
Monitor skin changes
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
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.

Injection reactions and hypersensitivity
Antibodies directed towards infliximab may develop and have been associated with increased frequency of infusion reactions when administered by intravenous infusion 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 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, 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 hepatitis B reactivation, 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 at least 6 months after birth.

Live vaccines or therapeutic infectious products should not be given during treatment with infliximab.

Pregnancy and Lactation

Pregnancy

Use infliximab with caution during 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 during the first trimester do not indicate an increased rate of malformation in the newborn.

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. Treatment in the second/third trimester should be reserved for justifiable indications. Discontinuation of therapy is recommended by gestational week 30. A detailed foetal ultrasound may be offered 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 during 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 (2020) 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
Anaphylactic reaction
Antibody formation
Apathy
Arrhythmias
Bronchospasm
Cardiac disorders
Cardiac failure
Cerebrovascular accident
Cheilitis
Chest pain
Chills
Cholecystitis
Circulatory failure
Complement factor abnormality
Confusion
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
Haematological reactions
Haematoma
Haemolytic anaemia
Headache
Hepatic failure
Hepatic impairment
Hepatitis
Hypersensitivity reactions
Hypertension
Hypoaesthesia
Hypotension
Idiopathic thrombocytopenic purpura (ITP)
Impaired healing
Infections
Injection site reactions
Insomnia
Interstitial lung disease
Jaundice
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
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
Vasculitis
Vasospasm
Vertigo
Visual disturbances

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: April 2020

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.

Summary of Product Characteristics: Remsima 120mg solution for injection. Celltrion Healthcare UK Limited. Revised February 2020.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501351/
Infliximab Last revised: 30 January 2020
Last accessed: 07 April 2020