Infliximab

Registered South African indications:

• Rheumatoid arthritis 
• Psoriatic arthritis
• Inflammatory bowel disease
• Ankylosing spondylitis
• Psoriasis 

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to other murine proteins
• Tuberculosis
• Severe infections
• Moderate or severe heart failure 

Cautions

• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Chronic infection
• History of recurrent infections
• Inactive ('latent') tuberculosis
• Risk factors for tuberculosis 
• Residence or travel to regions where invasive fungal infections are endemic
• Fistulising Crohn's disease with acute suppurative fistulas 
• Carriers of hepatitis B virus
• Pre-existing or recent onset of demyelinating disorders
• Chronic obstructive pulmonary disease
• Heavy smoking
• Previous malignancy
• History of extensive immunosuppressant therapy or prolonged photochemotherapy for psoriasis
• Colon dysplasia in ulcerative colitis 
• Mild heart failure
• Surgery
• Children
• Young adults < 22 years
• Switching between different biological disease modifying agents

Forms avail. in SA and covered in this monograph: inj

Rheumatoid arthritis

• IV: Initial: 3mg/kg, as an infusion, at 0, 2 and 6 weeks; Maintenance: 3mg/kg, as an infusion, 4-8 weekly; Max: 7.5mg/kg/8 weeks

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Infliximab should be given in combination with methotrexate

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If no response after 12 weeks, discontinue treatment

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The safety and efficacy of readministration after an infliximab-free interval of >16wks has not been established

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Crohn's disease - moderate to severe
Fistulising Crohn's disease 

• IV: Initial: 5mg/kg, as an infusion, at 0, 2 and 6 weeks; Maintenance: 5-10mg/kg, 8 weekly

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If no response after 6 weeks, discontinue treatment

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After initial doses at 0, 2 and 6 weeks, if there has been a response, patient can be placed on an 8 weekly maintenance regiment OR one can wait and only repeat the 5mg/kg dosage if signs and symptoms recur; This repeat dosage is then followed by a maintenance dosage of 5mg/kg, 8 weekly

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The safety and efficacy of readministration after an infliximab-free interval of >16wks has not been established

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Ankylosing spondylitis

• IV: Initial: 5mg/kg, as an infusion, at 0, 2 and 6 weeks; Maintenance: 5mg/kg, as an infusion, 6-8 weekly

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If no response after 6 weeks, discontinue treatment

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The safety and efficacy of readministration after an infliximab-free interval of >6-8wks has not been established

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Psoriasis
Psoriatic arthritis
Ulcerative colitis 

• IV: Initial: 5mg/kg, as an infusion, at 0, 2 and 6 weeks; Maintenance: 5mg/kg, as an infusion, 8 weekly

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Psoriasis and ulcerative colitis: If no response after 14 weeks, consider discontinuation of treatment

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The safety and efficacy of readministration after an infliximab-free interval of >8wks has not been established

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See additional prescribing points for administration directions

Paed. forms avail. in SA and covered in this monograph: inj

Crohn's disease
Ulcerative colitis

Younger than 6 years

• Not established for use

Older than 6 years

• See adult dosage

Pregnancy

• Caution
• The moderate number of prospectively collected pregnancies exposed to infliximab resulting in live birth with known outcomes, including approximately 1100 exposed during the first trimester, does not indicate an increase in the rate of malformation in the newborn
• Based on an observational study from Northern Europe, an increased risk (OR, 95% CI; p-value) for C-section (1.50, 1.14-1.96; p=0.0032), preterm birth (1.48, 1.05-2.09; p=0.024), small for gestational age (2.79, 1.54-5.04; p=0.0007), and low birth weight (2.03, 1.41-2.94; p=0.0002) was observed in women exposed during pregnancy to infliximab (with or without immunomodulators/corticosteroids, 270 pregnancies) as compared to women exposed to immunomodulators and/or corticosteroids only (6,460 pregnancies). The potential contribution of exposure to inflixumab and/or the severity of the underlying disease in these outcomes remains unclear
• Due to its inhibition of TNFα, infliximab administered during pregnancy could affect normal immune responses in the newborn. In a developmental toxicity study conducted in mice using an analogous antibody that selectively inhibits the functional activity of mouse TNFα, there was no indication of maternal toxicity, embryotoxicity or teratogenicity 
• The available clinical experience is limited. Infliximab should only be used during pregnancy if clearly needed
• Infliximab crosses the placenta and has been detected in the serum of infants up to 6 months following birth. After in utero exposure to infliximab, infants may be at increased risk of infection, including serious disseminated infection that can become fatal. Administration of live vaccines (e.g. BCG vaccine) to infants exposed to infliximab in utero is not recommended for at least 6 months after birth. Cases of agranulocytosis have also been reported

Breastfeeding

• Caution; not recommended
• It is unknown whether infliximab is excreted in human milk or absorbed systemically after ingestion. Because human immunoglobulins are excreted in milk, women must not breastfeed for at least 6 months after infliximab treatment

Renal Impairment

• Caution; no information available 

Hepatic Impairment

• Caution; no information available 

Elderly

• Caution; no dose adjustment recommended 

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Depression
• Insomnia
• Amnesia
• Agitation
• Confusion
• Somnolence
• Nervousness
• Apathy
• Headache
• Vertigo
• Dizziness
• Hypoaesthesia
• Paraesthesia
• Seizures
• Neuropathy
• Transverse myelitis
• Central nervous system demyelinating disorders
• Peripheral demyelinating disorders

Cardiovascular Disorders

• Tachycardia
• Chest pain
• Palpitation
• Cardiac failure
• Arrhythmia
• Syncope
• Bradycardia
• Cyanosis
• Pericardial effusion
• Myocardial ischaemia
• Myocardial infarction
• Hypotension
• Hypertension
• Flushing
• Peripheral ischaemia
• Thrombophlebitis
• Haematoma
• Circulatory failure
• Vasospasm

Respiratory Disorders

• Upper respiratory tract infection
• Sinusitis
• Lower respiratory tract infection 
• Dyspnoea
• Epistaxis
• Pulmonary oedema
• Bronchospasm
• Pleurisy
• Pleural effusion
• Interstitial lung disease

Gastrointestinal Disorders

• Abdominal pain
• Nausea
• Gastrointestinal haemorrhage
• Diarrhoea
• Dyspepsia
• Gastroesophageal reflux
• Constipation
• Intestinal perforation
• Intestinal stenosis
• Diverticulitis
• Pancreatitis
• Cheilitis

Hepatobiliary Disorders

• Abnormal hepatic function
• Increased transaminases
• Hepatitis
• Hepatocellular damage
• Cholecystitis
• Autoimmune hepatitis
• Jaundice
• Liver failure

Genitourinary Disorders

• Urinary tract infection
• Pyelonephritis
• Vaginitis

Musculoskeletal Disorders

• Arthralgia
• Myalgia
• Back pain

Skin and Subcutaneous Tissue Disorders

• New onset or worsening psoriasis including pustular psoriasis
• Urticaria
• Rash
• Pruritus
• Hyperhidrosis
• Dry skin
• Fungal dermatitis
• Eczema
• Alopecia
• Bullous eruption
• Onychomycosis
• Seborrhoea
• Rosacea
• Skin papilloma
• Hyperkeratosis
• Abnormal skin pigmentation
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome
• Erythema multiforme
• Furunculosis
• Worsening of symptoms of dermatomyositis
• Injection site reactions
• Ecchymosis
• Petechia
• Infusion site granulomatous lesion
• Infusion site oedema

Immune, Blood and Lymphatic System Disorders

• Viral infections
• Bacterial infections 
• Tuberculosis
• Fungal infections 
• Meningitis
• Opportunistic infections  
• Parasitic infections
• Hepatitis B reactivation
• Vaccine breakthrough infection
• Lymphoma
• Non-Hodgkin's lymphoma
• Hodgkin's disease
• Leukaemia
• Melanoma 
• Cervical cancer
• Hepatosplenic T-cell lymphoma
• Merkel cell carcinoma
• Neutropenia
• Leucopenia
• Anaemia
• Lymphadenopathy
• Thrombocytopenia
• Lymphopenia
• Lymphocytosis
• Agranulocytosis
• Thrombotic thrombocytopenic purpura
• Pancytopenia
• Haemolytic anaemia
• Idiopathic thrombocytopenic purpura
• Anaphylactic reaction
• Lupus-like syndrome
• Serum sickness 
• Serum sickness-like reaction
• Anaphylactic shock
• Vasculitis
• Sarcoid-like reaction
• Fever
• Impaired healing

Sensory Disorders

• Conjunctivitis
• Keratitis
• Periorbital oedema
• Hordeolum
• Endophthalmitis
• Transient visual loss occurring during or within 2 hours of infusion

Others

• Chills

• Methotrexate
• Other immunomodulators
• Biological immune modulators  
• Live vaccines
• Therapeutic infectious agents

• Signs and symptoms of infections (including tuberculosis)
• Hepatitis B virus screening
• Full blood count
• Hepatic function

Specific cases may require

• Dermatological examination
• Signs and symptoms of hypersensitivity reaction
• Latent tuberculosis screening
• Cardiac function
• Signs and symptoms of malignancy 

Administration directions

• Reconstitute each vial with 10ml sterile water for injection. (Note: dose may require several vials)
• Allow the reconstituted solution to stand for 5 minutes; Do not shake
• Further dilute the reconstituted solution of total dose to a final volume of 250ml with 0.9% sodium chloride
• The infusion concentration should range between 0.4 to 4mg/ml
• Use within 3 hours of reconstitution and dilution
• Do not infuse concomitantly in the same intravenous line with other agents

Infliximab is a chimeric monoclonal antibody. It binds with high affinity to both soluble and transmembrane forms of human tumour necrosis factor alpha but not to lymphotoxin-alpha. This results in an overall reduction in inflammation.

Injection (per 10ml) 100mg

• Remsima (Adcock Ingram)
• Revellex (Janssen) originator