Abatacept parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral formulations of abatacept for infusion and subcutaneous injection.
Drugs List
Therapeutic Indications
Uses
Active polyarticular juvenile idiopathic arthritis in combination with MTX
Psoriatic arthritis (unresp to DMARD) monotherapy or combination with MTX
Rheumatoid arthritis (unresp to DMARD/TNF inhib.) in comb with methotrexate
Severe active progressive rheumatoid arthritis: Combination treatment
Rheumatoid arthritis (RA)
Abatacept, in combination with methotrexate, is indicated for:
Treatment of moderate to severe active rheumatoid arthritis in adult patients who responded inadequately to previous therapy with one or more disease modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX) or a tumour necrosis factor (TNF)-alpha inhibitor.
Treatment of highly active and progressive disease in adult patients with rheumatoid arthritis (RA) not previously treated with methotrexate.
Psoriatic arthritis
As monotherapy or in combination with methotrexate, for adults with active psoriatic arthritis (PsA), when there has been an inadequate response to previous treatment with DMARDs, including MXT, and for patients that do not require additional systemic therapy for psoriatic skin lesions.
Polyarticular juvenile idiopathic arthritis (pJIA)
Infusion
Abatacept, in combination with methotrexate, is indicated for the treatment of moderate to severe active polyarticular juvenile idiopathic arthritis in paediatric patients 6 years of age and older who have had an insufficient response to other DMARDs.
Injection (pre-filled syringe only)
Abatacept, in combination with methotrexate, is indicated for the treatment of moderate to severe active polyarticular juvenile idiopathic arthritis in paediatric patients 2 years of age and older who have had an insufficient response to other DMARDs.
Dosage
Adults
Rheumatoid arthritis & Psoriatic arthritis (by infusion)
Bodyweight of greater than 100kg: 1000mg, repeated 2 weeks and 4 weeks after initial infusion, then every 4 weeks.
Bodyweight greater than or equal to 60kg to bodyweight less than or equal to 100kg: 750mg, repeated 2 weeks and 4 weeks after initial infusion, then every 4 weeks.
Bodyweight of less than 60kg: 500mg, repeated 2 weeks and 4 weeks after initial infusion, then every 4 weeks.
Rheumatoid arthritis (by injection)(pre-filled syringe and pre-filled pen)
If a single intravenous infusion is given to initiate treatment, the first 125mg subcutaneous injection of abatacept should be given within a day, followed by 125mg subcutaneous injections once weekly.
Patients who are unable to receive an infusion may initiate weekly injections of subcutaneous abatacept without an intravenous loading dose.
Psoriatic arthritis (by injection)(pre-filled syringe and pre-filled pen)
125mg once a week, administered by subcutaneous injection.
Children
Polyarticular Juvenile idiopathic arthritis (by intravenous infusion):
Children aged 6 to 18 years:
Bodyweight over 100kg: 1000mg, repeated 2 weeks and 4 weeks after initial infusion, then every 4 weeks.
Bodyweight 75kg to 100kg: 750mg, repeated 2 weeks and 4 weeks after initial infusion, then every 4 weeks.
Bodyweight less than 75kg: 10mg/kg, repeated 2 weeks and 4 weeks after initial infusion, then every 4 weeks.
Polyarticular Juvenile idiopathic arthritis (by injection)(pre-filled syringe):
Children aged 2 to 18 years:
Bodyweight over 50kg: 125mg weekly.
Bodyweight 25kg to 50kg: 87.5mg weekly.
Bodyweight 10kg to 25kg: 50mg weekly.
Patients with Renal Impairment
Not recommended for use in patients with renal impairment as there is no data for this population.
The Renal Drug Handbook suggests the following doses:
Glomerular Filtration Rate (GFR) 20 to 50 ml/minute: Dose as in normal renal function.
GFR 10 to 20 ml/minute: Dose as in normal renal function. Use with caution.
GFR less than 10 ml/minute: Dose as in normal renal function. Use with caution.
Additional Dosage Information
Infusion
Following the initial administration, abatacept should be given 2 and 4 weeks after the first infusion, then every 4 weeks thereafter.
If there is no response within 6 months of treatment, the continuation of the treatment should be reconsidered.
Injection (pre-filled syringe and pre-filled pen)
Patients transitioning from abatacept intravenous therapy to subcutaneous administration should administer the first subcutaneous dose instead of the next scheduled intravenous dose.
If a patient misses an injection of abatacept and is within three days of the planned date, the patient should be instructed to take the missed dose immediately and remain on the original weekly schedule. If the dose is missed by more than three days, the patient should be instructed when to take the next dose based on medical judgement.
Injection sites should be rotated and injections should never be given into areas where the skin is tender, bruised, red or hard.
Administration
Infusion
To be administered as a 30 minute intravenous infusion.
Injection (pre-filled syringe and pre-filled pen)
To be administered as a subcutaneous injection.
Contraindications
Children under 2 years
Uncontrolled systemic infection
Breastfeeding
Pregnancy
Precautions and Warnings
Elderly
Females of childbearing potential
History of recurrent infection
Predisposition to infection
Hepatic impairment
Renal impairment - glomerular filtration rate below 20ml/minute
Live virus vaccine should not be given for 3 months after treatment
Sodium content of formulation may be significant
Before starting therapy ensure immunisations are up to date in children
Exclude hepatitis prior to therapy
Monitor patients for non-melanoma skin cancer prior to and during treatment
Not all available products are licensed for all age groups
Not all presentations are licensed for all indications
Prior to starting therapy screen for latent tuberculosis
Treat and control infections prior to commencing therapy
Treatment to be initiated and supervised by a specialist
Monitor closely any patient who develops new infection while on treatment
Monitor patient constantly for signs of new infection
Discontinue if a serious infection develops
May affect immune response to live vaccines
May affect glucose tests
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue if serious allergic or anaphylactic reaction occurs
Female: Contraception required during and for 14 weeks after treatment
Abatacept is not recommended for use in combination with TNF antagonists. While transitioning from TNF antagonists therapy to abatacept therapy, patients should be monitored for signs of infection.
Co-administration of abatacept with biologic immunosuppressive or immunomodulatory agents could potentiate the effects of abatacept on the immune system.
Patients with juvenile idiopathic arthritis should be brought up to date with all immunisations in agreement with current immunisation guidelines prior to initiating abatacept therapy.
Glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) based glucose monitoring systems may react with the maltose present in abatacept infusion resulting in falsely elevated blood glucose readings on the day of infusion. Patients that require blood glucose monitoring should be advised to consider methods that do not react with maltose such as those based on glucose dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase, or glucose hexokinase test methods.
Pregnancy and Lactation
Pregnancy
Abatacept is contraindicated during pregnancy.
The manufacturer recommends abatacept is not used during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus. The manufacturer recommends that women of child bearing potential use effective contraception during treatment and up to 14 weeks after the last dose of abatacept.
Animal studies have shown teratogenic effects at high doses. At the time of writing there is limited human data and as such a potential risk cannot be ruled out.
Briggs (2015) notes that some sources recommend discontinuing treatment 10 to 18 weeks before pregnancy.
Abatacept crosses the human placenta despite its high molecular weight and may transfer into the serum of infants born to women treated with abatacept during pregnancy. Consequently, these infants may be at increased risk of infection.
The safety of administering live vaccines to infants exposed to abatacept in utero is unknown. Administration of live vaccines to infants exposed to abatacept in utero is not recommended for 14 weeks following the mother's last exposure to abatacept during pregnancy.
Lactation
Abatacept is contraindicated during breastfeeding.
The manufacturer recommends that breastfeeding should be discontinued during treatment with abatacept and for up to 14 weeks after the last dose of abatacept treatment.
Animal studies indicate that abatacept is excreted in the breast milk.
Although the molecular weight is high, excretion into breast milk is a possibility, especially because of the long elimination half life. However, the amount in human milk and the systemic bioavailability are unknown. The effects of this exposure on a nursing infant are also unknown, but the potential for adverse effects on an infants developing immune system should be considered (Briggs, 2015).
Side Effects
Abdominal pain
Abnormal liver function tests
Abscess
Acne
Alopecia
Amenorrhoea
Anaphylaxis
Anxiety
Aphthous stomatitis
Arthralgia
Asthenia
Bacteraemia
Basal cell carcinoma
Bradycardia
Bronchitis
Bronchospasm
Bruising
Conjunctivitis
Cough
Depression
Dermatitis
Diarrhoea
Dizziness
Dry eyes
Dry skin
Dyspepsia
Dyspnoea
Ear infection
Erythema
Exacerbation of obstructive pulmonary disease
Fatigue
Flushing
Fungal infection
Gastritis
Gastro-intestinal infection
Headache
Herpes simplex
Herpes zoster
Hot flushes
Hyperhidrosis
Hypersensitivity reactions
Hypertension
Hypotension
Increase in serum transaminases
Increased susceptibility and severity of infections
Infected skin ulcer
Influenza
Influenza-like syndrome
Injection site reactions
Leukopenia
Lower respiratory tract infection
Lymphoma
Menorrhagia
Migraine
Mouth ulcers
Nasopharyngitis
Nausea
Painful extremities
Palpitations
Paraesthesia
Pelvic inflammatory disease
Pharyngitis
Pneumonia
Pruritus
Psoriasis
Pyelonephritis
Pyrexia
Rash
Reduced visual acuity
Rhinitis
Sepsis
Sinusitis
Skin carcinoma
Skin papilloma
Sleep disturbances
Squamous cell carcinoma
Tachycardia
Throat tightness
Thrombocytopenia
Tooth infection
Tracheitis
Upper respiratory tract infection
Urinary tract infections
Urticaria
Vasculitis
Vertigo
Vomiting
Weight gain
Wheezing
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: May 2019
Reference Sources
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: Orencia 250mg powder for concentrate for solution for infusion. Bristol-Myers Squibb Pharmaceuticals Limited. Revised April 2019.
Summary of Product Characteristics: Orencia 50mg solution for injection (pre-filled syringe). Bristol-Myers Squibb Pharmaceuticals Limited. Revised April 2019.
Summary of Product Characteristics: Orencia 87.5mg solution for injection (pre-filled syringe). Bristol-Myers Squibb Pharmaceuticals Limited. Revised April 2019.
Summary of Product Characteristics: Orencia 125mg solution for injection (pre-filled syringe). Bristol-Myers Squibb Pharmaceuticals Limited. Revised April 2019.
Summary of Product Characteristics: Orencia 125mg solution for injection in pre-filled pen. Bristol-Myers Squibb Pharmaceuticals Limited. Revised April 2019.
The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.
NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 24 May 2019
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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