Drugs List

Therapeutic Indications

Uses

Renal transplant rejection - prevention

Prophylaxis of graft rejection in adults receiving a renal transplant in combination with corticosteroids and mycophenolic acid. The manufacturer recommends the addition of an interleukin-2 receptor antagonist for induction therapy.

Administration

For intravenous infusion over 30 minutes.

Infusion of the first dose should be given in the immediate preoperative period or during surgery, but before completion of the vascular anastomoses.

Contraindications

Children under 18 years
EBV-VCA-sero negative patients
Breastfeeding
Pregnancy

Precautions and Warnings

Cytomegalovirus infection
Females of childbearing potential
Panel reactive antibody titres >30%
Latent or healed tuberculosis
Liver transplant

Administration of live vaccines is not recommended
Cytomegalovirus prophylaxis recommended for 3 months following transplant
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Consider prophylactic anti-tuberculosis therapy if appropriate
Pneumocystis prophylaxis recommended for at least 6 months post transplant
Prior to starting therapy screen for latent tuberculosis
Treatment to be initiated and supervised by a specialist
Do not give other medication through the same intravenous line
Record name and batch number of administered product
Ensure patient EBV seropositive before starting treatment
Consider immunosuppressant adjustment in the event of PML
Consider PTLD or PML if new or worsening neurological symptoms occur
Advise patient to report headaches, seizures, confusion, visual disturbance
Oversuppression of immune system may increase susceptibility to infection
Risk of developing lymphoproliferative disorders
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue if serious allergic or anaphylactic reaction occurs
Female: Contraception required during and for 2 months after treatment
Advise patient on appropriate sun protection methods
Advise patient to avoid exposure to sunlight and UV rays during treatment

Patients receiving belatacept therapy are at an increased risk of post-transplant lymphoproliferative disorder (PTLD). Risk factors for PTLD include cytomegalovirus (CMV), T-cell depleting therapy and negative Epstein-Barr virus (EBV) serostatus. PTLD should be considered in patients with new or worsening neurologic, cognitive or behavioural symptoms.

Progressive multifocal leukoencephalopathy syndrome (PML) has been reported in some patients treated with this agent. If patients present with symptoms indicating PML such as worsening neurological, cognitive or behavioural signs or symptoms, an MRI should be performed. If PML is diagnosed, reduction or withdrawal of immunosuppression is recommended taking into account risk to the graft. Plasmapheresis may accelerate removal of belatacept when reduction of immunosuppression is required.

Increased mortality has been observed in liver transplant patients receiving belatacept.

The half-life of belatacept (8 to 10 days) should be taken into consideration when switching from belatacept to another immunosuppressant to avoid potential under or over immunosuppression.

Pregnancy and Lactation

Pregnancy

Belatacept is contraindicated in pregnancy.

Belatacept should be avoided in pregnancy unless clearly necessary due to limited data concerning its safety, although animal studies do not indicate harmful effects to foetal development. A pre and postnatal development study in rats observed limited immune function changes at 19 fold the typical human dose of 10 mg/kg.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Belatacept is contraindicated in breastfeeding.

Data is limited concerning whether belatacept is excreted in human milk, however animal studies in rats show excretion of belatacept in milk. Women should not breastfeed while treated with belatacept.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abnormal liver function tests
Acidosis
Adrenal suppression
Alkalosis
Anaemia
Anaphylaxis
Anxiety
Attention disturbances
Blood dyscrasias
Blood pressure changes
Breast changes
Burning sensation
Cardiac arrhythmias
Cardiac disorders
Cardiac failure
Cerebrovascular accident
Cervical dysplasia
Cognitive impairment
Convulsions
Cough
Cushingoid changes
Decreased appetite
Decreased blood glucose
Dehydration
Demyelinating disorders
Depression
Diabetes mellitus
Dream abnormalities
Dysgeusia
Dyslipidaemia
Dysphonia
Dyspnoea
Dysuria
Electrolyte disturbances
Encephalopathy
Eye disorder
Facial palsy
Fluid retention
Gastro-intestinal symptoms
Graft dysfunction
Haematoma
Haematuria
Haemolysis
Haemoptysis
Hair growth abnormal
Headache
Hemiparesis
Hepatic disorders
Hernia
Hypercoagulability of the blood
Hypoacusis
Hypocapnia
Hypogammaglobulinaemia
Hypoproteinaemia
Impaired healing
Increase in prostate specific antigen (PSA)
Increased libido
Increased sweating
Increased uric acid level
Infections
Infertility
Infusion-related symptoms
Insomnia
Intermittent claudication
Ketoacidosis
Leukopenia
Local reaction at injection site
Lymphocele
Malaise
Migraine
Mood changes
Musculoskeletal disturbances
Neoplasms
Neuropathy
Oedema
Pain
Pancreatitis
Paraesthesia
Possible alteration in tests for parathyroid function
Progressive multifocal leukoencephalopathy (PML)
Pyrexia
Raised C-reactive protein
Raised intracranial pressure
Renal disorders
Respiratory disorders
Restless legs
Serum creatinine increased
Shock
Skin disorder
Syncope
Tendon rupture
Thrombosis
Tinnitus
Urinary abnormalities
Urinary dysfunction
Vascular disorders
Vertigo
Visual disturbances
Weight changes

Presentation

Infusions containing belatacept

These products have been produced by recombinant technology using Chinese Hamster Ovary (CHO) cell lines.

Drugs List

Therapeutic Indications

Uses

Renal transplant rejection - prevention

Prophylaxis of graft rejection in adults receiving a renal transplant in combination with corticosteroids and mycophenolic acid. The manufacturer recommends the addition of an interleukin-2 receptor antagonist for induction therapy.

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local protocols for the relevant indication should be consulted.

Adults

Additional Dosage Information

Administration

For intravenous infusion over 30 minutes.

Infusion of the first dose should be given in the immediate preoperative period or during surgery, but before completion of the vascular anastomoses.

Contraindications

Children under 18 years
EBV-VCA-sero negative patients
Breastfeeding
Pregnancy

Precautions and Warnings

Cytomegalovirus infection
Females of childbearing potential
Panel reactive antibody titres >30%
Latent or healed tuberculosis
Liver transplant

Administration of live vaccines is not recommended
Cytomegalovirus prophylaxis recommended for 3 months following transplant
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Consider prophylactic anti-tuberculosis therapy if appropriate
Pneumocystis prophylaxis recommended for at least 6 months post transplant
Prior to starting therapy screen for latent tuberculosis
Treatment to be initiated and supervised by a specialist
Do not give other medication through the same intravenous line
Record name and batch number of administered product
Ensure patient EBV seropositive before starting treatment
Consider immunosuppressant adjustment in the event of PML
Consider PTLD or PML if new or worsening neurological symptoms occur
Advise patient to report headaches, seizures, confusion, visual disturbance
Oversuppression of immune system may increase susceptibility to infection
Risk of developing lymphoproliferative disorders
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue if serious allergic or anaphylactic reaction occurs
Female: Contraception required during and for 2 months after treatment
Advise patient on appropriate sun protection methods
Advise patient to avoid exposure to sunlight and UV rays during treatment

Patients receiving belatacept therapy are at an increased risk of post-transplant lymphoproliferative disorder (PTLD). Risk factors for PTLD include cytomegalovirus (CMV), T-cell depleting therapy and negative Epstein-Barr virus (EBV) serostatus. PTLD should be considered in patients with new or worsening neurologic, cognitive or behavioural symptoms.

Progressive multifocal leukoencephalopathy syndrome (PML) has been reported in some patients treated with this agent. If patients present with symptoms indicating PML such as worsening neurological, cognitive or behavioural signs or symptoms, an MRI should be performed. If PML is diagnosed, reduction or withdrawal of immunosuppression is recommended taking into account risk to the graft. Plasmapheresis may accelerate removal of belatacept when reduction of immunosuppression is required.

Increased mortality has been observed in liver transplant patients receiving belatacept.

The half-life of belatacept (8 to 10 days) should be taken into consideration when switching from belatacept to another immunosuppressant to avoid potential under or over immunosuppression.

Pregnancy and Lactation

Pregnancy

Belatacept is contraindicated in pregnancy.

Belatacept should be avoided in pregnancy unless clearly necessary due to limited data concerning its safety, although animal studies do not indicate harmful effects to foetal development. A pre and postnatal development study in rats observed limited immune function changes at 19 fold the typical human dose of 10 mg/kg.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Belatacept is contraindicated in breastfeeding.

Data is limited concerning whether belatacept is excreted in human milk, however animal studies in rats show excretion of belatacept in milk. Women should not breastfeed while treated with belatacept.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abnormal liver function tests
Acidosis
Adrenal suppression
Alkalosis
Anaemia
Anaphylaxis
Anxiety
Attention disturbances
Blood dyscrasias
Blood pressure changes
Breast changes
Burning sensation
Cardiac arrhythmias
Cardiac disorders
Cardiac failure
Cerebrovascular accident
Cervical dysplasia
Cognitive impairment
Convulsions
Cough
Cushingoid changes
Decreased appetite
Decreased blood glucose
Dehydration
Demyelinating disorders
Depression
Diabetes mellitus
Dream abnormalities
Dysgeusia
Dyslipidaemia
Dysphonia
Dyspnoea
Dysuria
Electrolyte disturbances
Encephalopathy
Eye disorder
Facial palsy
Fluid retention
Gastro-intestinal symptoms
Graft dysfunction
Haematoma
Haematuria
Haemolysis
Haemoptysis
Hair growth abnormal
Headache
Hemiparesis
Hepatic disorders
Hernia
Hypercoagulability of the blood
Hypoacusis
Hypocapnia
Hypogammaglobulinaemia
Hypoproteinaemia
Impaired healing
Increase in prostate specific antigen (PSA)
Increased libido
Increased sweating
Increased uric acid level
Infections
Infertility
Infusion-related symptoms
Insomnia
Intermittent claudication
Ketoacidosis
Leukopenia
Local reaction at injection site
Lymphocele
Malaise
Migraine
Mood changes
Musculoskeletal disturbances
Neoplasms
Neuropathy
Oedema
Pain
Pancreatitis
Paraesthesia
Possible alteration in tests for parathyroid function
Progressive multifocal leukoencephalopathy (PML)
Pyrexia
Raised C-reactive protein
Raised intracranial pressure
Renal disorders
Respiratory disorders
Restless legs
Serum creatinine increased
Shock
Skin disorder
Syncope
Tendon rupture
Thrombosis
Tinnitus
Urinary abnormalities
Urinary dysfunction
Vascular disorders
Vertigo
Visual disturbances
Weight changes

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: August 2015

Reference Sources

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press Accessed on 13 August 2015.

Summary of Product Characteristics: Nulojix 250mg powder for concentrate for solution for infusion. Bristol-Myers Squibb Pharma EEIG. Revised January 2022.