Calcineurin inhibitors

For ciclosporin eye preparations, please see section 11.4.2 Other anti-inflammatory preparations

Ciclosporin

• Capimune capsules 25mg, 50mg, 100mg (University Hospitals Plymouth NHS Trust Dermatology patients only) (£25.50 = 50mg x 30 capsules)
• Neoral capsules 10mg, 25mg, 50mg, 100mg (£35.97 = 50mg x 30 capsules)
• Neoral oral solution sugar free 100mg/1ml (£102.30 = 50ml)
• Sandimmun concentrate for solution for IV infusion 50mg/1ml, 250mg/5ml

Notes

1. West Devon: refer to individual shared care guidelines for use in Rheumatology and Dermatology conditions
   1. The prescribing of ciclosporin for all transplant-related care has been repatriated to secondary care.
2. South Devon: refer to individual shared care guidelines for use in Gastroenterology, Ophthalmology, Respiratory, and Rheumatology conditions
3. Prescribe by brand. Patients should be stabilised on a particular brand of ciclosporin because there are differences in bioavailability between products and switching between formulations without close monitoring may lead to clinically important changes in blood-ciclosporin concentration
4. Transplant patients - ciclosporin levels may be done locally (Torbay laboratory passes work on to Plymouth or Exeter) but for consistency of results it is better to send them to original treatment centre

For tacrolimus skin preparations, please see section 13.5.1 Preparations for eczema

Tacrolimus

• Immediate-release capsules:
  • Adoport capsules 500micrograms, 750micrograms, 1mg, 2mg, 5mg (£42.92 = 500micrograms x 50 capsules)
  • Prograf capsules 500micrograms, 1mg, 5mg (£61.88 = 500micrograms x 50 capsules)
• Immediate-release oral suspension:
  • Modigraf granules sachets 0.2mg, 1mg
• Modified-release capsules:
  • Advagraf modified-release capsules 500micrograms, 1mg, 3mg, 5mg
• Modified-release tablets:
  • Envarsus modified-release tablets 750micrograms, 1mg, 4mg
• Solution for infusion:
  • Prograf solution for infusion 5mg/1ml

Notes

1. Prescribe by brand. To ensure maintenance of therapeutic response when a patient is stabilised on a particular brand, oral tacrolimus products should be prescribed and dispensed by brand name only. See MHRA Drug Safety Update below.
2. Switching between tacrolimus brands requires careful supervision andtherapeutic monitoring by an appropriate specialist.
   1. Envarsus is not interchangeable with other oral tacrolimus containing products
3. Advagraf is included for use in liver transplant patient only.
4. Cardiomyopathy has been reported to occur primarily in children with tacrolimus blood trough concentrations much higher than the recommended maximum levels. Patients should be monitored by echocardiography for hypertrophic changes—consider dose reduction or discontinuation if these occur.
5. NICE TA481: Immunosuppressive therapy for kidney transplant in adults (October 2017)
   1. Immediate-release tacrolimus (Adoport, Capexion, Modigraf, Prograf, Tacni, Vivadex), when used as part of an immunosuppressive regimen, is recommended as an initial option to prevent organ rejection in adults having a kidney transplant
   2. Prolonged-release tacrolimus (Advagraf, Envarsus) is not recommended as an initial option to prevent organ rejection in adults having a kidney transplant
6. NICE TA482: Immunosuppressive therapy for kidney transplant in children and young people (October 2017):
   1. Immediate-release tacrolimus (Adoport, Capexion, Modigraf, Prograf, Tacni, Vivadex), when used as part of an immunosuppressive regimen, is recommended as an initial option to prevent organ rejection in children and young people having a kidney transplant
   2. Prolonged-release tacrolimus (Advagraf, Envarsus) isnot recommended as an initial option to prevent organ rejection inchildren and young people having a kidney transplant
7. Capexion capsules, Tacni capsules, and Vivadex capsules are discontinued.
8. MHRA Drug Safety Update (November 2017): Oral tacrolimus products: prescribe and dispense by brand name only, to minimise the risk of inadvertent switching between products, which has been associated with reports of toxicity and graft rejection

Voclosporin

• Capsules 7.9mg

Notes

1. NICE TA882: Voclosporin (Lupkynis) with mycophenolate mofetil is recommended, within its marketing authorisation, as an option for treating active class 3 to 5 (including mixed class 3 and 5, and 4 and 5) lupus nephritis in adults, only if the company provides it according to the commercial arrangement (May 2023).

Interleukin inhibitors

Basiliximab

• Powder and solvent for solution for injection vials 10mg, 20mg

Notes

1. NICE TA481: Basiliximab (Simulect), when used as part of an immunosuppressive regimen that includes a calcineurin inhibitor, is recommended as an initial option to prevent organ rejection in adults having a kidney transplant (October 2017).
2. NICE TA482: Basiliximab (Simulect), when used as part of an immunosuppressive regimen that includes a calcineurin inhibitor, is recommended as an initial option to prevent organ rejection in children and young people having a kidney transplant (October 2017).
3. MHRA Drug Safety Update (October 2014): Basiliximab (Simulect): indicated for renal transplantation only; efficacy and safety not shown in heart transplantation.

Secukinumab

• Solution for injection pre-filled pens 150mg/1ml, 300mg/2ml
• Solution for injection pre-filled syringes 150mg/1ml

Notes

1. NICE TA350: Secukinumab (Cosentyx) is recommended as an option for treating moderate to severe plaque psoriasis (July 2015), only when:
   1. the disease is severe, as defined by a total Psoriasis Area Severity Index (PASI) of 10 or more and a Dermatology Life Quality Index (DLQI) of more than 10
   2. the disease has failed to respond to standard systemic therapies, for example, ciclosporin, methotrexate and PUVA (psoralen and long‑wave ultraviolet radiation), or these treatments are contraindicated, or the person cannot tolerate them
   3. the company provides secukinumab with the discount agreed in the patient access scheme.
   4. Refer to TA350 for continuation criteria and other considerations.
2. NICE TA407: Secukinumab (Cosentyx) is recommended as an option for treating active ankylosing spondylitis in adults whose disease has responded inadequately to conventional therapy (non-steroidal anti-inflammatory drugs or TNF-alpha inhibitors), only if the company provides it with the discount agreed in the patient access scheme (September 2016). 
3. NICE TA719: Secukinumab (Cosentyx) is recommended as an option for treating active non-radiographic axial spondyloarthritis with objective signs of inflammation (shown by elevated C-reactive protein or MRI) that is not controlled well enough with non-steroidal anti-inflammatory drugs (NSAIDs) in adults (July 2021). It is recommended only if:
   1. tumour necrosis factor (TNF)-alpha inhibitors are not suitable or do not control the condition well enough and
   2. the company provides secukinumab according to the commercial arrangement.
   3. Refer to TA719 for continuation criteria and other considerations.
4. NICE TA445: Secukinumab (Cosentyx) alone, or in combination with methotrexate, is recommended as an option for treating active psoriatic arthritis in adults (May 2017), only if:
   1. it is used as described in the NICE technology appraisal guidance on etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis or
   2. the person has had a TNF‑alpha inhibitor but their disease has not responded within the first 12 weeks or has stopped responding after 12 weeks or
   3. TNF‑alpha inhibitors are contraindicated but would otherwise be considered (as described in NICE technology appraisal guidance on etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis), and
   4. the company provides it as agreed in the patient access scheme.
   5. Refer to TA445 for continuation criteria and other considerations.
5. NICE TA734: Secukinumab (Cosentyx) is recommended as an option for treating plaque psoriasis in children and young people aged 6 to 17 years (October 2021), only if:
   1. the disease is severe, as defined by a total Psoriasis Area and Severity Index (PASI) of 10 or more and
   2. the disease has not responded to other systemic treatments, including ciclosporin, methotrexate and phototherapy, or these options are contraindicated or not tolerated and
   3. the company provides the drug according to the commercial arrangement.
   4. Refer to TA734 for continuation criteria and other considerations.
6. NICE TA935: Secukinumab (Cosentyx) is recommended as an option for treating active moderate to severe hidradenitis suppurativa (acne inversa) in adults when it has not responded well enough to conventional systemic treatment (December 2023), only if:
   1. adalimumab is not suitable, did not work or has stopped working and
   2. the company provides it according to the commercial arrangements.
   3. Refer to TA935 for continuation criteria and other considerations.

Selective immunosuppressants

CellCept

(Mycophenolate mofetil)

• Capsules 250mg (£82.26 = 100 capsules)
• Tablets 500mg (£82.26 = 50 tablets)
• Oral suspension sugar free 1g/5ml (£115.16 = 175ml)
• Powder for solution for infusion 500mg (£9.12 x 1 vial)

Notes

1. Prescribe by brand
2. West Devon: refer to individual shared care guidelines for use in Rheumatology, or Dermatology conditions
3. South Devon: Mycophenolate is restricted to hospital only prescribing unless an exceptional arrangement to prescribe is agreed by the GP and specialist as being in the best interest of the patient
4. The prescribing of mycophenolate mofetil for the prevention of rejection in renal transplant patients has been repatriated to secondary care.
5. Mycophenolate mofetil has been used by the gastroenterologists for resistant Crohn's disease in patients unable to tolerate alternative immunosuppressants (unlicensed indication). It is not recommended for GP prescribing for this indication.
6. NICE TA481: Mycophenolate mofetil (Cellcept and non-branded versions), when used as part of an immunosuppressive regimen, is recommended as an initial option to prevent organ rejections in adults having a kidney transplant. (October 2017).
7. NICE TA482: Mycophenolate mofetil (Cellcept and non-branded versions), when used as part of an immunosuppressive regimen, is recommended as an initial option to prevent organ rejections in children and young people having a kidney transplant. (October 2017).
8. MHRA Drug Safety Update (January 2015): When using mycophenolate mofetil or any other medicine containing mycophenolic acid (MPA) as its active ingredient:
   1. Measure serum immunoglobulin levels if recurrent infections develop
   2. In cases of sustained, clinically relevant hypogammaglobulinaemia, consider appropriate clinical action. Take into account the potent cytostatic effects of MPA on B-lymphocytes and T-lymphocytes
   3. Consider bronchiectasis or pulmonary fibrosis if patients develop persistent respiratory symptoms, such as cough and dyspnoea
9. MHRA Drug Safety Update (December 2015): Mycophenolate mofetil, mycophenolic acid: new pregnancy-prevention advice for women and men and MHRA Drug Safety Update (February 2018): Mycophenolate mofetil, mycophenolic acid: updated contraception advice for male patients, and reminder for healthcare professionals prescribing mycophenolate to female patients. Please refer to the update for information.
   1. See also resources for: contraception for drugs with teratogenic potential, and prescribing in pregnancy and lactation

Myfortic

(Mycophenolic acid)

• Gastro-resistant tablets 180mg, 360mg (£96.72 = 180mg x 120 tablets)

Notes

1. Prescribe by brand
2. The prescribing of mycophenolic acid for the prevention of rejection in renal transplant patients has been repatriated to secondary care.
3. NICE TA481: Mycophenolate sodium (Myfortic, Ceptava) is not recommended as an initial option to prevent organ rejections in adults having a kidney transplant (October 2017).
4. NICE TA482: Mycophenolate sodium (Myfortic, Ceptava) is not recommended as an initial option to prevent organ rejections in children and young people having a kidney transplant (October 2017).
5. MHRA Drug Safety Update (January 2015): When using mycophenolate mofetil or any other medicine containing mycophenolic acid (MPA) as its active ingredient:
   1. Measure serum immunoglobulin levels if recurrent infections develop
   2. In cases of sustained, clinically relevant hypogammaglobulinaemia, consider appropriate clinical action. Take into account the potent cytostatic effects of MPA on B-lymphocytes and T-lymphocytes
   3. Consider bronchiectasis or pulmonary fibrosis if patients develop persistent respiratory symptoms, such as cough and dyspnoea.
6. MHRA Drug Safety Update (December 2015): Mycophenolate mofetil, mycophenolic acid: new pregnancy-prevention advice for women and men and MHRA Drug Safety Update (February 2018): Mycophenolate mofetil, mycophenolic acid: updated contraception advice for male patients, and reminder for healthcare professionals prescribing mycophenolate to female patients. Please refer to the update for information.
   1. See also resources for: contraception for drugs with teratogenic potential, and prescribing in pregnancy and lactation.

Sirolimus

• Tablets 500micrograms, 1mg, 2mg (£86.49 = 1mg x 30 tablets)
• Oral solution sugar free 1mg/1ml (£162.41 = 60ml)

Notes

1. NICE TA481:Sirolimus (Rapamune), is not recommended as an initial option to prevent organ rejection in adults having a kidney transplant (October 2017).
2. NICE TA482: Sirolimus (Rapamune), is not recommended as an initial option toprevent organ rejection in children and young people having a kidney transplant (October 2017).
3. MHRA Drug Safety Update (December 2014): Sirolimus: different immunoassays for therapeutic drug monitoring—risk of incorrect dose adjustment.

Abrocitinib

• Tablets 50mg, 100mg, 200mg

Notes

1. NICE TA814: Abrocitinib, tralokinumab or upadacitinib for treating moderate to severe atopic dermatitis (August 2022):
   1. Abrocitinib (Cibinqo) is recommended as an option for treating moderate to severe atopic dermatitis that is suitable for systemic treatment in adults and young people 12 years and over, only if:
      • the disease has not responded to at least 1 systemic immunosuppressant, or these are not suitable
      • the companies provide abrocitinib according to the commercial arrangement.
   2. Refer to TA814 for continuation criteria and other considerations.

Avacopan

• Capsules 10mg

Notes

1. NICE TA825: Avacopan (Tavneos) with a cyclophosphamide or rituximab regimen is recommended, within its marketing authorisation, as an option for treating severe active granulomatosis with polyangiitis or microscopic polyangiitis in adults, only if the company provides it according to the commercial arrangement (September 2022).

Belatacept

• Powder for solution for infusion vials 250mg

Notes

1. NICE TA481 and NICE TA482: Belatacept, is not recommended as an initial option to prevent organ rejection in children, young people, and adults having a kidney transplant (October 2017).

Belimumab

• Powder for solution for infusion vials 120mg, 400mg
• Solution for injection pre-filled pens 200mg/1ml
• Solution for injection pre-filled syringes 200mg

Notes

1. NICE TA752: Belimumab (Benlysta) is recommended as an option as add-on treatment for active autoantibody-positive systemic lupus erythematosus in people with high disease activity despite standard treatment (December 2021), only if:
   1. high disease activity is defined as at least 1 serological biomarker (positive anti-double-stranded DNA or low complement) and a SELENA-SLEDAI score of greater than or equal to 10
   2. treatment is continued beyond 24 weeks only if the SELENA-SLEDAI score has improved by 4 points or more
   3. the company provides belimumab according to the commercial arrangement.
2. MHRA Drug Safety Update (April 2019): Belimumab (Benlysta): increased risk of serious psychiatric events seen in clinical trials.

Belumosudil

• Tablets 200mg

Notes

1. NICE TA949: Belumosudil (Rezurock) is recommended, within its marketing authorisation, for treating chronic graft-versus-host disease in people 12 years and over after 2 or more systemic treatments, only if the company provides it according to the commercial arrangement (February 2024).

Dimethyl fumarate

• Gastro-resistant capsules 120mg, 240mg
• Gastro-resistant tablets 30mg, 120mg

Notes

1. NICE TA320: Dimethyl fumarate (Tecfidera) is recommended as an option for treating adults with active relapsing-remitting multiple sclerosis (normally defined as 2 clinically significant relapses in the previous 2 years), only when the criteria of the NICE TA are met (August 2014).
2. MHRA Drug Safety Update (January 2021): Dimethyl fumarate (Tecfidera): updated advice on the risk of progressive multifocal leukoencephalopathy (PML) associated with mild lymphopenia.
3. NICE TA475: Dimethyl fumarate (Skilarence) is recommended as an option for treating moderate to severe plaque psoriasis, only when the criteria of the NICE TA are met (September 2017).

Diroximel fumarate

• Gastro-resistant capsules 231mg

Notes

1. NICE TA794: Diroximel fumarate (Vumerity) is recommended as an option for treating active relapsing–remitting multiple sclerosis (normally defined as 2 clinically significant relapses in the previous 2 years) in adults (June 2022), only if:
   1. they do not have highly active or rapidly evolving severe relapsing–remitting multiple sclerosis and
   2. the company provides diroximel fumarate according to the commercial arrangement.

Fingolimod

• Capsules 500micrograms

Notes

1. NICE TA254 Fingolimod for the treatment of highly active relapsing–remitting multiple sclerosis (April 2012).
2. MHRA Drug Safety Update (January 2013) - Fingolimod: bradycardia and heart block – repeat enhanced cardiovascular monitoring when restarting fingolimod after treatment interruption. Starting fingolimod treatment, or re-starting fingolimod after treatment interruption, results in transient decreases in heart rate. In some patients it can also cause transient bradycardias and heart block. This risk is minimised through enhanced monitoring.
3. MHRA Drug Safety Update (September 2019): Fingolimod (Gilenya): increased risk of congenital malformations; new contraindication during pregnancy and in women of childbearing potential not using effective contraception
   1. Management of women of childbearing potential before and during fingolimod treatment
      • advise women that fingolimod increases the risk of congenital abnormalities and provide them with the new pregnancy-specific patient reminder card
      • exclude pregnancy before starting fingolimod and repeat pregnancy testing at suitable intervals during treatment (depending on contraceptive used and personal circumstance – see update for guidance)
      • ensure that an effective form of contraception is used during treatment and for 2 months after discontinuation
      • stop fingolimod 2 months before a pregnancy is planned and consider alternative treatments
   2. Management if pregnancy exposed
      • should a woman on fingolimod become pregnant, stop treatment immediately and refer to an obstetrician for close monitoring during pregnancy, including ultrasound assessments
   3. See also resources for: contraception for drugs with teratogenic potential, and prescribing in pregnancy and lactation.
4. MHRA Drug Safety Update (January 2021): Fingolimod (Gilenya): updated advice about the risks of serious liver injury and herpes meningoencephalitis
   1. Liver monitoring requirements and discontinuation criteria for fingolimod have been updated following reports of serious liver injury.
   2. Fatal cases of encephalitis and meningitis caused by herpes simplex and varicella zoster viruses have also been reported during treatment.
   3. Advise patients to seek urgent medical attention if they develop any clinical features of liver dysfunction or meningoencephalitis. Discontinue fingolimod if significant hepatic injury or herpes meningoencephalitis is confirmed.

Imlifidase

• Powder for solution for infusion vials 11mg

Notes

1. NICE TA809: Imlifidase (Idefirix) is recommended as a desensitisation treatment option for adults (July 2022) who are waiting for a kidney transplant from a deceased donor, are highly sensitised to human leukocyte antigens (HLA), or have a positive crossmatch with the donor and are unlikely to have a transplant under the available kidney allocation system (including prioritisation programmes for highly sensitised people). It is recommended only if:
   1. a maximum of 1 dose is given
   2. it is given in a specialist centre with experience of treating high sensitisation to HLA
   3. the company provides it according to the commercial arrangement.

Natalizumab

• Solution for infusion vials 300mg/15ml
• Solution for injection pre-filled syringes 150mg/1ml

Notes

1. NICE TA127: Natalizumab (branded or biosimilar) is recommended as an option for the treatment only of rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS) in adults; defined by 2 or more relapses in the previous year, and baseline MRI evidence of disease activity (August 2007).

Ozanimod

• Capsules 230micrograms, 460micrograms, 920micrograms

Notes

1. NICE TA828: Ozanimod (Zeposia) is recommended as an option for treating moderately to severely active ulcerative colitis in adults (October 2022), only if:
   1. conventional treatment cannot be tolerated or is not working well enough and infliximab is not suitable, or
   2. biological treatment cannot be tolerated or is not working well enough, and
   3. the company provides it according to the commercial arrangement.
2. NICE TA706: Ozanimod (Zeposia) is not recommended, within its marketing authorisation, for treating relapsing–remitting multiple sclerosis in adults with clinical or imaging features of active disease (June 2021).

Ponesimod

• Tablets 20mg
• Treatment initiation pack (contains 2 x 2mg tablets, 2 x 3mg tablets, 2 x 4mg tablets, 1 x 5mg tablet, 1 x 6mg tablet, 1 x 7mg tablet, 1 x 8mg tablet, 1 x 9mg tablet and 3 x 10mg tablets)

Notes

1. NICE TA767: Ponesimod (Ponvory) is recommended for treating relapsing–remitting multiple sclerosis with active disease defined by clinical or imaging features in adults, only if the company provides ponesimod according to the commercial arrangement (February 2022).

Siponimod

• Tablets 2mg

Notes

1. NICE TA656: Siponimod (Mayzent) is recommended, within its marketing authorisation, as an option for treating secondary progressive multiple sclerosis with evidence of active disease (that is, relapses or imaging features of inflammatory activity) in adults only if the company provides siponimod according to the commercial arrangement (November 2020).
2. Siponimod is predicted by the manufacturer to increase the risk of QT prolongation, and therefore concurrent use alongside drugs that prolong the QT interval should be avoided.

Teriflunomide

• Tablets 14mg

Notes

1. NICE TA303: Teriflunomide recommended for treating relapsing–remitting multiple sclerosis (January 2014).

Other immunosuppressants

Azathioprine

• Tablets 25mg, 50mg (£1.52 = 50mg x 56 tablets)
• Oral suspension 50mg/5ml (unlicensed preparation)
  

Indications

• Inflammatory bowel disease
• Rheumatoid arthritis
• Dermatological conditions
• Suppression of transplant rejection

Notes

1. West Devon: refer to individual shared care guidelines for use in Gastroenterology, Rheumatology, Hepatology, or Dermatology conditions.
2. South Devon: refer to shared care guidelines for use in Gastroenterology, Hepatology, Ophthalmology and Respiratory, or Rheumatology conditions.
3. Avoid concomitant use of azathioprine with allopurinol, unless supervised by an appropriate specialist.
4. Monitoring of azathioprine is essential.