Danicopan Administration Guidelines

Danicopan (Voydeya) binds to factor D to prevent alternative pathway-mediated haemolysis and deposition of complement C3 proteins on red blood cells, thereby helping to relieve the symptoms of PNH and improving disease control. Danicopan (Voydeya)is indicated as an add-on to Ravulizumab or Eculizumab/Eculizumab biosimilar for the treatment of adult patients with Paroxysmal Nocturnal Haemoglobinuria (PNH) who have residual haemolytic anaemia.

Danicopan (Voydeya), when added to C5-inhibitor treatment, has the ability to prevent haemolysis and increase haemoglobin levels.

Indications for Treatment with Danicopan (Voydeya)

Adult Patients fulfilling any of the following categories:

On C5 complement inhibitor treatment with clinically significant extravascular haemolysis (EVH) causing ongoing anaemia, and fatigue. Danicopan (Voydeya) as an add on treatment.

1. Clinically significant extravascular haemolysis while on treatment with a complement component 5 inhibitor (C5 inhibitor) and
2. With agreement with Joint Service colleagues at MDT

Risks

Meningococcal / Pneumococcal / Haemophilus Infection.

Meningococcal Infection:

1. Due to its mechanism of action, the use of Danicopan (Voydeya) increases the patient’s susceptibility to meningococcal infection. As this is an add on therapy for to a C5 complement inhibitor this should already be in place for meningococcal prevention. The opportunity should be taken for review of meningococcal vaccination status and antibody response as per PNH prevention protocols.
2. Patients should continue their long-term prophylactic antibiotics: Penicillin V 500mg twice daily for the duration of complement inhibition or if allergic to penicillin erythromycin 500mg twice daily.  Rescue antibiotic: ciprofloxacin 500mg twice daily x 10 days to be kept at home. Patients will contact the PNH team for advice if pyrexial / unwell.
3. Patients should be reminded of the risks and signs and symptoms of possible infection such as a temperature of 38c or above.

Pneumococcal / Haemophilus Infection:

Due to its mechanism of action, the use of Danicopan (Voydeya) potentially increases the patient’s susceptibility to Pneumococcal infection and Haemophilus influenzae type B infection.

All patients must be vaccinated prior to/ on the day of receiving Danicopan (Voydeya) with:

• Prevenar vaccine for Pneumococcal infection
• Menitorix for Haemophilus influenzae type B infection.

If patients have been on another proximal inhibitor such as Pegcetacoplan they may have been previously vaccinated.

Dosage

Danicopan (Voydeya) 150mg three times a days with the option for dose increase to 200mg BD if normalisation of Hb is not achieved after 3 months.

Patients with severe kidney disease: recommended starting dose of Danicopan (Voydeya)  is 100 mg three times a day. Dose increase can be undertaken to 150 mg three times a day.

Administration

Patients should have:

• Pre-treatment bloods taken: FBC, Retics, U&Es, LFTs, LDH, fasting lipids and cholesterol and PNH clone. Please contact PNH team with any concerns.
• Pregnancy test should be performed on females prior to commencement.
• Baseline observations including blood pressure, heart rate, temperature, and oxygen saturations.

First dose should be under nurse supervision. Danicopan (Voydeya) is a gel capsule.

Patient to be monitored for one hour and then post-treatment observations taken.

Dosing:

Initial dose of Danicopan (Voydeya) is three times a day, approximately 8 hours apart (plus or minus 2 hours).

It is possible for the PNH clinician to increase the dose.

Depending on the dose prescribed, the number of tablets per dose is as follows taken with food (meal or snack):

• 100 mg: one 100 mg tablet
• 150 mg: one 50 mg tablet and one 100 mg tablet
• 200 mg: two 100 mg tablets

Patient given contact numbers 0113 2068625/07920535918 and advised to ring with any problems.

Nurse specialist to ring following working day – follow up call.

Review

Nurse follow up in 2 weeks following 1^st dose. If medication tolerated, to send off registration forms and arrange further delivery of supplies.

All patients with PNH on Danicopan (Voydeya) will need clinical review initially at 6 weeks post commencement of medication and at least 3 monthly by the PNH National Service.

Please contact PNH team with any queries

Tel 0113 2068625 Out of hours 07920 535918

Email: pnh.leeds@nhs.net