Table 3 Recommended infusion protocol

Pre-Infusion

Concomitant medication: The evening before the 1st Alemtuzumab infusion for all infusion stages, orally:

   – H1 blockade eg. Cetirizine 1-0-1 (non-sedating H1 antihistamine)

   – H2 blockade eg Ranitidine 300 mg 1-0-1 (H2 receptor antagonist)

   – Herpes prophylaxis eg. Aciclovir 200 mg 1-0-1 (for HSV/VZV prophylaxis; for at least 4 weeks)

Infusion

1st year: infusion 5 days (Mon.-Fri.)

2nd year infusion 3 days (3 consecutive days)

Cardiovascular (BP, heart rate) + Body temperature (1×/30 min) Monitoring

   – 1st day of infusion course: Perform pregnancy test in female patients with childbearing potential

   – Insertion of peripheral permanent port (can also be used for other medications)

   1. 60 min. before Alemtuzumab infusion:

    a) Methylprednisolone 1 g i.v. as short infusion at the first 3 infusion days

    b) Paracetamol 1 g. i.v. as short infusion at all infusion days

   2. Alemtuzumab 12 mg i.v. via infusion pump (12 mg per day on each of 5 (or 3) days), is prepared as ready-to-use solution supply (volume 112 mL). Storage time of the infusion 8 h after preparation.

    - Target infusion period about 4 h (in case of side effects-especially at the start of the infusion-reduction of the infusion speed)

   3. NaCl infusion 100 mL over 30 min (infusion pump), to flush residual medication out of the infusion line (tube)

Also to note:

   – Monitoring until 2 h after infusion

   – Drinking adequate liquids (at least 2 l/d)

   – Availability of trained physician and medical personnel during the entire period of the infusion

Potential acute adverse events

   1. Anaphylaxia/anaphylactic shock (quite rare)

   2. Infusion-associated reactions (IAR):

   – Erythema, urticaria, pruritis, (fever, headache, fatigue)

   – Intensified neurological symptoms (Uhthoff Phenomenon!)

   ➔ STOP infusion and inform physician immediately!

   ➔ Fenistil 1 A (4 mg) i.v.

   ➔ In case of insufficient effect ➔ 250 mg prednisolone i.v.

Depending on severity of the IAR, continue infusion, but more slowly.

Routine follow-up care

   1. Aciclovir 200 mg 1-0-1 for 4 weeks from the first day of the infusion

   2. Antihistamine (e.g. cetirizine 1-0-1) for an additional week

   3. Paracetamol standby (if headache or fever appear)

First check-up appointment MS centre 4 weeks after infusion.

Procedural measures/follow up checks

   – Adequate infection protection including adjusting diet (no cheese from raw milk, raw fish/raw meat)

   – During the infusion course, avoid stomach-irritating foods such as fruit acids, carbonates, sharp or strong-smelling foods, no sodium glutamate-“bland diet”

   – If applicable, safe contraception methods for at least 4 months after the infusion course

   – Due to the known potential side effects, the regimen of follow-up check-ups organised and implemented by the MS centre must be strictly observed

   – Patients are instructed to observe a low threshold for making an acute appointment in case of infections. In this respect, the reduced immune competence and reduced lymphocyte count must be considered, especially in the first months after infusion, and a complete focus screening must be conducted.

   – The patient should be informed of the symptoms of possible side effects (eg. ATP, glomerulonephritis), and should inform the treating physician of them. An early appointment with the physician should also be made in case of infection.