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FILENAME Guidelines for CONTROLLED DOC NO: CCPG(H) C4

Rituximab

Guidelines for the administration of

Rituximab
1. Introduction

Administration of the anti-CD20 monoclonal antibody Rituximab is associated with severe

hypersensitivity reactions, potentially life threatening cytokine release syndrome, and more
rarely anaphylaxis1.

The risk of infusion reactions is greatest during the first exposure to Rituximab, and the
severity of reaction becomes less with subsequent cycles.
In order to reduce the likelihood of reactions occurring, whilst minimising treatment time for
the patient, the following guidelines should be followed.

2. Infusion rates

2.1 For first infusions where the dose of Rituximab is given as a single infusion

The initial infusion is 50mg/hr for the first 90 minutes.

Thereafter the rate should be increased in increments of 50mg/hr at 30 minute intervals.
The maximum rate should not exceed 300mg/hr.

The Rituximab rate calculator should be used to generate the correct infusion volumes,
using the First Infusion rate table.

NB the maximum rate of 300mg/hr is lower than the maximum rate in the SPC for
Rituximab, however this lower infusion rate matches rates used in some clinical trials 1, and
is adopted here as a more cautious approach to avoid infusion reactions.

2.2 For first infusion where the dose of Rituximab is split into two doses on
consecutive days

Day 1 The initial infusion is of 100mg in 100ml 0.9% sodium chloride over 4 hours (i.e. a
rate of 25mg/hr)

The rate calculator should not be used for this infusion

DATE OF ISSUE: 23.12.15 VERSION 2

REVIEWED BY A. BRYAN AUTHORISED BY: Dr J Addada PAGE 1 of 9
REVIEW DATE: 23.06.17

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FILENAME Guidelines for CONTROLLED DOC NO: CCPG(H) C4
Rituximab

Day 2 The remainder of the dose should be given as for first infusions above (i.e 50mg/hr
for 90 minutes, followed by increasing rates at 50mg/hr increments at 30 minutes
intervals, up to a maximum rate of 300mg/hr).

The Rituximab rate calculator should be used to generate the correct infusion volumes for
Day 2 only, using the First Infusion rate table.

2.3 Subsequent infusions

After the first infusion, subsequent infusions can be given at either the Licensed Rate or
the Rapid Rate depending on:

 The treatment regimen being given, and/or the condition being treated
(Section 4)
 Whether the patient had a reaction to the first infusion (Sections 4, 5 and
Appendix).

2.4 Licensed Rate

The initial rate is 100mg/hr over 30 minutes.

Subsequently the infusion should be increased in increments of 50mg/hr at 30 minute
intervals.
The maximum rate should not exceed 400mg/hr.

The Rituximab rate calculator should be used to generate the correct infusion volumes
using the Licensed Rate table.

2.5 Rapid Rate

The initial rate is 20% of the total dose of Rituximab over the first 30 minutes.
The remainder of the infusion (i.e 80% of the dose) should be given over 60 minutes.

The Rituximab rate calculator should be used to generate the correct infusion volumes
using the Rapid Rate table.

DATE OF ISSUE: 23.12.15 VERSION 2

REVIEWED BY A. BRYAN AUTHORISED BY: Dr J Addada PAGE 2 of 9
REVIEW DATE: 23.06.17

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FILENAME Guidelines for CONTROLLED DOC NO: CCPG(H) C4
Rituximab

3. Premedication

3.1 For all patients

All patients should receive premedication with the following:

 Paracetamol 1g oral
 Chlorphenamine 10mg IV bolus
 Hydrocortisone 100mg IV bolus

3.2 Patients receiving regimens containing corticosteroids as part of their

treatment
(e.g. RCHOP, RCVP, REPOCH)

 Patients receiving regimens containing Prednisolone as part of the treatment must

take their first day of corticosteroids (e.g. Prednisolone 100mg) as part of the
premedication

3.3 Patients receiving regimens which do not contain corticosteroids as part of

their treatment
(e.g. FCR, R-Bendamustine, R-Chlorambucil)

 Patients receiving regimens which do not contain corticosteroids should be given

additional premedication in the form of Prednisolone 100mg (or equivalent IV if
unable to tolerate oral medication) prior to their first dose of Rituximab (or both
days if having a split dose).
 This additional premedication can be omitted with subsequent cycles (i.e. from
cycle 2 onwards) provided the patient has not had a severe reaction (Grade 2 or
above) to the first Rituximab infusion.

Premedication must be given at least 30 minutes prior to commencing the

Rituximab infusion.

DATE OF ISSUE: 23.12.15 VERSION 2

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FILENAME Guidelines for CONTROLLED DOC NO: CCPG(H) C4
Rituximab

4. Infusion guidelines for specific regimens

4.1 Patients receiving regimens which do not include high dose corticosteroids as
part of the treatment
Patients having these regimes are more likely to have severe infusion reactions with the
first cycle of Rituximab. To avoid severe reactions the first cycle of Rituximab will be given
either as a split dose (Sect 4.1.1) or a single dose (Sect 4.1.2) depending on the presence
of risk factors outlined below.

4.1.1 Split dose Rituximab

Patients with CLL and WBC>25x109, or CLL or low grade NHL with bulky disease,
lymphoplasmacytic lymphoma or other risk factors for severe infusion reaction should
always be given split dose Rituximab for cycle 1 of chemotherapy.

Day 1: 100mg Rituximab in 100mls 0.9% Sodium chloride, given over 4 hours (i.e
25mg/hr).

Do not use the Rituximab rate calculator.

Day 2: the remainder of the Rituximab dose, given via the First Infusion rate using the
Rituximab rate calculator (see Appendix).

Cycle 2 should be given at the licensed rate, unless the patient has had a severe
infusion reaction (Grade 2 or more) to cycle 1, in which case cycle 2 should be given at
the first infusion rate.

Cycle 3 onwards may be given at the rapid rate provided the patient has previously
tolerated an infusion at the licensed rate.

4.1.2 Single dose Rituximab

Cycle 1 should be given at the first infusion rate

Cycle 2 should be given at the licensed rate, unless the patient has had a severe
infusion reaction (Grade 2 or more) to cycle 1, in which case cycle 2 should be given at
the first infusion rate.

Cycle 3 onwards may be given at the rapid rate provided the patient has previously
tolerated an infusion at the licensed rate.
DATE OF ISSUE: 23.12.15 VERSION 2
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FILENAME Guidelines for CONTROLLED DOC NO: CCPG(H) C4
Rituximab

4.2 Patients receiving chemotherapy containing corticosteroids

Some patients receiving chemotherapy containing corticosteroids have risk factors for
severe infusion reaction (e.g. very bulky disease, low grade NHL, high WCC, very high
grade NHL). Patients with risk factors for severe infusion reaction should be given split
dose Rituximab, otherwise single dose Rituximab may be given.

4.2.1 Split dose Rituximab

Day 1: 100mg Rituximab in 100mls 0.9% Sodium chloride, given over 4 hours (i.e
25mg/hr).

Do not use the Rituximab rate calculator.

Day 2: the remainder of the Rituximab dose, given via the first Infusion rate using the
Rituximab rate calculator (see Appendix).

Cycle 2 may be given at the rapid rate, unless the patient has had a severe infusion
reaction (Grade 2 or more) to cycle 1, in which case cycle 2 should be given at the
licensed rate.

Cycle 3 onwards may be given at the rapid rate provided the patient has previously
tolerated an infusion at the licensed rate.

4.2.2 Single dose Rituximab

Cycle 1 should be given at the first infusion rate

Cycle 2 should be given at the rapid rate, unless the patient has had a severe infusion
reaction (Grade 2 or more) to cycle 1, in which case cycle 2 should be given at the
licensed rate.

Cycle 3 onwards may be given at the rapid rate provided the patient has previously
tolerated an infusion at the licensed rate.

DATE OF ISSUE: 23.12.15 VERSION 2

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FILENAME Guidelines for CONTROLLED DOC NO: CCPG(H) C4
Rituximab

5. Infusion reactions

 Vital signs (temperature, blood pressure, pulse and respirations) should be

measured every 15 minutes during the first hour of the infusion , or until stable.
 Thereafter vital signs should be measured hourly until the end of the infusion.
 Toxicities related to infusion should be measured using the criteria in Table 1.
 If an infusion reaction of Grade 2 or greater occurs:

o Stop the infusion

o Contact the doctor

o If severe rigor is occurring, Pethidine 25mg IV slow bolus should be

administered without waiting for the doctor to arrive.

o Once the reaction has subsided, the Rituximab infusion may be started at
half the rate that was being given prior to the reaction.

o Patients may need to continue at the highest rate tolerated, rather than
increasing the rate further.

5.1 Subsequent infusions

If a patient is unable to tolerate infusion at a particular rate (e.g rapid rate) without a Grade
2 or greater reaction, subsequent infusions should be given at the fastest tolerated rate.

DATE OF ISSUE: 23.12.15 VERSION 2

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FILENAME Guidelines for CONTROLLED DOC NO: CCPG(H) C4
Rituximab

5.2 Table 1
Adverse Grade
event 1 2 3 4 5
Allergic Transient Rash: flushing; Symptomatic Anaphylaxis Death
reaction/hypersensitivity flushing or urticaria; dyspnoea; bronchospasm, with or
rash, fever drug fever ≥ 38°C without urticaria;
<38°C parenteral medications
indicated; allergy
related
oedema/angioedema;
hypotension
Cytokine release Mild Requires therapy or Prolonged recurrence Life threatening; pressor Death
syndrome/acute reaction: infusion interruption of symptoms following or ventilatory support
infusion reaction infusion but responds promptly initial improvement; indicated
interruption to symptomatic hospitalisation required
or other treatment for other clinical
intervention (e.g.antihistamines, IV sequelae
not fluids); prophylactic
indicated medications indicated
for ≤ 24 hrs

DATE OF ISSUE: 23.12.15 VERSION 2

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FILENAME Guidelines for CONTROLLED DOC NO: CCPG(H) C4
Rituximab

6. Using the infusion rate calculator

 The appropriate rate calculator for the regime and cycle should be generated in
clinic and attached to the prescription by the nurse generating the prescription. In
addition the rate specified should be annotated on the prescription.

 The rate calculator should be signed and dated by the nurse generating the
prescription or the doctor signing the prescription.

 The volume of the infusion should be given as 550mls for all doses of Rituximab
from 500mg to 900mg inclusive. Doses above and below these values should be
discussed with pharmacy.

Nurses administering Rituximab infusions should note that the actual volume of Rituximab
in the infusion bags may differ from 550ml. This difference should be ignored.

7. References

1. Ball, D. (2009) Guidance on the administration of Rituximab infusions, North

London Cancer Network,

2. Roche (2012) SPC Mabthera

DATE OF ISSUE: 23.12.15 VERSION 2

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FILENAME Guidelines for CONTROLLED DOC NO: CCPG(H) C4
Rituximab

Appendix: Infusion Rate Algorithm

CYCLE 1

Does patient have NO

Split dose YES Single dose
WCC>25, bulky disease st
1 infusion rate
or other risk factors
Day 1
100mg over 4hrs

Day 2
Remainder
st
1 infusion rate

≥ Grade 2 infusion reaction to

CYCLE 2 cycle 1?
YES

Licensed rate NO

Is patient on non YES YES Is patient on non

steroid containing steroid containing
regimen? regimen?
NO NO
Rapid rate

CYCLE 3

Licensed rate ≥ Grade 2 infusion Rapid rate

YES NO
reaction to cycle 2?

≥ Grade 2 infusion ≥ Grade 2 infusion

reaction to cycle 3? reaction to cycle 3?

YES NO YES NO

Continue at First Continue at Continue at

rate Licensed rate Rapid rate

DATE OF ISSUE: 23.12.15 VERSION 2

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REVIEW DATE: 23.06.17

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