Paediatric Rheumatology Cyclophosphamide Protocol
Nuffield Orthopaedic Centre and Children’s Hospital, Oxford
_________________________________________________________________________________________________________
Prescription Chart: Cyclophosphamide Regimen for Systemic Vasculitis &
Lupus.
Including Juvenile Dermatomyositis, Wegner’s Granulomatosis, Microscopic Polyarteritis, Polyarteritis
Nodosa, Unclassified Vasculitis, Scleroderma
Patients Name:
Date of birth:
Diagnosis:
Allergies:
Consultant:
Intravenous regimen
1. Methylprednisolone infusion 30mg/kg(Max 1g)in 100ml over at least 60mins
2
2. Ondansetron 5mg/m IV (Max 8mg) 15 minutes prior to Cyclophosphamide infusion (Metoclopramide
100micrograms/kg (Max 10mg) tds prn for 3 days for persistent nausea).
3. Mesna 3mg/kg IV 15 minutes prior to Cyclophosphamide infusion.
4. Cyclophosphamide 15mg/kg (Max 1g) slow infusion over 30 minutes.
2
5. IV fluids - hyperhydration rate = 125ml/m /hr for 4 hours of Dextrose 2.5% / Sodium Chloride 0.45%
with Mesna added at a dose equivalent to 100% Cyclophosphamide dose. N.B. May need to adjust
the amount of mesna in the bag of fluid to ensure the full Mesna dose is given.
6. Repeat every 14 days for 3 cycles then choose from below based on clinical response and
parental choice:
a. 3 cycles of oral regimen (go to page 6) – this is preferred option in normal circumstances
b. A further 3 cycles of IV cyclophosphamide (go to page 7) (if partial response and needs
bolus of methylprednispolone, or parent does not wish to give oral regimen, or close
monitoring of progress).
c. Escalate dose to 500-1000mg/m2 every 2-4 weeks (go to page 7) Dependent on response
to initial treatment and extent of organ involvement.
7. Request form to be given for GP to arrange blood test 2-3 days before the next infusion- Kamran’s
needs to be aware if this is happening
8. If partial response there is an option of a further 3 doses of 500-1000mg/m2 (go to page 8)
Oral regimen
1.
2.
3.
4.
5.
6.
Cyclophosphamide 15mg/kg (Max 1g) orally, total dose split over 3 consecutive days: Day 1, 2, 3.
Prednisolone: continue weaning regime.
Metoclopramide 100micrograms / kg ( Max 10mg) orally tds prn for 3 days for persistent nausea.
Oral fluids –
>20kg
1500ml per day plus 40ml/kg
10-20kg
1000mL per day plus 70ml/kg
Repeat in 21 days for 3 cycles.
Request forms for blood sampling THREE days before each repeat cycle.
Investigations-- Before each cycle: urea & electrolytes (U&E’s) and creatinine. Liver function tests (LFTs).
Full blood count (FBC). Then prior to each pulse.
Page 1 of 9
Produced by Nick Wilkinson and Rhoda Welsh, based on protocol of Connie Kon and Raashid Luqmani, Nuffield Orthopaedic Centre
updated 07/02/2013
Paediatric Rheumatology Cyclophosphamide Protocol
Nuffield Orthopaedic Centre and Children’s Hospital, Oxford
Name ( sticker):
Date of birth:
Kamran ward
GENERIC PROTOCOL
Must be completed before treatment starts
To be completed by treating Physician
Patient counselled on the following benefits of treatment?
Reduced mortality
Disease control
Prevention of premature organ failure
Patient counselled on the following risks of treatment?
Need for adequate contraception during treatment and for 3 months
afterwards
Infection
Reduced fertility – current guidelines
Malignancy
Adverse reactions
e.g. nausea, hair thinning, diarrhoea, mouth ulcers
Risk of developing or worsening diabetes (due to steroid therapy)
Transient steroid side effects
Haemorrhagic cystitis (bleeding from an irritated bladder)
Pre screening checklist
Blood tests taken within last 7 days; FBC, U&E, LFT, CRP
Chest x-ray within the last 3 months prior to 1st pulse in each cycle of
treatment
Copy of this policy explained to patient
Give patient – information sheet plus AR-UK sheet
Complete CHAQ
Peds Qol
If time available PVAS, BILAG, SLICC
N/A
















Date
Counselled by (name and signature)
Patient name and signature
Special Precautions: Cyclophosphamide is a human carcinogen. Contraception in both sexes is advised
during and for at least 3 months after therapy.
Contraindications: Pregnancy, lactation, hypersensitivity haemorrhagic cystitis and porphyria
Patient counselled? YES/NO
Patient given PIL? YES/NO
Page 2 of 9
Counselled by:
Produced by Nick Wilkinson and Rhoda Welsh, based on protocol of Connie Kon and Raashid Luqmani, Nuffield Orthopaedic Centre
updated 07/02/2013
Paediatric Rheumatology Cyclophosphamide Protocol
Nuffield Orthopaedic Centre and Children’s Hospital, Oxford
Name ( sticker):
Date of birth:
Kamran ward
Delay of treatment / Dose Modifications. CYC= Cyclophosphamide
9
Neutropenia - delay treatment until >1.5x10 /L, 25% dose reduction for all subsequent treatments.
Renal impairment-
Hepatic impairment
creatinine
97-150 mol/l
> 150 mol/l
25% CYC reduction (& discuss with consultant)
50-75% reduction (see GFR)
GFR
50-80ml/min/1.73m
2
15-49 ml/min/1.73m
2
<15ml/ min/1.73m
ALT / AST
>200 iu/l consider reducing dose and discuss with consultant
2
25% CYC reduction
50% CYC reduction
75% CYC reduction
No dose reduction of steroid in term of neutropenia or renal impairment.
Dose Calculations and modifications
Patient weight =
Initial dose of cyclophosphamide = weight x 15mg
Subsequent dose = initial dose x percentage reduction (see above)
FBC on day 12-13. If neutrophil <1.5x10/L or platelet <150x10/L wait 7 days and repeat FBC. If new result
within the safety parameters, give 75% cyclophosphamide dose; if count still low refer to consultant.
Date
HB
Platelets
Neutrophil
Creatinine
Bilirubin
ALT
BP
others
Page 3 of 9
Produced by Nick Wilkinson and Rhoda Welsh, based on protocol of Connie Kon and Raashid Luqmani, Nuffield Orthopaedic Centre
updated 07/02/2013
Paediatric Rheumatology Cyclophosphamide Protocol
Nuffield Orthopaedic Centre and Children’s Hospital, Oxford
IV REGIMEN doses 1-3
Dose # 1
Date:
Dose # 2
Date:
Dose # 3
Date:
Mesna – 3mg/kg
Methylprednisolone IV
30mg/kg (Max 1g)
Ondansetron 5mg/m2
(Max 8mg)
Cyclophosphamide
IV 15mg/kg (Max 1g)
Hydration 125ml/m2/hr
& Mesna 100% cyc
dose
Prednisolone
Prescribed by
Dr:
Checked by
Pharmacist:
Administered by
Nurse:
Nurse:
TTO: Please prescribe
Metoclopramide 100micrograms / kg (Max 10mg) orally tds prn for 3 days for persistent nausea.
Reduce Prednisolone maintenance dose if the patient is on it, but do not stop.
Hydration advice (as per protocol above) if to start oral regime
FOLLOW UP ARRANGEMENTS MADE
Date
Next Blood
Test
Pulse 1
Pulse 2
Pulse 3
Pulse 4
Pulse 5
Pulse 6
Next Clinic
Visit
Assessed by
Dr:
Page 4 of 9
Produced by Nick Wilkinson and Rhoda Welsh, based on protocol of Connie Kon and Raashid Luqmani, Nuffield Orthopaedic Centre
updated 07/02/2013
WARD
INTRAVENOUS PRESCRIPTION CHART
Kamran
Cyclophosphamide Regimen for Systemic Vasculitis
(15mg/ kg for juvenile dermatomyositis, vasculitis, JSLE and other organ threatening autoimmune disorders)
SURNAME
FIRST NAME
DATE
IV FLUID
-1:30
Sodium Chloride 0.9%
HOSP NUMBER
VOLUME
100ml
D.O.B.
WEIGHT:
DATE:
AGE
WEIGHT:
DATE:
ADDITIVES
RATE
Methylprednisolone ___mg
_____ml/hr
-0:15
Ondansetron__
Slow IV
bolus
-0:15
Mesna_________mg
Slow IV
bolus
0:00
0:10
Cyclophosphamide_
Dextrose 2.5% / Sodium Chloride
0.45%
Mesna________mg
ml
mg
Slow IV
bolus
____
ml/hr
HEIGHT
DURATI
ON
DRS SIG
1hr
SURFACE AREA
DATE &
TIME
ALLERGIES ?
NURSE
UNIT
NOTES
30mg/kg (max 1gram)
5mg/m2
(Max 8mg)
3mg/kg
Over 15
mins
Give via 3-way tap
into hydration fluids
Over 30
mins
Hydration rate =
125ml/m2/hr
Mesna dose = 100%
Cyclophosphamide
dose
Over 4
hours
(___mg per 500ml bag)
FBC must be checked pre-dose. Cyclophosphamide dose determined by consultant is 15mg/kg unless patient in a critical condition or has cytopenia (Platelets <
150x1012/ml, Neutrophil count < 1.5x109/ml, Hb < 8g/dl). If significant side effects (including cytopenia), subsequent doses to be reduced. If any concerns please
call Dr Nick Wilkinson (07944 723273) or Joel David via NOC switchboard or secretary (x38049)
Page 5 of 9
Produced by Nick Wilkinson and Rhoda Welsh, based on protocol of Connie Kon and Raashid Luqmani, Nuffield Orthopaedic Centre
07/02/2013
Paediatric Rheumatology Cyclophosphamide Protocol
Name ( sticker):
Date of birth:
Kamran ward
ORAL REGIMEN doses 4-6 (see next page if further IV doses required)
Prednisolone
Oral 10mg/kg divided over
three days
Cyclophosphamide
Oral 15mg/kg divided over
three days (Max 1g)
Metoclopramide
100micrograms/kg (Max
10mg) orally TDS prn for 3
days
Oral fluids
Dose no:
Date:
D1
D2
D3
D1
D2
D3
Dose no:
Date:
Dose no:
Date:
>20kg 1500ml /day + 40ml/kg
10-20kg 1000ml /day + 70ml/kg
Ongoing prednisolone
dose
Prescribed by
Dr:
Checked by
Pharmacist:
Administered by
Nurse:
Nurse:
TTO: ( Please have ready before the patient attends the ward)
Metoclopramide 100micrograms/kg (Max 10mg) orally tds prn for 3 days for persistent nausea,
Cyclophosphamide oral doses for Day 1, 2 and 3 (50mg tablets – round to nearest. Cyclophosphamide
liquid is unlicensed)
Prednisolone oral doses for Day 1, 2 and 3, and reduce Prednisolone maintenance dose as required.
If the patient has had at least one oral pulse, all the pulse medications can be prescribed on the TTO.
Hydration advice (as per protocol above)
COMMENTS/ OTHER DRUGS GIVEN
Page 6 of 9
Produced by Nick Wilkinson and Rhoda Welsh, based on protocol of Connie Kon and Raashid Luqmani, Nuffield Orthopaedic Centre
07/02/2013
Paediatric Rheumatology Cyclophosphamide Protocol
IV REGIMEN doses 4- 6
Consultant to choose from:
1. A further 3 cycles of IV cyclophosphamide (if partial response and needs bolus of
methylprednispolone, or parent does not wish to give oral regimen, or close monitoring of
progress).
2. Escalate dose to 500-1000mg/m2 every 2-4 weeks – dependent on response to initial treatment
and extent of organ involvement.
Dose # 4
Date:
Dose # 5
Date:
Dose # 6
Date:
Mesna – 3mg/kg
Methylprednisolone IV
30mg/kg (Max 1g)
Ondansetron 5mg/m2
(Max 8mg)
Cyclophosphamide
IV 15mg/kg or
500 – 1000mg/m2
(Max 1g)
Hydration 125ml/m2/hr
& Mesna 100% cyc
dose
Prednisolone
Prescribed by
Dr:
Checked by
Pharmacist:
Administered by
Nurse:
Nurse:
TTO: Please prescribe
Metoclopramide 100micrograms / kg (Max 10mg) orally tds prn for 3 days for persistent nausea.
Reduce Prednisolone maintenance dose if the patient is on it, but do not stop.
Hydration advice (as per protocol above) if to start oral regime
Page 7 of 9
Produced by Nick Wilkinson and Rhoda Welsh, based on protocol of Connie Kon and Raashid Luqmani, Nuffield Orthopaedic Centre
07/02/2013
Paediatric Rheumatology Cyclophosphamide Protocol
IV REGIMEN doses 7-9
Consultant decision:
500-1000mg/m2 every 2-4 weeks – if further improvement required following partial response.
Dose # 7
Date:
Dose # 8
Date:
Dose # 9
Date:
Mesna – 3mg/kg
Methylprednisolone IV
30mg/kg
Ondansetron (see
below)
Cyclophosphamide
500 – 1000mg/m2
(Max 1g)
Hydration 125ml/m2/hr
& Mesna 100% cyc
dose
Prednisolone
Prescribed by
Dr:
Checked by
Pharmacist:
Administered by
Nurse:
Nurse:
TTO: Please prescribe
Metoclopramide 100micrograms / kg (Max 10mg) orally tds prn for 3 days for persistent nausea.
Reduce Prednisolone maintenance dose if the patient is on it, but do not stop.
Hydration advice (as per protocol above) if to start oral regime
Page 8 of 9
Produced by Nick Wilkinson and Rhoda Welsh, based on protocol of Connie Kon and Raashid Luqmani, Nuffield Orthopaedic Centre
07/02/2013
Paediatric Rheumatology Cyclophosphamide Protocol
Name ( sticker):
Date of birth:
Kamran ward
ASSESSMENT OF RESPONSE
Patient assessed by consultant/SpR at baseline and following final pulse. Please refer to out-patient notes
for details
Date
Assessment eg BVAS, BILAG, SLEDAI, SLAM
TOXICITY: document any toxicity experienced.
E.g.Nausea, vomiting, diarrhoea, alopecia, haematological, stomatitis etc.
Date
Assessment
Reference: 1 Adu D, Pall A, Luqmani RA, Richards NT, Howie AJ, Emery P, Michael J, Savage CO, Bacon PA.Controlled trial of pulse
versus continuous prednisolone and cyclophosphamide in the treatment of systemic vasculitis. QJM. 1997 Jun;90(6):401-9.
Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association
(EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Bertsias GK, Tektonidou M,
Amoura Z et al. Ann Rheum Dis. 2012 Nov;71(11):1771-82. doi: 10.1136/annrheumdis-2012-201940. Epub 2012 Jul 31.
Page 9 of 9
Produced by Nick Wilkinson and Rhoda Welsh, based on protocol of Connie Kon and Raashid Luqmani, Nuffield Orthopaedic Centre
07/02/2013