Download Protocol - Doncaster LMC

Doncaster & Bassetlaw Area Prescribing Committee October 2009 V2.0
Shared Care Protocol for the Management of Inflammatory Arthritis &
Connective Tissue Disease for Adult services, over 16
1.0 INTRODUCTION
The use of disease modifying antirheumatic drugs (DMARDs) in treating early and
established stages of Inflammatory Arthritis (IA) and in managing Connective
Tissue diseases (CTD) is accepted practice. General Practitioners (GPs) are
becoming more involved in active management of these conditions with the
recognition that patients should be referred early for specialist advice and initiation
of disease modifying drugs.
This protocol sets out guidelines for treatment of CTD & IA and delineated
responsibilities when care is to be shared between Primary Care and
Rheumatology Specialist services.
Shared Care Protocols are intended to provide clear guidance to General
Practitioners (GPs) and hospital prescribers regarding the procedures to be
adopted when clinical (and therefore prescribing and financial) responsibility for a
patient’s treatment with a shared-care disease is transferred from secondary to
primary care.
GPs, as independent contractors, have the right to decline to take clinical and
prescribing responsibilities for a patient on their medical list who is being treated
elsewhere. However the reason for this action must be documented. In the view of
the Doncaster & Bassetlaw APC, it would be the exception for a GP to refuse to
take clinical and prescribing responsibilities for an individual drug, where shared
care guidelines for that drug have become common practice and where shared
care guidelines include adequate support, education, and information as approved
by the Doncaster & Bassetlaw APC.
If a specialist asks a GP to prescribe these drugs in relation to this disease, the
GP should reply to this request as soon as practicable. The doctor who prescribes
the medication legally assumes clinical responsibility for the drug and the
consequence of its use.
The Doncaster & Bassetlaw Hospitals NHS Foundation Trust is a multi-site trust
covering 2 PCT areas (Doncaster and Bassetlaw), with the Rheumatology
department split over the two main hospitals. The process of shared care
traditionally occurs for the DRI Rheumatology patients treated at Doncaster Royal
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Doncaster & Bassetlaw Area Prescribing Committee October 2009 V2.0
Infirmary. and for Bassetlaw patients primary care normally monitor DMARDs.
The reason for the difference dates back before the two hospitals merged as one
trust. This protocol should allow GPs to undertake either method.
While this document looks to medications used in the treatment of CT & IA
diseases, not all drugs will be covered by a shared care protocol for prescribing.
Drug Class
Traffic Light System Classification
Grey
Amber
Amber-G
Drugs that
suppress the
rheumatic
disease
process
Antimalarials
Drugs
affecting the
immune
response
Alkylating
drugs
Cytokine
modulators
Red
Gold (injectable
& oral)
Penicillamine
Sulfasalazine
Hydroxychloroquine
Azathioprine
Leflunomide
Methotrexate
(oral)
Abatacept1
Anakinra2
Ciclosporin
Methotrexate
(injectable)
Mycophenolate
Cyclophosphamide
Adalimumab
Etanercept
Infliximab
Rituximab
Grey - These medicines are not recommended for initiation in the Doncaster and Bassetlaw Health Care
Communities
Amber G – Drug must be initiated and titrated to stable dosage by specialist before GPs take over prescribing
responsibility. Once medical condition and drug dosage is stable, there is no specific requirement for ongoing
monitoring
Amber - Initiation and continued prescribing should only be undertaken under auspices of an agreed shared
care protocol
Red – Prescribing initiated and retained by specialist – Prescribing monitoring performed in secondary care
1
Abatacept - Abatacept is not recommended (within its marketing authorisation) for the treatment of people
with rheumatoid arthritis. Patients currently receiving abatacept for the treatment of rheumatoid arthritis
should have the option to continue therapy until they and their clinicians consider it appropriate to stop.
NICE TA 141 Abatacept for the treatment of rheumatoid arthritis April 2008
2 Anakinra: On the balance of its clinical benefits and cost effectiveness, anakinra is not recommended for the
treatment of RA, except in the context of a controlled, long-term clinical study. NICE CG79 The management
of rheumatoid arthritis in adults February 2009
2.0 Background Information
This shared care agreement includes, but is not restricted to, the treatment of
patients with any inflammatory arthritis or spondyloarthropathy and connective
tissue diseases such as SLE, discoid lupus, myositis, vasculitis as examples.
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Doncaster & Bassetlaw Area Prescribing Committee October 2009 V2.0
2.1
RheMOS System General
Doncaster Rheumatology unit use a monitoring system aided by a nationally
recognised program called RheMOS. This essentially is a software package that
can assess trends in a patient’s blood test parameters. It then highlights when a
patient deviates outside set parameters and has not had a blood test according to
their drugs’ protocol. This is then actioned by the Rheumatology team as
appropriate depending on the clinical situation. Patients are sent the regular blood
forms by the support staff in the post, which have a bar code on which highlights
to the Trust’s PAS system that it is a RheMOS patient. Recently, the Trust has
gone paperless for RheMOS blood results as they were not needed. The forms
are sent out each time the patient reaches the end of their group of forms and
then ring in on a dedicated phone line extension, which each patient is given. This
system also allows for tracking when patients do not attend for blood tests and the
departments own protocol for this is followed.
2.2
RheMOS DNA Protocol
If patents DNA blood tests, they are sent a reminder letter as soon as is
practicable, asking them to either attend for the blood test or contact on nurses
help line if there are problems. They are warned in the letter that it is dangerous to
continue the drug unmonitored and if they fail to have the blood test performed
treatment might need to be stopped. If the patient fails following this to have a
blood test performed or contact the department then a letter is sent to the patient,
their GP and whoever is prescribing the DMARD (ie hospital pharmacy) asking
them to stop the treatment and that if they continue to take the DMARD after this
then that is at their own risk. Contact numbers are again provided on the letter.
2.3
Pregnancy and Breast Feeding
When a patient is prescribed a DMARD there are significant issues regarding
pregnancy and family planning posed by the potency and potential teratogenic
potential of these drugs. The decision about when and what drugs should be
stopped is a decision that needs to be taken in secondary care. The decisions
potentially affect both male and female patients depending on the drugs being
used. Please see Appendix for specific advice on each drug. Overall the principle
is to use the least level of treatment to control the disease but in certain conditions
such as SLE, stopping some DMARD therapies has been shown to increase risk
of flare and consequent risk to mother and baby. Please refer to Appendix 1.
Breastfeeding should not be advised if a mother is on any DMARD, even those
felt to be safe during pregnancy, as small amounts are excreted in the breast milk.
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Doncaster & Bassetlaw Area Prescribing Committee October 2009 V2.0
2.4
Chicken Pox
Immunosuppressd Varicella Zoster Virus (VZV) naïve patients have a significant
risk of disseminated infection if exposed or contract infection. Therefore,
information is passed to all patients in secondary care on DMARD / steroid
therapy as what to do if they are exposed or contract chicken pox.
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2.5
Exposed to VZV and within incubation period
o Previous history of chicken pox
Only treat if develop active infection; usually aciclovir
o No history of chicken pox
 Urgent assessment of VZV antibodies
 If antibody status negative: treatment with pooled
immunoglobulin
 If antibody status positive: only treat with acyclovir if develop
infection
Active VZV Infection
o Previous history of infection – treat with acyclovir
o No history of chicken pox
 Urgent assessment of antibodies
 Detailed clinical assessment and anti-viral treatment dependent
on clinical presentation
Immunizations
No live vaccine should be given to any immunosuppressed patient.
All patients on methotrexate, azathioprine, ciclosporin, lefluonamide,
mycophenolate and cyclophosphamide should be offered annual flu vaccination
and the one off pneumococcal vaccine unless contraindicated.
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3.0 Drug treatment
For contraindications or further information please see the current BNF http://www.bnf.org.uk/bnf/bnf/current/index.htm or
summary of product characteristics for the individual drug http://www.medicines.org.uk/
Drug, dose & TLS listing
Adverse effects
Therapeutic Monitoring
Consultant
GP
Clinically relevant drug
interactions
1. Drugs that suppress the rheumatic disease process
1.1 Auranofin – Oral Gold (Amber)
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6 mg daily (initially in 2 divided
doses then if tolerated as a
single dose)
If response inadequate after 6
months, increase to 9 mg daily
(in 3 divided doses), discontinue
if no response after a further 3
months
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Diarrhoea
Rashes
Bone marrow
suppression*
Oral ulceration
Proteinuria
Permanent greyish skin
discolouration
(chrysiasis) with
prolonged use
Baseline:
- FBC, WBC, platelets, urinalysis, U&Es, LFT,
urinalysis for proteinuria and blood
Routine:
Every 4 weeks
- FBC, & urinalysis
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None
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None
Side effects
Symptom control
1.2 Sodium Aurothiomalate – Injectable Gold (Amber)
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10mg test dose followed by
50mg once weekly given by
deep IM injection
After significant response with
50mg weekly dose can be
reduced to every 2 weeks to
monthly
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Diarrhoea
Rashes
Bone marrow
suppression*
Oral ulceration
Proteinuria
Permanent greyish skin
discolouration
Baseline:
- FBC, WBC, urinalysis, U&Es, LFT, urinalysis for
proteinuria and blood
Routine:
Before each injection
 FBC, WBC,
 Urinalysis
When stable for 8 weeks it is permissible to work one
week in arrears for FBC.
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Doncaster & Bassetlaw Area Prescribing Committee October 2009 V2.0
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If a total dose of 1 gram has
been given & there has been no
response, treatment should stop.
If relapse occurs revert to 50mg
weekly until control reestablished
1.2 Penicillamine
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(chrysiasis) with
prolonged use
Vasomotor reaction flushing erythema,
weakness, hypertension.
Rarely – enterocolitis,
intra hepatic cholstasis,
pneumonitis.
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Side effects
Symptom control
(Amber)
Initially 125mg-250mg daily
before food for 1 month
increased by similar amounts at
intervals of not less than 4
weeks to usual maintenance
dose of 500-750mg daily in
divided doses.
Maximum dose of 1.5 gram
daily, if remission sustained for 6
months, reduction of daily dose
by 125mg-250mg every 12
weeks may be attempted
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Nausea
Bone marrow
suppression*
Rashes
Oral ulceration
Alteration of taste
Proteinuria
Baseline:
 FBC, differential WBC, U&E’s, creatinine &
urinalysis for proteinuria and blood
Routine:
Every 2 weeks for the first 3 months
 FBC, U&E & urinalysis
Every 4 weeks

FBC, U&E’s & urinalysis
 Side effects
 Symptom control
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Clozapine increases risk
of agranulocytosis.
Doncaster & Bassetlaw Area Prescribing Committee October 2009 V2.0
1.3 Sulfasalazine (Amber)
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Enteric coated tablets only
(Salazopyrin –EN
500mg per day increasing by
500mg per day each week to a
usual maintenance dose of 2
grams per day in divided doses.
If no response after 3 months
the dose may be increased to a
maximum of 3g/day (1.5g bd)
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Orange tears and urine
Nausea
Headache
Abdominal pain
Diarrhoea
Oral ulceration
Rashes
Oral ulceration
Bone marrow
suppression*
Hepatitis
Oligospermia
Baseline:
 FBC, WBC, creatinine, LFT
Routine
Fortnightly for 12 weeks
 FBC, WBC, LFT.
After 12 weeks at 3 monthly intervals for the first year
 FBC, WBC, LFT.
After 12 months at 6 monthly intervals (or 1 month
after dose increase)
 FBC, WBC,LFT
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None
Side effects
Symptom control
2. Antimalarials
2.1 Hydroxychloroquine (Amber-G)
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Initially 400mg in divided doses.
Can be reduced to 200mg after
6 months depending on clinical
response.
Maximum dose is 6.5mg/kg lean
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Indigestion, nausea, abdominal
cramps
Headache,
Tinnitus
Rashes
Baseline
 FBC, U&E, LFTs
 Ask about visual
impairment (eye
acuity)
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Amiodarone- increase risk of ventricular
arrhythmias. Avoid concomitant use
Doncaster & Bassetlaw Area Prescribing Committee October 2009 V2.0
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body weight per day or 400mg
per day, whichever is lower.
Smaller doses are needed in
patients weighing 60kg or less.
Review needed if no clinical
effect after 6 – 12 months of
treatment.
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Photosensitivity (sunblock
advised)
Retinopathy can occur after
prolonged treatment
Otoxicity
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Side effects
Symptom control
Annual Visual
symptomatology
3. Drugs affecting the immune response
3.1 Azathioprine (Amber)
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1 to 3mg/kg day adjusted for
clinical response
Check TPMT if possible to
starting
Often started 1mg/kg initially for
2-4 weeks until TPMT known
and then increase to 2mg/kg
Larger doses used under
secondary care supervision
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Nausea, vomiting, diarrhoea
Bone marrow suppression*
Rashes
Hepatic dysfunction
Baseline:
 FBC,LFT,U&E,TPMT
Routine:
Weekly for 6 weeks
 FBC, LFT’s
After 6 weeks at monthly
intervals
 FBC, LFT’s
At 6 monthly intervals
 U&E’s
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Dose changes:
FBC and LFT fortnightly for 6
weeks after any dose increase
 Side effects
 Symptom control
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Allopurinol-enhanced effects and
increased toxicity
Clozapine- avoid concomitant use
potential for causing agranulocytosis
Coumarins- anticoagulant effect
reduced
Sulfamethoxazole -increased risk of
haematological toxicity
Trimethoprim (also with cotrimoxazole)-increased risk of
haematological toxicity
Doncaster & Bassetlaw Area Prescribing Committee October 2009 V2.0
3.3 Leflunomide (Amber)
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Start on 10 -20mg od
Occasional
circumstances larger
doses have been
used.
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Gastrointestinal disturbance
Abdominal pain
Weight loss
Oral ulceration
Headache
Increase in blood pressure
Rashes
Bone marrow suppression*
Hepatitis
Baseline:
 LFTs, U&Es, creatinine and BP
 FBC including differential WBC count
Routine:
Monthly for the first 6 months then every 8 weeks
 FBC, differential WBC
 LFT & BP
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Side effects
Symptom control
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Colestyramine significantly
decreases the effect. Avoid
concomitant use unless
used to quickly discreet
Leflunomide from body in
cases such as overdose or
unexpected pregnancy
Doncaster & Bassetlaw Area Prescribing Committee October 2009 V2.0
Drug, dose & TLS
listing
Adverse effects
Therapeutic
Monitoring
Consultant
GP Lead Monitoring#
GP
Clinical relevant drug interactions
3.4 Methotrexate -oral (Amber)
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Initially be given at a
dose between 2.5 to
7.5mg once weekly,
increase to a
maintenance dose of
10 to 25mg once per
week.
Folic acid 5mg given 2
days after each dose
may reduce the
incidence of toxicity
Folic acid can be
increased up to 5mg
every day except on
Methotrexate day to
help control side
effects
The vast majority of
patients take Methotrexate
on a once weekly dosage.
For the minority that need
to take a twice weekly
dose, there is no evidence
that suggests that this is
more hazardous than a
once weekly dose
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Gastrointestinal disturbance
Rashes
Oral ulceration
Hepatic dysfunction
Bone marrow suppression*
Alopecia
Headaches
Rarely Pneumonitis
Rarely Pulmonary Fibrosis
Baseline:
 U&E, creatinine, LFTs, FBC, differential
WBC, platelets and chest x-ray
Routine:
Every 2 weeks for the first 6 weeks and then
monthly thereafter:
 FBC, WBC, U&E’s, LFT’s
Dose changes:
FBC, LFT’s and U&E’s fortnightly for 6 weeks
after any dose increase
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Ask about respiratory symptoms at monitoring
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Routine:
 FBC, & LFT’s monthly
 U&E every 6 months
Ask about respiratory symptoms at monitoring
#Doncaster PCT Local Enhanced Service
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Acitretin increases plasma concentration
Ciclosporin risk of toxicity
Clozapine increases risk of
agranulocytosis concomitant use should
be avoided
NSAID’s reduce excretion
Probenecid reduces excretion
Pyrimethamine increases antifolate
effect
Sulfamethoxazole (as Co-trimoxazole)
increases risk of haematological toxicity
Trimethoprim increases risk of
haematological toxicity
Side effects
Symptom control
* Bone Marrow Suppression may present with bruising, bleeding, fever, sore throat or any other signs of sepsis
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Doncaster & Bassetlaw Area Prescribing Committee October 2009 V2.0
4.0 SHARED CARE ARRANGEMENTS
Once a stable medication regime has been established (usually 3 months), physical
monitoring and prescribing of amber category drugs can be transferred to primary
care with agreement.
4.1
Aspects of care for which Secondary Care Team is responsible
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4.2
Diagnosis and assessment
Initiation and stabilisation of drug therapy, usually but not exceptionally, a
period of 3 months.
Patient/ family education
Ensure patient is fully informed of potential benefits and side effects of
treatment
Ensure patient’s guardian/carer is fully informed of the treatment.
Provide a comprehensive treatment package in addition to medications
including appropriate information/monitoring sheet(s)
Ensure that shared care arrangements are in place before transfer of
treatment
 That the patient/carer is clear what is being monitored and by
whom
 That the patient knows what significant adverse effects/events to
report urgently and to whom they should report (specialist or GP)
Any dose changes once the patient is established on treatment will be
conveyed in writing to the GP for the GP to prescribe.
Extra monitoring needed for dose changes will be organised by
Rheumatology team and conveyed to patient
Monitor side effects of medication via routine out-patient visits or nurse
telephone help line.
Report adverse events to the CSM
Monitor patient’s response to treatment
If patients are being monitored using RheMOS system, patients will be
sent blood forms and have the results analysed using the already
established system (see section 2.1)
If blood abnormalities occur secondary to DMARD picked up using
RheMOS, action appropriate to the abnormality will be organised via the
Rheumatology team.
If patients DNA their blood test monitoring as picked up on RheMOS, the
Rheumatology units protocol will followed (see appendix)
Aspects of care for which Primary Care Team is responsible

Ensure that shared care arrangements are in place before transfer of
treatment
 That the patient/carer is clear what is being monitored and by
whom
 That the patient knows what significant adverse effects/events to
report urgently and to whom they should report (specialist or GP)
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When the specialist initiates treatment, reply to the request for shared
care as soon as practicable
Confirm that proposed therapy is not contra-indicated because of
concurrent therapy for other conditions the patient may be suffering from
e.g. check drug-contraindications and drug-interactions. Contact specialist
team if possible interactions found and discuss with rheumatologist
Confirm the specialists have provided the patient/carer with appropriate
information sheet(s) for monitoring and/or to alert other clinical staff to the
treatment they are receiving. If appropriate information has not been
provided by the specialist, the GP must ensure the information is provided
Ensure patient’s guardian/carer is fully informed of the treatment
Monitor treatment as stated in the shared care protocol
Amend prescription as per requests from secondary care for dose
changes in patients on established treatment
Confirm with specialist which changes in these or other parameters
should trigger urgent referral back to the specialist
Seek specialist advice promptly as advised in the shared care protocol or
if signs/symptoms of changes occur consistent with DMARD adverse
event
Report adverse events to the CSM
If the drug has a black triangle status or is unlicensed, all events should
be reported even if casual relationship is not known or if the adverse
event is already known about
Report adverse events to the consultant sharing the care of the patient
Stop treatment on advice of specialist, or immediately if intolerable side
effects occur provided that it is safer to do so than to continue this therapy
4.3 Patient (or Carer’s) Responsibilities
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Discuss potential benefits and side effects of treatment with the specialist
and GP. Identify whether they have a clear picture of these from the
specialist and to raise any outstanding queries
Check that where possible the specialists have provided a patient-held
record or information sheet for monitoring and/or to alert other clinical staff
to the treatment they are receiving
Share any concerns they have in relation to treatment with the medicine
Report any adverse effects to their specialist or GP whilst taking the
medicine
Report to the specialist or GP if they do not have a clear understanding of
their treatment
Participate in the monitoring of therapy and the assessment of outcomes,
to assist health professionals to provide safe, appropriate treatment
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Doncaster & Bassetlaw Area Prescribing Committee October 2009 V2.0
5.0
PROCEDURE FOR ADOPTING SHARED CARE
5.1
General Procedure:
The specialist will send to the GP a diagnostic assessment report, a copy of the
shared care protocol and a shared care referral specifying who is responsible for
monitoring. Both the specialist and GP should sign the proforma with a record kept
in the GP and specialist records. Full details will be given of the prescribing regime
(brand, form, strength and dose of medication) and follow-up plan.
The patient will be asked to make arrangements with their GP for continued supply.
6.0
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REFERENCES
British National Formulary 56, September 2008
Arava Summary Product Characteristics
Auranofin Summary Product Characteristics
Distamine Summary Product Characteristics
Imuran Summary Product Characteristics
Maxtrex Summary Product Characteristics
Myocrisin Summary Product Characteristics.
Neoral Summary Product Characteristics
Plaquenil Summary Product Characteristics
Salazopyrin EN Summary Product Characteristics
NICE Technology Appraisal Guidance 141: Abatacept for the treatment of
rheumatoid arthritis April 2008
NICE Clinical Guidance 79: The management of rheumatoid arthritis in adults
February 2009
BSR/BHPR guideline for disease-modifying anti-rheumatic drug (DMARD)
therapy in consultation with the British Dermatologists, K Chakravarty et al.
Rheumatology 2008
NPSA Patient safety alert 13; Improving compliance with oral methotrexate
guidelines June 2006
7.0 SHARED CARE DEVELOPMENT
Written April 2009 By:
Clare Wilkinson, Consultant Rheumatologist Doncaster Royal Infirmary
Robert Stevens, Consultant Rheumatologist Doncaster Royal Infirmary
Roger Hancocks, Deputy Director of Pharmacy Doncaster Royal Infirmary
Joanna Hallatt, Head of Medicines Assurance Doncaster Primary Care Trust
Annabelle Coote, Consultant Rheumatologist Doncaster Royal Infirmary
Lesley Geddes, Rheumatology Nurse Prescriber Doncaster Royal Infirmary
Reviewed October 2009 By:
Doncaster & Bassetlaw Area prescribing Committee
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Doncaster & Bassetlaw Area Prescribing Committee October 2009 V2.0
Appendix 1 - Pregnancy
Auranofin
 Contraindicated
 Omit 3 - 6 months prior to first attempting to conceive
Azathioprine
 Can be used during pregnancy
 Physicians should weigh up risk of treatment versus risk
 Certain clinical scenarios such as SLE, evidence suggests reducing/withdrawing
treatment can lead to significant flare of disease
Ciclosporin
 Can be used in pregnancy with caution
 Will need close monitoring by physician
 If hypertension develops will need assessment to see if drug or pregnancy
related
D-Penicillamine
 Contraindicated
 Omit 3 - 6 months prior to first attempting to conceive
Hydroxychloroquine
 Can be used during pregnancy
Leflunomide
 Known to be teratogenic
 Should be avoided in women of child bearing age unless reliable contraception is
used
 If children are planned, women should discontinue for 2 years prior to conception
or have active metabolite removed rapidly by washout procedures such as
cholestyramine
 Men should not try for conception till 3 months after cessation of drug
Methotrexate
 Contraindicated in pregnancy
 Known to be teratogenic and abortifacient
 Both men and women advised to omit 3-6 months prior to trying to conceive
Mycophenolate Mofetil
 Contraindicated in pregnancy
 Need at least 6 weeks of discontinuation before trying to conceive
Sodium Aurothiomalate (injectable gold)
 Contraindicated in pregnancy
 Omit 3 – 6 months prior to trying to conceive
Sulfasalazine
 Caution if used during pregnancy
 Risk to unborn child vs benefit to mother needs to be assessed by physicians
involved
 Dose should not exceed 2g/day during pregnancy
 Daily supplement of folic acid should be given to those trying to conceive and
whilst pregnant when on sulfasalazine
 In men of child bearing potential may cause reversible oligospermia
With each patient, it is vital that discussion about the usage of reliable contraception
to be used whilst contraindicated drugs are omitted prior to trying to conceive is had.
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This Document will be reviewed in the light of new or emerging evidence or by October 2014