It is exciting times in the treatment of Multiple Sclerosis (MS) with the approval of two new oral therapies for the treatment of the relapsing remitting form of the disease; dimethyl fumarate and teriflunomide. There has been significant media attention and interest from patient groups and clinicians who welcome these new oral therapies. 

Dimethyl fumarate and teriflunomide have both been added to the Total Formulary after being accepted by the SMC for the treatment of adults with relapsing remitting multiple sclerosis (RRMS). These will offer an alternative to existing first line therapies, beta-interferon and glatiramer acetate, which are given by injection. The assessment, prescribing and monitoring of these treatments will continue to be undertaken by the specialist regional centre at the Neurological Institute, Southern General Hospital. 

Dimethyl fumarate (Tecfidera)

Dimethyl fumarate is accepted for use within NHS Scotland for the treatment of adult patients with RRMS. Two phase 3 clinical trials of dimethyl fumarate have been completed for RRMS, which included more than 2,000 people worldwide. Both studies evaluated the effect of on relapse rate, the progression of disability, and the damage to the brain caused by MS.

Dimethyl fumarate is administered orally twice daily and reduces relapse rate by approximately 50%.  Beta-interferon and glatiramer acetate, existing first line therapies, reduce relapse rates by around one-third. Although no direct comparison has been undertaken in a clinical trial setting, this suggests dimethyl fumarate may offer improved efficacy. Clinically relevant effects on disability worsening were also seen, though the trials were only of two years’ duration. The main side effects with dimethyl fumarate are flushing (approximately one third of patients) and gastrointestinal (GI) disturbance (diarrhoea, nausea, upper abdominal pain) which are most common in the first month.  GI side effects can be minimised by taking dimethyl fumarate with food. 

Teriflunomide (Aubagio®)

Teriflunomide is accepted for restricted use in RRMS.  Teriflunomide is not expected to be used for the treatment of patients with highly active disease.

The clinical trial programme for teriflunomide was similar to that for dimethyl fumarate. Teriflunomide is administered orally once daily and reduces relapse rate by approximately 30%. This suggests a similar effect to beta-interferon or glatiramer acetate, although again direct comparisons have not been made. Clinically relevant effects on disability worsening were also seen, though the trials were only of 2 - 2.5 years’ duration. The main side effects with teriflunomide are nausea, headaches, diarrhoea and hair thinning/loss. Teriflunomide requires fortnightly blood monitoring for the first six months of treatment and a washout procedure is recommended if patients need to discontinue therapy. 

Previous article: Novel oral anticoagulants

Next article: Tramadol and changes to controlled drug legislation

Inclusion of the NOACs (dabigatran, rivaroxaban, apixaban) on the NHSGGC Formulary is established for existing patients with non-valvular atrial fibrillation (AF) who are intolerant of, or poorly controlled on, warfarin. To date there has been cautious uptake of these new agents.

Supporting guidance is on GGC Prescribing which includes information to guide choice of NOAC and how to manage the transition period. Potentially suitable patients, with poor INR control (time in target range <60%), will be identified and highlighted to general practice by the Glasgow & Clyde Anticoagulation Service (GCAS).  

The role of NOACs in the management of new patients has been under consideration and the Heart Managed Clinical Network (MCN) is undertaking a review of the NHSGGC AF guideline. This will include a change which will support the option of prescribing a NOAC as a first-line alternative to warfarin where anticoagulation is indicated in patients newly diagnosed with non-valvular AF. The Formulary status of dabigatran and apixaban has been updated to reflect this change. The position for rivaroxaban is unchanged and is in line with SMC advice.

Patients are at high risk of a stroke before they are fully anticoagulated and the NOACs have the advantage of a quicker onset of action compared to warfarin, and can be immediately prescribed by the GP rather than awaiting referral to GCAS. The significant financial implications of introducing NOACs for new diagnoses of AF have been included in the Board’s financial plan for medicines for 2014/15. The updated guideline will be communicated in due course through PostScript and the Heart MCN.

Patients who are well controlled on warfarin should remain on warfarin; a switch to NOAC in these patients is discouraged and remains non-Formulary.

Next article: New oral therapies for multiple sclerosis

This edition can be accessed in PDF format here and contains articles on:

• Novel oral anticoagulant update
• New oral products for multiple sclerosis
• Tramadol to become controlled drug
• Nitrofurantoin in renal impairment
• Safety update: contraceptive interaction
• Kid’s corner: specials
• ADTC decisions summary and new guidelines
• New fluticasone COPD product
• Valsartan supply problems
• Clomipramine supply problems

First article: Novel oral anticoagulant update

Additions to the GGC Adult Formulary

Greater Glasgow and Clyde Area Drug and Therapeutics Committee (ADTC) met on 28th April 2014 and added the following medicines/indications/ formulations to the GGC Formulary.  Additions are to the Total Formulary unless specified otherwise.

Adapalene and benzoyl peroxide topical gel (Epiduo^®) for the cutaneous treatment of acne vulgaris when comedones, papules and pustules are present is included in the GGC Adult Formulary for the indication in question. It is restricted to the treatment of mild to moderate facial acne when monotherapy with benzoyl peroxide or adapalene is not considered appropriate.

For relevant SMC advice click here

Afatinib tablets (Giotrif^®), as monotherapy, for the treatment of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor-naïve adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutation(s) is included in the GGC Adult Formulary for the indication in question pending protocol.  It is restricted to specialist use in accordance with regional protocol.

For relevant SMC advice click here

Aflibercept infusion (Zaltrap^®) in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) chemotherapy, aflibercept is indicated in adults with metastatic colorectal cancer (mCRC) that is resistant to or has progressed after an oxaliplatin containing regimen and is included in the GGC Adult Formulary for the indication in question pending protocol.  It is restricted to specialist use in accordance with regional protocol.

For relevant SMC advice click here

Aflibercept intravitreal injection (Eylea^®) for the treatment of visual impairment due to macular oedema secondary to central retinal vein occlusion in adults is included in the GGC Adult Formulary for the indication in question. It is restricted to specialist use in accordance with local protocol.

For relevant SMC advice click here

Azithromycin infusion (Zedbac^®) for the treatment of community acquired pneumonia (CAP) and pelvic inflammatory disease (PID) due to susceptible organisms in adult patients where initial intravenous therapy is required is included in the GGC Adult Formulary for the indication in question. It is restricted to use on the advice of a microbiologist or infectious disease physician when the oral route of administration is compromised.  It is considered an Alert Antimicrobial.

For relevant SMC advice click here

Dapagliflozin tablets (Forxiga^®) for use in adults with type 2 diabetes mellitus to improve glycaemic control in combination with insulin is included in the GGC Adult Formulary.  It is restricted to use in combination with insulin, when insulin with diet and exercise, does not provide adequate glycaemic control.

For relevant SMC advice click here

Dimethyl fumerate (Tecfidera^®) for the treatment of adult patients with relapsing remitting multiple sclerosis is included in the GGC Adult Formulary for the indication in question. It is restricted to specialist use in accordance with local guidelines.

For relevant SMC advice click here

Fluticasone furoate and vilanterol dry powder inhaler (Relvar Ellipta^®) for the symptomatic treatment of adults with chronic obstructive pulmonary disease (COPD) with an exacerbation history despite regular bronchodilator therapy is included in the GGC Adult Formulary for the indication in question.  It is restricted to use in patients with severe COPD (FEV1 <50% predicted normal and two or more exacerbations in a year) in accordance with NHSGGC COPD Guidelines.

For relevant SMC advice click here

Lenalidomide hard capsules (Revlimid^®) for the treatment of patients with transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate is included in the GGC Adult Formulary for the indication in question pending protocol.  It is restricted to specialist use in accordance with regional protocol.

For relevant SMC advice click here

Lenalidomide hard capsules (Revlimid^®) in combination with dexamethasone, for the treatment of multiple myeloma in adult patients who have received at least one prior therapy is included in the GGC Adult Formulary for the indication in question pending protocol.  It is restricted to specialist use in accordance with regional protocol.

For relevant SMC advice click here

Lipegfilgrastim injection (Longuex^®) for the reduction in the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes) is included in the GGC Adult Formulary for the indication in question.  It is restricted to specialist use in accordance with regional protocol.

For relevant SMC advice click here

Macitentan tablets (Opsumit^®) as monotherapy or in combination is indicated for the long-term treatment of pulmonary arterial hypertension in adult patients of World Health Organisation Functional Class II to III and is included in the GGC Adult Formulary for the indication in question. It is restricted to initiation and prescribing by specialists in the Scottish Pulmonary Vascular Unit or similar specialists.

For relevant SMC advice click here

Rilpivirine, emtricitabine, tenofovir tablets (Eviplera^®) for the treatment of adults infected with human immunodeficiency virus type 1 (HIV-1) without known mutations associated with resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class, tenofovir or emtricitabine, and with viral load ≤100,000 HIV-1 RNA copies/mL is included in the GGC Adult Formulary for the indication in question. It is restricted to use by HIV specialists.

For relevant SMC advice click here

Solifenacin and tamsulosin modified-release tablets (Vesomni^®) for the treatment of moderate to severe storage symptoms (urgency, increased micturition frequency) and voiding symptoms associated with benign prostatic hyperplasia in men who are not adequately responding to treatment with monotherapy is included in the GGC Adult Formulary for the indication in question.

For relevant SMC advice click here

Teriflunomide tablets (Aubagio^®) for the treatment of adults with relapsing remitting multiple sclerosis (MS) is included in the GGC Adult Formulary for the indication in question. It is restricted to specialist use as an alternative to treatment with interferon beta or glatiramer acetate. Teriflunomide is not expected to be used for the treatment of patients with highly active disease.

For relevant SMC advice click here

Trastuzumab sub-cutaneous injection (Herceptin^®) for the treatment of adult patients with HER2 positive metastatic breast cancer (MBC) and early breast cancer (EBC) in a range of settings is included the GGC Adult Formulary for the indication in question pending protocol.  It is restricted to specialist use in accordance with regional protocol.

For relevant SMC advice click here

Ustekinumab sub-cutaneous injection (Stelara^®) for use alone or in combination with methotrexate, for the treatment of active psoriatic arthritis in adult patients when the response to previous non-biological disease-modifying anti-rheumatic drug therapy has been inadequate, is included in the GGC Adult Formulary for the indication in question. It is restricted to specialist use in patients with active psoriatic arthritis who have failed on, or are unsuitable for, treatment with an anti-TNF drug.

For relevant SMC advice click here

New medicines, indications and formulations not included in the GGC Adult Formulary or GGC Paediatric Formulary

The following are not included in the GGC Adult Formulary following the latest ADTC meeting. Where the reason is other than not recommended advice from SMC it is noted.  NB: these medicines may be included in the Formulary for other indications or for other formulations.  Please refer to Formulary.

Alogliptin tablets (Vipidia^®) for adults aged 18 years and older with type 2 diabetes mellitus to improve glycaemic control in combination with other glucose lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control is not included in the GGC Adult Formulary for the indication in question.

For relevant SMC advice click here

Insulin degludec (Tresiba^®) for the treatment of diabetes mellitus in adults is not included in the GGC Adult Formulary for the indication in question.

For relevant SMC advice click here

Saxagliptin tablets (Onglyza^®) as monotherapy in adult patients aged 18 years and older with type 2 diabetes mellitus to improve glycaemic control inadequately controlled by diet and exercise alone and for whom metformin is inappropriate due to contraindications or intolerance is not included in the GGC Adult Formulary for the indication in question.

For relevant SMC advice click here

Additions to GGC Paediatric Formulary

The following new medicines, indications or formulations have been considered for the GGC Paediatric Formulary.

Darunavir tablets, oral suspension (Prezista^®) when co-administered with low dose ritonavir in combination with other antiretroviral medicinal products for the treatment of human immunodeficiency virus (HIV-1) infection in paediatric patients 12 to 17 years of age and at least 40kg body weight who are: antiretroviral therapy (ART) naïve; or, ART-experienced with no darunavir resistance associated mutations and who have plasma HIV-1 RNA <100,000 copies/mL and CD4+ cell count ≥100 cells/mm3 is included in the GGC Paediatric Formulary for the indication in question. It is restricted to patients <18 years, to be prescribed under the supervision of specialists in paediatric HIV.

For relevant SMC advice click here

Zonisamide capsules (Zonegran^®) as adjunctive therapy in the treatment of partial seizures, with or without secondary generalisation, in adolescents, and children aged 6 years and above, is included in the GGC Paediatric Formulary for the indication in question. It is restricted to initiation on advice from specialists (paediatric neurologists or paediatricians with an expertise in epilepsy.

For relevant SMC advice click here

Other Formulary Decisions

Following formulary appeals:

Ulipristal acetate tablets (Esmya^®) for the pre-operative treatment of moderate-to-severe symptoms of uterine fibroids in adult women of reproductive age is included in the GGC Adult Formulary for the indication in question. It is restricted to specialist initiation with a restricted duration of treatment of 3 months.

Fosfomycin granules (Monuril^®) for the treatment of extended-spectrum beta-lactamases (ESBL) lower urinary tract infection (LUTI) in non-septic men and non-pregnant women as an oral alternative to current intravenous treatments is included in the GGC Adult Formulary for the indication in question. It is restricted to use on the advice of microbiologists or infectious disease physicians when laboratory results indicate sensitivity and according to local primary care or acute sector treatment protocols.

Other changes to Formulary:

Trospium chloride modified-release capsules (Regurin XL^®) for the symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as may occur in patients with overactive bladder is now included in the Preferred List of the GGC Adult Formulary.

Diclofenac (oral preparations) have been moved from the Preferred List of the GGC Adult Formulary to the Total Formulary.

Apixaban tablets (Eliquis^®) for the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (NVAF), with one or more risk factors has had its Formulary status amended.  In addition to patients poorly controlled on warfarin, newly diagnosed patients will have this available as a treatment option.  Patients who are well controlled on warfarin should remain on warfarin therapy.

Dabigatran etexilate tablets (Pradaxa^®) for the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors, has had its Formulary status amended.  In addition to patients poorly controlled on warfarin, newly diagnosed patients will have this available as a treatment option.  Patients who are well controlled on warfarin should remain on warfarin therapy.

Low Dose Naltrexone (LDN)

Naltrexone is an opioid-receptor antagonist which is used as an adjunct to prevent relapse in formerly opioid-dependent patients.  It has also been used in low doses of 3 to 4.5mg, which is a specially made formulation, for management of symptoms of multiple sclerosis (MS) (unlicensed use).

The UK Medicines Information Service has recently published a question and answer document of the evidence for the use of low dose naltrexone (LDN) in MS. In summary:
• Small pilot studies have shown that LDN is a relatively safe and well tolerated drug in people with MS and can improve some symptoms. However, a randomised, double blind, placebo controlled trial needs to be performed to fully assess the efficacy and safety of the drug.
• There is no published long term data on efficacy and safety of LDN when used for MS.
• One study did not find any evidence of incompatibility between LDN and interferon beta. LDN may block the analgesic effects of opioid drugs and they should not be used together.
• If LDN is used to treat MS, both the indication and product formulation are unlicensed.
• If LDN is taken, a positive beneficial response to LDN cannot be assured or guaranteed.
• There is not enough evidence based information to prove LDN is an effective treatment for MS.

Novel Oral Anticoagulants

NHS guidance states that patients with non-valvular atrial fibrillation (AF), who are believed to be complying with warfarin therapy but who have a poorly controlled INR should be considered for a novel oral anticoagulant (NOAC).  A poorly controlled INR for this purpose is defined as therapeutic less than 60% of the time.  Recent guidance from the Heart Managed Clinical Network (MCN) states that these patients will be identified by the Glasgow and Clyde Anticoagulation service (GCAS) who will contact the patient’s GP to suggest consideration of a switch to one of the NOACs.  The guidance provides information on factors which should be considered when making the decision to change to a NOAC and the choice between the three agents.

We have been made aware of industry employed “interface” pharmacists contacting practices offering to review AF patients and to identify patients suitable for switching to particular NOAC drugs.  Practices are strongly encouraged to decline such offers and follow the advice from GCAS.

The role of NOACs in the management of new patients has been under consideration and the Heart MCN is undertaking a review of the NHSGGC AF guideline. This will include a change which will support the option of prescribing a NOAC as a first-line alternative to warfarin where anticoagulation is indicated in patients newly diagnosed with non-valvular AF. The Formulary status of dabigatran and apixaban has been updated to reflect this change. The position for rivaroxaban is unchanged and is in line with SMC advice.

Chronic non-malignant pain opioid guidelines - updated

The updated NHSGGC Chronic Non-Malignant Pain Opioid Guidelines are now available in the Clinical Guideline Repository on StaffNet.
The guideline contains information on:
• Assessing for appropriateness of a trial of opioid treatment
• Need for regular assessment and review
• Choice of opioid and maximum recommended doses
• Opioid dose equivalences
• When to consider referral to pain clinic

Reducing Prescribing of Hypnotics and Anxiolytics

While it is recognised as good clinical practice to review patients on regular anxiolytic or hypnotic therapy with a view to withdrawal, it is recognised that there are some exclusion criteria which would make a stepwise reduction inappropriate. Exclusion criteria include (not exhaustive):
• Patients experiencing current crisis or illness requiring on going prescription
• Patients with severe mental health problems or prescribing by a psychiatrist
• Patients receiving benzodiazepines for management of epilepsy
• Patients with a chronic or acute condition where benzodiazepine is used to relieve muscle spasm
• Patients who are substance misusers attending community addiction team

For other patients there may be a need for caution when changing current treatment including (not exhaustive):
• Patients who are seriously ill or receiving palliative care
• Previous failed attempt at step down
• Where there is the potential for drug-drug/pharmacodynamic interactions.
• Patients with Parkinson’s Disease (PD) – PD specialist advice should be sought. Anxiety and sleep disturbance (often multifactorial, including REM sleep behaviour disorder) are very common, non-motor complex symptoms in PD and may be modulated by benzodiazepines. The interaction between dopaminergic and GABAergic neurones is complex and not fully understood.

Methotrexate and Trimethoprim Interaction

Concurrent administration of trimethoprim and methotrexate has been reported to cause haematological toxicity. Information available on the interaction is limited and the mechanism is not fully established but is thought to be due to the additive inhibition of dihydrofolate reductase by trimethoprim and methotrexate.  Although there are several case reports of this interaction in the published literature, the duration of trimethoprim therapy prior to the bone marrow suppression occurring is not always stated. There is information to suggest that it can occur as soon as two days after commencing trimethoprim as well as after long term use. Therefore there is a risk of a clinically significant interaction with short courses of trimethoprim of 3-7 days duration.  This would also apply to co-trimoxazole.

Depression Treatment Guideline

The Depression Treatment in Primary Care Guideline for NHSGGC has been revised. The guideline aims to bring together non-pharmacological and pharmacological management within a NHSGGC context.  The main changes are to remind prescribers:
• In general, increasing SSRI doses in depression does not improve efficacy.  Daily doses: '50's enough' for sertraline and '20's plenty' for fluxoxetine or citalopram to assess initial response.
• If patients are compliant with therapeutic antidepressant doses they should see some improvement within two to four weeks.
• More prescribing information has been included when treating patients with co-morbidities and to address common prescribing questions.

Vitamin B₁₂ Injections Prescribing Guidance

Hydroxocobalamin is the preferred form of vitamin B12 as it is retained longer in the body than cyanocobalamin and can be given at intervals up to 3 monthly for maintenance. Hydroxocobalamin injection is available as a pack of 5 vials and is subject to over-ordering and a high degree of waste.

To minimise waste and reduce the likelihood of over-ordering, practices may wish to consider a policy of:
- Prescribing a quantity of 1 vial on repeat
- Adding the frequency of injection to the dose instructions on prescription
- Prescribe as acute rather than repeat

Education of staff handling repeat prescription requests could also ensure that prescriptions are not issued before necessary.

To view this edition in PDF format click here.

Information included is specific to the use of medicines in the adult setting

Pharmacy Prioritisation and Referral

Background

Clinical pharmacists cannot review all patients in NHSGGC every day. In order to allocate clinical pharmacist resource where it is most needed, patients' pharmaceutical care needs must be assessed and prioritised accordingly.

Current model of clinical pharmacist service delivery

Until now the approach adopted has been to prioritise clinical areas for pharmacist input based on the perceived pharmaceutical risk.  In practice, this means that some wards are visited by a clinical pharmacist Monday to Friday while other clinical areas receive no visit at all.

It is known that in the "lower priority" areas not receiving a visit there will be some patients with a clear need for pharmaceutical care. Equally, some patients with little need for pharmacist input will be reviewed unnecessarily. 

Alternative models

(Based on prioritisation of patient need rather than clinical setting)

• Early GGC pilots of medical/nursing staff referring patients for pharmacy review were unsuccessful.  Referral rates were low and potentially appropriate patients were not referred. 
• A report from Tayside described an approach of assessing medical patients on admission and targeting resources to those at high risk requiring greater follow up. 

New NHSGGC model for pharmaceutical care service delivery

The planned approach for NHSGGC is a combination of the above strategies known as "Triage and Referral".  A triage assessment tool has been developed (Diagram 1).

Initial work showed the application of the simple tool by pharmacists was as sensitive in identifying patients with ongoing care issues as the opinion of an experienced pharmacist. 

Further studies in NHSGGC have validated this approach in patients in the medical and rehabilitation directorates.  The tool was highly sensitive in identifying patients with pharmaceutical care issues as the majority of care issues occurred in patients in the high risk (red) category.

As predicted, these studies also demonstrated that less clinical pharmacist time was spent monitoring low risk patients.  Adopting the revised service model will allow pharmacist resource to be refocussed on higher risk patients who are likely to need more time dedicated to their pharmaceutical care.  This includes patients who would not previously have been seen at all because their ward did not have a clinical pharmacist.

Diagram 1: The Patient Journey

Please note:  Discharge prescriptions will be reviewed by a pharmacist before being authorised for dispensing.  This is not a full clinical check and the pharmacist completing the check may not have all of the patient's clinical information available to them.  Further detail is available here.

Early implementer sites (Surgical Directorate, Western Infirmary and ECMS Directorate, Victoria Infirmary) report positive outcomes from the new model including:

• Increased medicines reconciliations completed
• Increased accuracy of discharge prescriptions
• Positive feedback from medical/nursing staff  
• Increased satisfaction of pharmacy staff

Referral

There are concerns that issues will be missed if a patient’s condition deteriorates or medication changes.  Therefore, there will be a simultaneous referral system for medical and nursing staff to refer a patient back to the pharmacy team if a patient’s status changes.  Additionally, each clinical area will have a named contact from the pharmacy technical team who will refer issues to the clinical pharmacy team as appropriate.  The processes and criteria for referral will be communicated in due course. 

Next steps

One key issue is keeping track of patients in this system, as at present it involves a great deal of paperwork and organisation. In development is a pharmacy view for electronic whiteboards which is being designed to highlight triage category and discharge status.  This is likely to help considerably with organisation of work and improve workflow.  Timescales for wider rollout of the triage and referral system across NHSGGC are largely dependent on this development.

Novel Oral Anticoagulants (NOACs) in Atrial Fibrillation: update

NOACs (dabigatran, rivaroxaban, apixaban) are currently included on the NHSGGC Formulary for existing patients with non-valvular atrial fibrillation (AF) who are intolerant of, or poorly controlled on, warfarin.  The Heart Managed Clinical Network (MCN) is undertaking a review of the NHSGGC AF guideline. This will include an option to prescribe a NOAC as a first-line anticoagulant in patients newly diagnosed with non-valvular AF. 

Please note:  Patients who are well controlled on warfarin should remain on warfarin; a switch to NOAC in these patients is discouraged and remains non-Formulary.

More detail can be found here  and the updated guideline will be communicated in future bulletins.

Tumour necrosis factor alpha inhibitors: risk of tuberculosis (TB)

Tumour necrosis factor alpha (TNF-alpha) inhibitors (adalimumab, certolizumab, etanercept, golimumab, and infliximab) may increase the risk of TB/reactivation of latent TB.  In patients on TNF-alpha inhibitors TB can be life threatening.  Prescribers are reminded that these medicines are contraindicated in TB or other severe infections.  Screening for TB should be undertaken before treatment commences and patients should also be monitored for severe infections during and after treatment.  More detail can be found  here.

Guideline News 

*NICE Guidelines are developed for prescribers in NHS England and Wales and as such may not always follow NHS Scotland prescribing policy e.g. SMC advice.  They should always be used in conjunction with relevant NHSGGC Formulary and Clinical Guidelines. 

Learning from incidents: Warfarin follow-up post-discharge

In the last quarter, approximately 8% of all medication incidents reported in NHSGGC involved an anticoagulant medication. In nearly 40% of these, new or existing patients were not appropriately referred to the Glasgow & Clyde Anticoagulant Service (GCAS) for follow up.  In general, this happens on average several times a week and has resulted in a number of serious incidents and patient harm.  

The case example below is used to demonstrate the clinical consequences of inappropriate follow-up to GCAS and the associated key learning points.

Case example

A patient on long term warfarin therapy was prescribed clarithromycin during a hospital admission and was discharged without a follow up GCAS appointment.  

(Clarithromycin can significantly enhance the anticoagulant effect of warfarin and the combination requires regular monitoring, both during the antibiotic treatment and for some time afterwards.)

One week after discharge, a pharmacist in the community identified the lack of follow-up for this patient and arranged a GCAS appointment.  However, before the appointment date, the patient was readmitted to hospital with signs of bleeding and a reported INR of 15. 

On review of the case, the Immediate Discharge Letter (IDL) stated that an appointment had been made but this had in fact been overlooked.

Key learning points

• Referral should not be left to the GP or the patient themselves. 
• Do not rely on GCAS appointments booked pre-admission without checking with GCAS; existing GCAS appointments are cancelled when a patient is admitted to hospital.
• Patients should normally be seen within 7 days of discharge (even if the patient is considered stable), but some may need to be seen sooner depending on factors such as drug interactions, stability of INR. Highlight any who may require an early appointment or who may have difficulty attending the clinic. 
• Information on the referral process is available in the Therapeutics Handbook and on the GCAS Prescribing, Monitoring and Referral Form.  

• The last 3 warfarin doses (as a minimum)
• The last 3 INRs (as a minimum)
• The advised dose on discharge
• Details of their next clinic appointment
• Factors potentially affecting warfarin requirements such as a change in diet or interacting medicines.  This is important, regardless of whether the patient is still taking the  medicine(s), as the effect on warfarin metabolism may be prolonged.   

Ensure that the date of the patient’s GCAS appointment is documented in both the patient’s yellow book and the IDL. 

• Often the dose on discharge cannot be advised until late afternoon on the day of discharge. As such information cannot be documented on the IDL until after a warfarin supply is issued from pharmacy, a specific dose cannot be written on the label of the dispensed warfarin.
• Staff must therefore ensure that the patient understands how to take their warfarin tablets before they leave hospital.   

• This helps ensure that appropriate information (see above) is communicated promptly to the GP.
• Patients not requiring a supply of medicines from pharmacy should still have a completed IDL before they leave the ward.

Adult Gentamicin Prescription Chart:  updated version

An updated version of the NHSGGC Adult Gentamicin Prescription, Administration and Monitoring chart will now be supplied against any new ward orders (please use up existing supplies before ordering the updated chart). 

Slight amendments to the current chart were agreed by the Antimicrobial Utilisation Committee.  The main change is the introduction of space to record creatinine concentrations – see screen shot below. 

All healthcare professionals involved in the treatment of patients with gentamicin are reminded of the need to monitor renal function.  The patient’s creatinine should be monitored daily and recorded on the gentamicin chart. 

Reminder:  How to safely prescribe WEEKLY oral alendronic acid

The most common dose of alendronic acid for the treatment of osteoporosis is 70mg WEEKLY.  To prevent inadvertent daily administration, follow the advice below: 

1. Write the word ‘WEEKLY’ in the ‘comments’ box.

2. Write the DAY of the week in the ‘comments’ box

3. Cross out the days of the week that the dose should not be given

Please note: Oral methotrexate and topical buprenorphine are other examples of medicines which have WEEKLY dosing schedules.

The latest edition is available here.

Articles cover the following topics:

• NHS Healthcare provision to Police Custody Suites
• Instalment Dispensing
• Saline Steripoules® on ScriptSwitch®
• Advice on use of Relvar Ellipta® (fluticasone furoate and vilanterol)
• Commonwealth Games Travel restrictions and treatment of overseas visitors
• Novel Oral Anticoagulants (NOACs)
• Community Pharmacy LES Programme for 2014/2015
• Pharmacy Champion - Glasgow City - North-East Sector
• Changes to Prescriptions

 Oral NSAIDs - An Update

To view this issue in PDF click here

Additions to the GGC Adult Formulary

Greater Glasgow and Clyde Area Drug and Therapeutics Committee (ADTC) met on 9^th June 2014 and added the following medicines/indications/ formulations to the GGC Formulary.  Additions are to the Total Formulary unless specified otherwise.

Aripiprazole long-acting injection (Abilify Maintena^®) for maintenance treatment of schizophrenia in adult patients stabilised with oral aripiprazole is included in the GGC Adult Formulary for the indication in question. It is restricted to use under the overall supervision of a psychiatrist.

For relevant SMC advice click here

Budesonide gastro-resistant granules (Budenofalk^®) for the induction of remission in patients with mild to moderate active Crohn’s disease affecting the ileum and/or ascending colon is included in the GGC Adult Formulary for the indication in question. It is restricted to initiation by, or on the advice of gastroenterologists.

For relevant SMC advice click here

Canagliflozin tablets (Invokana^®) for use in adults aged 18 years and older with type 2 diabetes mellitus to improve glycaemic control as add-on therapy with other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control is included in the GGC Adult Formulary. It is restricted to initiation by clinicians experienced in the management of diabetes for:

• dual therapy in combination with metformin when a sulphonylurea is inappropriate

• triple therapy in combination with metformin plus standard of care

• as an add-on to insulin therapy in combination with insulin plus standard of care. 

For relevant SMC advice click here

Certolizumab pegol injection (Cimzia^®) for the treatment of adult patients with severe active axial spondyloarthritis, comprising (1) Ankylosing spondylitis (AS) and (2) Axial spondyloarthritis without radiographic evidence of AS (nr-axSpA) is included in the GGC Adult Formulary for the indication in question. It is restricted to specialist use.

For relevant SMC advice click here

Defibrotide infusion (Defitelio^®) for the treatment of severe hepatic veno-occlusive disease (VOD) also known as sinusoidal obstruction syndrome (SOS) in haematopoietic stem-cell transplantation (HSCT) therapy is included in the GGC Adult Formulary for the indication in question. It is restricted to specialist use.

For relevant SMC advice click here

Dolutegravir tablets (Tivicay^®) for use in combination with other antiretroviral medicinal products for the treatment of Human Immunodeficiency Virus (HIV) infected adults and adolescents above 12 years of age is included in the GGC Adult Formulary for the indication in question. It is restricted to use by HIV specialists.

For relevant SMC advice click here

Fluticasone furoate and vilanterol dry powder inhaler (Relvar Ellipta^®) for the regular treatment of asthma in adults and adolescents aged 12 years and older where use of a combination medicinal product (long-acting beta2-agonist and inhaled corticosteroid) is appropriate in patients not adequately controlled with inhaled corticosteroids and 'as needed' inhaled short-acting beta2-agonists is included in the GGC Adult Formulary for the indication in question.

Prescribing note: Fluticasone furoate is a high-potency inhaled steroid (with a dose of 92micrograms once daily broadly equivalent to 250micrograms twice daily of fluticasone propionate). When used for asthma, due consideration for the likelihood of step-down should be given prior to initiation as there are no available step-down options containing a dose lower than 92 microgram of fluticasone furoate.

For relevant SMC advice click here

Sofosbuvir tablets (Sovaldi^®) for use in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults is included in the GGC Adult formulary for the indication in question pending protocol.  It is restricted to specialist use in accordance with local protocol (under development).

For relevant SMC advice click here

New medicines, indications and formulations not included in the GGC Adult Formulary or GGC Paediatric Formulary

The following are not included in the GGC Adult Formulary following the latest ADTC meeting. Where the reason is other than not recommended advice from SMC it is noted.  NB: these medicines may be included in the Formulary for other indications or for other formulations.  Please refer to Formulary.

Avanafil tablets (Spedra^®) for the treatment of erectile dysfunction in adult men is not included in the GGC Adult Formulary for the indication in question.

For relevant SMC advice click here

Cobicistat tablets (Tybost^®) as a pharmacokinetic enhancer of atazanavir 300 mg once daily or darunavir 800 mg once daily as part of antiretroviral combination therapy in human immunodeficiency virus-1 (HIV-1) infected adults is not included in the GGC Adult Formulary for the indication in question.

For relevant SMC advice click here

Infliximab infusion (Remicade^®) for the treatment of moderately to severely active ulcerative colitis in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine or azathioprine, or who are intolerant to or have medical contraindications for such therapies is not included in the GGC Adult Formulary for the indication in question.

For relevant SMC advice click here

Natalizumab infusion (Tysabri^®) as a single disease modifying therapy in highly active relapsing remitting multiple sclerosis (RRMS) for adult patients aged 18 years and over with high disease activity despite treatment with glatiramer acetate is not included in the GGC Adult Formulary for the indication in question.

For relevant SMC advice click here

Paclitaxel Albumin infusion (Abraxane^®) for use in combination with gemcitabine for the first-line treatment of adult patients with metastatic adenocarcinoma of the pancreas is not included in the GGC Adult Formulary for the indication in question.

For relevant SMC advice click here

Other Formulary Decisions

UT 380^® short/standard intra-uterine device for contraception is now included as an additional choice within the Preferred List of the GGC Adult Formulary.

Diprobase^® cream for the use as an emollient for dry skin conditions has been moved to the Total Formulary. Zerobase^® Cream is the nearest Preferred List option.

Tramadol: Change in Legal Status to Schedule 3 Controlled Drug

• Tramadol is now classed as a controlled drug
• Prescribing: Tramadol must now be prescribed as a controlled drug (CD). Note the requirements for interval of supply, amount per supply plus daily dose to be included if prescribing by instalments. Prescriptions are only valid for 28 days. The GP software providers are making changes to the systems.
• Good practice recommendation is no more than 30 days supply per prescription
• Storage: There is no need to store in the CD cupboard. 
• Recording: No requirement to be recorded in the CD register.
• Stock orders: Orders must conform to CD requisition requirements.
• PGDs: tramadol will not be able to be included on any PGDs. The national PGD for community pharmacy urgent supply will be amended.
• Destruction: Tramadol, like all Schedule 2-4 CDs, should be denatured by use of a CD destruction kit before disposal in pharmaceutical waste.

A memo has been sent to all NHSGGC practices.

Gluten-Free Food Service from Community Pharmacies

Practice staff and prescribing support teams are asked to note that all non-care home patients with a confirmed diagnosis of coeliac disease (CD) and dermatitis herpetiformis (DH) who are registered with the practice are eligible to access the service from their local pharmacy. This is regardless whether the patient currently obtains their GF foods on GP10 or not.

Please note that all registration forms should be signed by the GP. This is the instruction to the pharmacy for the transfer of care for the patient and therefore, the form cannot be signed another member of the practice staff.
When a patient is registered with a particular pharmacy they will receive an annual health check which will include assessment of the patients understanding of and concordance with gluten-free diet; vitamin/mineral supplementation; symptoms and Body Mass Index. A summary of this will be sent to the GP.

Patients who receive sweet biscuits on GP10 must also be provided with the “Patient Form for Additional Gluten-Free Units and Sweet Biscuits” to allow the pharmacy to supply a maximum of two units of these products within the patient’s normal food unit allowance. This Patient Form must also be signed by the GP.

Domperidone

Further to the information in a previous bulletin, the MHRA have recently provided new information on the prescribing of domperidone. Due to the increased risk of serious cardiac side effects, domperidone use is now restricted:
• to the relief of nausea and vomiting symptoms
• contra-indicated in people with conditions where cardiac conduction is or may be impaired, cardiac diseases such as congestive heart failure, taking other drugs known to prolong QT or potent CYP3A4 inhibitors, and those with severe hepatic impairment.  These patients should have treatment reviewed at next routine appointment and switched to an alternative if required
• Maximum oral dose for patients over 12 years and weight 35kg or more: 30mg in 24 hours (10mg up to three times a day)
• Maximum oral dose for children under 12 years and weighing less than 35kg: 0.75mg/kg body weight (0.25mg/kg body weight up to three times a day)
• Maximum suppository dose (adults and adolescents over 35kg weight): 60mg in 24 hours (30mg twice a day)
• Maximum treatment duration is 7 days

UKMI have produced advice on alternative management options for patients with Dyspepsia/Reflux and gastroparesis.

Medicines for Children have a patient information leaflet on use of domperidone for reflux.

Dual Antiplatelet Therapy

Clopidogrel or ticagrelor are indicated as part of a dual anti-platelet therapy (DAPT) regimen along with indefinite aspirin for management of patients with acute coronary syndrome (ACS) and/or undergoing percutaneous coronary intervention (PCI). The NHSGGC Guideline for Antiplatelet Therapy in Secondary Prevention of Coronary Heart Disease makes recommendations for DAPT duration in accordance with clinical circumstances.

Systems are in place to prevent inappropriate continuation of DAPT. These include the immediate discharge letter stating recommended length of therapy, the patient and their General Practitioner (GP) being provided with an information leaflet and in the case of patients undergoing PCI at Golden Jubilee National Hospital (GJNH), a letter from the Prescribing Team advising the GP when DAPT should be stopped. Despite this, DAPT is often continued inappropriately.

Prescribing was audited in 43 Practices in Glasgow North East during April and May 2014.  More detailed results of this audit will be included in the next PostScript bulletin in July 2014.

The key findings:
Following publication of the antiplatelet guideline in May 2013, patients receiving a drug-eluting stent should have been prescribed DAPT for 26 weeks.
• 26% of patients had therapy recommended for 26 weeks
• Reasons for non-guideline durations were not routinely recorded.

70% of patients had emergency or elective PCI with the rest managed medically. Patients treated medically should receive 12 weeks of therapy, and this correlates with the number of patients prescribed 12 weeks therapy suggesting appropriate duration.
• 37.6% of patients exceeded the intended duration
• 76.8% of these were prescribed clopidogrel and 19% ticagrelor.
• A total of 7,537 weeks excess therapy was prescribed (average 11.9 weeks per patient)
• The cost of excess treatment was £8,386.  Had this been entirely for ticagrelor, the associated cost would have been £102,880.

202 (46.2%) of the 437 patients undergoing PCI at GJNH had Prescribing Team correspondence recommending DAPT cessation filed in the patient notes. A notable difference existed in the average excess duration between the groups who did receive a letter (20 weeks) and did not receive a letter (41 weeks).   Just over half the patients received the correct duration of treatment and that was regardless of whether the practice received a letter or not.

157 interventions were undertaken; 90 were to discontinue inappropriate DAPT. Had this intervention not been undertaken, there would have been an ongoing drug cost of £7700 per annum. As ticagrelor supersedes clopidogrel for ACS, it is anticipated that this would be greater in future. 26 patients had the intended stop date annotated on their prescription in accordance with best practice, as outlined in PostScript Primary Care (September 2013).

Patient Group Directions

A Patient Group Direction (PGD) is a legal document which requires approval by the health board before healthcare practitioners may work under it. In NHSGGC these documents are approved by a subgroup of the Area Drug and Therapeutics Committee (ADTC). The administration of the sub group distributes new and reviewed PGDs to appropriate practitioners by cascading the documents either through line managers or clinical leaders as appropriate. As the ADTC PGD sub group administration will know the best person to contact to answer any questions, any queries about the content of a PGD should ideally be referred directly to them rather than a line manager or clinical leader.

For any queries about an NHSGGC PGD please email Jacqueline.richardson@ggc.scot.nhs.uk

This edition can be accessed in PDF format here and contains articles on:

• Dual Antiplatelet Therapy
• Safety Update: Domperidone
• PPIs and clostridium difficile
• Drug induced photosensitivity
• Non-Medical update
• PostScript Extra NSAIDS
• ADTC decisions

ADTC decisions are here including:

Non-medical update

• Minor surgery or other invasive procedures for people taking novel oral anticoagulants (NOACs): dentists and others who perform minor procedures, eg administer joint injections have criteria to assess suitability for those patients taking warfarin. Recent information has been presented to the NMP podiatry forum on the relevance of concomitant treatment with NOACs. This covers issues such as timing of next dose, effect of renal impairment on timings. Specific advice for apixaban, dabigatran and rivaroxaban can be found on Staffnet.
• The new absorbent dressing of choice in all care settings in NHSGGC is now Premierpore instead of Mepore; with supplies available in wholesalers. Community pharmacists have been notified to run down current stock of Mepore.  

PostScript Extra: NSAIDs

There is a new PostScript Extra bulletin on Oral NSAIDs available here. This is an update to the previous version and is in line with the new anti-inflammatory guideline on nonsteroidal oral medicines which will shortly be posted on StaffNet. Naproxen and ibuprofen are the oral NSAIDs of choice taking into consideration the patient's GI and cardiovascular risks. The lowest effective dose should be used to control the patient's symptoms for the shortest duration possible.

At this time of year, with improving weather and the peak holiday period, the incidence of reactions to sun increase. Some medicines cause particular problems. Dr Paula E Beattie, Consultant Dermatologist at the Royal Hospital for Sick Children described some of the issues.

Drug photosensitivity reactions occur when a drug or metabolite within the skin interacts with ultraviolet (UV) radiation in sunlight. The drug may be ingested, injected or rarely applied topically. The vast majority of photosensitive reactions are phototoxic reactions.

The majority of drugs absorb UV wavelengths. A phototoxic reaction occurs when the drug present in the skin absorbs UV wavelengths specific to that chemical, becomes excited and produces a photochemical reaction which damages cellular components resulting in inflammation.

It can occur in any subject with sufficient exposure to the drug and to UV radiation; for example, doxycycline at a dose of 100mg will photosensitise 10-20% of individuals in Western Europe but at a dose of 200mg in summer months or in sunnier climates will photosensitise a much higher proportion.

Various patterns of phototoxicity are recognised:

• most manifest as an exaggerated sunburn reaction and so the diagnosis is often missed
• recurrent immediate erythema (redness) can give way to a chronic exposed site dermatitis with drugs given long term, eg thiazides.
• recurrent phototoxicity may sometimes be associated with photocarcinogenesis, eg vorioconazole. 
• an immediate prickling, burning, erythema and swelling can also be seen, sometimes with delayed erythema and pigmentation. This pattern is most commonly seen after chlorpromazine and amiodarone (slate grey pigmentation)
• exposed site telangiectasia can occur when calcium channel antagonists target blood vessels
• increased skin fragility and blistering (pseudoporphyria) can occur with NSAID, tetracyclines, furosemide, amiodarone and fluroquinolones
• photo-onycholysis, where the nail separates from the bed, can occur with doxycycline.

A small proportion of reactions may be attributed to mechanisms other than phototoxicity, see below. Many will cause a typical pattern of reaction but some may cause photosensitivity by more than one mechanism, eg phenothiazines.

Photoallergy is a rare type IV hypersensitivity reaction which occurs most commonly with a topical chemical, eg sunscreen or NSAIDs, to form a photoallergen which presents as an exposed site dermatitis.

Knowledge of drug interaction with wavelength absorption can inform advice to patients on duration of photoprotection required. Potentially scheduling evening dosing of drugs such as flouroquinolones which have a short effect may help avoid phototoxicity. 

Advice to patients when prescribing a potentially phototoxic drug

• Use photoprotection, including clothing and hats. Clothing should be of a fine weave so that light is not transmitted when held up to the light.
• Avoid the sun between the hours of 11am and 3pm and seek shade when outdoors. Note that shade from trees and umbrellas is not total shade and that variable exposure still occurs. UVA can also be transmitted through glass.
• Sunscreen should be very high factor. Most individuals apply it at a thickness that achieves a SPF 5-20 from an SPF50 sunscreen. Apply liberally and reapply frequently.
• Sunscreens can be prescribed in primary care only for protection in abnormal cutaneous photosensitivity resulting from genetic disorders or photodermatoses including vitiligo, those resulting from radiotherapy; chronic or recurrent herpes labialis. The NHSGGC Preferred List option is Sunsense Ultra (SPF 50+).

Clostridium difficile infection (CDI) is one of the important healthcare associated infection in Scottish hospitals. It is life-threatening (reported mortality rate 10 - 30%) and has the potential for person to person spread within healthcare settings. Particularly at risk are patients who are aged > 65 years, frail, immunocompromised or who have chronic obstructive pulmonary disease or cardiovascular disease. Across Scotland, rates of CDI have levelled off after a period of significant decreases but there is a need for new strategies to address the burden of CDI that still remains.

PPIs have been identified as a risk factor for CDI but, historically, the evidence has been conflicting. Four recently published meta-analyses provide further evidence that the use of PPIs can increase the risk of CDI and its recurrence, albeit there is general agreement with regards the low quality of available evidence. The recently published CDI guidelines from Health Protection Scotland, suggest that consideration should be given to stopping or reviewing the need for PPIs in patients with or at high risk of CDI.

There is also evidence that PPIs may be linked to other adverse clinical outcomes, while a number of studies (from the UK and the US) suggest that between 60-86% of PPIs may be being used inappropriately.

A significant amount of work has been undertaken in recent years in primary care to ensure PPI therapy is reviewed regularly. There is also guidance available on prescribing PPIS for patients discharged from hospital.

This additional information reminds prescribers of the need for ongoing review of patients prescribed PPIs to consider whether doses can be decreased or therapy stopped rather than continued indefinitely.

The MHRA has recently recommended changes to the use of domperidone, including restricting the dose and duration of use, to minimise the known risks of potentially serious cardiac adverse effects.

There are now no drugs on the UK market licensed as prokinetic agents. Metoclopramide has also recently had restrictions placed on its use due to extrapyramidal adverse effects. It should only be used short-term (up to 5 days) and should not be used in chronic conditions such as gastroparesis, dyspepsia and GORD, nor as an adjunct in surgical and radiological procedures.

• Domperidone is now only licensed for nausea and vomiting.
• Domperidone should be used at the lowest effective dose for the shortest possible duration. The maximum treatment duration should not usually exceed one week.
• The new recommended dose in adults (and adolescents ≥ 35kg where licensed) is 10mg orally up to three times daily (maximum dose of 30mg daily). Adults and adolescents weighing ≥ 35kg may be given 30mg twice daily rectally as suppositories.
• In children under 12 years of age and less than 35kg, the recommended maximum oral dose is 0.25mg/kg body weight up to three times a day.
• Domperidone is contraindicated in severe hepatic impairment, conditions where cardiac conduction is, or could be, impaired or where there is underlying cardiac disease, and when co-administered with QT-prolonging medicines or potent CYP3A4 inhibitors.

Advice on alternative management of patients with GORD / dyspepsia and gastroparesis has been produced by UKMI and is available at http://www.midlandsmedicines.nhs.uk/filestore/domperidone%20GI%20restrictions%20May%202014.pdf

Medicines for Children, a partnership of bodies including the Royal College of Paediatrics and Child Health and the Neonatal and Paediatric Pharmacists’ Group has information on use of domperidone in children at http://www.medicinesforchildren.org.uk/search-for-a-leaflet/domperidone-for-gastro-oesophageal-reflux/.

Practices have already been advised on appropriate timescales and mechanisms for managing this change.

Clopidogrel or ticagrelor are indicated as part of a dual anti-platelet therapy (DAPT) regimen along with indefinite aspirin for management of patients with acute coronary syndrome (ACS) and / or undergoing percutaneous coronary intervention (PCI). The NHSGGC Guideline for Antiplatelet Therapy in Secondary Prevention of Coronary Heart Disease makes recommendations for DAPT duration in accordance with clinical circumstances.

Risks of inappropriate treatment

Concerns have been raised previously about the potential for patients to be continued on treatment after the anticipated stop date. Extended treatment means that patients continue to be exposed to the risk of adverse effects without additional clinical benefit.

Systems have been put in place to prevent inappropriate continuation of DAPT. These include the immediate discharge letter stating recommended duration of therapy, the patient and their GP being provided with an information leaflet and in the case of patients undergoing PCI at Golden Jubilee National Hospital (GJNH), a letter from the Prescribing Team advising the GP when DAPT should be stopped. Despite this, DAPT might not always be stopped at the correct time.

Auditing practice

Prescribing was audited in Glasgow North East during April and May 2014.

• 43 practices were involved
• 631 patients were reviewed; an average of 15 per practice.
• 81% of patients had DAPT commenced on a cardiology ward or directly by GJNH.
• General medical, medicine for the elderly and surgical wards were responsible for a small proportion of initiations.
• The intended duration of therapy was generally readily identifiable.

The antiplatelet guideline published in May 2013 recommended that patients receiving a drug-eluting stent should generally be prescribed DAPT for 26 weeks. The audit identified that:

• 26% of patients had therapy recommended for 26 weeks
• Approximately one third of patients were recommended 12 weeks’ therapy
• Another third were recommended a duration of 52 weeks (in line with previous advice).
• 17 patients had 52 weeks therapy requested post-guideline launch (June 2013 onwards)
• 4 patients had lifelong DAPT specified.
• Reason for therapy duration deviating from the guideline was not always recorded.

70% of patients had emergency or elective PCI with the rest managed medically. Patients treated medically should receive 12 weeks of therapy; this correlates well with actual practice.

Almost 40% of patients (237) exceeded the intended duration; 77% of these were prescribed clopidogrel and 19% received ticagrelor.

• A total of 7,537 weeks of excess therapy was prescribed
• This averages 12 weeks per patient
  • range 1 – 504 weeks
• The cost of excess treatment was £8,386. The cost of clopidogrel has reduced dramatically in recent years; if this pattern to continued, but with ticagrelor as the predominant agent, costs would have been in excess of £100,000.

Almost half of the patients undergoing PCI at GJNH had Prescribing Team correspondence recommending DAPT cessation in the patient record. A notable difference existed in the average excess duration between the groups who did receive a letter (20 weeks) and did not receive a letter (41 weeks). Just over half the patients received the correct duration of treatment and that was ireespective of whether the practice received a letter.

Changing practice following audit

A variety of actions and evaluations were undertaken as a direct result of the audit:

• 157 clinical interventions were undertaken
• In 90 cases inappropriate DAPT was discontinued.
• This prevented an ongoing annual drug cost of £7,700.
• 26 patients had the intended stop date annotated on their prescription in accordance with best practice, as outlined in PostScript Primary Care (September 2013) http://www.ggcprescribing.org.uk/media/uploads/ps_primary_care/pspc_september_2013.pdf.

Practices are advised to review processes for managing advice on duration of DAPT therapy, eg by use of stop dates on the prescription.

Varenicline (Champix^®) PGD

The community pharmacy Smokefree smoking cessation support service is part of the Public Health Service element of the community pharmacy contract. It aims to provide extended access to smoking cessation support, including the provision of patient centred behavioural support and evidence-based pharmacotherapy. In addition to NRT, accredited pharmacists can now supply varenicline under a national Patient Group Direction (PGD) as part of this service to suitable patients who have previously tried to stop smoking using NRT.

When a patient starts a quit attempt using varenicline as part of this service, the pharmacy will inform the patient’s GP by a standard letter following the first consultation.  GPs should add this to their prescribing system as a drug prescribed/supplied outwith the practice, see PostScript 78 for more details. Instructions for EMIS and Vision can be found in the Prescribing Resources section of the NHSGGC Prescribing website. For further details about the service and inclusion/exclusion criteria within the PGD please see the NHS circular.

Subcutaneous methotrexate

Metoject^® is the preferred brand of parenteral methotrexate in GGC. For use in rheumatology, patients are started on parenteral methotrexate in secondary care and trained in self administration by Rheumatology Nurses at hospital clinics, but ongoing prescribing and blood monitoring is undertaken in primary care. The manufacturer has advised that from 1st July, the pre-filled syringe product will be replaced by Metoject^® PEN, a single use pre-filled auto-injector device for self administration. Affected patients have been informed of the upcoming change by the Prescribing Support Team, and have been issued with a copy of the manufacturer’s patient leaflet and a letter from the Rheumatology MCN Clinical Lead with contact details of Rheumatology Nurses if they require more training or support. Community pharmacists should receive a printed instruction booklet for the patient with every order for Metoject^® PEN device and have been asked to counsel the patient on its use and record it on the patient’s Chronic Medication Service, High Risk Medicine, Pharmacy Care Record.

Unfortunately the new PEN device description has not been included in the EMIS dictionary at the time of the change over. The new device will be prescribable on EMIS in NHSGGC on Release E which will be downloaded to Phase 1 sites on 8th August, and rolled out to all practices in NHSGGC over six weeks in four phases. For Vision, the description is included in July’s Gemscript. Prescriptions for the new device may require to be handwritten until the description is available on IT prescribing systems.
Further information is available from the manufacturer’s website.

Clostridium difficile and PPIs

Proton pump inhibitors (PPIs) have been identified as a risk factor for C. difficile infection(CDI) but evidence has been historically conflicting.  Four meta-analyses recently published provide further evidence that use of PPIs can increase the risk of C. difficile infection and its recurrence.  The Scottish Antimicrobial Prescribing Group has consulted with Scottish experts in gastroenterology and confirmed that there is a willingness to work together with primary care colleagues to reduce inappropriate PPI use which may reduce C. difficile infection and provide other clinical benefits.

A number of studies from the UK and the US suggest that 60-86% of PPIs may be used inappropriately. The recently published C. difficile infection guidelines from Health Protection Scotland, suggest that consideration should be given to stopping/reviewing the need for PPIs in patients with or at high risk of CDI (includes current or recent antibiotic treatment, increasing age, immunosuppression, prolonged hospital stay, serious underlying diseases, surgical procedures).  Prescribers are reminded of the NHSGGC guidance on PPI durations following discharge from hospital.

Rates of C. difficile infection have reduced significantly in the hospital setting but there have been recent reports of increasing community associated disease in patients without common risk factors such as age or recent antibiotics. This suggests there are other risk factors which are not well understood, and PPIs have been suggested.

PPIs have also been associated with an increased risk of spine, lower arm and total fractures and pneumonia, both community and hospital acquired.  Thus improved use of PPIs could have a number of benefits.

One of the Scottish Government National Therapeutic indicators relates to the volume of PPIs prescribed and encourages a reduction in their use.  Clinicians should regularly review patients prescribed these medicines to ensure that continued prescribing only occurs when clinically necessary and at the lowest possible dose.

Gabapentin - abuse potential

Gabapentin is believed to be one of the drugs most widely abused in the prison population but little is known about the potential for abuse among patients with drug and alcohol problems and in the wider chronic pain population as a whole. Abuse has been described in concurrent users of methadone and dependence also seems to have been reported in patients without any previous history of substance abuse.

There is currently limited knowledge of the extent of the problem and the population likely to abuse the drug is not well characterised. However, prescribers should be aware of the potential for abuse and ensure that gabapentin is only prescribed where it is clearly indicated. They should also be alert to signs of gabapentin misuse such as early requests for repeat prescriptions.  As with other drugs with potential for misuse, prescribers should closely monitor individual usage and may wish to consult the relevant clinical guidelines for alternative prescribing options if misuse is identified.

Buccal midazolam

Buccal midazolam is used as a rescue medication for status epilepticus and is often supported by a product specific administration protocol for care staff who must ensure that the protocol matches the prescribed midazolam.

Recent reports have highlighted issues around buccal midazolam prescribing and administration where patients have received incorrect formulations or doses. Different buccal midazolam preparations and strengths are available but are not interchangeable.

Epistatus^® (10mg/ml) was the first (unlicensed) preparation available but Buccolam^® (5mg/ml) is currently the only licensed product available (for patients up to 18 years of age). Normal guidance would be to prescribe a licensed product in preference to an unlicensed one. In this instance, it is not recommended changing a patient once they are established on one preparation due to the risk of patient harm.

Sucralfate (Antepsin^®) shortage

There is currently a long-term supply problem with both sucralfate suspension and tablets.  It is anticipated that there will be no supplies available until the end of this year.  Clinicians should review the need for this preparation on a case by case basis and switch to a licensed formulary alternative where appropriate. Where the recommendation to prescribe this has come from a specialist, GPs may wish to seek their advice for ongoing treatment.

Visitors from overseas - Guidance for General Practice

The XX Commonwealth Games will take place in Glasgow from 23rd July - 3rd August and will be the largest multi-sport event ever held in Scotland.  Visitors to Glasgow may seek medical care from general practice and guidance has been produced to assist practices with queries that may arise such as entitlement to NHS treatment.

Community pharmacies can provide emergency supplies of medication to patients from within the EEA and Switzerland at the patient or prescriber’s request.  Patients from outwith this area may be referred to a local surgery or out of hours service.

Gameplan is a useful document by NES for community pharmacy preparedness for the Games, however there are useful sources of information such as foreign tablet identification references which may be useful within general practice also.

RIP PostScript - Rebranding

From next month, the PostScript family of bulletins will be re-branded as ‘Medicines Update’ with the website and new smartphone app being titled GGC Medicines.

Information below is specific to the use of medicines in the adult setting.

The GGC Medicines App is now available for Apple mobile devices and will be launched for Android devices by the end of August 2014. Once downloaded much of the content is available without an internet connection.  Access is provided to the following resources:

1. Therapeutics Handbook

This GGC handbook is a well established aid for prescribers in the immediate management of >100 common medical conditions.  The printed version is still available in all clinical areas (a summary of the major changes to this edition can be found here). Users may however find the additional functionality of the App version appealing.

Features of Therapeutic Handbook accessed via GGC Medicines App 

• Portable
• Easy to navigate and search
• Guidelines, reformatted to work well on the small screen (Figure 1) with flowcharts as pdfs that open on request
• Users can bookmark their most referred to guidelines and annotate/email their own notes

2.Gentamicin/Vancomycin Electronic Calculators

User friendly and fully validated dose calculators for these high risk medicines.  (Also accessible via StaffNet).

3. Formulary (requires internet connection)

Access to full NHSGGC Formulary and regular updates.

4.  Medicines Update Bulletins  (requires internet connection)

Formerly known as Postscript this edition marks the re-launch of these bulletins as Medicines Update.  The bulletins provide information on:

• Medicines safety messages
• Recent GGC incidents and associated learning
• New Guidelines (local & national)
• Major changes to Formulary/prescribing practices

This bulletin is GGC Medicines Update Acute however there is a range of Medicines Update bulletins available (click here for further information). 

GGC Medicines website

Formerly known as the GGC prescribing website (www.ggcmedicines.org.uk/) provides access to the following:

• Searchable PDF of Therapeutics Handbook
• Formulary & Updates
• Medicines Update Bulletins
• Medicines Policies (e.g. Unlicensed Medicines Policy)

Poor documentation of allergies and intolerances can result in the administration of inappropriate medicines to patients with the potential to cause significant harm. In addition, preferred therapies may be replaced with more toxic/costly/less effective alternatives if a reaction recorded as an ‘allergy’ is actually an ‘intolerance’ (e.g. nausea following penicillin administration).

A recent audit of 268 in-patient medicine charts at a GGC hospital looked at the frequency and quality of allergy/intolerance documentation. Key findings included;

• 20.5% of patients did not have the allergy section completed in their medical notes
• 17.9% of patients did not have the allergy section completed on their medicine chart
• 18.8% of patients with a blank allergy status on their medicine chart had a known allergy
• 14.6% of patients with a blank allergy chart were prescribed and given a penicillin, a medication group known to cause potentially serious allergic reactions
• Where allergies were recorded in the notes or on medicine charts, <20% had a descriptive nature of the allergy documented

Case studies Penicillin allergy 

The following recent GGC incidents demonstrate the potential consequences of the above findings:

Case 1

Anaphylaxis occurred after administration of co-amoxiclav. Penicillin allergy was documented on the kardex. The senior medical staff, junior medical staff and nurse did not check the allergy section (or with the patient) before recommending, prescribing or administering the co-amoxiclav.

Case 2

Administration of amoxicillin resulted in another patient suffering anaphylaxis.  The doctor and nurse had asked the patient about penicillin allergy but the patient had not mentioned it. On investigation, penicillin allergy was documented on the Emergency Care Summary allergy section.

In both these cases, treatment for anaphylaxis was required but the patient made a full recovery. 

Other factors associated with reports of inadvertent administration of penicillin include lack of awareness of which antimicrobials contain penicillin.  Generic prescribing (e.g. co-amoxiclav rather than Augmentin^®, piperacillin/tazobactam instead of Tazocin^®) can reduce this risk; see StaffNet for further information.

KEY MESSAGES

All healthcare professionals prescribing, administering and checking medication should be aware of the patient’s allergy status. In particular they should;

• Establish an accurate allergy status (including the nature of any allergies/intolerances) as part of medicines reconciliation (check 2 sources; do not rely only on the patient to tell you).
• Record the patient’s allergy status (including the nature of any allergies/intolerances) in the medical notes and on the medicine chart.
• Check the patient’s allergy status before prescribing or administering any medicine to them. DO NOT take a blank allergy status as an indication that the patient has no known allergies. For nursing staff administering medicines, this is an essential part of the NHS GGC ‘Chance to Check’ (StaffNet link) process.

Information below is specific to the use of medicines in the adult setting.  

Acute Kidney Injury (AKI) and Prescribing

AKI is common in hospitalised patients with intercurrent illness, multiple co-morbidities and polypharmacy.  It is defined as a sudden and sustained decline in Glomerular Filtration Rate (GFR) leading to an accumulation of urea and other chemicals, with or without, a drop in urine output. It is categorised in 3 stages from I (mild) to III (severe), as described in the table below.

Early recognition and prompt management of AKI is important, as even a small rise in creatinine during an acute admission has been associated with prolonged hospital stay, increased morbidity and an increased likelihood of death.  For information on the management of AKI see the Therapeutics Handbook and for prescribing advice in AKI see the box below.

Table 1 – Stages of AKI

Definition of AKI Stages

Stage I

 Cr  >150 – 200% from baseline  or

Acute increase of Cr>25 micromol/L/48 hours or

Urine output < 0.5 ml/kg/hour for > 6 hours

Stage II                   

Cr > 200 - 300% from baseline or

Urine output < 0.5 ml/kg/hour > 12 hours

Stage III

Cr > 300% baseline or 

Cr > 350 micromol/L or

Urine output < 0.3 ml/kg/hour for 24 hours or

Anuric for 12 hours or 

Requires renal replacement therapy, irrespective of Cr

Key Messages for Prescribing in AKI

• Seek specialist advice if prescribing for a patient on dialysis. 
• Avoid nephrotoxic drugs where possible (e.g. gentamicin, vancomycin and some antifungals, antivirals, IV contrast media and cytotoxics).
• Stop medicines which can reduce renal perfusion (e.g. ACE Inhibitors, angiotensin II antagonists and NSAIDs) or exacerbate extracellular fluid volume depletion (e.g. diuretics).
• Do NOT place too much value on a single creatinine measurement.  If the serum creatinine is rising rapidly and/or the patient is not passing urine then the GFR is likely to be zero.
• Formulae used to calculate estimated Glomerular Filtration Rate (eGFR)  or Creatinine Clearance (CrCl) are only valid when the serum creatinine is stable. Use of such formulae for prescribing in AKI can lead to drug toxicity (and potentially exacerbate AKI).
• Consider re-introducing medicines once the AKI has resolved (it may be appropriate to leave this for some weeks until renal function has completely stabilised).
• Patients re-starting (or starting) ACE Inhibitors, angiotensin II antagonists and NSAIDs should be educated on the need to stop therapy during periods of illness associated with dehydration e.g. diarrhoea.

Chronic Kidney Disease (CKD) and Prescribing

eGFR is a useful tool to detect chronic kidney disease (CKD) but it can also be used to guide drug dosing in some patients with CKD (see key messages box below).

Although renal function is increasingly reported as eGFR, published information on the effects of renal impairment on drug elimination is usually stated in terms of CrCl and this can lead to confusion. The key messages below provide guidance on how to prescribe for patients with CKD.

Key Messages for Prescribing in CKD

• Seek specialist advice if prescribing for a patient on dialysis.
• Avoid nephrotoxic drugs where possible (e.g. gentamicin, vancomycin and some antifungals, antivirals, IV contrast media and cytotoxics).
• In elderly patients the creatinine can look ‘normal’ but due to reduced muscle mass, assume at least mild renal impairment.
• In practice, eGFR can be considered interchangeable with CrCl if the patient is of normal build and height i.e. the reported eGFR can be used to guide dosing even if the published information refers to CrCl.  The exceptions are:

• Patients at both extremes of body weight
• Patients prescribed potentially toxic drugs with a small safety margin.  (The BNF and/or local guidelines should be consulted for individual drugs.  Examples include gentamicin, vancomycin and digoxin).  
  
  In these patient groups, CrCl should be used to adjust drug doses; the ‘Cockcroft Gault’ equation can be used to estimate CrCl. 

REMEMBER

Prescribing in CKD:

Use CrCl in preference to eGFR for

1.  drugs with a small safety margin

2.  patients at extremes of body weight

Prescribing in AKI:

Use eGFR or CrCl with extreme caution and seek advice from pharmacy if necessary.