NHS Greater Glasgow & Clyde Area Drug and Therapeutics Committee
Greater Glasgow and Clyde Medicines
Medicines Update

PostScript 75 (May 2013)

This edition contains articles on:

 

  • New treatment in stem cell transplantation
  • Webwatch: Medicines Awareness Service
  • Kid’s corner: Prescribing liquid medicines
  • ADTC decisions
  • Medical conditions, drugs and driving
  • Rivaroxban for acute DVT / PE
  • Ticagrelor for ACS
  • New clinical guidelines; nutritional guidelines

 

New treatment in stem cell transplantation

 

Peripheral blood stem cell (PBSC) mobilisation followed by autologous stem cell transplantation (ASCT) is the most effective treatment option for many patients with haematological malignancies such as Multiple Myeloma, Hodgkin’s disease or Non-Hodgkin’s Lymphoma.

 

Currently, granulocyte colony stimulating factor (G-CSF) or G-CSF plus chemotherapy are the most commonly used methods for stem cell collection. However, up to 30% of patients cannot mobilise enough cells with these methods and are unable to proceed to ASCT.

 

Plerixafor was accepted by the Scottish Medicines Consortium in 2010 and its introduction has improved the process of harvesting stem cells. It is prescribed by haematology specialists in accordance with the regional protocol.

 

Plerixafor blocks the action of the CXCR4 chemokine receptor which is involved in the retention of stem cells in the bone marrow. As plerixafor is a release factor and not a growth factor, it does not initiate growth and maturation of stem cells in the bone marrow but acts to free these cells into the circulating blood. It therefore has the ability to “rescue” heavily pre-treated patients who have failed stem cell mobilisation in the past or appear to be failing standard G-CSF plus chemotherapy mobilisation. In a three-year period (August 2009 – September 2012) clinicians at the WoSCC have used this treatment in 16% of mobilisation episodes.

 

Plerixafor is administered as a subcutaneous injection the night before anticipated stem cell collection. Local audit demonstrates a 92% success rate. It has an average cost of £8,650 per patient, but this must be considered within the overall context of ASCT which is a very high cost treatment area.

 

Allowing patients to proceed to transplant as intended is very important for the patient and the service. Plerixafor contributes to the cost-effectiveness of the medicine due to elimination of the need for re-mobilisation using conventional methods.

 

Webwatch: NICE / UKMi Medicines Awareness Service

 

NICE is working in association with UKMi to deliver a new Medicines Awareness Service. This email subscription service provides daily and weekly access to current awareness and evidence-based medicines information sent direct in your inbox.

 

The Medicines Awareness Service will highlight:

  • New guidance publications from key sources such as NICE and other accredited UK guidance producers
  • Key evidence published in selected major journals
  • Information aggregated from news stories, press releases and safety alerts
  • New and updated prescribing information to inform clinical practice including drug appraisals, evidence summaries and reviews

 

The Medicine Awareness Daily bulletin provides information and links to the latest published evidence, policies, guidelines, evidence summaries and press releases. Medicine Awareness Weekly will contain a round-up of the key stories covered by Medicines Awareness Daily. This weekly service also includes the NICE Medicines Evidence Commentary, information on new evidence on medicines currently in use for NHS commissioners, prescribers and prescribing managers provided by the Medicines and Prescribing Centre at NICE.

 

Subscribers to the NeLM Newsletter and/or the NICE Medicines and Prescribing Centre daily and weekly medicines awareness alerts will automatically be signed up to this new service and can amend their subscriptions to personalise the content. Find out more here.

 

Kid’s corner: Prescribing liquid medicines

 

Vigilance is required with medicines available in a range of strengths.

 

There can be confusion when different strength liquid preparations of the same drug are available, especially when they are unusual drugs that are less familiar to GPs and pharmacists.

 

Examples: Did you know?

  • Furosemide is available in liquid preparations in four different strengths: 5mg/5ml, 20mg/5ml, 40mg/5ml and 50mg/5ml.
  • Spironolactone is available in five different strengths: 5mg/5ml, 10mg/5ml, 25mg/5ml, 50mg/5ml and 100mg/5ml.

 

Several incidents have occurred with the liquid formulations of diuretics. A patient was discharged from Yorkhill on furosemide 6mg three times a day and spironolactone 6mg three times a day. The strength of furosemide dispensed from the hospital was 20mg/5ml and spironolactone was 50mg/5ml. In community the patient received furosemide 5mg/5ml and spironolactone 5mg/5ml strengths but the same volumes were given. This meant doses of 1.5mg furosemide three times daily and 0.6mg spironolactone three times daily. The patient was clinically well despite the significant under dosing. A similar incident occurred which lead to admission to intensive care. The main factor that contributed to this error was that the medicines were prescribed and dispensed in volume rather than dose.

 

Recommended actions

  • Be aware that a number of preparations are available in different strengths, some of which are licensed and some are not.
  • Where possible, only prescribe the formulation recommended by the specialists.
  • If a drug is recommended by secondary care, or appears on a prescription that is unfamiliar, take steps to familiarise yourselves with the drug.
  • Using unlicensed preparations carries risks. Ensure clinical systems are in place to check that unlicensed strengths are highlighted.
  • Take care when selecting preparations on computer systems.

 

And finally,

  • For inpatient prescribing, ensure you state the dose of liquid medicines in terms of the dose required, ie as the number of micrograms, milligrams or grams rather than the volume.
  • Ensure communication for ongoing prescribing by GPs or others in primary care includes clear information on the strength of the preparation, the intended dose and the required volume.

 

ADTC decisions summary

 

See here for full list of medicines and details of indications and restrictions.

 

 

Medical conditions, drugs and driving

 

The DVLA has a useful web resource for medical professionals providing information on driving with different medical conditions and the implications for holders of group 1 licences (cars and motorcycles) and group 2 licences (commercial vehicles).

 

Changes to the medical licensing process have been introduced to ensure those working in the health services can provide clear advice on fitness to drive. There is a medical A-Z guide to help motorists understand whether they need to notify DVLA about a medical condition and a learning module on medical conditions and driver licensing awareness making it easier for health care professionals to understand their responsibilities.

 

Recent changes include updates to the visual standards and updates for those drivers with epilepsy. The standards for people with diabetes were updated in 2011. Hypoglycaemia whilst driving is serious and requires immediate action. The recommendations differ for groups of patients with diabetes depending on the type of treatment and awareness of hypoglycaemia.

 

Rivaroxaban for DVT / PE

 

Rivaroxaban is approved in NHSGGC for the treatment of acute deep vein thrombosis (DVT) and / or pulmonary embolism (PE) in patients scheduled for finite (usually 3-6 months) anticoagulant therapy. Patients who require long term anticoagulation should receive low molecular weight heparin (LMWH) initially then transferring to warfarin, while those with underlying cancer or who are pregnant should be offered LMWH rather than warfarin, as per existing guidelines.

 

Two large randomised, open-label studies compared fixed dose oral rivaroxaban with LMWH transferring to warfarin in acute DVT and PE. Rivaroxaban was non-inferior to LMWH plus warfarin. Major bleeding events were similar in the DVT study but less frequent in the rivaroxaban arm of the PE study. Rivaroxaban does not require routine anticoagulant monitoring and has few drug or food interactions.

 

Anticoagulation with rivaroxaban has a rapid onset and so can be used in place of LMWH, however local guidelines recommend therapeutic LMWH until the DVT or PE diagnosis is confirmed. The first rivaroxaban dose is given 20-24h after the last dose of LMWH. Rivaroxaban should be taken with food at a dose of 15mg twice daily for 21 days, then reduced to 20mg daily until treatment stops. Rivaroxaban is contra-indicated if creatinine clearance (CrCl) is <15ml/min. If CrCl is 15-29 ml/min, use with caution and consider reducing the dose from day 22mg to 15mg daily in patients with a high bleeding risk.

 

Rivaroxaban will normally be started in secondary care, and the first 21 days’ medication supplied. Treatment from day 22 onwards is prescribed by the GP. Discharge information will include clear instructions for switching to GP-prescribed once daily dosing and the date when rivaroxaban therapy should stop. A template rivaroxaban discharge letter is included in the guideline.  Patients should be issued with a Rivaroxaban Alert Card from pharmacy and do not need to be referred to an anticoagulant clinic.

 

Ticagrelor for ACS

 

Ticagrelor has been added to the NHSGGC Adult Formulary for patients with troponin positive acute coronary syndrome (ACS, defined as unstable angina, non ST elevation myocardial infarction [NSTEMI] or ST elevation myocardial infarction [STEMI]).

 

Ticagrelor plus low-dose aspirin is now the dual antiplatelet therapy (DAPT) regimen of choice for patients who present with an ACS instead of clopidogrel. This follows agreement between cardiologists from the West of Scotland Heath Boards and the Golden Jubilee National Hospital. Ticagrelor does not replace clopidogrel for any other indication.

 

Evidence from The Study of Platelet Inhibition and Patient Outcomes (PLATO) showed that ticagrelor significantly reduces the frequency of cardiovascular events in patients with ACS (NNT 54) and reduces cardiovascular mortality (NNT 91). There was no difference in the rates of major bleeding compared to clopidogrel.

 

The ticagrelor dose is 90mg twice daily. Durations of treatment are different from those with clopidogrel:

 

  • Patients treated medically: three months’ DAPT.  
  • Angioplasty alone or angioplasty with insertion of a bare metal stent: three months’ DAPT. 
  • Angioplasty with drug eluting stent insertion: six months’ DAPT (a reduction from twelve months with aspirin / clopidogrel).
  • Long-term antiplatelet monotherapy remains low-dose aspirin.

 

All patients, irrespective of treatment duration, will receive the first month of treatment from hospital (one week if they are discharged with a monitored dose system). To support continuity of treatment, a patient information leaflet will be supplied on discharge which indicates the duration of treatment and anticipated stop-date. Any variance from this will be annotated on the Immediate Discharge Letter.

 

Side effects with ticagrelor are similar to clopidogrel, with the exception of dyspnoea which has been reported in 14% of patients (versus 8% with clopidogrel in PLATO). If persistent and troublesome, consideration should be given to switching to clopidogrel for the rest of the treatment course.

 

The metabolism of ticagrelor is inhibited by clarithromycin and other potent CYP3A4 inhibitors. These drugs should be avoided during ticagrelor treatment or the patient switched to clopidogrel.

 

A shared care protocol has been agreed with the LMC and the revised Antiplatelet Therapy in the Secondary Prevention of Coronary Heart Disease guideline will be placed on Staffnet.

 

New guidelines

 

The clinical guidelines below were posted onto the electronic resource directory on Staffnet.

 

Nutritional Guidelines

 

The Therapeutics Sub Committee of the ADTC has produced a range of new guidelines to support improved prescribing and supply of oral nutritional supplements in primary care.

 

Ongoing review of prescribing practice indicates that a significant number of patients are inappropriately receiving on-going prescriptions for these products. The annual cost of prescribing in NHSGGC is approximately £4 million. Ideally, patients should be identified as being at risk of malnutrition using a validated screening tool and receive first line dietary advice to maximise dietary intake before consideration of any oral nutritional supplement. The guidelines offer good practice guidance for all healthcare professionals.

 

Current evidence suggests that sip feeds are of more benefit in those patients with a BMI <20 kg/m2 and are useful in increasing their energy and protein intakes. Used appropriately, these supplements can reduce mortality, reduce complications, reduce hospital stay and result in weight gain.

 

Sip feeds are normally supplementary to food and should be taken between meals evenly spread over the day. An effective dose is one to two bottles daily (300 - 660kcals) for a maximum of two or three months. Patients should be assessed regularly for compliance and continued need. Evidence suggests sip feeds are of less benefit after 6 months.

 

Formulary choices are:

  • Ensure® Plus Milkshake Style (220mls = 330kcals) - A milk-based supplement
  • Ensure® Plus Fibre (200mls = 300kcals) – A milk-based supplement with added fibre
  • Ensure® Plus Yoghurt Style (220mls = 330kcals)– A milk-based supplement with yoghurt taste
  • Ensure® Plus Juce (220mls = 330kcals) – A juice based supplement
  • Ensure ® Plus Savoury (220mls = 330kcals)
  • Enshake- 1x96.5g sachet = 600kcals made up with fresh milk – not nutritionally complete

 

Guidance on nutritional assessment includes advice on how to assess if patients are at risk of refeeding syndrome. This can occur on the initiation of oral, enteral or parenteral nutrition support. Patients at high risk should be monitored by healthcare professionals with appropriate knowledge and experience in nutrition requirements and nutrition support.

 

Guidelines have also been approved for patients in the community who are receiving enteral feeding.