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

PostScript 77 (Sept '13)

This edition contains articles on:

  • Safety updates including diclofenac, metoclopramide, codeine in children
  • Kid’s corner: melatonin
  • Osteoporosis update
  • ADTC decisions
  • Webwatch: Choice and medication
  • Reviewing tiotropium
  • New guidelines and primary care app

 

Safety updates

Diclofenac

The MHRA has issued a drug safety alert on diclofenac following a Europe wide review of cardiovascular safety. Available data indicate that the arterial thrombotic risk with diclofenac is similar to that of the selective COX-2 inhibitors. The new advice applies to all systemic formulations.

 

Consistent with COX-2 inhibitors, diclofenac is now contraindicated in those with:

  • ischaemic heart disease
  • peripheral arterial disease
  • cerebrovascular disease
  • established congestive heart failure (New York Heart Association [NYHA] classification II–IV).

 

Patients with these conditions should have ongoing need for NSAID treatment reviewed at their next routine GP appointment and, if necessary, switched to an alternative treatment.

 

The NHSGGC oral anti-inflammatory guideline recommends naproxen or ibuprofen for patients where an NSAID is required and is clinically appropriate taking into account individual patient risk factors including cardiovascular and gastrointestinal risk.

 

Anti-inflammatory drugs should generally be prescribed at the lowest effective dose for the shortest duration possible. Refer to the guideline for further advice.

 

Diclofenac is currently on the Preferred List of the GGC Adult Formulary. Any change will be communicated in due course.

 

Ketoconazole

The MHRA have also advised that oral ketoconazole should no longer be prescribed for fungal infections. Liver injury such as hepatitis is a known side effect of antifungal medicines; however the incidence and the seriousness are higher with oral ketoconazole than with other antifungals. Topical formulations have low systemic absorption and can continue to be used.

 

Metoclopramide

The benefits and risks of metoclopramide have been reviewed following concerns over side effects and efficacy. This found the risks of neurological effects, eg extrapyramidal disorders and tardive dyskinesia outweigh the benefits in long-term or high-dose treatment. There are restrictions to the dose and duration of use to help minimise the risk of adverse effects. The risks are higher in children.

 

Metoclopramide should only be prescribed for short-term use (up to five days). Those on long term therapy should be reviewed with advice sought from the clinician who initiated therapy if required.

 

In adults, metoclopramide remains indicated for:

  • prevention of postoperative nausea and vomiting
  • radiotherapy-induced nausea and vomiting
  • delayed (but not acute) chemotherapy-induced nausea and vomiting
  • symptomatic treatment of nausea and vomiting, including that associated with acute migraine (where it may also be used to improve absorption of oral analgesics)

 

In children, age 1–18 years, metoclopramide should only be used:

  • second-line for prevention of delayed chemotherapy-induced nausea and vomiting
  • for treatment of established postoperative nausea and vomiting

 

DOSE      Usual dose  Max daily dose 
Adults  

 10mg

up to three times a day

 30mg (or 500 micrograms/kg)

Children, 1–18 years

 100 – 150 micrograms / kg

up to three times a day  

 500 micrograms/kg
Children < 1 year

 contraindicated 

 

 

 

Nitrofurantoin

The MHRA have issued a reminder on precautions for use of nitrofurantoin. The antibacterial efficacy in urinary tract infections depends on the renal secretion of nitrofurantoin into the urinary tract. In patients with renal impairment, secretion is reduced, which can result in treatment failure.

 

The SPC and MHRA state it is contraindicated where creatinine clearance < 60ml/min. Advice in GGC Therapeutics Handbook is to avoid in patients with eGFR < 20ml/min/1.73m2 and contact microbiology for an alternative.

 

The Antimicrobial Management Team is seeking national clarification on the variation but advise no change to current practice at present. Healthcare professionals should be aware of a patient’s current renal function when prescribing, especially for elderly patients.

 

Kid’s Corner: Codeine restrictions

The use of codeine has been restricted in children because of reports of morphine toxicity. Codeine should only be used for acute moderate pain in children older than 12 years of age and only if the pain cannot be relieved by other analgesics, eg paracetamol or ibuprofen.

 

A significant risk of serious and life-threatening adverse reactions has been identified in children with obstructive sleep apnoea who received codeine after tonsillectomy or adenoidectomy (or both). Codeine is now contraindicated in all children below 18 years who undergo these procedures for obstructive sleep apnoea.

 

Yorkhill have reviewed their pain protocols. Dihydrocodeine is now the preferred opioid with a focus on optimising other analgesics.

 

Kid’s Corner: Melatonin

A shared care protocol has been approved for the use of melatonin as a sleep aid for children over 2 years of age with neuro-developmental disorders and chronic sleep disturbances. Initiation and titration of the drug is undertaken by secondary care with care transferred to the GP once the patient has been stabilised on the medicine.

 

Melatonin is a hormone produced by the pineal gland which has sleep-inducing properties and plays a major role in the synchronisation of the circadian rhythm. It is often prescribed in children who have disturbed sleep patterns, eg delayed onset, frequent nocturnal awakenings, early morning waking.  Sleep difficulties are common in children with neuro-developmental conditions such as ADHD and autism. 

 

Product choice is complicated due to licensing issues. The preferred product (BioMelatonin® 3mg tablet) is licensed as a medicinal product elsewhere in the EU, but not in the UK. The modified release tablet (Circadin® 2mg) is only licensed in the UK for adults 55 years and older. Both products are included in the NHSGGC Paediatric Formulary. Clinicians should standardise their prescribing to these two products. In specific circumstances unlicensed specials or imported products can be obtained.

 

Response to melatonin is variable. Therapeutic doses range from 3mg – 6mg daily. A maximum of 12mg daily may be used but benefits above 9mg are rarely seen. The lack of evidence for specific mg/kg dosing means there is little point in making small changes to dosage regimes. Doses can safely be altered by 2-3mg using the recommended products.

 

Melatonin may be stopped suddenly without any withdrawal effects. Tolerance is unlikely to develop from chronic (or acute) usage. It is generally well tolerated with few side effects, although it has been associated with headaches, nausea and dizziness.

 

BioMelatonin tablets can also be crushed and mixed with small amounts of food or liquids such as water, juice or milk. The modified release product is particularly useful for children with a fragmented sleep pattern who wake up through the night. The simultaneous use of the standard and modified release preparations may be helpful in some children.

 

Community pharmacists who receive a GP10 prescription for melatonin should normally dispense the recommended products. If an unlicensed imported product is requested, a clinician’s letter detailing the special need, as per MHRA guidance, must be provided with the prescription before a supply can be made. If unclear, the pharmacist should question the rationale for using the other preparation. 

 

Taking a break from bisphosphonates

The NHSGGC Osteoporosis Subgroup has recently produced guidance promoting review of patients on long-term treatment with oral bisphosphonates for fracture risk reduction. The review seeks to identify patients who are eligible for a drug “holiday”.

 

Background

Depending on the drug studied, clinical trials of bisphosphonate therapy have shown a reduced risk of vertebral, non-vertebral and hip fracture in osteoporotic patients.  Although bisphosphonates have a very short plasma half-life, their mode of action sees them incorporated into the bone matrix structure and they are retained for many years. 

This means that if bisphosphonate therapy is discontinued, the drug remains within the body and as old bone is remodelled, the medicine is released and potentially becomes active again.  NHSGGC Formulary guidance on drugs affecting bone metabolism is available here

 

Why the need for bisphosphonate “holiday” guidance?

As clinical trials typically last for three years, the long-term safety and benefit issues remain unclear.  Potential adverse effects of long-term therapy have been described during recent years.  These include;

  • increased risk of osteonecrosis of the jaw
  • atypical stress fractures (although the incidence at doses used to treat osteoporosis remains uncertain)
  • oesophageal cancer

 

Prescribers should review treatment considering the potential increased risk of harm balanced against the ongoing benefits of treatment. The purpose of the guidelines is aid this decision making.

 

The guidance is underpinned by an assessment of risk of fracture and prescribers need to take into account risk factors such as patient’s age, fracture history, T-score, FRAX score and a subjective assessment of patient frailty.  The WHO fracture risk assessment tool (FRAX) can be used to determine a patient’s absolute fracture risk.

 

Prescribers should be aware that the guideline is designed to cover most patients’ circumstances, but the criteria will not suit every individual patient. In these cases, clinical judgement should be used to determine whether continuing or ceasing oral bisphosphonate therapy is in the patient’s best interest.  In general, compliance and persistence with oral bisphosphonate therapy can be variable. An accurate compliance history should be obtained from the patient before a clinical decision is made.

 

Further information and guidance can be obtained from the Falls Prevention Pharmacy Team (0141 201 5313) or the relevant Fracture Liaison Service / Bone Metabolism Clinic.

 

Measuring and prescribing Vitamin D in adult patients with osteomalacia or osteoporosis

The main aim of vitamin D treatment is the prevention of osteomalacia, a condition characterised by malaise, multifocal bone pain with tenderness, proximal myopathy. It is also associated with abnormal biochemistry.

 

The NHSGGC Osteoporosis Subgroup has released guidance for the measuring and prescribing of vitamin D in adult patients with osteomalacia, osteoporosis or increased risk of fracture.

 

Vitamin D should be measured in patients with:

  • low adjusted serum calcium or osteomalacia
  • malabsorption syndromes
  • chronic kidney disease and attending specialist clinic
  • osteoporosis and not already on calcium / vitamin D before giving first dose of IV bisphosphonate or denosumab to reduce risk of drug induced hypocalcaemia.

 

Vitamin D should not be measured:

  • for routine monitoring of prescribed vitamin D at a dose of less than 5000 units per day,
  • in patients on alfacalcidol or calcitriol,
  • as a general test investigating general tiredness, chronic fatigue / fibromyalgia or non-specific aches & pains.

 

The flowchart developed by the subgroup outlines when to prescribe vitamin D and what to prescribe. Guidance regarding vitamin D deficiency or insufficiency in the general adult population is currently under development.

 

 

ADTC decisions summary

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

 

Some additions to the Adult Total Formulary:

  • Argatroban: heparin-induced thrombocytopenia
  • Pirfenidone: mild to moderate idiopathic pulmonary fibrosis. Restricted to specialist use in accordance with protocol and agreement of an interstitial lung disease multidisciplinary team.
  • Ranubizumab: visual impairment due to diabetic macular oedema.
  • Sugammadex: for specialist use for routine reversal of neuromuscular blockade induced by rocuronium or vecuronium in high risk adults.

 

The following medicine was removed

  • Ketoconazole (oral): See above. MHRA advise it should no longer be used for fungal infections. Some patients may be at an increased risk of liver damage and the risk outweighs the benefits.

 

The following medicines were among those added to the Paediatric Formulary

  • Adalimumab: severe active Crohn’s disease. Restricted to specialist use.

 

        

Webwatch: Choice & Medication

Patients with a mental illness frequently seek information about their medicines. There are a variety of sources available. After lobbying from the Scottish Mental Health Pharmacy Strategy Group, NHS24 has funded a Scotland wide subscription to the NHS Inform mental health website. Select the “Choice & Medication” link.  The website is accessible to healthcare staff, patients and carers and is an ideal source of information about medicines used in mental health to patients.

 

The Choice & Medication site is managed by a team of NHS pharmacists based in England. It contains information on mental health conditions and the medicines used to treat them. The information is in a variety of formats and there is a range of printable leaflets about medicines. Mental Health Pharmacy Services use this resource as their standard source of patient information about drugs for mental health conditions.

 

Reviewing Tiotropium

The last edition of PostScript noted the removal of Spiriva Respimat® from the GGC Adult Formulary. The Respiratory MCN has produced the following advice for prescribers undertaking reviews of patients who were previously prescribed this medicine.

 

Tiotropium Handihaler remains on the NHSGGC Preferred List and, until further clinical data is available, remains the long acting antimuscarinic treatment of choice for patients with COPD in line with NHSGGC COPD primary care guidelines.

 

All patients prescribed Spiriva® (tiotropium) Respimat be identified and reviewed at the next available opportunity, either in acute or primary care.

  • As part of the review, the patient's overall condition should be taken into account e.g. cardiovascular risk factors as well as response to treatment.
  • Alternative treatment should be considered in at risk patients including those with known cardiac rhythm disorders and in those with severe COPD (FEV1< 50%).

Alternative treatment options include:

  • long acting beta agonists, eg formoterol Easyhaler®,
  • tiotropium Handihaler®
  • where appropriate an inhaled corticosteroid / LABA combination inhaler in patients with an FEV1 < 50% and at least 2 exacerbations over 12months

 

Report all suspected adverse reactions to tiotropium via the Yellow Card reporting scheme.

 

Primary Care Antimicrobial Guidelines App

GP Antibiotics is a simple, searchable, pocket reference for the current NHSGGC adult and paediatric antimicrobial guidelines developed by the antimicrobial team. It is free to download from the Apple App Store or Android’s Google Play Store. Prescribers should find this useful, particularly for house calls or care home visits.

 

New guidelines

The clinical guidelines below were posted onto Staffnet: